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Sample records for biologically active molecules

  1. An insight into the biological activities of heterocyclic-fatty acid hybrid molecules.

    Science.gov (United States)

    Venepally, Vijayendar; Reddy Jala, Ram Chandra

    2017-12-01

    Heterocyclic compounds are the interesting core structures for the development of new bioactive compounds. Fatty acids are derived from renewable raw materials and exhibit various biological activities. Several researchers are amalgamating these two bioactive components to yield bioactive hybrid molecules with some desirable features. Heterocyclic-fatty acid hybrid derivatives are a new class of heterocyclic compounds with a broad range of biological activities and significance in the field of medicinal chemistry. Over the last few years, many research articles emphasized the significance of heterocyclic-fatty acid hybrid derivatives. The present review article focuses the developments in designing and biological evaluation of heterocyclic-fatty acid hybrid molecules. Copyright © 2017. Published by Elsevier Masson SAS.

  2. Synthesis of molecules of biological interest labelled with high specific activity tritium

    International Nuclear Information System (INIS)

    Petillot, Yves

    1975-01-01

    Labelled molecules are artificial organic compounds possessing one or several radioactive or steady isotopic atoms. Using tritium to label molecules presents several benefits: a raw material easy to obtain with a high purity and at reasonable cost; synthesised labelled molecules displaying high specific activities very interesting in molecular biology; high resolution of radiographies; relatively simple and quick introduction of tritium atoms in complex molecules. Thus, this report for graduation in organic chemistry addresses the synthesis and study of new labelled molecules which belong to families of organic compounds which have fundamental activities in biology: uridine 3 H-5,6 and thymidine 3 H-methyl which are nucleotides which intervene under the form of phosphates in the synthesis of nucleic acids, oestradiol 3 H-2,4,6,7 which is a powerful estrogenic hormone which naturally secreted by the ovary; and noradrenaline 3 H-1,1' and dopamine 3 H-1,2 which are usually secreted by adrenal medulla and have multiple actions on the nervous system

  3. Myricetin: A Dietary Molecule with Diverse Biological Activities

    Directory of Open Access Journals (Sweden)

    Deepak Kumar Semwal

    2016-02-01

    Full Text Available Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities.

  4. Raman Optical Activity of Biological Molecules

    Science.gov (United States)

    Blanch, Ewan W.; Barron, Laurence D.

    Now an incisive probe of biomolecular structure, Raman optical activity (ROA) measures a small difference in Raman scattering from chiral molecules in right- and left-circularly polarized light. As ROA spectra measure vibrational optical activity, they contain highly informative band structures sensitive to the secondary and tertiary structures of proteins, nucleic acids, viruses and carbohydrates as well as the absolute configurations of small molecules. In this review we present a survey of recent studies on biomolecular structure and dynamics using ROA and also a discussion of future applications of this powerful new technique in biomedical research.

  5. Electro-induced reactions of biologically important molecules

    International Nuclear Information System (INIS)

    Kocisek, J.

    2010-01-01

    The thesis presents the results of research activities in the field of electron interactions with biologically relevant molecules which was carried out during my PhD studies at the Department of Experimental Physics, Comenius University in Bratislava. Electron induced interactions with biologically relevant molecules were experimentally studied using crossed electron-molecule beams experiment. The obtained results, were presented in four publications in international scientific journals. First study of deals with electron impact ionisation of furanose alcohols [see 1. in list of author publications on page 22]. It has been motivated by most important works in the field of electron induced damages of DNA bases [4]. Studied 3-hydroxytetrahydrofuran and tetrahydrofurfuryl alcohol, are important model molecules for more complex biological systems (e.g. deoxyribose).The influence of hydroxyl group on stabilisation of the positive ions of the molecules, together with the stability of furan ring in ionized form are main themes of the study. The studies of small amides and aminoacids are connected to scientific studies in the field of formation of the aminoacids and other biologically relevant molecules in space and works trying to explain electron induced processes in more complex molecules[12, 13, 24]. The most important results were obtained for aminoacid Serine [see 2. in list of author publications on page 22]. We have showed that additional OH group of Serine considerably lower the reaction enthalpy limit of reactions resulting to formation of neutral water molecules, in comparison to other amino acids. Also the study of (M-H)- reaction channel using the electron beam with FWHM under 100 meV is of high importance in the field. The last part of the thesis is focused on the electron interactions with organosilane compounds. Materials prepared from organosilane molecules in plasmas have wide range of applications in both biology and medicine. We have studied electron

  6. Application of terahertz spectroscopy for characterization of biologically active organic molecules in natural environment

    Science.gov (United States)

    Karaliūnas, Mindaugas; Jakštas, Vytautas; Nasser, Kinan E.; Venckevičius, Rimvydas; Urbanowicz, Andrzej; Kašalynas, Irmantas; Valušis, Gintaras

    2016-09-01

    In this work, a comparative research of biologically active organic molecules in its natural environment using the terahertz (THz) time domain spectroscopy (TDS) and Fourier transform spectroscopy (FTS) systems is carried out. Absorption coefficient and refractive index of Nicotiana tabacum L. leaves containing nicotine, Cannabis sativa L. leaves containing tetrahydrocannabinol, and Humulu lupulus L. leaves containing α-acids, active organic molecules that obtain in natural environment, were measured in broad frequency range from 0.1 to 13 THz at room temperature. In the spectra of absorption coefficient the features were found to be unique for N. tabacum, C. sativa and H. lupulus. Moreover, those features can be exploited for identification of C. sativa sex and N. tabacum origin. The refractive index can be also used to characterize different species.

  7. Novel approaches for single molecule activation and detection

    CERN Document Server

    Benfenati, Fabio; Torre, Vincent

    2014-01-01

    How can we obtain tools able to process and exchange information at the molecular scale In order to do this, it is necessary to activate and detect single molecules under controlled conditions. This book focuses on the generation of biologically-inspired molecular devices. These devices are based on the developments of new photonic tools able to activate and stimulate single molecule machines. Additionally, new light sensitive molecules can be selectively activated by photonic tools. These technological innovations will provide a way to control activation of single light-sensitive molecules, a

  8. Single molecule force spectroscopy: methods and applications in biology

    International Nuclear Information System (INIS)

    Shen Yi; Hu Jun

    2012-01-01

    Single molecule measurements have transformed our view of biomolecules. Owing to the ability of monitoring the activity of individual molecules, we now see them as uniquely structured, fluctuating molecules that stochastically transition between frequently many substrates, as two molecules do not follow precisely the same trajectory. Indeed, it is this discovery of critical yet short-lived substrates that were often missed in ensemble measurements that has perhaps contributed most to the better understanding of biomolecular functioning resulting from single molecule experiments. In this paper, we give a review on the three major techniques of single molecule force spectroscopy, and their applications especially in biology. The single molecular study of biotin-streptavidin interactions is introduced as a successful example. The problems and prospects of the single molecule force spectroscopy are discussed, too. (authors)

  9. Biological mechanisms, one molecule at a time

    Science.gov (United States)

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

  10. Multifunctional and biologically active matrices from multicomponent polymeric solutions

    Science.gov (United States)

    Kiick, Kristi L. (Inventor); Yamaguchi, Nori (Inventor)

    2010-01-01

    The present invention relates to a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of biologically active agents. In particular the invention relates to a functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin. Examples of active molecules that may be used with the multicomponent polymer of the invention include, for example, a drug, a biopolymer, for example a growth factor, a protein, a peptide, a nucleotide, a polysaccharide, a biological macromolecule or the like. The invention is further directed to the formation of functionalized crosslinked matrices, such as hydrogels, that include at least one functionalized compatibilizing polymer capable of assembly.

  11. 2012 Gordon Research Conference, Single molecule approaches to biology, July 15-20 2012

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, Julio M. [Columbia Univ., New York, NY (United States)

    2012-04-20

    Single molecule techniques are rapidly occupying a central role in biological research at all levels. This transition was made possible by the availability and dissemination of robust techniques that use fluorescence and force probes to track the conformation of molecules one at a time, in vitro as well as in live cells. Single-molecule approaches have changed the way many biological problems are studied. These novel techniques provide previously unobtainable data on fundamental biochemical processes that are essential for all forms of life. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of the molecular systems that underpin the functioning of living cells. Hence, our conference seeks to disseminate the implementation and use of single molecule techniques in the pursuit of new biological knowledge. Topics covered include: Molecular Motors on the Move; Origin And Fate Of Proteins; Physical Principles Of Life; Molecules and Super-resolution Microscopy; Nanoswitches In Action; Active Motion Or Random Diffusion?; Building Blocks Of Living Cells; From Molecular Mechanics To Physiology; Tug-of-war: Force Spectroscopy Of Single Proteins.

  12. Imidazole: Having Versatile Biological Activities

    Directory of Open Access Journals (Sweden)

    Amita Verma

    2013-01-01

    Full Text Available Imidazoles have occupied a unique position in heterocyclic chemistry, and its derivatives have attracted considerable interests in recent years for their versatile properties in chemistry and pharmacology. Imidazole is nitrogen-containing heterocyclic ring which possesses biological and pharmaceutical importance. Thus, imidazole compounds have been an interesting source for researchers for more than a century. The imidazole ring is a constituent of several important natural products, including purine, histamine, histidine, and nucleic acid. Being a polar and ionisable aromatic compound, it improves pharmacokinetic characteristics of lead molecules and thus is used as a remedy to optimize solubility and bioavailability parameters of proposed poorly soluble lead molecules. There are several methods used for the synthesis of imidazole-containing compounds, and also their various structure reactions offer enormous scope in the field of medicinal chemistry. The imidazole derivatives possess extensive spectrum of biological activities such as antibacterial, anticancer, antitubercular, antifungal, analgesic, and anti-HIV activities. This paper aims to review the biological activities of imidazole during the past years.

  13. Radiometallating antibodies and biologically active peptides

    International Nuclear Information System (INIS)

    Mercer-Smith, J.A.; Roberts, J.C.; Lewis, D.; Newmyer, S.L.; Schulte, L.D.; Burns, T.P.; Mixon, P.L.; Jeffery, A.L.; Schreyer, S.A.; Cole, D.A.; Figard, S.D.; Lennon, V.A.; Hayashi, M.; Lavallee, D.K.

    1990-01-01

    We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N-benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have on functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies, and we have also developed methods to label smaller biologically active molecules, such as autoantigenic peptides. The autoantigenic peptides, fragments of the acetylcholine receptor, are under investigation for myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules and the radiometallation chemistry will be discussed

  14. Biological Nanopores: Confined Spaces for Electrochemical Single-Molecule Analysis.

    Science.gov (United States)

    Cao, Chan; Long, Yi-Tao

    2018-02-20

    Nanopore sensing is developing into a powerful single-molecule approach to investigate the features of biomolecules that are not accessible by studying ensemble systems. When a target molecule is transported through a nanopore, the ions occupying the pore are excluded, resulting in an electrical signal from the intermittent ionic blockade event. By statistical analysis of the amplitudes, duration, frequencies, and shapes of the blockade events, many properties of the target molecule can be obtained in real time at the single-molecule level, including its size, conformation, structure, charge, geometry, and interactions with other molecules. With the development of the use of α-hemolysin to characterize individual polynucleotides, nanopore technology has attracted a wide range of research interest in the fields of biology, physics, chemistry, and nanoscience. As a powerful single-molecule analytical method, nanopore technology has been applied for the detection of various biomolecules, including oligonucleotides, peptides, oligosaccharides, organic molecules, and disease-related proteins. In this Account, we highlight recent developments of biological nanopores in DNA-based sensing and in studying the conformational structures of DNA and RNA. Furthermore, we introduce the application of biological nanopores to investigate the conformations of peptides affected by charge, length, and dipole moment and to study disease-related proteins' structures and aggregation transitions influenced by an inhibitor, a promoter, or an applied voltage. To improve the sensing ability of biological nanopores and further extend their application to a wider range of molecular sensing, we focus on exploring novel biological nanopores, such as aerolysin and Stable Protein 1. Aerolysin exhibits an especially high sensitivity for the detection of single oligonucleotides both in current separation and duration. Finally, to facilitate the use of nanopore measurements and statistical analysis

  15. Sustainable production of biologically active molecules of marine based origin.

    Science.gov (United States)

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Different design of enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation

    NARCIS (Netherlands)

    Stamellou, E.; Storz, D.; Botov, S.; Ntasis, E.; Wedel, J.; Sollazzo, S.; Kraemer, B. K.; van Son, W.; Seelen, M.; Schmalz, H. G.; Schmidt, A.; Hafner, M.; Yard, B. A.

    2014-01-01

    Acyloxydiene-Fe(CO)(3) complexes can act as enzyme-triggered CO-releasing molecules (ET-CORMs). Their biological activity strongly depends on the mother compound from which they are derived, i.e, cyclohexenone or cyclohexanedione, and on the position of the ester functionality they harbour. The

  17. Use of various ionization modes for the study of molecules of biological interest

    International Nuclear Information System (INIS)

    Forest, E.

    1987-01-01

    For the last ten years a revolutionary advance in mass spectrometry applied to molecules of biological interest occurred, chiefly concerning ionization with the emergence of many new modes allowing non volatile, polar or thermally labile sample analysis. Some examples of spectra obtained on high mass molecules such as vitamins, protein fragments, porphyrins (chlorophyll or hemoglobin active site), polysaccharides, are presented using some of the new modes [fr

  18. The Biological Activities of Sesterterpenoid-Type Ophiobolins

    Directory of Open Access Journals (Sweden)

    Wei Tian

    2017-07-01

    Full Text Available Ophiobolins (Ophs are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A–W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR cells and cancer stem cells (CSCs. Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure–activity relationship to lay the foundation for the future developments and applications of these promising molecules.

  19. The Biological Activities of Sesterterpenoid-Type Ophiobolins.

    Science.gov (United States)

    Tian, Wei; Deng, Zixin; Hong, Kui

    2017-07-18

    Ophiobolins (Ophs) are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A-W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR) cells and cancer stem cells (CSCs). Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure-activity relationship to lay the foundation for the future developments and applications of these promising molecules.

  20. A Tryptoline Ring-Distortion Strategy Leads to Complex and Diverse Biologically Active Molecules from the Indole Alkaloid Yohimbine.

    Science.gov (United States)

    Paciaroni, Nicholas G; Ratnayake, Ranjala; Matthews, James H; Norwood, Verrill M; Arnold, Austin C; Dang, Long H; Luesch, Hendrik; Huigens, Robert W

    2017-03-28

    High-throughput screening (HTS) is the primary driver to current drug-discovery efforts. New therapeutic agents that enter the market are a direct reflection of the structurally simple compounds that make up screening libraries. Unlike medically relevant natural products (e.g., morphine), small molecules currently being screened have a low fraction of sp 3 character and few, if any, stereogenic centers. Although simple compounds have been useful in drugging certain biological targets (e.g., protein kinases), more sophisticated targets (e.g., transcription factors) have largely evaded the discovery of new clinical agents from screening collections. Herein, a tryptoline ring-distortion strategy is described that enables the rapid synthesis of 70 complex and diverse compounds from yohimbine (1); an indole alkaloid. The compounds that were synthesized had architecturally complex and unique scaffolds, unlike 1 and other scaffolds. These compounds were subjected to phenotypic screens and reporter gene assays, leading to the identification of new compounds that possessed various biological activities, including antiproliferative activities against cancer cells with functional hypoxia-inducible factors, nitric oxide inhibition, and inhibition and activation of the antioxidant response element. This tryptoline ring-distortion strategy can begin to address diversity problems in screening libraries, while occupying biologically relevant chemical space in areas critical to human health. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Surface functionalization of bioactive glasses with natural molecules of biological significance, Part I: Gallic acid as model molecule

    Science.gov (United States)

    Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

    2013-12-01

    Gallic acid (3,4,5-trihydroxybenzoic acid, GA) and its derivatives are a group of biomolecules (polyphenols) obtained from plants. They have effects which are potentially beneficial to heath, for example they are antioxidant, anticarcinogenic and antibacterial, as recently investigated in many fields such as medicine, food and plant sciences. The main drawbacks of these molecules are both low stability and bioavailability. In this research work the opportunity to graft GA to bioactive glasses is investigated, in order to deliver the undamaged biological molecule into the body, using the biomaterial surfaces as a localized carrier. GA was considered for functionalization since it is a good model molecule for polyphenols and presents several interesting biological activities, like antibacterial, antioxidant and anticarcinogenic properties. Two different silica based bioactive glasses (SCNA and CEL2), with different reactivity, were employed as substrates. UV photometry combined with the Folin&Ciocalteu reagent was adopted to test the concentration of GA in uptake solution after functionalization. This test verified how much GA consumption occurred with surface modification and it was also used on solid samples to test the presence of GA on functionalized glasses. XPS and SEM-EDS techniques were employed to characterize the modification of material surface properties and functional group composition before and after functionalization.

  2. Effect of gamma irradiation on biological activity of thyrotropin

    Energy Technology Data Exchange (ETDEWEB)

    Strbak, V; Macho, L; Sedlak, J; Hromadova, M

    1976-03-01

    The biological activity of thyrotropin (TSH) was tested after sterilization by 0.5 and 12.5 Mrad of gamma irradiation. It was found that the biological activity (McKenzie's assay) of TSH irradiated in dry state was not affected during the first month after sterilization by doses of 0.5 and 2.5 Mrad. However, substantial decrease of TSH biological activity was observed 3 to 5 months after the irradiation, the lower activity being after the former dose. The irradiation of TSH by 12.5 Mrad in dry state and by 0.5 and 2.5 Mrad in solution resulted in a decrease of biological activity already during first month. The structural changes in the molecule of TSH were apparently not very extensive, since a decrease of disulfide bonds from 0.96 to 0.77 M per 1M of TSH was found immediately after the irradiation, while uv absorbancy and electrophoretic mobility on polyacrylamide gel electrophoresis were unaffected. These changes were followed by the decrease of TSH stability during storage in dry state. It is hypothesized that TSH molecule may be affected in ..beta.. subunit or in its connection with ..cap alpha...

  3. Effect of gamma irradiation on biological activity of thyrotropin

    International Nuclear Information System (INIS)

    Strbak, V.; Macho, L.; Sedlak, J.; Hromadova, M.

    1976-01-01

    The biological activity of thyrotropin (TSH) was tested after sterilization by 0.5 and 12.5 Mrad of gamma radiation. It was found that the biological activity (McKenzie's assay) of TSH irradiated in dry state was not affected during the first month after sterilization by doses of 0.5 and 2.5 Mrad. However, substantial decrease of TSH biological activity was observed 3 to 5 months after the irradiation, the lower activity after the 0.5 Mrad dose. The irradiation of TSH by 12.5 Mrad in dry state and by 0.5 and 2.5 Mrad in solution resulted in decreased biological activity already during the first month. The structural changes in the TSH molecule were apparently not very extensive, as a decrease of disulfide bonds from 0.96 to 0.77 M per 1 M of TSH was found immediately after the irradiation, while UV absorbancy and electrophoretic mobility on polyacrylamide gel electrophoresis were unaffected. These changes were followed by a decrease of TSH stability during storage in dry state. It is hypothesized that a TSH molecule may be affected in a β subunit or in its connection with α. (author)

  4. Nano- and micro-fabrication for single-molecule biological studies

    NARCIS (Netherlands)

    Huang, Z.

    2012-01-01

    Heterogeneity is a general feature in biological system. In order to avoid possible misleading effects of ensemble averaging, and to ensure a correct understanding of the biological system, it is very important to look into individuals, such as a single bio-molecule or a single cell, for details.

  5. Electrochemically etched nanoporous silicon membrane for separation of biological molecules in mixture

    Science.gov (United States)

    Burham, Norhafizah; Azlan Hamzah, Azrul; Yunas, Jumril; Yeop Majlis, Burhanuddin

    2017-07-01

    This paper presents a technique for separating biological molecules in mixture using nanoporous silicon membrane. Nanopores were formed using electrochemical etching process (ECE) by etching a prefabricated silicon membrane in hydrofluoric acid (HF) and ethanol, and then directly bonding it with PDMS to form a complete filtration system for separating biological molecules. Tygon S3™ tubings were used as fluid interconnection between PDMS molds and silicon membrane during testing. Electrochemical etching parameters were manipulated to control pore structure and size. In this work, nanopores with sizes of less than 50 nm, embedded on top of columnar structures have been fabricated using high current densities and variable HF concentrations. Zinc oxide was diluted with deionized (DI) water and mixed with biological molecules and non-biological particles, namely protein standard, serum albumin and sodium chloride. Zinc oxide particles were trapped on the nanoporous silicon surface, while biological molecules of sizes up to 12 nm penetrated the nanoporous silicon membrane. The filtered particles were inspected using a Zetasizer Nano SP for particle size measurement and count. The Zetasizer Nano SP results revealed that more than 95% of the biological molecules in the mixture were filtered out by the nanoporous silicon membrane. The nanoporous silicon membrane fabricated in this work is integratable into bio-MEMS and Lab-on-Chip components to separate two or more types of biomolecules at once. The membrane is especially useful for the development of artificial kidney.

  6. A semantic web ontology for small molecules and their biological targets.

    Science.gov (United States)

    Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

    2010-05-24

    A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

  7. Applications of Engineered DNA-Binding Molecules Such as TAL Proteins and the CRISPR/Cas System in Biology Research

    Directory of Open Access Journals (Sweden)

    Toshitsugu Fujita

    2015-09-01

    Full Text Available Engineered DNA-binding molecules such as transcription activator-like effector (TAL or TALE proteins and the clustered regularly interspaced short palindromic repeats (CRISPR and CRISPR-associated proteins (Cas (CRISPR/Cas system have been used extensively for genome editing in cells of various types and species. The sequence-specific DNA-binding activities of these engineered DNA-binding molecules can also be utilized for other purposes, such as transcriptional activation, transcriptional repression, chromatin modification, visualization of genomic regions, and isolation of chromatin in a locus-specific manner. In this review, we describe applications of these engineered DNA-binding molecules for biological purposes other than genome editing.

  8. Parameters of biological activity in colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Š.; Topolčan, O.; Holubec jr., L.; Levý, M.; Pecen, Ladislav; Svačina, Š.

    2011-01-01

    Roč. 31, č. 1 (2011), s. 373-378 ISSN 0250-7005 Institutional research plan: CEZ:AV0Z10300504 Keywords : colorectal cancer * biological activity * prognosis * tumor markers * angiogenetic factors * metalloproteinases * adhesion molecules Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011

  9. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

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

  10. Suppression and enhancement of non-native molecules within biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E.A. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)]. E-mail: e.jones@postgrad.manchester.ac.uk; Lockyer, N.P. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom); Vickerman, J.C. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)

    2006-07-30

    With the aim of evaluating the potential of SIMS to provide molecular information from small molecules within biological systems, here we investigate the effect of different biological compounds as they act as matrices. The results highlight the fact that the chemical environment of a molecule can have a significant effect on its limit of detection. This has implications for the imaging of drugs and xenobiotics in tissue sections and other biological matrices. A 1:1 mixture of the organic acid 2,4,6-trihydroxyacetophenone and the dipeptide valine-valine demonstrates that almost complete suppression of the [M + H]{sup +} ion of one compound can be caused by the presence of a compound of higher proton affinity. The significance of this is highlighted when two similar drug molecules, atropine (a neutral molecule) and ipratropium bromide (a quaternary nitrogen containing salt) are mixed with brain homogenate. The atropine [M + H]{sup +} ion shows significant suppression whilst the [M - Br]{sup +} of ipratopium bromide is detected at an intensity that can be rationalised by its decreased surface concentration. By investigating the effect of two abundant tissue lipids, cholesterol and dipalmitoylphosphatidyl choline (DPPC), on the atropine [M + H]{sup +} signal detected in mixtures with these lipids we see that the DPPC has a strong suppressing effect, which may be attributed to gas phase proton transfer.

  11. Coinhibitory molecules in cancer biology and therapy.

    Science.gov (United States)

    Mocellin, Simone; Benna, Clara; Pilati, Pierluigi

    2013-04-01

    The adaptive immune response is controlled by checkpoints represented by coinhibitory molecules, which are crucial for maintaining self-tolerance and minimizing collateral tissue damage under physiological conditions. A growing body of preclinical evidence supports the hypothesis that unleashing this immunological break might be therapeutically beneficial in the fight against cancer, as it would elicit an effective antitumor immune response. Remarkably, recent clinical trials have demonstrated that this novel strategy can be highly effective in the treatment of patients with cancer, as shown by the paradigmatic case of ipilimumab (a monoclonal antibody blocking the coinhibitory molecule cytotoxic T lymphocyte associated antigen-4 [CTLA4]) that is opening a new era in the therapeutic approach to a chemoresistant tumor such as cutaneous melanoma. In this review we summarize the biology of coinhibitory molecules, overview the experimental and clinical attempts to interfere with these immune checkpoints to treat cancer and critically discuss the challenges posed by such a promising antitumor modality. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-06-01

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

  13. SINGLE MOLECULE APPROACHES TO BIOLOGY, 2010 GORDON RESEARCH CONFERENCE, JUNE 27-JULY 2, 2010, ITALY

    Energy Technology Data Exchange (ETDEWEB)

    Professor William Moerner

    2010-07-09

    The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together, and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site in

  14. Single molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update

    Science.gov (United States)

    Widom, Julia R.; Dhakal, Soma; Heinicke, Laurie A.; Walter, Nils G.

    2015-01-01

    Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution, and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy. PMID:25212907

  15. "Life-bearing molecules" versus "life-embodying systems": Two contrasting views on the what-is-life (WIL) problem persisting from the early days of molecular biology to the post-genomic cell- and organism-level biology.

    Science.gov (United States)

    Sato, Naoki

    2018-05-01

    "What is life?" is an ultimate biological quest for the principle that makes organisms alive. This 'WIL problem' is not, however, a simple one that we have a straightforward strategy to attack. From the beginning, molecular biology tried to identify molecules that bear the essence of life: the double helical DNA represented replication, and enzymes were micro-actuators of biological activities. A dominating idea behind these mainstream biological studies relies on the identification of life-bearing molecules, which themselves are models of life. Another, prevalent idea emphasizes that life resides in the whole system of an organism, but not in some particular molecules. The behavior of a complex system may be considered to embody the essence of life. The thermodynamic view of life system in the early 20th century was remodeled as physics of complex systems and systems biology. The two views contrast with each other, but they are no longer heritage of the historical dualism in biology, such as mechanism/materialism versus vitalism, or reductionism versus holism. These two views are both materialistic and mechanistic, and act as driving forces of modern biology. In reality, molecules function in a context of systems, whereas systems presuppose functional molecules. A key notion to reconcile this conflict is that subjects of biological studies are given before we start to study them. Cell- or organism-level biology is destined to the dialectic of molecules and systems, but this antagonism can be resolved by dynamic thinking involving biological evolution. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Experimental and Computational Characterization of Biological Liquid Crystals: A Review of Single-Molecule Bioassays

    Directory of Open Access Journals (Sweden)

    Sungsoo Na

    2009-09-01

    Full Text Available Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins.

  17. Summary of diamino pyrazoles derived and study their biological activities

    International Nuclear Information System (INIS)

    Hagui, Marwa

    2016-01-01

    The work involves the synthesis of new heterocyclic structures diamino pyrazoles derivatives that are present in many natural products and products of pharmacological and therapeutic interests and study their biological activities. In order to develop a radiotracer interest and use in diagnostic nuclear medicine, we are interested to synthesis a pyrazole derivative with the precursor [Re(CO)5Br] and studying the antibacterial and antifungal activity of 3.5-diamino pyrazole and even thioamide complex rhenium. The objectives of our workout: 1/ Synthesis of molecules 3,5-diamino pyrazole and thioamide. 2/ Synthesis of 3,5-diamino pyrazole-rhenium complex. 3/ The in vitro study: Bacteriological Tests (Study of antibacterial and antifungal activity of 3,5-diamino pyrazole and thioamide). The first part of this work concerns the chemical synthesis of molecules such as: thioamide, Amp z1 Ampz2 and then we had synthesized the complex 3,5-diamino pyrazole-rhenium. Similarly we determined the physicochemical characteristics of the compounds synthesized by CLHP, CCM and RMN ( 1 H, 13 C). The second part is devoted to the study in vitro of biological activities of the synthesized molecules and complex 3,5 diaminopyrazole-rhenium with concentration 1 mg/mL and 2 mg/mL. The results allow us to say that the thioamide and Ampz2 have antibacterial activity against S. enterica and Ampz2 has low activity against S. aureus and P. aeruginossa. Other pyrazole derivatives have no significant antibacterial and antifungal activity. The results also show that the synthesized compounds of concentration 2 mg/mL in relation to the inhibition zones of amoxicillin and DMSO: 1/ Escherichia coli, there is antibacterial activity for thioamide, and the Amp z1-Re Ampz2 compound. 2/ Staphylococcus aureus, the complex Ampz 1-Re and the thioamide have significant antibacterial activity. 3/ Salmonella, we observe that the thioamide molecules, Ampz2 and Amp z1-Re have significant antibacterial activity

  18. Role of Muramyl Dipeptide in Lipopolysaccharide-Mediated Biological Activity and Osteoclast Activity

    Directory of Open Access Journals (Sweden)

    Hideki Kitaura

    2018-01-01

    Full Text Available Lipopolysaccharide (LPS is an endotoxin and bacterial cell wall component that is capable of inducing inflammation and immunological activity. Muramyl dipeptide (MDP, the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is another inflammation-inducing molecule that is ubiquitously expressed by bacteria. Several studies have shown that inflammation-related biological activities were synergistically induced by interactions between LPS and MDP. MDP synergistically enhances production of proinflammatory cytokines that are induced by LPS exposure. Injection of MDP induces lethal shock in mice challenged with LPS. LPS also induces osteoclast formation and pathological bone resorption; MDP enhances LPS induction of both processes. Furthermore, MDP enhances the LPS-induced receptor activator of NF-κB ligand (RANKL expression and toll-like receptor 4 (TLR4 expression both in vivo and in vitro. Additionally, MDP enhances LPS-induced mitogen-activated protein kinase (MAPK signaling in stromal cells. Taken together, these findings suggest that MDP plays an important role in LPS-induced biological activities. This review discusses the role of MDP in LPS-mediated biological activities, primarily in relation to osteoclastogenesis.

  19. Biologically Active Macrocyclic Compounds – from Natural Products to Diversity‐Oriented Synthesis

    DEFF Research Database (Denmark)

    Madsen, Charlotte Marie; Clausen, Mads Hartvig

    2011-01-01

    Macrocyclic compounds are attractive targets when searching for molecules with biological activity. The interest in this compound class is increasing, which has led to a variety of methods for tackling the difficult macrocyclization step in their synthesis. This microreview highlights some recent...... developments in the synthesis of macrocycles, with an emphasis on chemistry developed to generate libraries of putative biologically active compounds....

  20. Expedient construction of small molecule macroarrays via sequential palladium- and copper-mediated reactions and their ex situ biological testing.

    Science.gov (United States)

    Frei, Reto; Breitbach, Anthony S; Blackwell, Helen E

    2012-05-01

    We report the highly efficient syntheses of a series of focused libraries in the small molecule macroarray format using Suzuki-Miyaura and copper-catalyzed azide-alkyne cycloaddition (or "click") reactions. The libraries were based on stilbene and triazole scaffolds, which are known to have a broad range of biological activities, including quorum-sensing (QS) modulation in bacteria. The library products were generated in parallel on the macroarray in extremely short reaction times (~10-20 min) and isolated in excellent purities. Biological testing of one macroarray library post-cleavage (ex situ) revealed several potent agonists of the QS receptor, LuxR, in Vibrio fischeri. These synthetic agonists, in contrast to others that we have reported, were only active in the presence of the native QS signal in V. fischeri, which is suggestive of a different mode of activity. Notably, the results presented herein showcase the ready compatibility of the macroarray platform with chemical reactions that are commonly utilized in small molecule probe and drug discovery today. As such, this work serves to expand the utility of the small molecule macroarray as a rapid and operationally straightforward approach toward the synthesis and screening of bioactive agents.

  1. Bone regeneration with biomaterials and active molecules delivery.

    Science.gov (United States)

    D' Este, Matteo; Eglin, David; Alini, Mauro; Kyllonen, Laura

    2015-01-01

    The combination of biomaterials and drug delivery strategies is a promising avenue towards improved synthetic bone substitutes. With the delivery of active species biomaterials can be provided with the bioactivity they still lack for improved bone regeneration. Recently, a lot of research efforts have been put towards this direction. Biomaterials for bone regeneration have been supplemented with small or biological molecules for improved osteoprogenitor cell recruitment, osteoinductivity, anabolic or angiogenic response, regulation of bone metabolism and others. The scope of this review is to summarize the most recent results in this field.

  2. Novel nuclear magnetic resonance techniques for studying biological molecules

    International Nuclear Information System (INIS)

    Laws, David D.

    2000-01-01

    Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. In this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone (φ/ψ) dihedral angles by comparing experimentally determined 13 C a , chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of α-helical and β-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly β-sheet.

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

    DEFF Research Database (Denmark)

    Owens, T; Zeine, R

    1989-01-01

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

  4. Maleimide-activated aryl diazonium salts for electrode surface functionalization with biological and redox-active molecules.

    Science.gov (United States)

    Harper, Jason C; Polsky, Ronen; Wheeler, David R; Brozik, Susan M

    2008-03-04

    A versatile and simple method is introduced for formation of maleimide-functionalized surfaces using maleimide-activated aryl diazonium salts. We show for the first time electrodeposition of N-(4-diazophenyl)maleimide tetrafluoroborate on gold and carbon electrodes which was characterized via voltammetry, grazing angle FTIR, and ellipsometry. Electrodeposition conditions were used to control film thickness and yielded submonolayer-to-multilayer grafting. The resulting phenylmaleimide surfaces served as effective coupling agents for electrode functionalization with ferrocene and the redox-active protein cytochrome c. The utility of phenylmaleimide diazonium toward formation of a diazonium-activated conjugate, followed by direct electrodeposition of the diazonium-modified DNA onto the electrode surface, was also demonstrated. Effective electron transfer was obtained between immobilized molecules and the electrodes. This novel application of N-phenylmaleimide diazonium may facilitate the development of bioelectronic devices including biofuel cells, biosensors, and DNA and protein microarrays.

  5. Periradicular Tissue Responses to Biologically Active Molecules or MTA When Applied in Furcal Perforation of Dogs' Teeth

    Directory of Open Access Journals (Sweden)

    Anna Zairi

    2012-01-01

    Full Text Available The aim of this study was the comparative evaluation of inflammatory reactions and tissue responses to four growth factors, or mineral trioxide aggregate (MTA, or a zinc-oxide-eugenol-based cement (IRM as controls, when used for the repair of furcal perforations in dogs’ teeth. Results showed significantly higher inflammatory cell response in the transforming growth factorβ1 (TGFβ1 and zinc-oxide-eugenol-based cement (IRM groups and higher rates of epithelial proliferation in the TGFβ1, basic fibroblast growth factor (bFGF, and insulin growth factor-I (IGF-I groups compared to the MTA. Significantly higher rates of bone formation were found in the control groups compared to the osteogenic protein-1 (OP-1. Significantly higher rates of cementum formation were observed in the IGF-I and bFGF groups compared to the IRM. None of the biologically active molecules can be suggested for repairing furcal perforations, despite the fact that growth factors exerted a clear stimulatory effect on cementum formation and inhibited collagen capsule formation. MTA exhibited better results than the growth factors.

  6. A Review on Phytoconstituents and Biological activities of Cuscuta species.

    Science.gov (United States)

    Ahmad, Ateeque; Tandon, Sudeep; Xuan, Tran Dang; Nooreen, Zulfa

    2017-08-01

    The genus Cuscuta belonging to the Cuscutaceae family comprises of about 100-170 species spread around the world. Although several species have been studied for their phytochemical characterization and biological activities but still many species are yet unexplored till date. Cuscuta are parasitic plants generally of yellow, orange, red or rarely green color. The Cuscuta species were reported rich in flavonoid and glycosidic constituents along with alkaloids, fatty acids, fixed oil, minerals, essential oil and others phytomolecules also etc. Flavonoids and other molecules of Cuscuta species were reported for different types of biological activities such as antiproliferative activity, antioxidant activity, anti-inflammatory, hepatoprotective, antimicrobial and anxiolytic activity, while some other flavonoids have exhibited potential antiviral and anticancer especially in ovarian and breast cancer activities. This review is an attempt to compile all the available data for the 24 different of Cuscuta species on the basis of different types of phytochemical constituents and biological studies as above. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Single molecules and nanotechnology

    CERN Document Server

    Vogel, Horst

    2007-01-01

    This book focuses on recent advances in the rapidly evolving field of single molecule research. These advances are of importance for the investigation of biopolymers and cellular biochemical reactions, and are essential to the development of quantitative biology. Written by leading experts in the field, the articles cover a broad range of topics, including: quantum photonics of organic dyes and inorganic nanoparticles their use in detecting properties of single molecules the monitoring of single molecule (enzymatic) reactions single protein (un)folding in nanometer-sized confined volumes the dynamics of molecular interactions in biological cells The book is written for advanced students and scientists who wish to survey the concepts, techniques and results of single molecule research and assess them for their own scientific activities.

  8. Liposomal packaging generates Wnt protein with in vivo biological activity.

    Directory of Open Access Journals (Sweden)

    Nathan T Morrell

    2008-08-01

    Full Text Available Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.

  9. Novel nuclear magnetic resonance techniques for studying biological molecules

    Energy Technology Data Exchange (ETDEWEB)

    Laws, David Douglas [Univ. of California, Berkeley, CA (United States)

    2000-06-01

    Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. In this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone (Φ/Ψ) dihedral angles by comparing experimentally determined 13Ca, chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of α-helical and β-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly β-sheet.

  10. Mass amplifying probe for sensitive fluorescence anisotropy detection of small molecules in complex biological samples.

    Science.gov (United States)

    Cui, Liang; Zou, Yuan; Lin, Ninghang; Zhu, Zhi; Jenkins, Gareth; Yang, Chaoyong James

    2012-07-03

    Fluorescence anisotropy (FA) is a reliable and excellent choice for fluorescence sensing. One of the key factors influencing the FA value for any molecule is the molar mass of the molecule being measured. As a result, the FA method with functional nucleic acid aptamers has been limited to macromolecules such as proteins and is generally not applicable for the analysis of small molecules because their molecular masses are relatively too small to produce observable FA value changes. We report here a molecular mass amplifying strategy to construct anisotropy aptamer probes for small molecules. The probe is designed in such a way that only when a target molecule binds to the probe does it activate its binding ability to an anisotropy amplifier (a high molecular mass molecule such as protein), thus significantly increasing the molecular mass and FA value of the probe/target complex. Specifically, a mass amplifying probe (MAP) consists of a targeting aptamer domain against a target molecule and molecular mass amplifying aptamer domain for the amplifier protein. The probe is initially rendered inactive by a small blocking strand partially complementary to both target aptamer and amplifier protein aptamer so that the mass amplifying aptamer domain would not bind to the amplifier protein unless the probe has been activated by the target. In this way, we prepared two probes that constitute a target (ATP and cocaine respectively) aptamer, a thrombin (as the mass amplifier) aptamer, and a fluorophore. Both probes worked well against their corresponding small molecule targets, and the detection limits for ATP and cocaine were 0.5 μM and 0.8 μM, respectively. More importantly, because FA is less affected by environmental interferences, ATP in cell media and cocaine in urine were directly detected without any tedious sample pretreatment. Our results established that our molecular mass amplifying strategy can be used to design aptamer probes for rapid, sensitive, and selective

  11. Single Molecule Fluorescence: from Physical Fascination to Biological Relevance

    OpenAIRE

    Segers-Nolten, Gezina M.J.

    2003-01-01

    Confocal fluorescence microscopy is particularly well-known from the beautiful images that have been obtained with this technique from cells. Several cellular components could be nicely visualized simultaneously by staining them with different fluorophores. Not only for ensemble applications but also in single molecule research confocal fluorescence microscopy became a popular technique. In this thesis the possibilities are shown to study a complicated biological process, which is Nucleotide ...

  12. Biological compost stability influences odor molecules production measured by electronic nose during food-waste high-rate composting

    International Nuclear Information System (INIS)

    D'Imporzano, Giuliana; Crivelli, Fernando; Adani, Fabrizio

    2008-01-01

    Composting is a technique that is used to convert organic waste into agriculturally useful products. Composting is an aerobic, solid-state biological process, which typically can be divided into two phases, a high-rate composting phase and a curing phase. High-rate composting plays an important role during the composting process, owing to the high microbial activity occurring during this phase. It requires an accurate plant design to prevent the formation of anaerobic conditions and odors. The formation of anaerobic conditions mainly depends on the rate of O 2 consumption needed to degrade the substrate, i.e., the biological stability of the substrate. In this study, we investigated the relationship between the biological activity, measured by the dynamic respiration index (DRI) and the odor molecules production, measured by an electronic nose (EN) during two food-waste high-rate composting processes. Although the O 2 concentration in the biomass free air space (FAS) was kept optimal (O 2 > 140 ml l -1 , v/v) during composting, strong anaerobic conditions developed. This was indicated by the high levels of sulfur compounds, methane, and hydrogen in the outlet air stream. Both the high level of O 2 consumption, needed to degrade the high-degradable water-soluble organic matter and the low water O 2 solubility, caused by high temperature reached in this stage (up to 60 deg. C), led to the anaerobic conditions observed in the biofilm-particle level. The application of the partial least square (PLS) analysis demonstrated a good regression between the DRI and the odor molecules produced that was detected by the EN (R 2 = 0.991; R 2 CV = 0.990), signifying the usefulness of the DRI as a parameter to estimate the potential production of odor molecules of the biomass

  13. Biomimetic Nanoarchitectures for the Study of T Cell Activation with Single-Molecule Control

    Science.gov (United States)

    Cai, Haogang

    Physical factors in the environment of a cell affect its function and behavior in a variety of ways. There is increasing evidence that, among these factors, the geometric arrangement of receptor ligands plays an important role in setting the conditions for critical cellular processes. The goal of this thesis is to develop new techniques for probing the role of extracellular ligand geometry, with a focus on T cell activation. In this work, top-down molecular-scale nanofabrication and bottom-up selective self-assembly were combined in order to present functional nanomaterials (primarily biomolecules) on a surface with precise spatial control and single-molecule resolution. Such biomolecule nanoarrays are becoming an increasingly important tool in surface-based in vitro assays for biosensing, molecular and cellular studies. The nanoarrays consist of metallic nanodots patterned on glass coverslips using electron beam and nanoimprint lithography, combined with self-aligned pattern transfer. The nanodots were then used as anchors for the immobilization of biological ligands, and backfilled with a protein-repellent passivation layer of polyethylene glycol. The passivation efficiency was improved to minimize nonspecific adsorption. In order to ensure true single-molecule control, we developed an on-chip protocol to measure the molecular occupancy of nanodot arrays based on fluorescence photobleaching, while accounting for quenching effects by plasmonic absorption. We found that the molecular occupancy can be interpreted as a packing problem, with the solution depending on the nanodot size and the concentration of self-assembly reagents, where the latter can be easily adjusted to control the molecular occupancy according to the dot size. The optimized nanoarrays were used as biomimetic architectures for the study of T cell activation with single-molecule control. T cell activation involves an elaborate arrangement of signaling, adhesion, and costimulatory molecules

  14. Investigating organic molecules responsible of auxin-like activity of humic acid fraction extracted from vermicompost

    Energy Technology Data Exchange (ETDEWEB)

    Scaglia, Barbara, E-mail: barbara.scaglia@unimi.it [Gruppo Ricicla Labs – DiSAA, Università degli Studi di Milano, Via Celoria 2 (Italy); Nunes, Ramom Rachide; Rezende, Maria Olímpia Oliveira [Laboratório de Química Ambiental, Universidade de São Paulo, Instituto de Química de São Carlos, Avenida Trabalhador São Carlense, 400, São Carlos (Brazil); Tambone, Fulvia [Gruppo Ricicla Labs – DiSAA, Università degli Studi di Milano, Via Celoria 2 (Italy); Adani, Fabrizio, E-mail: fabrizio.adani@unimi.it [Gruppo Ricicla Labs – DiSAA, Università degli Studi di Milano, Via Celoria 2 (Italy)

    2016-08-15

    This work studied the auxin-like activity of humic acids (HA) obtained from vermicomposts produced using leather wastes plus cattle dung at different maturation stages (fresh, stable and mature). Bioassays were performed by testing HA concentrations in the range of 100–6000 mg carbon L{sup −1}. {sup 13}C CPMAS-NMR and GC–MS instrumental methods were used to assess the effect of biological processes and starting organic mixtures on HA composition. Not all HAs showed IAA-like activity and in general, IAA-like activity increased with the length of the vermicomposting process. The presence of leather wastes was not necessary to produce the auxin-like activity of HA, since HA extracted from a mix of cattle manure and sawdust, where no leather waste was added, showed IAA-like activity as well. CPMAS {sup 13}CNMR revealed that HAs were similar independently of the mix used and that the humification process involved the increasing concentration of pre-existing alkali soluble fractions in the biomass. GC/MS allowed the identification of the molecules involved in IAA-like effects: carboxylic acids and amino acids. The concentration of active molecules, rather than their simple presence in HA, determined the bio-stimulating effect, and a good linear regression between auxin-like activity and active stimulating molecules concentration was found (R{sup 2} = − 0.85; p < 0.01, n = 6). - Highlights: • Vermicomposting converts waste into organic fertilizer. • Vermicomposts can have biostimulating effect for the presence of hormone-like molecules. • Auxine-like activity was associated to the vermicompost humic acid fraction (HA). • HA carboxylic acids and amino acids, were reported to act as auxin-like molecules. • A linear regression was found between molecules and auxin-like activity.

  15. Single-Molecule Sensing with Nanopore Confinement: from Chemical Reactions to Biological Interactions.

    Science.gov (United States)

    Lin, Yao; Ying, Yi-Lun; Gao, Rui; Long, Yi-Tao

    2018-03-25

    The nanopore can generate an electrochemical confinement for single-molecule sensing which help understand the fundamental chemical principle in nanoscale dimensions. By observing the generated ionic current, individual bond-making and bond-breaking steps, single biomolecule dynamic conformational changes and electron transfer processes that occur within pore can be monitored with high temporal and current resolution. These single-molecule studies in nanopore confinement are revealing information about the fundamental chemical and biological processes that cannot be extracted from ensemble measurements. In this concept, we introduce and discuss the electrochemical confinement effects on single-molecule covalent reactions, conformational dynamics of individual molecules and host-guest interactions in protein nanopores. Then, we extend the concept of nanopore confinement effects to confine electrochemical redox reactions in solid-state nanopores for developing new sensing mechanisms. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Protein-based nanostructures as carriers for photo-physically active molecules in biosystems

    OpenAIRE

    Delcanale, Pietro

    2017-01-01

    In nature, many proteins function as carriers, being able to bind, transport and possibly release a ligand within a biological system. Protein-based carriers are interesting systems for drug delivery, with the remarkable advantage of being water-soluble and, as inherent components of biosystems, highly bio-compatible. This work focuses on the use of protein-based carriers for the delivery of hydrophobic photo-physically active molecules, whose structure and chemical properties lead to spontan...

  17. Assigned and unassigned distance geometry: applications to biological molecules and nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Billinge, Simon J. L. [Columbia Univ., New York, NY (United States). Applied Physics and Applied Mathematics; Brookhaven National Lab. (BNL), Upton, NY (United States). X-ray Scattering Group; Duxbury, Phillip M. [Michigan State Univ., East Lansing, MI (United States). Dept. of Physics and Astronomy; Gonçalves, Douglas S. [Univ. Federal de Santa Catarina,; Lavor, Carlile [Univ. of Campinas (UNICAMP), Sao Paulo (Brazil). Dept. of Applied Mathematics (IMECC-UNICAMP); Mucherino, Antonio [Univ. de Rennes, Rennes (France). Institut de Recherche en Informatique et Systemes Aleatoires

    2016-04-04

    Here, considering geometry based on the concept of distance, the results found by Menger and Blumenthal originated a body of knowledge called distance geometry. This survey covers some recent developments for assigned and unassigned distance geometry and focuses on two main applications: determination of three-dimensional conformations of biological molecules and nanostructures.

  18. Synthesis, Physical Characterization and Biological Activity of Some Schiff Base Complexes

    Directory of Open Access Journals (Sweden)

    R. Rajavel

    2008-01-01

    Full Text Available Structural modification of organic molecule has considerable biological relevance. Further, coordination of a biomolecules to the metal ions significantly alters the effectiveness of the biomolecules. In view of the antimicrobial activity ligand [bis-(2-aminobenzaldehyde] malonoyl dihydrazone], metal complexes with Cu(II, Ni(II, Zn(II and oxovanadium(IV have been synthesized and found to be potential antimicrobial agents. An attempt is also made to correlate the biological activities with geometry of the complexes. The complexes have been characterized by elemental analysis, molar conductance, spectra and cyclicvoltammetric measurements. The structural assessment of the complexes has been carried out based on electronic, infrared and molar conductivity values.

  19. Study of radionuclides speciation with biological molecules of interest by spectrometric techniques

    International Nuclear Information System (INIS)

    Lourenco, V.

    2007-07-01

    Mechanisms of complexation and accumulation of the radionuclides at the cellular and molecular level are complex and poorly known because the studies on these subjects are scarce. Within the framework of this thesis, we studied the interactions of these cations with biological molecules of interest. We chose to focus on an actinide: uranium (VI) as well as europium as an analogue of trivalent actinides. The selected biological molecules are the phyto-chelatins: their role is to protect cells against intrusions from nonessential heavy metals (thus toxic). These proteins are likely to be implied in the mechanisms of sequestration of radionuclides in living organisms. However, their structure is complex, this is why, in order to better include/understand their reactivity, we extended our studies to lower entities which constitute them (amino acid: glycine, glutamic acid and cysteine; polypeptides: glutathione reduced and oxidized forms). In particular, we determined solution speciation (stoichiometry, structure) as well as the complexing constants associated with the formation with these species. These studies were undertaken by Time Resolved Laser induced Fluorescence (TRLIF), Electro-Spray-Mass Spectrometry (ES-MS), Nuclear Magnetic Resonance (NMR), Fourier Transform Infra-Rouge spectroscopy (FTIR) and Extended X-ray Absorption Fine Structure Spectroscopy (EXAFS).The determination of the complexation constants enabled us to conclude that the complexing capacity of these molecules with respect to radionuclides was moderate (log 10 K 1 ≤ 3, pH 3 or 6), the formed species are mononuclear with only one ligand molecule (1:1). The interaction is performed via oxygenated (hard) groups. The direct complexation of europium with phyto-chelatins at acidic pH was studied jointly by TRLIF and ES-MS. The complexing capacity of these molecules is much higher than that of GSH from which they result. The interaction of europium with metallothioneins is, on the contrary, lower than

  20. Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo

    Science.gov (United States)

    Ye, Deju; Shuhendler, Adam J.; Cui, Lina; Tong, Ling; Tee, Sui Seng; Tikhomirov, Grigory; Felsher, Dean W.; Rao, Jianghong

    2014-06-01

    Directed self-assembly of small molecules in living systems could enable a myriad of applications in biology and medicine, and already this has been used widely to synthesize supramolecules and nano/microstructures in solution and in living cells. However, controlling the self-assembly of synthetic small molecules in living animals is challenging because of the complex and dynamic in vivo physiological environment. Here we employ an optimized first-order bioorthogonal cyclization reaction to control the self-assembly of a fluorescent small molecule, and demonstrate its in vivo applicability by imaging caspase-3/7 activity in human tumour xenograft mouse models of chemotherapy. The fluorescent nanoparticles assembled in situ were imaged successfully in both apoptotic cells and tumour tissues using three-dimensional structured illumination microscopy. This strategy combines the advantages offered by small molecules with those of nanomaterials and should find widespread use for non-invasive imaging of enzyme activity in vivo.

  1. Deciphering the perturbation effect of urea on the supramolecular host-guest interaction of biologically active hydrophobic molecule inside the nanocavity of cyclodextrins

    Energy Technology Data Exchange (ETDEWEB)

    Maity, Banibrata; Chatterjee, Aninda; Ahmed, Sayeed Ashique; Seth, Debabrata, E-mail: debabrata@iitp.ac.in

    2017-03-15

    The present work articulates the supramolecular interaction and the formation of host-guest complex between the biologically active hydrophobic coumarin derivative and cyclodextrins by using several spectroscopic, calorimetric and microscopic techniques. All the studies clearly revealed that in presence of cyclodextrins (CDs), coumarin forms 1:1 stoichiometric complex. From all the study, we have found that with gradual increasing the cavity diameter of the hosts, the binding efficiency of the complexes gradually increases. The small population of the non emissive twisted intramolecular charge transfer (TICT) state of coumarin molecule turns into highly emissive in presence of γ-CD owing to its greater cavity diameter. The emissive TICT band is not found in β-CD complex due to its comparative small hydrophilic exterior and less polar environment. The present finding also interpret the perturbation effect of urea on host-guest complexes. In the presence of urea, the TICT emissive band of γ-CD is completely diminished. From, {sup 1}H NMR study it was observed that –NEt{sub 2} moiety of 7-DCCAE molecule is deeply buried inside the hydrophobic cavity of the CDs and forms host-guest complexes. Isothermal titration calorimetry measurement also indicates the formation of 1:1 host-guest complexes.

  2. Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities

    Directory of Open Access Journals (Sweden)

    Mireille Fouillaud

    2016-03-01

    Full Text Available Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi′s productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances.

  3. Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities.

    Science.gov (United States)

    Fouillaud, Mireille; Venkatachalam, Mekala; Girard-Valenciennes, Emmanuelle; Caro, Yanis; Dufossé, Laurent

    2016-03-25

    Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi's productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances.

  4. Biological response of HeLa cells to gold nanoparticles coated with organic molecules.

    Science.gov (United States)

    Cardoso Avila, P E; Rangel Mendoza, A; Pichardo Molina, J L; Flores Villavicencio, L L; Castruita Dominguez, J P; Chilakapati, M K; Sabanero Lopez, M

    2017-08-01

    In this work, gold nanospheres functionalized with low weight organic molecules (4-aminothiphenol and cysteamine) were synthesized in a one-step method for their in vitro cytotoxic evaluation on HeLa cells. To enhance the biocompatibility of the cysteamine-capped GNPs, BSA was used due to its broad PH stability and high binding affinity to gold nanoparticles. Besides, the widely reported silica coated gold nanorods were tested here to contrast their toxic response against our nanoparticles coated with organic molecules. Our results shown, the viability measured at 1.9×10 -5 M did not show significant differences against negative controls for all the samples; however, the metabolic activity of HeLa cells dropped when they were exposed to silica gold nanorods in the range of concentrations from 2.9×10 -7 M to 3.0×10 -4 M, while in the cases of gold nanospheres, we found that only at concentrations below 1.9×10 -5 M metabolic activity was normal. Our preliminary results did not indicate any perceivable harmful toxicity to cell membrane, cytoskeleton or nucleus due to our nanospheres at 1.9×10 -5 M. Additional test should be conducted in order to ensure a safe use of them for biological applications, and to determine the extent of possible damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. From Molecules to Living Organisms : an Interplay between Biology and Physics : Lecture Notes of the Les Houches School of Physics

    CERN Document Server

    Nury, Hughes; Parcy, François; Ruigrok, Rob W H; Ziegler, Christine; Cugliandolo, Leticia F; Session CII

    2016-01-01

    The aim of this book is to provide new ideas for studying living matter by a simultaneous understanding of behavior from molecules to the cell, to the whole organism in the light of physical concepts. Indeed, forces guide most biological phenomena. In some cases these forces can be well-described and thus used to model a particular biological phenomenon. This is exemplified here by the study of membranes, where their shapes and curvatures can be modeled using a limited number of parameters that are measured experimentally. The growth of plants is another example where the combination of physics, biology and mathematics leads to a predictive model. The laws of thermodynamics are essential, as they dictate the behavior of proteins, or more generally biological molecules, in an aqueous environment. Integrated studies from the molecule to a larger scale need a combination of cutting-edge approaches, such as the use of new X-ray sources, in-cell NMR, cryo-electron microscopy or single-molecule microscopy. Some are...

