WorldWideScience

Sample records for macromolecular bioactive agents

  1. Liver-targeting macromolecular MRI contrast agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Macromolecular ligands with liver-targeting group (pyridoxamine, PM) PHEA-DTPA-PM and PAEA-DTPA-PM were prepared by the incorporation of different amount of diethylenetriaminepentaacetic acid monopyridoxamine group (DTPA-PM) into poly-a, b-[N-(2-hydroxyethyl)-L- aspartamide] (PHEA) and poly-a, b-[N-(2-aminoethyl)-L-aspartamide] (PAEA). The macromolecular ligands thus obtained were further complexed with gadolinium chloride to give macromolecular MRI contrast agents with different Gd(Ⅲ) contents. These macromolecular ligands and their gadolinium complexes were characterized by 1H NMR, IR, UV and elementary analysis. Relaxivity studies showed that these polyaspartamide gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of the liver in rats and experimental data of biodistribution in mice indicate that these macromolecular MRI contrast agents containing pyridoxamine exhibit liver-targeting property.

  2. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  3. Cyclodextrins as encapsulation agents for plant bioactive compounds.

    Science.gov (United States)

    Pinho, Eva; Grootveld, Martin; Soares, Graça; Henriques, Mariana

    2014-01-30

    Plants possess a wide range of molecules capable of improve healing: fibre, vitamins, phytosterols, and further sulphur-containing compounds, carotenoids, organic acid anions and polyphenolics. However, they require an adequate level of protection from the environmental conditions to prevent losing their structural integrity and bioactivity. Cyclodextrins are cyclic oligosaccharides arising from the degradation of starch, which can be a viable option as encapsulation technique. Cyclodextrins are inexpensive, friendly to humans, and also capable of improving the biological, chemical and physical properties of bioactive molecules. Therefore, the aim of this review is to highlight the use of cyclodextrins as encapsulating agents for bioactive plant molecules in the pharmaceutical field.

  4. Enzymatic biotransformation of terpenes as bioactive agents.

    Science.gov (United States)

    Sultana, Nighat; Saify, Zafar Saeed

    2013-12-01

    The plant-derived terpenoids are considered to be the most potent anticancer, anti-inflammatory and anticarcinogenic compounds known. Enzymatic biotransformation is a very useful approach to expand the chemical diversity of natural products. Recent enzymatic biotransformation studies on terpenoids have resulted in the isolation of novel compounds. 14-hydroxy methyl caryophyllene oxide produced from caryophyllene oxide showed a potent inhibitory activity against the butyryl cholinesterase enzyme, and was found to be more potent than parent caryophyllene oxide. The metabolites 3β,7β-dihydroxy-11-oxo-olean-12-en-30-oic acid, betulin, betulonic acid, argentatin A, incanilin, 18β glycyrrhetinic acid, 3,11-dioxo-olean-12-en-30-oic acid produced from 18β glycyrrhetinic acid were screened against the enzyme lipoxygenase. 3,11-Dioxo-olean-12-en-30-oic acid, was found to be more active than the parent compound. The metabolites 3β-hydroxy sclareol 18α-hydroxy sclareol, 6α,18α-dihydroxy sclareol, 11S,18α-dihydroxy sclareol, and 1β-hydroxy sclareol and 11S,18α-dihydroxy sclareol produced from sclareol were screened for antibacterial activity. 1β-Hydroxy sclareol was found to be more active than parent sclareol. There are several reports on natural product enzymatic biotransformation, but few have been conducted on terpenes. This review summarizes the classification, advantages and agents of enzymatic transformation and examines the potential role of new enzymatically transformed terpenoids and their derivatives in the chemoprevention and treatment of other diseases.

  5. Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Jenjob, Ratchapol [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of); Kun, Na [Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743 (Korea, Republic of); Ghee, Jung Yeon [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Shen, Zheyu; Wu, Xiaoxia [Division of Functional Materials and Nano-Devices, Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, 519 Zhuangshi Street, Zhenhai District, Ningbo, Zhejiang 315201 (China); Cho, Steve K., E-mail: scho@gist.ac.kr [Division of Liberal Arts and Science, GIST College, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Lee, Don Haeng [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Internal Medicine, School of Medicine, Inha University Hospital, Incheon 420-751 (Korea, Republic of); Yang, Su-Geun, E-mail: Sugeun.Yang@Inha.ac.kr [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of)

    2016-04-01

    In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd{sup 3+}, chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd{sup 3+} in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd{sup 3+} incubated with Ca{sup 2+} was performed by using a dialysis membrane (MWCO 100–500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd{sup 3+}, the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd{sup 3+} were released from Gd-DTPA-Pullulan after 2 h incubation with Ca{sup 2+} and Fe{sup 2+}, respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. - Highlights: • Macromolecule (pullulan) conjugated Gd contrast agent (Gd-DTPA-Pullulan) showed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h) in comparison with Gd-EOB-DTPA • Gd-DTPA-pullulan T1 contrast agent exhibited strong chelation stability against Gd. • The extended blood circulation attributed the enhanced and prolonged MR contrast on abdominal region of rats. • The extended blood circulation may provide prolonged MR acquisition time window in clinics.

  6. Engineered plant biomass particles coated with bioactive agents

    Energy Technology Data Exchange (ETDEWEB)

    Dooley, James H; Lanning, David N

    2013-07-30

    Plant biomass particles coated with a bioactive agent such as a fertilizer or pesticide, characterized by a length dimension (L) aligned substantially parallel to a grain direction and defining a substantially uniform distance along the grain, a width dimension (W) normal to L and aligned cross grain, and a height dimension (H) normal to W and L. In particular, the L.times.H dimensions define a pair of substantially parallel side surfaces characterized by substantially intact longitudinally arrayed fibers, the W.times.H dimensions define a pair of substantially parallel end surfaces characterized by crosscut fibers and end checking between fibers, and the L.times.W dimensions define a pair of substantially parallel top and bottom surfaces.

  7. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    Science.gov (United States)

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  8. Coaxial electrospinning for encapsulation and controlled release of fragile water-soluble bioactive agents.

    Science.gov (United States)

    Jiang, Hongliang; Wang, Liqun; Zhu, Kangjie

    2014-11-10

    Coaxial electrospinning is a robust technique for one-step encapsulation of fragile, water-soluble bioactive agents, including growth factors, DNA and even living organisms, into core-shell nanofibers. The coaxial electrospinning process eliminates the damaging effects due to direct contact of the agents with organic solvents or harsh conditions during emulsification. The shell layer serves as a barrier to prevent the premature release of the water-soluble core contents. By varying the structure and composition of the nanofibers, it is possible to precisely modulate the release of the encapsulated agents. Promising work has been done with coaxially electrospun non-woven mats integrated with bioactive agents for use in tissue engineering, in local delivery and in wound healing, etc. This paper reviews the origins of the coaxial electrospinning method, its updated status and potential future developments for controlled release of the class of fragile, water-soluble bioactive agents.

  9. Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other Pathogenic Viruses

    DEFF Research Database (Denmark)

    Schandock, Franziska; Riber, Camilla Frich; Röcker, Annika

    2017-01-01

    . This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure...