  6. Aspartate and glutamate mimetic structures in biologically active compounds.

    Science.gov (United States)

    Stefanic, Peter; Dolenc, Marija Sollner

    2004-04-01

    Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic side-chain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In the development of new biologically active compounds that possess the ability to modulate these processes, compounds offering the same type of interactions are being designed. Thus, using a peptidomimetic design approach, glutamate and aspartate mimetics are incorporated into the structure of final biologically active compounds. This review covers different bioisosteric replacements of carboxylic acid alone, as well as mimetics of the whole amino acid structure. Amino acid analogs presented include those with different distances between anionic moieties, and analogs with additional functional groups that result in conformational restriction or alternative interaction sites. The article also provides an overview of different cyclic structures, including various cycloalkane, bicyclic and heterocyclic analogs, that lead to conformational restriction. Higher di- and tripeptide mimetics in which carboxylic acid functionality is incorporated into larger molecules are also reviewed. In addition to the mimetic structures presented, emphasis in this article is placed on their steric and electronic properties. These mimetics constitute a useful pool of fragments in the design of new biologically active compounds, particularly in the field of RGD mimetics and excitatory amino acid agonists and antagonists.

  7. On the mechanism of biological activation by tritium.

    Science.gov (United States)

    Rozhko, T V; Badun, G A; Razzhivina, I A; Guseynov, O A; Guseynova, V E; Kudryasheva, N S

    2016-06-01

    The mechanism of biological activation by beta-emitting radionuclide tritium was studied. Luminous marine bacteria were used as a bioassay to monitor the biological effect of tritium with luminescence intensity as the physiological parameter tested. Two different types of tritium sources were used: HTO molecules distributed regularly in the surrounding aqueous medium, and a solid source with tritium atoms fixed on its surface (tritium-labeled films, 0.11, 0.28, 0.91, and 2.36 MBq/cm(2)). When using the tritium-labeled films, tritium penetration into the cells was prevented. The both types of tritium sources revealed similar changes in the bacterial luminescence kinetics: a delay period followed by bioluminescence activation. No monotonic dependences of bioluminescence activation efficiency on specific radioactivities of the films were found. A 15-day exposure to tritiated water (100 MBq/L) did not reveal mutations in bacterial DNA. The results obtained give preference to a "non-genomic" mechanism of bioluminescence activation by tritium. An activation of the intracellular bioluminescence process develops without penetration of tritium atoms into the cells and can be caused by intensification of trans-membrane cellular processes stimulated by ionization and radiolysis of aqueous media. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Single-molecule experiments in biological physics: methods and applications.

    Science.gov (United States)

    Ritort, F

    2006-08-16

    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

  9. Single-molecule experiments in biological physics: methods and applications

    International Nuclear Information System (INIS)

    Ritort, F

    2006-01-01

    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives. (topical review)

  10. Biologic role of activated leukocyte cell adhesion molecule overexpression in breast cancer cell lines and clinical tumor tissue.

    Science.gov (United States)

    Hein, Sibyll; Müller, Volkmar; Köhler, Nadine; Wikman, Harriet; Krenkel, Sylke; Streichert, Thomas; Schweizer, Michaela; Riethdorf, Sabine; Assmann, Volker; Ihnen, Maike; Beck, Katrin; Issa, Rana; Jänicke, Fritz; Pantel, Klaus; Milde-Langosch, Karin

    2011-09-01

    The activated leukocyte cell adhesion molecule (ALCAM) is overexpressed in many mammary tumors, but controversial results about its role and prognostic impact in breast cancer have been reported. Therefore, we evaluated the biologic effects of ALCAM expression in two breast cancer cell lines and a larger cohort of mammary carcinomas. By stable transfections, MCF7 cells with ALCAM overexpression and MDA-MB231 cells with reduced ALCAM levels were generated and analyzed in functional assays and cDNA microarrays. In addition, an immunohistochemical study on 347 patients with breast cancer with long-term follow-up and analysis of disseminated tumor cells (DTCs) was performed. In both cell lines, high ALCAM expression was associated with reduced cell motility. In addition, ALCAM silencing in MDA-MB231 cells resulted in lower invasive potential, whereas high ALCAM expression was associated with increased apoptosis in both cell lines. Among genes which were differentially expressed in clones with altered ALCAM expression, there was an overlap of 15 genes between both cell lines, among them cathepsin D, keratin 7, gelsolin, and ets2 whose deregulation was validated by western blot analysis. In MDA-MB231 cells, we observed a correlation with VEGF expression which was validated by enzyme-linked immuno sorbent assay (ELISA). Our IHC results on primary breast carcinomas showed that ALCAM expression was associated with an estrogen receptor-positive phenotype. In addition, strong ALCAM immunostaining correlated with nodal involvement and the presence of tumor cells in bone marrow. By Kaplan-Meier analysis, strong ALCAM expression in ductal carcinomas correlated with shorter recurrence-free intervals (P=0.048) and overall survival (OAS, P=0.003). Our results indicate that the biologic role of ALCAM in breast cancer is complex, but overexpression might be relevant for outcome in ductal carcinomas.

  11. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

    Directory of Open Access Journals (Sweden)

    Nocerino N

    2014-03-01

    Full Text Available Nunzia Nocerino,1 Andrea Fulgione,1 Marco Iannaccone,1 Laura Tomasetta,1 Flora Ianniello,1 Francesca Martora,1 Marco Lelli,2 Norberto Roveri,2 Federico Capuano,3 Rosanna Capparelli1 1Department of Agriculture Special Biotechnology Center Federico II, CeBIOTEC Biotechnology, University of Naples Federico II, Naples, 2Department of Chemistry, G Ciamician, Alma Mater Studiorum, University of Bologna, Bologna, 3Department of Food Inspection IZS ME, Naples, Italy Abstract: The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA. We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. Keywords: lactoferrin, hydroxyapatite nanocrystals, biomimetism, biological activity, drug delivery

  12. Adhesion molecules levels in blood correlate with MRI activity and clinical activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Millers, A.; Enina, G.; Platkajis, A.; Metra, M.; Kukaine, R.

    2002-01-01

    Research into pathogenesis of multiple sclerosis (MS) has prompted efforts to identify immunological markers associated with disease activity. Adhesion molecules ICAM-1 and VCAM-1 are associated with inflammatory mediated blood-brain barrier (BBB) dysfunction. In this study investigates the correlation between blood level of circulating ICAM-1 and VCAM-1 and magnetic resonance imaging (MRI) activity in different clinical phases of patients with MS. We show that RRMS and SPMS patients in clinically active phase with Gd-enhancing lesions in CNS had higher blood levels of cICAM-1 and cVCAM-1 compared these parameters levers of RRMS patients in remission stage. These results suggest that cICAM-1 and cVCAM-1 is a sensitive indicator of disease activity associated with BBB inflammatory dysfunction. Elevated blood level of cICAM-1 more strongly correlated with clinical activity and BBB damage, than cVCAM-1 and that could be used as biological marker of disease activity. Circulating VCAM-1 as an early indicator of BBB disturbance, may also serve as marker of beneficial activity in relapses phase of MS course. (authors)

  13. Study of radionuclides speciation with biological molecules of interest by spectrometric techniques

    International Nuclear Information System (INIS)

    Lourenco, V.

    2007-07-01

    Mechanisms of complexation and accumulation of the radionuclides at the cellular and molecular level are complex and poorly known because the studies on these subjects are scarce. Within the framework of this thesis, we studied the interactions of europium (analogue of trivalent actinides) and uranium (VI) (actinide) with biological molecules of interest: phyto-chelatins. Their role is to protect cells against intrusions from nonessential heavy metals (thus toxic). These proteins are likely to be implied in the mechanisms of sequestration of radionuclides in living organisms. However, their structure is complex, this is why, in order to better understand their reactivity, we extended our studies to lower entities which constitute them (amino acids and glutathione). We determined solution speciation (stoichiometry, structure) as well as the complexing constants associated with the formation of these species. These studies were undertaken by Time Resolved Laser induced Fluorescence (TRLIF), Electro-Spray Mass Spectrometry (ES-MS), Nuclear Magnetic Resonance (NMR), Fourier Transform Infra-Rouge spectroscopy (FTIR) and Extended X-ray Absorption Fine Structure Spectroscopy (EXAFS). The determination of the complexation constants enabled us to conclude that the complexing capacity of these molecules with respect to radionuclides was moderate (log 10 K 1 < 3, pH 3 or 6), the formed species are mononuclear with only one ligand molecule (1:1). The interaction is performed via oxygenated (hard) groups. The direct complexation of europium with phyto-chelatins at acidic pH was studied jointly by TRLIF and ES-MS. The complexing capacity of these molecules is much higher than that of GSH from which they result. In addition to studies undertaken on synthetic solutions reproducing the 'biological' conditions (pH close to neutrality, ionic strength 0.1 mol/L, etc), tests of cellular contamination were realized. The quantification of integrated europium showed that those are able to

  14. Biologic activity of the novel small molecule STAT3 inhibitor LLL12 against canine osteosarcoma cell lines

    Directory of Open Access Journals (Sweden)

    Couto Jason I

    2012-12-01

    Full Text Available Abstract Background STAT3 [1] has been shown to be dysregulated in nearly every major cancer, including osteosarcoma (OS. Constitutive activation of STAT3, via aberrant phosphorylation, leads to proliferation, cell survival and resistance to apoptosis. The present study sought to characterize the biologic activity of a novel allosteric STAT3 inhibitor, LLL12, in canine OS cell lines. Results We evaluated the effects of LLL12 treatment on 4 canine OS cell lines and found that LLL12 inhibited proliferation, induced apoptosis, reduced STAT3 phosphorylation, and decreased the expression of several transcriptional targets of STAT3 in these cells. Lastly, LLL12 exhibited synergistic anti-proliferative activity with the chemotherapeutic doxorubicin in the OS lines. Conclusion LLL12 exhibits biologic activity against canine OS cell lines through inhibition of STAT3 related cellular functions supporting its potential use as a novel therapy for OS.

  15. Protease activated receptors (PARS) mediation in gyroxin biological activity

    International Nuclear Information System (INIS)

    Silva, Jose Alberto Alves da

    2009-01-01

    Gyroxin is a serine protease enzyme from the South American rattlesnake (Crotalus durissus terrificus) venom; it is only partially characterized and has multiple activities. Gyroxin induces blood coagulation, blood pressure decrease and a neurotoxic behavior named barrel rotation. The mechanisms involved in this neurotoxic activity are not known. Whereas gyroxin is a member of enzymes with high potential to become a new drug with clinical applications such as thrombin, batroxobin, ancrod, tripsyn and kalicrein, it is important to find out how gyroxin works. The analysis on agarose gel electrophoresis and circular dichroism confirmed the molecules' integrity and purity. The gyroxin intravenous administration in mice proved its neurotoxicity (barrel rotation). In vivo studies employing intravital microscopy proved that gyroxin induces vasodilation with the participation of protease activated receptors (PARs), nitric oxide and Na+K+ATPase. The leukocytes' adherence and rolling counting indicated that gyroxin has no pro inflammatory activity. Gyroxin induced platelet aggregation, which was blocked by inhibitors of PAR1 and PAR4 receptors (SCH 79797 and tcY-NH 2 , respectively). Finally, it was proved that the gyroxin temporarily alter the permeability of the blood brain barrier (BBB). Our study has shown that both the protease-activated receptors and nitric oxide are mediators involved in the biological activities of gyroxin. (author)

  16. Enantio-specific C(sp3)-H activation catalyzed by ruthenium nanoparticles: application to isotopic labeling of molecules of biological interest

    International Nuclear Information System (INIS)

    Taglang, Celine

    2015-01-01

    Isotopic labeling with deuterium and tritium is extensively used in chemistry, biology and pharmaceutical research. Numerous methods of labeling by isotopic exchange allow high isotopic enrichments but generally require harsh conditions (high temperatures, acidity). As a consequence, a general, regioselective and smooth labeling method that might be applicable to a wide diversity of substrates remains to develop. In the first part of this thesis, we demonstrated that the use of ruthenium nanoparticles, synthesized by Pr. Bruno Chaudret's team (INSA Toulouse), allowed the mild (2 bar of deuterium gas at 55 C), effective and selective H/D exchange reaction of a large variety of nitrogen-containing compounds, such as pyridines, indoles and primary, secondary and tertiary alkyl amines. The usefulness and the efficiency of this novel methodology was demonstrated by the deuteration of eight nitrogen-containing molecules of biological interest without altering their chemical and stereochemical properties. However, the conservation of the original stereochemistry of an activated chiral C-H center remains a major issue. We studied the reactivity of RuNP(at)PVP on different categories of nitrogen-containing substrates (amines, aminoacids and peptides) in water or in organic solvents. Our results showed that C-H activation of chiral carbons C(sp3) took place efficiently, selectively and, in all cases, with total retention of configuration. The wide range of applications of this procedure was demonstrated by the labeling of three chiral amines, fourteen aminoacids, three aromatic amino esters and four peptides. Moreover, our collaboration with Pr. Romuald Poteau's team (INSA Toulouse) led to the identification of two mechanisms by ab initio simulation in agreement with our experimental results: the σ-bond metathesis mechanism and the oxidative addition mechanism. These two mechanisms imply two vicinal ruthenium atoms leading to the formation an original

  17. Membranolytic Activity of Bile Salts: Influence of Biological Membrane Properties and Composition

    Directory of Open Access Journals (Sweden)

    Alfred Blume

    2007-10-01

    Full Text Available The two main steps of the membranolytic activity of detergents: 1 the partitioning of detergent molecules in the membrane and 2 the solubilisation of the membrane are systematically investigated. The interactions of two bile salt molecules, sodium cholate (NaC and sodium deoxycholate (NaDC with biological phospholipid model membranes are considered. The membranolytic activity is analysed as a function of the hydrophobicity of the bile salt, ionic strength, temperature, membrane phase properties, membrane surface charge and composition of the acyl chains of the lipids. The results are derived from calorimetric measurements (ITC, isothermal titration calorimetry. A thermodynamic model is described, taking into consideration electrostatic interactions, which is used for the calculation of the partition coefficient as well as to derive the complete thermodynamic parameters describing the interaction of detergents with biological membranes (change in enthalpy, change in free energy, change in entropy etc. The solubilisation properties are described in a so-called vesicle-to-micelle phase transition diagram. The obtained results are supplemented and confirmed by data obtained from other biophysical techniques (DSC differential scanning calorimetry, DLS dynamic light scattering, SANS small angle neutron scattering.

  18. Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis

    Directory of Open Access Journals (Sweden)

    Bianca Ivanescu

    2015-01-01

    Full Text Available Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation.

  19. Laser desorption/ionization mass spectrometry for direct profiling and imaging of small molecules from raw biological materials

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Sangwon [Iowa State Univ., Ames, IA (United States)

    2008-01-01

    Matrix-assisted laser desorption/ionization(MALDI) mass spectrometry(MS) has been widely used for analysis of biological molecules, especially macromolecules such as proteins. However, MALDI MS has a problem in small molecule (less than 1 kDa) analysis because of the signal saturation by organic matrixes in the low mass region. In imaging MS (IMS), inhomogeneous surface formation due to the co-crystallization process by organic MALDI matrixes limits the spatial resolution of the mass spectral image. Therefore, to make laser desorption/ionization (LDI) MS more suitable for mass spectral profiling and imaging of small molecules directly from raw biological tissues, LDI MS protocols with various alternative assisting materials were developed and applied to many biological systems of interest. Colloidal graphite was used as a matrix for IMS of small molecules for the first time and methodologies for analyses of small metabolites in rat brain tissues, fruits, and plant tissues were developed. With rat brain tissues, the signal enhancement for cerebroside species by colloidal graphite was observed and images of cerebrosides were successfully generated by IMS. In addition, separation of isobaric lipid ions was performed by imaging tandem MS. Directly from Arabidopsis flowers, flavonoids were successfully profiled and heterogeneous distribution of flavonoids in petals was observed for the first time by graphite-assisted LDI(GALDI) IMS.

  20. Small molecule screening identifies targetable zebrafish pigmentation pathways

    DEFF Research Database (Denmark)

    Colanesi, Sarah; Taylor, Kerrie L; Temperley, Nicholas D

    2012-01-01

    Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investig......Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish...... and investigate the effects of a few of these compounds in further detail. We identified and confirmed 57 compounds that altered pigment cell patterning, number, survival, or differentiation. Additional tissue targets and toxicity of small molecules are also discussed. Given that the majority of cell types...

  1. Effect of biological activated carbon pre-treatment to control organic fouling in the microfiltration of biologically treated secondary effluent.

    Science.gov (United States)

    Pramanik, Biplob Kumar; Roddick, Felicity A; Fan, Linhua

    2014-10-15

    Biological activated carbon (BAC) filtration was investigated as a pre-treatment for reducing the organic fouling of a microfiltration membrane (0.1 μm polyvinylidene fluoride) in the treatment of a biologically treated secondary effluent (BTSE) from a municipal wastewater treatment plant. BAC treatment of the BTSE resulted in a marked improvement in permeate flux, which was attributed to the effective removal of organic foulants and particulates. Although the BAC removed significantly less dissolved organic carbon than the granular activated carbon (GAC) treatment which was used as a control for comparison, it led to a markedly greater flux. This was attributed to the effective removal of the very high molecular weight substances such as biopolymers by the BAC through biodegradation and adsorption of those molecules on the biofilm. Size exclusion chromatography showed the BAC treatment led to approximately 30% reduction in these substances, whereas the GAC did not greatly remove these molecules. The BAC treatment led to a greater reduction of loosely-attached and firmly-attached membrane surface foulant, and this was confirmed by attenuated total reflection-fourier transform infrared spectroscopy analysis. This study demonstrated the potential of BAC pre-treatment for reducing organic fouling and thus improving flux for the microfiltration of BTSE. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Structural Basis for Selective Small Molecule Kinase Inhibition of Activated c-Met

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, Keith W.; Patel, Sangita B.; Allison, Timothy J.; Byrne, Noel J.; Darke, Paul L.; Ford, Rachael E.; Guerin, David J.; Hall, Dawn L.; Kornienko, Maria; Lu, Jun; Munshi, Sanjeev K.; Reid, John C.; Shipman, Jennifer M.; Stanton, Elizabeth F.; Wilson, Kevin J.; Young, Jonathon R.; Soisson, Stephen M.; Lumb, Kevin J. (Merck)

    2012-03-15

    The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix {alpha}C and the G loop to generate a viable active site. Helix {alpha}C adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

  3. Ethylene glycol monolayer protected nanoparticles: synthesis, characterization, and interactions with biological molecules.

    Science.gov (United States)

    Zheng, Ming; Li, Zhigang; Huang, Xueying

    2004-05-11

    The usefulness of the hybrid materials of nanoparticles and biological molecules on many occasions depends on how well one can achieve a rational design based on specific binding and programmable assembly. Nonspecific binding between nanoparticles and biomolecules is one of the major barriers for achieving their utilities in a biological system. In this paper, we demonstrate a new approach to eliminate nonspecific interactions between nanoparticles and biological molecules by shielding the nanoparticle with a monolayer of ethylene glycol. A direct synthesis of di-, tri-, and tetra(ethylene glycol)-protected gold nanoparticles (Au-S-EGn, n = 2, 3, and 4) was achieved under the condition that the water content was optimized in the range of 9-18% in the reaction mixture. With controlled ratio of [HAuCl4]/[EGn-SH] at 2, the synthesized particles have an average diameter of 3.5 nm and a surface plasma resonance band around 510 nm. Their surface structures were confirmed by 1H NMR spectra. These gold nanoparticles are bonded with a uniform monolayer with defined lengths of 0.8, 1.2, and 1.6 nm for Au-S-EG2, Au-S-EG3, and Au-S-EG4, respectively. They have great stabilities in aqueous solutions with a high concentration of electrolytes as well as in organic solvents. Thermogravimetric analysis revealed that the ethylene glycol monolayer coating is ca. 14% of the total nanoparticle weight. Biological binding tests by using ion-exchange chromatography and gel electrophoresis demonstrated that these Au-S-EGn (n = 2, 3, or 4) nanoparticles are free of any nonspecific bindings with various proteins, DNA, and RNA. These types of nanoparticles provide a fundamental starting material for designing hybrid materials composed of metallic nanoparticles and biomolecules.

  4. Molecular locks and keys: the role of small molecules in phytohormone research

    Directory of Open Access Journals (Sweden)

    Sandra eFonseca

    2014-12-01

    Full Text Available Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signalling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signalling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function.Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signalling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated responses. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds.

  5. Detection, Characterization, and Biological Effect of Quorum-Sensing Signaling Molecules in Peanut-Nodulating Bradyrhizobia

    Directory of Open Access Journals (Sweden)

    Walter Giordano

    2012-03-01

    Full Text Available Bacteria of the genus Bradyrhizobium are able to establish a symbiotic relationship with peanut (Arachis hypogaea root cells and to fix atmospheric nitrogen by converting it to nitrogenous compounds. Quorum sensing (QS is a cell-cell communication mechanism employed by a variety of bacterial species to coordinate behavior at a community level through regulation of gene expression. The QS process depends on bacterial production of various signaling molecules, among which the N-acylhomoserine lactones (AHLs are most commonly used by Gram-negative bacteria. Some previous reports have shown the production of QS signaling molecules by various rhizobia, but little is known regarding mechanisms of communication among peanut-nodulating strains. The aims of this study were to identify and characterize QS signals produced by peanut-nodulating bradyrhizobial strains and to evaluate their effects on processes related to cell interaction. Detection of AHLs in 53 rhizobial strains was performed using the biosensor strains Agrobacterium tumefaciens NTL4 (pZLR4 and Chromobacterium violaceum CV026 for AHLs with long and short acyl chains, respectively. None of the strains screened were found to produce AHLs with short acyl chains, but 14 strains produced AHLs with long acyl chains. These 14 AHL-producing strains were further studied by quantification of β-galactosidase activity levels (AHL-like inducer activity in NTL4 (pZLR4. Strains displaying moderate to high levels of AHL-like inducer activity were subjected to chemical identification of signaling molecules by high-performance liquid chromatography coupled to mass spectrometry (LC-MS/MS. For each AHL-producing strain, we found at least four different AHLs, corresponding to N-hexanoyl-DL-homoserine lactone (C6, N-(3-oxodecanoyl-L-homoserine lactone (3OC10, N-(3-oxododecanoyl-L-homoserine lactone (3OC12, and N-(3-oxotetradecanoyl-L-homoserine lactone (3OC14. Biological roles of 3OC10, 3OC12, and 3OC14 AHLs

  6. Nucleic Acids as Information Molecules.

    Science.gov (United States)

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

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

    Science.gov (United States)

    Degrazio, Dominick

    . A packaging component within a container-closure system that is incompatible with the therapeutic biologic can potentially compromise patient safety, drug productivity, and product quality. Thus, each primary, parenteral packaging component within a container-closure system should be optimized to preserve the efficacy and therapeutic activity of a biologic. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure system incompatibilities with therapeutic biologics at a mechanistic level. © PDA, Inc. 2015.

  8. Ab Initio Calculations of the Electronic Structures and Biological Functions of Protein Molecules

    Science.gov (United States)

    Zheng, Haoping

    2003-04-01

    The self-consistent cluster-embedding (SCCE) calculation method reduces the computational effort from M3 to about M1 (M is the number of atoms in the system) with unchanged calculation precision. So the ab initio, all-electron calculation of the electronic structure and biological function of protein molecule becomes a reality, which will promote new proteomics considerably. The calculated results of two real protein molecules, the trypsin inhibitor from the seeds of squash Cucurbita maxima (CMTI-I, 436 atoms) and the Ascaris trypsin inhibitor (912 atoms, two three-dimensional structures), are presented. The reactive sites of the inhibitors are determined and explained. The precision of structure determination of inhibitors are tested theoretically.

  9. Adamantoylated biologically active small peptides and glycopeptides structurally related to the bacterial peptidoglycan.

    Science.gov (United States)

    Frkanec, Ruža; Vranešić, Branka; Tomić, Srdjanka

    2013-01-01

    A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity, particularly immunomodulating properties. A series of compounds containing the adamantyl residues coupled to peptides and glycopeptides characteristic for bacterial peptidoglycan was described. The new adamantylpeptides and adamantylglycopeptides were prepared starting from N-protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the starting material was D,L-(adamantyl-glycine) the condensation products with the dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were separated, characterized, and tested for immunostimulating activity. An HPLC method for purity testing was developed and adapted for the particular compounds.

  10. Extracting physics of life at the molecular level: A review of single-molecule data analyses.

    Science.gov (United States)

    Colomb, Warren; Sarkar, Susanta K

    2015-06-01

    Studying individual biomolecules at the single-molecule level has proved very insightful recently. Single-molecule experiments allow us to probe both the equilibrium and nonequilibrium properties as well as make quantitative connections with ensemble experiments and equilibrium thermodynamics. However, it is important to be careful about the analysis of single-molecule data because of the noise present and the lack of theoretical framework for processes far away from equilibrium. Biomolecular motion, whether it is free in solution, on a substrate, or under force, involves thermal fluctuations in varying degrees, which makes the motion noisy. In addition, the noise from the experimental setup makes it even more complex. The details of biologically relevant interactions, conformational dynamics, and activities are hidden in the noisy single-molecule data. As such, extracting biological insights from noisy data is still an active area of research. In this review, we will focus on analyzing both fluorescence-based and force-based single-molecule experiments and gaining biological insights at the single-molecule level. Inherently nonequilibrium nature of biological processes will be highlighted. Simulated trajectories of biomolecular diffusion will be used to compare and validate various analysis techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Single Fluorescent Molecules as Nano-Illuminators for Biological Structure and Function

    Science.gov (United States)

    Moerner, W. E.

    2011-03-01

    Since the first optical detection and spectroscopy of a single molecule in a solid (Phys. Rev. Lett. {62}, 2535 (1989)), much has been learned about the ability of single molecules to probe local nanoenvironments and individual behavior in biological and nonbiological materials in the absence of ensemble averaging that can obscure heterogeneity. Because each single fluorophore acts a light source roughly 1 nm in size, microscopic imaging of individual fluorophores leads naturally to superlocalization, or determination of the position of the molecule with precision beyond the optical diffraction limit, simply by digitization of the point-spread function from the single emitter. For example, the shape of single filaments in a living cell can be extracted simply by allowing a single molecule to move through the filament (PNAS {103}, 10929 (2006)). The addition of photoinduced control of single-molecule emission allows imaging beyond the diffraction limit (super-resolution) and a new array of acronyms (PALM, STORM, F-PALM etc.) and advances have appeared. We have used the native blinking and switching of a common yellow-emitting variant of green fluorescent protein (EYFP) reported more than a decade ago (Nature {388}, 355 (1997)) to achieve sub-40 nm super-resolution imaging of several protein structures in the bacterium Caulobacter crescentus: the quasi-helix of the actin-like protein MreB (Nat. Meth. {5}, 947 (2008)), the cellular distribution of the DNA binding protein HU (submitted), and the recently discovered division spindle composed of ParA filaments (Nat. Cell Biol. {12}, 791 (2010)). Even with these advances, better emitters would provide more photons and improved resolution, and a new photoactivatable small-molecule emitter has recently been synthesized and targeted to specific structures in living cells to provide super-resolution images (JACS {132}, 15099 (2010)). Finally, a new optical method for extracting three-dimensional position information based on

  12. Inactivation of biological substances by local heating

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Masahiro [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.

    1982-09-01

    Mechanism of inactivation of biological substances caused by local heating was investigated. The effect of hot-zone formation by local heating on reaction of radicals was previously evaluated. The thermal increase in a hot zone due to low energy LET x-rays had little effect on reactibility of the radicals, but, in a hot zone caused by high energy LET x-rays, formed radicals seemed immediately react to active biological molecules to inactivate them. Direct thermal effect on biological molecules was analysed. Thermal increase in a hot zone may induce degenaration of biological molecules which seems to occur in a short time judged from the extension of a hot zone and the duration of high temperature.

  13. The synthesis and biological evaluation of integrin receptor targeting molecules as potential radiopharmaceuticals

    Science.gov (United States)

    Pellegrini, Paul

    This thesis reports on the synthesis, characterisation and biological evaluation of a number of metal complexes designed to interact with the alphavbeta3 integrin receptor, an important biological target that is heavily involved in angiogenesis, and thus cancer related processes. Two approaches were used to synthesise the integrin-avid targets. The first was to attach a variety of bifunctional chelators (BFC's) for the incorporation of different metal centres to a known integrin antagonist, L-748,415, developed by Merck. The BFC's used were the hydrazinonicotinamide (HYNIC) and monoamine monoamide dithiol (MAMA) systems for coordination to Tc-99m and rhenium of which was used as a characterization surrogate for the unstable Tc core. The 1,4,7,10-tetraazacyclotridecanetetraacetic acid (TRITA) BFC was attached for the inclusion of copper and lutetium. This 'conjugate' approach was designed to yield information on how the BFC and the linker length would affect the affinity for the integrin receptor. The second approach was an 'integrated' method where the chelation moiety was integral to the biologically relevant part of the molecule, which in the case of the alphavbeta3 integrin receptor, is the arginine-glycine-aspartic acid (RGD) mimicking sequence. Two complexes were created with a modified MAMA derivative placed between a benzimidazole moiety (arginine mimick) and the aspartic acid mimicking terminal carboxylic acid to see how it would affect binding while keeping the molecular weight relatively low. The molecules were tested in vitro against purified human alphavbeta3 integrin receptor protein in a solid phase receptor binding assay to evaluate their inhibition constants against a molecule of known high affinity and selectivity in [I125]L-775,219, the I125 labelled alphavbeta3 integrin antagonist. The radiolabelled analogues were also tested in vivo against the A375 human melanoma cell line transplanted into balb/c nude mice as well as Fischer rats implanted

  14. Discovery of curcumin, a component of golden spice, and its miraculous biological activities.

    Science.gov (United States)

    Gupta, Subash C; Patchva, Sridevi; Koh, Wonil; Aggarwal, Bharat B

    2012-03-01

    1. Curcumin is the active ingredient of the dietary spice turmeric and has been consumed for medicinal purposes for thousands of years. Modern science has shown that curcumin modulates various signalling molecules, including inflammatory molecules, transcription factors, enzymes, protein kinases, protein reductases, carrier proteins, cell survival proteins, drug resistance proteins, adhesion molecules, growth factors, receptors, cell cycle regulatory proteins, chemokines, DNA, RNA and metal ions. 2. Because of this polyphenol's potential to modulate multiple signalling molecules, it has been reported to possess pleiotropic activities. First demonstrated to have antibacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, antiproliferative, wound healing, antinociceptive, antiparasitic and antimalarial properties as well. Animal studies have suggested that curcumin may be active against a wide range of human diseases, including diabetes, obesity, neurological and psychiatric disorders and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys and gastrointestinal and cardiovascular systems. 3. Although many clinical trials evaluating the safety and efficacy of curcumin against human ailments have already been completed, others are still ongoing. Moreover, curcumin is used as a supplement in several countries, including India, Japan, the US, Thailand, China, Korea, Turkey, South Africa, Nepal and Pakistan. Although inexpensive, apparently well tolerated and potentially active, curcumin has not been approved for the treatment of any human disease. 4. In the present article, we discuss the discovery and key biological activities of curcumin, with a particular emphasis on its activities at the molecular and cellular levels, as well as in animals and humans. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell

  15. Machine learning models identify molecules active against the Ebola virus in vitro [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2017-01-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  16. Machine learning models identify molecules active against the Ebola virus in vitro [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-10-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  17. Machine learning models identify molecules active against the Ebola virus in vitro [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2016-01-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  18. Developing powerful tritide technique: Organic and biological molecule labeling

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    Complex hydrides are very important reagents in organic synthesis due to the range of reducing powers and selectivities available from different agents. Unfortunately, the availability of these compounds for radiosynthesis has been extremely limited due to the difficulty of making them with adequate levels of tritium. Investigators at the Lawrence Berkeley Laboratory (LBL) National Tritium Labeling Facility have developed a new addition to the repertoire of the tritium-labeling chemist. The new method allows site-specific incorporation of tritium into organic and biological molecules by efficient reduction processes. Exceptionally reactive and selective reducing agents are prepared and used for labeling in a on-pot process. Three new tritide reagents - supertritide (lithium triethyl borotritide), LiAlT 4 (lithium aluminum tritide), and L-Selectride (sterically hindered lithium tri-sec-butyl borotritide) - have been synthesized at carrier-free levels, and have been demonstrated to be fully reactive. The availability of these versatile and reactive reagents gives the tritium radiochemist great control over chemoselectivity and stereoselectivity. The LBL tritide reagents can drive numerous conventional chemical reactions, and have been used to reduce p-toluene sulfonates, amides, lactones, esters, and aldehydes. These reactions produce good yields and result in products with maximum specific activities. The reagents clearly exhibit superior reactivity and may be used in many more synthetic processes than sodium borohydride, which is the currently used reagent. In addition, tritide reagents such as L-selectride have been shown to give greater control over stereochemistry and selectivity than sodium borohydride

  19. Prion-like nanofibrils of small molecules (PriSM): A new frontier at the intersection of supramolecular chemistry and cell biology.

    Science.gov (United States)

    Zhou, Jie; Du, Xuewen; Xu, Bing

    2015-01-01

    Formed by non-covalent interactions and not defined at genetic level, the assemblies of small molecules in biology are complicated and less explored. A common morphology of the supramolecular assemblies of small molecules is nanofibrils, which coincidentally resembles the nanofibrils formed by proteins such as prions. So these supramolecular assemblies are termed as prion-like nanofibrils of small molecules (PriSM). Emerging evidence from several unrelated fields over the past decade implies the significance of PriSM in biology and medicine. This perspective aims to highlight some recent advances of the research on PriSM. This paper starts with description of the intriguing similarities between PriSM and prions, discusses the paradoxical features of PriSM, introduces the methods for elucidating the biological functions of PriSM, illustrates several examples of beneficial aspects of PriSM, and finishes with the promises and current challenges in the research of PriSM. We anticipate that the research of PriSM will contribute to the fundamental understanding at the intersection of supramolecular chemistry and cell biology and ultimately lead to a new paradigm of molecular (or supramolecular) therapeutics for biomedicine.

  20. Giardia lamblia: identification of molecules that contribute to direct mast cell activation.

    Science.gov (United States)

    Muñoz-Cruz, Samira; Gomez-García, Argelia; Matadamas-Martínez, Félix; Alvarado-Torres, Juan A; Meza-Cervantez, Patricia; Arriaga-Pizano, Lourdes; Yépez-Mulia, Lilián

    2018-06-02

    Mast cells play a central role in the early clearance of the intestinal parasite Giardia lamblia. In a previous study, we reported that G. lamblia live trophozoites or trophozoite-derived total soluble extract induced direct activation (IgE-independent) of mast cells and release of IL-6 and TNF-α. To identify the Giardia molecules and the mast cell receptors involved in this activation, trophozoite-derived total soluble proteins separated into three fractions (F1-F3) were evaluated for its ability to activate mast cells in vitro. F2 activated mast cells in a greater extent than F1 and F3. Furthermore, F2 induced the release of IL-6 and TNF-α by mast cells. TLR2 and TLR4 expression increased slightly after mast cell stimulation with either F2 or total soluble extract; however, these receptors were not involved in F2 or total soluble extract-induced proinflammatory cytokine production. Proteins present in F2 as unique and high-intensity bands identified by liquid chromatography coupled with tandem mass spectrometry, include molecules with important biological activities such as enolase and arginine deiminase (ADI). Recombinant ADI and enolase were tested for their ability to activate mast cells, but only ADI induced a significant release of IL-6 and TNF-α. ADI product, citrulline but not ammonium, also induced mast cell release of TNF-α. Interestingly, recombinant ADI still stimulated the secretion of TNF-α by mast cells in a arginine-free medium, although in a lower extend that in the presence of arginine, indicating that either ADI itself can stimulate mast cells or through its metabolic product, citrulline.

  1. X-ray structure analyses of biological molecules and particles in Japan. A brief history and future prospect

    International Nuclear Information System (INIS)

    Nakasako, Masayoshi; Yamamoto, Masaki

    2015-01-01

    In Japan, X-ray structure analyses of molecules and particles from biology started in the 1970s. The structure analysis methods have been developed through the innovation of various techniques in advance, and have contributed for understanding the elementary and microscopic processes in life. Here we summarize briefly the history of X-ray structure analyses for structural biology in Japan and think about the prospect. (author)

  2. TOPICAL REVIEW: Single-molecule experiments in biological physics: methods and applications

    Science.gov (United States)

    Ritort, F.

    2006-08-01

    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

  3. Dynamics of initial ionization events in biological molecules: Formation and fate of free radicals. Final technical report, May 1, 1994--December 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Castleman, A.W. Jr.

    1997-08-01

    Study of early time events following the absorption of electromagnetic radiation in biological systems has potentially significant impact on several areas of importance. In this context, the studies being conducted under this program provided insight into the conformational changes as well as the reactions leading to a variety of transformations that culminate from hydrogen atom and proton transfer events. These studies enabled an investigation of molecular details of structure-function relationships. In a second aspect of the program, investigations were conducted to provide basic underpinning research that contributed to a quantification of the behavior of radionuclides and pollutants associated with advanced energy activities after these materials emanate from their source and become transferred through the environment to the biota and human receptor. The approach to elucidating factors governing the difference between reactions in the gas and condensed phase was to study the initiating steps at progressively higher degrees of cluster aggregation. The author employed ultrafast laser techniques, in combination with selected molecules, carefully prepared in tailored compositions, to investigation the primary mechanisms involved in various molecular functional groups following the absorption of electromagnetic radiation. He also studied various molecules representing chromophores in such biologically important molecules as tyrosine and amines.

  4. Dynamics of Activated Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Mullin, Amy S. [Univ. of Maryland, College Park, MD (United States)

    2016-11-16

    Experimental studies have been performed to investigate the collisional energy transfer processes of gas-phase molecules that contain large amounts of internal energy. Such molecules are prototypes for molecules under high temperature conditions relevant in combustion and information about their energy transfer mechanisms is needed for a detailed understanding and modeling of the chemistry. We use high resolution transient IR absorption spectroscopy to measure the full, nascent product distributions for collisions of small bath molecules that relax highly vibrationally excited pyrazine molecules with E=38000 cm-1 of vibrational energy. To perform these studies, we developed new instrumentation based on modern IR light sources to expand our experimental capabilities to investigate new molecules as collision partners. This final report describes our research in four areas: the characterization of a new transient absorption spectrometer and the results of state-resolved collision studies of pyrazine(E) with HCl, methane and ammonia. Through this research we have gained fundamental new insights into the microscopic details of relatively large complex molecules at high energy as they undergo quenching collisions and redistribute their energy.

  5. Handbook of Single-Molecule Biophysics

    CERN Document Server

    Hinterdorfer, Peter

    2009-01-01

    The last decade has seen the development of a number of novel biophysical methods that allow the manipulation and study of individual biomolecules. The ability to monitor biological processes at this fundamental level of sensitivity has given rise to an improved understanding of the underlying molecular mechanisms. Through the removal of ensemble averaging, distributions and fluctuations of molecular properties can be characterized, transient intermediates identified, and catalytic mechanisms elucidated. By applying forces on biomolecules while monitoring their activity, important information can be obtained on how proteins couple function to structure. The Handbook of Single-Molecule Biophysics provides an introduction to these techniques and presents an extensive discussion of the new biological insights obtained from them. Coverage includes: Experimental techniques to monitor and manipulate individual biomolecules The use of single-molecule techniques in super-resolution and functional imaging Single-molec...

  6. Exploring matter through photons and neutrons: from biological molecules to designer materials

    International Nuclear Information System (INIS)

    Chidambaram, R.; Hosur, M.V.; Ramanadham, M.; Godwal, B.K.

    2000-01-01

    Understanding structure-property relationships of naturally occurring materials has been the aim of scientific research for centuries. The discovery of short wavelength x-rays and neutrons in the 20th century provided a means of studying molecular structure. The methodology of x-ray and neutron diffraction has been successfully applied to determine structures of molecules across disciplines of physics, chemistry, biology, biochemistry and medicine. Typical applications in physics include study of phase transformations, elasticity measurements, magnetic structure, surface scattering etc. In chemistry, the applications have ranged from routine structure determinations of reaction intermediates or natural products to refinement of quantum chemical parameters of atomic and molecular charge densities. The science of crystallography has had a profound effect on the disciplines of biology and medicine. A whole new discipline and industry was created when the structure of DNA was discovered through x-ray diffraction

  7. Insects: an underrepresented resource for the discovery of biologically active natural products

    Directory of Open Access Journals (Sweden)

    Lauren Seabrooks

    2017-07-01

    Full Text Available Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.

  8. Interactions of electrons with biologically important molecules

    International Nuclear Information System (INIS)

    Pisklova, K.; Papp, P.; Stano, M.

    2012-01-01

    For the study of interactions of low-energy electrons with the molecules in the gas phase, the authors used electron-molecule cross-beam apparatus. The experiment is carried out in high vacuum, where molecules of the tested compound are inducted through a capillary. For purposes of this experiment the sample was electrically heated to 180 Deg C., giving a bundle of GlyGly molecules into the gas phase. The resulting signals can be evaluated in two different modes: mass spectrum - at continuous electron energy (e.g. 100 eV) they obtained the signal of intensity of the ions according to their mass to charge ratio; ionization and resonance spectra - for selected ion mass when the authors received the signal of intensity of the ions, depending on the energy of interacting electron.

  9. A Synthetic Biology Project - Developing a single-molecule device for screening drug-target interactions.

    Science.gov (United States)

    Firman, Keith; Evans, Luke; Youell, James

    2012-07-16

    This review describes a European-funded project in the area of Synthetic Biology. The project seeks to demonstrate the application of engineering techniques and methodologies to the design and construction of a biosensor for detecting drug-target interactions at the single-molecule level. Production of the proteins required for the system followed the principle of previously described "bioparts" concepts (a system where a database of biological parts - promoters, genes, terminators, linking tags and cleavage sequences - is used to construct novel gene assemblies) and cassette-type assembly of gene expression systems (the concept of linking different "bioparts" to produce functional "cassettes"), but problems were quickly identified with these approaches. DNA substrates for the device were also constructed using a cassette-system. Finally, micro-engineering was used to build a magnetoresistive Magnetic Tweezer device for detection of single molecule DNA modifying enzymes (motors), while the possibility of constructing a Hall Effect version of this device was explored. The device is currently being used to study helicases from Plasmodium as potential targets for anti-malarial drugs, but we also suggest other potential uses for the device. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Nano-sensing of the orientation of fluorescing molecules with active coated nano-particles

    DEFF Research Database (Denmark)

    Arslanagic, Samel; Ziolkowski, Richard W.

    2015-01-01

    The potential of using active coated nano-particles to determine the orientation of fluorescing molecules is reported. By treating each fluorescing molecule as an electric Hertzian dipole, single and multiple fluorescing molecules emitting coherently and incoherently in various orientations...... are considered in the presence of active coated nano-particles. It is demonstrated that in addition to offering a means to determine the orientation of a single molecule or the over-all orientation of the molecules surrounding it, the nature of the far-field response from the active coated nano...

  11. In situ single molecule imaging of cell membranes: linking basic nanotechniques to cell biology, immunology and medicine

    Science.gov (United States)

    Pi, Jiang; Jin, Hua; Yang, Fen; Chen, Zheng W.; Cai, Jiye

    2014-10-01

    The cell membrane, which consists of a viscous phospholipid bilayer, different kinds of proteins and various nano/micrometer-sized domains, plays a very important role in ensuring the stability of the intracellular environment and the order of cellular signal transductions. Exploring the precise cell membrane structure and detailed functions of the biomolecules in a cell membrane would be helpful to understand the underlying mechanisms involved in cell membrane signal transductions, which could further benefit research into cell biology, immunology and medicine. The detection of membrane biomolecules at the single molecule level can provide some subtle information about the molecular structure and the functions of the cell membrane. In particular, information obtained about the molecular mechanisms and other information at the single molecule level are significantly different from that detected from a large amount of biomolecules at the large-scale through traditional techniques, and can thus provide a novel perspective for the study of cell membrane structures and functions. However, the precise investigations of membrane biomolecules prompts researchers to explore cell membranes at the single molecule level by the use of in situ imaging methods, as the exact conformation and functions of biomolecules are highly controlled by the native cellular environment. Recently, the in situ single molecule imaging of cell membranes has attracted increasing attention from cell biologists and immunologists. The size of biomolecules and their clusters on the cell surface are set at the nanoscale, which makes it mandatory to use high- and super-resolution imaging techniques to realize the in situ single molecule imaging of cell membranes. In the past few decades, some amazing imaging techniques and instruments with super resolution have been widely developed for molecule imaging, which can also be further employed for the in situ single molecule imaging of cell membranes. In

  12. The role of medicaments, exosomes and miRNA molecules in modulation of macrophage immune activity

    Directory of Open Access Journals (Sweden)

    Katarzyna Nazimek

    2015-01-01

    Full Text Available Macrophages play an important role in innate immunity, in induction and orchestration of acquired immune response as well as in the maintenance of tissue homeostasis. Macrophages as antigen presenting cells induce or inhibit the development of immune response and as effector cells play an important role in innate immunity to infectious agents and in delayed--type hypersensitivity as well. Thus, either up- or down-regulation of their activity leads to the impairment of different biological processes. This often results in the development of immunological diseases or inflammatory response associated with metabolic, cardiovascular or neuroendocrine disorders. Therefore, the possibility of modulation of macrophage function should allow for elaboration of new effective therapeutic strategies. Noteworthy, interaction of medicaments with macrophages may directly mediate their therapeutic activity or is an additional beneficial effect increasing efficacy of treatment. Further, macrophage differentiation is regulated by miRNA-223, while expression of miRNA-146 and miRNA-155 may modulate and/or be a result of the current cell phenotype. Present review is focused on the current knowledge about the action of medicaments, microRNA molecules, exosomes and related vesicles on macrophages leading to modulation of their biological activity.

  13. Graphene as a transparent conductive support for studying biological molecules by transmission electron microscopy

    International Nuclear Information System (INIS)

    Nair, R. R.; Anissimova, S.; Novoselov, K. S.; Blake, P.; Blake, J. R.; Geim, A. K.; Zan, R.; Bangert, U.; Golovanov, A. P.; Morozov, S. V.; Latychevskaia, T.

    2010-01-01

    We demonstrate the application of graphene as a support for imaging individual biological molecules in transmission electron microscope (TEM). A simple procedure to produce free-standing graphene membranes has been designed. Such membranes are extremely robust and can support practically any submicrometer object. Tobacco mosaic virus has been deposited on graphene samples and observed in a TEM. High contrast has been achieved even though no staining has been applied.

  14. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment.

    Science.gov (United States)

    Hyer, Marc L; Milhollen, Michael A; Ciavarri, Jeff; Fleming, Paul; Traore, Tary; Sappal, Darshan; Huck, Jessica; Shi, Judy; Gavin, James; Brownell, Jim; Yang, Yu; Stringer, Bradley; Griffin, Robert; Bruzzese, Frank; Soucy, Teresa; Duffy, Jennifer; Rabino, Claudia; Riceberg, Jessica; Hoar, Kara; Lublinsky, Anya; Menon, Saurabh; Sintchak, Michael; Bump, Nancy; Pulukuri, Sai M; Langston, Steve; Tirrell, Stephen; Kuranda, Mike; Veiby, Petter; Newcomb, John; Li, Ping; Wu, Jing Tao; Powe, Josh; Dick, Lawrence R; Greenspan, Paul; Galvin, Katherine; Manfredi, Mark; Claiborne, Chris; Amidon, Benjamin S; Bence, Neil F

    2018-02-01

    The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade. TAK-243 treatment caused depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses. Due to its specificity and potency, TAK-243 allows for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment.

  15. Single molecule optical measurements of orientation and rotations of biological macromolecules.

    Science.gov (United States)

    Shroder, Deborah Y; Lippert, Lisa G; Goldman, Yale E

    2016-11-22

    Subdomains of macromolecules often undergo large orientation changes during their catalytic cycles that are essential for their activity. Tracking these rearrangements in real time opens a powerful window into the link between protein structure and functional output. Site-specific labeling of individual molecules with polarized optical probes and measurement of their spatial orientation can give insight into the crucial conformational changes, dynamics, and fluctuations of macromolecules. Here we describe the range of single molecule optical technologies that can extract orientation information from these probes, review the relevant types of probes and labeling techniques, and highlight the advantages and disadvantages of these technologies for addressing specific inquiries.

  16. Publishing activities improves undergraduate biology education.

    Science.gov (United States)

    Smith, Michelle K

    2018-06-01

    To improve undergraduate biology education, there is an urgent need for biology instructors to publish their innovative active-learning instructional materials in peer-reviewed journals. To do this, instructors can measure student knowledge about a variety of biology concepts, iteratively design activities, explore student learning outcomes and publish the results. Creating a set of well-vetted activities, searchable through a journal interface, saves other instructors time and encourages the use of active-learning instructional practices. For authors, these publications offer new opportunities to collaborate and can provide evidence of a commitment to using active-learning instructional techniques in the classroom.

  17. Essential Oils’ Chemical Characterization and Investigation of Some Biological Activities: A Critical Review

    Science.gov (United States)

    Dhifi, Wissal; Bellili, Sana; Jazi, Sabrine; Bahloul, Nada; Mnif, Wissem

    2016-01-01

    This review covers literature data summarizing, on one hand, the chemistry of essential oils and, on the other hand, their most important activities. Essential oils, which are complex mixtures of volatile compounds particularly abundant in aromatic plants, are mainly composed of terpenes biogenerated by the mevalonate pathway. These volatile molecules include monoterpenes (hydrocarbon and oxygenated monoterpens), and also sesquiterpenes (hydrocarbon and oxygenated sesquiterpens). Furthermore, they contain phenolic compounds, which are derived via the shikimate pathway. Thanks to their chemical composition, essential oils possess numerous biological activities (antioxidant, anti-inflammatory, antimicrobial, etc…) of great interest in food and cosmetic industries, as well as in the human health field. PMID:28930135

  18. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy

    Science.gov (United States)

    Neuman, Keir C.; Nagy, Attila

    2012-01-01

    Single-molecule force spectroscopy has emerged as a powerful tool to investigate the forces and motions associated with biological molecules and enzymatic activity. The most common force spectroscopy techniques are optical tweezers, magnetic tweezers and atomic force microscopy. These techniques are described and illustrated with examples highlighting current capabilities and limitations. PMID:18511917

  19. Preparation of iodoinsulin with preserved biological activity. [/sup 125/I, /sup 127/I

    Energy Technology Data Exchange (ETDEWEB)

    Dominiczak, M [Akademia Medyczna, Gdansk (Poland)

    1978-01-01

    The paper presents a method of receiving iodoinsulin with preserved biological activity. As a raw material, recrystallized bovine insulin produced by ''Polfa'' was used. Chloramine T was used as an oxidizing agent in the iodide reaction. Insulin was labelled with /sup 125/I or /sup 127/I at a molar concentration of 0.6/n NaI to insulin. Obtained product contained about 0.3 iodine atoms per insulin molecule. Specific radioactivity of the iodoinsulin was between 77 and 147 ..mu..Ci/..mu..g. Such an insulin was over 95% precipitable with trichloroacetic acid. Its immunological reactivity varied from 89% to 100% while its biological activity, determined using the consumption of glucose by the fatty tissue of rat epididymis was 92% +- 24% of the native insulin activity. The half-life of /sup 125/I-insulin in the rat blood circulation was determined the clearance curve being biphasic. The half-life of the first phase (shorter one) was 0.64 +- 0.2 minute while the longer phase 8.89 +- 2.16 minutes.

  20. Study of radionuclides speciation with biological molecules of interest by spectrometric techniques; Etude de la speciation des radionucleides avec les molecules d'interet biologique par approche spectrometrique

    Energy Technology Data Exchange (ETDEWEB)

    Lourenco, V

    2007-07-15

    Mechanisms of complexation and accumulation of the radionuclides at the cellular and molecular level are complex and poorly known because the studies on these subjects are scarce. Within the framework of this thesis, we studied the interactions of these cations with biological molecules of interest. We chose to focus on an actinide: uranium (VI) as well as europium as an analogue of trivalent actinides. The selected biological molecules are the phyto-chelatins: their role is to protect cells against intrusions from nonessential heavy metals (thus toxic). These proteins are likely to be implied in the mechanisms of sequestration of radionuclides in living organisms. However, their structure is complex, this is why, in order to better include/understand their reactivity, we extended our studies to lower entities which constitute them (amino acid: glycine, glutamic acid and cysteine; polypeptides: glutathione reduced and oxidized forms). In particular, we determined solution speciation (stoichiometry, structure) as well as the complexing constants associated with the formation with these species. These studies were undertaken by Time Resolved Laser induced Fluorescence (TRLIF), Electro-Spray-Mass Spectrometry (ES-MS), Nuclear Magnetic Resonance (NMR), Fourier Transform Infra-Rouge spectroscopy (FTIR) and Extended X-ray Absorption Fine Structure Spectroscopy (EXAFS).The determination of the complexation constants enabled us to conclude that the complexing capacity of these molecules with respect to radionuclides was moderate (log{sub 10}K{sub 1} {<=} 3, pH 3 or 6), the formed species are mononuclear with only one ligand molecule (1:1). The interaction is performed via oxygenated (hard) groups. The direct complexation of europium with phyto-chelatins at acidic pH was studied jointly by TRLIF and ES-MS. The complexing capacity of these molecules is much higher than that of GSH from which they result. The interaction of europium with metallothioneins is, on the contrary

  1. Single Molecule Detection in Living Biological Cells using Carbon Nanotube Optical Probes

    Science.gov (United States)

    Strano, Michael

    2009-03-01

    Nanoscale sensing elements offer promise for single molecule analyte detection in physically or biologically constrained environments. Molecular adsorption can be amplified via modulation of sharp singularities in the electronic density of states that arise from 1D quantum confinement [1]. Single-walled carbon nanotubes (SWNT), as single molecule optical sensors [2-3], offer unique advantages such as photostable near-infrared (n-IR) emission for prolonged detection through biological media, single-molecule sensitivity and, nearly orthogonal optical modes for signal transduction that can be used to identify distinct classes of analytes. Selective binding to the SWNT surface is difficult to engineer [4]. In this lecture, we will briefly review the immerging field of fluorescent diagnostics using band gap emission from SWNT. In recent work, we demonstrate that even a single pair of SWNT provides at least four optical modes that can be modulated to uniquely fingerprint chemical agents by the degree to which they alter either the emission band intensity or wavelength. We validate this identification method in vitro by demonstrating detection and identification of six genotoxic analytes, including chemotherapeutic drugs and reactive oxygen species (ROS), which are spectroscopically differentiated into four distinct classes. We also demonstrate single-molecule sensitivity in detecting hydrogen peroxide, one of the most common genotoxins and an important cellular signal. Finally, we employ our sensing and fingerprinting method of these analytes in real time within live 3T3 cells, demonstrating the first multiplexed optical detection from a nanoscale biosensor and the first label-free tool to optically discriminate between genotoxins. We will also discuss our recent efforts to fabricate biomedical sensors for real time detection of glucose and other important physiologically relevant analytes in-vivo. The response of embedded SWNT in a swellable hydrogel construct to

  2. Biological Activities of Hydrazone Derivatives

    Directory of Open Access Journals (Sweden)

    S. Güniz Küçükgüzel

    2007-08-01

    Full Text Available There has been considerable interest in the development of novel compounds with anticonvulsant, antidepressant, analgesic, antiinflammatory, antiplatelet, antimalarial, antimicrobial, antimycobacterial, antitumoral, vasodilator, antiviral and antischistosomiasis activities. Hydrazones possessing an azometine -NHN=CH- proton constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations have been guiding for the development of new hydrazones that possess varied biological activities.

  3. Impact of biological activated carbon pre-treatment on the hydrophilic fraction of effluent organic matter for mitigating fouling in microfiltration.

    Science.gov (United States)

    Pramanik, Biplob Kumar; Roddick, Felicity A; Fan, Linhua

    2017-07-24

    The hydrophilic (HPI) fraction of effluent organic matter, which has protein and carbohydrate contents, has a high propensity to foul low-pressure membranes. Biological activated carbon (BAC) filtration was examined as a pre-treatment for reducing the fouling of a microfiltration (MF) membrane (0.1 µm PVDF) by the HPI organic fraction extracted from a biologically treated secondary effluent (BTSE). Although the BAC removed less dissolved organic carbon, carbohydrate and protein from the HPI fraction than the granular activated carbon treatment which was used for comparison, it led to better improvement in permeate flux. This was shown to be due to the removal/breakdown of the HPI fraction resulting in less deposition of these organics on the membrane, many components of which are high molecular weight biopolymers (such as protein and carbohydrate molecules) through biodegradation and adsorption of those molecules on the biofilm and activated carbon. This study established the potential of BAC pre-treatment for reducing the HPI fouling of the membrane and thus improving the performance for the MF of BTSE for water reclamation.

  4. A brief introduction to single-molecule fluorescence methods

    NARCIS (Netherlands)

    Wildenberg, S.M.J.L.; Prevo, B.; Peterman, E.J.G.; Peterman, EJG; Wuite, GJL

    2011-01-01

    One of the more popular single-molecule approaches in biological science is single-molecule fluorescence microscopy, which is the subject of the following section of this volume. Fluorescence methods provide the sensitivity required to study biology on the single-molecule level, but they also allow

  5. A brief introduction to single-molecule fluorescence methods

    NARCIS (Netherlands)

    van den Wildenberg, Siet M.J.L.; Prevo, Bram; Peterman, Erwin J.G.

    2018-01-01

    One of the more popular single-molecule approaches in biological science is single-molecule fluorescence microscopy, which will be the subject of the following section of this volume. Fluorescence methods provide the sensitivity required to study biology on the single-molecule level, but they also

  6. Voltammetric detection of biological molecules using chopped carbon fiber.

    Science.gov (United States)

    Sugawara, Kazuharu; Yugami, Asako; Kojima, Akira

    2010-01-01

    Voltammetric detection of biological molecules was carried out using chopped carbon fibers produced from carbon fiber reinforced plastics that are biocompatible and inexpensive. Because chopped carbon fibers normally are covered with a sizing agent, they are difficult to use as an electrode. However, when the surface of a chopped carbon fiber was treated with ethanol and hydrochloric acid, it became conductive. To evaluate the functioning of chopped carbon fibers, voltammetric measurements of [Fe(CN)(6)](3-) were carried out. Redoxes of FAD, ascorbic acid and NADH as biomolecules were recorded using cyclic voltammetry. The sizing agents used to bundle the fibers were epoxy, polyamide and polyurethane resins. The peak currents were the greatest when using the chopped carbon fibers that were created with epoxy resins. When the electrode response of the chopped carbon fibers was compared with that of a glassy carbon electrode, the peak currents and the reversibility of the electrode reaction were sufficient. Therefore, the chopped carbon fibers will be useful as disposable electrodes for the sensing of biomolecules.

  7. A small molecule (pluripotin as a tool for studying cancer stem cell biology: proof of concept.

    Directory of Open Access Journals (Sweden)

    Susan D Mertins

    Full Text Available BACKGROUND: Cancer stem cells (CSC are thought to be responsible for tumor maintenance and heterogeneity. Bona fide CSC purified from tumor biopsies are limited in supply and this hampers study of CSC biology. Furthermore, purified stem-like CSC subpopulations from existing tumor lines are unstable in culture. Finding a means to overcome these technical challenges would be a useful goal. In a first effort towards this, we examined whether a chemical probe that promotes survival of murine embryonic stem cells without added exogenous factors can alter functional characteristics in extant tumor lines in a fashion consistent with a CSC phenotype. METHODOLOGY/PRINCIPAL FINDINGS: The seven tumor lines of the NCI60 colon subpanel were exposed to SC-1 (pluripotin, a dual kinase and GTPase inhibitor that promotes self-renewal, and then examined for tumorigenicity under limiting dilution conditions and clonogenic activity in soft agar. A statistically significant increase in tumor formation following SC-1 treatment was observed (p<0.04. Cloning efficiencies and expression of putative CSC surface antigens (CD133 and CD44 were also increased. SC-1 treatment led to sphere formation in some colon tumor lines. Finally, SC-1 inhibited in vitro kinase activity of RSK2, and another RSK2 inhibitor increased colony formation implicating a role for this kinase in eliciting a CSC phenotype. CONCLUSIONS/SIGNIFICANCE: These findings validate a proof of concept study exposure of extant tumor lines to a small molecule may provide a tractable in vitro model for understanding CSC biology.

  8. bcl::Cluster : A method for clustering biological molecules coupled with visualization in the Pymol Molecular Graphics System.

    Science.gov (United States)

    Alexander, Nathan; Woetzel, Nils; Meiler, Jens

    2011-02-01

    Clustering algorithms are used as data analysis tools in a wide variety of applications in Biology. Clustering has become especially important in protein structure prediction and virtual high throughput screening methods. In protein structure prediction, clustering is used to structure the conformational space of thousands of protein models. In virtual high throughput screening, databases with millions of drug-like molecules are organized by structural similarity, e.g. common scaffolds. The tree-like dendrogram structure obtained from hierarchical clustering can provide a qualitative overview of the results, which is important for focusing detailed analysis. However, in practice it is difficult to relate specific components of the dendrogram directly back to the objects of which it is comprised and to display all desired information within the two dimensions of the dendrogram. The current work presents a hierarchical agglomerative clustering method termed bcl::Cluster. bcl::Cluster utilizes the Pymol Molecular Graphics System to graphically depict dendrograms in three dimensions. This allows simultaneous display of relevant biological molecules as well as additional information about the clusters and the members comprising them.

  9. Nothing in Evolution Makes Sense Except in the Light of Genomics: Read–Write Genome Evolution as an Active Biological Process

    Directory of Open Access Journals (Sweden)

    James A. Shapiro

    2016-06-01

    Full Text Available The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess “Read–Write Genomes” they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification.

  10. Biological activities of Lavandula angustifolia essential oil

    OpenAIRE

    Bílková, Zuzana

    2013-01-01

    Zuzana Bílková, Biological activities of Lavandula angustifolia essential oil, Thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, thesis author: PharmDr. Jan Martin, PhD., Hradec Králové, 2013, 72 pages. The thesis called "Biological activities of Lavandula angustifolia essential oil" is interested in biological activities of Lavandula angustifolia essential oil, specifically antifungal, antioxidant, anti-inflammatory, cytotoxicity, nematicidal and repellency activit...

  11. Biological activity analysis of native and recombinant streptokinase using clot lysis and chromogenic substrate assay.

    Science.gov (United States)

    Mahboubi, Arash; Sadjady, Seyyed Kazem; Mirzaei Saleh Abadi, Mohammad; Azadi, Saeed; Solaimanian, Roya

    2012-01-01

    DETERMINATION OF STREPTOKINASE ACTIVITY IS USUALLY ACCOMPLISHED THROUGH TWO ASSAY METHODS: a) Clot lysis, b) Chromogenic substrate assay. In this study the biological activity of two streptokinase products, namely Streptase®, which is a native product and Heberkinasa®, which is a recombinant product, was determined against the third international reference standard using the two forementioned assay methods. The results indicated that whilst the activity of Streptase® was found to be 101 ± 4% and 97 ± 5% of the label claim with Clot lysis and Chromogenic substrate assay respectively, for Heberkinasa® the potency values obtained were 42 ± 5% and 92.5 ± 2% of the label claim respectively. To shed some light on the reason for this finding, the n-terminal sequence of the streptokinase molecules present in the two products was determined. The results showed slight differences in the amino acid sequence of the recombinant product in comparison to the native one at the amino terminus. This finding supports those of other workers who found that n-terminal sequence of the streptokinase molecule can have significant effect on the activity of this protein.

  12. Brassinosteroids: synthesis and biological activities

    Czech Academy of Sciences Publication Activity Database

    Oklešťková, Jana; Rárová, Lucie; Kvasnica, Miroslav; Strnad, Miroslav

    2015-01-01

    Roč. 14, č. 6 (2015), s. 1053-1072 ISSN 1568-7767 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Brassinosteroids * Chemical synthesis * Plant biological activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.686, year: 2015

  13. Bio-active molecules modified surfaces enhanced mesenchymal stem cell adhesion and proliferation

    International Nuclear Information System (INIS)

    Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

    2017-01-01

    Surface modification of the substrate as a component of in vitro cell culture and tissue engineering, using bio-active molecules including extracellular matrix (ECM) proteins or peptides derived ECM proteins can modulate the surface properties and thereby induce the desired signaling pathways in cells. The aim of this study was to evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs) on glass substrates modified with fibronectin (Fn), collagen (Coll), RGD peptides (RGD) and designed peptide (R-pept) as bio-active molecules. The glass coverslips were coated with fibronectin, collagen, RGD peptide and R-peptide. Bone marrow mesenchymal stem cells were cultured on different substrates and the adhesion behavior in early incubation times was investigated using scanning electron microscopy (SEM) and confocal microscopy. The MTT assay was performed to evaluate the effect of different bio-active molecules on MSCs proliferation rate during 24 and 72 h. Formation of filopodia and focal adhesion (FA) complexes, two steps of cell adhesion process, were observed in MSCs cultured on bio-active molecules modified coverslips, specifically in Fn coated and R-pept coated groups. SEM image showed well adhesion pattern for MSCs cultured on Fn and R-pept after 2 h incubation, while the shape of cells cultured on Coll and RGD substrates indicated that they might experience stress condition in early hours of culture. Investigation of adhesion behavior, as well as proliferation pattern, suggests R-peptide as a promising bio-active molecule to be used for surface modification of substrate in supporting and inducing cell adhesion and proliferation. - Highlights: • Bioactive molecules modified surface is a strategy to design biomimicry scaffold. • Bi-functional Tat-derived peptide (R-pept) enhanced MSCs adhesion and proliferation. • R-pept showed similar influences to fibronectin on FA formation and attachment.

  14. Application of Fourier transform infrared ellipsometry to assess the concentration of biological molecules

    Science.gov (United States)

    Garcia-Caurel, Enric; Drevillon, Bernard; De Martino, Antonello; Schwartz, Laurent

    2002-12-01

    Spectroscopic ellipsometry is a noninvasive optical characterization technique mainly used in the semiconductor field to characterize bare substrates and thin films. In particular, it allows the gathering of information concerning the physical structure of the sample, such as roughness and film thickness, as well as its optical response. In the mid-infrared (IR) range each molecule exhibits a characteristic absorption fingerprint, which makes this technique chemically selective. Phase-modulated IR ellipsometry does not require a baseline correction procedure or suppression of atmospheric CO2 and water-vapor absorption bands, thus greatly reducing the subjectivity in data analysis. We have found that ellipsometric measurements of thin films, such as the solid residuals left on a plane surface after evaporation of a liquid drop containing a given compound in solution, are particularly favorable for dosing purposes because the intensity of IR absorptions shows a linear behavior along a wide range of solution concentrations of the given compound. Our aim is to illustrate with a concrete example and to justify theoretically the linearity experimentally found between radiation absorption and molecule concentration. For the example, we prepared aqueous solutions of glycogen, a molecule of huge biological importance currently tested in biochemical analyses, at concentrations ranging from 1 mg/l to 1 g/l, which correspond to those found in physiological conditions. The results of this example are promising for the application of ellipsometry for dosing purposes in biochemistry and biomedicine.

  15. A review exploring biological activities of hydrazones

    Directory of Open Access Journals (Sweden)

    Garima Verma

    2014-01-01

    Full Text Available The development of novel compounds, hydrazones has shown that they possess a wide variety of biological activities viz. antimicrobial, anticonvulsant, antidepressant, anti-inflammatory, analgesic, antiplatelet, antimalarial, anticancer, antifungal, antitubercular, antiviral, cardio protective etc., Hydrazones/azomethines/imines possess-NHN = CH- and constitute an important class of compounds for new drug development. A number of researchers have synthesized and evaluated the biological activities of hydrazones. This review aims at highlighting the diverse biological activities of hydrazones.

  16. Single molecule optical measurements of orientation and rotations of biological macromolecules

    OpenAIRE

    Shroder, Deborah Y; Lippert, Lisa G; Goldman, Yale E

    2016-01-01

    The subdomains of macromolecules often undergo large orientation changes during their catalytic cycles that are essential for their activity. Tracking these rearrangements in real time opens a powerful window into the link between protein structure and functional output. Site-specific labeling of individual molecules with polarized optical probes and measuring their spatial orientation can give insight into the crucial conformational changes, dynamics, and fluctuations of macromolecules. Here...

  17. Genus Pouteria: chemistry and biological activity

    Directory of Open Access Journals (Sweden)

    Cíntia A. M. Silva

    Full Text Available The genus Pouteria belongs to the family Sapotaceae and can be widely found around the World. These plants have been used as building material, as food, because the eatable fruits, as well as remedies in folk medicine. Some biological activities have been reported to species of this genus such as antioxidant, anti-inflammatory, antibacterial and antifungal. However, the real potential of this genus as source of new drugs or phytomedicines remains unknown. Therefore, a review of the so far known chemical composition and biological activities of this genus is presented to stimulate new studies about the species already reported moreover that species have no reference about chemistry or biological activities could be found until now.

  18. Role of signaling lymphocytic activation molecule in T helper cell responses

    Directory of Open Access Journals (Sweden)

    Jan E. de Vries

    1998-01-01

    Full Text Available Signaling lymphocytic activation molecule (SLAM; CDw150 is a 70 kDa glycoprotein. Signaling lymphocytic activation molecule is constitutively expressed on memory T cells, CD56+ T cells, a subset of T cell receptor γδ+ cells, immature thymocytes and, at low levels, on a proportion of peripheral blood B cells. Signaling lymphocytic activation molecule is rapidly upregulated on all T and B cells after activation. Engagement of SLAM by F(ab’2 fragments of an anti-SLAM monoclonal antibody (mAb A12 enhances antigen-specific T cell proliferation. In addition, mAb A12 was directly mitogenic for T cell clones and activated T cells. T cell proliferation induced by mAb A12 is independent of interleukin (IL-2, IL-4, IL-12 and IL-15, but is cyclosporin A sensitive. Ligation of SLAM during antigen-specific T cell proliferation resulted in upregulation of interferon (IFN-γ production, even by allergen-specific T helper cell (Th 2 clones, whereas the levels of IL-4 and IL-5 production were only marginally affected. The mAb A12 was unable to induce IL-4 and IL-5 production by Th1 clones. Co-stimulation of skin-derived Der P1-specific Th2 cells from patients with atopic dermatitis via SLAM resulted in the generation of a population of IFN-γ-producing cells, thereby reverting their phenotype to a Th0 pattern. Signaling lymphocytic activation molecule is a high-affinity self ligand mediating homophilic cell interaction. In addition, soluble SLAM enhances both T and B cell proliferation. Collectively, these data indicate that SLAM molecules act both as receptors and ligands that are not only involved in T cell expansion but also drive the expanding T cells during immune responses into the Th0/Th1 pathway. This suggests that signaling through SLAM plays a role in directing Th0/Th1 development.

  19. Serum levels of tumor necrosis factor-α and soluble adhesion molecules in relation to magnetic resonance imaging results and clinical activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Millers, A.; Metra, M.; Mastina, M.; Platkajis, A.; Kukaine, R.

    2001-01-01

    One direction of research in pathogenesis of multiple sclerosis (MS) has been to identify immunological markers associated with disease activity that are capable of predicting subsequent course of disease and are sensitive to intervention by immunomodulatory therapies. Adhesion molecules and tumor necrosis factor-α of the cytokine superfamily are associated with inflammation-mediated blood-brain barrier dysfunction and demyelination in the central nervous system (CNS). This study investigates the relationship between the serum level of soluble vascular adhesion molecule-1 (sVCAM), soluble intercellular adhesion molecule-1 (alCAM), tumor necrosis factor-α (TNF-α) and magnetic resonance imaging (MRI) activity in 18 patients with relapsing-remitting (RR) MS with different clinical activity. Patients with active gadolinium (Gd)-enhanced lesions on MRI showed a higher serum level of TNF-α, sVCA-1, slCAM-1 than RR MS patients without Gd-enhanced lesions. Control individuals (n=10) without MRI abnormalities had significantly lower serum levels of the above immunological parameters. These results suggest that serum levels of TNF-α and adhesion molecules slCAM-1 in RR MS patients are correlated with Gd-enhanced MRI and disease clinical activity and that they can be used as biological markers of disease activity. The soluble form of VCAM levels in peripheral blood did not correlate with disease activity and Gd-enhanced lesions of MRI. sVCAM as an early indicator of blood-brain barrier dysfunction may also serve as marker of beneficial activity in the relapsing phase of MS course. (authors)

  20. Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities

    OpenAIRE

    Sergeiko, Anastasia; Poroikov, Vladimir V; Hanuš, Lumir O; Dembitsky, Valery M

    2008-01-01

    Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward ...

  1. Leaf-specific pathogenesis-related 10 homolog, PgPR-10.3, shows in silico binding affinity with several biologically important molecules

    Directory of Open Access Journals (Sweden)

    Jin Haeng Han

    2015-10-01

    Conclusion: Although ginseng PR-10.3 gene is expressed in all organs of 3-wk-old plantlets, its expression is restricted to leaves in mature 2-yr-old ginseng plants. The putative binding property of PgPR-10.3 with Re is intriguing. Further verification of binding affinity with other biologically important molecules in the large hydrophobic cavity of PgPR-10.3 may provide an insight into the biological features of PR-10 proteins.

  2. The Molecule Cloud - compact visualization of large collections of molecules

    Directory of Open Access Journals (Sweden)

    Ertl Peter

    2012-07-01

    Full Text Available Abstract Background Analysis and visualization of large collections of molecules is one of the most frequent challenges cheminformatics experts in pharmaceutical industry are facing. Various sophisticated methods are available to perform this task, including clustering, dimensionality reduction or scaffold frequency analysis. In any case, however, viewing and analyzing large tables with molecular structures is necessary. We present a new visualization technique, providing basic information about the composition of molecular data sets at a single glance. Summary A method is presented here allowing visual representation of the most common structural features of chemical databases in a form of a cloud diagram. The frequency of molecules containing particular substructure is indicated by the size of respective structural image. The method is useful to quickly perceive the most prominent structural features present in the data set. This approach was inspired by popular word cloud diagrams that are used to visualize textual information in a compact form. Therefore we call this approach “Molecule Cloud”. The method also supports visualization of additional information, for example biological activity of molecules containing this scaffold or the protein target class typical for particular scaffolds, by color coding. Detailed description of the algorithm is provided, allowing easy implementation of the method by any cheminformatics toolkit. The layout algorithm is available as open source Java code. Conclusions Visualization of large molecular data sets using the Molecule Cloud approach allows scientists to get information about the composition of molecular databases and their most frequent structural features easily. The method may be used in the areas where analysis of large molecular collections is needed, for example processing of high throughput screening results, virtual screening or compound purchasing. Several example visualizations of large

  3. Single molecule insights on conformational selection and induced fit mechanism

    DEFF Research Database (Denmark)

    Hatzakis, Nikos

    2014-01-01

    . To describe the molecular basis of this behavior, two main mechanisms have been advanced: 'induced fit' and 'conformational selection'. Our understanding of these models relies primarily on NMR, computational studies and kinetic measurements. These techniques report the average behavior of a large ensemble...... of unsynchronized molecules, often masking intrinsic dynamic behavior of proteins and biologically significant transient intermediates. Single molecule measurements are emerging as a powerful tool for characterizing protein function. They offer the direct observation and quantification of the activity, abundance...

  4. Biophysics of DNA-Protein Interactions From Single Molecules to Biological Systems

    CERN Document Server

    Williams, Mark C

    2011-01-01

    This book presents a concise overview of current research on the biophysics of DNA-protein interactions. A wide range of new and classical methods are presented by authors investigating physical mechanisms by which proteins interact with DNA. For example, several chapters address the mechanisms by which proteins search for and recognize specific binding sites on DNA, a process critical for cellular function. Single molecule methods such as force spectroscopy as well as fluorescence imaging and tracking are described in these chapters as well as other parts of the book that address the dynamics of protein-DNA interactions. Other important topics include the mechanisms by which proteins engage DNA sequences and/or alter DNA structure. These simple but important model interactions are then placed in the broader biological context with discussion of larger protein-DNA complexes . Topics include replication forks, recombination complexes, DNA repair interactions, and ultimately, methods to understand the chromatin...

  5. Actinobacteria from arid and desert habitats: diversity and biological activity

    Directory of Open Access Journals (Sweden)

    Joachim eWink

    2016-01-01

    Full Text Available Abstract The lack of new antibiotics in the pharmaceutical pipeline guides more and more researchers to leave the classical isolation procedures and to look in special niches and ecosystems. Bioprospecting of extremophilic Actinobacteria through mining untapped strains and avoiding resiolation of known biomolecules is among the most promising strategies for this purpose. With this approach, members of acidtolerant, alkalitolerant, psychrotolerant, thermotolerant, halotolerant and xerotolerant Actinobacteria have been obtained from respective habitats. Among these, little survey exists on the diversity of Actinobacteria in arid areas, which are often adapted to relatively high temperatures, salt concentrations, and radiation. Therefore, arid and desert habitats are special ecosystems which can be recruited for the isolation of uncommon Actinobacteria with new metabolic capability.At the time of this writing, members of Streptomyces, Micromonospora, Saccharothrix, Streptosporangium, Cellulomonas, Amycolatopsis, Geodermatophilus, Lechevalieria, Nocardia and Actinomadura are reported from arid habitats. However, metagenomic data present dominant members of the communities in desiccating condition of areas with limited water availability that are not yet isolated. Furthermore, significant diverse types of polyketide synthase (PKS and nonribosomal peptide synthetase (NRPS genes are detected in xerophilic and xerotolerant Actinobacteria and some bioactive compounds are reported from them. Rather than pharmaceutically active metabolites, molecules with protection activity against drying such as Ectoin and Hydroxyectoin with potential application in industry and agriculture have also been identified from xerophilic Actinobacteria. In addition, numerous biologically active small molecules are expected to be discovered from arid adapted Actinobacteria in the future. In the current survey, the diversity and biotechnological potential of Actinobacteria

  6. Actinobacteria from Arid and Desert Habitats: Diversity and Biological Activity.

    Science.gov (United States)

    Mohammadipanah, Fatemeh; Wink, Joachim

    2015-01-01

    The lack of new antibiotics in the pharmaceutical pipeline guides more and more researchers to leave the classical isolation procedures and to look in special niches and ecosystems. Bioprospecting of extremophilic Actinobacteria through mining untapped strains and avoiding resiolation of known biomolecules is among the most promising strategies for this purpose. With this approach, members of acidtolerant, alkalitolerant, psychrotolerant, thermotolerant, halotolerant and xerotolerant Actinobacteria have been obtained from respective habitats. Among these, little survey exists on the diversity of Actinobacteria in arid areas, which are often adapted to relatively high temperatures, salt concentrations, and radiation. Therefore, arid and desert habitats are special ecosystems which can be recruited for the isolation of uncommon Actinobacteria with new metabolic capability. At the time of this writing, members of Streptomyces, Micromonospora, Saccharothrix, Streptosporangium, Cellulomonas, Amycolatopsis, Geodermatophilus, Lechevalieria, Nocardia, and Actinomadura are reported from arid habitats. However, metagenomic data present dominant members of the communities in desiccating condition of areas with limited water availability that are not yet isolated. Furthermore, significant diverse types of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes are detected in xerophilic and xerotolerant Actinobacteria and some bioactive compounds are reported from them. Rather than pharmaceutically active metabolites, molecules with protection activity against drying such as Ectoin and Hydroxyectoin with potential application in industry and agriculture have also been identified from xerophilic Actinobacteria. In addition, numerous biologically active small molecules are expected to be discovered from arid adapted Actinobacteria in the future. In the current survey, the diversity and biotechnological potential of Actinobacteria obtained from arid ecosystems

  7. Actinobacteria from Arid and Desert Habitats: Diversity and Biological Activity

    Science.gov (United States)

    Mohammadipanah, Fatemeh; Wink, Joachim

    2016-01-01

    The lack of new antibiotics in the pharmaceutical pipeline guides more and more researchers to leave the classical isolation procedures and to look in special niches and ecosystems. Bioprospecting of extremophilic Actinobacteria through mining untapped strains and avoiding resiolation of known biomolecules is among the most promising strategies for this purpose. With this approach, members of acidtolerant, alkalitolerant, psychrotolerant, thermotolerant, halotolerant and xerotolerant Actinobacteria have been obtained from respective habitats. Among these, little survey exists on the diversity of Actinobacteria in arid areas, which are often adapted to relatively high temperatures, salt concentrations, and radiation. Therefore, arid and desert habitats are special ecosystems which can be recruited for the isolation of uncommon Actinobacteria with new metabolic capability. At the time of this writing, members of Streptomyces, Micromonospora, Saccharothrix, Streptosporangium, Cellulomonas, Amycolatopsis, Geodermatophilus, Lechevalieria, Nocardia, and Actinomadura are reported from arid habitats. However, metagenomic data present dominant members of the communities in desiccating condition of areas with limited water availability that are not yet isolated. Furthermore, significant diverse types of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes are detected in xerophilic and xerotolerant Actinobacteria and some bioactive compounds are reported from them. Rather than pharmaceutically active metabolites, molecules with protection activity against drying such as Ectoin and Hydroxyectoin with potential application in industry and agriculture have also been identified from xerophilic Actinobacteria. In addition, numerous biologically active small molecules are expected to be discovered from arid adapted Actinobacteria in the future. In the current survey, the diversity and biotechnological potential of Actinobacteria obtained from arid ecosystems

  8. Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology.

    Science.gov (United States)

    Fujie, Tomoya; Hara, Takato; Kaji, Toshiyuki

    2016-01-01

    Bio-organometallics is a research strategy of biology that uses organic-inorganic hybrid molecules. The molecules are expected to exhibit useful bioactivities based on the unique structure formed by interaction between the organic structure and intramolecular metal(s). However, studies on both biology and toxicology of organic-inorganic hybrid molecules have been incompletely performed. There can be two types of toxicological studies of bio-organometallics; one is evaluation of organic-inorganic hybrid molecules and the other is analysis of biological systems from the viewpoint of toxicology using organic-inorganic hybrid molecules. Our recent studies indicate that cytotoxicity of hybrid molecules containing a metal that is nontoxic in inorganic forms can be more toxic than that of hybrid molecules containing a metal that is toxic in inorganic forms when the structure of the ligand is the same. Additionally, it was revealed that organic-inorganic hybrid molecules are useful for analysis of biological systems important for understanding the toxicity of chemical compounds including heavy metals.

  9. Biologically active compounds to develop bioelectronics and bio photonics

    Science.gov (United States)

    Mishra, Ashok Kumar; Tiwari, Satya Prakash

    2018-05-01

    Recent reports on biomaterials and biological systems at nano scale provide researchers with a fertile ground with regard to materials, enabling bioelectronics, bio sensing and new nanotechnologies that cover a wide range of applications. The signal transductions have been reported for many biological phenomenons and new field of biophysics namely Biosensors and Bioelectronics have been emerged out. The advances in the study of various aspects of bio molecules like electrical, optical, thermal etc has established the interesting area of research like biophotonics, nanobiotechnology, molecular solid, molecular liquids, bio instrumentation etc. The present study discusses the some aspects and applications of the bioprocess yields nanostructures that are nearly flawless in composition, stereo specific in structure, and flexible. Furthermore, these biomaterials are environment friendly because they are biodegradable in nature. Biological compounds are self assembled into complex nanostructures and behave like a system possessing long range hierarchical nanoscale order. In addition, chemical modification and genetic engineering can be used to modify bio materials to enhance a specific property. Various biomaterials have been reported which allow nanostructure control for nano photonic applications. The dielectric and conduction properties of the bio molecules have been the subject of many investigations. As a result, there exist a wealth of valuable information on the charge transport and rotational properties of many bio molecules. Amino acids and proteins, nucleic acids, lipids, cell and tissues have been characterized over a wide frequency spectrum ranging from a few hertz to Giga hertz. In certain cases, dielectric measurements have been exploited to probe the physical changes taking place in biologically important structures, for example, in lipid phase transition process in membrane. The phase transition in membrane may be analyzed by applying the theory for

  10. Application of magnetic iron oxide nanoparticles in stabilization process of biological molecules

    Directory of Open Access Journals (Sweden)

    Mohammad Hossien Salmani

    2017-07-01

    Conclusion: Co-precipitation method is an easy way to prepare magnetic nanoparticles of iron with a large surface and small particle size, which increases the ability of these particles to act as a suitable carrier for enzyme stabilization. Adequate modification of the surface of these nanoparticles enhances their ability to bind to biological molecules. The immobilized protein or enzyme on magnetic nanoparticles are more stable against structural changes, temperature and pH in comparison with un-stabilized structures, and it is widely used in various sciences, including protein isolation and purification, pharmaceutical science, and food analysis. Stabilization based on the covalent bonds and physical absorption is nonspecific, which greatly limits their functionality. The process of stabilization through bio-mediums provide a new method to overcome the selectivity problem.

  11. Discovery of the First Interstellar Chiral Molecule: Propylene Oxide

    Science.gov (United States)

    Carroll, Brandon; McGuire, Brett A.; Loomis, Ryan; Finneran, Ian A.; Jewell, Philip; Remijan, Anthony; Blake, Geoffrey

    2016-06-01

    Life on Earth relies on chiral molecules, that is, species not superimposable on their mirror images. This manifests itself as a reliance on a single molecular handedness, or homochirality that is characteristic of life and perhaps most readily apparent in the large enhancement in biological activity of particular amino acid and sugar enantiomers. Yet, the ancestral origin of biological homochirality remains a mystery. The non-racemic ratios in some organics isolated from primitive meteorites hint at a primordial chiral seed but even these samples have experienced substantial processing during planetary assembly, obscuring their complete histories. To determine the underlying origin of any enantiomeric excess, it is critical to understand the molecular gas from which these molecules originated. Here, we present the first extra-solar, astronomical detection of a chiral molecule, propylene oxide (CH_3CHCH_2O), in absorption toward the Galactic Center. With the detection of propylene oxide, we at last have a target for broad-ranging searches for the possible cosmic origin of the homochirality of life.

  12. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

    Science.gov (United States)

    Tien, Shin-Ming; Hsu, Chih-Yuan; Chen, Bor-Sen

    2016-01-01

    Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

  13. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

    Directory of Open Access Journals (Sweden)

    Shin-Ming Tien

    Full Text Available Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

  14. [Cycloferon biological activity characteristics].

    Science.gov (United States)

    Utkina, T M; Potekhina, L P; Kartashova, O L; Vasilchenko, A S

    2014-01-01

    Study the effect of cycloferon in experimental and clinical conditions on persistence properties of aurococci as well as features of their morpho-functional reaction by atomic force microscopy. The study was carried out in 12 Staphylococcus aureus clones isolated from mucous membrane of nose anterior part of a resident carrier. The effect of cycloferon in vivo was evaluated in 26 resident staphylococci carriers under the control of anti-carnosine activity of staphylococci. Anti-carnosine activity was determined by O.V. Bukharin et al. (1999), biofilm formation -by G.A. O'Toole et al. (2000). Staphylococci treated with cycloferon were studied by atomic force microscopy in contact mode using scanning probe SMM-2000 microscope. The decrease of persistence properties of staphylococci under the effect of cycloferon in vitro and in vivo may be examined as one of the mechanisms of biological activity of the preparation. A significant increase of S. aureus surface roughness and changes in their morphology under the effect of cycloferon allow stating the disorder of barrier functions in the aurococci cell wall. The data obtained expand the understanding of cycloferon biological activity mechanisms.

  15. Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.

    Science.gov (United States)

    Burns, Michael C; Sun, Qi; Daniels, R Nathan; Camper, DeMarco; Kennedy, J Phillip; Phan, Jason; Olejniczak, Edward T; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

    2014-03-04

    Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in ∼30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.

  16. Review of the inhibition of biological activities of food-related selected toxins by natural compounds.

    Science.gov (United States)

    Friedman, Mendel; Rasooly, Reuven

    2013-04-23

    There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term 'chemical genetics' has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet.

  17. Thermal Stabilization of Biologics with Photoresponsive Hydrogels.

    Science.gov (United States)

    Sridhar, Balaji V; Janczy, John R; Hatlevik, Øyvind; Wolfson, Gabriel; Anseth, Kristi S; Tibbitt, Mark W

    2018-03-12

    Modern medicine, biological research, and clinical diagnostics depend on the reliable supply and storage of complex biomolecules. However, biomolecules are inherently susceptible to thermal stress and the global distribution of value-added biologics, including vaccines, biotherapeutics, and Research Use Only (RUO) proteins, requires an integrated cold chain from point of manufacture to point of use. To mitigate reliance on the cold chain, formulations have been engineered to protect biologics from thermal stress, including materials-based strategies that impart thermal stability via direct encapsulation of the molecule. While direct encapsulation has demonstrated pronounced stabilization of proteins and complex biological fluids, no solution offers thermal stability while enabling facile and on-demand release from the encapsulating material, a critical feature for broad use. Here we show that direct encapsulation within synthetic, photoresponsive hydrogels protected biologics from thermal stress and afforded user-defined release at the point of use. The poly(ethylene glycol) (PEG)-based hydrogel was formed via a bioorthogonal, click reaction in the presence of biologics without impact on biologic activity. Cleavage of the installed photolabile moiety enabled subsequent dissolution of the network with light and release of the encapsulated biologic. Hydrogel encapsulation improved stability for encapsulated enzymes commonly used in molecular biology (β-galactosidase, alkaline phosphatase, and T4 DNA ligase) following thermal stress. β-galactosidase and alkaline phosphatase were stabilized for 4 weeks at temperatures up to 60 °C, and for 60 min at 85 °C for alkaline phosphatase. T4 DNA ligase, which loses activity rapidly at moderately elevated temperatures, was protected during thermal stress of 40 °C for 24 h and 60 °C for 30 min. These data demonstrate a general method to employ reversible polymer networks as robust excipients for thermal stability of complex

  18. Activation of TRPM7 channels by small molecules under physiological conditions.

    Science.gov (United States)

    Hofmann, T; Schäfer, S; Linseisen, M; Sytik, L; Gudermann, T; Chubanov, V

    2014-12-01

    Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a cation channel covalently linked to a protein kinase domain. TRPM7 is ubiquitously expressed and regulates key cellular processes such as Mg(2+) homeostasis, motility, and proliferation. TRPM7 is involved in anoxic neuronal death, cardiac fibrosis, and tumor growth. The goal of this work was to identify small molecule activators of the TRPM7 channel and investigate their mechanism of action. We used an aequorin bioluminescence-based assay to screen for activators of the TRPM7 channel. Valid candidates were further characterized using patch clamp electrophysiology. We identified 20 drug-like compounds with various structural backbones that can activate the TRPM7 channel. Among them, the δ opioid antagonist naltriben was studied in greater detail. Naltriben's action was selective among the TRP channels tested. Naltriben activates TRPM7 currents without prior depletion of intracellular Mg(2+) even under conditions of low PIP2. Moreover, naltriben interfered with the effect of the TRPM7 inhibitor NS8593. Finally, our experiments with TRPM7 variants carrying mutations in the pore, TRP, and kinase domains indicate that the site of TRPM7 activation by this small-molecule ligand is most likely located in or near the TRP domain. In conclusion, we identified the first organic small-molecule activators of TRPM7 channels, thus providing new experimental tools to study TRPM7 function in native cellular environments.

  19. The use of semiempirical quantum chemical methods in studying the properties of large series of biologically active molecules

    International Nuclear Information System (INIS)

    Koeseoglu, Y.

    2004-01-01

    In this work, the productivity (temporal characteristics) of the so-called Electron Topological Method (ETM) proposed for the structure-activity relationships (SAR) investigation is studied. The method is standing aside the methods proposed for quantitative SAR (QSAR) studies because of the essential difference in the languages chosen for the compound structures description. ETM uses Electron Topological Matrices of Contiguity (ETMC) that include the most comprehensive data on the electronic structure of compounds and their topology. The flexibility of real molecules is taken into account in terms of two parameters, Δ 1 and Δ 2 , that characterise the accuracy allowed for atomic properties (diagonal matrix elements) and for bonds (non-diagonal ones). The dependence of the feature realisation on different values of Δ 1 and Δ 2 is studied and its graphical representation is given

  20. Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass

    DEFF Research Database (Denmark)

    Toft, P; Tønnesen, Else Kirstine; Zülow, I

    1997-01-01

    Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open...... open-heart and abdominal surgery. The proportion of CD11a/CD18-positive lymphocytes rose from 67.6 +/- 8% to 86.4 +/- 3% after aortic declamping (p ... was associated with increased expression of the adhesion molecule CD11a/CD18 on lymphocytes, while the expression of activation molecules on lymphocytes was unchanged....

  1. Small molecule probes for cellular death machines.

    Science.gov (United States)

    Li, Ying; Qian, Lihui; Yuan, Junying

    2017-08-01

    The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need. Here, we provide an overview of small molecule modulators for necroptosis and ferroptosis, two non-apoptotic cell death mechanisms, and discuss the molecular pathways and relevant pathophysiological mechanisms revealed by the judicial applications of such small molecule probes. We suggest that the development and applications of small molecule probes for non-apoptotic cell death mechanisms provide an outstanding example showcasing the power of chemical biology in exploring novel biological mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Charge migration induced by attosecond pulses in bio-relevant molecules

    International Nuclear Information System (INIS)

    Calegari, Francesca; Castrovilli, Mattea C; Nisoli, Mauro; Trabattoni, Andrea; Palacios, Alicia; Ayuso, David; Martín, Fernando; Greenwood, Jason B; Decleva, Piero

    2016-01-01

    After sudden ionization of a large molecule, the positive charge can migrate throughout the system on a sub-femtosecond time scale, purely guided by electronic coherences. The possibility to actively explore the role of the electron dynamics in the photo-chemistry of bio-relevant molecules is of fundamental interest for understanding, and perhaps ultimately controlling, the processes leading to damage, mutation and, more generally, to the alteration of the biological functions of the macromolecule. Attosecond laser sources can provide the extreme time resolution required to follow this ultrafast charge flow. In this review we will present recent advances in attosecond molecular science: after a brief description of the results obtained for small molecules, recent experimental and theoretical findings on charge migration in bio-relevant molecules will be discussed. (topical review)

  3. Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies

    Directory of Open Access Journals (Sweden)

    André Luiz Lourenço

    2015-04-01

    Full Text Available The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p displayed IC50 values ranging from 29 to 84 µM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations.

  4. Unequal Activities of Enantiomers via Biological Receptors: Examples of Chiral Drug, Pesticide, and Fragrance Molecules

    Science.gov (United States)

    Mannschreck, Albrecht; Kiesswetter, Roland; von Angerer, Erwin

    2007-01-01

    A molecule coming from outside an organism can form a ligand-receptor complex. Upon its formation, a message is transmitted, for example, to certain cells. In this way, two enantiomers can emit messages that differ, either quantitatively or qualitatively. In the present article, these facts are taken as a common basis for the actions of chiral…

  5. Biological Mimics: A New Paradigm in the Detection of Toxic Compounds

    Science.gov (United States)

    Monty, Chelsea Nicole

    2009-01-01

    The purpose of this thesis is to introduce a new idea: using biological mimics in the detection of toxic compounds. Biological mimics imitate the active site of a given enzyme or have catalytic chemistry similar to enzymes and can be used in place of biological molecules to provide longer stability and simpler operation. In the following text the…

  6. Signaling lymphocytic activation molecules Slam and cancers: friends or foes?

    Science.gov (United States)

    Fouquet, Gregory; Marcq, Ingrid; Debuysscher, Véronique; Bayry, Jagadeesh; Rabbind Singh, Amrathlal; Bengrine, Abderrahmane; Nguyen-Khac, Eric; Naassila, Mickael; Bouhlal, Hicham

    2018-03-23

    Signaling Lymphocytic Activation Molecules (SLAM) family receptors are initially described in immune cells. These receptors recruit both activating and inhibitory SH2 domain containing proteins through their Immunoreceptor Tyrosine based Switch Motifs (ITSMs). Accumulating evidence suggest that the members of this family are intimately involved in different physiological and pathophysiological events such as regulation of immune responses and entry pathways of certain viruses. Recently, other functions of SLAM, principally in the pathophysiology of neoplastic transformations have also been deciphered. These new findings may prompt SLAM to be considered as new tumor markers, diagnostic tools or potential therapeutic targets for controlling the tumor progression. In this review, we summarize the major observations describing the implications and features of SLAM in oncology and discuss the therapeutic potential attributed to these molecules.

  7. Proteolytic activation transforms heparin cofactor II into a host defense molecule.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Tollefsen, Douglas M; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-06-15

    The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity.

  8. Challenges of biological sample preparation for SIMS imaging of elements and molecules at subcellular resolution

    International Nuclear Information System (INIS)

    Chandra, Subhash

    2008-01-01

    Secondary ion mass spectrometry (SIMS) based imaging techniques capable of subcellular resolution characterization of elements and molecules are becoming valuable tools in many areas of biology and medicine. Due to high vacuum requirements of SIMS, the live cells cannot be analyzed directly in the instrument. The sample preparation, therefore, plays a critical role in preserving the native chemical composition for SIMS analysis. This work focuses on the evaluation of frozen-hydrated and frozen freeze-dried sample preparations for SIMS studies of cultured cells with a CAMECA IMS-3f dynamic SIMS ion microscope instrument capable of producing SIMS images with a spatial resolution of 500 nm. The sandwich freeze-fracture method was used for fracturing the cells. The complimentary fracture planes in the plasma membrane were characterized by field-emission secondary electron microscopy (FESEM) in the frozen-hydrated state. The cells fractured at the dorsal surface were used for SIMS analysis. The frozen-hydrated SIMS analysis of individual cells under dynamic primary ion beam (O 2 + ) revealed local secondary ion signal enhancements correlated with the water image signals of 19 (H 3 O) + . A preferential removal of water from the frozen cell matrix in the Z-axis was also observed. These complications render the frozen-hydrated sample type less desirable for subcellular dynamic SIMS studies. The freeze-drying of frozen-hydrated cells, either inside the instrument or externally in a freeze-drier, allowed SIMS imaging of subcellular chemical composition. Morphological evaluations of fractured freeze-dried cells with SEM and confocal laser scanning microscopy (CLSM) revealed well-preserved mitochondria, Golgi apparatus, and stress fibers. SIMS analysis of fractured freeze-dried cells revealed well-preserved chemical composition of even the most highly diffusible ions like K + and Na + in physiologically relevant concentrations. The high K-low Na signature in individual cells

  9. Challenges of biological sample preparation for SIMS imaging of elements and molecules at subcellular resolution

    Science.gov (United States)

    Chandra, Subhash

    2008-12-01

    Secondary ion mass spectrometry (SIMS) based imaging techniques capable of subcellular resolution characterization of elements and molecules are becoming valuable tools in many areas of biology and medicine. Due to high vacuum requirements of SIMS, the live cells cannot be analyzed directly in the instrument. The sample preparation, therefore, plays a critical role in preserving the native chemical composition for SIMS analysis. This work focuses on the evaluation of frozen-hydrated and frozen freeze-dried sample preparations for SIMS studies of cultured cells with a CAMECA IMS-3f dynamic SIMS ion microscope instrument capable of producing SIMS images with a spatial resolution of 500 nm. The sandwich freeze-fracture method was used for fracturing the cells. The complimentary fracture planes in the plasma membrane were characterized by field-emission secondary electron microscopy (FESEM) in the frozen-hydrated state. The cells fractured at the dorsal surface were used for SIMS analysis. The frozen-hydrated SIMS analysis of individual cells under dynamic primary ion beam (O 2+) revealed local secondary ion signal enhancements correlated with the water image signals of 19(H 3O) +. A preferential removal of water from the frozen cell matrix in the Z-axis was also observed. These complications render the frozen-hydrated sample type less desirable for subcellular dynamic SIMS studies. The freeze-drying of frozen-hydrated cells, either inside the instrument or externally in a freeze-drier, allowed SIMS imaging of subcellular chemical composition. Morphological evaluations of fractured freeze-dried cells with SEM and confocal laser scanning microscopy (CLSM) revealed well-preserved mitochondria, Golgi apparatus, and stress fibers. SIMS analysis of fractured freeze-dried cells revealed well-preserved chemical composition of even the most highly diffusible ions like K + and Na + in physiologically relevant concentrations. The high K-low Na signature in individual cells

  10. Irradiation of biological molecules (DNA and RNA bases) by proton impact in the velocity range of the Bragg peak (20-150 keV/amu)

    International Nuclear Information System (INIS)

    Tabet, J.

    2007-11-01

    The aim of this work was to study the ionization of DNA and RNA base molecules by proton impact at energies between 20 and 150 keV/amu. The experiments developed over the course of this project made it possible not only to study the fragmentation of uracil, thymine, adenine, and cytosine, but also to measure absolute cross sections for different ionization processes initiated by proton interactions with these important biological molecules. Firstly, the experimental system enabled the contributions of two key ionization processes to be separated: direct ionization and electron capture. The corresponding mass spectra were measured and analyzed on an event-by-event basis. For uracil, the branching ratios for these two processes were measured as function of the projectile velocity. Secondly, we have developed a system to measure absolute cross sections for the electron capture process. The production rate of neutral atoms compared to protons was measured for the four biological molecules: uracil, cytosine, thymine, and adenine at different vaporization temperatures. This production rate varies as a function of the thickness of the target jet traversed by the protons. Accordingly, a deposit experiment was developed in order to characterize the density of molecules in the targeted gas jets. Theoretical and experimental study of the total effusion and density-profile of the gaseous molecular beams enabled us to deduce the thickness of the target jets traversed by the protons. Thus it was possible to determine absolute cross sections for the ionization of each of the four isolated biological molecules by 80 keV protons impact. To our knowledge, this work provides the first experimental absolute cross sections for DNA and RNA base ionization processes initiated by proton impact in the velocity range corresponding to the Bragg peak. (author)

  11. In silico Screening and Evaluation of the Anticonvulsant Activity of Docosahexaenoic Acid-Like Molecules in Experimental Models of Seizures.

    Science.gov (United States)

    Gharibi Loron, Ali; Sardari, Soroush; Narenjkar, Jamshid; Sayyah, Mohammad

    2017-01-01

    Resistance to antiepileptic drugs and the intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. Acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid (DHA) make it as a good candidate for designing and development of the new anticonvulsant medications. Ten DHA-based molecules were screened based on in silico screening of DHA-like molecules by root-mean-square deviation of atomic positions, the biological activity score of Professional Association for SQL Server, and structural requirements suggested by pharmacophore design. Anticonvulsant activity was tested against clonic seizures induced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) and tonic seizures induced by maximal electroshock (MES, 50 mA, 50 Hz, 1 ms duration) by intracerebroventricular (i.c.v.) injection of the screened compounds to mice. Among screened compounds, 4-Phenylbutyric acid, 4-Biphenylacetic acid, phenylacetic acid, and 2-Phenylbutyric acid showed significant protective activity in pentylenetetrazole test with ED50 values of 4, 5, 78, and 70 mM, respectively. In MES test, shikimic acid and 4-tert-Butylcyclo-hexanecarboxylic acid showed significant activity with ED50 values 29 and 637 mM, respectively. Effective compounds had no mortality in mice up to the maximum i.c.v. injectable dose of 1 mM. Common electrochemical features and three-dimensional spatial structures of the effective compounds suggest the involvement of the anticonvulsant mechanisms similar to the parent compound DHA.

  12. Overview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years

    Science.gov (United States)

    Wang, Lingchong; Wang, Xiangyu; Wu, Hao; Liu, Rui

    2014-01-01

    Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits. PMID:25257786

  13. Improved Dye Stability in Single-Molecule Fluorescence Experiments

    Science.gov (United States)

    EcheverrÍa Aitken, Colin; Marshall, R. Andrew; Pugi, Joseph D.

    Complex biological systems challenge existing single-molecule methods. In particular, dye stability limits observation time in singlemolecule fluorescence applications. Current approaches to improving dye performance involve the addition of enzymatic oxygen scavenging systems and small molecule additives. We present an enzymatic oxygen scavenging system that improves dye stability in single-molecule experiments. Compared to the currently-employed glucose-oxidase/catalase system, the protocatechuate-3,4-dioxygenase system achieves lower dissolved oxygen concentration and stabilizes single Cy3, Cy5, and Alexa488 fluorophores. Moreover, this system possesses none of the limitations associated with the glucose oxidase/catalase system. We also tested the effects of small molecule additives in this system. Biological reducing agents significantly destabilize the Cy5 fluorophore as a function of reducing potential. In contrast, anti-oxidants stabilize the Cy3 and Alexa488 fluorophores. We recommend use of the protocatechuate-3,4,-dioxygenase system with antioxidant additives, and in the absence of biological reducing agents. This system should have wide application to single-molecule fluorescence experiments.

  14. Coupling chemical and biological catalysis: a flexible paradigm for producing biobased chemicals.

    Science.gov (United States)

    Schwartz, Thomas J; Shanks, Brent H; Dumesic, James A

    2016-04-01

    Advances in metabolic engineering have allowed for the development of new biological catalysts capable of selectively de-functionalizing biomass to yield platform molecules that can be upgraded to biobased chemicals using high efficiency continuous processing allowed by heterogeneous chemical catalysis. Coupling these disciplines overcomes the difficulties of selectively activating COH bonds by heterogeneous chemical catalysis and producing petroleum analogues by biological catalysis. We show that carboxylic acids, pyrones, and alcohols are highly flexible platforms that can be used to produce biobased chemicals by this approach. More generally, we suggest that molecules with three distinct functionalities may represent a practical upper limit on the extent of functionality present in the platform molecules that serve as the bridge between biological and chemical catalysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Modification degrees at specific sites on heparan sulphate: an approach to measure chemical modifications on biological molecules with stable isotope labelling

    Science.gov (United States)

    Wu, Zhengliang L.; Lech, Miroslaw

    2005-01-01

    Chemical modification of biological molecules is a general mechanism for cellular regulation. A quantitative approach has been developed to measure the extent of modification on HS (heparan sulphates). Sulphation on HS by sulphotransferases leads to variable sulphation levels, which allows cells to tune their affinities to various extracellular proteins, including growth factors. With stable isotope labelling and HPLC-coupled MS, modification degrees at various O-sulphation sites could be determined. A bovine kidney HS sample was first saturated in vitro with 34S by an OST (O-sulphotransferase), then digested with nitrous acid and analysed with HPLC-coupled MS. The 34S-labelled oligosaccharides were identified based on their unique isotope clusters. The modification degrees at the sulphotransferase recognition sites were obtained by calculating the intensities of isotopic peaks in the isotope clusters. The modification degrees at 3-OST-1 and 6-OST-1 sites were examined in detail. This approach can also be used to study other types of chemical modifications on biological molecules. PMID:15743272

  16. Single-active-electron potentials for molecules in intense laser fields

    DEFF Research Database (Denmark)

    Abu-Samha, Mahmoud; Madsen, Lars Bojer

    2010-01-01

    Single-active-electron potentials are computed for selected molecules, and molecular wave functions with the correct asymptotic behavior are produced. Asymptotic expansion coefficients are extracted from the wave functions and used to compute alignment-dependent ionization yields from molecular...

  17. A Brief Introduction to Single-Molecule Fluorescence Methods.

    Science.gov (United States)

    van den Wildenberg, Siet M J L; Prevo, Bram; Peterman, Erwin J G

    2018-01-01

    One of the more popular single-molecule approaches in biological science is single-molecule fluorescence microscopy, which will be the subject of the following section of this volume. Fluorescence methods provide the sensitivity required to study biology on the single-molecule level, but they also allow access to useful measurable parameters on time and length scales relevant for the biomolecular world. Before several detailed experimental approaches will be addressed, we will first give a general overview of single-molecule fluorescence microscopy. We start with discussing the phenomenon of fluorescence in general and the history of single-molecule fluorescence microscopy. Next, we will review fluorescent probes in more detail and the equipment required to visualize them on the single-molecule level. We will end with a description of parameters measurable with such approaches, ranging from protein counting and tracking, single-molecule localization super-resolution microscopy, to distance measurements with Förster Resonance Energy Transfer and orientation measurements with fluorescence polarization.

  18. Single-molecule imaging and manipulation of biomolecular machines and systems.

    Science.gov (United States)

    Iino, Ryota; Iida, Tatsuya; Nakamura, Akihiko; Saita, Ei-Ichiro; You, Huijuan; Sako, Yasushi

    2018-02-01

    Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration. We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems. Single-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines. Quantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: "What is life?" This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Cell Adhesion Molecule and Lymphocyte Activation Marker Expression during Experimental Vaginal Candidiasis

    Science.gov (United States)

    Wormley, Floyd L.; Chaiban, Joseph; Fidel, Paul L.

    2001-01-01

    Cell-mediated immunity by Th1-type CD4+ T cells is the predominant host defense mechanism against mucosal candidiasis. However, studies using an estrogen-dependent murine model of vaginal candidiasis have demonstrated little to no change in resident vaginal T cells during infection and no systemic T-cell infiltration despite the presence of Candida-specific systemic Th1-type responses in infected mice. The present study was designed to further investigate these observations by characterizing T-cell activation and cell adhesion molecule expression during primary and secondary C. albicans vaginal infections. While flow cytometry analysis of activation markers showed some evidence for activation of CD3+ draining lymph node and/or vaginal lymphocytes during both primary and secondary vaginal Candida infection, CD3+ cells expressing the homing receptors and integrins α4β7, αM290β7, and α4β1 in draining lymph nodes of mice with primary and secondary infections were reduced compared to results for uninfected mice. At the local level, few vaginal lymphocytes expressed integrins, with only minor changes observed during both primary and secondary infections. On the other hand, immunohistochemical analysis of vaginal cell adhesion molecule expression showed increases in mucosal addressin cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression during both primary and secondary infections. Altogether, these data suggest that although the vaginal tissue is permissive to cellular infiltration during a vaginal Candida infection, the reduced numbers of systemic cells expressing the reciprocal cellular adhesion molecules may preempt cellular infiltration, thereby limiting Candida-specific T-cell responses against infection. PMID:11447188

  20. Phytohormones as Important Biologically Active Molecules – Their Simple Simultaneous Detection

    Directory of Open Access Journals (Sweden)

    Ladislav Havel

    2009-05-01

    Full Text Available Phytohormones, their functions, synthesis and effects, are of great interest. To study them in plant tissues accurate and sensitive methods are required. In the present study we aimed at optimizing experimental conditions to separate and determine not only plant hormones but also their metabolites, by liquid chromatography coupled with a UV-VIS detector. The mixture we analyzed was composed of benzyladenine, kinetin, trans-zeatin, cis-zeatin, dihydrozeatin, meta-topolin, ortho-topolin, α-naphthalene acetic acid, indole-3-acetic acid, trans-zeatin-7-glucoside, trans-zeatin-O-glucoside, trans-zeatin-9-riboside, meta-topolin-9-riboside and ortho-topolin-9-riboside. We measured the calibration dependences and estimated limits of detection and quantification under the optimal chromatographic conditions (column: Polaris C18; mobile phase: gradient starting at 2:98 (methanol:0.001% TFA and was increasing to 55:45 during twenty minutes, and then decreasing for 10 min to 35:65, flow rate: 200 µL·min-1, temperature: 50 °C, wavelength: 210 nm. The detection limits for the target molecules were estimated as tens of ng per mL. We also studied the effect of flax extracts on the phytohormones’ signals. Recovery of aliphatic and aromatic cytokinins, metabolites of cytokinins and auxinswere within the range from 87 to 105 %. The experimental conditions were tested on a mass selective detector. In addition we analysed a commercial product used for stimulation of roots formation in cuttings of poorly rooting plants. The determined content of α-naphthalene acetic acid was in good agreement with that declared by the manufacturer.