  10. Sulfated polysaccharides as bioactive agents from marine algae.

    Science.gov (United States)

    Ngo, Dai-Hung; Kim, Se-Kwon

    2013-11-01

    Recently, much attention has been paid by consumers toward natural bioactive compounds as functional ingredients in nutraceuticals. Marine algae are considered as valuable sources of structurally diverse bioactive compounds. Marine algae are rich in sulfated polysaccharides (SPs) such as carrageenans in red algae, fucoidans in brown algae and ulvans in green algae. These SPs exhibit many health beneficial nutraceutical effects such as antioxidant, anti-allergic, anti-human immunodeficiency virus, anticancer and anticoagulant activities. Therefore, marine algae derived SPs have great potential to be further developed as medicinal food products or nutraceuticals in the food industry. This contribution presents an overview of nutraceutical effects and potential health benefits of SPs derived from marine algae. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Cyclodextrins as encapsulation agents for plant bioactive compounds

    OpenAIRE

    Pinho, Eva Patrícia Paiva Santos; Grootveld, Martin; Soares, Graça M. B.; Henriques, Mariana

    2014-01-01

    Abstract Plants possess a wide range of molecules capable of improve healing: fibre, vitamins, phytosterols, and further sulphur-containing compounds, carotenoids, organic acid anions and polyphenolics. However, they require an adequate level of protection from the environmental conditions to prevent losing their structural integrity and bioactivity. Cyclodextrins are cyclic oligosaccharides arising from the degradation of starch, which can be a viable option as encapsulation technique. Cy...

  12. The use of trimethylamine N-oxide as a primary precipitating agent and related methylamine osmolytes as cryoprotective agents for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Haley; Venkat, Murugappan; Hti Lar Seng, Nang San; Cahn, Jackson [Whitman College, Walla Walla, Washington (United States); Juers, Douglas H., E-mail: juersdh@whitman.edu [Whitman College, Walla Walla, Washington (United States); Whitman College, Walla Walla, Washington (United States)

    2012-01-01

    The stabilizing osmolyte trimethylamine N-oxide (TMAO) is shown to be an efficient primary precipitant for protein crystal growth. In addition to TMAO, two other methylamine osmolytes, sarcosine and betaine, are shown to be effective cryoprotective agents for protein crystal cooling. Both crystallization and cryoprotection are often bottlenecks for high-resolution X-ray structure determination of macromolecules. Methylamine osmolytes are known stabilizers of protein structure. One such osmolyte, trimethylamine N-oxide (TMAO), has seen occasional use as an additive to improve macromolecular crystal quality and has recently been shown to be an effective cryoprotective agent for low-temperature data collection. Here, TMAO and the related osmolytes sarcosine and betaine are investigated as primary precipitating agents for protein crystal growth. Crystallization experiments were undertaken with 14 proteins. Using TMAO, seven proteins crystallized in a total of 13 crystal forms, including a new tetragonal crystal form of trypsin. The crystals diffracted well, and eight of the 13 crystal forms could be effectively cryocooled as grown with TMAO as an in situ cryoprotective agent. Sarcosine and betaine produced crystals of four and two of the 14 proteins, respectively. In addition to TMAO, sarcosine and betaine were effective post-crystallization cryoprotective agents for two different crystal forms of thermolysin. Precipitation reactions of TMAO with several transition-metal ions (Fe{sup 3+}, Co{sup 2+}, Cu{sup 2+} and Zn{sup 2+}) did not occur with sarcosine or betaine and were inhibited for TMAO at lower pH. Structures of proteins from TMAO-grown crystals and from crystals soaked in TMAO, sarcosine or betaine were determined, showing osmolyte binding in five of the 12 crystals tested. When an osmolyte was shown to bind, it did so near the protein surface, interacting with water molecules, side chains and backbone atoms, often at crystal contacts.

  13. Predominately Uncultured Microbes as Sources of Bioactive Agents

    Science.gov (United States)

    Newman, David J.

    2016-01-01

    In this short review, I am discussing the relatively recent awareness of the role of symbionts in plant, marine-invertebrates and fungal areas. It is now quite obvious that in marine-invertebrates, a majority of compounds found are from either as yet unculturable or poorly culturable microbes, and techniques involving “state of the art” genomic analyses and subsequent computerized analyses are required to investigate these interactions. In the plant kingdom evidence is amassing that endophytes (mainly fungal in nature) are heavily involved in secondary metabolite production and that mimicking the microbial interactions of fermentable microbes leads to involvement of previously unrecognized gene clusters (cryptic clusters is one name used), that when activated, produce previously unknown bioactive molecules. PMID:27917159

  14. Endophytic and Epiphytic Microbes as Sources of Bioactive Agents

    Directory of Open Access Journals (Sweden)

    David J. Newman

    2015-05-01

    Full Text Available Beginning with the report by Stierle and Strobel in 1993 on taxol(R production by an endophytic fungus 1, it is possible that a number of the agents now used as leads to treatments of diseases in man, are not produced by the plant or invertebrate host from which they were first isolated and identified.They are probably the product of a microbe in, on or around the macroorganism. At times there is an intricate dance between a precursor produced by a microbe, and interactions within the macroorganism, or in certain cases, a fungus, that ends up with the production of a novel agent that has potential as a treatment for a human disease. This report will give examples from insects, plants and marine invertebrates.

  15. Endophytic and Epiphytic Microbes as ``Sources'' of Bioactive Agents

    Science.gov (United States)

    Newman, David; Cragg, Gordon

    2015-05-01

    Beginning with the report by Stierle and Strobel in 1993 on taxol(R) production by an endophytic fungus 1, it is possible that a number of the agents now used as leads to treatments of diseases in man, are not produced by the plant or invertebrate host from which they were first isolated and identified.They are probably the product of a microbe in, on or around the macroorganism. At times there is an intricate “dance” between a precursor produced by a microbe, and interactions within the macroorganism, or in certain cases, a fungus, that ends up with the production of a novel agent that has potential as a treatment for a human disease. This report will give examples from insects, plants and marine invertebrates.