  1. Life's First Handshake - Discovery of the Interstellar Chiral Molecule Propylene Oxide

    Science.gov (United States)

    McGuire, Brett A.; Carroll, P. Brandon; Loomis, Ryan A.; Finneran, Ian A.; Jewell, Philip R.; Remijan, Anthony J.; Blake, Geoffrey A.

    2016-06-01

    Life on Earth relies on chiral molecules, that is, species not superimposable on their mirror images. This manifests itself in the selection of a single molecular handedness, or homochirality, across the biosphere, and is perhaps most readily apparent in the large enhancement in biological activity of particular amino acid and sugar enantiomers. Yet, the ancestral origin of biological homochirality remains a mystery. The non-racemic ratios in some organics isolated from primitive meteorites hint at a primordial chiral seed, but even these samples have experienced substantial processing during planetary assembly, obscuring their complete histories. To determine the underlying origin of any enantiomeric excess, it is critical to understand the molecular gas from which these molecules originated. Here, we present the first extra-solar, astronomical detection of a chiral molecule, propylene oxide (CH3CHCH2O), in absorption toward the Galactic Center. We discuss the implications of the detection on observational searches to determine a primordial chiral excess, as well as the state of laboratory efforts in these areas.

  2. Neutron structural biology

    Energy Technology Data Exchange (ETDEWEB)

    Niimura, Nobuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    Neutron diffraction provides an experimental method of directly locating hydrogen atoms in protein which play important roles in physiological functions. However, there are relatively few examples of neutron crystallography in biology since it takes a lot of time to collect a sufficient number of Bragg reflections due to the low flux of neutrons illuminating the sample. In order to overcome the flux problem, we have successfully developed the neutron IP, where the neutron converter, {sup 6}Li or Gd, was mixed with a photostimulated luminescence material on flexible plastic support. Neutron Laue diffraction 2A data from tetragonal lysozyme were collected for 10 days with neutron imaging plates, and 960 hydrogen atoms in the molecule and 157 bound water molecules were identified. These results explain the proposed hydrolysis mechanism of the sugar by the lysozyme molecule and that lysozyme is less active at pH7.0. (author)

  3. STRUCTURES AND BIOLOGICAL ACTIVITY OF CUPROPHYLLINS

    Directory of Open Access Journals (Sweden)

    Martynov A.V.

    2017-06-01

    Full Text Available Chlorophylls (a, b are the porphyrin compounds and most common chemical in the plant’s world. In fact, these compounds are an obligatory intermediate product both in energy metabolism and in plant catabolism. At the same time, currently there are few pharmaceutical preparations on the pharmaceutical market based on chlorophylls. Dyes based on hydrolyzed chlorophyll are successfully used in the food industry. Commercial chlorophylline is a copper complex of hydrolyzed chlorophylls. As shown earlier in TLC, the chlorophyllin mixture contains a large number of different compounds. It is like water-soluble saponified derivatives in the form of sodium-magnesium complexes, and similar structures in the form of a complex with copper. The latter are more brightly colored, soluble in water and widely used as coloring agents in cooking. In this case, if the initial chlorophyll was not found to have a pronounced biological activity, the substituted derivatives in the form of copper complexes possessed a number of new unique biological properties. Non-hydrolyzed hydrophobic cuprophylline obtained from eucalyptus leaves possessed high antimicrobial activity to most strains of staphylococci, inclusion resistant to antimicrobials and multiresistant strains. This drug is called Chlorophyllipt, it is allowed to be used as a medicinal product and is one of the oldest antibacterial drugs from plants on the market. It is marketed as ethanoic and oily solutions for topical use, and as an alcohol solution for intravenous injections. Its main purpose is the fight against staphylococcal infections. Recently, found that the oral administration of chlorophyllipt activates cellular immunity and indirectly exhibits antiviral activity. Another compound of cuprophyllin is water-soluble chlorophyllin. Some authors show the variability of the structure and biological activity of cuprophyllins. Different derivatives of chlorophyll have different biological activity

  4. Energy dependence of effective atomic numbers for photon energy absorption and photon interaction: Studies of some biological molecules in the energy range 1 keV-20 MeV

    DEFF Research Database (Denmark)

    Manohara, S.R.; Hanagodimath, S.M.; Gerward, Leif

    2008-01-01

    Effective atomic numbers for photon energy absorption, Z(PEA,eff), and for photon interaction, Z(PI,eff), have been calculated by a direct method in the photon-energy region from 1 keV to 20 MeV for biological molecules, such as fatty acids (lauric, myristic, palmitic, stearic, oleic, linoleic......, linolenic, arachidonic, and arachidic acids), nucleotide bases (adenine, guanine, cytosine, uracil, and thymine), and carbohydrates (glucose, sucrose, raffinose, and starch). The Z(PEA, eff) and Z(PI, eff) values have been found to change with energy and composition of the biological molecules. The energy...

  5. Preface: Special Topic on Single-Molecule Biophysics.

    Science.gov (United States)

    Makarov, Dmitrii E; Schuler, Benjamin

    2018-03-28

    Single-molecule measurements are now almost routinely used to study biological systems and processes. The scope of this special topic emphasizes the physics side of single-molecule observations, with the goal of highlighting new developments in physical techniques as well as conceptual insights that single-molecule measurements bring to biophysics. This issue also comprises recent advances in theoretical physical models of single-molecule phenomena, interpretation of single-molecule signals, and fundamental areas of statistical mechanics that are related to single-molecule observations. A particular goal is to illustrate the increasing synergy between theory, simulation, and experiment in single-molecule biophysics.

  6. Radical inactivation of a biological sulphydryl molecule

    International Nuclear Information System (INIS)

    Lin, W.S.; Lal, M.; Gaucher, G.M.; Armstrong, D.A.

    1977-01-01

    Reactive species produced from the free radical-induced chain oxidation of low molecular weight sulphydryl-containing molecules in aerated solutions deactivate the sulphydryl-containing enzyme papain, forming both reparable mixed disulphides and non-reparable products. This inactivation is highly efficient for penicillamine and glutathione, but almost negligible with cysteine, which is a protector of papain for [cysteine] / [papain] >= 5 under all conditions used. In the case of glutathione, superoxide dismutase caused only a small reduction in the inactivation and peroxide yields were small, implying that the deactivating species are not .O 2 - but RSOO. radicals or products from them. For penicillamine, however, dimutase was highly effective and the peroxide yields were relatively large, demonstrating that .O 2 - or a radical with similar capabilities for forming H 2 O 2 and being deactivated by dismutase was involved. Although in the presence of dismutase penicillamine is a better protector of non-reparable papain inactivation than glutathione, it suffers from a deficiency in that the papain-penicillamine mixed disulphide, which is always formed, cannot be repaired by spontaneous reaction with RSH molecules. (author)

  7. Tracking problems and possible solutions in the quantitative determination of small molecule drugs and metabolites in biological fluids using liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Bakhtiar, Ray; Majumdar, Tapan K

    2007-01-01

    During the last decade, quantification of low molecular weight molecules using liquid chromatography-tandem mass spectrometry in biological fluids has become a common procedure in many preclinical and clinical laboratories. This overview highlights a number of issues involving "small molecule drugs", bioanalytical liquid chromatography-tandem mass spectrometry, which are frequently encountered during assay development. In addition, possible solutions to these issues are proposed with examples in some of the case studies. Topics such as chromatographic peak shape, carry-over, cross-talk, standard curve non-linearity, internal standard selection, matrix effect, and metabolite interference are presented. Since plasma is one of the most widely adopted biological fluid in drug discovery and development, the focus of this discussion will be limited to plasma analysis. This article is not intended to be a comprehensive overview and readers are encouraged to refer to the citations herein.

  8. Microwave assistant synthesis, crystal structure and biological activity of a 1,2,4-triazole compound

    International Nuclear Information System (INIS)

    Ke, W.; Sun, N.B.

    2013-01-01

    The title compound (C/sub 17/H/sub 14/F/sub 2/N/sub 4/SO) were synthesized and recrystallized from CH/sub 3/CN. The compound was characterized by 1h-nmr, ftir, ms, hrms and x-ray diffraction. the compound crystallized in the monoclinic space group c2/c with a = 27.532(6), b 8.9596(18), c 14.609(3) alpha = 90, beta = 112.59(3), lambda =90 degree, gamma = 3327.1(12) alpha 3, z = 8 and r = 0.0327 for 2596 observed reflections with 1 > 2 (i). x-ray analysis reveals that not only intermolecular N-H-N interactions, but also C-H Pie stacking interactions exist in the adjacent molecules. The biological activities results showed that it exhibited significant herbicidal activity towards brassica napus. (author)

  9. Impact of dehydration of purslane on retention of bioactive molecules and antioxidant activity.

    Science.gov (United States)

    Shanker, Niharika; Debnath, Sukumar

    2015-10-01

    Purslane (Portulaca oleracea L.) has several health benefits, such as it reduces risk of CVD, obesity and diabetes. The objective of the study was to investigate the effect of different drying on retention of bioactive molecules, such as omega-3 fatty acids, total phenolic content and antiradical activity of purslane. Five different dehydration methods including microwave (100 MW, 5 min), tray, vacuum, low temperature low humidity, infrared were used at 55-60 °C for 5-7 h for dehydration of purslane. Three solvents, viz. water, ethanol and methanol were used for extraction of bioactive molecules from purslane. Total polyphenol content, antiradical activity and rehydration ratio of the bioactive molecules were determined. Results revealed that total PUFA, α-linolenic acid (ALA), total polyphenol content and antiradical activity were found to retain in the dried purslane in the range of (47.9-59.9 %), (42.5-50 %), (188-408GAE/100 g) and (33.0-88.8 mg/100 g) respectively. The highest values of ALA, total polyphenol content and antiradical activity were found to obtain in the vacuum dried sample. Rehydration ratio was found in the range of 3.2-4.3 and vacuum dried purslane showed maximum rehydration. It could be concluded that vacuum dehydration of purslane is an effective method for retention of bioactive molecules and good rehydration behaviour of dried purslane.

  10. Glycomics: revealing the dynamic ecology and evolution of sugar molecules.

    Science.gov (United States)

    Springer, Stevan A; Gagneux, Pascal

    2016-03-01

    Sugars are the most functionally and structurally diverse molecules in the biological world. Glycan structures range from tiny single monosaccharide units to giant chains thousands of units long. Some glycans are branched, their monosaccharides linked together in many different combinations and orientations. Some exist as solitary molecules; others are conjugated to proteins and lipids and alter their collective functional properties. In addition to structural and storage roles, glycan molecules participate in and actively regulate physiological and developmental processes. Glycans also mediate cellular interactions within and between individuals. Their roles in ecology and evolution are pivotal, but not well studied because glycan biochemistry requires different methods than standard molecular biology practice. The properties of glycans are in some ways convenient, and in others challenging. Glycans vary on organismal timescales, and in direct response to physiological and ecological conditions. Their mature structures are physical records of both genetic and environmental influences during maturation. We describe the scope of natural glycan variation and discuss how studying glycans will allow researchers to further integrate the fields of ecology and evolution. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Bioactive Molecule-loaded Drug Delivery Systems to Optimize Bone Tissue Repair.

    Science.gov (United States)

    Oshiro, Joao Augusto; Sato, Mariana Rillo; Scardueli, Cassio Rocha; Lopes de Oliveira, Guilherme Jose Pimentel; Abucafy, Marina Paiva; Chorilli, Marlus

    2017-01-01

    Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Small molecule annotation for the Protein Data Bank.

    Science.gov (United States)

    Sen, Sanchayita; Young, Jasmine; Berrisford, John M; Chen, Minyu; Conroy, Matthew J; Dutta, Shuchismita; Di Costanzo, Luigi; Gao, Guanghua; Ghosh, Sutapa; Hudson, Brian P; Igarashi, Reiko; Kengaku, Yumiko; Liang, Yuhe; Peisach, Ezra; Persikova, Irina; Mukhopadhyay, Abhik; Narayanan, Buvaneswari Coimbatore; Sahni, Gaurav; Sato, Junko; Sekharan, Monica; Shao, Chenghua; Tan, Lihua; Zhuravleva, Marina A

    2014-01-01

    The Protein Data Bank (PDB) is the single global repository for three-dimensional structures of biological macromolecules and their complexes, and its more than 100,000 structures contain more than 20,000 distinct ligands or small molecules bound to proteins and nucleic acids. Information about these small molecules and their interactions with proteins and nucleic acids is crucial for our understanding of biochemical processes and vital for structure-based drug design. Small molecules present in a deposited structure may be attached to a polymer or may occur as a separate, non-covalently linked ligand. During curation of a newly deposited structure by wwPDB annotation staff, each molecule is cross-referenced to the PDB Chemical Component Dictionary (CCD). If the molecule is new to the PDB, a dictionary description is created for it. The information about all small molecule components found in the PDB is distributed via the ftp archive as an external reference file. Small molecule annotation in the PDB also includes information about ligand-binding sites and about covalent and other linkages between ligands and macromolecules. During the remediation of the peptide-like antibiotics and inhibitors present in the PDB archive in 2011, it became clear that additional annotation was required for consistent representation of these molecules, which are quite often composed of several sequential subcomponents including modified amino acids and other chemical groups. The connectivity information of the modified amino acids is necessary for correct representation of these biologically interesting molecules. The combined information is made available via a new resource called the Biologically Interesting molecules Reference Dictionary, which is complementary to the CCD and is now routinely used for annotation of peptide-like antibiotics and inhibitors. © The Author(s) 2014. Published by Oxford University Press.

  13. Torque Measurement at the Single Molecule Level

    Science.gov (United States)

    Forth, Scott; Sheinin, Maxim Y.; Inman, James; Wang, Michelle D.

    2017-01-01

    Methods for exerting and measuring forces on single molecules have revolutionized the study of the physics of biology. However, it is often the case that biological processes involve rotation or torque generation, and these parameters have been more difficult to access experimentally. Recent advances in the single molecule field have led to the development of techniques which add the capability of torque measurement. By combining force, displacement, torque, and rotational data, a more comprehensive description of the mechanics of a biomolecule can be achieved. In this review, we highlight a number of biological processes for which torque plays a key mechanical role. We describe the various techniques that have been developed to directly probe the torque experienced by a single molecule, and detail a variety of measurements made to date using these new technologies. We conclude by discussing a number of open questions and propose systems of study which would be well suited for analysis with torsional measurement techniques. PMID:23541162

  14. Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots.

    Science.gov (United States)

    Hess, H; Ross, Jennifer L

    2017-09-18

    Biological systems have evolved to harness non-equilibrium processes from the molecular to the macro scale. It is currently a grand challenge of chemistry, materials science, and engineering to understand and mimic biological systems that have the ability to autonomously sense stimuli, process these inputs, and respond by performing mechanical work. New chemical systems are responding to the challenge and form the basis for future responsive, adaptive, and active materials. In this article, we describe a particular biochemical-biomechanical network based on the microtubule cytoskeletal filament - itself a non-equilibrium chemical system. We trace the non-equilibrium aspects of the system from molecules to networks and describe how the cell uses this system to perform active work in essential processes. Finally, we discuss how microtubule-based engineered systems can serve as testbeds for autonomous chemical robots composed of biological and synthetic components.

  15. A Selective Assay to Detect Chitin and Biologically Active Nano-Machineries for Chitin-Biosynthesis with Their Intrinsic Chitin-Synthase Molecules

    Directory of Open Access Journals (Sweden)

    Hildgund Schrempf

    2010-09-01

    Full Text Available A new assay system for chitin has been developed. It comprises the chitin-binding protein ChbB in fusion with a His-tag as well as with a Strep-tag, the latter of which was chemically coupled to horseradish peroxidase. With the resulting complex, minimal quantities of chitin are photometrically detectable. In addition, the assay allows rapid scoring of the activity of chitin-synthases. As a result, a refined procedure for the rapid purification of yeast chitosomes (nano-machineries for chitin biosynthesis has been established. Immuno-electronmicroscopical studies of purified chitosomes, gained from a yeast strain carrying a chitin-synthase gene fused to that for GFP (green-fluorescence protein, has led to the in situ localization of chitin-synthase-GFP molecules within chitosomes.

  16. Ethnobotanical and biological activities of Leptadenia pyrotechnica ...

    African Journals Online (AJOL)

    Conclusion: This review includes the substance of different ethnobotanical uses, phytochemistry and exclusive capability of this plant in the field of anti-microbial and human disease activities. Key words: Leptadenia pyrotechnica, Biological activities, Desert plant, Ethnobotanical, Phytochemical activity, phytochemistry.

  17. Bone Scan in Detection of Biological Activity in Nonhypertrophic Fracture Nonunion

    OpenAIRE

    Gandhi, Sunny J.; Rabadiya, Bhavdeep

    2017-01-01

    Biological activity of the fracture site is very important factor in treatment planning of fracture nonunion. If no biological activity is detected, then an autologous bone graft can be supplemented or osteogenic supplementations, such as bone morphogenetic protein is given. If biological activity is present, then secure fixation is sufficient to achieve bony union. Biological activity of nonunions is usually assessed by conventional radiographs. The presence of callus formation is usually as...

  18. Expression and characterization of recombinant single-chain salmon class I MHC fused with beta2-microglobulin with biological activity

    DEFF Research Database (Denmark)

    Zhao, Heng; Stet, René J M; Skjødt, Karsten

    2008-01-01

    Heterodimeric class I major histocompatibility complex (MHC) molecules consist of a putative 45-kDa heavy chain and a 12-kDa beta2-microglobulin (beta2m) light chain. The knowledge about MHC genes in Atlantic salmon accumulated during the last decade has allowed us to generate soluble and stable ...... MHC class I molecules with biological activity. We report here the use of a bacterial expression system to produce the recombinant single-chain MHC molecules based on a specific allele Sasa-UBA*0301. This particular allele was selected because previous work has shown its association...... antibodies were successfully produced against both the MHC class I heavy chain and beta(2)m, and showed binding to the recombinant molecule. The recombinant complex Sasabeta2mUBA*0301 was expressed and isolated; the production was scaled up by adjusting to its optimal conditions. Subsequently......, the recombinant proteins were purified by affinity chromatography using mAb against beta2m and alpha3. Eluates were analyzed by Western blot and refolded by the removal of denaturant. The correct folding was confirmed by measuring its binding capacity against mAb produced to recognize the native form of MHC...

  19. Inhibiting prolyl isomerase activity by hybrid organic-inorganic molecules containing rhodium(II) fragments.

    Science.gov (United States)

    Coughlin, Jane M; Kundu, Rituparna; Cooper, Julian C; Ball, Zachary T

    2014-11-15

    A small molecule containing a rhodium(II) tetracarboxylate fragment is shown to be a potent inhibitor of the prolyl isomerase FKBP12. The use of small molecules conjugates of rhodium(II) is presented as a general strategy for developing new protein inhibitors based on distinct structural and sequence features of the enzyme active site. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Immobilization of small molecules and proteins by radio-derivatized polystyrene

    International Nuclear Information System (INIS)

    Varga, J.M.; Fritsch, P.

    1990-01-01

    When molded polystyrene (PS) products (e.g., microtiter plates) or latex particles are irradiated with high-energy (1-10 Mrads) gamma rays in the presence of nonpolymerizable small molecules such as aromatic amines, some of these molecules incorporate into PS, which leads to the formation of radio-derivatized PS (RDPS). Two classes of RDPS can be identified regarding their ability for immobilization of biologically important molecules: (1) reactive RDPS that are able to form covalent bonds with molecules such as proteins without the help of cross-linkers, and (2) functionalized RDPS that can be used for the immobilization of molecules with activators (e.g., carbodiimides) or cross-linkers. The method can be used for the production of low-noise supports for binding assays. Most of the RDPS can be produced without impairment of the optical quality of PS, making derivatized microtiter plates suitable for colorimetric assays. The principle can be applied for the preparation of affinity sorbents, e.g., for high-performance affinity chromatography and for the immobilization of enzymes using latex PS particles

  1. Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity.

    Science.gov (United States)

    Kimani, Stanley G; Kumar, Sushil; Bansal, Nitu; Singh, Kamalendra; Kholodovych, Vladyslav; Comollo, Thomas; Peng, Youyi; Kotenko, Sergei V; Sarafianos, Stefan G; Bertino, Joseph R; Welsh, William J; Birge, Raymond B

    2017-03-08

    TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6. These inhibitors effectively block Gas6-inducible Axl receptor activation with low micromolar IC 50s in cell-based reporter assays, inhibit Gas6-inducible motility in Axl-expressing cell lines, and suppress H1299 lung cancer tumor growth in a mouse xenograft NOD-SCIDγ model. Furthermore, using homology models and biochemical verifications, we show that RU301 and 302 also inhibit Gas6 inducible activation of Mertk and Tyro3 suggesting they can act as pan-TAM inhibitors that block the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. Together, these observations establish that small molecules that bind to the interface between TAM Ig1 domain and Gas6 Lg1 domain can inhibit TAM activation, and support the further development of small molecule Gas6-TAM interaction inhibitors as a novel class of cancer therapeutics.

  2. Part A. Neutron activation analysis of selenium and vanadium in biological matrices. Part B. Isomeric transition activation in aqueous solutions of alkyl bromides

    International Nuclear Information System (INIS)

    Ebrahim, A.

    1988-01-01

    Several procedures were evaluated for determination of selenium in biological fluids and vanadium in biological tissues by neutron activation analysis (NAA) employing 77m Se and 52 V isotopes, respectively. Procedures for determination of total selenium, trimethylselenonium (TMSe) ion and selenite (SeO 3 2- ) ion in urine and serum and for total selenoamino acids in urine were developed by utilizing anion exchange chromatography and molecular NAA. A pre-column derivatization of selenoamino acids with o-phthalaldehyde was necessary for their determination. Also an analytical approach was developed for determination of trace vanadium in liver samples from normal and diabetic rats as well as human and cow. Reactions of bromine-80 activated by radiative neutron capture and bromine-82 activated by isomeric transition were investigated in aqueous solutions of bromomethane and 1-bromobutane. Bromine-80 organic yields decreased with decreasing solute concentrations. The tendency for aggregation of the solute molecules diminished as the solute concentration approached zero where the probable state of the solute approached a monomolecular dispersion. Unlike reactions of 80 Br born by 79 Br(n,γ) 80 Br reaction, the total organic product yields resulting from the 82m Br(I.T.) 82 Br process showed no solute concentration dependence

  3. Physical activity and biological maturation: a systematic review

    Directory of Open Access Journals (Sweden)

    Eliane Denise Araújo Bacil

    2015-03-01

    Full Text Available OBJECTIVE: To analyze the association between physical activity (PA and biological maturation in children and adolescents. DATA SOURCE: We performed a systematic review in April 2013 in the electronic databases of PubMed/MEDLINE, SportDiscus, Web of Science and LILACS without time restrictions. A total of 628 potentially relevant articles were identified and 10 met the inclusion criteria for this review: cross-sectional or longitudinal studies, published in Portuguese, English or Spanish, with schoolchildren aged 9-15 years old of both genders. DATA SYNTHESIS: Despite the heterogeneity of the studies, there was an inverse association between PA and biological maturation. PA decreases with increased biological and chronological age in both genders. Boys tend to be more physically active than girls; however, when controlling for biological age, the gender differences disappear. The association between PA and timing of maturation varies between the genders. Variation in the timing of biological maturation affects the tracking of PA in early adolescent girls. This review suggests that mediators (BMI, depression, low self-esteem, and concerns about body weight can explain the association between PA and biological maturation. CONCLUSIONS: There is an association between PA and biological maturation. PA decreases with increasing biological age with no differences between genders. As for the timing of biological maturation, this association varies between genders.

  4. On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry.

    Science.gov (United States)

    Long, Marcus J C; Poganik, Jesse R; Aye, Yimon

    2016-03-23

    Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is "tethering"-a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein-protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: "multifunctional scaffolding" versus "on-demand targeting". By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms.

  5. Structure and Structure-activity Relationship of Functional Organic Molecules

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ Research theme The group is made up of junior scientists from the State Key Laboratory of Elemento-organic Chemistry, Nankai University.The scientists focus their studis on the structure and structure-activity relationship of functional organic molecules not only because it has been the basis of their research, but also because the functional study of organic compounds is now a major scientific issue for organic chemists around the world.

  6. Loranthus micranthus Linn.: Biological Activities and Phytochemistry

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2013-01-01

    Full Text Available Loranthus micranthus Linn. is a medicinal plant from the Loranthaceae family commonly known as an eastern Nigeria species of the African mistletoe and is widely used in folkloric medicine to cure various ailments and diseases. It is semiparasitic plant because of growing on various host trees and shrubs and absorbing mineral nutrition and water from respective host. Hence, the phytochemicals and biological activities of L. micranthus demonstrated strong host and harvesting period dependency. The leaves have been proved to possess immunomodulatory, antidiabetic, antimicrobial, antihypertensive, antioxidant, antidiarrhoeal, and hypolipidemic activities. This review summarizes the information and findings concerning the current knowledge on the biological activities, pharmacological properties, toxicity, and chemical constituents of Loranthus micranthus.

  7. Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass

    DEFF Research Database (Denmark)

    Toft, P; Tønnesen, Else Kirstine; Zülow, I

    1997-01-01

    Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open...

  8. The aims of systems biology: between molecules and organisms.

    Science.gov (United States)

    Noble, D

    2011-05-01

    The systems approach to biology has a long history. Its recent rapid resurgence at the turn of the century reflects the problems encountered in interpreting the sequencing of the genome and the failure of that immense achievement to provide rapid and direct solutions to major multi-factorial diseases. This paper argues that systems biology is necessarily multilevel and that there is no privileged level of causality in biological systems. It is an approach rather than a separate discipline. Functionality arises from biological networks that interact with the genome, the environment and the phenotype. This view of biology is very different from the gene-centred views of neo-Darwinism and molecular biology. In neuroscience, the systems approach leads naturally to 2 important conclusions: first, that the idea of 'programs' in the brain is confusing, and second, that the self is better interpreted as a process than as an object. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity.

    Science.gov (United States)

    Chen, Yun; Yao, Fangke; Ming, Ke; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo

    2016-12-13

    Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.

  10. Light controllable catalytic activity of Au clusters decorated with photochromic molecules

    Science.gov (United States)

    Guo, Na; Meng Yam, Kah; Zhang, Chun

    2018-06-01

    By ab initio calculations, we show that when decorated with a photochromic molecule, the catalytic activity of an Au nanocluster can be reversibly controlled by light. The combination of a photochromic thiol-pentacarbonyl azobenzene (TPA) molecule and an Au8 cluster is chosen as a model catalyst. The TPA molecule has two configurations (trans and cis) that can be reversibly converted to each other upon photo-excitation. Our calculations show that when the TPA takes the trans configuration, the combined system (trans-Au8) is an excellent catalyst for CO oxidation. The reaction barrier of the catalyzed CO oxidation is less than 0.4 eV. While, the reaction barrier of CO oxidation catalyzed by cis-Au8 is very high (>2.7 eV), indicating that the catalyst is inactive. These results pave the way for a new class of light controllable nanoscale catalysts.

  11. The yeast three-hybrid system as an experimental platform to identify proteins interacting with small signaling molecules in plant cells: Potential and limitations

    Directory of Open Access Journals (Sweden)

    Stéphanie eCottier

    2011-12-01

    Full Text Available Chemical genetics is a powerful scientific strategy that utilizes small bioactive molecules as experimental tools to unravel biological processes. Bioactive compounds occurring in nature represent an enormous diversity of structures that can be used to dissect functions of biological systems. Once the bioactivity of a natural or synthetic compound has been critically evaluated the challenge remains to identify its molecular target and mode of action, which usually is a time consuming and labor-intensive process. To facilitate this task, we decided to implement the yeast three-hybrid (Y3H technology as a general experimental platform to scan the whole Arabidopsis proteome for targets of small signaling molecules. The Y3H technology is based on the yeast two-hybrid system and allows direct cloning of proteins that interact in vivo with a synthetic hybrid ligand, which comprises the biologically active molecule of interest covalently linked to methotrexate (Mtx. In yeast nucleus the hybrid ligand connects two fusion proteins: the Mtx part binding to dihydrofolate reductase fused to a DNA binding domain (encoded in the yeast strain, and the bioactive molecule part binding to its potential protein target fused to a DNA activating domain (encoded on a cDNA expression vector. During cDNA library screening, the formation of this ternary, transcriptional activator complex leads to reporter gene activation in yeast cells, and thereby allows selection of the putative targets of small bioactive molecules of interest. Here we present the strategy and experimental details for construction and application of a Y3H platform, including chemical synthesis of different hybrid ligands, construction of suitable cDNA libraries, the choice of yeast strains, and appropriate screening conditions. Based on the results obtained and the current literature we discussed the perspectives and limitations of the Y3H approach for identifying targets of small bioactive molecules.

  12. Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology

    Science.gov (United States)

    2011-01-01

    Single-molecule measurement techniques have illuminated unprecedented details of chemical behavior, including observations of the motion of a single molecule on a surface, and even the vibration of a single bond within a molecule. Such measurements are critical to our understanding of entities ranging from single atoms to the most complex protein assemblies. We provide an overview of the strikingly diverse classes of measurements that can be used to quantify single-molecule properties, including those of single macromolecules and single molecular assemblies, and discuss the quantitative insights they provide. Examples are drawn from across the single-molecule literature, ranging from ultrahigh vacuum scanning tunneling microscopy studies of adsorbate diffusion on surfaces to fluorescence studies of protein conformational changes in solution. PMID:21338175

  13. Semiexperimental equilibrium structures for building blocks of organic and biological molecules: the B2PLYP route.

    Science.gov (United States)

    Penocchio, Emanuele; Piccardo, Matteo; Barone, Vincenzo

    2015-10-13

    The B2PLYP double hybrid functional, coupled with the correlation-consistent triple-ζ cc-pVTZ (VTZ) basis set, has been validated in the framework of the semiexperimental (SE) approach for deriving accurate equilibrium structures of molecules containing up to 15 atoms. A systematic comparison between new B2PLYP/VTZ results and several equilibrium SE structures previously determined at other levels, in particular B3LYP/SNSD and CCSD(T) with various basis sets, has put in evidence the accuracy and the remarkable stability of such model chemistry for both equilibrium structures and vibrational corrections. New SE equilibrium structures for phenylacetylene, pyruvic acid, peroxyformic acid, and phenyl radical are discussed and compared with literature data. Particular attention has been devoted to the discussion of systems for which lack of sufficient experimental data prevents a complete SE determination. In order to obtain an accurate equilibrium SE structure for these situations, the so-called templating molecule approach is discussed and generalized with respect to our previous work. Important applications are those involving biological building blocks, like uracil and thiouracil. In addition, for more general situations the linear regression approach has been proposed and validated.

  14. Ordinary differential equations with applications in molecular biology.

    Science.gov (United States)

    Ilea, M; Turnea, M; Rotariu, M

    2012-01-01

    Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances

  15. Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy

    Directory of Open Access Journals (Sweden)

    Shan L

    2015-09-01

    Full Text Available Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of South Dakota, Vermillion, SD, USA; 3Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6-isothiocyanate-arginine-paclitaxel (FA-FITC-Arg-PTX and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu-PTX, composed of folic acid (FA, target, amino acids (Arg or Glu, linker, and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. Keywords: multi-small molecules, paclitaxel, prodrugs, targeting, tumor therapy

  16. Applications of thermal neutron scattering in biology, biochemistry and biophysics

    International Nuclear Information System (INIS)

    Worcester, D.L.

    1977-01-01

    Biological applications of thermal neutron scattering have increased rapidly in recent years. The following categories of biological research with thermal neutron scattering are presently identified: crystallography of biological molecules; neutron small-angle scattering of biological molecules in solution (these studies have already included numerous measurements of proteins, lippoproteins, viruses, ribosomal subunits and chromatin subunit particles); neutron small-angle diffraction and scattering from biological membranes and membrane components; and neutron quasielastic and inelastic scattering studies of the dynamic properties of biological molecules and materials. (author)

  17. Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity

    Directory of Open Access Journals (Sweden)

    Yun Chen

    2016-12-01

    Full Text Available Traditional Chinese Medicine (TCM has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.

  18. Dynamics of water molecules in the active-site cavity of human cytochromes P450

    DEFF Research Database (Denmark)

    Rydberg, Patrik; Rod, Thomas Holm; Olsen, Lars

    2007-01-01

    We have studied the dynamics of water molecules in six crystal structures of four human cytochromes P450, 2A6, 2C8, 2C9, and 3A4, with molecular dynamics simulations. In the crystal structures, only a few water molecules are seen and the reported sizes of the active-site cavity vary a lot....... In the simulations, the cavities are completely filled with water molecules, although with approximately 20% lower density than in bulk water. The 2A6 protein differs from the other three in that it has a very small cavity with only two water molecules and no exchange with the surroundings. The other three proteins...... channels, through which there is a quite frequent exchange of water molecules (one molecule is exchanged every 30-200 ps), except in 2A6. Most of the channels are observed also in the crystal structures, but two to three channels in each protein open only during the simulations. There are no water...

  19. Synthetic biology era: Improving antibiotic's world.

    Science.gov (United States)

    Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

    2017-06-15

    The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge. Copyright © 2017. Published by Elsevier Inc.

  20. Single Molecule Biophysics Experiments and Theory

    CERN Document Server

    Komatsuzaki, Tamiki; Takahashi, Satoshi; Yang, Haw; Silbey, Robert J; Rice, Stuart A; Dinner, Aaron R

    2011-01-01

    Discover the experimental and theoretical developments in optical single-molecule spectroscopy that are changing the ways we think about molecules and atoms The Advances in Chemical Physics series provides the chemical physics field with a forum for critical, authoritative evaluations of advances in every area of the discipline. This latest volume explores the advent of optical single-molecule spectroscopy, and how atomic force microscopy has empowered novel experiments on individual biomolecules, opening up new frontiers in molecular and cell biology and leading to new theoretical approaches

  1. Thin film composition with biological substance and method of making

    International Nuclear Information System (INIS)

    Campbell, A.A.; Song, L.

    1999-01-01

    The invention provides a thin-film composition comprising an underlying substrate of a first material including a plurality of attachment sites; a plurality of functional groups chemically attached to the attachment sites of the underlying substrate; and a thin film of a second material deposited onto the attachment sites of the underlying substrate, and a biologically active substance deposited with the thin-film. Preferably the functional groups are attached to a self assembling monolayer attached to the underlying substrate. Preferred functional groups attached to the underlying substrate are chosen from the group consisting of carboxylates, sulfonates, phosphates, optionally substituted, linear or cyclo, alkyl, alkene, alkyne, aryl, alkylaryl, amine, hydroxyl, thiol, silyl, phosphoryl, cyano, metallocenyl, carbonyl, and polyphosphate. Preferred materials for the underlying substrate are selected from the group consisting of a metal, a metal alloy, a plastic, a polymer, a proteic film, a membrane, a glass or a ceramic. The second material is selected from the group consisting of inorganic crystalline structures, inorganic amorphous structures, organic crystalline structures, and organic amorphous structures. Preferred second materials are phosphates, especially calcium phosphates and most particularly calcium apatite. The biologically active molecule is a protein, peptide, DNA segment, RNA segment, nucleotide, polynucleotide, nucleoside, antibiotic, antimicrobial, radioisotope, chelated radioisotope, chelated metal, metal salt, anti-inflammatory, steroid, nonsteroid anti-inflammatory, analgesic, antihistamine, receptor binding agent, or chemotherapeutic agent, or other biologically active material. Preferably the biologically active molecule is an osteogenic factor consisting of the compositions listed above

  2. Finding optimal interaction interface alignments between biological complexes

    KAUST Repository

    Cui, Xuefeng; Naveed, Hammad; Gao, Xin

    2015-01-01

    Motivation: Biological molecules perform their functions through interactions with other molecules. Structure alignment of interaction interfaces between biological complexes is an indispensable step in detecting their structural similarities, which

  3. Quantitative assessment of biological impact using transcriptomic data and mechanistic network models

    International Nuclear Information System (INIS)

    Thomson, Ty M.; Sewer, Alain; Martin, Florian; Belcastro, Vincenzo; Frushour, Brian P.; Gebel, Stephan; Park, Jennifer; Schlage, Walter K.; Talikka, Marja; Vasilyev, Dmitry M.; Westra, Jurjen W.; Hoeng, Julia; Peitsch, Manuel C.

    2013-01-01

    Exposure to biologically active substances such as therapeutic drugs or environmental toxicants can impact biological systems at various levels, affecting individual molecules, signaling pathways, and overall cellular processes. The ability to derive mechanistic insights from the resulting system responses requires the integration of experimental measures with a priori knowledge about the system and the interacting molecules therein. We developed a novel systems biology-based methodology that leverages mechanistic network models and transcriptomic data to quantitatively assess the biological impact of exposures to active substances. Hierarchically organized network models were first constructed to provide a coherent framework for investigating the impact of exposures at the molecular, pathway and process levels. We then validated our methodology using novel and previously published experiments. For both in vitro systems with simple exposure and in vivo systems with complex exposures, our methodology was able to recapitulate known biological responses matching expected or measured phenotypes. In addition, the quantitative results were in agreement with experimental endpoint data for many of the mechanistic effects that were assessed, providing further objective confirmation of the approach. We conclude that our methodology evaluates the biological impact of exposures in an objective, systematic, and quantifiable manner, enabling the computation of a systems-wide and pan-mechanistic biological impact measure for a given active substance or mixture. Our results suggest that various fields of human disease research, from drug development to consumer product testing and environmental impact analysis, could benefit from using this methodology. - Highlights: • The impact of biologically active substances is quantified at multiple levels. • The systems-level impact integrates the perturbations of individual networks. • The networks capture the relationships between

  4. Cell biochemistry studied by single-molecule imaging.

    Science.gov (United States)

    Mashanov, G I; Nenasheva, T A; Peckham, M; Molloy, J E

    2006-11-01

    Over the last decade, there have been remarkable developments in live-cell imaging. We can now readily observe individual protein molecules within living cells and this should contribute to a systems level understanding of biological pathways. Direct observation of single fluorophores enables several types of molecular information to be gathered. Temporal and spatial trajectories enable diffusion constants and binding kinetics to be deduced, while analyses of fluorescence lifetime, intensity, polarization or spectra give chemical and conformational information about molecules in their cellular context. By recording the spatial trajectories of pairs of interacting molecules, formation of larger molecular complexes can be studied. In the future, multicolour and multiparameter imaging of single molecules in live cells will be a powerful analytical tool for systems biology. Here, we discuss measurements of single-molecule mobility and residency at the plasma membrane of live cells. Analysis of diffusional paths at the plasma membrane gives information about its physical properties and measurement of temporal trajectories enables rates of binding and dissociation to be derived. Meanwhile, close scrutiny of individual fluorophore trajectories enables ideas about molecular dimerization and oligomerization related to function to be tested directly.

  5. Synthesis and biological activity of some heterocyclic compounds ...

    Indian Academy of Sciences (India)

    Administrator

    lactam) moiety. 23 such as penicillin, cephalosporin and carbapenem (figure 2). It is also associated with a variety of therapeutic activities. 24–28. In continuation of our work to develop potential antimicrobial molecules,. 29,30 we report here the ...

  6. Computational structural biology: methods and applications

    National Research Council Canada - National Science Library

    Schwede, Torsten; Peitsch, Manuel Claude

    2008-01-01

    ... sequencing reinforced the observation that structural information is needed to understand the detailed function and mechanism of biological molecules such as enzyme reactions and molecular recognition events. Furthermore, structures are obviously key to the design of molecules with new or improved functions. In this context, computational structural biology...

  7. Small molecules: the missing link in the central dogma.

    Science.gov (United States)

    Schreiber, Stuart L

    2005-07-01

    Small molecules have critical roles at all levels of biological complexity and yet remain orphans of the central dogma. Chemical biologists, working with small molecules, expand our understanding of these central elements of life.

  8. Transport of biologically active material in laser cutting.

    Science.gov (United States)

    Frenz, M; Mathezloic, F; Stoffel, M H; Zweig, A D; Romano, V; Weber, H P

    1988-01-01

    The transport of biologically active material during laser cutting with CO2 and Er lasers is demonstrated. This transport mechanism removes particles from the surface of gelatin, agar, and liver samples into the depth of the laser-formed craters. The transport phenomenon is explained by a contraction and condensation of enclosed hot water vapor. We show by cultivating transported bacteria in agar that biological particles can survive the shock of the transport. Determination of the numbers of active cells evidences a more pronounced activity of the cultivated bacteria after impact with an Er laser than with a CO2 laser.

  9. Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2.

    Science.gov (United States)

    Mi, Huaiyu; Schreiber, Falk; Moodie, Stuart; Czauderna, Tobias; Demir, Emek; Haw, Robin; Luna, Augustin; Le Novère, Nicolas; Sorokin, Anatoly; Villéger, Alice

    2015-09-04

    The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Activity Flow language represents the influences of activities among various entities within a network. Unlike SBGN PD and ER that focus on the entities and their relationships with others, SBGN AF puts the emphasis on the functions (or activities) performed by the entities, and their effects to the functions of the same or other entities. The nodes (elements) describe the biological activities of the entities, such as protein kinase activity, binding activity or receptor activity, which can be easily mapped to Gene Ontology molecular function terms. The edges (connections) provide descriptions of relationships (or influences) between the activities, e.g., positive influence and negative influence. Among all three languages of SBGN, AF is the closest to signaling pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

  10. Biological Activity of Curcuminoids Isolated from Curcuma longa

    Directory of Open Access Journals (Sweden)

    Simay Çıkrıkçı

    2008-04-01

    Full Text Available Curcumin is the most important fraction of turmeric which is responsible for its biological activity. In this study, isolation and biological assessment of turmeric and curcumin have been discussed against standard bacterial and mycobacterial strains such as E.coli , S.aureus, E.feacalis, P.aeuroginosa, M.smegmatis, M.simiae, M.kansasii, M. terrae, M.szulgai and the fungi Candida albicans. The antioxidant activity of curcumin and turmeric were also determined by the CUPRAC method.

  11. Single-molecule techniques in biophysics: a review of the progress in methods and applications

    Science.gov (United States)

    Miller, Helen; Zhou, Zhaokun; Shepherd, Jack; Wollman, Adam J. M.; Leake, Mark C.

    2018-02-01

    Single-molecule biophysics has transformed our understanding of biology, but also of the physics of life. More exotic than simple soft matter, biomatter lives far from thermal equilibrium, covering multiple lengths from the nanoscale of single molecules to up to several orders of magnitude higher in cells, tissues and organisms. Biomolecules are often characterized by underlying instability: multiple metastable free energy states exist, separated by levels of just a few multiples of the thermal energy scale k B T, where k B is the Boltzmann constant and T absolute temperature, implying complex inter-conversion kinetics in the relatively hot, wet environment of active biological matter. A key benefit of single-molecule biophysics techniques is their ability to probe heterogeneity of free energy states across a molecular population, too challenging in general for conventional ensemble average approaches. Parallel developments in experimental and computational techniques have catalysed the birth of multiplexed, correlative techniques to tackle previously intractable biological questions. Experimentally, progress has been driven by improvements in sensitivity and speed of detectors, and the stability and efficiency of light sources, probes and microfluidics. We discuss the motivation and requirements for these recent experiments, including the underpinning mathematics. These methods are broadly divided into tools which detect molecules and those which manipulate them. For the former we discuss the progress of super-resolution microscopy, transformative for addressing many longstanding questions in the life sciences, and for the latter we include progress in ‘force spectroscopy’ techniques that mechanically perturb molecules. We also consider in silico progress of single-molecule computational physics, and how simulation and experimentation may be drawn together to give a more complete understanding. Increasingly, combinatorial techniques are now used, including

  12. Using Active Learning to Teach Concepts and Methods in Quantitative Biology.

    Science.gov (United States)

    Waldrop, Lindsay D; Adolph, Stephen C; Diniz Behn, Cecilia G; Braley, Emily; Drew, Joshua A; Full, Robert J; Gross, Louis J; Jungck, John A; Kohler, Brynja; Prairie, Jennifer C; Shtylla, Blerta; Miller, Laura A

    2015-11-01

    This article provides a summary of the ideas discussed at the 2015 Annual Meeting of the Society for Integrative and Comparative Biology society-wide symposium on Leading Students and Faculty to Quantitative Biology through Active Learning. It also includes a brief review of the recent advancements in incorporating active learning approaches into quantitative biology classrooms. We begin with an overview of recent literature that shows that active learning can improve students' outcomes in Science, Technology, Engineering and Math Education disciplines. We then discuss how this approach can be particularly useful when teaching topics in quantitative biology. Next, we describe some of the recent initiatives to develop hands-on activities in quantitative biology at both the graduate and the undergraduate levels. Throughout the article we provide resources for educators who wish to integrate active learning and technology into their classrooms. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  13. An enzymatic deconjugation method for the analysis of small molecule active drugs on antibody-drug conjugates.

    Science.gov (United States)

    Li, Yi; Gu, Christine; Gruenhagen, Jason; Yehl, Peter; Chetwyn, Nik P; Medley, Colin D

    2016-01-01

    Antibody-drug conjugates (ADCs) are complex therapeutic agents that use the specific targeting properties of antibodies and the highly potent cytotoxicity of small molecule drugs to selectively eliminate tumor cells while limiting the toxicity to normal healthy tissues. Two critical quality attributes of ADCs are the purity and stability of the active small molecule drug linked to the ADC, but these are difficult to assess once the drug is conjugated to the antibody. In this study, we report a enzyme deconjugation approach to cleave small molecule drugs from ADCs, which allows the drugs to be subsequently characterized by reversed-phase high performance liquid chromatography. The model ADC we used in this study utilizes a valine-citrulline linker that is designed to be sensitive to endoproteases after internalization by tumor cells. We screened several proteases to determine the most effective enzyme. Among the 3 cysteine proteases evaluated, papain had the best efficiency in cleaving the small molecule drug from the model ADC. The deconjugation conditions were further optimized to achieve complete cleavage of the small molecule drug. This papain deconjugation approach demonstrated excellent specificity and precision. The purity and stability of the active drug on an ADC drug product was evaluated and the major degradation products of the active drug were identified. The papain deconjugation method was also applied to several other ADCs, with the results suggesting it could be applied generally to ADCs containing a valine-citrulline linker. Our results indicate that the papain deconjugation method is a powerful tool for characterizing the active small molecule drug conjugated to an ADC, and may be useful in ensuring the product quality, efficacy and the safety of ADCs.

  14. Friction mediated by redox-active supramolecular connector molecules.

    Science.gov (United States)

    Bozna, B L; Blass, J; Albrecht, M; Hausen, F; Wenz, G; Bennewitz, R

    2015-10-06

    We report on a friction study at the nanometer scale using atomic force microscopy under electrochemical control. Friction arises from the interaction between two surfaces functionalized with cyclodextrin molecules. The interaction is mediated by connector molecules with (ferrocenylmethyl)ammonium end groups forming supramolecular complexes with the cyclodextrin molecules. With ferrocene connector molecules in solution, the friction increases by a factor of up to 12 compared to control experiments without connector molecules. The electrochemical oxidation of ferrocene to ferrocenium causes a decrease in friction owing to the lower stability of ferrocenium-cyclodextrin complex. Upon switching between oxidative and reduction potentials, a change in friction by a factor of 1.2-1.8 is observed. Isothermal titration calorimetry reveals fast dissociation and rebinding kinetics and thus an equilibrium regime for the friction experiments.

  15. Carrier-free labelling of urokinase with fluorine-18 by preserving the biological activity

    International Nuclear Information System (INIS)

    Mueller-Platz, C.M.

    1982-03-01

    Fluorine-18 is particularly suitable for the regional location of clot formation using positron emission tomography. The radioisotope however cannot be directly incorporated in the urokinase as the enzyme is only stable in aqueous solution, F - sub(aq) is unreactive in protic solutions. 18 F-fluoroacetic acid was therefore selected as intermediate step for labelling urokinase. 18 F-fluoroacetic acid can be well activated by water-soluble [N-ethyl-N'-(dimethyl amino)propyl] carbodiimide and form a covalent bond as activated acid on the free amino groups of the urokinase. Different labelled preparations were thus investigated on the activity of the labelled enzyme. It could be shown in some cases that already after a slight drop of the total enzyme activity, all labelled urokinase molecules were biologically inactive. By changing the reaction conditions (pH value and reaction time) a method was found however in which not only was the enzyme activity of the preparation completely maintained but also that of the radiochemical yield corresponding radioactivity eluted with the bonding urokinase. The carrier-free labelling of urokinase starting with 18 F - was achieved with an overall radiochemical yield of 8 per cent for a synthesis time of 110 min. The method enables a sufficient amount of activity to be produced for the in-vivo application to the location of thrombus in patients. (orig./MG) [de

  16. Ficus carica L. (Moraceae: Phytochemistry, Traditional Uses and Biological Activities

    Directory of Open Access Journals (Sweden)

    Shukranul Mawa

    2013-01-01

    Full Text Available This paper describes the botanical features of Ficus carica L. (Moraceae, its wide variety of chemical constituents, its use in traditional medicine as remedies for many health problems, and its biological activities. The plant has been used traditionally to treat various ailments such as gastric problems, inflammation, and cancer. Phytochemical studies on the leaves and fruits of the plant have shown that they are rich in phenolics, organic acids, and volatile compounds. However, there is little information on the phytochemicals present in the stem and root. Reports on the biological activities of the plant are mainly on its crude extracts which have been proven to possess many biological activities. Some of the most interesting therapeutic effects include anticancer, hepatoprotective, hypoglycemic, hypolipidemic, and antimicrobial activities. Thus, studies related to identification of the bioactive compounds and correlating them to their biological activities are very useful for further research to explore the potential of F. carica as a source of therapeutic agents.

  17. Single Molecule Analysis Research Tool (SMART: an integrated approach for analyzing single molecule data.

    Directory of Open Access Journals (Sweden)

    Max Greenfeld

    Full Text Available Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data.

  18. Biological Effects of Radiation

    International Nuclear Information System (INIS)

    Jatau, B.D.; Garba, N.N.; Yusuf, A.M.; Yamusa, Y. A.; Musa, Y.

    2013-01-01

    In earlier studies, researchers aimed a single particle at the nucleus of the cell where DNA is located. Eighty percent of the cells shot through the nucleus survived. This contradicts the belief that if radiation slams through the nucleus, the cell will die. But the bad news is that the surviving cells contained mutations. Cells have a great capacity to repair DNA, but they cannot do it perfectly. The damage left behind in these studies from a single particle of alpha radiation doubled the damage that is already there. This proved, beyond a shadow of doubt, those there biological effects occur as a result of exposure to radiation, Radiation is harmful to living tissue because of its ionizing power in matter. This ionization can damage living cells directly, by breaking the chemical bonds of important biological molecules (particularly DNA), or indirectly, by creating chemical radicals from water molecules in the cells, which can then attack the biological molecules chemically. At some extent these molecules are repaired by natural biological processes, however, the effectiveness of this repair depends on the extent of the damage. The interaction of ionizing with the human body, arising either from external sources outside the body or from internal contamination of the body by radioactive materials, leads to the biological effects which may later show up as a clinical symptoms. Basically, this formed the baseline of this research to serve as a yardstick for creating awareness about radiation and its resulting effects.

  19. Single molecule image formation, reconstruction and processing: introduction.

    Science.gov (United States)

    Ashok, Amit; Piestun, Rafael; Stallinga, Sjoerd

    2016-07-01

    The ability to image at the single molecule scale has revolutionized research in molecular biology. This feature issue presents a collection of articles that provides new insights into the fundamental limits of single molecule imaging and reports novel techniques for image formation and analysis.

  20. Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

    Science.gov (United States)

    Neumann, Heinz; Neumann-Staubitz, Petra

    2010-06-01

    Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

  1. Low pressure tritiation of molecules

    International Nuclear Information System (INIS)

    Moran, T.F.; Powers, J.C.; Lively, M.O.

    1980-01-01

    A method is described of tritiating sensitive biological molecules by depositing molecules of the substance to be tritiated on a supporting substrate in an evacuated vacuum chamber near, but not in the path of, an electron beam which traverses the chamber, admitting tritium gas into the chamber, and subjecting the tritium to the electron beam. Vibrationally excited tritium gas species are generated which collide and react with the substance thus incorporating tritium atoms into the substance. (U.K.)

  2. A small-molecule switch for Golgi sulfotransferases.

    Science.gov (United States)

    de Graffenried, Christopher L; Laughlin, Scott T; Kohler, Jennifer J; Bertozzi, Carolyn R

    2004-11-30

    The study of glycan function is a major frontier in biology that could benefit from small molecules capable of perturbing carbohydrate structures on cells. The widespread role of sulfotransferases in modulating glycan function makes them prime targets for small-molecule modulators. Here, we report a system for conditional activation of Golgi-resident sulfotransferases using a chemical inducer of dimerization. Our approach capitalizes on two features shared by these enzymes: their requirement of Golgi localization for activity on cellular substrates and the modularity of their catalytic and localization domains. Fusion of these domains to the proteins FRB and FKBP enabled their induced assembly by the natural product rapamycin. We applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and GlcNAc6ST-2, which collaborate in the sulfation of L-selectin ligands. Both the activity and specificity of the inducible enzymes were indistinguishable from their WT counterparts. We further generated rapamycin-inducible chimeric enzymes comprising the localization domain of a sulfotransferase and the catalytic domain of a glycosyltransferase, demonstrating the generality of the system among other Golgi enzymes. The approach provides a means for studying sulfate-dependent processes in cellular systems and, potentially, in vivo.

  3. Computational design of molecules for an all-quinone redox flow battery.

    Science.gov (United States)

    Er, Süleyman; Suh, Changwon; Marshak, Michael P; Aspuru-Guzik, Alán

    2015-02-01

    Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH 2 ) ( i.e. , two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships.

  4. Development of novel small molecules for imaging and drug release

    Science.gov (United States)

    Cao, Yanting

    Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the

  5. A Conceptual Framework for Organizing Active Learning Experiences in Biology Instruction

    Science.gov (United States)

    Gardner, Joel; Belland, Brian R.

    2012-01-01

    Introductory biology courses form a cornerstone of undergraduate instruction. However, the predominantly used lecture approach fails to produce higher-order biology learning. Research shows that active learning strategies can increase student learning, yet few biology instructors use all identified active learning strategies. In this paper, we…

  6. Implication of Crystal Water Molecules in Inhibitor Binding at ALR2 Active Site

    Directory of Open Access Journals (Sweden)

    Hymavati

    2012-01-01

    Full Text Available Water molecules play a crucial role in mediating the interaction between a ligand and a macromolecule. The solvent environment around such biomolecule controls their structure and plays important role in protein-ligand interactions. An understanding of the nature and role of these water molecules in the active site of a protein could greatly increase the efficiency of rational drug design approaches. We have performed the comparative crystal structure analysis of aldose reductase to understand the role of crystal water in protein-ligand interaction. Molecular dynamics simulation has shown the versatile nature of water molecules in bridge H bonding during interaction. Occupancy and life time of water molecules depend on the type of cocrystallized ligand present in the structure. The information may be useful in rational approach to customize the ligand, and thereby longer occupancy and life time for bridge H-bonding.