  16. The surface modification of TiN nano-particles using macromolecular coupling agents, and their resulting dispersibility

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Guojun, E-mail: chengguojun0436@126.com [School of Chemistry and Chemical Engineering, Anhui University, Hefei 230039 (China); School of Materials Science and Engineering, Anhui University of Science and Technology, Huainan 232001 (China); Qian, Jiasheng, E-mail: qianjs@ahu.edu.cn [School of Chemistry and Chemical Engineering, Anhui University, Hefei 230039 (China); Miao, Jibin; Yang, Bin; Xia, Ru; Chen, Peng [School of Chemistry and Chemical Engineering, Anhui University, Hefei 230039 (China)

    2014-05-01

    Graphical abstract: The hydroxyl groups on the surface of nano-TiN particles interacted with the silanol groups [-Si-OCH{sub 3}] of a F-MCA to form an organic coating layer that hindered the aggregation of the nano-TiN. The obvious agglomeration and homogeneous dispersion can be seen in TEM images. - Highlights: • The dispersible TiN nano-particles were prepared to increase its surface activity. • Surface hydrophobicity increased due to being modified by F-MCA. • TiN nano-particles modified with F-MCA shows good dispersion in anhydrous ethanol. • The coupling agents are tightly absorbed on the surface of particles by chemisorption. • Modified TiN nano-particles can be widely used in polymers with great compatibility. - Abstract: Titanium nitride (TiN) nano-particles were modified by the grafting of a random copolymerization functionalized macromolecular coupling agent (F-MCA) via a direct blending method. The hydroxyl groups on the surface of the nano-TiN particles interact with the silanol groups [-Si-OCH{sub 3}] of the F-MCA to form an organic coating layer. The formation of covalent bonds [Ti-O-Si] was verified using Fourier transform infrared spectroscopy. An X-ray diffraction analysis suggests that the presence of the F-MCA inhibited the growth of the crystal plane but did not change the crystal structure of the TiN. Thermogravimetric analysis and contact angle measurement indicated that the F-MCA molecules were adsorbed or anchored to the surface of the nano-TiN particles, which hindered their aggregation. Pristine nano-TiN particles are poorly dispersed in ethyl acetate. Compared with the pristine TiN particles, the modified TiN particles show good dispersibility and form a stable colloidal dispersion in ethyl acetate. The surface hydrophobicity of the modified TiN increases, and the F-MCA molecules are anchored on the surface of the TiN particles. TiN particles modified by a F-MCA can be used in polymer blends, thermoplastic elastomers and polymer

  17. Macromolecular Prodrugs of Ribavirin

    DEFF Research Database (Denmark)

    Riber, Camilla Frich; Hinton, Tracey M; Gajda, Paulina

    2017-01-01

    The requirement for new antiviral therapeutics is an ever present need. Particularly lacking are broad spectrum antivirals that have low toxicity. We develop such agents based on macromolecular prodrugs whereby both the polymer chain and the drug released from the polymer upon cell entry have ant...

  18. Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

  19. Bioactive Dental Composites and Bonding Agents Having Remineralizing and Antibacterial Characteristics.

    Science.gov (United States)

    Zhang, Ke; Zhang, Ning; Weir, Michael D; Reynolds, Mark A; Bai, Yuxing; Xu, Hockin H K

    2017-10-01

    Current dental restorative materials are typically inert and replace missing tooth structures. This article reviews efforts in the development of a new generation of bioactive materials designed to not only replace the missing tooth volume but also possess therapeutic functions. Composites and bonding agents with remineralizing and antibacterial characteristics have shown promise in replacing lost minerals, inhibiting recurrent caries, neutralizing acids, repelling proteins, and suppressing biofilms and acid production. Furthermore, they have demonstrated a low cytotoxicity similar to current resins, with additional benefits to protect the dental pulp and promote tertiary dentin formation. This new class of bioactive materials shows promise in reversing lesions and inhibiting caries. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Bioactive and wood-associated stilbenes as multifunctional antimicrobial and health promoting agents (BIOSTIMUL)

    Energy Technology Data Exchange (ETDEWEB)

    Wright, A. von (Kuopio Univ., Department of Biosciences (Finland))

    2008-07-01

    Plant polyphenolics have a wide range of bioactivities. Coniferous trees are a rich source of stilbenes, such as pinosylvin in the genus Pinus. Pinosylvin is structurally very similar to resveratrol, a stilbene found in grapes and red berries, and which is reported to have beneficial health effects such as prevention of cardiovascular diseases, tumourigenesis, and according to recent findings, also type II diabetes. In our previous studies the bioactivities of pinosylvin (antimicrobial effects and cytotoxic activities against cancer cells) were very similar to those of resveratrol. In this project we elucidate the potential of pinosylvin and as derivatives in food applications as multifunctional antimicrobial agents with positive health effects (including prevention of type II diabetes) highlighting results. (orig.)

  1. Bioactive and wood-associated stilbenes as multifunctional antimicrobial and health promoting agents - BIOSTIMUL

    Energy Technology Data Exchange (ETDEWEB)

    Wright, A. von (Univ. of Eastern Finland, Kuopio (Finland). Dept. of Biosciences.), Email: atte.vonWright@uef.fi

    2010-10-15

    Plant polyphenolics have a wide range of bioactivities. Coniferous trees are a rich source of stilbenes, such as pinosylvin in the genus Pinus. Pinosylvin is structurally very similar to resveratrol, a stilbene found in grapes and red berries, and which is reported to have beneficial health effects such as prevention of cardiovascular diseases, tumourigenesis, and according to recent findings, also type II diabetes. In our previous studies the bioactivities of pinosylvin (antimicrobial effects and cytotoxic activities against cancer cells) were very similar to those of resveratrol. In this project we elucidate the potential of pinosylvin and its derivatives in food applications as multifunctional antimicrobial agents with positive health effects (including prevention of type II diabetes) highlighting results. (orig.)

  2. Bioactive and wood-associated stilbenes as multifunctional antimicrobial and health promoting agents - BIOSTIMUL

    Energy Technology Data Exchange (ETDEWEB)

    Wright, A. von (Univ. of Kuopio, Dept. of Biosciences (Finland)), email: atte.vonWright@uku.fi

    2009-10-15

    Plant polyphenolics have a wide range of bioactivities. Coniferous trees are a rich source of stilbenes, such as pinosylvin in the genus Pinus. Pinosylvin is structurally very similar to resveratrol, a stilbene found in grapes and red berries, and which is reported to have beneficial health effects such as prevention of cardiovascular diseases, tumourigenesis, and according to recent findings, also type 2 diabetes. In our previous studies the bioactivities of pinosylvin (antimicrobial effects and cytotoxic activities against cancer cells) were very similar to those of resveratrol. In this project we elucidate the potential of pinosylvin and its derivatives in food applications as multifunctional antimicrobial agents with positive health effects (including prevention of type 2 diabetes) highlighting results. (orig.)

  3. Preclinical imaging and translational animal models of cancer for accelerated clinical implementation of nanotechnologies and macromolecular agents.

    Science.gov (United States)

    De Souza, Raquel; Spence, Tara; Huang, Huang; Allen, Christine

    2015-12-10

    The majority of animal models of cancer have performed poorly in terms of predicting clinical performance of new therapeutics, which are most often first evaluated in patients with advanced, metastatic disease. The development and use of metastatic models of cancer may enhance clinical translatability of preclinical studies focused on the development of nanotechnology-based drug delivery systems and macromolecular therapeutics, potentially accelerating their clinical implementation. It is recognized that the development and use of such models are not without challenge. Preclinical imaging tools offer a solution by allowing temporal and spatial characterization of metastatic lesions. This paper provides a review of imaging methods applicable for evaluation of novel therapeutics in clinically relevant models of advanced cancer. An overview of currently utilized models of oncology in small animals is followed by image-based development and characterization of visceral metastatic cancer models. Examples of imaging tools employed for metastatic lesion detection, evaluation of anti-tumor and anti-metastatic potential and biodistribution of novel therapies, as well as the co-development and/or use of imageable surrogates of response, are also discussed. While the focus is on development of macromolecular and nanotechnology-based therapeutics, examples with small molecules are included in some cases to illustrate concepts and approaches that can be applied in the assessment of nanotechnologies or macromolecules.