  7. Interrogating the activities of conformational deformed enzyme by single-molecule fluorescence-magnetic tweezers microscopy

    Science.gov (United States)

    Guo, Qing; He, Yufan; Lu, H. Peter

    2015-01-01

    Characterizing the impact of fluctuating enzyme conformation on enzymatic activity is critical in understanding the structure–function relationship and enzymatic reaction dynamics. Different from studying enzyme conformations under a denaturing condition, it is highly informative to manipulate the conformation of an enzyme under an enzymatic reaction condition while monitoring the real-time enzymatic activity changes simultaneously. By perturbing conformation of horseradish peroxidase (HRP) molecules using our home-developed single-molecule total internal reflection magnetic tweezers, we successfully manipulated the enzymatic conformation and probed the enzymatic activity changes of HRP in a catalyzed H2O2–amplex red reaction. We also observed a significant tolerance of the enzyme activity to the enzyme conformational perturbation. Our results provide a further understanding of the relation between enzyme behavior and enzymatic conformational fluctuation, enzyme–substrate interactions, enzyme–substrate active complex formation, and protein folding–binding interactions. PMID:26512103

  8. Single-molecule fluorescence microscopy review: shedding new light on old problems.

    Science.gov (United States)

    Shashkova, Sviatlana; Leake, Mark C

    2017-08-31

    Fluorescence microscopy is an invaluable tool in the biosciences, a genuine workhorse technique offering exceptional contrast in conjunction with high specificity of labelling with relatively minimal perturbation to biological samples compared with many competing biophysical techniques. Improvements in detector and dye technologies coupled to advances in image analysis methods have fuelled recent development towards single-molecule fluorescence microscopy, which can utilize light microscopy tools to enable the faithful detection and analysis of single fluorescent molecules used as reporter tags in biological samples. For example, the discovery of GFP, initiating the so-called 'green revolution', has pushed experimental tools in the biosciences to a completely new level of functional imaging of living samples, culminating in single fluorescent protein molecule detection. Today, fluorescence microscopy is an indispensable tool in single-molecule investigations, providing a high signal-to-noise ratio for visualization while still retaining the key features in the physiological context of native biological systems. In this review, we discuss some of the recent discoveries in the life sciences which have been enabled using single-molecule fluorescence microscopy, paying particular attention to the so-called 'super-resolution' fluorescence microscopy techniques in live cells, which are at the cutting-edge of these methods. In particular, how these tools can reveal new insights into long-standing puzzles in biology: old problems, which have been impossible to tackle using other more traditional tools until the emergence of new single-molecule fluorescence microscopy techniques. © 2017 The Author(s).

  9. Single molecule detection, thermal fluctuation and life

    Science.gov (United States)

    YANAGIDA, Toshio; ISHII, Yoshiharu

    2017-01-01

    Single molecule detection has contributed to our understanding of the unique mechanisms of life. Unlike artificial man-made machines, biological molecular machines integrate thermal noises rather than avoid them. For example, single molecule detection has demonstrated that myosin motors undergo biased Brownian motion for stepwise movement and that single protein molecules spontaneously change their conformation, for switching to interactions with other proteins, in response to thermal fluctuation. Thus, molecular machines have flexibility and efficiency not seen in artificial machines. PMID:28190869

  10. Biological activities of some Xylooligosaccharides from ...

    African Journals Online (AJOL)

    Xylooligosaccharides (XOS's) exhibited considerable biological activities and be incorporated into many food products and in pharmaceutical and drug industry. XOS's were produced from xylose-containing polysaccharides (XPS's) obtained from natural, xylan-rich, agro-industrial wastes, i.e., corncobs and sugarcane ...

  11. Protease activated receptors (PARS) mediation in gyroxin biological activity; Mediacao dos receptores ativados por proteases (PARs) em atividades biologicas da giroxina

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Jose Alberto Alves da

    2009-07-01

    Gyroxin is a serine protease enzyme from the South American rattlesnake (Crotalus durissus terrificus) venom; it is only partially characterized and has multiple activities. Gyroxin induces blood coagulation, blood pressure decrease and a neurotoxic behavior named barrel rotation. The mechanisms involved in this neurotoxic activity are not known. Whereas gyroxin is a member of enzymes with high potential to become a new drug with clinical applications such as thrombin, batroxobin, ancrod, tripsyn and kalicrein, it is important to find out how gyroxin works. The analysis on agarose gel electrophoresis and circular dichroism confirmed the molecules' integrity and purity. The gyroxin intravenous administration in mice proved its neurotoxicity (barrel rotation). In vivo studies employing intravital microscopy proved that gyroxin induces vasodilation with the participation of protease activated receptors (PARs), nitric oxide and Na+K+ATPase. The leukocytes' adherence and rolling counting indicated that gyroxin has no pro inflammatory activity. Gyroxin induced platelet aggregation, which was blocked by inhibitors of PAR1 and PAR4 receptors (SCH 79797 and tcY-NH{sub 2}, respectively). Finally, it was proved that the gyroxin temporarily alter the permeability of the blood brain barrier (BBB). Our study has shown that both the protease-activated receptors and nitric oxide are mediators involved in the biological activities of gyroxin. (author)

  12. Exploring sets of molecules from patents and relationships to other active compounds in chemical space networks

    Science.gov (United States)

    Kunimoto, Ryo; Bajorath, Jürgen

    2017-09-01

    Patents from medicinal chemistry represent a rich source of novel compounds and activity data that appear only infrequently in the scientific literature. Moreover, patent information provides a primary focal point for drug discovery. Accordingly, text mining and image extraction approaches have become hot topics in patent analysis and repositories of patent data are being established. In this work, we have generated network representations using alternative similarity measures to systematically compare molecules from patents with other bioactive compounds, visualize similarity relationships, explore the chemical neighbourhood of patent molecules, and identify closely related compounds with different activities. The design of network representations that combine patent molecules and other bioactive compounds and view patent information in the context of current bioactive chemical space aids in the analysis of patents and further extends the use of molecular networks to explore structure-activity relationships.

  13. Biological activity of SV40 DNA

    International Nuclear Information System (INIS)

    Abrahams, P.J.

    1978-01-01

    This thesis deals with a study on the biological activity of SV40 DNA. The transforming activity of SV40 DNA and DNA fragments is investigated in order to define as precisely as possible the area of the viral genome that is involved in the transformation. The infectivity of SV40 DNA is used to study the defective repair mechanisms of radiation damages of human xeroderma pigmentosum cells. (C.F.)

  14. Ground-state thermodynamics of bistable redox-active donor-acceptor mechanically interlocked molecules.

    Science.gov (United States)

    Fahrenbach, Albert C; Bruns, Carson J; Cao, Dennis; Stoddart, J Fraser

    2012-09-18

    Fashioned through billions of years of evolution, biological molecular machines, such as ATP synthase, myosin, and kinesin, use the intricate relative motions of their components to drive some of life's most essential processes. Having control over the motions in molecules is imperative for life to function, and many chemists have designed, synthesized, and investigated artificial molecular systems that also express controllable motions within molecules. Using bistable mechanically interlocked molecules (MIMs), based on donor-acceptor recognition motifs, we have sought to imitate the sophisticated nanoscale machines present in living systems. In this Account, we analyze the thermodynamic characteristics of a series of redox-switchable [2]rotaxanes and [2]catenanes. Control and understanding of the relative intramolecular movements of components in MIMs have been vital in the development of a variety of applications of these compounds ranging from molecular electronic devices to drug delivery systems. These bistable donor-acceptor MIMs undergo redox-activated switching between two isomeric states. Under ambient conditions, the dominant translational isomer, the ground-state coconformation (GSCC), is in equilibrium with the less favored translational isomer, the metastable-state coconformation (MSCC). By manipulating the redox state of the recognition site associated with the GSCC, we can stimulate the relative movements of the components in these bistable MIMs. The thermodynamic parameters of model host-guest complexes provide a good starting point to rationalize the ratio of GSCC to MSCC at equilibrium. The bistable [2]rotaxanes show a strong correlation between the relative free energies of model complexes and the ground-state distribution constants (K(GS)). This relationship does not always hold for bistable [2]catenanes, most likely because of the additional steric and electronic constraints present when the two rings are mechanically interlocked with each other

  15. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    Review Article. A Review of the Secondary Metabolites and Biological. Activities of Tinospora crispa ... triterpenes have been isolated, some of which have also shown corresponding biological activities. The current review is an update on the .... were found to exhibit higher antioxidative potency than the synthetic antioxidant.

  16. Active learning in the lecture theatre using 3D printed objects.

    Science.gov (United States)

    Smith, David P

    2016-01-01

    The ability to conceptualize 3D shapes is central to understanding biological processes. The concept that the structure of a biological molecule leads to function is a core principle of the biochemical field. Visualisation of biological molecules often involves vocal explanations or the use of two dimensional slides and video presentations. A deeper understanding of these molecules can however be obtained by the handling of objects. 3D printed biological molecules can be used as active learning tools to stimulate engagement in large group lectures. These models can be used to build upon initial core knowledge which can be delivered in either a flipped form or a more didactic manner. Within the teaching session the students are able to learn by handling, rotating and viewing the objects to gain an appreciation, for example, of an enzyme's active site or the difference between the major and minor groove of DNA. Models and other artefacts can be handled in small groups within a lecture theatre and act as a focal point to generate conversation. Through the approach presented here core knowledge is first established and then supplemented with high level problem solving through a "Think-Pair-Share" cooperative learning strategy. The teaching delivery was adjusted based around experiential learning activities by moving the object from mental cognition and into the physical environment. This approach led to students being able to better visualise biological molecules and a positive engagement in the lecture. The use of objects in teaching allows the lecturer to create interactive sessions that both challenge and enable the student.

  17. Holography and coherent diffraction with low-energy electrons: A route towards structural biology at the single molecule level.

    Science.gov (United States)

    Latychevskaia, Tatiana; Longchamp, Jean-Nicolas; Escher, Conrad; Fink, Hans-Werner

    2015-12-01

    The current state of the art in structural biology is led by NMR, X-ray crystallography and TEM investigations. These powerful tools however all rely on averaging over a large ensemble of molecules. Here, we present an alternative concept aiming at structural analysis at the single molecule level. We show that by combining electron holography and coherent diffraction imaging estimations concerning the phase of the scattered wave become needless as the phase information is extracted from the data directly and unambiguously. Performed with low-energy electrons the resolution of this lens-less microscope is just limited by the De Broglie wavelength of the electron wave and the numerical aperture, given by detector geometry. In imaging freestanding graphene, a resolution of 2Å has been achieved revealing the 660.000 unit cells of the graphene sheet from a single data set. Once applied to individual biomolecules the method shall ultimately allow for non-destructive imaging and imports the potential to distinguish between different conformations of proteins with atomic resolution. Copyright © 2015. Published by Elsevier B.V.

  18. Neutron activation analysis of biological substances

    International Nuclear Information System (INIS)

    Ordogh, M.

    1978-08-01

    A Bowen cabbage sample was used as a reference material for the neutron activation studies, and the method was checked by the analysis of other biological substances (blood or serum etc.). For nondestructive measurements also some non-trace elements were determined in order to decide whether the activation analysis is a useful means for such measurements. The new activation analysis procedure was used for biomedical studies as, e.g., for trace element determination in body fluids, and for the analysis of inorganic components in air samples. (R.P.)

  19. Mutation of cysteine-88 in the Saccharomyces cerevisiae RAD6 protein abolishes its ubiquitin-conjugating activity and its various biological functions

    International Nuclear Information System (INIS)

    Sung, P.; Prakash, S.; Prakash, L.

    1990-01-01

    The RAD6 gene of Saccharomyces cerevisiae is required for DNA repair, DNA damage-induced mutagenesis, and sporulation. RAD6 protein is a ubiquitin-conjugating enzyme (E2) that has been shown to attach multiple molecules of ubiquitin to histones H2A and H2B. We have now examined whether the E2 activity of RAD6 is involved in its various biological functions. Since the formation of a thioester adduct between E2 and ubiquitin is necessary for E2 activity, the single cysteine residue (Cys-88) present in RAD6 was changed to alanine or valine. The mutant proteins were overproduced in yeast cells and purified to near homogeneity. We show that the rad6 Ala-88 and rad6 Val-88 mutant proteins lack the capacity for thioester formation with ubiquitin and, as a consequence, are totally devoid of any E2 activity. The rad6 Ala-88 and rad6 Val-88 mutations confer a defect in DNA repair, mutagenesis, and sporulation equivalent to that in the rad6 null allele. We suggest that the biological functions of RAD6 require its E2 activity. (author)

  20. The Dark Matter of Biology.

    Science.gov (United States)

    Ross, Jennifer L

    2016-09-06

    The inside of the cell is full of important, yet invisible species of molecules and proteins that interact weakly but couple together to have huge and important effects in many biological processes. Such "dark matter" inside cells remains mostly hidden, because our tools were developed to investigate strongly interacting species and folded proteins. Example dark-matter species include intrinsically disordered proteins, posttranslational states, ion species, and rare, transient, and weak interactions undetectable by biochemical assays. The dark matter of biology is likely to have multiple, vital roles to regulate signaling, rates of reactions, water structure and viscosity, crowding, and other cellular activities. We need to create new tools to image, detect, and understand these dark-matter species if we are to truly understand fundamental physical principles of biology. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Synthesis of molecular complexes for small molecule activation

    International Nuclear Information System (INIS)

    Andrez, Julie

    2016-01-01

    The redox chemistry of f-elements is drawing the attention of inorganic chemists due to their unusual reaction pathways. Notably low-valent f-element complexes have been shown to be able to activate small molecules such as CO_2 and N_2 in mild conditions. Compared to d-block metals, f-elements present a coordination chemistry dominated by electrostatic interactions and steric constraints. Molecular complexes of f-elements could thus provide new catalytic routes to transform small molecules into valuable chemicals. However the redox chemistry of low valent f-elements is dominated by single-electron transfers while the reductions of CO_2 and N_2 require multi-electronic processes. Accordingly the first approach of this PhD work was the use of redox active ligands as electron reservoir to support f-element centres increasing the electron number available for reduction events. The coordination of uranium with tridentate Schiff base ligand was investigated and led to isolation of a dinuclear electron-rich species able to undertake up to eight-electron reduction combining the redox activity of the ligands and the uranium centres. In order to obtain electron-rich compounds potentially able to polarize the C=O bond of CO_2, the synthesis of hetero-bimetallic species supported by salophen Schiff base ligand was also studied. In a second approach we have used bulky ligands with strong donor-character to tune the reducing abilities of low valent f-elements. In this case a bimolecular electron-transfer process is often observed. The reactivity of the U(III) siloxid complex [U(OSi(OtBu)_3)_4K] was further investigated. Notably, reaction with Ph_3PS led to the formation of a terminal U(IV) sulfide complex with multiple U-S bond which was analysed by DFT studies to better understand the bonding nature. Preliminary studies on the role of the counter-cation (M) in the system [U(OSi(OtBu)_3)_4M] on the outcome of the reactivity with CS_2 and CO_2 have also been performed. The

  2. Small-molecule inhibitors of phosphatidylcholine transfer protein/StarD2 identified by high-throughput screening.

    Science.gov (United States)

    Wagle, Neil; Xian, Jun; Shishova, Ekaterina Y; Wei, Jie; Glicksman, Marcie A; Cuny, Gregory D; Stein, Ross L; Cohen, David E

    2008-12-01

    Phosphatidylcholine transfer protein (PC-TP, also referred to as StarD2) is a highly specific intracellular lipid-binding protein that catalyzes the transfer of phosphatidylcholines between membranes in vitro. Recent studies have suggested that PC-TP in vivo functions to regulate fatty acid and glucose metabolism, possibly via interactions with selected other proteins. To begin to address the relationship between activity in vitro and biological function, we undertook a high-throughput screen to identify small-molecule inhibitors of the phosphatidylcholine transfer activity of PC-TP. After adapting a fluorescence quench assay to measure phosphatidylcholine transfer activity, we screened 114,752 compounds of a small-molecule library. The high-throughput screen identified 14 potential PC-TP inhibitors. Of these, 6 compounds exhibited characteristics consistent with specific inhibition of PC-TP activity, with IC(50) values that ranged from 4.1 to 95.0muM under conditions of the in vitro assay. These compounds should serve as valuable reagents to elucidate the biological function of PC-TP. Because mice with homozygous disruption of the PC-TP gene (Pctp) are sensitized to insulin action and relatively resistant to the development of atherosclerosis, these inhibitors may also prove to be of value in the management of diabetes and atherosclerotic cardiovascular diseases.

  3. A novel small molecule, Rosline, inhibits growth and induces caspase-dependent apoptosis in human lung cancer cells A549 through a reactive oxygen species-dependent mechanism.

    Science.gov (United States)

    Zhao, Ting; Feng, Yang; Jin, Wenling; Pan, Hui; Li, Haizhou; Zhao, Yang

    2016-06-01

    Chemical screening using synthetic small molecule libraries has provided a huge amount of novel active molecules. It generates lead compound for drug development and brings focus on molecules for mechanistic investigations on many otherwise intangible biological processes. In this study, using non-small cell lung cancer cell A549 to screen against a structurally novel and diverse synthetic small molecule library of 2,400 compounds, we identified a molecule named rosline that has strong anti-proliferation activity on A549 cells with a 50% cell growth inhibitory concentration (IC50 ) of 2.87 ± 0.39 µM. We showed that rosline treatment increased the number of Annexin V-positive staining cell, as well as G2/M arrest in their cell cycle progression. Further, we have demonstrated that rosline induces a decrease of mitochondrial membrane potential (Δφm ) and an increase of caspases 3/7 and 9 activities in A549 cells, although having no effect on the activity of caspase 8. Moreover, we found that rosline could induce the production of reactive oxygen species (ROS) and inhibit the phosphorylation of signaling molecule Akt in A549 cells. Alternatively, an antioxidant N-acetyl-L-cysteine (NAC) significantly attenuated rosline's effects on the mitochondrial membrane potential, caspases 3/7 and 9 activities, cell viabilities and the phosphorylation of Akt. Our results demonstrated that ROS played an important role in the apoptosis of A549 cells induced by rosline. © 2016 International Federation for Cell Biology.

  4. Nonlinear signaling on biological networks: The role of stochasticity and spectral clustering

    Science.gov (United States)

    Hernandez-Hernandez, Gonzalo; Myers, Jesse; Alvarez-Lacalle, Enrique; Shiferaw, Yohannes

    2017-03-01

    Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switchlike properties which are critical to their biological function. In this study we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector. However, at high coupling, transitions are insensitive to network structure since the network can be activated by stochastic transitions of a few nodes. Thus this work identifies important features of biological signaling networks that may underlie their biological

  5. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

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

    2017-01-02

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

  6. Computational Systems Chemical Biology

    OpenAIRE

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

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  7. The half-lives of biological activity of some pesticides in water

    OpenAIRE

    Kyaw Myint Oo,

    2001-01-01

    In the absence of analytical methods, the half-lives of biological activity of pesticides can be estimated by bioassays. To determine the half-lives of biological acivity of pesticides to fish, static bioassays were conducted in the laboratory with ten different formulations of pesticides using Labeo rohita as a bio-indicator. The half-lives of biological activity for ten different pesticides in soft water at pH 7.5 and 27░C, ranged from 4.6 days to 11.8 days. The half-life of biological acti...

  8. A new experiment to investigate the origin of optical activity using a low energy positron beam of controlled helicity. [molecular biology

    Science.gov (United States)

    Gidley, D. W.; Rich, A.; Van House, J. C.; Zitzewitz, P. W.

    1981-01-01

    Previous experiments undertaken in search of a correlation between the origin of optical activity in biological molecules and the helicity of beta particles emitted in nuclear beta decay have not provided any useful results. A description is presented of an experiment in which a low energy polarized positron beam of controlled helicity interacts with an optically active material to form positronium in vacuum. Advantages of the current study compared to the previous experiments are mainly related to a much greater sensitivity. Initially, it will be possible to detect a helicity-dependent asymmetry in triplet positronium formation of 1 part in 10,000. Improvements to better than 1 part in 100,000 should be attainable.

  9. Phosphate Activation via Reduced Oxidation State Phosphorus (P. Mild Routes to Condensed-P Energy Currency Molecules

    Directory of Open Access Journals (Sweden)

    Claire R. Cousins

    2013-07-01

    Full Text Available The emergence of mechanisms for phosphorylating organic and inorganic molecules is a key step en route to the earliest living systems. At the heart of all contemporary biochemical systems reside reactive phosphorus (P molecules (such as adenosine triphosphate, ATP as energy currency molecules to drive endergonic metabolic processes and it has been proposed that a predecessor of such molecules could have been pyrophosphate [P2O74−; PPi(V]. Arguably the most geologically plausible route to PPi(V is dehydration of orthophosphate, Pi(V, normally a highly endergonic process in the absence of mechanisms for activating Pi(V. One possible solution to this problem recognizes the presence of reactive-P containing mineral phases, such as schreibersite [(Fe,Ni3P] within meteorites whose abundance on the early Earth would likely have been significant during a putative Hadean-Archean heavy bombardment. Here, we propose that the reduced oxidation state P-oxyacid, H-phosphite [HPO32−; Pi(III] could have activated Pi(V towards condensation via the intermediacy of the condensed oxyacid pyrophosphite [H2P2O52−; PPi(III]. We provide geologically plausible provenance for PPi(III along with evidence of its ability to activate Pi(V towards PPi(V formation under mild conditions (80 °C in water.

  10. Synthesis of new bioactive aminophosphonates and study of their antioxidant, anti-inflammatory and antibacterial activities as well the assessment of their toxicological activity

    Science.gov (United States)

    Damiche, Rebiha; Chafaa, Salah

    2017-02-01

    Two new categories of α-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%.

  11. Biological activity of liposomal vanillin.

    Science.gov (United States)

    Castan, Leniher; Del Toro, Grisel; Fernández, Adolfo A; González, Manuel; Ortíz, Emilia; Lobo, Daliana

    2013-06-01

    This article presents a study of vanillin encapsulation inside multilamellar liposomes, with emphasis on the evaluation of antioxidant activity, the hemolytic effect, and the antisickling properties of these products. Egg phosphatidylcholine-cholesterol and egg phosphatidylcholine-cholesterol-1-O-decylglycerol liposomes were prepared by mechanical dispersion, all with vanillin included. Vesicles were characterized by determination of encapsulation efficiency and vanillin retention capacity. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The hemolytic effect of liposomes was also evaluated by spectrophotometry, as well as the antisickling activity by the Huck test using optical microscopy. Results showed that the lipid composition of liposomes did not significantly affect the encapsulation efficiency. Stable vesicles were obtained with a high retention percentage of vanillin. Liposomes exhibited a high capture of the DPPH radical compared to free vanillin and 1-O-decylglycerol (C10) in solution. Vesicles caused no significant hemolisys in normal erythrocytes, nor in those coming from patients with sickle cell anemia. Vanillin encapsulated in liposomes retained its antisickling activity, with a greater effect for C10-containing vesicles. Our results show that vanillin encapsulation in liposomes is a way to enhance the pharmacologic properties of this molecule using a suitable vehicle.

  12. A novel biological active multilayer film based on polyoxometalate with pendant support-ligand

    International Nuclear Information System (INIS)

    Ma Huiyuan; Peng Jun; Han Zhangang; Yu Xia; Dong Baoxia

    2005-01-01

    A novel nanosized biological active multilayer film composed of polyoxometalate (POM) anion α-[SiW 11 O 39 Co(H 2 PO 4 )] 7- (abbr. SiW 11 Co-PO 4 ) and poly(diallyldi methylammonium chloride) (abbr. PDDA) was fabricated by layer-by-layer self-assembly (LBL). The composition and growth processes of the films have been determined by X-ray photoelectron spectra (XPS) and ultraviolet-visible absorption spectra (UV). The composite film was formed by the alternate adsorption of SiW 11 Co-PO 4 and PDDA, and the deposition process was quantitative and highly reproducible from layer to layer. The morphology of the film was studied by atomic force microscopy (AFM), which showed that the film was relatively uniform and smooth, and POM anions aggregated into nanoclusters distributing on the surface uniformly. The film exhibited favorable electrochemical behavior of POM indicated by cyclic voltammetry (CV). The film can immobilize the DNA molecules via Mg 2+ -bridging medium

  13. Small Molecule Modulator of p53 Signaling Pathway: Application for Radiosensitizing or Radioprotection Agents

    International Nuclear Information System (INIS)

    Oh, Sang Taek; Cho, Mun Ju; Gwak, Jung Sug; Ryu, Min Jung; Song, Jie Young; Yun, Yeon Sook

    2009-01-01

    The tumor suppressor p53 is key molecule to protect the cell against genotoxic stress and..the most frequently mutated..protein..in cancer cells. Lack of functional p53..is accompanied by high rate of genomic instability, rapid tumor progression, resistance to anticancer therapy, and increased angiogenesis. In response to DNA damage, p53 protein rapidly accumulated through attenuated proteolysis and is also activated as transcription factor. Activated p53 up-regulates target genes involved in cell cycle arrest and/or apoptosis and then lead to suppression of malignant transformation and the maintenance of genomic integrity. Chemical genetics is a new technology to uncover the signaling networks that regulated biological phenotype using exogenous reagents such as small molecules. Analogous to classical forward genetic screens in model organism, this approach makes use of high throughput, phenotypic assay to identify small molecules that disrupt gene product function in a way that alters a phenotype of interest. Recently, interesting small molecules were identified from cell based high throughput screening and its target protein or mechanism of action were identified by various methods including affinity chromatography, protein array profiling, mRNA or phage display, transcription profiling, and RNA interference

  14. Small Molecule Modulator of p53 Signaling Pathway: Application for Radiosensitizing or Radioprotection Agents

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang Taek; Cho, Mun Ju; Gwak, Jung Sug; Ryu, Min Jung [PharmacoGenomics Research Center, Inje University, Busan (Korea, Republic of); Song, Jie Young; Yun, Yeon Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-05-15

    The tumor suppressor p53 is key molecule to protect the cell against genotoxic stress and..the most frequently mutated..protein..in cancer cells. Lack of functional p53..is accompanied by high rate of genomic instability, rapid tumor progression, resistance to anticancer therapy, and increased angiogenesis. In response to DNA damage, p53 protein rapidly accumulated through attenuated proteolysis and is also activated as transcription factor. Activated p53 up-regulates target genes involved in cell cycle arrest and/or apoptosis and then lead to suppression of malignant transformation and the maintenance of genomic integrity. Chemical genetics is a new technology to uncover the signaling networks that regulated biological phenotype using exogenous reagents such as small molecules. Analogous to classical forward genetic screens in model organism, this approach makes use of high throughput, phenotypic assay to identify small molecules that disrupt gene product function in a way that alters a phenotype of interest. Recently, interesting small molecules were identified from cell based high throughput screening and its target protein or mechanism of action were identified by various methods including affinity chromatography, protein array profiling, mRNA or phage display, transcription profiling, and RNA interference.

  15. Anisotropy in highly charged ion induced molecule fragmentation

    International Nuclear Information System (INIS)

    Juhasz, Z.; Sulik, B.; Fremont, F.; Chesnel, J.Y.; Hajaji, A.

    2006-01-01

    Complete text of publication follows. Studying fragmentation processes of biologically relevant molecules due to highly charged ion impact is important to understand radiation damage in biological tissues. Energy spectra of the charged molecule fragments may reveal the different fragmentation patterns meanwhile the angular distributions of the fragments characterize the dependence of fragmentation probability on the initial orientation of the molecule. The research to explore the angular distribution of the molecule fragments has only recently been started[1]. In 2006 we performed measurements at ARIBE facility at GANIL, Caen (France), in order to investigate orientation effects in molecule fragmentation. Fragmentation of H 2 O, C 6 H 6 and CH 4 , which represent different level of symmetry, have been studied by 60 keV N 6+ ion impact. Energy spectra of the charged fragments at different observation angles have been taken. As our example spectra show the different protonic peaks can be attributed to different fragmentation processes. Significant anisotropy can be seen in the different processes. The strongest evidence for the anisotropy can be seen in the spectra of C 6 H 6 , where the spectra appear isotropic in almost the whole observed energy range except one peak, which has a strong angular dependence and is maximal around 90 deg. (author)

  16. Investigation of polyelectrolyte desorption by single molecule force spectroscopy

    International Nuclear Information System (INIS)

    Friedsam, C; Seitz, M; Gaub, H E

    2004-01-01

    Single molecule force spectroscopy has evolved into a powerful method for the investigation of intra- and intermolecular interactions at the level of individual molecules. Many examples, including the investigation of the dynamic properties of complex biological systems as well as the properties of covalent bonds or intermolecular transitions within individual polymers, are reported in the literature. The technique has recently been extended to the systematic investigation of desorption processes of individual polyelectrolyte molecules adsorbed on generic surfaces. The stable covalent attachment of polyelectrolyte molecules to the AFM-tip provides the possibility of performing long-term measurements with the same set of molecules and therefore allows the in situ observation of the impact of environmental changes on the adsorption behaviour of individual molecules. Different types of interactions, e.g. electrostatic or hydrophobic interactions, that determine the adsorption process could be identified and characterized. The experiments provided valuable details that help to understand the nature and the properties of non-covalent interactions, which is helpful with regard to biological systems as well as for technical applications. Apart from this, desorption experiments can be utilized to characterize the properties of surfaces or polymer coatings. Therefore they represent a versatile tool that can be further developed in terms of various aspects

  17. Biological activity of selected plants with adaptogenic effect

    Directory of Open Access Journals (Sweden)

    Eva Ivanišová

    2016-05-01

    Full Text Available The aim of this study was to determine biological activity of plants with adaptogenic effect: Panax ginseng Mayer., Withania somnifera L., Eleuterococcus senticosus Rupr. et Maxim., Astragallus membranaceus Fisch. and Codonopsis pilosulae Franch. The antioxidant activity was detected by DPPH and phosphomolybdenum method, total polyphenol content with Folin – Ciocalteu reagent, flavonoids content by aluminium chloride method. The detection of antimicrobial activity was carried out by disc diffusion method against three species of Gram-negative bacteria: Escherichia coli CCM 3988, Salmonella enterica subsp. enterica CCM 3807, Yersinia enterocolitica CCM 5671 and two Gram-positive bacteria: Bacillus thuringiensis CCM 19, Stapylococcus aureus subsp. aureus CCM 2461. Results showed that plants with adaptogenic effect are rich for biologically active substances. The highest antioxidant activity by DPPH method was determined in the sample of Eleuterococcus senticosus (3.15 mg TEAC – Trolox equivalent antioxidant capacity per g of sample and by phosphomolybdenum method in the sample of Codonopsis pilosulae (188.79 mg TEAC per g of sample. In the sample of Panax ginseng was measured the highest content of total polyphenols (8.10 mg GAE – galic acid equivalent per g of sample and flavonoids (3.41 μg QE – quercetin equivalent per g of sample. All samples also showed strong antimicrobial activity with the best results in Panax ginseng and Withania somnifera in particular for species Yersinia enterocolitica CCM 5671 and Salmonella enterica subsp. enterica CCM 3807. The analyzed species of plant with high value of biological activity can be used more in the future, not only in food, but also in cosmetics and pharmaceutical industries.

  18. Mouse CD23 regulates monocyte activation through an interaction with the adhesion molecule CD11b/CD18.

    Science.gov (United States)

    Lecoanet-Henchoz, S; Plater-Zyberk, C; Graber, P; Gretener, D; Aubry, J P; Conrad, D H; Bonnefoy, J Y

    1997-09-01

    CD23 is expressed on a variety of hemopoietic cells. Recently, we have reported that blocking CD23 interactions in a murine model of arthritis resulted in a marked improvement of disease severity. Here, we demonstrate that CD11b, the alpha chain of the beta 2 integrin adhesion molecule complex CD11b/CD18 expressed on monocytes interacts with CD23. Using a recombinant fusion protein (ZZ-CD23), murine CD23 was shown to bind to peritoneal macrophages and peripheral blood cells isolated from mice as well as the murine macrophage cell line, RAW. The interactions between mouse ZZ-CD23 and CD11b/CD18-expressing cells were significantly inhibited by anti-CD11b monoclonal antibodies. A functional consequence was then demonstrated by inducing an up-regulation of interleukin-6 (IL-6) production following ZZ-CD23 incubation with monocytes. The addition of Fab fragments generated from the monoclonal antibody CD11b impaired this cytokine production by 50%. Interestingly, a positive autocrine loop was identified as IL-6 was shown to increase CD23 binding to macrophages. These results demonstrate that similar to findings using human cells, murine CD23 binds to the surface adhesion molecule, CD11b, and these interactions regulate biological activities of murine myeloid cells.

  19. Discovery of novel small molecule activators of β-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Folkert Verkaar

    Full Text Available Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β-catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling.

  20. Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

    Science.gov (United States)

    Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

    2015-12-01

    Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.

  1. Application of activation techniques to biological analysis

    International Nuclear Information System (INIS)

    Bowen, H.J.M.

    1981-01-01

    Applications of activation analysis in the biological sciences are reviewed for the period of 1970 to 1979. The stages and characteristics of activation analysis are described, and its advantages and disadvantages enumerated. Most applications involve activation by thermal neutrons followed by either radiochemical or instrumental determination. Relatively little use has been made of activation by fast neutrons, photons, or charged particles. In vivo analyses are included, but those based on prompt gamma or x-ray emission are not. Major applications include studies of reference materials, and the elemental analysis of plants, marine biota, animal and human tissues, diets, and excreta. Relatively little use of it has been made in biochemistry, microbiology, and entomology, but it has become important in toxicology and environmental science. The elements most often determined are Ag, As, Au, Br, Ca, Cd, Cl, Co, Cr, Cs, Cu, Fe, Hg, I, K, Mn, Mo, Na, Rb, Sb, Sc, Se, and Zn, while few or no determinations of B, Be, Bi, Ga, Gd, Ge, H, In, Ir, Li, Nd, Os, Pd, Pr, Pt, Re, Rh, Ru, Te, Tl, or Y have been made in biological materials

  2. Biological activity and photostability of biflorin micellar nanostructures.

    Science.gov (United States)

    Santana, Edson R B; Ferreira-Neto, João P; Yara, Ricardo; Sena, Kêsia X F R; Fontes, Adriana; Lima, Cláudia S A

    2015-05-13

    Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR) and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9%) and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS). The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures' photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.

  3. Biological Activity and Photostability of Biflorin Micellar Nanostructures

    Directory of Open Access Journals (Sweden)

    Edson R. B. Santana

    2015-05-01

    Full Text Available Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9% and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS. The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures’ photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.

  4. Biological activation of carbon filters.

    Science.gov (United States)

    Seredyńska-Sobecka, Bozena; Tomaszewska, Maria; Janus, Magdalena; Morawski, Antoni W

    2006-01-01

    To prepare biological activated carbon (BAC), raw surface water was circulated through granular activated carbon (GAC) beds. Biological activity of carbon filters was initiated after about 6 months of filter operation and was confirmed by two methods: measurement of the amount of biomass attached to the carbon and by the fluorescein diacetate (FDA) test. The effect of carbon pre-washing on WG-12 carbon properties was also studied. For this purpose, the nitrogen adsorption isotherms at 77K and Fourier transform-infrared (FT-IR) spectra analyses were performed. Moreover, iodine number, decolorizing power and adsorption properties of carbon in relation to phenol were studied. Analysis of the results revealed that after WG-12 carbon pre-washing its BET surface increased a little, the pH value of the carbon water extract decreased from 11.0 to 9.4, decolorizing power remained at the same level, and the iodine number and phenol adsorption rate increased. In preliminary studies of the ozonation-biofiltration process, a model phenol solution with concentration of approximately 10mg/l was applied. During the ozonation process a dose of 1.64 mg O(3)/mg TOC (total organic carbon) was employed and the contact time was 5 min. Four empty bed contact times (EBCTs) in the range of 2.4-24.0 min were used in the biofiltration experiment. The effectiveness of purification was measured by the following parameters: chemical oxygen demand (COD(Mn)), TOC, phenol concentration and UV(254)-absorbance. The parameters were found to decrease with EBCT.

  5. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Galitski, Timothy P.

    2008-04-01

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

  6. Inference problems in structural biology

    DEFF Research Database (Denmark)

    Olsson, Simon

    The structure and dynamics of biological molecules are essential for their function. Consequently, a wealth of experimental techniques have been developed to study these features. However, while experiments yield detailed information about geometrical features of molecules, this information is of...

  7. [BIOLOGICAL ACTIVITY OF ANTIMICROBIAL PEPTIDES FROM CHICKENS THROMBOCYTES].

    Science.gov (United States)

    Sycheva, M V; Vasilchenko, A S; Rogozhin, E A; Pashkova, T M; Popova, L P; Kartashova, O L

    2016-01-01

    Isolation and study of biological activity of antimicrobial peptides from chickens thrombocytes. Peptides from chickens thrombocytes, obtained by reverse-phase high-performance liquid chromatography method with stepped and linear gradients of concentration increase of the organic solvent were used in the study. Their antimicrobial activity was determined by microtitration method in broth; mechanism of biological effect--by using fluorescent spectroscopy method with DNA-tropic dyes. Individual fractions of peptides were isolated from chickens thrombocytes, that possess antimicrobial activity against Staphylococcus aureus P209 and Escherichia coli K12. A disruption of integrity of barrier structures of microorganisms under the effect of thrombocyte antimicrobial peptides and predominance of cells with damaged membrane in the population of E. coli was established. The data obtained on antimicrobial activity and mechanism of bactericidal effect of the peptide fractions from chickens thrombocytes isolated for the first time expand the understanding of functional properties of chickens thrombocytes and open a perspective for their further study with the aim of use as antimicrobial means.

  8. β-Glucans: Relationships between Modification, Conformation and Functional Activities

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    2017-02-01

    Full Text Available β-glucan is a type of polysaccharide which widely exists in bacteria, fungi, algae, and plants, and has been well known for its biological activities such as enhancing immunity, antitumor, antibacterial, antiviral, and wound healing activities. The conformation of β-glucan plays a crucial role on its biological activities. Therefore, β-glucans obtained from different sources, while sharing the same basic structures, often show different bioactivities. The basic structure and inter-molecular forces of polysaccharides can be changed by modification, which leads to the conformational transformation in solution that can directly affect bioactivity. In this review, we will first determine different ways to modify β-glucan molecules including physical methods, chemical methods, and biological methods, and then reveal the relationship of the flexible helix form of the molecule chain and the helix conformation to their bioactivities. Last, we summarize the scientific challenges to modifying β-glucan’s conformation and functional activity, and discuss its potential future development.

  9. Marine natural flavonoids: chemistry and biological activities.

    Science.gov (United States)

    Martins, Beatriz T; Correia da Silva, Marta; Pinto, Madalena; Cidade, Honorina; Kijjoa, Anake

    2018-05-04

    As more than 70% of the world's surface is covered by oceans, marine organisms offer a rich and unlimited resource of structurally diverse bioactive compounds. These organisms have developed unique properties and bioactive compounds that are, in majority of them, unparalleled by their terrestrial counterparts due to the different surrounding ecological systems. Marine flavonoids have been extensively studied in the last decades due to a growing interest concerning their promising biological/pharmacological activities. The most common classes of marine flavonoids are flavones and flavonols, which are mostly isolated from marine plants. Although most of flavonoids are hydroxylated and methoxylated, some marine flavonoids possess an unusual substitution pattern, not commonly found in terrestrial organisms, namely the presence of sulphate, chlorine, and amino groups. This review presents, for the first time in a systematic way, the structure, natural occurrence, and biological activities of marine flavonoids.

  10. Monitoring Biological Activity at Geothermal Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Peter Pryfogle

    2005-09-01

    The economic impact of microbial growth in geothermal power plants has been estimated to be as high as $500,000 annually for a 100 MWe plant. Many methods are available to monitor biological activity at these facilities; however, very few plants have any on-line monitoring program in place. Metal coupon, selective culturing (MPN), total organic carbon (TOC), adenosine triphosphate (ATP), respirometry, phospholipid fatty acid (PLFA), and denaturing gradient gel electrophoresis (DGGE) characterizations have been conducted using water samples collected from geothermal plants located in California and Utah. In addition, the on-line performance of a commercial electrochemical monitor, the BIoGEORGE?, has been evaluated during extended deployments at geothermal facilities. This report provides a review of these techniques, presents data on their application from laboratory and field studies, and discusses their value in characterizing and monitoring biological activities at geothermal power plants.

  11. Baltic cyanobacteria- A source of biologically active compounds

    Digital Repository Service at National Institute of Oceanography (India)

    Mazur-Marzec, H.; Błaszczyk, A.; Felczykowska, A.; Hohlfeld, N.; Kobos, J.; Toruńska-Sitarz, A.; PrabhaDevi; Montalva`o, S.; DeSouza, L.; Tammela, P.; Mikosik, A.; Bloch, S.; Nejman-Faleńczyk, B.; Węgrzyn, G.

    cyanobacteria, enzyme activity, enzyme inhibitors, immunological activity, natural products, nonribosomal peptides, plant growth regulators 2 INTRODUCTION Cyanobacteria are Gram-negative bacteria which are widely distributed in many water bodies..., immunological, 4 antimicrobial and plant growth tests. The overall aim of the experiments was to identify strains showing the most promising biological activity for potential biotechnological application. MATERIALS AND METHODS Isolation, culture...

  12. How to measure load-dependent kinetics of individual motor molecules without a force clamp

    DEFF Research Database (Denmark)

    Sung, J.; Mortensen, Kim; Spudich, J.A.

    2017-01-01

    Single-molecule force spectroscopy techniques, including optical trapping, magnetic trapping, and atomic force microscopy, have provided unprecedented opportunities to understand biological processes at the smallest biological length scales. For example, they have been used to elucidate the molec......Single-molecule force spectroscopy techniques, including optical trapping, magnetic trapping, and atomic force microscopy, have provided unprecedented opportunities to understand biological processes at the smallest biological length scales. For example, they have been used to elucidate...... functions at the single molecule level, such as conformational changes and force-generation of individual motor proteins or force-dependent kinetics in molecular interactions. Here, we describe a new method, “Harmonic Force Spectroscopy (HFS).” With a conventional dual-beam optical trap and a simple...... concepts, experimental setup, step-by-step experimental protocol, theory, data analysis, and results....

  13. Along the Central Dogma-Controlling Gene Expression with Small Molecules.

    Science.gov (United States)

    Schneider-Poetsch, Tilman; Yoshida, Minoru

    2018-05-04

    The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. In the process of dissecting mechanisms of gene expression, specific small-molecule inhibitors played an important role and became valuable tools of investigation. Small molecules offer significant advantages over genetic tools, as they allow inhibiting a process at any desired time point, whereas mutating or altering the gene of an important regulator would likely result in a dead organism. With the advent of modern sequencing technology, it has become possible to monitor global cellular effects of small-molecule treatment and thereby overcome the limitations of classical biochemistry, which usually looks at a biological system in isolation. This review focuses on several molecules, especially natural products, that have played an important role in dissecting gene expression and have opened up new fields of investigation as well as clinical venues for disease treatment. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  14. Sources and basic threats of biological safety

    International Nuclear Information System (INIS)

    Nazarova, O.D.

    2010-01-01

    Full text: Biological safety of any state is connected with development of its public protection against biological weapons and opportunity to prevent bio terrorist attacks. That's why in modern social-economic and geo-political conditions, the problem of biological safety strengthening become significant, which is connected with migration process globalization, development of bio-technology and dramatically increased risk of pathogenic germ infections proliferation, which can be used as biological weapon. Despite of undertaken efforts by world community on full prohibition of biological weapon, its proliferation in the world still takes place. Biology revolution during second and third millennium lead to development not only biotechnology but new achievements in medicine, agriculture and other fields of economy, but also created scientific and research preconditions for development of advanced biological means of mass destruction, that make it more attractive for achieving superiority and assigned targets: low developments costs, opportunity to create it by one small laboratory with two-three high qualified specialists bio technologists; tremendous impact effect: one substance gram can contain from one till one hundreds quintillions (10"1"8 - 10"2"0) active pathogen molecules and in case if they belong to amplificated RNA and DNA, each molecule getting to organism, will multiply and contaminate environment (the last one is its principal difference from chemical weapon); bypass of organism immunological barriers and specific vaccinations; unusual clinic finding, hard diagnosis; weakness of traditional medications and treatment methods; lack of material destruction; opportunity of tight-lipped developments; opportunity of tight-lipped application; opportunity of delayed effect; opportunity of selective influence on specific population (by use of genetic, climatic and cultural specifications of race, nations and nationalities). Above mentioned specifications create

  15. Assessing Student Behaviors and Motivation for Actively Learning Biology

    Science.gov (United States)

    Moore, Michael Edward

    Vision and Change states that one of the major changes in the way we design biology courses should be a switch in approach from teacher-centered learning to student-centered learning and identifies active learning as a recommended methods. Studies show performance benefits for students taking courses that use active learning. What is unknown is why active learning is such an effective instructional tool and the limits of this instructional method’s ability to influence performance. This dissertation builds a case in three steps for why active learning is an effective instructional tool. In step one, I assessed the influence of different types of active learning (clickers, group activities, and whole class discussions) on student engagement behavior in one semester of two different introductory biology courses and found that active learning positively influenced student engagement behavior significantly more than lecture. For step two, I examined over four semesters whether student engagement behavior was a predictor of performance and found participation (engagement behavior) in the online (video watching) and in-class course activities (clicker participation) that I measure were significant predictors of performance. In the third, I assessed whether certain active learning satisfied the psychological needs that lead to students’ intrinsic motivation to participate in those activities when compared over two semesters and across two different institutions of higher learning. Findings from this last step show us that student’s perceptions of autonomy, competency, and relatedness in doing various types of active learning are significantly higher than lecture and consistent across two institutions of higher learning. Lastly, I tie everything together, discuss implications of the research, and address future directions for research on biology student motivation and behavior.

  16. Chemistry and biology by new multiple choice

    International Nuclear Information System (INIS)

    Seo, Hyeong Seok; Kim, Seong Hwan

    2003-02-01

    This book is divided into two parts, the first part is about chemistry, which deals with science of material, atom structure and periodic law, chemical combination and power between molecule, state of material and solution, chemical reaction and an organic compound. The second part give description of biology with molecule and cell, energy in cells and chemical synthesis, molecular biology and heredity, function on animal, function on plant and evolution and ecology. This book has explanation of chemistry and biology with new multiple choice.

  17. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    Science.gov (United States)

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-03-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

  18. Carbon Monoxide: An Essential Signalling Molecule

    Science.gov (United States)

    Mann, Brian E.

    Carbon monoxide (CO), like nitric oxide (NO), is an essential signalling molecule in humans. It is active in the cardiovascular system as a vasodilator. In addition, CO possesses anti-inflammatory, anti-apoptotic and anti-proliferative properties and protects tissues from hypoxia and reperfusion injury. Some of its applications in animal models include suppression of organ graft rejection and safeguarding the heart during reperfusion after cardiopulmonary bypass surgery. CO also suppresses arteriosclerotic lesions following angioplasty, reverses established pulmonary hypertension and mitigates the development of post-operative ileus in the murine small intestine and the development of cerebral malaria in mice as well as graft-induced intimal hyperplasia in pigs. There have been several clinical trials using air-CO mixtures for the treatment of lung-, heart-, kidney- and abdominal-related diseases. This review examines the research involving the development of classes of compounds (with particular emphasis on metal carbonyls) that release CO, which could be used in clinically relevant conditions. The review is drawn not only from published papers in the chemical literature but also from the extensive biological literature and patents on CO-releasing molecules (CO-RMs).

  19. Exploring rhizosphere bacteria of Eichhornia crassipes for metal tolerance and biological activity

    Digital Repository Service at National Institute of Oceanography (India)

    PrabhaDevi; Gomez, S.; Ribeiro, M.; Deshpande, S.A.; Singh, K.S.; DeSouza, L.

    Cl3, They were further screened for antibiotic sensitivity and biological activity according to Kirby-Bauer disc diffusion method The MTB under metal stress condition showed significant biological activity against clinical pathogens, fouling...

  20. Comparative study of biological activity of glutathione, sodium ...

    African Journals Online (AJOL)

    Glutathione (GSH) and sodium tungstate (Na2WO4) are important pharmacological agents. They provide protection to cells against cytotoxic agents and thus reduce their cytotoxicity. It was of interest to study the biological activity of these two pharmacological active agents. Different strains of bacteria were used and the ...

  1. Single molecule measurements of DNA helicase activity with magnetic tweezers and t-test based step-finding analysis

    Science.gov (United States)

    Seol, Yeonee; Strub, Marie-Paule; Neuman, Keir C.

    2016-01-01

    Magnetic tweezers is a versatile and easy to implement single-molecule technique that has become increasingly prevalent in the study of nucleic acid based molecular motors. Here, we provide a description of the magnetic tweezers instrument and guidelines for measuring and analyzing DNA helicase activity. Along with experimental methods, we describe a robust method of single-molecule trajectory analysis based on the Student’s t-test that accommodates continuous transitions in addition to the discrete transitions assumed in most widely employed analysis routines. To illustrate the single-molecule unwinding assay and the analysis routine, we provide DNA unwinding measurements of Escherichia coli RecQ helicase under a variety of conditions (Na+, ATP, temperature, and DNA substrate geometry). These examples reveal that DNA unwinding measurements under various conditions can aid in elucidating the unwinding mechanism of DNA helicase but also emphasize that environmental effects on DNA helicase activity must be considered in relation to in vivo activity and mechanism. PMID:27131595

  2. Identification of intrinsic catalytic activity for electrochemical reduction of water molecules to generate hydrogen

    KAUST Repository

    Shinagawa, Tatsuya; Takanabe, Kazuhiro

    2015-01-01

    Insufficient hydronium ion activities at near-neutral pH and under unbuffered conditions induce diffusion-limited currents for hydrogen evolution, followed by a reaction with water molecules to generate hydrogen at elevated potentials. The observed

  3. Biological Activities of Royal Jelly - Review

    Directory of Open Access Journals (Sweden)

    Crenguţa I. Pavel

    2011-10-01

    Full Text Available Royal jelly is a secretion product of the cephalic glands of nurse bees that has been used for centuries for itsextraordinary properties and health effects. This bibliographic study aims to review many of the scientific findingsand research that prove many of the remarkable various actions, effects and some uses of royal jelly. There are takeninto consideration numerous biological properties and effects of royal jelly: antioxidant, neurotrophic, hipoglicemiant, hipocholesterolemiant and hepatoprotective, hypotensive and blood pressure regulatory, antitumor, antibiotic, anti-inflammatory, immunomodulatory and anti-allergic, general tonic and antiaging. Royal jelly is one ofthe most studied bee products, but there still remains much to reveal about its biochemistry and biological activity infuture research for our health and life benefit.

  4. Biological activity of antitumoural MGBG: the structural variable.

    Science.gov (United States)

    Marques, M P M; Gil, F P S C; Calheiros, R; Battaglia, V; Brunati, A M; Agostinelli, E; Toninello, A

    2008-05-01

    The present study aims at determining the structure-activity relationships (SAR's) ruling the biological function of MGBG (methylglyoxal bis(guanylhydrazone)), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase displaying anticancer activity, involved in the biosynthesis of the naturally occurring polyamines spermidine and spermine. In order to properly understand its biochemical activity, MGBG's structural preferences at physiological conditions were ascertained, by quantum mechanical (DFT) calculations.

  5. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites.

    Science.gov (United States)

    Kevin Ii, Dion A; Meujo, Damaris Af; Hamann, Mark T

    2009-02-01

    As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics.

  6. 1H NMR analysis of complexation of hydrotropic agents nicotinamide and caffeine with aromatic biologically active molecules in aqueous solution

    Science.gov (United States)

    Lantushenko, Anastasia O.; Mukhina, Yulia V.; Veselkov, Kyrill A.; Davies, David B.; Veselkov, Alexei N.

    2004-07-01

    NMR spectroscopy has been used to elucidate the molecular mechanism of solubilization action of hydrotropic agents nicotinamide (NA) and caffeine (CAF). Hetero-association of NA with riboflavine-mononucleotide (FMN) and CAF with low soluble in aqueous solution synthetic analogue of antibiotic actinomycin D, actinocyl-bis-(3-dimethylaminopropyl) amine (Actill), has been investigated by 500 MHz 1H NMR spectroscopy. Concentration and temperature dependences of proton chemical shifts have been analysed in terms of a statistical-thermodynamic model of indefinite self- and heteroassociation of aromatic molecules. The obtained results enable to conclude that NA-FMN and CAF-Actill intermolecular complexes are mainly stabilized by the stacking interactions of the aromatic chromophores. Hetero-association of the investigated molecules plays an important role in solubilization of aromatic drugs by hydrotropic agents nicotinamide and caffeine.

  7. Pragmatic turn in biology: From biological molecules to genetic content operators.

    Science.gov (United States)

    Witzany, Guenther

    2014-08-26

    Erwin Schrödinger's question "What is life?" received the answer for decades of "physics + chemistry". The concepts of Alain Turing and John von Neumann introduced a third term: "information". This led to the understanding of nucleic acid sequences as a natural code. Manfred Eigen adapted the concept of Hammings "sequence space". Similar to Hilbert space, in which every ontological entity could be defined by an unequivocal point in a mathematical axiomatic system, in the abstract "sequence space" concept each point represents a unique syntactic structure and the value of their separation represents their dissimilarity. In this concept molecular features of the genetic code evolve by means of self-organisation of matter. Biological selection determines the fittest types among varieties of replication errors of quasi-species. The quasi-species concept dominated evolution theory for many decades. In contrast to this, recent empirical data on the evolution of DNA and its forerunners, the RNA-world and viruses indicate cooperative agent-based interactions. Group behaviour of quasi-species consortia constitute de novo and arrange available genetic content for adaptational purposes within real-life contexts that determine epigenetic markings. This review focuses on some fundamental changes in biology, discarding its traditional status as a subdiscipline of physics and chemistry.

  8. Single Molecule Spectroscopy in Chemistry, Physics and Biology Nobel Symposium

    CERN Document Server

    Gräslund, Astrid; Widengren, Jerker

    2010-01-01

    Written by the leading experts in the field, this book describes the development and current state-of-the-art in single molecule spectroscopy. The application of this technique, which started 1989, in physics, chemistry and biosciences is displayed.

  9. Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass

    DEFF Research Database (Denmark)

    Toft, P; Tønnesen, Else Kirstine; Zülow, I

    1997-01-01

    Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open-heart...... open-heart and abdominal surgery. The proportion of CD11a/CD18-positive lymphocytes rose from 67.6 +/- 8% to 86.4 +/- 3% after aortic declamping (p open-heart as well as abdominal operations. Thus CPB...

  10. Advanced biological activated carbon filter for removing pharmaceutically active compounds from treated wastewater.

    Science.gov (United States)

    Sbardella, Luca; Comas, Joaquim; Fenu, Alessio; Rodriguez-Roda, Ignasi; Weemaes, Marjoleine

    2018-04-28

    Through their release of effluents, conventional wastewater treatment plants (WWTPs) represent a major pollution point sources for pharmaceutically active compounds (PhACs) in water bodies. The combination of a biological activated carbon (BAC) filter coupled with an ultrafiltration (UF) unit was evaluated as an advanced treatment for PhACs removal at pilot scale. The BAC-UF pilot plant was monitored for one year. The biological activity of the biofilm that developed on the granular activated carbon (GAC) particles and the contribution of this biofilm to the overall removal of PhACs were evaluated. Two different phases were observed during the long-term monitoring of PhACs removal. During the first 9200 bed volumes (BV; i.e., before GAC saturation), 89, 78, 83 and 79% of beta-blockers, psychiatric drugs, antibiotics and a mix of other therapeutic groups were removed, respectively. The second phase was characterized by deterioration of the overall performances during the period between 9200 and 13,800 BV. To quantify the respective contribution of adsorption and biodegradation, a lab-scale setup was operated for four months and highlighted the essential role played by GAC in biofiltration units. Physical adsorption was indeed the main removal mechanism. Nevertheless, a significant contribution due to biological activity was detected for some PhACs. The biofilm contributed to the removal of 22, 25, 30, 32 and 35% of ciprofloxacin, bezafibrate, ofloxacin, azithromycin and sulfamethoxazole, respectively. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Biological activity of selected plants with adaptogenic effect

    OpenAIRE

    Eva Ivanišová; Miroslava Kačániová; Jana Petrová; Radka Staňková; Lucia Godočíková; Tomáš Krajčovič; Štefan Dráb

    2016-01-01

    The aim of this study was to determine biological activity of plants with adaptogenic effect: Panax ginseng Mayer., Withania somnifera L., Eleuterococcus senticosus Rupr. et Maxim., Astragallus membranaceus Fisch. and Codonopsis pilosulae Franch. The antioxidant activity was detected by DPPH and phosphomolybdenum method, total polyphenol content with Folin – Ciocalteu reagent, flavonoids content by aluminium chloride method. The detection of antimicrobial activity was carried out by disc diff...