  4. Marine bioactive agents: a short review on new marine antidiabetic compounds

    Directory of Open Access Journals (Sweden)

    Sonal Ramrao Barde

    2015-06-01

    Full Text Available From medicinal point of view, marine environment is a diversified source of several biologically active compounds that are relatively untapped. Exploitation of marine resources may provide valuable leads which carry economic and scientific potential. Diabetes is a metabolic disorder and a major cause of mortality and morbidity in both developed and developing countries. Several antidiabetics are available but the major limitations of these synthetic drugs are cost, effectiveness and adverse effects. The relative safety of drugs from natural source is the main reason behind exploring marine resources as a source of therapeutic, food and nutritional compounds. Marine resources provide many compounds including polyphenols, peptides, pigments, phlorotannins and sterols that could be used for the treatment of diabetes and associated complications. The present review focuses on potential marine resources that provide bioactive agents for diabetes treatment.

  5. Multi-modal magnetic resonance imaging and histology of vascular function in xenografts using macromolecular contrast agent hyperbranched polyglycerol (HPG-GdF).

    Science.gov (United States)

    Baker, Jennifer H E; McPhee, Kelly C; Moosvi, Firas; Saatchi, Katayoun; Häfeli, Urs O; Minchinton, Andrew I; Reinsberg, Stefan A

    2016-01-01

    Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for MRI. HPG-GdF is a 583 kDa hyperbranched polyglycerol doubly tagged with Gd and Alexa 647 nm dye, making it both MR and histologically visible. In this study we examined the location of HPG-GdF in whole-tumor xenograft sections matched to in vivo DCE-MR images of both HPG-GdF and Gadovist. Despite its large size, we have shown that HPG-GdF extravasates from some tumor vessels and accumulates over time, but does not distribute beyond a few cell diameters from vessels. Fractional plasma volume (fPV) and apparent permeability-surface area product (aPS) parameters were derived from the MR concentration-time curves of HPG-GdF. Non-viable necrotic tumor tissue was excluded from the analysis by applying a novel bolus arrival time (BAT) algorithm to all voxels. aPS derived from HPG-GdF was the only MR parameter to identify a difference in vascular function between HCT116 and HT29 colorectal tumors. This study is the first to relate low and high molecular weight contrast agents with matched whole-tumor histological sections. These detailed comparisons identified tumor regions that appear distinct from each other using the HPG-GdF biomarkers related to perfusion and vessel leakiness, while Gadovist-imaged parameter measures in the same regions were unable to detect variation in vascular function. We have established HPG-GdF as a biocompatible multi-modal high molecular weight contrast agent with application for examining vascular function in both MR and histological modalities. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Facile Fabrication of Water Dispersible Latex Particles with Homogeneous or Chain-Segregated Surface from RAFT Polymerization Using a Mixture of Two Macromolecular Chain Transfer Agents.

    Science.gov (United States)

    Sun, Li; Hong, Liangzhi; Wang, Chaoyang

    2016-04-01

    Water dispersible latex particles with randomly mixed shells or chain segregated surface are synthesized from one-pot reversible addition-fragmentation chain transfer heterogeneous polymerization of benzyl methacrylate (BzMA) using a mixture of poly(glycerol monomethacrylate) (PGMA) and poly(2,3-bis(succinyloxy)propyl methacrylate) (PBSPMA) macromolecular chain transfer agents. In methanol, the two in situ synthesized PGMA-b-PBzMA and PBSPMA-b-PBzMA diblock copolymers coaggregate into spherical micelles, which contain PBzMA core and discrete PGMA and PBSPMA nanodomains on the shell. In contrast, in water-methanol mixture (V/V = 9/1), latex particles with homogeneous distribution of PGMA and PBSPMA polymer chains on the shell are obtained. The reasons leading to formation of latex particles with homogenous or chain-segregated surface are discussed, and polymerization kinetics and physical state of PBSPMA in methanol and water-methanol mixtures are ascribed. These polymeric micelles with patterned functional group on the surface are potentially important for application in supracolloidal hierarchical assemblies and catalysis.

  7. Nanocomposite scaffolds with tunable mechanical and degradation capabilities: co-delivery of bioactive agents for bone tissue engineering.

    Science.gov (United States)

    Cattalini, Juan P; Roether, Judith; Hoppe, Alexander; Pishbin, Fatemeh; Haro Durand, Luis; Gorustovich, Alejandro; Boccaccini, Aldo R; Lucangioli, Silvia; Mouriño, Viviana

    2016-10-21

    Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.

  8. Nano/microfibrous polymeric constructs loaded with bioactive agents and designed for tissue engineering applications: a review.

    Science.gov (United States)

    Puppi, Dario; Zhang, Xuanmiao; Yang, Likai; Chiellini, Federica; Sun, Xun; Chiellini, Emo

    2014-10-01

    Nano/microfibrous polymeric constructs present various inherent advantages, such as highly porous architecture and high surface to volume ratio, making them attractive for tissue engineering purposes. Electrospinning is the most preferred technique for the fabrication of polymeric nanofibrous assemblies that can mimic the physical functions of native extracellular matrix greatly favoring cells attachment and thus influencing their morphology and activities. Different approaches have been developed to apply polymeric microfiber fabrication techniques (e.g. wet-spinning) for the obtainment of scaffolds with a three-dimensional network of micropores suitable for effective cells migration. Progress in additive manufacturing technology has led to the development of complex scaffold's shapes and microfibrous structures with a high degree of automation, good accuracy and reproducibility. Various loading methods, such as direct blending, coaxial electrospinning and microparticles incorporation, are enabling to develop customized strategies for the biofunctionalization of nano/microfibrous scaffolds with a tailored kinetics of release of different bioactive agents, ranging from small molecules, such as antibiotics, to protein drugs, such as growth factors, and even cells. Recent activities on the combination of different processing techniques and loading methods for the obtainment of biofunctionalized polymeric constructs with a complex multiscale structure open new possibilities for the development of biomimetic scaffolds endowed with a hierarchical architecture and a sophisticated release kinetics of different bioactive agents. This review is aimed at summarizing current advances in technologies and methods for manufacturing nano/microfibrous polymeric constructs suitable as tissue engineering scaffolds, and for their combination with different bioactive agents to promote tissue regeneration and therapeutic effects.

  9. Susceptibility of three clinical isolates of Actinomodura madurae to α-pinene, the bioactive agent of Pinus pinaster turpentine oil

    Directory of Open Access Journals (Sweden)

    Stojković D.

    2008-01-01

    Full Text Available In vitro susceptibility of the turpentine oil obtained from Pinus pinaster oleoresin was evaluated against three Sudanese clinical isolates of Actinomadura madurae, which is the main causative agent of actinomycetoma. The minimum inhibitory concentrations (MICs of the oil ranged from 100.3 to 124.8 μL/mL, and the minimum microbicidal concentrations (MMCs were between 100.3 and 150.0 μL/mL. α-Pinene exhibited prominent bioactivity with MICs ranging between 3.3 and 5.0 μL/mL, while its MMC was 10.0 μL/mL against the same clinical isolates. Pinus pinaster turpentine oil and α-pinene might be useful agents in the treatment of mycetoma caused by A. madurae.

  10. Bioactive and Structural Metabolites of Pseudomonas and Burkholderia Species Causal Agents of Cultivated Mushrooms Diseases1

    Science.gov (United States)

    Andolfi, Anna; Cimmino, Alessio; Cantore, Pietro Lo; Iacobellis, Nicola Sante; Evidente, Antonio

    2008-01-01

    Pseudomonas tolaasii, P. reactans and Burkholderia gladioli pv. agaricicola, are responsible of diseases on some species of cultivated mushrooms. The main bioactive metabolites produced by both Pseudomonas strains are the lipodepsipeptides (LDPs) tolaasin I and II and the so called White Line Inducing Principle (WLIP), respectively, LDPs which have been extensively studied for their role in the disease process and for their biological properties. In particular, their antimicrobial activity and the alteration of biological and model membranes (red blood cell and liposomes) was established. In the case of tolaasin I interaction with membranes was also related to the tridimensional structure in solution as determined by NMR combined with molecular dynamic calculation techniques. Recently, five news minor tolaasins, tolaasins A–E, were isolated from the culture filtrates of P. tolaasii and their chemical structure was determined by extensive use of NMR and MS spectroscopy. Furthermore, their antimicrobial activity was evaluated on target micro-organisms (fungi—including the cultivated mushrooms Agaricus bisporus, Lentinus edodes, and Pleurotus spp.—chromista, yeast and bacteria). The Gram positive bacteria resulted the most sensible and a significant structure-activity relationships was apparent. The isolation and structure determination of bioactive metabolites produced by B. gladioli pv. agaricicola are still in progress but preliminary results indicate their peptide nature. Furthermore, the exopolysaccharide (EPS) from the culture filtrates of B. gladioli pv. agaricicola, as well as the O-chain and lipid A, from the lipopolysaccharide (LPS) of the three bacteria, were isolated and the structures determined. PMID:19787100

  11. Bioactive and structural metabolites of pseudomonas and burkholderia species causal agents of cultivated mushrooms diseases.

    Science.gov (United States)

    Andolfi, Anna; Cimmino, Alessio; Cantore, Pietro Lo; Iacobellis, Nicola Sante; Evidente, Antonio

    2008-05-09

    Pseudomonas tolaasii, P. reactans and Burkholderia gladioli pv. agaricicola, are responsible of diseases on some species of cultivated mushrooms. The main bioactive metabolites produced by both Pseudomonas strains are the lipodepsipeptides (LDPs) tolaasin I and II and the so called White Line Inducing Principle (WLIP), respectively, LDPs which have been extensively studied for their role in the disease process and for their biological properties. In particular, their antimicrobial activity and the alteration of biological and model membranes (red blood cell and liposomes) was established. In the case of tolaasin I interaction with membranes was also related to the tridimensional structure in solution as determined by NMR combined with molecular dynamic calculation techniques. Recently, five news minor tolaasins, tolaasins A-E, were isolated from the culture filtrates of P. tolaasii and their chemical structure was determined by extensive use of NMR and MS spectroscopy. Furthermore, their antimicrobial activity was evaluated on target micro-organisms (fungi-including the cultivated mushrooms Agaricus bisporus, Lentinus edodes, and Pleurotus spp.-chromista, yeast and bacteria). The Gram positive bacteria resulted the most sensible and a significant structure-activity relationships was apparent. The isolation and structure determination of bioactive metabolites produced by B. gladioli pv. agaricicola are still in progress but preliminary results indicate their peptide nature. Furthermore, the exopolysaccharide (EPS) from the culture filtrates of B. gladioli pv. agaricicola, as well as the O-chain and lipid A, from the lipopolysaccharide (LPS) of the three bacteria, were isolated and the structures determined.

  12. Bioactivity-guided fractionation identifies amygdalin as a potent neurotrophic agent from herbal medicine Semen Persicae extract.

    Science.gov (United States)

    Yang, Chuanbin; Zhao, Jia; Cheng, Yuanyuan; Li, Xuechen; Rong, Jianhui

    2014-01-01

    Herbal medicine Semen Persicae is widely used to treat blood stasis in Chinese medicine and other oriental folk medicines. Although little is known about the effects of Semen Persicae and its active compounds on neuron differentiation, our pilot study showed that Semen Persicae extract promoted neurite outgrowth in rat dopaminergic PC12 cells. In the present study, we developed a bioactivity-guided fractionation procedure for the characterization of the neurotrophic activity of Semen Persicae extract. The resultant fractions were assayed for neurite outgrowth in PC12 cells based on microscopic assessment. Through liquid-liquid extraction and reverse phase HPLC separation, a botanical glycoside amygdalin was isolated as the active compound responsible for the neurotrophic activity of Semen Persicae extract. Moreover, we found that amygdalin rapidly induced the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). A specific ERK1/2 inhibitor PD98059 attenuated the stimulatory effect of amygdalin on neurite outgrowth. Taken together, amygdalin was identified as a potent neurotrophic agent from Semen Persicae extract through a bioactivity-guided fractional procedure. The neurotrophic activity of amygdalin may be mediated by the activation of ERK1/2 pathway.

  13. Bioactivity-Guided Fractionation Identifies Amygdalin as a Potent Neurotrophic Agent from Herbal Medicine Semen Persicae Extract

    Directory of Open Access Journals (Sweden)

    Chuanbin Yang

    2014-01-01

    Full Text Available Herbal medicine Semen Persicae is widely used to treat blood stasis in Chinese medicine and other oriental folk medicines. Although little is known about the effects of Semen Persicae and its active compounds on neuron differentiation, our pilot study showed that Semen Persicae extract promoted neurite outgrowth in rat dopaminergic PC12 cells. In the present study, we developed a bioactivity-guided fractionation procedure for the characterization of the neurotrophic activity of Semen Persicae extract. The resultant fractions were assayed for neurite outgrowth in PC12 cells based on microscopic assessment. Through liquid-liquid extraction and reverse phase HPLC separation, a botanical glycoside amygdalin was isolated as the active compound responsible for the neurotrophic activity of Semen Persicae extract. Moreover, we found that amygdalin rapidly induced the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2. A specific ERK1/2 inhibitor PD98059 attenuated the stimulatory effect of amygdalin on neurite outgrowth. Taken together, amygdalin was identified as a potent neurotrophic agent from Semen Persicae extract through a bioactivity-guided fractional procedure. The neurotrophic activity of amygdalin may be mediated by the activation of ERK1/2 pathway.