  12. Regularities in positronium formation for atoms and molecules

    International Nuclear Information System (INIS)

    Machacek, J R; Buckman, S J; Sullivan, J P; Blanco, F; Garcia, G

    2016-01-01

    In an effort to aid the modelling of positron and positronium (Ps) transport in biological media we have compiled recent experimental results for the total Ps formation in positron scattering from atoms and molecules. A simple function was found to adequately describe the total Ps formation cross section for both atoms and molecules. The parameters of this function describe the magnitude and shape of the Ps formation cross section and are compared to physical characteristics of the target atoms and molecules. A general trend in the magnitude of the total Ps formation cross section is observed as a function of the target atom/molecule dipole polarisability. The functional form may enable quick estimation of the Ps cross section for molecules for which experimental measurements or theoretical estimates do not exist. (paper)

  13. Probabilistic biological network alignment.

    Science.gov (United States)

    Todor, Andrei; Dobra, Alin; Kahveci, Tamer

    2013-01-01

    Interactions between molecules are probabilistic events. An interaction may or may not happen with some probability, depending on a variety of factors such as the size, abundance, or proximity of the interacting molecules. In this paper, we consider the problem of aligning two biological networks. Unlike existing methods, we allow one of the two networks to contain probabilistic interactions. Allowing interaction probabilities makes the alignment more biologically relevant at the expense of explosive growth in the number of alternative topologies that may arise from different subsets of interactions that take place. We develop a novel method that efficiently and precisely characterizes this massive search space. We represent the topological similarity between pairs of aligned molecules (i.e., proteins) with the help of random variables and compute their expected values. We validate our method showing that, without sacrificing the running time performance, it can produce novel alignments. Our results also demonstrate that our method identifies biologically meaningful mappings under a comprehensive set of criteria used in the literature as well as the statistical coherence measure that we developed to analyze the statistical significance of the similarity of the functions of the aligned protein pairs.

  14. Prediction of new bioactive molecules using a Bayesian belief network.

    Science.gov (United States)

    Abdo, Ammar; Leclère, Valérie; Jacques, Philippe; Salim, Naomie; Pupin, Maude

    2014-01-27

    Natural products and synthetic compounds are a valuable source of new small molecules leading to novel drugs to cure diseases. However identifying new biologically active small molecules is still a challenge. In this paper, we introduce a new activity prediction approach using Bayesian belief network for classification (BBNC). The roots of the network are the fragments composing a compound. The leaves are, on one side, the activities to predict and, on another side, the unknown compound. The activities are represented by sets of known compounds, and sets of inactive compounds are also used. We calculated a similarity between an unknown compound and each activity class. The more similar activity is assigned to the unknown compound. We applied this new approach on eight well-known data sets extracted from the literature and compared its performance to three classical machine learning algorithms. Experiments showed that BBNC provides interesting prediction rates (from 79% accuracy for high diverse data sets to 99% for low diverse ones) with a short time calculation. Experiments also showed that BBNC is particularly effective for homogeneous data sets but has been found to perform less well with structurally heterogeneous sets. However, it is important to stress that we believe that using several approaches whenever possible for activity prediction can often give a broader understanding of the data than using only one approach alone. Thus, BBNC is a useful addition to the computational chemist's toolbox.

  15. Chemical activation of molecules by metals: Experimental studies of electron distributions and bonding

    International Nuclear Information System (INIS)

    Lichienberger, D.L.

    1990-10-01

    This quarter has witnessed further progress both in our experimental methods of photoelectron spectroscopy and in our understanding the fundamental relationships between ionization energies and the chemistry of transition metal species. Progress continues on the new gas phase photoelectron spectrometer that combine improved capabilities for HeI/HeII UPS, XPS, and Auger investigations of organometallic molecules. Several measurements have been accomplished this year that were not possible previously. We have published the formal relationship between measured molecular ionization energies and thermodynamic bond dissociation energies, and applied the relationships to homonuclear and heteronuclear diatomic molecules, multiple bonds, and metal-ligand bonds. Studies of C-H bond activation have continued with examination of different degrees of Si-H bond addition to metals. the electronic effects of intermolecular interactions have been observed by comparing the ionizations of metal complexes in the gas phase with the ionizations of monolayer solid organometallic films prepared in ultra-high vacuum. The orientations of the molecules have been determined by scanning tunneling microscopy. Especially interesting has been the recent application of these techniques to the characterization of the soccer-ball shaped C 60 molecule, buckminsterfullerene. Studies of the following complexes are described : Fe, Os, Nb, Mo, Rh, Re, Al, and Mn. 19 refs

  16. Systems Biology

    Indian Academy of Sciences (India)

    IAS Admin

    study and understand the function of biological systems, particu- larly, the response of such .... understand the organisation and behaviour of prokaryotic sys- tems. ... relationship of the structure of a target molecule to its ability to bind a certain ...

  17. Active learning in the lecture theatre using 3D printed objects [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    David P. Smith

    2016-06-01

    Full Text Available The ability to conceptualize 3D shapes is central to understanding biological processes. The concept that the structure of a biological molecule leads to function is a core principle of the biochemical field. Visualisation of biological molecules often involves vocal explanations or the use of two dimensional slides and video presentations. A deeper understanding of these molecules can however be obtained by the handling of objects. 3D printed biological molecules can be used as active learning tools to stimulate engagement in large group lectures. These models can be used to build upon initial core knowledge which can be delivered in either a flipped form or a more didactic manner. Within the teaching session the students are able to learn by handling, rotating and viewing the objects to gain an appreciation, for example, of an enzyme’s active site or the difference between the major and minor groove of DNA. Models and other artefacts can be handled in small groups within a lecture theatre and act as a focal point to generate conversation. Through the approach presented here core knowledge is first established and then supplemented with high level problem solving through a "Think-Pair-Share" cooperative learning strategy. The teaching delivery was adjusted based around experiential learning activities by moving the object from mental cognition and into the physical environment. This approach led to students being able to better visualise biological molecules and a positive engagement in the lecture. The use of objects in teaching allows the lecturer to create interactive sessions that both challenge and enable the student.

  18. Biologic activity of porphyromonas endodontalis complex lipids.

    Science.gov (United States)

    Mirucki, Christopher S; Abedi, Mehran; Jiang, Jin; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran E; Clark, Robert B; Nichols, Frank C

    2014-09-01

    Periapical infections secondary to pulpal necrosis are associated with bacterial contamination of the pulp. Porphyromonas endodontalis, a gram-negative organism, is considered to be a pulpal pathogen. P. gingivalis is phylogenetically related to P. endodontalis and synthesizes several classes of novel complex lipids that possess biological activity, including the capacity to promote osteoclastogenesis and osteoclast activation. The purpose of this study was to extract and characterize constituent lipids of P. endodontalis and evaluate their capacity to promote proinflammatory secretory responses in the macrophage cell line, RAW 264.7, as well as their capacity to promote osteoclastogenesis and inhibit osteoblast activity. Constituent lipids of both organisms were fractionated by high-performance liquid chromatography and were structurally characterized using electrospray mass spectrometry or electrospray-mass spectrometry/mass spectrometry. The virulence potential of P. endodontalis lipids was then compared with known biologically active lipids isolated from P. gingivalis. P. endodontalis total lipids were shown to promote tumor necrosis factor alpha secretion from RAW 264.7 cells, and the serine lipid fraction appeared to account for the majority of this effect. P. endodontalis lipid preparations also increased osteoclast formation from RAW 264.7 cells, but osteoblast differentiation in culture was inhibited and appeared to be dependent on Toll-like receptor 2 expression. These effects underscore the importance of P. endodontalis lipids in promoting inflammatory and bone cell activation processes that could lead to periapical pathology. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  19. Solid-state nanopores for scanning single molecules and mimicking biology

    NARCIS (Netherlands)

    Kowalczyk, S.W.

    2011-01-01

    Solid-state nanopores, nanometer-size holes in a thin synthetic membrane, are a versatile tool for the detection and manipulation of charged biomolecules. This thesis describes mostly experimental work on DNA translocation through solid-state nanopores, which we study at the single-molecule level.

  20. Chemical composition analysis and in vitro biological activities of ten essential oils in human skin cells

    Directory of Open Access Journals (Sweden)

    Xuesheng Han

    2017-12-01

    Full Text Available Research on the biological effects of essential oils on human skin cells is scarce. In the current study, we primarily explored the biological activities of 10 essential oils (nine single and one blend in a pre-inflamed human dermal fibroblast system that simulated chronic inflammation. We measured levels of proteins critical for inflammation, immune responses, and tissue-remodeling processes. The nine single oils were distilled from Citrus bergamia (bergamot, Coriandrum sativum (cilantro, Pelargonium graveolens (geranium, Helichrysum italicum (helichrysum, Pogostemon cablin (patchouli, Citrus aurantium (petitgrain, Santalum album (sandalwood, Nardostachys jatamansi (spikenard, and Cananga odorata (ylang ylang. The essential oil blend (commercial name Immortelle is composed of oils from frankincense, Hawaiian sandalwood, lavender, myrrh, helichrysum, and rose. All the studied oils were significantly anti-proliferative against these cells. Furthermore, bergamot, cilantro, and spikenard essential oils primarily inhibited protein molecules related to inflammation, immune responses, and tissue-remodeling processes, suggesting they have anti-inflammatory and wound healing properties. Helichrysum and ylang ylang essential oils, as well as Immortelle primarily inhibited tissue remodeling-related proteins, suggesting a wound healing property. The data are consistent with the results of existing studies examining these oils in other models and suggest that the studied oils may be promising therapeutic candidates. Further research into their biological mechanisms of action is recommended. The differential effects of these essential oils suggest that they exert activities by different mechanisms or pathways, warranting further investigation. The chemical composition of these oils was analyzed using gas chromatography–mass spectrometry. Keywords: Anti-proliferation, Bergamot, Cilantro, Anti-inflammatory, Spikenard, Wound healing

  1. The Importance of Spatiotemporal Information in Biological Motion Perception: White Noise Presented with a Step-like Motion Activates the Biological Motion Area.

    Science.gov (United States)

    Callan, Akiko; Callan, Daniel; Ando, Hiroshi

    2017-02-01

    Humans can easily recognize the motion of living creatures using only a handful of point-lights that describe the motion of the main joints (biological motion perception). This special ability to perceive the motion of animate objects signifies the importance of the spatiotemporal information in perceiving biological motion. The posterior STS (pSTS) and posterior middle temporal gyrus (pMTG) region have been established by many functional neuroimaging studies as a locus for biological motion perception. Because listening to a walking human also activates the pSTS/pMTG region, the region has been proposed to be supramodal in nature. In this study, we investigated whether the spatiotemporal information from simple auditory stimuli is sufficient to activate this biological motion area. We compared spatially moving white noise, having a running-like tempo that was consistent with biological motion, with stationary white noise. The moving-minus-stationary contrast showed significant differences in activation of the pSTS/pMTG region. Our results suggest that the spatiotemporal information of the auditory stimuli is sufficient to activate the biological motion area.

  2. Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

    Directory of Open Access Journals (Sweden)

    Burkhard Koenig

    2011-01-01

    Full Text Available N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.

  3. Activation of stress signaling molecules in bat brain during arousal from hibernation.

    Science.gov (United States)

    Lee, Moonyong; Choi, Inho; Park, Kyoungsook

    2002-08-01

    Induction of glucose-regulated proteins (GRPs) is a ubiquitous intracellular response to stresses such as hypoxia, glucose starvation and acidosis. The induction of GRPs offers some protection against these stresses in vitro, but the specific role of GRPs in vivo remains unclear. Hibernating bats present a good in vivo model to address this question. The bats must overcome local high oxygen demand in tissue by severe metabolic stress during arousal thermogenesis. We used brain tissue of a temperate bat Rhinolopus ferrumequinum to investigate GRP induction by high metabolic oxygen demand and to identify associated signaling molecules. We found that during 30 min of arousal, oxygen consumption increased from nearly zero to 11.9/kg/h, which was about 8.7-fold higher than its active resting metabolic rate. During this time, body temperature rose from 7 degrees C to 35 degrees C, and levels of TNF-alpha and lactate in brain tissue increased 2-2.5-fold, indicating a high risk of oxygen shortage. Concomitantly, levels of GRP75, GRP78 and GRP94 increased 1.5-1.7-fold. At the same time, c-Jun N-terminal protein kinase (JNK) activity increased 6.4-fold, and extracellular signal-regulated protein kinase (ERK) activity decreased to a similar degree (6.1-fold). p38 MAPK activity was very low and remained unchanged during arousal. In addition, survival signaling molecules protein kinase B (Akt) and protein kinase C (PKC) were activated 3- and 5-fold, respectively, during arousal. Taken together, our results showed that bat brain undergoes high oxygen demand during arousal from hibernation. Up-regulation of GRP proteins and activation of JNK, PKCgamma and Akt may be critical for neuroprotection and the survival of bats during the repeated process.

  4. A Starting Point for Fluorescence-Based Single-Molecule Measurements in Biomolecular Research

    Directory of Open Access Journals (Sweden)

    Alexander Gust

    2014-09-01

    Full Text Available Single-molecule fluorescence techniques are ideally suited to provide information about the structure-function-dynamics relationship of a biomolecule as static and dynamic heterogeneity can be easily detected. However, what type of single-molecule fluorescence technique is suited for which kind of biological question and what are the obstacles on the way to a successful single-molecule microscopy experiment? In this review, we provide practical insights into fluorescence-based single-molecule experiments aiming for scientists who wish to take their experiments to the single-molecule level. We especially focus on fluorescence resonance energy transfer (FRET experiments as these are a widely employed tool for the investigation of biomolecular mechanisms. We will guide the reader through the most critical steps that determine the success and quality of diffusion-based confocal and immobilization-based total internal reflection fluorescence microscopy. We discuss the specific chemical and photophysical requirements that make fluorescent dyes suitable for single-molecule fluorescence experiments. Most importantly, we review recently emerged photoprotection systems as well as passivation and immobilization strategies that enable the observation of fluorescently labeled molecules under biocompatible conditions. Moreover, we discuss how the optical single-molecule toolkit has been extended in recent years to capture the physiological complexity of a cell making it even more relevant for biological research.

  5. Preparation of translationally cold neutral molecules.

    Science.gov (United States)

    Di Domenicantonio, Giulia; Bertsche, Benjamin; Osterwalder, Andreas

    2011-01-01

    Efforts at EPFL to obtain translationally cold neutral molecules are described. Active deceleration of polar molecules is performed by confining the molecules in moving three-dimensional electrostatic traps, and by appropriately choosing the velocity of those traps. Alternatively, cold molecules can be obtained by velocity filtering. Here, the velocity of the molecules is not changed, but instead the cold molecules are extracted from a thermal sample by using the competition between the electrostatic force and the centrifugal force inside a bent electrostatic guide for polar molecules.

  6. Biological activity of Stevia rebaudiana Bertoni and their relationship to health.

    Science.gov (United States)

    Ruiz-Ruiz, Jorge Carlos; Moguel-Ordoñez, Yolanda Beatriz; Segura-Campos, Maira Rubi

    2017-08-13

    The leaves of Stevia rebaudiana Bertoni has nutrients and phytochemicals, which make it an adequate source for the extraction and production of functional food ingredients. Preclinical and clinical studies suggest therapeutic and pharmacological applications for stevia and their extracts because they are not toxic and exhibit several biological activities. This review presents the biological activity of Stevia rebaudiana Bertoni and their relationship to antidiabetic, anticariogenic, antioxidant, hypotensive, antihypertensive, antimicrobial, anti-inflammatory and antitumor activities. Consumption and adverse effects were also reviewed.

  7. Chemical reactivities of some interstellar molecules

    Energy Technology Data Exchange (ETDEWEB)

    Chadha, M S

    1980-01-01

    Work in the area of chemical evolution during the last 25 years has revealed the formation of a large number of biologically important molecules produced from simple starting materials under relatively simple experimental conditions. Much of this work has resulted from studies under atmospheres simulating that of the primitive earth or other planets. During the last decade, progress has also been made in the identification of chemical constituents of interstellar medium. A number of these molecules are the same as those identified in laboratory experiments. Even though the conditions of the laboratory experiments are vastly different from those of the cool, low-density interstellar medium, some of the similarities in composition are too obvious to go unnoticed. The present paper highlights some of the similarities in the composition of prebiotic molecules and those discovered in the interstellar medium. Also the chemical reactions which some of the common molecules e.g., NH3, HCN, H2CO, HC(triple bond)-C-CN etc. can undergo are surveyed.

  8. A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs

    Science.gov (United States)

    Pereira, Florbela; Latino, Diogo A. R. S.; Gaudêncio, Susana P.

    2014-01-01

    The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature. PMID:24473174

  9. New approaches to estimation of peat deposits for production of biologically active compounds

    Science.gov (United States)

    Stepchenko, L. M.; Yurchenko, V. I.; Krasnik, V. G.; Syedykh, N. J.

    2009-04-01

    It is known, that biologically active preparations from peat increase animals productivity as well as resistance against stress-factors and have adaptogeneous, antioxidant, immunomodulative properties. Optymal choice of peat deposits for the production of biologically active preparations supposes the detailed comparative analysis of peat properties from different deposits. For this the cadastre of peat of Ukraine is developed in the humic substances laboratory named after prof. Khristeva L.A. (Dnipropetrovsk Agrarian University, Ukraine). It based on the research of its physical and chemical properties, toxicity and biological activity, and called Biocadastre. The Biocadastre is based on the set of parameters, including the descriptions of physical and chemical properties (active acidity, degree of decomposition, botanical composition etc.), toxicity estimation (by parabyotyc, infusorial, inhibitor and other tests), biological activity indexes (growth-promoting, antioxidative, adaptogeneous, immunomodulative antistress and other actions). The blocks of Biocadastre indexes are differentiated, taking into account their use for creation the preparations for vegetable, animals and microorganisms. The Biocadastre will allow to choose the peat deposits, most suitable for the production of different biologically active preparations, both wide directed and narrow spectrum of action, depending on application fields (medicine, agriculture, veterinary medicine, microbiological industry, balneology, cosmetology).

  10. Biologically Active Compounds of Plant Foods: Prospective Impact ...

    African Journals Online (AJOL)

    On the other hand, other biologically active compounds impair health by ... of essential elements through different mechanisms and giving astringent taste, odor, ... The health benefits of selected substances from Ethiopian food crops need to ...

  11. Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine.

    Science.gov (United States)

    Egorova, Ksenia S; Gordeev, Evgeniy G; Ananikov, Valentine P

    2017-05-24

    Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.

  12. Confined Catalysis in the g-C3N4/Pt(111) Interface: Feasible Molecule Intercalation, Tunable Molecule-Metal Interaction, and Enhanced Reaction Activity of CO Oxidation.

    Science.gov (United States)

    Wang, Shujiao; Feng, Yingxin; Yu, Ming'an; Wan, Qiang; Lin, Sen

    2017-09-27

    The deposition of a two-dimensional (2D) atomic nanosheet on a metal surface has been considered as a new route for tuning the molecule-metal interaction and surface reactivity in terms of the confinement effect. In this work, we use first-principles calculations to systematically explore a novel nanospace constructed by placing a 2D graphitic carbon nitride (g-C 3 N 4 ) nanosheet over a Pt(111) surface. The confined catalytic activity in this nanospace is investigated using CO oxidation as a model reaction. With the inherent triangular pores in the g-C 3 N 4 overlayer being taken advantage of, molecules such as CO and O 2 can diffuse to adsorb on the Pt(111) surface underneath the g-C 3 N 4 overlayer. Moreover, the mechanism of intercalation is also elucidated, and the results reveal that the energy barrier depends mainly on the properties of the molecule and the channel. Importantly, the molecule-catalyst interaction can be tuned by the g-C 3 N 4 overlayer, considerably reducing the adsorption energy of CO on Pt(111) and leading to enhanced reactivity in CO oxidation. This work will provide important insight for constructing a promising nanoreactor in which the following is observed: The molecule intercalation is facile; the molecule-metal interaction is efficiently tuned; the metal-catalyzed reaction is promoted.

  13. The mechanism and properties of bio-photon emission and absorption in protein molecules in living systems

    Science.gov (United States)

    Pang, Xiao-feng

    2012-05-01

    The mechanism and properties of bio-photon emission and absorption in bio-tissues were studied using Pang's theory of bio-energy transport, in which the energy spectra of protein molecules are obtained from the discrete dynamic equation. From the energy spectra, it was determined that the protein molecules could both radiate and absorb bio-photons with wavelengths of energy level transitions of the excitons. These results were consistent with the experimental data; this consisted of infrared absorption data from collagen, bovine serum albumin, the protein-like molecule acetanilide, plasma, and a person's finger, and the laser-Raman spectra of acidity I-type collagen in the lungs of a mouse, and metabolically active Escherichia coli. We further elucidated the mechanism responsible for the non-thermal biological effects produced by the infrared light absorbed by the bio-tissues, using the above results. No temperature rise was observed; instead, the absorbed infrared light promoted the vibrations of amides as well the transport of the bio-energy from one place to other in the protein molecules, which changed their conformations. These experimental results, therefore, not only confirmed the validity of the mechanism of bio-photon emission, and the newly developed theory of bio-energy transport mentioned above, but also explained the mechanism and properties of the non-thermal biological effects produced by the absorption of infrared light by the living systems.

  14. Silychristin: Skeletal Alterations and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Biedermann, David; Buchta, M.; Holečková, Veronika; Sedlák, David; Valentová, Kateřina; Cvačka, Josef; Bednárová, Lucie; Křenková, Alena; Kuzma, Marek; Škuta, Ctibor; Peikerová, Žaneta; Bartůněk, Petr; Křen, Vladimír

    2016-01-01

    Roč. 79, č. 12 (2016), s. 3086-3092 ISSN 0163-3864 R&D Projects: GA ČR(CZ) GA15-03037S; GA MZd(CZ) NV16-27317A; GA MŠk LO1220; GA MŠk LM2015063; GA MŠk(CZ) LD15081 Institutional support: RVO:61388971 ; RVO:68378050 ; RVO:61388963 Keywords : Silychristin * skeletal alterations * biological activities Subject RIV: CC - Organic Chemistry Impact factor: 3.281, year: 2016

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

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammad Abdel-Mawgoud

    2018-03-01

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

  16. Biological activity of soils strongly polluted with sulfur

    Energy Technology Data Exchange (ETDEWEB)

    Krol, M; Maliszewska, W; Siuta, J

    1972-01-01

    Studies were carried out on soils strongly polluted with sulfur and acidified (to pH 1.4). The soils were subjected to an intensive liming. In field and pot experiments, the authors determined: the total quantity of bacteria, actinomycetes, fungi, azotobacter, nitrifiers, proteolytic activity of microorganisms, activity of ammonifiers and the number of sulfur-oxidizing and sulfate-reducing bacteria. It was found that intensive liming of sulfur-affected soils restored their biological activity. 8 references, 5 figures, 1 table.

  17. Topoisomerase I as a Biomarker: Detection of Activity at the Single Molecule Level

    DEFF Research Database (Denmark)

    Proszek, Joanna; Roy, Amit; Jakobsen, Ann-Katrine

    2014-01-01

    in hTopI have been reported to result in CPT resistance. Therefore, hTOPI gene copy number, mRNA level, protein amount, and enzyme activity have been studied to explain differences in cellular response to CPT. We show that Rolling Circle Enhanced Enzyme Activity Detection (REEAD), allowing measurement...... of hTopI cleavage-religation activity at the single molecule level, may be used to detect posttranslational enzymatic differences influencing CPT response. These differences cannot be detected by analysis of hTopI gene copy number, mRNA amount, or protein amount, and only become apparent upon measuring...

  18. Biologically active substances from Zanthoxylum capense(thumb.) Harv.

    CSIR Research Space (South Africa)

    Steyn, PS

    1998-08-01

    Full Text Available A chemical investigation into the composition of Zanthoxylum capense yielded several biologically active compounds, including pellitorine. A convenient HPLC method was developed to determine the presence of pellitorine in crude extracts from plants...

  19. Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC.

    Science.gov (United States)

    Lightfoot, J Timothy; DE Geus, Eco J C; Booth, Frank W; Bray, Molly S; DEN Hoed, Marcel; Kaprio, Jaakko; Kelly, Scott A; Pomp, Daniel; Saul, Michael C; Thomis, Martine A; Garland, Theodore; Bouchard, Claude

    2018-04-01

    Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity. Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

  20. 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.

  1. Electron Scattering From Atoms, Molecules, Nuclei, and Bulk Matter

    CERN Document Server

    Whelan, Colm T

    2005-01-01

    Topics that are covered include electron scattering in the scanning TEM; basic theory of inelastic electron imaging; study of confined atoms by electron excitation; helium bubbles created in extreme pressure with application to nuclear safety; lithium ion implantation; electron and positron scattering from clusters; electron scattering from physi- and chemi-absorbed molecules on surfaces; coincidence studies; electron scattering from biological molecules; electron spectroscopy as a tool for environmental science; electron scattering in the presence of intense fields; electron scattering from astrophysical molecules; electon interatctions an detection of x-ray radiation.

  2. Biological activities of Curcuma longa L.

    Directory of Open Access Journals (Sweden)

    Araújo CAC

    2001-01-01

    Full Text Available There are several data in the literature indicating a great variety of pharmacological activities of Curcuma longa L. (Zingiberaceae, which exhibit anti-inflammatory, anti-human immunodeficiency virus, anti-bacteria, antioxidant effects and nematocidal activities. Curcumin is a major component in Curcuma longa L., being responsible for its biological actions. Other extracts of this plant has been showing potency too. In vitro, curcumin exhibits anti-parasitic, antispasmodic, anti-inflammatory and gastrointestinal effects; and also inhibits carcinogenesis and cancer growth. In vivo, there are experiments showing the anti-parasitic, anti-inflammatory potency of curcumin and extracts of C. longa L. by parenteral and oral application in animal models. In this present work we make an overview of the pharmacological activities of C. longa L., showing its importance.

  3. Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Naylor, Paul H; Egan, James E; Berinstein, Neil L; Kast, W Martin

    2016-05-01

    Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

  4. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Christine M. [Brandeis Univ., Waltham, MA (United States)

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  5. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins

    DEFF Research Database (Denmark)

    Thiel, Steffen

    2007-01-01

    Mannan-binding lectin (MBL), L-ficolin, M-ficolin and H-ficolin are all complement activating soluble pattern recognition molecules with recognition domains linked to collagen-like regions. All four may form complexes with four structurally related proteins, the three MBL-associated serine...... proteases (MASPs), MASP-1, MASP-2 and MASP-3, and a smaller MBL-associated protein (MAp19). The four recognition molecules recognize patterns of carbohydrate or acetyl-group containing ligands. After binding to the relevant targets all four are able to activate the complement system. We thus have a system...... where four different and/or overlapping patterns of microbial origin or patterns of altered-self may be recognized, but in all cases the signalling molecules, the MASPs, are shared. MASP-1 and MASP-3 are formed from one gene, MASP1/3, by alternative splicing generating two different mRNAs from a single...

  6. Brown Spider (Loxosceles genus Venom Toxins: Tools for Biological Purposes

    Directory of Open Access Journals (Sweden)

    Andrea Senff-Ribeiro

    2011-03-01

    Full Text Available Venomous animals use their venoms as tools for defense or predation. These venoms are complex mixtures, mainly enriched of proteic toxins or peptides with several, and different, biological activities. In general, spider venom is rich in biologically active molecules that are useful in experimental protocols for pharmacology, biochemistry, cell biology and immunology, as well as putative tools for biotechnology and industries. Spider venoms have recently garnered much attention from several research groups worldwide. Brown spider (Loxosceles genus venom is enriched in low molecular mass proteins (5–40 kDa. Although their venom is produced in minute volumes (a few microliters, and contain only tens of micrograms of protein, the use of techniques based on molecular biology and proteomic analysis has afforded rational projects in the area and permitted the discovery and identification of a great number of novel toxins. The brown spider phospholipase-D family is undoubtedly the most investigated and characterized, although other important toxins, such as low molecular mass insecticidal peptides, metalloproteases and hyaluronidases have also been identified and featured in literature. The molecular pathways of the action of these toxins have been reported and brought new insights in the field of biotechnology. Herein, we shall see how recent reports describing discoveries in the area of brown spider venom have expanded biotechnological uses of molecules identified in these venoms, with special emphasis on the construction of a cDNA library for venom glands, transcriptome analysis, proteomic projects, recombinant expression of different proteic toxins, and finally structural descriptions based on crystallography of toxins.

  7. Correlation between the dielectric properties and biological activities of human ex vivo hepatic tissue

    International Nuclear Information System (INIS)

    Wang, Hang; You, Fusheng; Fu, Feng; Dong, Xiuzhen; Shi, Xuetao; He, Yong; Yang, Min; Yan, Qingguo

    2015-01-01

    Dielectric properties are vital biophysical features of biological tissues, and biological activity is an index to ascertain the active state of tissues. This study investigated the potential correlation between the dielectric properties and biological activities of human hepatic tissue with prolonged ex vivo time through correlation and regression analyses. The dielectric properties of 26 cases of normal human hepatic tissue at 10 Hz to 100 MHz were measured from 15 min after isolation to 24 h at 37 °C with 90% humidity. Cell morphologies, including nucleus area (NA) and alteration rate of intercellular area (ICAR), were analyzed as indicators of biological activities. Conductivity, complex resistivity, and NA exhibited opposing changes 1 h after isolation. Relative permittivity and ex vivo time were not closely correlated (p > 0.05). The dielectric properties measured at low frequencies (i.e. <1 MHz) were more sensitive than those measured at high frequencies in reflecting the biological activity of ex vivo tissue. Highly significant correlations were found between conductivity, resistivity and the ex vivo time (p < 0.05) as well as conductivity and the cell morphology (p < 0.05). The findings indicated that establishing the correlation between the dielectric properties and biological activities of human hepatic tissue is of great significance for promoting the role of dielectric properties in biological science, particularly in human biology. (paper)

  8. Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action

    International Nuclear Information System (INIS)

    Zhang, Haimou; Qin, Gangjian; Liang, Gang; Li, Jinan; Chiu, Isaac; Barrington, Robert A.; Liu, Dongxu

    2007-01-01

    Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-κB activation and nuclear translocation in an IκBα-dependent manner. The inhibitory effects were associated with reduction of inhibitor IκB kinase activity and stabilization of the NF-κB inhibitor IκB. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations

  9. Protein stability and enzyme activity at extreme biological temperatures

    International Nuclear Information System (INIS)

    Feller, Georges

    2010-01-01

    Psychrophilic microorganisms thrive in permanently cold environments, even at subzero temperatures. To maintain metabolic rates compatible with sustained life, they have improved the dynamics of their protein structures, thereby enabling appropriate molecular motions required for biological activity at low temperatures. As a consequence of this structural flexibility, psychrophilic proteins are unstable and heat-labile. In the upper range of biological temperatures, thermophiles and hyperthermophiles grow at temperatures > 100 0 C and synthesize ultra-stable proteins. However, thermophilic enzymes are nearly inactive at room temperature as a result of their compactness and rigidity. At the molecular level, both types of extremophilic proteins have adapted the same structural factors, but in opposite directions, to address either activity at low temperatures or stability in hot environments. A model based on folding funnels is proposed accounting for the stability-activity relationships in extremophilic proteins. (topical review)

  10. Biological activities of xanthatin from Xanthium strumarium leaves.

    Science.gov (United States)

    Nibret, Endalkachew; Youns, Mahamoud; Krauth-Siegel, R Luise; Wink, Michael

    2011-12-01

    The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis. Copyright © 2011 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2013-02-26

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

  12. Biological activities of some Fluoroquinolones-metal complexes

    African Journals Online (AJOL)

    McRoy

    Background: Metal ions play a vital role in the design of more biologically active drugs. Aim: The paper reviewed the .... 2H2O by direct reaction of copper(II) sulphate pentahydrate with ciprofloxacin in distilled water. ... membered ring and the chloride ion completes the seven coordination around the Ca2+ion.[37-39].

  13. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

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

    2015-08-01

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

  14. Surface Passivation for Single-molecule Protein Studies

    Science.gov (United States)

    Chandradoss, Stanley D.; Haagsma, Anna C.; Lee, Young Kwang; Hwang, Jae-Ho; Nam, Jwa-Min; Joo, Chirlmin

    2014-01-01

    Single-molecule fluorescence spectroscopy has proven to be instrumental in understanding a wide range of biological phenomena at the nanoscale. Important examples of what this technique can yield to biological sciences are the mechanistic insights on protein-protein and protein-nucleic acid interactions. When interactions of proteins are probed at the single-molecule level, the proteins or their substrates are often immobilized on a glass surface, which allows for a long-term observation. This immobilization scheme may introduce unwanted surface artifacts. Therefore, it is essential to passivate the glass surface to make it inert. Surface coating using polyethylene glycol (PEG) stands out for its high performance in preventing proteins from non-specifically interacting with a glass surface. However, the polymer coating procedure is difficult, due to the complication arising from a series of surface treatments and the stringent requirement that a surface needs to be free of any fluorescent molecules at the end of the procedure. Here, we provide a robust protocol with step-by-step instructions. It covers surface cleaning including piranha etching, surface functionalization with amine groups, and finally PEG coating. To obtain a high density of a PEG layer, we introduce a new strategy of treating the surface with PEG molecules over two rounds, which remarkably improves the quality of passivation. We provide representative results as well as practical advice for each critical step so that anyone can achieve the high quality surface passivation. PMID:24797261

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

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy

    2013-12-01

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

  16. Advances and challenges in electron-molecule scattering physics-A Report of the 14th International Symposium on Electron-Molecule Collisions and Swarms

    Energy Technology Data Exchange (ETDEWEB)

    Khakoo, M A [Department of Physics, California State University, Fullerton, CA 92831 (United States); Lima, M A P [Departamento de Eletronica Quantica, Instituto de Fisica ' Gleb Wataghin' -UNICAMP, Caixa Postal 6165, 13083-970 Campinas (Brazil); Tennyson, J [Department of Physics and Astronomy, University College, Gower Street, London WC1E 6BT (United Kingdom)

    2006-07-15

    A report is presented of the 13th International Symposium on Electron-Molecule Collisions Physics (Instituto de Fisica, Unicamp, Campinas, Brazil, 27-30 July 2005). This workshop covered low-energy electron interactions with atoms, molecules and condensed matter systems. Several important aspects of this symposium were to bring together theory and experimental advances in this field for gaseous targets as well as showcasing the increasing diversity of electron-molecule collision applications in condensed matter and biological applications. A summary session was held wherein were discussed aspects of the future of the field, including the development of new theoretical and experimental capabilities.

  17. Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Konstantinos M. Kasiotis

    2017-09-01

    Full Text Available Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor (ER binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  18. Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Science.gov (United States)

    Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

    2017-09-01

    Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  19. High-temperature Ionization-induced Synthesis of Biologically Relevant Molecules in the Protosolar Nebula

    Science.gov (United States)

    Bekaert, David V.; Derenne, Sylvie; Tissandier, Laurent; Marrocchi, Yves; Charnoz, Sebastien; Anquetil, Christelle; Marty, Bernard

    2018-06-01

    Biologically relevant molecules (hereafter biomolecules) have been commonly observed in extraterrestrial samples, but the mechanisms accounting for their synthesis in space are not well understood. While electron-driven production of organic solids from gas mixtures reminiscent of the photosphere of the protosolar nebula (PSN; i.e., dominated by CO–N2–H2) successfully reproduced key specific features of the chondritic insoluble organic matter (e.g., elementary and isotopic signatures of chondritic noble gases), the molecular diversity of organic materials has never been investigated. Here, we report that a large range of biomolecules detected in meteorites and comets can be synthesized under conditions typical of the irradiated gas phase of the PSN at temperatures = 800 K. Our results suggest that organic materials—including biomolecules—produced within the photosphere would have been widely dispersed in the protoplanetary disk through turbulent diffusion, providing a mechanism for the distribution of organic meteoritic precursors prior to any thermal/photoprocessing and subsequent modification by secondary parent body processes. Using a numerical model of dust transport in a turbulent disk, we propose that organic materials produced in the photosphere of the disk would likely be associated with small dust particles, which are coupled to the motion of gas within the disk and therefore preferentially lofted into the upper layers of the disk where organosynthesis occurs.

  20. Biological activities of radiation-degraded carrageenan

    International Nuclear Information System (INIS)

    Relleve, Lorna; Dela Rosa, Alumanda; ABAD, Lucille; Aranilla, Charito; Aliganga, Anne Kathrina; Yoshii, Fumio; Kume, Tamikazu; Nagasawa, Naotsugu

    2001-01-01

    Carrageenans were irradiated in solid state to doses 50-1000 kGy in air at ambient temperature. Changes in their molecular weight and functional properties with respect to their FT-IR and UV spectra were evaluated. Irradiation of carrageenans resulted in a rapid decrease of molecular weight indicating main chain scission in their polymeric structures. Formations of some compounds were evident by new absorption peaks in their UV and FT-IR spectra and quantitative analyses of the FT-IR spectra which, in addition, support that there is a breakdown in the carrageenan structure. Irradiated carrageenans were investigated for their plant growth-promoting activity. Carrageenans were added to the nutrient solutions for rice seedlings under non-circulating hydroponics cultivation. Irradiated carrageenan induced weight gain in treated rice seedlings. Maximum weight gain was obtained with KC irradiated at 100 kGy while treatment with IC at 500 kGy. IC exhibited less growth promoting properties than KC. The growth of fungi on the roots disappeared with treatment of IC and KC irradiated at 500 kGy. Growth promotion of some leafy vegetables was also observed with application of degraded KC. The carrageenan molecule has been broken down to smaller molecule (s) or compound (s) that can be absorbed effectively as nourishment factors and anti-microbial agents by plants. (author)

  1. Biological activities of radiation-degraded carrageenan

    Energy Technology Data Exchange (ETDEWEB)

    Relleve, Lorna; Dela Rosa, Alumanda; ABAD, Lucille; Aranilla, Charito; Aliganga, Anne Kathrina [Philippine Nuclear Research Institute, Quezon City (Philippines); Yoshii, Fumio; Kume, Tamikazu; Nagasawa, Naotsugu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    Carrageenans were irradiated in solid state to doses 50-1000 kGy in air at ambient temperature. Changes in their molecular weight and functional properties with respect to their FT-IR and UV spectra were evaluated. Irradiation of carrageenans resulted in a rapid decrease of molecular weight indicating main chain scission in their polymeric structures. Formations of some compounds were evident by new absorption peaks in their UV and FT-IR spectra and quantitative analyses of the FT-IR spectra which, in addition, support that there is a breakdown in the carrageenan structure. Irradiated carrageenans were investigated for their plant growth-promoting activity. Carrageenans were added to the nutrient solutions for rice seedlings under non-circulating hydroponics cultivation. Irradiated carrageenan induced weight gain in treated rice seedlings. Maximum weight gain was obtained with KC irradiated at 100 kGy while treatment with IC at 500 kGy. IC exhibited less growth promoting properties than KC. The growth of fungi on the roots disappeared with treatment of IC and KC irradiated at 500 kGy. Growth promotion of some leafy vegetables was also observed with application of degraded KC. The carrageenan molecule has been broken down to smaller molecule (s) or compound (s) that can be absorbed effectively as nourishment factors and anti-microbial agents by plants. (author)

  2. Drug and bioactive molecule screening based on a bioelectrical impedance cell culture platform

    Directory of Open Access Journals (Sweden)

    Ramasamy S

    2014-12-01

    Full Text Available Sakthivel Ramasamy,1 Devasier Bennet,1 Sanghyo Kim1,2 1Department of Bionanotechnology, Gachon University, Gyeonggi-Do, Republic of Korea; 2Graduate Gachon Medical Research Institute, Gil Medical Center, Incheon, Republic of Korea Abstract: This review will present a brief discussion on the recent advancements of bioelectrical impedance cell-based biosensors, especially the electric cell-substrate impedance sensing (ECIS system for screening of various bioactive molecules. The different technical integrations of various chip types, working principles, measurement systems, and applications for drug targeting of molecules in cells are highlighted in this paper. Screening of bioactive molecules based on electric cell-substrate impedance sensing is a trial-and-error process toward the development of therapeutically active agents for drug discovery and therapeutics. In general, bioactive molecule screening can be used to identify active molecular targets for various diseases and toxicity at the cellular level with nanoscale resolution. In the innovation and screening of new drugs or bioactive molecules, the activeness, the efficacy of the compound, and safety in biological systems are the main concerns on which determination of drug candidates is based. Further, drug discovery and screening of compounds are often performed in cell-based test systems in order to reduce costs and save time. Moreover, this system can provide more relevant results in in vivo studies, as well as high-throughput drug screening for various diseases during the early stages of drug discovery. Recently, MEMS technologies and integration with image detection techniques have been employed successfully. These new technologies and their possible ongoing transformations are addressed. Select reports are outlined, and not all the work that has been performed in the field of drug screening and development is covered. Keywords: screening of bioactive agents, impedance-based cell

  3. A Novel Class of Small Molecule Agonists with Preference for Human over Mouse TLR4 Activation.

    Directory of Open Access Journals (Sweden)

    Jason D Marshall

    Full Text Available The best-characterized Toll-like receptor 4 (TLR4 ligands are lipopolysaccharide (LPS and its chemically modified and detoxified variant, monophosphoryl lipid A (MPL. Although both molecules are active for human TLR4, they demonstrate a potency preference for mouse TLR4 based on data from transfected cell lines and primary cells of both species. After a high throughput screening process of small molecule libraries, we have discovered a new class of TLR4 agonist with a species preference profile differing from MPL. Products of the 4-component Ugi synthesis reaction were demonstrated to potently trigger human TLR4-transfected HEK cells but not mouse TLR4, although inclusion of the human MD2 with mTLR4 was able to partially recover activity. Co-expression of CD14 was not required for optimal activity of Ugi compounds on transfected cells, as it is for LPS. The species preference profile for the panel of Ugi compounds was found to be strongly active for human and cynomolgus monkey primary cells, with reduced but still substantial activity for most Ugi compounds on guinea pig cells. Mouse, rat, rabbit, ferret, and cotton rat cells displayed little or no activity when exposed to Ugi compounds. However, engineering the human versions of TLR4 and MD2 to be expressed in mTLR4/MD2 deficient mice allowed for robust activity by Ugi compounds both in vitro and in vivo. These findings extend the range of compounds available for development as agonists of TLR4 and identify novel molecules which reverse the TLR4 triggering preference of MPL for mouse TLR4 over human TLR4. Such compounds may be amenable to formulation as more potent human-specific TLR4L-based adjuvants than typical MPL-based adjuvants.

  4. Objectives of research activities in Biology Branch, Chalk River Nuclear Laboratories, 1976

    International Nuclear Information System (INIS)

    1977-03-01

    The primary responsibility assigned to the Biology Branch within the framework of CRNL has been an active engagement in basic research related to the assessment of radiation hazards, particularly those to be expected after exposure to relatively low doses of radiation delivered at low dose-rates. The present group is characterized by a broad interest in the entire chain of events by which the initial radiation-induced changes in the living cell are translated into biological effects, with a special focus of attention on the mechanisms by which the initial damage can be largely repaired and by which the risks to man are modified under different circumstances. The basic concepts in radiation biology and risk estimates are reviewed in the light of recent literature on these topics. The current and proposed research activities of the Biology Branch are described. General and specific recommendations for future activities are given. (author)

  5. Synthetic Biology: Putting Synthesis into Biology

    Science.gov (United States)

    Liang, Jing; Luo, Yunzi; Zhao, Huimin

    2010-01-01

    The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

  6. Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects.

    Directory of Open Access Journals (Sweden)

    Marzia Scarpari

    Full Text Available Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin, immune system stimulator (e,g, lentinan, antitumor agents (e.g. krestin, PSK and hypolipidemic agents (e.g. lovastatin inter alia. In this study, we focused on the Chinese medicinal mushroom "yun zhi", Trametes versicolor, traditionally used for (cit. "replenish essence and qi (vital energy". Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied.

  7. Ethnobotany, chemistry, and biological activities of the genus Tithonia (Asteraceae).

    Science.gov (United States)

    Chagas-Paula, Daniela A; Oliveira, Rejane B; Rocha, Bruno A; Da Costa, Fernando B

    2012-02-01

    The genus Tithonia is an important source of diverse natural products, particularly sesquiterpene lactones, diterpenes, and flavonoids. The collected information in this review attempts to summarize the recent developments in the ethnobotany, biological activities, and secondary metabolite chemistry of this genus. More than 100 structures of natural products from Tithonia are reported in this review. The species that has been most investigated in this genus is T. diversifolia, from which ca. 150 compounds were isolated. Biological studies are described to evaluate the anti-inflammatory, analgesic, antimalarial, antiviral, antidiabetic, antidiarrhoeal, antimicrobial, antispasmodic, vasorelaxant, cancer-chemopreventive, cytotoxic, toxicological, bioinsecticide, and repellent activities. A few of these studies have been carried out with isolated compounds from Tithonia species, but the majority has been conducted with different extracts. The relationship between the biological activity and the toxicity of compounds isolated from the plants of this genus as well as T. diversifolia extracts still remains unclear, and mechanisms of action remain to be determined. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  8. [Physico-chemical features of dinitrosyl iron complexes with natural thiol-containing ligands underlying biological activities of these complexes].

    Science.gov (United States)

    Vanin, A F; Borodulin, R R; Kubrina, L N; Mikoian, V D; Burbaev, D Sh

    2013-01-01

    Current notions and new experimental data of the authors on physico-chemical features of dinitrosyl iron complexes with natural thiol-containing ligands (glutathione or cysteine), underlying the ability of the complexes to act as NO molecule and nitrosonium ion donors, are considered. This ability determines various biological activities of dinitrosyl iron complexes--inducing long-lasting vasodilation and thereby long-lasting hypotension in human and animals, inhibiting pellet aggregation, increasing red blood cell elasticity, thereby stimulating microcirculation, and reducing necrotic zone in animals with myocardial infarction. Moreover, dinitrosyl iron complexes are capable of accelerating skin wound healing, improving the function of penile cavernous tissue, blocking apoptosis development in cell cultures. When decomposed dinitrosyl iron complexes can exert cytotoxic effect that can be used for curing infectious and carcinogenic pathologies.

  9. Physio-chemical evaluation and biological activity of Ajuga ...

    African Journals Online (AJOL)

    Physio-chemical evaluation and biological activity of Ajuga bracteosa wall and Viola odoroto Linn. Anwar Ali Shad, M. Zeeshan, Hina Fazal, Hamid Ullah Shah, Shabir Ahmed, Hasem Abeer, E. F. Abd_Allah, Riaz Ullah, Hamid Afridi, Akash tariq, Muhammad Adnan Asma ...

  10. Students’ learning activities while studying biological process diagrams

    NARCIS (Netherlands)

    Kragten, M.; Admiraal, W.; Rijlaarsdam, G.

    2015-01-01

    Process diagrams describe how a system functions (e.g. photosynthesis) and are an important type of representation in Biology education. In the present study, we examined students’ learning activities while studying process diagrams, related to their resulting comprehension of these diagrams. Each

  11. Occurrence, biological activity and synthesis of drimane sesquiterpenoids

    NARCIS (Netherlands)

    Jansen, B.J.M.; Groot, de Æ.

    2004-01-01

    In this review the names, structures and occurrence of all new drimanes and rearranged drimanes, which have been published between January 1990 and January 2003 have been collected. Subjects that have been treated are biosynthesis, analysis, biological activities, with special attention to cytotoxic

  12. Toward Generalization of Iterative Small Molecule Synthesis.

    Science.gov (United States)

    Lehmann, Jonathan W; Blair, Daniel J; Burke, Martin D

    2018-02-01

    Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the "building block approach", i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach.

  13. Toward Generalization of Iterative Small Molecule Synthesis

    Science.gov (United States)

    Lehmann, Jonathan W.; Blair, Daniel J.; Burke, Martin D.

    2018-01-01

    Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach. PMID:29696152

  14. Exploring in vivo cholesterol-mediated interactions between activated EGF receptors in plasma membrane with single-molecule optical tracking

    International Nuclear Information System (INIS)

    Lin, Chien Y.; Huang, Jung Y.; Lo, Leu-Wei

    2016-01-01

    The first step in many cellular signaling processes occurs at various types of receptors in the plasma membrane. Membrane cholesterol can alter these signaling pathways of living cells. However, the process in which the interaction of activated receptors is modulated by cholesterol remains unclear. In this study, we measured single-molecule optical trajectories of epidermal growth factor receptors moving in the plasma membranes of two cancerous cell lines and one normal endothelial cell line. A stochastic model was developed and applied to identify critical information from single-molecule trajectories. We discovered that unliganded epidermal growth factor receptors may reside nearby cholesterol-riched regions of the plasma membrane and can move into these lipid domains when subjected to ligand binding. The amount of membrane cholesterol considerably affects the stability of correlated motion of activated epidermal growth factor receptors. Our results provide single-molecule evidence of membrane cholesterol in regulating signaling receptors. Because the three cell lines used for this study are quite diverse, our results may be useful to shed light on the mechanism of cholesterol-mediated interaction between activated receptors in live cells

  15. Effects of biology teachers' professional knowledge and cognitive activation on students' achievement

    Science.gov (United States)

    Förtsch, Christian; Werner, Sonja; von Kotzebue, Lena; Neuhaus, Birgit J.

    2016-11-01

    This study examined the effects of teachers' biology-specific dimensions of professional knowledge - pedagogical content knowledge (PCK) and content knowledge (CK) - and cognitively activating biology instruction, as a feature of instructional quality, on students' learning. The sample comprised 39 German secondary school teachers whose lessons on the topic neurobiology were videotaped twice. Teachers' instruction was coded with regard to cognitive activation using a rating manual. Multilevel path analysis results showed a positive significant effect of cognitive activation on students' learning and an indirect effect of teachers' PCK on students' learning mediated through cognitive activation. These findings highlight the importance of PCK in preservice biology teachers' education. Items of the rating manual may be used to provide exemplars of concrete teaching situations during university seminars for preservice teacher education or professional development initiatives for in-service teachers.

  16. Central dogma at the single-molecule level in living cells.

    Science.gov (United States)

    Li, Gene-Wei; Xie, X Sunney

    2011-07-20

    Gene expression originates from individual DNA molecules within living cells. Like many single-molecule processes, gene expression and regulation are stochastic, that is, sporadic in time. This leads to heterogeneity in the messenger-RNA and protein copy numbers in a population of cells with identical genomes. With advanced single-cell fluorescence microscopy, it is now possible to quantify transcriptomes and proteomes with single-molecule sensitivity. Dynamic processes such as transcription-factor binding, transcription and translation can be monitored in real time, providing quantitative descriptions of the central dogma of molecular biology and the demonstration that a stochastic single-molecule event can determine the phenotype of a cell.

  17. Quantum biological gravitational wave detectors

    International Nuclear Information System (INIS)

    Kopvillem, U.Kh.

    1985-01-01

    A possibility of producing biological detectors of gravitational waves is considered. High sensitivity of biological systems to outer effects can be ensured by existence of molecule subgroups in Dicke states. Existence of clusters in Dicke state-giant electric dipoles (GED) is supposed in the Froehlich theory. Comparison of biological and physical detectors shows that GED systems have unique properties for detection of gravitational waves if the reception range is narrow

  18. Possible reaction pathways of the lincomycin molecule according to the DFT calculation method

    Directory of Open Access Journals (Sweden)

    Eren Bahar

    2017-01-01

    Full Text Available Human-used antibiotics are eliminated from the body with little or no transformation at all. Traces of eliminated antibiotics enter the receiving environment directly since they cannot be treated in prevalent wastewater treatment facilities. Thus, wastewaters containing traces of antibiotics have to be treated accordingly. Lincomycin is subsequently isolated from Streptomyces lincolnensis. Lincomycin and its derivatives are antibiotics exhibiting biological activity against Gram-positive bacteria, and are natural antibiotics in the environment as pollutants. This study aims to predict the degradation mechanism of lincomycin molecule in the gaseous phase and aqueous media. Probable reaction path of lincomycin molecule with OH radicals was analyzed. Optimized geometry was calculated via Gauss View 5. Subsequently, the lowest energy status was determined through geometric optimization via Gaussian 09 program. Aiming to determine the intermediates in photocatalytic degradation mechanism of lincomycin, geometric optimization of the molecule was realized through DFT method. Activation energy for the probable reaction path was calculated, and their most stable state from the thermodynamic perspective determined for the gaseous phase and aqueous media. Impact of water solvent was investigated using the conductor-like screening solvation model (COSMO. The predicted mechanism was confirmed by comparison with experimental results on simple structures reported in literature.

  19. Physics of biological membranes

    Science.gov (United States)

    Mouritsen, Ole G.

    The biological membrane is a complex system consisting of an aqueous biomolecular planar aggregate of predominantly lipid and protein molecules. At physiological temperatures, the membrane may be considered a thin (˜50Å) slab of anisotropic fluid characterized by a high lateral mobility of the various molecular components. A substantial fraction of biological activity takes place in association with membranes. As a very lively piece of condensed matter, the biological membrane is a challenging research topic for both the experimental and theoretical physicists who are facing a number of fundamental physical problems including molecular self-organization, macromolecular structure and dynamics, inter-macromolecular interactions, structure-function relationships, transport of energy and matter, and interfacial forces. This paper will present a brief review of recent theoretical and experimental progress on such problems, with special emphasis on lipid bilayer structure and dynamics, lipid phase transitions, lipid-protein and lipid-cholesterol interactions, intermembrane forces, and the physical constraints imposed on biomembrane function and evolution. The paper advocates the dual point of view that there are a number of interesting physics problems in membranology and, at the same time, that the physical properties of biomembranes are important regulators of membrane function.

  20. Assessing Student Behaviors and Motivation for Actively Learning Biology

    Science.gov (United States)

    Moore, Michael Edward

    2017-01-01

    Vision and Change states that one of the major changes in the way we design biology courses should be a switch in approach from teacher-centered learning to student-centered learning and identifies active learning as a recommended methods. Studies show performance benefits for students taking courses that use active learning. What is unknown is…

  1. Biological Activity Alterations of Human Amniotic Membrane Pre and Post Irradiation Tissue Banking.

    Science.gov (United States)

    Nemr, Waleed; Bashandy, A S; Araby, Eman; Khamiss, O

    Innate immunity of Human Amniotic Membrane (HAM) and its highly active secretome that rich with various types of growth factors and anti-inflammatory substances proposed it as a promising material for many medical studies and applications. This study evaluate the biological activity of cultivated HAM pre and post tissue banking process in which freeze-dried HAM was sterilized by 25 KGray (kGy) dose of γ radiation. The HAM's antimicrobial activity, viability, growth of isolated human amniotic epithelial cells (HAECs), hematopoietic stimulation of co-cultivated murine bone marrow cells (mammalian model), scaffold efficiency for fish brain building up (non-mammalian model) and self re-epithelialization after trypsin denuding treatment were examined as supposed biological activity features. Native HAM revealed viability indications and was active to kill all tested microorganisms; 6 bacterial species (3 Gram-positive and 3 Gram-negative) and Candida albicans as a pathogenic fungus. Also, HAM activity promoted colony formation of murine hematopoietic cells, Tilapia nilotica brain fragment building-up and self re-epithelialization after trypsin treatment. In contrary, radiation-based tissue banking of HAM caused HAM cellular death and consequently lacked almost all of examined biological activity features. Viable HAM was featured with biological activity than fixed HAM prepared by irradiation tissue banking.