  14. Lecithin organogel: A unique micellar system for the delivery of bioactive agents in the treatment of skin aging

    Directory of Open Access Journals (Sweden)

    Sushil Raut

    2012-02-01

    Full Text Available Skin aging is an unavoidable aspect of human life. Premature skin aging can result from poor care, environmental pollutants, and ultraviolet radiation exposure. Wrinkles, lines, spots, uneven skin tone, and pigmentation are often indicators of skin aging. One cannot avoid aging but cosmetics and pharmaceutical approaches can minimize and delay the damage. Topical applications of biocompatible and biodegradable vehicles have been explored for delivering anti-aging compounds. Lecithin organogel (LO is an effective vehicle for topical delivery of many bioactive agents used in aging treatment. Lecithin is cell component isolated from soya beans or eggs and purified to show excellent gelation in non-polar solvents when combined with water. LO can form a heat-stable, resistant to microbial growth, visco-elastic, optically transparent, and non-birefringent micellar system. It serves as an organic medium to enhance dermal permeation of poorly permeable drugs by effectively partitioning into the skin. Its ability to dissolve in hydrophilic as well as in lipophilic drugs makes it a dynamic vehicle, which can be explored as a carrier for anti-aging agents.

  15. Bioassays Against Pinewood Nematode: Assessment of a Suitable Dilution Agent and Screening for Bioactive Essential Oils

    OpenAIRE

    Ana Cristina Figueiredo; Luis G. Pedro; Barroso, José G.; Maria Teresa Tinoco; Luís Silva Dias; Mendes, Marta D.; Jorge M. S. Faria; Pedro Barbosa; Manuel Mota

    2012-01-01

    Acetone was investigated and found to be an appropriate alternative to Triton X-100 as a solvent of essential oils in bioassays aimed to investigate their effects on pinewood nematode (Bursaphelenchus xylophilus) mortality. Therefore it was used as dilution agent to screen the effectiveness of fifty two essential oils against this pest. Thirteen essential oils were highly effective, resulting in more than 90% pinewood nematode mortality at 2 mg/mL, with six of them resulting in 100% mortality...

  16. Comparison of bioactive glass, mineral trioxide aggregate, ferric sulfate, and formocresol as pulpotomy agents in rat molar.

    Science.gov (United States)

    Salako, Nathanael; Joseph, Bobby; Ritwik, Priyanshi; Salonen, Jukka; John, Preethi; Junaid, T A

    2003-12-01

    Bioactive glass (BAG) is often used as a filler material for repair of dental bone defects. Although there is evidence of osteogenic potential of this material, it is not clear yet whether the material exhibits potential for dentinogenesis. Hence, the aim of the present study was to evaluate BAG as a pulpotomy agent and to compare it with three commercially available pulpotomy agents such as formocresol (FC), ferric sulfate (FS), and mineral trioxide aggregate (MTA). Pulpotomies were performed in 80 maxillary first molars of Sprague Dawley rats, and pulp stumps were covered with BAG, FC, FS, and MTA. Histologic analysis was performed at 2 weeks and then at 4 weeks after treatment. Experimental samples were compared with contra-lateral normal maxillary first molars. At 2 weeks, BAG showed inflammatory changes in the pulp. After 4 weeks, some samples showed normal pulp histology, with evidence of vasodilation. At 2 weeks, MTA samples showed some acute inflammatory cells around the material with evidence of macrophages in the radicular pulp. Dentine bridge formation with normal pulp histology was a consistent finding at 2 and 4 weeks with MTA. Ferric sulfate showed moderate inflammation of pulp with widespread necrosis in coronal pulp at 2 and 4 weeks. Formocresol showed zones of atrophy, inflammation, and fibrosis. Fibrosis was more extensive at 4 weeks with evidence of calcification in certain samples. Among the materials tested, MTA performed ideally as a pulpotomy agent causing dentine bridge formation while simultaneously maintaining normal pulpal histology. It appeared that BAG induced an inflammatory response at 2 weeks with resolution of inflammation at 4 weeks.

  17. Macromolecular Antioxidants and Dietary Fiber in Edible Seaweeds.

    Science.gov (United States)

    Sanz-Pintos, Nerea; Pérez-Jiménez, Jara; Buschmann, Alejandro H; Vergara-Salinas, José Rodrigo; Pérez-Correa, José Ricardo; Saura-Calixto, Fulgencio

    2017-02-01

    Seaweeds are rich in different bioactive compounds with potential uses in drugs, cosmetics and the food industry. The objective of this study was to analyze macromolecular antioxidants or nonextractable polyphenols, in several edible seaweed species collected in Chile (Gracilaria chilensis, Callophyllis concepcionensis, Macrocystis pyrifera, Scytosyphon lomentaria, Ulva sp. and Enteromorpha compressa), including their 1st HPLC characterization. Macromolecular antioxidants are commonly ignored in studies of bioactive compounds. They are associated with insoluble dietary fiber and exhibit significant biological activity, with specific features that are different from those of both dietary fiber and extractable polyphenols. We also evaluated extractable polyphenols and dietary fiber, given their relationship with macromolecular antioxidants. Our results show that macromolecular antioxidants are a major polyphenol fraction (averaging 42% to total polyphenol content), with hydroxycinnamic acids, hydroxybenzoic acids and flavonols being the main constituents. This fraction also showed remarkable antioxidant capacity, as determined by 2 complementary assays. The dietary fiber content was over 50% of dry weight, with some samples exhibiting the target proportionality between soluble and insoluble dietary fiber for adequate nutrition. Overall, our data show that seaweed could be an important source of commonly ignored macromolecular antioxidants. © 2017 Institute of Food Technologists®.

  18. Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Phuong-Thuy T. Phan

    2017-04-01

    Full Text Available In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+ strains (methicillin-sensitive Staphylococcus aureus (MSSA ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA ATCC 43300, and Streptococcus faecalis (S. faecalis ATCC 29212 and one Gram-(− strain (Escherichia coli (E. coli ATCC 25922. The 2-salicyloylbenzofuran heterocycles were generated by Rap–Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O-ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition and quantitative (MIC antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+ bacterial strains including S. faecalis, MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06–0.12 mM. Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM (8f and 0.12 mM (8h. Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.

  19. Macromolecular Crystallization in Microgravity

    Science.gov (United States)

    Snell, Edward H.; Helliwell, John R.

    2004-01-01

    The key concepts that attracted crystal growers, macromolecular or solid state, to microgravity research is that density difference fluid flows and sedimentation of the growing crystals are greatly reduced. Thus, defects and flaws in the crystals can be reduced, even eliminated, and crystal volume can be increased. Macromolecular crystallography differs from the field of crystalline semiconductors. For the latter, crystals are harnessed for their electrical behaviors. A crystal of a biological macromolecule is used instead for diffraction experiments (X-ray or neutron) to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal of a biological macromolecule then the more molecular structure detail that can be extracted. This structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences with major potential in understanding disease pathologies. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry, and mathematics meet to enable insight to the basic fundamentals of life. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment, and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyze the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural

  20. Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent.

    Science.gov (United States)

    Shaikh, Mubarak H; Subhedar, Dnyaneshwar D; Arkile, Manisha; Khedkar, Vijay M; Jadhav, Nandadeep; Sarkar, Dhiman; Shingate, Bapurao B

    2016-01-15

    In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37μg/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range=14.14-47.11μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents.

  1. Chiral lactic hydrazone derivatives as potential bioactive antibacterial agents: Synthesis, spectroscopic, structural and molecular docking studies

    Science.gov (United States)

    Noshiranzadeh, Nader; Heidari, Azam; Haghi, Fakhri; Bikas, Rahman; Lis, Tadeusz

    2017-01-01

    A series of novel chiral lactic-hydrazone derivatives were synthesized by condensation of (S)-lactic acid hydrazide with salicylaldehyde derivatives and characterized by elemental analysis and spectroscopic studies (FT-IR, 1H NMR and 13C NMR spectroscopy). The structure of one compound was determined by single crystal X-ray analysis. Antibacterial activity of the synthesized compounds was studied against Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli and Pseudomonas aeruginosa as bacterial cultures by broth microdilution method. All of the synthesized compounds showed good antibacterial activity with MIC range of 64-512 μg/mL. Compounds (S,E)-2-hydroxy-N-(2-hydroxy-5-nitrobenzylidene)propanehydrazide (5) and (S,E)-2-hydroxy-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)propanehydrazide (7) were the most effective antibacterial derivatives against S. aureus and E. coli respectively with a MIC value of 64 μg/mL. Bacterial biofilm formation assay showed that these compounds significantly inhibited biofilm formation of P. aeruginosa. Also, in silico molecular docking studies were performed to show lipoteichoic acid synthase (LtaS) inhibitory effect of lactic hydrazone derivatives. The association between electronic and structural effects of some substituents on the benzylidene moiety and the biological activity of these chiral compounds were studied. Structural studies show that compound with higher hydrogen bonding interactions show higher antibacterial activity. The results show chiral hydrazone derivatives based on lactic acid hydrazide could be used as potential lead compounds for developing novel antibacterial agents.

  2. Separation and characterization of the two diastereomers for [Gd(DTPA-bz-NH2)(H2O)]2-, a common synthon in macromolecular MRI contrast agents: their water exchange and isomerization kinetics.

    Science.gov (United States)

    Burai, László; Tóth, Eva; Sour, Angélique; Merbach, André E

    2005-05-16

    Chiral, bifunctional poly(amino carboxylate) ligands are commonly used for the synthesis of macromolecular, Gd(III)-based MRI contrast agents, prepared in the objective of increasing relaxivity or delivering the paramagnetic Gd(III) to a specific site (targeting). Complex formation with such ligands results in two diastereomeric forms for the complex which can be separated by HPLC. We demonstrated that the diastereomer ratio for Ln(III) DTPA derivatives (approximately 60:40) remains constant throughout the lanthanide series, in contrast to Ln(III) EPTPA derivatives, where it varies as a function of the cation size with a maximum for the middle lanthanides (DTPA(5-) = diethylenetriaminepentaacetate; EPTPA(5-) = ethylenepropylenetriaminepentaacetate). The interconversion of the two diastereomers, studied by HPLC, is a proton-catalyzed process (k(obs) = k(1)[H(+)]). It is relatively fast for [Gd(EPTPA-bz-NH(2))(H(2)O)](2-) but slow enough for [Gd(DTPA-bz-NH(2))(H(2)O)](2-) to allow investigation of pure individual isomers (isomerization rate constants are k(1) = (3.03 +/- 0.07) x 10(4) and 11.6 +/- 0.5 s(-1) M(-1) for [Gd(EPTPA-bz-NH(2))(H(2)O)](2)(-) and [Gd(DTPA-bz-NH(2))(H(2)O)](2-), respectively). Individual water exchange rates have been determined for both diastereomers of [Gd(DTPA-bz-NH(2))(H(2)O)](2-) by a variable-temperature (17)O NMR study. Similarly to Ln(III) EPTPA derivatives, k(ex) values differ by a factor of 2 (k(ex)(298) = (5.7 +/- 0.2) x 10(6) and (3.1 +/- 0.1) x 10(6) s(-1)). This variance in the exchange rate has no consequence on the proton relaxivity of the two diastereomers, since it is solely limited by fast rotation. However, such difference in k(ex) will affect proton relaxivity when these diastereomers are linked to a slowly rotating macromolecule. Once the rotation is optimized, slow water exchange will limit relaxivity; thus, a factor of 2 in the exchange rate can lead to a remarkably different relaxivity for the diastereomer complexes

  3. Macromolecular crystallization in microgravity

    Energy Technology Data Exchange (ETDEWEB)

    Snell, Edward H [Biophysics Group, NASA Marshall Space Flight Center, Code XD42, Huntsville, AL 35812 (United States); Helliwell, John R [Department of Chemistry, The University of Manchester, Manchester, M13 9PL (United Kingdom)

    2005-04-01

    Density difference fluid flows and sedimentation of growing crystals are greatly reduced when crystallization takes place in a reduced gravity environment. In the case of macromolecular crystallography a crystal of a biological macromolecule is used for diffraction experiments (x-ray or neutron) so as to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal then the greater the molecular structure detail that can be extracted. It is this structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences, with major potential in understanding disease pathologies. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyse the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural advances. Finally, limitations and alternatives to microgravity and future directions for this research are covered. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry and mathematics meet to enable insight to the fundamentals of life. As the reader will see, there is a great deal of physics involved when the microgravity environment is applied to crystallization, some of it known, and undoubtedly much yet to

  4. Dextran: A promising macromolecular drug carrier

    Directory of Open Access Journals (Sweden)

    Dhaneshwar Suneela

    2006-01-01

    Full Text Available Over the past three decades intensive efforts have been made to design novel systems able to deliver the drug more effectively to the target site. The ongoing intense search for novel and innovative drug delivery systems is predominantly a consequence of the well-established fact that the conventional dosage forms are not sufficiently effective in conveying the drug compound to its site of action and once in the target area, in releasing the active agent over a desired period of time. The potential use of macromolecular prodrugs as a means of achieving targeted drug delivery has attracted considerable interest in recent years. Macromolecules such as antibodies, lipoproteins, lectins, proteins, polypeptides, polysaccharides, natural as well as synthetic polymers offer potential applicabilities as high molecular weight carriers for various therapeutically active compounds. Dextrans serve as one of the most promising macromolecular carrier candidates for a wide variety of therapeutic agents due to their excellent physico-chemical properties and physiological acceptance. The present contribution attempts to review various features of the dextran carrier like its source, structural and physico-chemical characteristics, pharmacokinetic fate and its applications as macromolecular carrier with special emphasis on dextran prodrugs.

  5. Microgravity and Macromolecular Crystallography

    Science.gov (United States)

    Kundrot, Craig E.; Judge, Russell A.; Pusey, Marc L.; Snell, Edward H.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Macromolecular crystal growth has been seen as an ideal experiment to make use of the reduced acceleration environment provided by an orbiting spacecraft. The experiments are small, simply operated and have a high potential scientific and economic impact. In this review we examine the theoretical reasons why microgravity should be a beneficial environment for crystal growth and survey the history of experiments on the Space Shuttle Orbiter, on unmanned spacecraft, and on the Mir space station. Finally we outline the direction for optimizing the future use of orbiting platforms.