  2. Detection of biologically active diterpenoic acids by Raman Spectroscopy

    DEFF Research Database (Denmark)

    Talian, Ivan; Orinak, Andrej; Efremov, Evtim V.

    2010-01-01

    Three poorly detectable, biologically active diterpenoic acids, kaurenoic, abietic, and gibberellic acid, were studied by using different modes of Raman spectroscopy. Because of their structural similarities, in the absence of strongly polarizable groups, conventional Raman spectroscopy is not su......Three poorly detectable, biologically active diterpenoic acids, kaurenoic, abietic, and gibberellic acid, were studied by using different modes of Raman spectroscopy. Because of their structural similarities, in the absence of strongly polarizable groups, conventional Raman spectroscopy...... few enhanced Raman lines. SERS spectra with 514-nm excitation with Ag colloids were also relatively weak. The best SERS spectrawere obtained with 785-nm excitation on a novel nanostructured substrate, 'black silicon' coated with a 400-nm gold layer. The spectra showed clear differences...

  3. Biological activities of secondary metabolites of the order Zoanthids

    Directory of Open Access Journals (Sweden)

    Zahra Aminikhoei

    2015-11-01

    Full Text Available The phylum Cnidaria is a large, diverse and ecologically important group of marine invertebrates, which produce powerful toxins and venoms. The number of marine natural product from cnidarians isolated from class Anthozoa. Among the Anthozoa, the order of zoanthids are sessile, clonal and mostly brightly colored invertebrate which produce high biodiversity of cytolitic, neurotoxic and cardiotoxic compounds. Zoanthids containing palytoxins are reportedly among the most toxic marine organisms known. In addition, a high concentration of zoanthamine alkaloids extracted from this group.The zoanthamine alkaloids were isolated over 20 years ago, exhibit a broad range of biological activities.The best studied and most well-known biological activity of zoanthamine derivative significantly suppressed bone resorption and enhanced bone formation.

  4. Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules.

    Science.gov (United States)

    Toshima, Kazunobu

    2013-05-01

    Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

  5. Massively Parallel Single-Molecule Manipulation Using Centrifugal Force

    Science.gov (United States)

    Wong, Wesley; Halvorsen, Ken

    2011-03-01

    Precise manipulation of single molecules has led to remarkable insights in physics, chemistry, biology, and medicine. However, two issues that have impeded the widespread adoption of these techniques are equipment cost and the laborious nature of making measurements one molecule at a time. To meet these challenges, we have developed an approach that enables massively parallel single- molecule force measurements using centrifugal force. This approach is realized in the centrifuge force microscope, an instrument in which objects in an orbiting sample are subjected to a calibration-free, macroscopically uniform force- field while their micro-to-nanoscopic motions are observed. We demonstrate high- throughput single-molecule force spectroscopy with this technique by performing thousands of rupture experiments in parallel, characterizing force-dependent unbinding kinetics of an antibody-antigen pair in minutes rather than days. Currently, we are taking steps to integrate high-resolution detection, fluorescence, temperature control and a greater dynamic range in force. With significant benefits in efficiency, cost, simplicity, and versatility, single-molecule centrifugation has the potential to expand single-molecule experimentation to a wider range of researchers and experimental systems.

  6. Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines.

    Science.gov (United States)

    Myers, Rachel; Grundy, Megan; Rowe, Cliff; Coviello, Christian M; Bau, Luca; Erbs, Philippe; Foloppe, Johann; Balloul, Jean-Marc; Story, Colin; Coussios, Constantin C; Carlisle, Robert

    2018-01-01

    The treatment of cancer using nanomedicines is limited by the poor penetration of these potentially powerful agents into and throughout solid tumors. Externally controlled mechanical stimuli, such as the generation of cavitation-induced microstreaming using ultrasound (US), can provide a means of improving nanomedicine delivery. Notably, it has been demonstrated that by focusing, monitoring and controlling the US exposure, delivery can be achieved without damage to surrounding tissue or vasculature. However, there is a risk that such stimuli may disrupt the structure and thereby diminish the activity of the delivered drugs, especially complex antibody and viral-based nanomedicines. In this study, we characterize the impact of cavitation on four different agents, doxorubicin (Dox), cetuximab, adenovirus (Ad) and vaccinia virus (VV), representing a scale of sophistication from a simple small-molecule drug to complex biological agents. To achieve tight regulation of the level and duration of cavitation exposure, a "cavitation test rig" was designed and built. The activity of each agent was assessed with and without exposure to a defined cavitation regime which has previously been shown to provide effective and safe delivery of agents to tumors in preclinical studies. The fluorescence profile of Dox remained unchanged after exposure to cavitation, and the efficacy of this drug in killing a cancer cell line remained the same. Similarly, the ability of cetuximab to bind its epidermal growth factor receptor target was not diminished following exposure to cavitation. The encoding of the reporter gene luciferase within the Ad and VV constructs tested here allowed the infectivity of these viruses to be easily quantified. Exposure to cavitation did not impact on the activity of either virus. These data provide compelling evidence that the US parameters used to safely and successfully delivery nanomedicines to tumors in preclinical models do not detrimentally impact on the

  7. Teaching Old Dyes New Tricks: Biological Probes Built from Fluoresceins and Rhodamines.

    Science.gov (United States)

    Lavis, Luke D

    2017-06-20

    Small-molecule fluorophores, such as fluorescein and rhodamine derivatives, are critical tools in modern biochemical and biological research. The field of chemical dyes is old; colored molecules were first discovered in the 1800s, and the fluorescein and rhodamine scaffolds have been known for over a century. Nevertheless, there has been a renaissance in using these dyes to create tools for biochemistry and biology. The application of modern chemistry, biochemistry, molecular genetics, and optical physics to these old structures enables and drives the development of novel, sophisticated fluorescent dyes. This critical review focuses on an important example of chemical biology-the melding of old and new chemical knowledge-leading to useful molecules for advanced biochemical and biological experiments.

  8. Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

    Science.gov (United States)

    Senavirathne, Gayan; Bertram, Jeffrey G.; Jaszczur, Malgorzata; Chaurasiya, Kathy R.; Pham, Phuong; Mak, Chi H.; Goodman, Myron F.; Rueda, David

    2015-12-01

    Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ~5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer.

  9. Single-molecule pull-down (SiMPull) for new-age biochemistry: methodology and biochemical applications of single-molecule pull-down (SiMPull) for probing biomolecular interactions in crude cell extracts.

    Science.gov (United States)

    Aggarwal, Vasudha; Ha, Taekjip

    2014-11-01

    Macromolecular interactions play a central role in many biological processes. Protein-protein interactions have mostly been studied by co-immunoprecipitation, which cannot provide quantitative information on all possible molecular connections present in the complex. We will review a new approach that allows cellular proteins and biomolecular complexes to be studied in real-time at the single-molecule level. This technique is called single-molecule pull-down (SiMPull), because it integrates principles of conventional immunoprecipitation with the powerful single-molecule fluorescence microscopy. SiMPull is used to count how many of each protein is present in the physiological complexes found in cytosol and membranes. Concurrently, it serves as a single-molecule biochemical tool to perform functional studies on the pulled-down proteins. In this review, we will focus on the detailed methodology of SiMPull, its salient features and a wide range of biological applications in comparison with other biosensing tools. © 2014 WILEY Periodicals, Inc.

  10. SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

    OpenAIRE

    El Mokhtar Essassi; R. Bouhfid; Y. Kandri Rodi; S. Ferfra; H. Benzeid; Y. Ramli

    2010-01-01

    Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

  11. Direct single-molecule dynamic detection of chemical reactions.

    Science.gov (United States)

    Guan, Jianxin; Jia, Chuancheng; Li, Yanwei; Liu, Zitong; Wang, Jinying; Yang, Zhongyue; Gu, Chunhui; Su, Dingkai; Houk, Kendall N; Zhang, Deqing; Guo, Xuefeng

    2018-02-01

    Single-molecule detection can reveal time trajectories and reaction pathways of individual intermediates/transition states in chemical reactions and biological processes, which is of fundamental importance to elucidate their intrinsic mechanisms. We present a reliable, label-free single-molecule approach that allows us to directly explore the dynamic process of basic chemical reactions at the single-event level by using stable graphene-molecule single-molecule junctions. These junctions are constructed by covalently connecting a single molecule with a 9-fluorenone center to nanogapped graphene electrodes. For the first time, real-time single-molecule electrical measurements unambiguously show reproducible large-amplitude two-level fluctuations that are highly dependent on solvent environments in a nucleophilic addition reaction of hydroxylamine to a carbonyl group. Both theoretical simulations and ensemble experiments prove that this observation originates from the reversible transition between the reactant and a new intermediate state within a time scale of a few microseconds. These investigations open up a new route that is able to be immediately applied to probe fast single-molecule physics or biophysics with high time resolution, making an important contribution to broad fields beyond reaction chemistry.

  12. Opportunities for Merging Chemical and Biological Synthesis

    Science.gov (United States)

    Wallace, Stephen; Balskus, Emily P.

    2014-01-01

    Organic chemists and metabolic engineers use largely orthogonal technologies to access small molecules like pharmaceuticals and commodity chemicals. As the use of biological catalysts and engineered organisms for chemical production grows, it is becoming increasingly evident that future efforts for chemical manufacture will benefit from the integration and unified expansion of these two fields. This review will discuss approaches that combine chemical and biological synthesis for small molecule production. We highlight recent advances in combining enzymatic and non-enzymatic catalysis in vitro, discuss the application of design principles from organic chemistry for engineering non-biological reactivity into enzymes, and describe the development of biocompatible chemistry that can be interfaced with microbial metabolism. PMID:24747284

  13. Identifying a Small Molecule Blocking Antigen Presentation in Autoimmune Thyroiditis.

    Science.gov (United States)

    Li, Cheuk Wun; Menconi, Francesca; Osman, Roman; Mezei, Mihaly; Jacobson, Eric M; Concepcion, Erlinda; David, Chella S; Kastrinsky, David B; Ohlmeyer, Michael; Tomer, Yaron

    2016-02-19

    We previously showed that an HLA-DR variant containing arginine at position 74 of the DRβ1 chain (DRβ1-Arg74) is the specific HLA class II variant conferring risk for autoimmune thyroid diseases (AITD). We also identified 5 thyroglobulin (Tg) peptides that bound to DRβ1-Arg74. We hypothesized that blocking the binding of these peptides to DRβ1-Arg74 could block the continuous T-cell activation in thyroiditis needed to maintain the autoimmune response to the thyroid. The aim of the current study was to identify small molecules that can block T-cell activation by Tg peptides presented within DRβ1-Arg74 pockets. We screened a large and diverse library of compounds and identified one compound, cepharanthine that was able to block peptide binding to DRβ1-Arg74. We then showed that Tg.2098 is the dominant peptide when inducing experimental autoimmune thyroiditis (EAT) in NOD mice expressing human DRβ1-Arg74. Furthermore, cepharanthine blocked T-cell activation by thyroglobulin peptides, in particular Tg.2098 in mice that were induced with EAT. For the first time we identified a small molecule that can block Tg peptide binding and presentation to T-cells in autoimmune thyroiditis. If confirmed cepharanthine could potentially have a role in treating human AITD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. γ-Oryzanol reduces adhesion molecule expression in vascular endothelial cells via suppression of nuclear factor-κB activation.

    Science.gov (United States)

    Sakai, Satoshi; Murata, Takahisa; Tsubosaka, Yoshiki; Ushio, Hideki; Hori, Masatoshi; Ozaki, Hiroshi

    2012-04-04

    γ-Oryzanol (γ-ORZ) is a mixture of phytosteryl ferulates purified from rice bran oil. In this study, we examined whether γ-ORZ represents a suppressive effect on the lipopolysaccharide (LPS)-induced adhesion molecule expression on vascular endothelium. Treatment with LPS elevated the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in bovine aortic endothelial cells (BAECs). Pretreatment with γ-ORZ dose-dependently decreased the LPS-mediated expression of these genes. Western blotting also revealed that pretreatment with γ-ORZ dose-dependently inhibited LPS-induced VCAM-1 expression in human umbilical vein endothelial cells. Consistently, pretreatment with γ-ORZ dose-dependently reduced LPS-induced U937 monocyte adhesion to BAECs. In immunofluorescence, LPS caused nuclear factor-κB (NF-κB) nuclear translocation in 40% of BAECs, which indicates NF-κB activation. Pretreatment with γ-ORZ, as well as its components (cycloartenyl ferulate, ferulic acid, or cycloartenol), dose-dependently inhibited LPS-mediated NF-κB activation. Collectively, our results suggested that γ-ORZ reduced LPS-mediated adhesion molecule expression through NF-κB inhibition in vascular endothelium.

  15. Biological activity and chemical profile of Lavatera thuringiaca L. extracts obtained by different extraction approaches.

    Science.gov (United States)

    Mašković, Pavle Z; Veličković, Vesna; Đurović, Saša; Zeković, Zoran; Radojković, Marija; Cvetanović, Aleksandra; Švarc-Gajić, Jaroslava; Mitić, Milan; Vujić, Jelena

    2018-01-01

    Lavatera thuringiaca L. is herbaceous perennial plant from Malvaceae family, which is known for its biological activity and richness in polyphenolic compounds. Despite this, the information regarding the biological activity and chemical profile is still insufficient. Aim of this study was to investigate biological potential and chemical profile of Lavatera thuringiaca L., as well as influence of applied extraction technique on them. Two conventional and four non-conventional extraction techniques were applied in order to obtain extracts rich in bioactive compound. Extracts were further tested for total phenolics, flavonoids, condensed tannins, gallotannins and anthocyanins contents using spectrophotometric assays. Polyphenolic profile was established using HPLC-DAD analysis. Biological activity was investigated regarding antioxidant, cytotoxic and antibacterial activities. Four antioxidant assays were applied as well as three different cell lines for cytotoxic and fifteen bacterial strain for antibacterial activity. Results showed that subcritical water extraction (SCW) dominated over the other extraction techniques, where SCW extract exhibited the highest biological activity. Study indicates that plant Lavatera thuringiaca L. may be used as a potential source of biologically compounds. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.

    Science.gov (United States)

    Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad

    2018-02-18

    Peptides are fragments of proteins with significant biological activities. These peptides are encoded in the protein sequence. Initially, such peptides are inactive in their parental form, unless proteolytic enzymes are released. These peptides then exhibit various functions and play a therapeutic role in the body. Besides the therapeutic and physiological activities of peptides, the main purpose of this study was to highlight the safety aspects of peptides. We performed an organized search of available literature using PubMed, Google Scholar, Medline, EMBASE, Reaxys and Scopus databases. All the relevant citations including research and review articles about the toxicity of biologically active peptides were evaluated and gathered in this study. Biological peptides are widely used in the daily routine ranging from food production to the cosmetics industry and also they have a beneficial role in the treatment and prevention of different diseases. These peptides are manufactured by both chemical and biotechnological techniques, which show negligible toxicity, however, some naturally occurring peptides and enzymes may induce high toxicity. Depending upon the demand and expected use in the food or pharmaceutical industry, we need different approaches to acertain the safety of these peptides preferentially through in silico methods. Intestinal wall disruption, erythrocytes and lymphocytes toxicity, free radical production, enzymopathic and immunopathic tissue damage and cytotoxicity due to the consumption of peptides are the main problems in the biological system that lead to various complicated disorders. Therefore, before considering biologically active peptides for food production and for therapeutic purpose, it is first necessary to evaluate the immunogenicity and toxicities of peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Composite microsphere-functionalized scaffold for the controlled release of small molecules in tissue engineering

    Directory of Open Access Journals (Sweden)

    Laura Pandolfi

    2016-01-01

    Full Text Available Current tissue engineering strategies focus on restoring damaged tissue architectures using biologically active scaffolds. The ideal scaffold would mimic the extracellular matrix of any tissue of interest, promoting cell proliferation and de novo extracellular matrix deposition. A plethora of techniques have been evaluated to engineer scaffolds for the controlled and targeted release of bioactive molecules to provide a functional structure for tissue growth and remodeling, as well as enhance recruitment and proliferation of autologous cells within the implant. Recently, novel approaches using small molecules, instead of growth factors, have been exploited to regulate tissue regeneration. The use of small synthetic molecules could be very advantageous because of their stability, tunability, and low cost. Herein, we propose a chitosan–gelatin scaffold functionalized with composite microspheres consisting of mesoporous silicon microparticles and poly(dl-lactic-co-glycolic acid for the controlled release of sphingosine-1-phospate, a small molecule of interest. We characterized the platform with scanning electron microscopy, Fourier transform infrared spectroscopy, and confocal microscopy. Finally, the biocompatibility of this multiscale system was analyzed by culturing human mesenchymal stem cells onto the scaffold. The presented strategy establishes the basis of a versatile scaffold for the controlled release of small molecules and for culturing mesenchymal stem cells for regenerative medicine applications.

  18. Acoustic input and efferent activity regulate the expression of molecules involved in cochlear micromechanics

    Science.gov (United States)

    Lamas, Veronica; Arévalo, Juan C.; Juiz, José M.; Merchán, Miguel A.

    2015-01-01

    Electromotile activity in auditory outer hair cells (OHCs) is essential for sound amplification. It relies on the highly specialized membrane motor protein prestin, and its interactions with the cytoskeleton. It is believed that the expression of prestin and related molecules involved in OHC electromotility may be dynamically regulated by signals from the acoustic environment. However little is known about the nature of such signals and how they affect the expression of molecules involved in electromotility in OHCs. We show evidence that prestin oligomerization is regulated, both at short and relatively long term, by acoustic input and descending efferent activity originating in the cortex, likely acting in concert. Unilateral removal of the middle ear ossicular chain reduces levels of trimeric prestin, particularly in the cochlea from the side of the lesion, whereas monomeric and dimeric forms are maintained or even increased in particular in the contralateral side, as shown in Western blots. Unilateral removal of the auditory cortex (AC), which likely causes an imbalance in descending efferent activity on the cochlea, also reduces levels of trimeric and tetrameric forms of prestin in the side ipsilateral to the lesion, whereas in the contralateral side prestin remains unaffected, or even increased in the case of trimeric and tetrameric forms. As far as efferent inputs are concerned, unilateral ablation of the AC up-regulates the expression of α10 nicotinic Ach receptor (nAChR) transcripts in the cochlea, as shown by RT-Quantitative real-time PCR (qPCR). This suggests that homeostatic synaptic scaling mechanisms may be involved in dynamically regulating OHC electromotility by medial olivocochlear efferents. Limited, unbalanced efferent activity after unilateral AC removal, also affects prestin and β-actin mRNA levels. These findings support that the concerted action of acoustic and efferent inputs to the cochlea is needed to regulate the expression of major

  19. Small-molecule xenomycins inhibit all stages of the Plasmodium life cycle.

    Science.gov (United States)

    Erath, Jessey; Gallego-Delgado, Julio; Xu, Wenyue; Andriani, Grasiella; Tanghe, Scott; Gurova, Katerina V; Gudkov, Andrei; Purmal, Andrei; Rydkina, Elena; Rodriguez, Ana

    2015-03-01

    Widespread resistance to most antimalaria drugs in use has prompted the search for novel candidate compounds with activity against Plasmodium asexual blood stages to be developed for treatment. In addition, the current malaria eradication programs require the development of drugs that are effective against all stages of the parasite life cycle. We have analyzed the antimalarial properties of xenomycins, a novel subclass of small molecule compounds initially isolated for anticancer activity and similarity to quinacrine in biological effects on mammalian cells. In vitro studies show potent activity of Xenomycins against Plasmodium falciparum. Oral administration of xenomycins in mouse models result in effective clearance of liver and blood asexual and sexual stages, as well as effective inhibition of transmission to mosquitoes. These characteristics position xenomycins as antimalarial candidates with potential activity in prevention, treatment and elimination of this disease. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. New uracil derivatives and their biological activity

    International Nuclear Information System (INIS)

    Hudecova, D.; Striganova, J.; Chovanec, P.; Uher, M.

    1998-01-01

    Present study is concentrated to the research of antimicrobial activity of some derivatives of the uracil and 1,3-dimethyluracyl. The antimicrobial effects of these compounds have been tested on various strains of bacteria, yeasts, and filamentous fungi. The highest antimicrobial effects were found with dithiocarbamato-derivatives, which were effective against pathogenic and non-pathogenic bacteria (IC 50 = 7-25 μg cm -3 ), yeasts (IC 50 = 9-60 μg cm -3 ) and filamentous fungi.The most sensitive fungus to dithiocarbamato-derivatives was Botritis cinerea. It seems to be apparent that the presence of the -NH-C(S)-S- group in molecules of derivatives of uracil and and 1,3-dimethyluracyl influencing the incorporation rate [ 14 ]-adenine and 14 ]-leucine into the biomolecules and also markedly inhibits oxygen consumption (IC 50 = 58 μg cm -3 ). The same derivative demonstrated no mutagenic activity. (authors)

  1. Bomb pulse biology

    Energy Technology Data Exchange (ETDEWEB)

    Falso, Miranda J. Sarachine [Center for Accelerator Mass Spectrometry, Mail Stop L-397, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551 (United States); Buchholz, Bruce A., E-mail: buchholz2@llnl.gov [Center for Accelerator Mass Spectrometry, Mail Stop L-397, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551 (United States)

    2013-01-15

    The past decade has seen an explosion in use of the {sup 14}C bomb pulse to do fundamental cell biology. Studies in the 1960s used decay counting to measure tissue turnover when the atmospheric {sup 14}C/C concentration was changing rapidly. Today bulk tissue measurements are of marginal interest since most of the carbon in the tissue resides in proteins, lipids and carbohydrates that turn over rapidly. Specific cell types with specialized functions are the focus of cell turnover investigations. Tissue samples need to be fresh or frozen. Fixed or preserved samples contain petroleum-derived carbon that has not been successfully removed. Cell or nuclear surface markers are used to sort specific cell types, typically by fluorescence-activated cell sorting (FACS). Specific biomolecules need to be isolated with high purity and accelerator mass spectrometry (AMS) measurements must accommodate samples that generally contain less than 40 {mu}g of carbon. Furthermore, all separations must not add carbon to the sample. Independent means such as UV absorbance must be used to confirm molecule purity. Approaches for separating specific proteins and DNA and combating contamination of undesired molecules are described.

  2. SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    El Mokhtar Essassi

    2010-04-01

    Full Text Available Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

  3. Far-Infrared Spectroscopy of Weakly Bound Hydrated Cluster Molecules

    DEFF Research Database (Denmark)

    Andersen, Jonas

    The thermodynamic properties of condensed phases, the functionality of many materials and the molecular organization in biological organisms are all governed by the classes of non-covalent interactions that occur already on the microscopic scale between pairs of molecules. A detailed investigation...... of the intermolecular interactions between prototypical molecular assemblies are valuable for accurate descriptions of larger supramolecular systems such as materials, gas hydrates and biological macromolecules. The aim of this PhD dissertation is to investigate intermolecular interactions fora series of medium...... vibrational bands of the cluster molecules in the challenging far-infrared and terahertz spectral regions.A key parameter in the validation of the performance of theoretical predictions for weak non-covalent intermolecular interactions is the dissociation energy D0 that depends heavily on the class of large...

  4. The PH Domain of PDK1 Exhibits a Novel, Phospho-Regulated Monomer-Dimer Equilibrium With Important Implications for Kinase Domain Activation: Single Molecule and Ensemble Studies†

    Science.gov (United States)

    Ziemba, Brian P.; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J.

    2013-01-01

    Phosphoinositide-Dependent Kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4-5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric state(s) of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. The present study investigates the binding of purified WT and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single molecule and ensemble measurements. Single molecule analysis of the brightness of fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric, while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single molecule analysis of 2-D diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little protein penetration into the bilayer as observed for other PH domains. The 2-D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that enables greater protein insertion into

  5. Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2

    Directory of Open Access Journals (Sweden)

    Mi Huaiyu

    2015-06-01

    Full Text Available The Systems Biological Graphical Notation (SBGN is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD, Entity Relationship (ER and Activity Flow (AF, allow for the representation of different aspects of biological and biochemical systems at different levels of detail.

  6. Biological AMS at Uppsala University: Status report

    International Nuclear Information System (INIS)

    Salehpour, Mehran; Forsgard, Niklas; Possnert, Goeran

    2010-01-01

    In January 2007 a new research program was initiated at Uppsala University focusing on the biological applications of AMS. We have used a 5 MV Pelletron Tandem accelerator to study biological samples. With Microdosing applications in mind, a variety of measurements have been performed on human blood, plasma and urine that have been labeled with a 14 C-labeled pharmaceutical drug covering a concentration range, spanning 3 orders of magnitude. Furthermore, by studying small sample amounts and low concentrations, we have demonstrated sensitivity in the hundred zeptomole range for a small pharmaceutical substance in human blood. Another application of interest, based on the enhanced 14 C activity from the cold war bomb-peak, is dating of DNA molecules providing fundamental data for the regenerative medicine and stem cell research community. We show data on a sensitive carrier method for measuring the isotopic ratio of small biological sample in the few μgC range.

  7. Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.

    Science.gov (United States)

    An, M; Pratley, J E; Haig, T

    2001-02-01

    Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy.

  8. Theoretical investigation of the degradation mechanisms in host and guest molecules used in OLED active layers

    KAUST Repository

    Winget, Paul; Hong, Minki; Bredas, Jean-Luc

    2014-01-01

    systems. We identify degradation pathways and define new strategies to guide the synthesis of stable materials for OLED applications for both phosphorescent emitters and organic host materials. The chemical reactivity of these molecules in the active

  9. Biological activities of Rumex dentatus L: Evaluation of methanol ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-15

    Dec 15, 2009 ... of different the extracts of R. dentatus effectively inhibited tumor ... Plants contain thousands of biologically active mole- .... The vials were kept open over night with .... between prokaryotic and eukaryotic cells (Stachel and.

  10. Biological oscillations: Fluorescence monitoring by confocal microscopy

    Science.gov (United States)

    Chattoraj, Shyamtanu; Bhattacharyya, Kankan

    2016-09-01

    Fluctuations play a vital role in biological systems. Single molecule spectroscopy has recently revealed many new kinds of fluctuations in biological molecules. In this account, we focus on structural fluctuations of an antigen-antibody complex, conformational dynamics of a DNA quadruplex, effects of taxol on dynamics of microtubules, intermittent red-ox oscillations at different organelles in a live cell (mitochondria, lipid droplets, endoplasmic reticulum and cell membrane) and stochastic resonance in gene silencing. We show that there are major differences in these dynamics between a cancer cell and the corresponding non-cancer cell.

  11. [Evaluation of the total biological activity and allergenic composition of allergenic extracts].

    Science.gov (United States)

    Lombardero, M; González, R; Duffort, O; Juan, F; Ayuso, R; Ventas, P; Cortés, C; Carreira, J

    1986-01-01

    In the present study, a complete procedure is presented in order to standardize allergenic extracts, the meaning of which is the measurement of the total allergenic activity and the determination of the allergenic composition. The measurement of the biological activity comprises 2 steps: Preparation of Reference Extracts and determination of their "in vivo" activity. Evaluation of the total allergenic activity of extracts for clinical use. Reference extracts were prepared from the main allergens and their "in vivo" biological activity was determined by a quantitative skin prick test in a sample of at least 30 allergic patients. By definition, the protein concentration of Reference Extract that produces, in the allergic population, a geometric mean wheal of 75 mm.2 has an activity of 100 biological units (BUs). The determination of the biological activity of a problem extract is made by RAST inhibition. The sample is compared with the corresponding Reference Extract by this technique and, from this comparison, it is possible to quantify the activity of the problem extract in biologic units (BUs) with clinical significance. Likewise, different techniques have been used to determine the allergenic composition of extracts. These techniques comprise 2 steps: Separation of the components of the extract. Identification of the components that bind specific human IgE. The separation of the components of the extract has been carried out by isoelectric focusing (IEF) and electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE). In order to identify the allergenic components, an immunoblotting technique has been employed. The separated components in the IEF gel or SDS-PAGE gel are transferred to a nitrocellulose sheet and later on, this membrane is overlaid with a serum pool from allergic patients and a mouse monoclonal anti-human IgE, labelled with 125I. Finally, the autoradiography of the nitrocellulose membrane is obtained. In this way it is possible to compare

  12. Generation of structurally novel short carotenoids and study of their biological activity.

    Science.gov (United States)

    Kim, Se H; Kim, Moon S; Lee, Bun Y; Lee, Pyung C

    2016-02-23

    Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4'-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli.

  13. Reconstructing Causal Biological Networks through Active Learning.

    Directory of Open Access Journals (Sweden)

    Hyunghoon Cho

    Full Text Available Reverse-engineering of biological networks is a central problem in systems biology. The use of intervention data, such as gene knockouts or knockdowns, is typically used for teasing apart causal relationships among genes. Under time or resource constraints, one needs to carefully choose which intervention experiments to carry out. Previous approaches for selecting most informative interventions have largely been focused on discrete Bayesian networks. However, continuous Bayesian networks are of great practical interest, especially in the study of complex biological systems and their quantitative properties. In this work, we present an efficient, information-theoretic active learning algorithm for Gaussian Bayesian networks (GBNs, which serve as important models for gene regulatory networks. In addition to providing linear-algebraic insights unique to GBNs, leading to significant runtime improvements, we demonstrate the effectiveness of our method on data simulated with GBNs and the DREAM4 network inference challenge data sets. Our method generally leads to faster recovery of underlying network structure and faster convergence to final distribution of confidence scores over candidate graph structures using the full data, in comparison to random selection of intervention experiments.

  14. Rapid localization of carbon 14-labeled molecules in biological samples by ion mass microscopy

    International Nuclear Information System (INIS)

    Hindie, E.; Escaig, F.; Coulomb, B.; Lebreton, C.; Galle, P.

    1989-01-01

    We report here on the ability of secondary ion mass spectrometry (SIMS) to provide rapid imaging of the intracellular distribution of 14 C-labeled molecules. The validity of this method, using mass discrimination of carbon 14 atoms, was assessed by imaging the distribution of two molecules of well-known metabolism, [ 14 C]-thymidine and [ 14 C]-uridine, incorporated by human fibroblasts in culture. As expected, 14 C ion images showed the presence of [ 14 C]-thymidine in the nucleus of dividing cells, whereas [ 14 C]-uridine was present in the cytoplasm as well as the nucleus of all cells, with a large concentration in the nucleoli. The time required to obtain the distribution images with the SMI 300 microscope was less than 6 min, whereas microautoradiography, the classical method for mapping the tissue distribution of 14 C-labeled molecules, usually requires exposure times of several months. Secondary ion mass spectrometry using in situ mass discrimination is proposed here as a very sensitive method which permits rapid imaging of the subcellular distribution of molecules labeled with carbon 14

  15. Synthetic Approaches and Biological Activities of 4-Hydroxycoumarin Derivatives

    Directory of Open Access Journals (Sweden)

    Oee-Sook Park

    2009-11-01

    Full Text Available The main purpose of this review is to summarize recent chemical syntheses and structural modifications of 4-hydroxycoumarin and its derivatives, of interest due to their characteristic conjugated molecular architecture and biological activities.

  16. Spectroscopic study of biologically active glasses

    Science.gov (United States)

    Szumera, M.; Wacławska, I.; Mozgawa, W.; Sitarz, M.

    2005-06-01

    It is known that the chemical activity phenomenon is characteristic for some inorganic glasses and they are able to participate in biological processes of living organisms (plants, animals and human bodies). An example here is the selective removal of silicate-phosphate glass components under the influence of biological solutions, which has been applied in designing glasses acting as ecological fertilizers of controlled release rate of the nutrients for plants. The structure of model silicate-phosphate glasses containing the different amounts of the glass network formers, i.e. Ca 2+ and Mg 2+, as a binding components were studied. These elements besides other are indispensable of the normal growth of plants. In order to establish the function and position occupied by the particular components in the glass structure, the glasses were examined by FTIR spectroscopy (with spectra decomposition) and XRD methods. It has been found that the increasing amount of MgO in the structure of silicate-phosphate glasses causes the formation of domains the structure of which changes systematically from a structure of the cristobalite type to a structure corresponding to forsterite type. Whilst the increasing content of CaO in the structure of silicate-phosphate glasses causes the formation of domains the structure of which changes from a structure typical for cristobalite through one similar to the structure of calcium orthophosphate, to a structure corresponding to calcium silicates. The changing character of domains structure is the reason of different chemical activity of glasses.

  17. The formation of urea in space. I. Ion-molecule, neutral-neutral, and radical gas-phase reactions

    Science.gov (United States)

    Brigiano, Flavio Siro; Jeanvoine, Yannick; Largo, Antonio; Spezia, Riccardo

    2018-02-01

    Context. Many organic molecules have been observed in the interstellar medium thanks to advances in radioastronomy, and very recently the presence of urea was also suggested. While those molecules were observed, it is not clear what the mechanisms responsible to their formation are. In fact, if gas-phase reactions are responsible, they should occur through barrierless mechanisms (or with very low barriers). In the past, mechanisms for the formation of different organic molecules were studied, providing only in a few cases energetic conditions favorable to a synthesis at very low temperature. A particularly intriguing class of such molecules are those containing one N-C-O peptide bond, which could be a building block for the formation of biological molecules. Urea is a particular case because two nitrogen atoms are linked to the C-O moiety. Thus, motivated also by the recent tentative observation of urea, we have considered the synthetic pathways responsible to its formation. Aims: We have studied the possibility of forming urea in the gas phase via different kinds of bi-molecular reactions: ion-molecule, neutral, and radical. In particular we have focused on the activation energy of these reactions in order to find possible reactants that could be responsible for to barrierless (or very low energy) pathways. Methods: We have used very accurate, highly correlated quantum chemistry calculations to locate and characterize the reaction pathways in terms of minima and transition states connecting reactants to products. Results: Most of the reactions considered have an activation energy that is too high; but the ion-molecule reaction between NH2OHNH2OH2+ and formamide is not too high. These reactants could be responsible not only for the formation of urea but also of isocyanic acid, which is an organic molecule also observed in the interstellar medium.

  18. Recent Advances in Momordica charantia: Functional Components and Biological Activities

    Directory of Open Access Journals (Sweden)

    Shuo Jia

    2017-11-01

    Full Text Available Momordica charantia L. (M. charantia, a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia.

  19. Recent Advances in Momordica charantia: Functional Components and Biological Activities.

    Science.gov (United States)

    Jia, Shuo; Shen, Mingyue; Zhang, Fan; Xie, Jianhua

    2017-11-28

    Momordica charantia L. ( M. charantia ), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia .

  20. Data-mining of potential antitubercular activities from molecular ingredients of traditional Chinese medicines.

    Science.gov (United States)

    Jamal, Salma; Scaria, Vinod

    2014-01-01

    Background. Traditional Chinese medicine encompasses a well established alternate system of medicine based on a broad range of herbal formulations and is practiced extensively in the region for the treatment of a wide variety of diseases. In recent years, several reports describe in depth studies of the molecular ingredients of traditional Chinese medicines on the biological activities including anti-bacterial activities. The availability of a well-curated dataset of molecular ingredients of traditional Chinese medicines and accurate in-silico cheminformatics models for data mining for antitubercular agents and computational filters to prioritize molecules has prompted us to search for potential hits from these datasets. Results. We used a consensus approach to predict molecules with potential antitubercular activities from a large dataset of molecular ingredients of traditional Chinese medicines available in the public domain. We further prioritized 160 molecules based on five computational filters (SMARTSfilter) so as to avoid potentially undesirable molecules. We further examined the molecules for permeability across Mycobacterial cell wall and for potential activities against non-replicating and drug tolerant Mycobacteria. Additional in-depth literature surveys for the reported antitubercular activities of the molecular ingredients and their sources were considered for drawing support to prioritization. Conclusions. Our analysis suggests that datasets of molecular ingredients of traditional Chinese medicines offer a new opportunity to mine for potential biological activities. In this report, we suggest a proof-of-concept methodology to prioritize molecules for further experimental assays using a variety of computational tools. We also additionally suggest that a subset of prioritized molecules could be used for evaluation for tuberculosis due to their additional effect against non-replicating tuberculosis as well as the additional hepato-protection offered by

  1. Biologically Active Metabolites Synthesized by Microalgae

    Directory of Open Access Journals (Sweden)

    Michele Greque de Morais

    2015-01-01

    Full Text Available Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

  2. A novel theory: biological processes mostly involve two types of mediators, namely general and specific mediators Endogenous small radicals such as superoxide and nitric oxide may play a role of general mediator in biological processes.

    Science.gov (United States)

    Mo, Jian

    2005-01-01

    A great number of papers have shown that free radicals as well as bioactive molecules can play a role of mediator in a wide spectrum of biological processes, but the biological actions and chemical reactivity of the free radicals are quite different from that of the bioactive molecules, and that a wide variety of bioactive molecules can be easily modified by free radicals due to having functional groups sensitive to redox, and the significance of the interaction between the free radicals and the bioactive molecules in biological processes has been confirmed by the results of some in vitro and in vivo studies. Based on these evidence, this article presented a novel theory about the mediators of biological processes. The essentials of the theory are: (a) mediators of biological processes can be classified into general and specific mediators; the general mediators include two types of free radicals, namely superoxide and nitric oxide; the specific mediators include a wide variety of bioactive molecules, such as specific enzymes, transcription factors, cytokines and eicosanoids; (b) a general mediator can modify almost any class of the biomolecules, and thus play a role of mediator in nearly every biological process via diverse mechanisms; a specific mediator always acts selectively on certain classes of the biomolecules, and may play a role of mediator in different biological processes via a same mechanism; (c) biological processes are mostly controlled by networks of their mediators, so the free radicals can regulate the last consequence of a biological process by modifying some types of the bioactive molecules, or in cooperation with these bioactive molecules; the biological actions of superoxide and nitric oxide may be synergistic or antagonistic. According to this theory, keeping the integrity of these networks and the balance between the free radicals and the bioactive molecules as well as the balance between the free radicals and the free radical scavengers

  3. The importance of extremophile cyanobacteria in the production of biologically active compounds

    Directory of Open Access Journals (Sweden)

    Drobac-Čik Aleksandra V.

    2007-01-01

    Full Text Available Due to their ability to endure extreme conditions, terrestrial cyanobacteria belong to a group of organisms known as "extremophiles". Research so far has shown that these organisms posses a great capacity for producing biologically active compounds (BAC. The antibacterial and antifungal activities of methanol extracts of 21 cyanobacterial strains belonging to Anabaena and Nostoc genera, previously isolated from different soil types and water resources in Serbia, were evaluated. In general, larger number of cyanobacterial strains showed antifungal activity. In contrast to Nostoc, Anabaena strains showed greater diversity of antibacterial activity (mean value of percentages of sensitive targeted bacterial strains 3% and 25.9% respectively. Larger number of targeted fungi was sensitive to cultural liquid extract (CL, while crude cell extract (CE affected more bacterial strains. According to this investigation, the higher biological activity of terrestrial strains as representatives of extremophiles may present them as significant BAC producers. This kind of investigation creates very general view of cyanobacterial possibility to produce biologically active compounds but it points out the necessity of exploring terrestrial cyanobacterial extremophiles as potentially excellent sources of these substances and reveals the most prospective strains for further investigations.

  4. Single-molecule stochastic times in a reversible bimolecular reaction

    Science.gov (United States)

    Keller, Peter; Valleriani, Angelo

    2012-08-01

    In this work, we consider the reversible reaction between reactants of species A and B to form the product C. We consider this reaction as a prototype of many pseudobiomolecular reactions in biology, such as for instance molecular motors. We derive the exact probability density for the stochastic waiting time that a molecule of species A needs until the reaction with a molecule of species B takes place. We perform this computation taking fully into account the stochastic fluctuations in the number of molecules of species B. We show that at low numbers of participating molecules, the exact probability density differs from the exponential density derived by assuming the law of mass action. Finally, we discuss the condition of detailed balance in the exact stochastic and in the approximate treatment.

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

    Science.gov (United States)

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

    2016-01-29

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

  6. Designing and testing a classroom curriculum to teach preschoolers about the biology of physical activity: The respiration system as an underlying biological causal mechanism

    Science.gov (United States)

    Ewing, Tracy S.

    The present study examined young children's understanding of respiration and oxygen as a source of vital energy underlying physical activity. Specifically, the purpose of the study was to explore whether a coherent biological theory, characterized by an understanding that bodily parts (heart and lungs) and processes (oxygen in respiration) as part of a biological system, can be taught as a foundational concept to reason about physical activity. The effects of a biology-based intervention curriculum designed to teach preschool children about bodily functions as a part of the respiratory system, the role of oxygen as a vital substance and how physical activity acts an energy source were examined. Participants were recruited from three private preschool classrooms (two treatment; 1 control) in Southern California and included a total of 48 four-year-old children (30 treatment; 18 control). Findings from this study suggested that young children could be taught relevant biological concepts about the role of oxygen in respiratory processes. Children who received biology-based intervention curriculum made significant gains in their understanding of the biology of respiration, identification of physical and sedentary activities. In addition these children demonstrated that coherence of conceptual knowledge was correlated with improved accuracy at activity identification and reasoning about the inner workings of the body contributing to endurance. Findings from this study provided evidence to support the benefits of providing age appropriate but complex coherent biological instruction to children in early childhood settings.

  7. Radiation degradation of carbohydrates and their biological activities for plants

    International Nuclear Information System (INIS)

    Kume, T.; Nagasawa, N.; Matsuhashi, S.

    2000-01-01

    Radiation effects on carbohydrates such as chitosan, sodium alginate, carrageenan, cellulose, pectin have been investigated to improve the biological activities. These carbohydrates were easily degraded by irradiation and induced various kinds of biological activities such as anti-bacterial activity, promotion of plant growth, suppression of heavy metal stress, phytoalexins induction. Pectic fragments obtained from degraded pectin induced the phytoalexins such as glyceollins in soybean and pisatin in pea. The irradiated chitosan shows the higher elicitor activity for pisatin than that of pectin. For the plant growth promotion, alginate derived from brown marine algae, chitosan and ligno-cellulosic extracts show a strong activity. Kappa and iota carrageenan derived from red marine algae can promote growth of rice and the highest effect was obtained with kappa irradiated at 100 kGy. Some radiation degraded carbohydrates suppressed the damage of heavy metals on plants. The effects of irradiated carbohydrates on transportation of heavy metals have been investigated by PETIS (Positron Emitting Tracer Imaging System) and autoradiography using 48 V and 62 Zn. (author)

  8. Intercellular adhesion molecules (ICAMs) and spermatogenesis

    Science.gov (United States)

    Xiao, Xiang; Mruk, Dolores D.; Cheng, C. Yan

    2013-01-01

    BACKGROUND During the seminiferous epithelial cycle, restructuring takes places at the Sertoli–Sertoli and Sertoli–germ cell interface to accommodate spermatogonia/spermatogonial stem cell renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation since developing germ cells, in particular spermatids, move ‘up and down’ the seminiferous epithelium. Furthermore, preleptotene spermatocytes differentiated from type B spermatogonia residing at the basal compartment must traverse the blood–testis barrier (BTB) to enter the adluminal compartment to prepare for meiosis at Stage VIII of the epithelial cycle, a process also accompanied by the release of sperm at spermiation. These cellular events that take place at the opposite ends of the epithelium are co-ordinated by a functional axis designated the apical ectoplasmic specialization (ES)—BTB—basement membrane. However, the regulatory molecules that co-ordinate cellular events in this axis are not known. METHODS Literature was searched at http://www.pubmed.org and http://scholar.google.com to identify published findings regarding intercellular adhesion molecules (ICAMs) and the regulation of this axis. RESULTS Members of the ICAM family, namely ICAM-1 and ICAM-2, and the biologically active soluble ICAM-1 (sICAM-1) are the likely regulatory molecules that co-ordinate these events. sICAM-1 and ICAM-1 have antagonistic effects on the Sertoli cell tight junction-permeability barrier, involved in Sertoli cell BTB restructuring, whereas ICAM-2 is restricted to the apical ES, regulating spermatid adhesion during the epithelial cycle. Studies in other epithelia/endothelia on the role of the ICAM family in regulating cell movement are discussed and this information has been evaluated and integrated into studies of these proteins in the testis to create a hypothetical model, depicting how ICAMs regulate junction restructuring events during spermatogenesis. CONCLUSIONS ICAMs are crucial

  9. Suitable activated stable nuclide tracer technique and its applications in biology and medicine

    International Nuclear Information System (INIS)

    Zhang Weicheng

    1989-01-01

    Stable isotopes as tracers in biology and medicine have been more extensively used. Mass spectrometry has been a classic technique in the analysis of stable isotopes because it is very sensitive and precise. Activation analysis has recently been introduced as an analytical tool. Its fast speed and simplicity is a great advantage for handling large batches of samples in isotopic tracer experiments. The combination of enriched stable isotope tracer studies and activation analysis techniques has become an ideal and reliable technique, especially in the fields of biology and medicine. This paper presents a survey of the fundamental principle, the character and the applications in biology and medicine for the suitable activated stable isotope tracer techniques

  10. Impact of some herbicides on the biomass activity in biological treatment plants and biodegradability enhancement by a photo-Fenton process.

    Science.gov (United States)

    Benzaquén, T B; Benzzo, M T; Isla, M A; Alfano, O M

    2013-01-01

    In recent years, the use of agrochemicals has increased because they are essential for profitable agricultural production. Herbicides are heavily demanded compounds and among these, the most marketed are 2,4-D, atrazine and acetochlor. They have characteristics that can cause problems to humans and the environment. Therefore, it is necessary to design systems that can reduce these compounds to harmless molecules. This work aims at evaluating the possibility of incorporating these herbicides into degradable effluents in a biological treatment system, without reducing its efficiency. For this purpose, studies of organic matter degradability in the presence of these agrochemicals were performed. A synthetic effluent based on glucose and mineral salts was inoculated with microorganisms. Glucose consumption and biomass concentration were assessed. Subsequently, preliminary studies were performed to test the viability of degradation of the most harmful compound with an advanced oxidation process (AOP). The results showed that the incorporation of these herbicides into degradable effluents in a biological treatment system has a negative impact on microorganisms. Therefore, the application of an AOP, such as the Fenton or photo-Fenton processes, prior to a biological treatment was found to degrade these substances to simpler and less toxic molecules.

  11. Single-molecule dataset (SMD): a generalized storage format for raw and processed single-molecule data.

    Science.gov (United States)

    Greenfeld, Max; van de Meent, Jan-Willem; Pavlichin, Dmitri S; Mabuchi, Hideo; Wiggins, Chris H; Gonzalez, Ruben L; Herschlag, Daniel

    2015-01-16

    Single-molecule techniques have emerged as incisive approaches for addressing a wide range of questions arising in contemporary biological research [Trends Biochem Sci 38:30-37, 2013; Nat Rev Genet 14:9-22, 2013; Curr Opin Struct Biol 2014, 28C:112-121; Annu Rev Biophys 43:19-39, 2014]. The analysis and interpretation of raw single-molecule data benefits greatly from the ongoing development of sophisticated statistical analysis tools that enable accurate inference at the low signal-to-noise ratios frequently associated with these measurements. While a number of groups have released analysis toolkits as open source software [J Phys Chem B 114:5386-5403, 2010; Biophys J 79:1915-1927, 2000; Biophys J 91:1941-1951, 2006; Biophys J 79:1928-1944, 2000; Biophys J 86:4015-4029, 2004; Biophys J 97:3196-3205, 2009; PLoS One 7:e30024, 2012; BMC Bioinformatics 288 11(8):S2, 2010; Biophys J 106:1327-1337, 2014; Proc Int Conf Mach Learn 28:361-369, 2013], it remains difficult to compare analysis for experiments performed in different labs due to a lack of standardization. Here we propose a standardized single-molecule dataset (SMD) file format. SMD is designed to accommodate a wide variety of computer programming languages, single-molecule techniques, and analysis strategies. To facilitate adoption of this format we have made two existing data analysis packages that are used for single-molecule analysis compatible with this format. Adoption of a common, standard data file format for sharing raw single-molecule data and analysis outcomes is a critical step for the emerging and powerful single-molecule field, which will benefit both sophisticated users and non-specialists by allowing standardized, transparent, and reproducible analysis practices.

  12. Photoinduced electron transfer in some photosensitive molecules ...

    Indian Academy of Sciences (India)

    Unknown

    redox reactions of substrates like biological molecules,11,12 dyes,13,14 alcohols15,16 etc. Colloidal ... state which is characterised by a phenomenon of dual fluorescence. In the present ... The dried solid was transferred to quartz cell under vacuum ... Recently Grätzel et al34 have developed the dye-sensitized meso-.

  13. Bacteroides species produce Vibrio harveyi autoinducer 2-related molecules.

    Science.gov (United States)

    Antunes, Luis Caetano Martha; Ferreira, Lívia Queiroz; Ferreira, Eliane Oliveira; Miranda, Karla Rodrigues; Avelar, Kátia Eliane Santos; Domingues, Regina Maria Cavalcanti Pilotto; Ferreira, Maria Candida de Souza

    2005-10-01

    Quorum sensing is a density-dependent gene regulation mechanism that has been described in many bacterial species in the last decades. Bacteria that use quorum sensing as part of their gene regulation circuits produce molecules called autoinducers that accumulate in the environment and activate target genes in a quorum-dependent way. Some specific clues led us to hypothesize that Bacteroides species can produce autoinducers and possess a quorum sensing system. First, Bacteroides are anaerobic bacteria that are frequently involved in polymicrobial infections. These infections often involve Pseudomonas aeruginosa and Staphylococcus aureus, two of the best understood examples of bacteria that employ quorum sensing systems as part of their pathogenesis. Also, studies have detected the presence of a quorum sensing gene involved in the production of autoinducers in Porphyromonas gingivalis, a species closely related to the Bacteroides genus. These and other evidences prompted us to investigate if Bacteroides strains could produce autoinducer molecules that could be detected by a Vibrio harveyi reporter system. In this paper, we show that supernatants of B. fragilis, B. vulgatus and B. distasonis strains are able to stimulate the V. harveyi quorum sensing system 2. Also, we were able to demonstrate that the stimulation detected is due to the production of autoinducer molecules and not the growth of reporter strains after addition of supernatant. Moreover, the phenomenon observed does not seem to represent the degradation of repressors possibly present in the culture medium used. We could also amplify bands from some of the strains tested using primers designed to the luxS gene of Escherichia coli. Altogether, our results show that B. fragilis, B. vulgatus and B. distasonis (but possibly some other species) can produce V. harveyi autoinducer 2-related molecules. However, the role of such molecules in the biology of these organisms remains unknown.

  14. Useful oriented immobilization of antibodies on chimeric magnetic particles: direct correlation of biomacromolecule orientation with biological activity by AFM studies.

    Science.gov (United States)

    Marciello, Marzia; Filice, Marco; Olea, David; Velez, Marisela; Guisan, José M; Mateo, Cesar

    2014-12-16

    The preparation and performance of a suitable chimeric biosensor based on antibodies (Abs) immobilized on lipase-coated magnetic particles by means of a standing orienting strategy are presented. This novel system is based on hydrophobic magnetic particles coated with modified lipase molecules able to orient and further immobilize different Abs in a covalent way without any previous site-selective chemical modification of biomacromolecules. Different key parameters attending the process were studied and optimized. The optimal preparation was performed using a controlled loading (1 nmol Ab g(-1) chimeric support) at pH 9 and a short reaction time to recover a biological activity of about 80%. AFM microscopy was used to study and confirm the Abs-oriented immobilization on lipase-coated magnetic particles and the final achievement of a highly active and recyclable chimeric immune sensor. This direct technique was demonstrated to be a powerful alternative to the indirect immunoactivity assay methods for the study of biomacromolecule-oriented immobilizations.

  15. Biological activity of phenolic compounds present in buckwheat plants

    Czech Academy of Sciences Publication Activity Database

    Kalinová, J.; Tříska, Jan; Vrchotová, Naděžda

    2005-01-01

    Roč. 16, č. 1 (2005), s. 123-129 ISSN 0971-4693 Institutional research plan: CEZ:AV0Z60870520 Keywords : biological activity, extract, Fagopyrum esculenthum Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.686, year: 2005

  16. Biologically active polymers from spontaneous carotenoid oxidation: a new frontier in carotenoid activity.

    Directory of Open Access Journals (Sweden)

    James B Johnston

    Full Text Available In animals carotenoids show biological activity unrelated to vitamin A that has been considered to arise directly from the behavior of the parent compound, particularly as an antioxidant. However, the very property that confers antioxidant activity on some carotenoids in plants also confers susceptibility to oxidative transformation. As an alternative, it has been suggested that carotenoid oxidative breakdown or metabolic products could be the actual agents of activity in animals. However, an important and neglected aspect of the behavior of the highly unsaturated carotenoids is their potential to undergo addition of oxygen to form copolymers. Recently we reported that spontaneous oxidation of ß-carotene transforms it into a product dominated by ß-carotene-oxygen copolymers. We now report that the polymeric product is biologically active. Results suggest an overall ability to prime innate immune function to more rapidly respond to subsequent microbial challenges. An underlying structural resemblance to sporopollenin, found in the outer shell of spores and pollen, may allow the polymer to modulate innate immune responses through interactions with the pattern recognition receptor system. Oxygen copolymer formation appears common to all carotenoids, is anticipated to be widespread, and the products may contribute to the health benefits of carotenoid-rich fruits and vegetables.

  17. Determination of biologically active phenols and polyphenols in various objects by chromatographic techniques

    International Nuclear Information System (INIS)

    Kochetova, M V; Semenistaya, E N; Larionov, Oleg G; Revina, A A

    2007-01-01

    Chromatographic techniques for determination of biologically active phenols and polyphenols are considered. Various methods for sample preparation and detection are compared. The advantages of high performance liquid chromatography with spectrophotometric detection for determination of antioxidants are demonstrated. Data on determination of biologically active phenols and polyphenols published in the period from 1995 to 2005 are analysed.

  18. Charged particle activation analysis of phosphorus in biological materials

    International Nuclear Information System (INIS)

    Masumoto, K.; Yagi, M.

    1983-01-01

    Charged particle activation analysis of phosphorus in biological materials using the 31 P(α,n) sup(34m)Cl reaction has been studied. Since sup(34m)Cl is also produced by the 32 S(α,pn) and the 35 Cl(α,α'n) reactions, the thick-target yield curves on phosphorus, sulfur and chlorine were determined in order to choose the optimum irradiation conditions. As a result, it was found that the activation analysis for phosphorus without interferences from sulfur and chlorine is possible by bombarding with less than 17 MeV alphas. The applicability of this method to biological samples was then examined by irradiating several standard reference materials. It was confirmed that phosphorus can readily be determined at the detection limit of 1μg free from interferences due to the matrix elements. (author)

  19. Biological activities and medicinal properties of Cajanus cajan (L Millsp.

    Directory of Open Access Journals (Sweden)

    Dilipkumar Pal

    2011-01-01

    Full Text Available Cajanus cajan (L Millsp. (Sanskrit: Adhaki, Hindi: Arhar, English: Pigeon pea, Bengali: Tur (family: Fabaceae is the most important grain legume crop of rain-fed agriculture in semi-arid tropics. It is both a food crop and a cover/forage crop with high levels of proteins and important amino acids like methionine, lysine and tryptophan. During the last few decades extensive studies have been carried out regarding the chemistry of C. cajan and considerable progress has been achieved regarding its biological activities and medicinal applications. This review article gives an overview on the biological activities of the compounds isolated, pharmacological actions and clinical studies of C. cajan extracts apart from its general details.

  20. Biological activities and medicinal properties of Cajanus cajan (L) Millsp.

    Science.gov (United States)

    Pal, Dilipkumar; Mishra, Pragya; Sachan, Neetu; Ghosh, Ashoke K

    2011-10-01

    Cajanus cajan (L) Millsp. (Sanskrit: Adhaki, Hindi: Arhar, English: Pigeon pea, Bengali: Tur) (family: Fabaceae) is the most important grain legume crop of rain-fed agriculture in semi-arid tropics. It is both a food crop and a cover/forage crop with high levels of proteins and important amino acids like methionine, lysine and tryptophan. During the last few decades extensive studies have been carried out regarding the chemistry of C. cajan and considerable progress has been achieved regarding its biological activities and medicinal applications. This review article gives an overview on the biological activities of the compounds isolated, pharmacological actions and clinical studies of C. cajan extracts apart from its general details.

  1. News: Synthetic biology leading to specialty chemicals

    Science.gov (United States)

    Synthetic biology can combine the disciplines of biology, engineering, and chemistry productively to form molecules of great scientific and commercial value. Recent advances in the new field are explored for their connection to new tools that have been used to elucidate productio...

  2. Activating and inhibiting connections in biological network dynamics

    Directory of Open Access Journals (Sweden)

    Knight Rob

    2008-12-01

    Full Text Available Abstract Background Many studies of biochemical networks have analyzed network topology. Such work has suggested that specific types of network wiring may increase network robustness and therefore confer a selective advantage. However, knowledge of network topology does not allow one to predict network dynamical behavior – for example, whether deleting a protein from a signaling network would maintain the network's dynamical behavior, or induce oscillations or chaos. Results Here we report that the balance between activating and inhibiting connections is important in determining whether network dynamics reach steady state or oscillate. We use a simple dynamical model of a network of interacting genes or proteins. Using the model, we study random networks, networks selected for robust dynamics, and examples of biological network topologies. The fraction of activating connections influences whether the network dynamics reach steady state or oscillate. Conclusion The activating fraction may predispose a network to oscillate or reach steady state, and neutral evolution or selection of this parameter may affect the behavior of biological networks. This principle may unify the dynamics of a wide range of cellular networks. Reviewers Reviewed by Sergei Maslov, Eugene Koonin, and Yu (Brandon Xia (nominated by Mark Gerstein. For the full reviews, please go to the Reviewers' comments section.

  3. In vitro and in vivo activity of a novel antifungal small molecule against Candida infections.

    Directory of Open Access Journals (Sweden)

    Sarah Sze Wah Wong

    Full Text Available Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC 0.2-1.6 µg/ml. In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use.

  4. Aktivitas Biologis Imunoglobulin Yolk Anti Parvovirus Setelah Perlakuan Suhu (BIOLOGY ACTIVITIES OF IgY PARVOVIRUS AFTER HEAT TREATMENT

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Agung Suartini

    2016-02-01

    Full Text Available This study aims to determine the effect of temperature on the biological activity of various crude and precipitate specific Immunoglobulin (IgY Canine parvovirus (CPV. Hiperimun serum conducted on Isa Brown chickens injected with antigen CPV. Crude yolk Ig preparations derived from chicken serum without purification while the yolk Ig preparations precipitates obtained by the chicken serum was precipitated with ammonium sulfate and dialyzed. Both types of Ig yolk given treatment temperature 50ºC, 60ºC, 70ºC, and 80ºC for 15 minutes. To test Gel Precipitation Test (AGPT is performed to determine whether there is a specific IgY CPV in the serum of chickens. Biological activity of both types of Ig detected with Barriers Haemagglutination test (HI. The design used in this study is completely randomized design factorial. The results of this study indicate that the temperature was highly significant on the activities of IgY crude and precipitates. Activities IgY crude and precipitate down to the treatment temperature of 50ºC, 60ºC, 70ºC, and 80ºC. Geometric Mean Titer crude IgY respectively - were 26.67, 26, 25.33, and <2º Unit HI while IgY precipitates are respectively 26.33, 25.67, 24, and <2º Unit HI. Based on the results of this study concluded that the biological activity of crude IgY better than IgY precipitates after treatment of a wide range of temperatures.

  5. Computational study on the inhibition mechanism of cruzain by nitrile-containing molecules.

    Science.gov (United States)

    Méndez-Lucio, Oscar; Romo-Mancillas, Antonio; Medina-Franco, José L; Castillo, Rafael

    2012-05-01

    Cysteine proteases from parasites as well as from mammals are promising drug targets for parasitic infections and systemic human diseases, respectively. Many reversible and irreversible inhibitors of this very large class of proteins have been designed. Among others, molecules with a nitrile moiety, which is a group that is susceptible to a nucleophilic attack by the enzyme, have been identified as good inhibitors. Although it is known that the nitrile group binds covalently to Cys25, there are no reports about the energetics involved in the mechanism of this process. Herein, density functional theory and quantum semi-empirical calculations were conducted in order to study the molecular recognition of cysteine proteases by nitrile-containing molecules. Results reported in this paper suggest an interaction that starts with a nucleophilic attack from the Cys25 to the inhibitor followed by a proton transfer from His162. Only one transition state was detected; however, we found the existence of an energy plateau in the potential energy surface. Based on the proposed mechanism, some structural features that could improve the biological activity of nitrile-containing molecules toward cysteine proteases are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Influence of the water molecules near surface of viral protein on virus activation process

    Energy Technology Data Exchange (ETDEWEB)

    O, Shepelenko S; S, Salnikov A; V, Rak S; P, Goncharova E; B, Ryzhikov A, E-mail: shep@vector.nsc.r, E-mail: shep@ngs.r [Federal State Research Institution State Research Center of Virology and Biotechnology VECTOR of the Federal Service for Surveillance in Consumer Rights Protection and Human Well-being (FSRI SRC VB VECTOR) Koltsovo, Novosibirsk Region (Russian Federation)

    2009-06-01

    The infection of a cell with influenza virus comprises the stages of receptor binding to the cell membrane, endocytosis of virus particle, and fusion of the virus envelope and cell endosome membrane, which is determined by the conformational changes in hemagglutinin, a virus envelope protein, caused by pH decrease within the endosome. The pH value that induces conformation rearrangements of hemagglutinin molecule considerably varies for different influenza virus strains, first and foremost, due to the differences in amino acid structure of the corresponding proteins. The main goal of this study was to construct a model making it possible to assess the critical pH value characterizing the fusogenic activity of influenza virus hemagglutinin from the data on hemagglutinin structure and experimental verification of this model. Under this model, we assume that when the electrostatic force between interacting hemagglutinin molecules in the virus envelop exceeds a certain value, the hemagglutinin HA1 subunits are arranged so that they form a cavity sufficient for penetration of water molecules. This event leads to an irreversible hydration of the inner fragments of hemagglutinin molecule in a trimer and to the completion of conformational changes. The geometry of electrostatic field in hemagglutinin trimer was calculated taking into account the polarization effects near the interface of two dielectrics, aqueous medium and protein macromolecule. The critical pH values for the conformational changes in hemagglutinin were measured by the erythrocyte hemolysis induced by influenza virus particles when decreasing pH. The critical pH value conditionally separating the pH range into the regions with and without the conformational changes was calculated for several influenza virus H1N1 and H3N2 strains based on the data on the amino acid structure of the corresponding hemagglutinin molecules. Comparison of the theoretical and experimental values of critical pH values for

  7. Synthetic biology of polyketide synthases

    DEFF Research Database (Denmark)

    Yuzawa, Satoshi; Backman, Tyler W.H.; Keasling, Jay D.

    2018-01-01

    ). The modules are composed of enzymatic domains that share sequence and functional similarity across all known PKSs. We have used the nomenclature of synthetic biology to classify the enzymatic domains and modules as parts and devices, respectively, and have generated detailed lists of both. In addition, we...... realize the potential that synthetic biology approaches bring to this class of molecules....

  8. Identification of intrinsic catalytic activity for electrochemical reduction of water molecules to generate hydrogen

    KAUST Repository

    Shinagawa, Tatsuya

    2015-01-01

    Insufficient hydronium ion activities at near-neutral pH and under unbuffered conditions induce diffusion-limited currents for hydrogen evolution, followed by a reaction with water molecules to generate hydrogen at elevated potentials. The observed constant current behaviors at near neutral pH reflect the intrinsic electrocatalytic reactivity of the metal electrodes for water reduction. This journal is © the Owner Societies.

  9. Effect of organic molecules on hydrolysis of peptide bond: A DFT study

    International Nuclear Information System (INIS)

    Makshakova, Olga; Ermakova, Elena

    2013-01-01

    Highlights: ► DFT study of the effects of small organic molecules on the hydrolysis reactions of peptide bonds. ► Organic molecules can activate nonenzymatic hydrolysis reaction. ► Influence of organic acids on activation energy barrier correlates with their electronegativity. - Abstract: The activation and inhibition effects of small organic molecules on peptide hydrolysis have been studied using a model compound dialanine and DFT approach. Solvent-assisted and non-assisted concerted mechanisms were analyzed. Several transition states for the systems: alanine dipeptide–water molecule in complexes with alcohol molecules, acetonitrile, dimethylsulfoxide, propionic, lactic and pyruvic acids and water molecules were localized. The formation of hydrogen bonds between dipeptide, reactive water molecule and molecules of solvents influences the activation energy barrier of the peptide bond hydrolytic reaction. Strong effect of organic acids on the activation energy barrier correlates with their electronegativity. Acetonitrile can act as an inhibitor of reaction. Mechanisms of regulation of the activation energy barrier are discussed in the terms of donor-acceptor interactions

  10. Biological Activities and Chemical Composition of Methanolic Extracts of Selected Autochthonous Microalgae Strains from the Red Sea

    Directory of Open Access Journals (Sweden)

    Hugo Pereira

    2015-06-01

    Full Text Available Four lipid-rich microalgal species from the Red Sea belonging to three different genera (Nannochloris, Picochlorum and Desmochloris, previously isolated as novel biodiesel feedstocks, were bioprospected for high-value, bioactive molecules. Methanol extracts were thus prepared from freeze-dried biomass and screened for different biological activities. Nannochloris sp. SBL1 and Desmochloris sp. SBL3 had the highest radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl, and the best copper and iron chelating activities. All species had potent butyrylcholinesterase inhibitory activity (>50% and mildly inhibited tyrosinase. Picochlorum sp. SBL2 and Nannochloris sp. SBL4 extracts significantly reduced the viability of tumoral (HepG2 and HeLa cells with lower toxicity against the non-tumoral murine stromal (S17 cells. Nannochloris sp. SBL1 significantly reduced the viability of Leishmania infantum down to 62% (250 µg/mL. Picochlorum sp. SBL2 had the highest total phenolic content, the major phenolic compounds identified being salicylic, coumaric and gallic acids. Neoxanthin, violaxanthin, zeaxanthin, lutein and β-carotene were identified in the extracts of all strains, while canthaxanthin was only identified in Picochlorum sp. SBL2. Taken together, these results strongly suggest that the microalgae included in this work could be used as sources of added-value products that could be used to upgrade the final biomass value.

  11. Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Madsen, Christian M; Arfelt, Kristine N

    2013-01-01

    The Epstein-Barr virus induced gene 2 (EBI2) was recently identified as the first oxysterol-activated 7TM receptor. EBI2 is essential for B cell trafficking within lymphoid tissues and thus the humoral immune response in general. Here we characterize the antagonism of the non-peptide molecule GSK...

  12. Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity

    Science.gov (United States)

    Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

    2013-01-01

    Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

  13. Small molecule fluoride toxicity agonists.

    Science.gov (United States)

    Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

    2015-04-23

    Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Spectral parameters and biological activity of macromolecular compounds of humic etiology

    Directory of Open Access Journals (Sweden)

    M. V. Zykova

    2017-01-01

    Full Text Available Materials and methods. 18 native humic acids (HAs were received from nine representative types of peat of the Tomsk region. Two extraction methods were used: sodium hydroxide and sodium pyrophosphate. Molecular structure parameters were investigated by IR-spectroscopy. The assessement of qualitative and quantitative features of the IR-spectra of 18 different humic acids was made. When HAs with mouse macrophages were cultured their ability to influence the NO-stimulation was determined. Thus, the biological activity of HAs and its dependence on the parameters of the molecular structure were studied.Results. The results of infrared spectroscopy showed that the HAs of upland types of peat contain more carbonyl, carboxyl, and ester groups, and HAs of lowland types of peat contain more aromatic carbon, phenolic and alcoholic hydroxyl, ether and carbohydrate fragments. The results of biological activity showed that HAs from upland types of peat induce the formation of nitrogen oxide, wherein the cell activation decreases with HAs obtained by alkali. All types of HAs from lowland types of peat contain an admixture of endotoxin. Some HAs obtained by sodium pyrophosphate have higher immunotropic activity; the HAs can cause antigen-specific stimulation of cells. The activity of HAs does not depend on endotoxin admixture. The results of molecular spectroscopy showed that the most biologically active HAs have higher aromaticity and higher concentration of oxygen-containing functional groups. This result can be used as a marker factor in the standardization of HAs. 

  15. Models for synthetic biology.

    Science.gov (United States)

    Kaznessis, Yiannis N

    2007-11-06

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

  16. Implications of the use of experimental activities in biology education in public schools

    Directory of Open Access Journals (Sweden)

    Vânia Cardoso da Silva Morais

    2016-04-01

    Full Text Available This study aimed to verify the influence of a didactic sequence with experimental activities on student motivation in relation to the subject matter Biology and check the possibility of applying such a result having as input the cultural-historical perspective and the dynamic of the three pedagogical moments. The work is part of a Master Degree research developed with 70 students from a high school in Patos de Minas city. The analysis of the data collected through observation, questionnaires, reports, testimonies of students, filming and photography of biology classes, points out that the use of experimental activities in Biology classes contributed to the increase of student motivation relating to Biology classes favoring the teaching-learning process and also to promote a converge between the scientific knowledge and reality of the students besides encourage their self-esteem and investigative sense. The results also indicate that it is possible to develop at school a didactic sequence based on the complementarity of two different theoretical lines like the dynamics of the three moments and in the historical and cultural perspective. Based on above considerations, we believe that the use of experimental activities following didactics positively influences student motivation in relation to Biology, favoring the teaching and learning of Biology. However, it is the whole of this, as the theory and the posture of motivating teachers, allowed approximation between scientific knowledge and reality of the students, enabling greater learning of biological concepts.

  17. Synthesis and biological activity of a new class of insecticides: the N-(5-aryl-1,3,4-thiadiazol-2-yl)amides.

    Science.gov (United States)

    Eckelbarger, Joseph D; Parker, Marshall H; Yap, Maurice Ch; Buysse, Ann M; Babcock, Jonathan M; Hunter, Ricky; Adelfinskaya, Yelena; Samaritoni, Jack G; Garizi, Negar; Trullinger, Tony K

    2017-04-01

    Optimization studies on a high-throughput screening (HTS) hit led to the discovery of a series of N-(6-arylpyridazin-3-yl)amides with insecticidal activity. It was hypothesized that the isosteric replacement of the pyridazine ring with a 1,3,4-thiadiazole ring could lead to more potent biological activity and/or a broader sap-feeding pest spectrum. The resulting N-(5-aryl-1,3,4-thiadiazol-2-yl)amides were explored as a new class of insecticides. Several methods for 2-amino-1,3,4-thiadiazole synthesis were used for the preparation of key synthetic intermediates. Subsequent coupling to variously substituted carboxylic acid building blocks furnished the final targets, which were tested for insecticidal activity against susceptible strains of Aphis gossypii (Glover) (cotton aphid), Myzus persicae (Sulzer) (green peach aphid) and Bemisia tabaci (Gennadius) (sweetpotato whitefly). Structure-activity relationship (SAR) studies on both the amide tail and the aryl A-ring of novel N-(5-aryl-1,3,4-thiadiazol-2-yl)amides led to a new class of insecticidal molecules active against sap-feeding insect pests. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  18. Control of unidirectional transport of single-file water molecules through carbon nanotubes in an electric field.

    Science.gov (United States)

    Su, Jiaye; Guo, Hongxia

    2011-01-25

    The transport of water molecules through nanopores is not only crucial to biological activities but also useful for designing novel nanofluidic devices. Despite considerable effort and progress that has been made, a controllable and unidirectional water flow is still difficult to achieve and the underlying mechanism is far from being understood. In this paper, using molecular dynamics simulations, we systematically investigate the effects of an external electric field on the transport of single-file water molecules through a carbon nanotube (CNT). We find that the orientation of water molecules inside the CNT can be well-tuned by the electric field and is strongly coupled to the water flux. This orientation-induced water flux is energetically due to the asymmetrical water-water interaction along the CNT axis. The wavelike water density profiles are disturbed under strong field strengths. The frequency of flipping for the water dipoles will decrease as the field strength is increased, and the flipping events vanish completely for the relatively large field strengths. Most importantly, a critical field strength E(c) related to the water flux is found. The water flux is increased as E is increased for E ≤ E(c), while it is almost unchanged for E > E(c). Thus, the electric field offers a level of governing for unidirectional water flow, which may have some biological applications and provides a route for designing efficient nanopumps.

  19. Perspective: Mechanochemistry of biological and synthetic molecules

    Energy Technology Data Exchange (ETDEWEB)

    Makarov, Dmitrii E., E-mail: makarov@cm.utexas.edu [Department of Chemistry and Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas 78712 (United States)

    2016-01-21

    Coupling of mechanical forces and chemical transformations is central to the biophysics of molecular machines, polymer chemistry, fracture mechanics, tribology, and other disciplines. As a consequence, the same physical principles and theoretical models should be applicable in all of those fields; in fact, similar models have been invoked (and often repeatedly reinvented) to describe, for example, cell adhesion, dry and wet friction, propagation of cracks, and action of molecular motors. This perspective offers a unified view of these phenomena, described in terms of chemical kinetics with rates of elementary steps that are force dependent. The central question is then to describe how the rate of a chemical transformation (and its other measurable properties such as the transition path) depends on the applied force. I will describe physical models used to answer this question and compare them with experimental measurements, which employ single-molecule force spectroscopy and which become increasingly common. Multidimensionality of the underlying molecular energy landscapes and the ensuing frequent misalignment between chemical and mechanical coordinates result in a number of distinct scenarios, each showing a nontrivial force dependence of the reaction rate. I will discuss these scenarios, their commonness (or its lack), and the prospects for their experimental validation. Finally, I will discuss open issues in the field.

  20. Perspective: Mechanochemistry of biological and synthetic molecules

    International Nuclear Information System (INIS)

    Makarov, Dmitrii E.

    2016-01-01

    Coupling of mechanical forces and chemical transformations is central to the biophysics of molecular machines, polymer chemistry, fracture mechanics, tribology, and other disciplines. As a consequence, the same physical principles and theoretical models should be applicable in all of those fields; in fact, similar models have been invoked (and often repeatedly reinvented) to describe, for example, cell adhesion, dry and wet friction, propagation of cracks, and action of molecular motors. This perspective offers a unified view of these phenomena, described in terms of chemical kinetics with rates of elementary steps that are force dependent. The central question is then to describe how the rate of a chemical transformation (and its other measurable properties such as the transition path) depends on the applied force. I will describe physical models used to answer this question and compare them with experimental measurements, which employ single-molecule force spectroscopy and which become increasingly common. Multidimensionality of the underlying molecular energy landscapes and the ensuing frequent misalignment between chemical and mechanical coordinates result in a number of distinct scenarios, each showing a nontrivial force dependence of the reaction rate. I will discuss these scenarios, their commonness (or its lack), and the prospects for their experimental validation. Finally, I will discuss open issues in the field

  1. Biological treatment of textile mill wastewater in the. presence of activated carbon

    International Nuclear Information System (INIS)

    Liaquat, F.; Hassan, M.; Mahboob, S.; Rehman, A.; Liaquat, S.; Khalid, Z.M.

    2005-01-01

    The main goal of this study was to find out effectiveness of biological treatment for the reduction in chemical oxygen demand (COD) and biological oxygen demand (BOD) of the textile processing industrial wastewater in the absence and presence of granular activated carbon (GAC) in shake flask experiment. To check the pollution level, physio-chemical analysis of effluent from Amtex industry (Faisalabad) was carried out. The outlet effluent contained high value of COD (1100 mg/l), BOD (309 mg/l) with pH 9.2, electrical conductivity (Ec) 3.7 mS/m, total dissolved solids (TDS) (2640 mg/l), total solids (TS) (3060 mg/l), total suspended solids (TSS) (420 19/l) and phenol (.34 mg/l). After initial period of activated sludge adaptation to wastewater, shake flask batch cultures (with and without activated carbon) were operated on lab scale. The COD and BOD were noted after very 12 hours for 3 days. The maximum reduction in COD (82%) and BOD (90%) was observed biological treatment in presence of activated carbon at retention time of 72 hours. (author)

  2. The Role of Vitamin D in the Immune System as a Pro-survival Molecule.

    Science.gov (United States)

    Chirumbolo, Salvatore; Bjørklund, Geir; Sboarina, Andrea; Vella, Antonio

    2017-05-01

    Vitamin D is a fascinating and attractive molecule that has gained particular attention in medicine in recent years. Its immunomodulatory and anti-inflammatory potential might resemble the activity of many nature-derived molecules (eg, flavonoids), but its role in biology was selected during a long evolutionary pathway to dampen the damaging effect of cell stress response and of the immune reaction. In this sense, this molecule can be considered an ancient hormone that serves, in its primary role, as a pro-survival agent. The goal of this review was to elucidate this topic. The article reviews current literature on the field, focusing on issues regarding the role of vitamin D in immunity. Vitamin D participates in the survival machinery used by the cell, and in particular it plays a major role in synchronizing calcium oscillatory signaling to allow cell autophagy or apoptosis during a stress response. Vitamin D should be better highlighted in its molecular action and vitamin D receptor genomics to conceive a more suited therapeutic supplementation protocol in clinics. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  3. Electrostatic similarities between protein and small molecule ligands facilitate the design of protein-protein interaction inhibitors.

    Directory of Open Access Journals (Sweden)

    Arnout Voet

    Full Text Available One of the underlying principles in drug discovery is that a biologically active compound is complimentary in shape and molecular recognition features to its receptor. This principle infers that molecules binding to the same receptor may share some common features. Here, we have investigated whether the electrostatic similarity can be used for the discovery of small molecule protein-protein interaction inhibitors (SMPPIIs. We have developed a method that can be used to evaluate the similarity of electrostatic potentials between small molecules and known protein ligands. This method was implemented in a software called EleKit. Analyses of all available (at the time of research SMPPII structures indicate that SMPPIIs bear some similarities of electrostatic potential with the ligand proteins of the same receptor. This is especially true for the more polar SMPPIIs. Retrospective analysis of several successful SMPPIIs has shown the applicability of EleKit in the design of new SMPPIIs.

  4. Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review

    Directory of Open Access Journals (Sweden)

    Ranga Rao Ambati

    2014-01-01

    Full Text Available There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications.

  5. Refolding techniques for recovering biologically active recombinant proteins from inclusion bodies.

    Science.gov (United States)

    Yamaguchi, Hiroshi; Miyazaki, Masaya

    2014-02-20

    Biologically active proteins are useful for studying the biological functions of genes and for the development of therapeutic drugs and biomaterials in a biotechnology industry. Overexpression of recombinant proteins in bacteria, such as Escherichia coli, often results in the formation of inclusion bodies, which are protein aggregates with non-native conformations. As inclusion bodies contain relatively pure and intact proteins, protein refolding is an important process to obtain active recombinant proteins from inclusion bodies. However, conventional refolding methods, such as dialysis and dilution, are time consuming and, often, recovered yields of active proteins are low, and a trial-and-error process is required to achieve success. Recently, several approaches have been reported to refold these aggregated proteins into an active form. The strategies largely aim at reducing protein aggregation during the refolding procedure. This review focuses on protein refolding techniques using chemical additives and laminar flow in microfluidic chips for the efficient recovery of active proteins from inclusion bodies.

  6. Refolding Techniques for Recovering Biologically Active Recombinant Proteins from Inclusion Bodies

    Directory of Open Access Journals (Sweden)

    Hiroshi Yamaguchi

    2014-02-01

    Full Text Available Biologically active proteins are useful for studying the biological functions of genes and for the development of therapeutic drugs and biomaterials in a biotechnology industry. Overexpression of recombinant proteins in bacteria, such as Escherichia coli, often results in the formation of inclusion bodies, which are protein aggregates with non-native conformations. As inclusion bodies contain relatively pure and intact proteins, protein refolding is an important process to obtain active recombinant proteins from inclusion bodies. However, conventional refolding methods, such as dialysis and dilution, are time consuming and, often, recovered yields of active proteins are low, and a trial-and-error process is required to achieve success. Recently, several approaches have been reported to refold these aggregated proteins into an active form. The strategies largely aim at reducing protein aggregation during the refolding procedure. This review focuses on protein refolding techniques using chemical additives and laminar flow in microfluidic chips for the efficient recovery of active proteins from inclusion bodies.

  7. Small-molecule inhibitor leads of ribosome-inactivating proteins developed using the doorstop approach.

    Directory of Open Access Journals (Sweden)

    Yuan-Ping Pang

    2011-03-01

    Full Text Available Ribosome-inactivating proteins (RIPs are toxic because they bind to 28S rRNA and depurinate a specific adenine residue from the α-sarcin/ricin loop (SRL, thereby inhibiting protein synthesis. Shiga-like toxins (Stx1 and Stx2, produced by Escherichia coli, are RIPs that cause outbreaks of foodborne diseases with significant morbidity and mortality. Ricin, produced by the castor bean plant, is another RIP lethal to mammals. Currently, no US Food and Drug Administration-approved vaccines nor therapeutics exist to protect against ricin, Shiga-like toxins, or other RIPs. Development of effective small-molecule RIP inhibitors as therapeutics is challenging because strong electrostatic interactions at the RIP•SRL interface make drug-like molecules ineffective in competing with the rRNA for binding to RIPs. Herein, we report small molecules that show up to 20% cell protection against ricin or Stx2 at a drug concentration of 300 nM. These molecules were discovered using the doorstop approach, a new approach to protein•polynucleotide inhibitors that identifies small molecules as doorstops to prevent an active-site residue of an RIP (e.g., Tyr80 of ricin or Tyr77 of Stx2 from adopting an active conformation thereby blocking the function of the protein rather than contenders in the competition for binding to the RIP. This work offers promising leads for developing RIP therapeutics. The results suggest that the doorstop approach might also be applicable in the development of other protein•polynucleotide inhibitors as antiviral agents such as inhibitors of the Z-DNA binding proteins in poxviruses. This work also calls for careful chemical and biological characterization of drug leads obtained from chemical screens to avoid the identification of irrelevant chemical structures and to avoid the interference caused by direct interactions between the chemicals being screened and the luciferase reporter used in screening assays.

  8. Scents and sensibility: how biology perceives chemistry

    Directory of Open Access Journals (Sweden)

    Stuart Firestein

    2014-07-01

    odor can be detected by several receptors and any given receptor can bind any of several presumably related odors. In our analogy, the keys fit very loosely to differing degrees into many locks. Chemists are particularly interested in those parts of a molecule that are likely to participate in various sorts of reactions and synthetic manipulations. These would include such things as the functional group (aldehyde, acid, ester, etc. or if there are double bonds or charge carrying atoms. However, what is relevant to the synthetic chemist may not be important to the biological system, and in particular to the odor receptor protein. Thus we should begin by taking a biological approach to odor chemistry. For example the definition of an odorant cannot be made chemically – many chemical compounds that appear nearly identical to a known odorant may have a different smell or none at all. The only definition of an odorant is that it binds to an odor receptor to give rise to a biological response. Precisely what parts of a chemical compound influence that binding is one of the most challenging questions in biology. The actual perception of an odorant depends on the particular combination of receptors that are activated. In a complex mixture of tens to hundreds of different odor molecules this can quickly become a very complicated matrix of activated receptors with an astronomical number of combinations. An open question is whether evolution has perhaps found a simplified way of performing this apparently incalculable task. One possible solution would be the existence of a few dozen common chemical structures that would serve as primary features from which all other odors are constructed. This would be similar to the way the visual system can perceive thousands of hues of light by combining only three (blue, green and red primary “colors” or wavelengths. Although the idea of primaries in olfaction has been discussed for several decades it was largely abandoned after the

  9. Using Active Learning in a Studio Classroom to Teach Molecular Biology

    Science.gov (United States)

    Nogaj, Luiza A.

    2013-01-01

    This article describes the conversion of a lecture-based molecular biology course into an active learning environment in a studio classroom. Specific assignments and activities are provided as examples. The goal of these activities is to involve students in collaborative learning, teach them how to participate in the learning process, and give…

  10. Transmembrane α-Helix 2 and 7 Are Important for Small Molecule-Mediated Activation of the GLP-1 Receptor

    DEFF Research Database (Denmark)

    Underwood, Christina Rye; Møller Knudsen, Sanne; Schjellerup Wulff, Birgitte

    2011-01-01

    Glucagon-like peptide-1 (GLP-1) activates the GLP-1 receptor (GLP-1R), which belongs to family B of the G-protein-coupled receptors. We previously identified a selective small molecule ligand, compound 2, that acted as a full agonist and allosteric modulator of GLP-1R. In this study, the structur......Glucagon-like peptide-1 (GLP-1) activates the GLP-1 receptor (GLP-1R), which belongs to family B of the G-protein-coupled receptors. We previously identified a selective small molecule ligand, compound 2, that acted as a full agonist and allosteric modulator of GLP-1R. In this study......, the structurally related small molecule, compound 3, stimulated cAMP production from GLP-1R, but not from the homologous glucagon receptor (GluR). The receptor selectivity encouraged a chimeric receptor approach to identify domains important for compound 3-mediated activation of GLP-1R. A subsegment of the GLP-1R...... transmembrane domain containing TM2 to TM5 was sufficient to transfer compound 3 responsiveness to GluR. Therefore, divergent residues in this subsegment of GLP-1R and GluR are responsible for the receptor selectivity of compound 3. Functional analyses of other chimeric receptors suggested that the existence...

  11. Tests of biological activity of metabolites from Penicillium expansum (Link Thom various isolates

    Directory of Open Access Journals (Sweden)

    Halina Borecka

    2013-12-01

    Full Text Available Aqrobacterium tumefaciens and cucumber, mustard and linseeds were compared as test organisms for evaluation of the biological activity of patulin. It was found that the reaction of cucumber seeds and linseed to the patulin concentrations was more pronounced than that of mustard and Aqrobacterium tumefaciens. The activity of metabolites produced by Penicillium expansum was investigated with the use of cucumber seeds. As measure of activity served the percentage of radicule growth inhibition was compared with the growth in control seeds. The biological activity of the metabolites was specific for the isolates, those from apples being more active. Thirty two isolates from pears and 34 from apples were examined.

  12. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

  13. Some aspects of radiation-induced free-radical chemistry of biologically important molecules

    International Nuclear Information System (INIS)

    Sonntag, C. von

    1992-01-01

    Biologically relevant material is usually associated with considerable amounts of water. When ionizing radiation interacts with such material one must consider two modes of energy deposition: the direct effect (ionizing radiation is absorbed by the biomolecules) and the indirect effect (ionizing radiation is absorbed by the surrounding water). In the direct effect, radical cations plus electrons, and excited states of the biomolecules are formed. In the indirect effect the water is decomposed resulting in the formation of the water radicals OH,H and e aq - . These reactive intermediates then interact with the biomolecules. When such systems are irradiated oxygen is often present. As a result of this, the radicals formed in the biomolecules by the various routes are converted into the corresponding peroxyl radicals. In certain cases, e.g. with the nucleobases of DNA, radical cations can be produced in dilute aqueous solutions by radiation-generated SO 4 - radicals, and the fate of these nucleobase radical cations studied by pulse radiolysis and product analysis. Attention will be drawn to the fact that frequently some of the reaction products of the radical cations with water are identical to those formed by OH radical attack, but that there are also marked differences. Similarly, protonation of radical anions (formed by the reaction of solvated electrons with the biomolecules) and the reaction of H-atoms with these molecules can lead to radical intermediates with considerably differing characteristics. Our present knowledge of the variety of reactions of the peroxyl radicals occurring in aqueous solutions will be briefly discussed, emphasizing the large variety of HO 2 /O 2 - elimination reactions and pointing to the reversibility of the oxygen addition (RO 2 →R + O 2 ) in some systems recently studied. (author)

  14. Isoprenoid-derived plant signaling molecules: biosynthesis and biological importance

    Czech Academy of Sciences Publication Activity Database

    Tarkowská, Danuše; Strnad, Miroslav

    2018-01-01

    Roč. 247, č. 5 (2018), s. 1051-1066 ISSN 0032-0935 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Dimethylallyl diphosphate * Isopentenyl diphosphate * Isoprenoids * Phytoecdysteroids * Plant hormones * Terpenoids Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemical research methods Impact factor: 3.361, year: 2016

  15. Supramolecular assembly of biological molecules purified from bovine nerve cells: from microtubule bundles and necklaces to neurofilament networks

    International Nuclear Information System (INIS)

    Needleman, Daniel J; Jones, Jayna B; Raviv, Uri; Ojeda-Lopez, Miguel A; Miller, H P; Li, Y; Wilson, L; Safinya, C R

    2005-01-01

    With the completion of the human genome project, the biosciences community is beginning the daunting task of understanding the structures and functions of a large number of interacting biological macromolecules. Examples include the interacting molecules involved in the process of DNA condensation during the cell cycle, and in the formation of bundles and networks of filamentous actin proteins in cell attachment, motility and cytokinesis. In this proceedings paper we present examples of supramolecular assembly based on proteins derived from the vertebrate nerve cell cytoskeleton. The axonal cytoskeleton in vertebrate neurons provides a rich example of bundles and networks of neurofilaments, microtubules (MTs) and filamentous actin, where the nature of the interactions, structures, and structure-function correlations remains poorly understood. We describe synchrotron x-ray diffraction, electron microscopy, and optical imaging data, in reconstituted protein systems purified from bovine central nervous system, which reveal unexpected structures not predicted by current electrostatic theories of polyelectrolyte bundling, including three-dimensional MT bundles and two-dimensional MT necklaces

  16. European activities in space radiation biology and exobiology

    International Nuclear Information System (INIS)

    Horneck, G.

    1996-01-01

    In view of the space station era, the European Space Agency has initiated a review and planning document for space life sciences. Radiation biology includes dosimetry of the radiation field and its modification by mass shielding, studies on the biological responses to radiation in space, on the potential impact of space flight environment on radiation effects, and assessing the radiation risks and establishing radiation protection guidelines. To reach a better understanding of the processes leading to the origin, evolution and distribution of life, exobiological activities include the exploration of the solar system, the collection and analysis of extraterrestrial samples and the utilization of space as a tool for testing the impact of space environment on organics and resistant life forms. (author)

  17. Radio-active waste disposal and deep-sea biology

    International Nuclear Information System (INIS)

    Rice, A.L.

    1978-01-01

    The deep-sea has been widely thought of as a remote, sparsely populated, and biologically inactive environment, well suited to receive the noxious products of nuclear fission processes. Much of what is known of abyssal biology tends to support this view, but there are a few disquieting contra-indications. The realisation, in recent years, that many animal groups show a previously unsuspected high species diversity in the deep-sea emphasized the paucity of our knowledge of this environment. More dramatically, the discovery of a large, active, and highly mobile abysso-bentho-pelagic fauna changed the whole concept of abyssal life. Finally, while there is little evidence for the existence of vertical migration patterns linking the deep-sea bottom communities with those of the overlying water layers, there are similarly too few negative results for the possibility of such transport mechanisms to be dismissed. In summary, biological knowledge of the abyss is insufficient to answer the questions raised in connection with deep-sea dumping, but in the absence of adequate answers it might be dangerous to ignore the questions

  18. Biological Activities and Phytochemicals of Swietenia macrophylla King

    Directory of Open Access Journals (Sweden)

    Habsah Abdul Kadir

    2013-08-01

    Full Text Available Swietenia macrophylla King (Meliaceae is an endangered and medicinally important plant indigenous to tropical and subtropical regions of the World. S. macrophylla has been widely used in folk medicine to treat various diseases. The review reveals that limonoids and its derivatives are the major constituents of S. macrophylla. There are several data in the literature indicating a great variety of pharmacological activities of S. macrophylla, which exhibits antimicrobial, anti-inflammatory, antioxidant effects, antimutagenic, anticancer, antitumor and antidiabetic activities. Various other activities like anti-nociceptive, hypolipidemic, antidiarrhoeal, anti-infective, antiviral, antimalarial, acaricidal, antifeedant and heavy metal phytoremediation activity have also been reported. In view of the immense medicinal importance of S. macrophylla, this review aimed at compiling all currently available information on its ethnomedicinal uses, phytochemistry and biological activities of S. macrophylla, showing its importance.

  19. Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

    Science.gov (United States)

    Simm, Jaak; Klambauer, Günter; Arany, Adam; Steijaert, Marvin; Wegner, Jörg Kurt; Gustin, Emmanuel; Chupakhin, Vladimir; Chong, Yolanda T; Vialard, Jorge; Buijnsters, Peter; Velter, Ingrid; Vapirev, Alexander; Singh, Shantanu; Carpenter, Anne E; Wuyts, Roel; Hochreiter, Sepp; Moreau, Yves; Ceulemans, Hugo

    2018-05-17

    In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Biological activities (anti-inflammatory and anti-oxidant) of fractions ...

    African Journals Online (AJOL)

    Biological activities (anti-inflammatory and anti-oxidant) of fractions and methanolic extract of Philonotis hastate (Duby Wijk & MargaDant). ... The fractions and methanolic extract exhibited moderate antioxidant potentials with various models. The flavonoid contents of the methanol extract and fractions ranged between 1.70 ...

  1. Proximate composition, phytochemical screening, GC-MS studies of biologically active cannabinoids and antimicrobial activities of Cannabis indica

    Directory of Open Access Journals (Sweden)

    Muhammad Saqib Isahq

    2015-11-01

    Full Text Available Objective: To investigate the proximate composition, minerals analysis, phytochemical screening, gas chromatography-mass spectrometry (GC-MS studies of active cannabinoids and antimicrobial activities of Cannabis indica (C. indica leaves, stems, and seeds. Methods: Standard qualitative protocols of phytochemical screening were accomplished for the identification of biologically active phytochemicals. Minerals in plant samples were analyzed by using atomic absorption spectrophotometer. The resins of C. indica were analyzed for medicinally active cannabinoid compounds by GC-MS. The sample for GC-MS study was mixed with small quantity of n-hexane and 30 mL of acetonitrile solution for the identification of cannabinoids. Agar well diffusion method was used for antibacterial activity. For antifungal activity, the tested fungal strains were sub-cultured on Sabouraud’s dextrose agar at 28 °C. Results: Mineral analysis revealed the presence of sodium, potassium, magnesium and some other minerals in all parts of C. indica. Phytochemical investigation showed the presence of alkaloids, saponins, tannins, flavonoids, sterols and terpenoids. C. indica divulged wide spectrum of antibacterial activities against Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, and Proteus mirabilis. The extracts of plant leaves, seeds and stems showed significant antifungal activities against Aspergillus niger, Aspergillus parasiticus, and Aspergillus oryzae. The biologically active cannabinoids of delta-9-tetrahydrocannabinol (25.040% and cannabidiol (resorcinol, 2-p-mentha-1,8-dien-4-yl-5-pentyl (50.077% were found in Cannabis resin in high percentage. Conclusions: The findings of the study suggested that the existence of biologically active remedial cannabinoids in elevated concentrations and antimicrobial bioassays of C. indica make it a treasured source to be used in herbal preparation for various ailments.

  2. Effects of heat on the biological activity of wild Cordyceps sinensis

    Directory of Open Access Journals (Sweden)

    Pengkai Wu

    2015-01-01

    Conclusions: These results suggested that heat treatment does not adversely affect SOD or DNase activity, polysaccharide content, or cordycepin dissolution. Thus, heat treatment might be a safe processing method to extend the storage time of wild C. sinensis without compromising biological activity.

  3. Validação em métodos cromatográficos para análises de pequenas moléculas em matrizes biológicas Chromatographic methods validation for analysis of small molecules in biological matrices

    OpenAIRE

    Neila Maria Cassiano; Juliana Cristina Barreiro; Lúcia Regina Rocha Martins; Regina Vincenzi Oliveira; Quezia Bezerra Cass

    2009-01-01

    Chromatographic methods are commonly used for analysis of small molecules in different biological matrices. An important step to be considered upon a bioanalytical method's development is the capacity to yield reliable and reproducible results. This review discusses validation procedures adopted by different governmental agencies, such as Food and Drug Administration (USA), European Union (EU) and Agência Nacional de Vigilância Sanitária (BR) for quantification of small molecules by bioanalyt...

  4. Mechanochemical Association Reaction of Interfacial Molecules Driven by Shear.

    Science.gov (United States)

    Khajeh, Arash; He, Xin; Yeon, Jejoon; Kim, Seong H; Martini, Ashlie

    2018-05-29

    Shear-driven chemical reaction mechanisms are poorly understood because the relevant reactions are often hidden between two solid surfaces moving in relative motion. Here, this phenomenon is explored by characterizing shear-induced polymerization reactions that occur during vapor phase lubrication of α-pinene between sliding hydroxylated and dehydroxylated silica surfaces, complemented by reactive molecular dynamics simulations. The results suggest that oxidative chemisorption of the α-pinene molecules at reactive surface sites, which transfers oxygen atoms from the surface to the adsorbate molecule, is the critical activation step. Such activation takes place more readily on the dehydroxylated surface. During this activation, the most strained part of the α-pinene molecules undergoes a partial distortion from its equilibrium geometry, which appears to be related to the critical activation volume for mechanical activation. Once α-pinene molecules are activated, association reactions occur between the newly attached oxygen and one of the carbon atoms in another molecule, forming ether bonds. These findings have general implications for mechanochemistry because they reveal that shear-driven reactions may occur through reaction pathways very different from their thermally induced counterparts and specifically the critical role of molecular distortion in such reactions.

  5. In vitro gamma irradiation of some purified polypeptide hormones and their biological and radioimmunological activity

    International Nuclear Information System (INIS)

    Hromadova, M.; Macho, L.; Strbak, V.; Vigas, M.; Mikulaj, L.

    1979-01-01

    Some polypeptide hormones (adrenocorticotropin - ACTH, human and bovine growth hormone - GH, human menopausal gonadotropin - HMG, human luteinizing hormone - LH, and bovine thyrotropin - TSH) were irradiated either with 2.5 or 12.5 Mrad (1.1 Mrad/h) or both and their biological activity or immunoreactivity was tested within few days or 3 to 5 months after irradiation. Biological activity of irradiated ACTH (estimation of corticosterone released into medium by incubated adrenals - Saffran and Schally 1955) was not decreased in both time intervals tested. Ten days after irradiation of bovine GH no changes in biological activity (tibia test - Wilhelmi 1973) were found. No decrease of biological activity of irradiated HMG (augmentation of ovarian and uterine weight - Butt 1973) was found 4 months after irradiation and, finaly, no decrease of bovine TSH activity (radioiodine release from prelabelled thyroid in mice - McKenzie 1958) was found 2 to 30 days after irradiation with 2.5 Mrad, while a decrease was observed after 12.5 Mrad. Three to five months after irradiation, however, there was a decrease of biological activity after both doses. The immunological reactivity of irradiated HMG and LH did not differ from that of nonirradiated samples. The same was found with human GH after 2.5 Mrad, while a decrease of reactivity after 12.5 Mrad was detected. It was concluded that, in most of cases, the sterilizing dose of gamma radiation (2.5 Mrad) did not affect the biological activity of polypeptide hormones and that their sensitivity to irradiation appears to differ. (author)

  6. Assessing the reliability of predictive activity coefficient models for molecules consisting of several functional groups

    Directory of Open Access Journals (Sweden)

    R. P. Gerber

    2013-03-01

    Full Text Available Currently, the most successful predictive models for activity coefficients are those based on functional groups such as UNIFAC. In contrast, these models require a large amount of experimental data for the determination of their parameter matrix. A more recent alternative is the models based on COSMO, for which only a small set of universal parameters must be calibrated. In this work, a recalibrated COSMO-SAC model was compared with the UNIFAC (Do model employing experimental infinite dilution activity coefficient data for 2236 non-hydrogen-bonding binary mixtures at different temperatures. As expected, UNIFAC (Do presented better overall performance, with a mean absolute error of 0.12 ln-units against 0.22 for our COSMO-SAC implementation. However, in cases involving molecules with several functional groups or when functional groups appear in an unusual way, the deviation for UNIFAC was 0.44 as opposed to 0.20 for COSMO-SAC. These results show that COSMO-SAC provides more reliable predictions for multi-functional or more complex molecules, reaffirming its future prospects.

  7. Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data.

    Science.gov (United States)

    Kyoda, Koji; Tohsato, Yukako; Ho, Kenneth H L; Onami, Shuichi

    2015-04-01

    Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  8. Novel bacterial gas sensor proteins with transition metal-containing prosthetic groups as active sites.

    Science.gov (United States)

    Aono, Shigetoshi

    2012-04-01

    Gas molecules function as signaling molecules in many biological regulatory systems responsible for transcription, chemotaxis, and other complex physiological processes. Gas sensor proteins play a crucial role in regulating such biological systems in response to gas molecules. New sensor proteins that sense oxygen or nitric oxide have recently been found, and they have been characterized by X-ray crystallographic and/or spectroscopic analysis. It has become clear that the interaction between a prosthetic group and gas molecules triggers dynamic structural changes in the protein backbone when a gas sensor protein senses gas molecules. Gas sensor proteins employ novel mechanisms to trigger conformational changes in the presence of a gas. In gas sensor proteins that have iron-sulfur clusters as active sites, the iron-sulfur clusters undergo structural changes, which trigger a conformational change. Heme-based gas sensor proteins reconstruct hydrogen-bonding networks around the heme and heme-bound ligand. Gas sensor proteins have two functional states, on and off, which are active and inactive, respectively, for subsequent signal transduction in response to their physiological effector molecules. To fully understand the structure-function relationships of gas sensor proteins, it is vital to perform X-ray crystal structure analyses of full-length proteins in both the on and off states.

  9. Small-Molecule Inhibitors of the SOX18 Transcription Factor.

    Science.gov (United States)

    Fontaine, Frank; Overman, Jeroen; Moustaqil, Mehdi; Mamidyala, Sreeman; Salim, Angela; Narasimhan, Kamesh; Prokoph, Nina; Robertson, Avril A B; Lua, Linda; Alexandrov, Kirill; Koopman, Peter; Capon, Robert J; Sierecki, Emma; Gambin, Yann; Jauch, Ralf; Cooper, Matthew A; Zuegg, Johannes; Francois, Mathias

    2017-03-16

    Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors. We identified two compounds, which inspired a series of synthetic SOX18 inhibitors, able to interfere with the SOX18 HMG DNA-binding domain, and to disrupt HMG-dependent protein-protein interaction with RBPJ. These compounds also perturbed SOX18 transcriptional activity in a cell-based reporter gene system. This approach may prove useful in developing a new class of anti-angiogenic compounds based on the inhibition of TF activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Mobility of chemisorbed molecules and surface regeneration of active centers during dehydration of isopropanol on aluminium oxide and aluminosilicate

    International Nuclear Information System (INIS)

    Makhlis, L.A.; Vasserberg, V.Eh.

    1976-01-01

    By a differential isotope method involving 14 C the authors have investigated the surface mobility of chemisorbed molecules of isopropanol during its dehydration in an adsorption layer on aluminium oxide and aluminosilicate. The chemisorbed alcohol molecules possess marked surface mobility which plays a decisive part in the mechanism of surface regeneration of the active catalyst centers in the process of dehydration. The cessation of the reaction long before the adsorbed alcohol is completely used up is explained by the hypothesis that there is local overpopulation of the active sectors by water formed by the reaction; this hinders further surface regeneration and repetition of the elementary events of dehydration

  11. Syntheses of therapeutically active labelled molecules for metabolic and pharmacokinetic studies. Synthesis, preservation and radiochemical purity problems

    International Nuclear Information System (INIS)

    Pichat, L.

    1977-01-01

    Molecules labelled with radioactive isotopes are without question an essential tool for metabolic and pharmacokinetic studies. Carbon 14 is often preferred to tritium since it allows better observation of the fate of carbonated structures. The fact that 14 CO 2 alone is used as basic material is the distinguishing feature of syntheses with isotopic carbon. In many cases the synthesis schemes of labelled drugs diverge considerably or entirely from those normally adopted for the unlabelled product. It is usually necessary to work on micro-quantities in order to maintain high specific activities, which implies the use of special synthesis techniques and of chromatographic separation and purification methods. Radiochemical purity tests are carried out by thin layer, column and gas phase chromatography, purity and identity checks by mass spectrometry and by 13 C and proton RMN. Labelled products are radiolysed by interaction of excited species with the molecules of the compound, a phenomenon much faster with tritiated than with 14 C-labelled molecules. The radiolysis rates may be reduced by molecule dilution. For ethical reasons it is not convenient to use 14 C molecules in human experiments, but molecular labelled with stable isotopes ( 13 C, 15 N, D) can serve instead [fr

  12. Review of the genus Ipomoea: traditional uses, chemistry and biological activities

    Directory of Open Access Journals (Sweden)

    Marilena Meira

    Full Text Available Approximately 600-700 species of Ipomoea, Convolvulaceae, are found throughout tropical and subtropical regions of the world. Several of those species have been used as ornamental plants, food, medicines or in religious ritual. The present work reviews the traditional uses, chemistry and biological activities of Ipomoea species and illustrates the potential of the genus as a source of therapeutic agents. These species are used in different parts of the world for the treatment of several diseases, such as, diabetes, hypertension, dysentery, constipation, fatigue, arthritis, rheumatism, hydrocephaly, meningitis, kidney ailments and inflammations. Some of these species showed antimicrobial, analgesic, spasmolitic, spasmogenic, hypoglycemic, hypotensive, anticoagulant, anti-inflammatory, psychotomimetic and anticancer activities. Alkaloids, phenolics compounds and glycolipids are the most common biologically active constituents from these plant extracts.

  13. The PH domain of phosphoinositide-dependent kinase-1 exhibits a novel, phospho-regulated monomer-dimer equilibrium with important implications for kinase domain activation: single-molecule and ensemble studies.

    Science.gov (United States)

    Ziemba, Brian P; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J

    2013-07-16

    Phosphoinositide-dependent kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology, this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric states of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. This study investigates the binding of purified wild-type (WT) and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single-molecule and ensemble measurements. Single-molecule analysis of the brightness of the fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single-molecule analysis of two-dimensional (2D) diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate as a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little penetration of the protein into the bilayer as observed for other PH domains. The 2D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that allows

  14. An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors.

    Science.gov (United States)

    Cacace, Angela; Banks, Martyn; Spicer, Timothy; Civoli, Francesca; Watson, John

    2003-09-01

    G-protein-coupled receptors (GPCRs) are the most successful target proteins for drug discovery research to date. More than 150 orphan GPCRs of potential therapeutic interest have been identified for which no activating ligands or biological functions are known. One of the greatest challenges in the pharmaceutical industry is to link these orphan GPCRs with human diseases. Highly automated parallel approaches that integrate ultra-high throughput and focused screening can be used to identify small molecule modulators of orphan GPCRs. These small molecules can then be employed as pharmacological tools to explore the function of orphan receptors in models of human disease. In this review, we describe methods that utilize powerful ultra-high-throughput screening technologies to identify surrogate ligands of orphan GPCRs.

  15. Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

    Science.gov (United States)

    Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

    2017-12-01

    Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

  16. Machine Learning Approaches Toward Building Predictive Models for Small Molecule Modulators of miRNA and Its Utility in Virtual Screening of Molecular Databases.

    Science.gov (United States)

    Periwal, Vinita; Scaria, Vinod

    2017-01-01

    The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules. Here, we describe a computational strategy based on machine learning for creation of predictive models from high-throughput biological screens for virtual screening of small molecules with the potential to inhibit microRNAs. Such models could be potentially used for computational prioritization of small molecules before performing high-throughput biological assay.

  17. Isolation and characterization of biologically active venom protein from sea snake Enhydrina schistosa.

    Science.gov (United States)

    Damotharan, Palani; Veeruraj, Anguchamy; Arumugam, Muthuvel; Balasubramanian, Thangavel

    2015-03-01

    The present study is designed to investigate the isolation and characterization of biological and biochemical active venom protein from sea snake, Enhydrina schistosa. The highest purification peaks in ion-exchange chromatography on DEAE-cellulose column were obtained for fraction numbers 39-49 when eluted with 0.35-0.45 M NaCl. Eighty per cent purity was obtained in the final stage of purification, and a single protein band of about 44 kDa was visualized in SDS-polyacrylamide gel under reducing condition. Purified venom protein expressed as haemolytic, cytotoxicity and proteolytic activities with lethal concentration (LC50 ) at 2.0 μg/mL. Venom protein exhibits enzymatic activity and hydrolyzed casein and gelatin. Gelatinolytic activity was optimal at pH 5-9. In conclusion, the present results suggested that the sea snake venom might be feasible sources for biologically active substances. Thus, this low molecular weight component of the venom protein could be used in potentially serve biological and pharmaceutical aspects. © 2014 Wiley Periodicals, Inc.

  18. Strategies for structuring interdisciplinary education in Systems Biology: an European perspective

    NARCIS (Netherlands)

    Cvijovic, Marija; Höfer, Thomas; Acimovic, Jure; Alberghina, Lilia; Almaas, Eivind; Besozzi, Daniela; Blomberg, Anders; Bretschneider, Till; Cascante, Marta; Collin, Olivier; Atauri, de Pedro; Depner, Cornelia; Dickinson, Robert; Dobrzynski, Maciej; Fleck, C.; Garcia-Ojalvo, Jordi; Gonze, Didier; Hahn, Jens; Hess, Heide Marie; Hollmann, Susanne; Krantz, Marcus; Kummer, Ursula; Lundh, Torbjörn; Martial, Gifta; Martins dos Santos, V.A.P.; Mauer-Oberthür, Angela; Regierer, Babette; Skene, Barbara; Stalidzans, Egils; Stelling, Jörg; Teusink, Bas; Workman, Christopher T.; Hohmann, Stefan

    2016-01-01

    Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological

  19. Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology.

    Science.gov (United States)

    Karchesy, Joseph J; Kelsey, Rick G; González-Hernández, M P

    2018-05-01

    Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of southeast Alaska, western Canada, and inland forests along the Cascades to northern California, USA. These trees have few microbial or animal pests, attributable in part to the distinct groups of biologically active secondary metabolites their tissues store for chemical defense. Here we summarize the new yellow-cedar compounds identified and their biological activities, plus new or expanded activities for tissues, extracts, essential oils and previously known compounds since the last review more than 40 years ago. Monoterpene hydrocarbons are the most abundant compounds in foliage, while heartwood contains substantial quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins have been isolated from inner bark. Biological activities expressed by one or more compounds in these groups include fungicide, bactericide, sporicide, acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer. The diversity of organisms impacted by whole tissues, essential oils, extracts, or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes, bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood component with sufficient activity against arthropods to warrant research focused toward potential development as a commercial repellent and biopesticide for ticks, mosquitoes and possibly other arthropods that vector human and animal pathogens.

  20. Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes

    Directory of Open Access Journals (Sweden)

    Figarella K

    2015-12-01

    Full Text Available The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. The chemotherapy currently in use is not adequate because of their side effects, resistance occurrence, and recurrences. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Here, we report the synthesis of ergosterone coupled molecules and the characterization of their biological activity on Leishmania mexicana promastigotes. Molecule synthesis involved three steps: ergosterone formation using Jones oxidation, synthesis of Girard reagents, and coupling reaction. All compounds were obtained in good yield and high purity. Results show that ergosterone-triazol molecules (Erg-GTr and Erg-GTr2 exhibit an antiproliferative effect in low micromolar range with a selectivity index ~10 when compared to human dermic fibroblasts. Addition of Erg-GTr or Erg-GTr2 to parasites led to a rapid [Ca2+]cyt increase and acidocalcisomes alkalinization, indicating that Ca2+ was released from this organelle. Evaluation of cell death markers revealed some apoptosis-like indicators, as phosphatidylserine exposure, DNA damage, and cytosolic vacuolization and autophagy exacerbation. Furthermore, mitochondrion hyperpolarization and superoxide production increase were detected already 6 hours after drug addition, denoting that oxidative stress is implicated in triggering the observed phenotype. Taken together our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.