  6. Effects of Non-phosphate Macro-molecular Water-retention Agents on Meat Quality%大分子无磷持水剂对肉类品质的影响

    Institute of Scientific and Technical Information of China (English)

    王黎明; 李晶; 龙志芳; 彭恒

    2016-01-01

    It was investigated in this paper that the effects of non-phosphate macro-molecular water-retention agents on the water-retention ability, sensory quality and oxidation resistance of fish meat, shrimp meat and pork. The results showed that sodium alginate can improve obviously the water-retention ability, sensory quality and oxidation resistance of fish meat, shrimp meat and pork. While pectin, xanthan gum, water soluble chitosan can increase obviously the water-retention ability and oxidation resistance of fish meat, shrimp meat and pork. Glucan can improve obviously the water-retention ability and sensory quality of fish meat, shrimp meat and pork.%主要研究常用大分子无磷持水剂对鱼肉、猪肉、虾仁的持水能力、感官品质以及抗氧化能力的影响,以便配制出效果更好的肉类无磷保水剂。研究结果表明,海藻酸钠对鱼肉、虾仁、猪肉的持水能力、感官品质以及抗氧化能力都提高较多,而果胶、黄原胶、水溶性壳聚糖则对鱼肉、虾仁、猪肉的持水能力和抗氧化能力的改善效果较好,聚葡萄糖对鱼肉、虾仁、猪肉的持水能力、感官品质的提高效果较好。

  7. Bioactive behaviour of sol-gel derived antibacterial bioactive glass

    Energy Technology Data Exchange (ETDEWEB)

    Bellantone, M.; Hench, L.L. [Imperial Coll. of Science, Technology and Medicine, London (United Kingdom). Dept. of Materials

    2001-07-01

    A new four-component bioactive glass containing Ag{sub 2}O was produced via the sol-gel process. This system releases Ag{sup +} which is a powerful antibacterial agent. The work reported herein is a comparative study of the bioactivity levels of conventional bioactive glass and of the new antibacterial glass. On the basis of XRD patterns, FTIR spectra, and ICP data, the bioactive behaviour of the two biomaterials is nearly equivalent. (orig.)

  8. Bioactivity-guided fractionation identifies amygdalin as a potent neurotrophic agent from herbal medicine semen persicae extract

    OpenAIRE

    Chuanbin Yang; Jia Zhao; Yuanyuan Cheng; Xuechen Li; Jianhui Rong

    2014-01-01

    Herbal medicine Semen Persicae is widely used to treat blood stasis in Chinese medicine and other oriental folk medicines. Although little is known about the effects of Semen Persicae and its active compounds on neuron differentiation, our pilot study showed that Semen Persicae extract promoted neurite outgrowth in rat dopaminergic PC12 cells. In the present study, we developed a bioactivity-guided fractionation procedure for the characterization of the neurotrophic activity of Semen Persicae...

  9. Liver-targeting macromolecular MRI contrast agents

    Institute of Scientific and Technical Information of China (English)

    XU; Mianyi

    2001-01-01

    Chitosans with various degrees of deacetylation (D.D.), which were used as standard sample for FTIR determination, were prepared from completely deacetylated chitosan by homogeneous N-acetylation reaction. By combining four probable probe bands, i.e. 1655, 1560, 1380 and 1320 cm-1, eight probable reference bands, i.e. 3430, 2920, 2880, 1425, 1155, 1070, 1030 and 895 cm-1 and two baseline methods, the most suitable ratios Aprobe band/Areference band from IR spectra to determine the degree of acetylation of chitosan were evaluated from 48 combinations to be A1560/A2880, A1560/A2920 and A1655/A3430(A1560/A2880 is mostly recommended). The second baseline method, i.e. linking between adjacent two valleys, was better for measuring the absorbances of 1560 and 1655 cm-1 bands. The determination range of the D.D. (1%-100%) covered almost the whole range. The standard curves with A1560/A2880 and A1655/A3430 were also suitable for the determination of degree of substitution of other N-acylated chitosan, such as N-propionyl chitosan, N-butyryl chitosan and N-hexanoyl chitosan.

  10. Sol-gel synthesis of bioactive glass porous scaffolds with addition of porogen agent; Sintese sol-gel de scaffolds porosos de vidro bioativo com adicao de agente porogenico

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes, F.B.A.P.; Barrioni, B.R.; Oliveira, A.C.X.; Oliveira, A.A.R.; Pereira, M.M., E-mail: fabianabapg@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Escola de Engenharia. Dept. Engenharia Metalurgica e de Materiais

    2016-10-15

    The use of biomaterials capable of generating a biological response has been one of the biggest progresses in regenerative medicine, due to their ability to support growth stimulation and damaged tissue regeneration. In this context, bioceramics, particularly bioactive glass (BG), were the subject of many studies. The technique of porogen agent addition for the synthesis of scaffolds is an interesting procedure, because several types of porogen agents can be used. The aim of the present work was to obtain scaffolds using four porogen agents and to evaluate the effects that a change in treatment temperature can have on their crystallinity. Scaffolds of sol-gel bioactive glass 100S (100% SiO{sub 2}) using as porogen agents paraffin 1, paraffin 2, wax and CMC (carboxymethyl cellulose) were synthesized and characterized. As the best results were obtained with paraffin 1, scaffolds 58S (60%SiO{sub 2} -36%CaO-4%P{sub 2}O{sub 5} ) and 100S using paraffin 1 as porogen agent were prepared. The scaffolds were submitted to different treatment temperatures to evaluate the effect on their crystallinity. Pore structure was analyzed by scanning electron microscopy and micro-computed tomography. Scaffolds presented satisfactory pore size and pore size distribution, important characteristics for scaffolds because they allow cell migration, nutrient transport, vascularisation and tissue ingrowth. X-ray powder diffraction showed the amorphous nature of the scaffolds. At 900 °C, scaffolds BG 58S and 100S showed a small increase in crystallinity. BET analysis (N{sub 2} -adsorption) indicated a mesoporous structure. The specific surface area varied from 73.2 m{sup 2} /g for scaffold 58S treated at 800 °C to 331.2 m{sup 2} /g for scaffold 100S treated at 800 °C. The materials obtained showed no toxic effects by MTT cytotoxicity assays. Results showed that the development of scaffolds is possible using porogen agents, with 3D interconnected porous structure and might therefore be a

  11. Bioactive substances

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.

    Chemistry related to certain bioactive molecules, from Indian Ocean Region, developed into drugs or which served as models for the synthesis of more effective bioactive substances or in use in fundamental studies of physiological and biochemical...

  12. Synthesis and bioactive evaluations of novel benzotriazole compounds as potential antimicrobial agents and the interaction with calf thymus DNA

    Indian Academy of Sciences (India)

    Yu Ren; Hui Zhen Zhang; Shao Lin Zhang; Yun Lei Luo; Ling Zhang; Cheng He Zhou; Rong Xia Geng

    2015-12-01

    A novel series of benzotriazole derivatives were synthesized and characterized by NMR, IR and MS spectra. The bioactive assay manifested that most of the new compounds exhibited moderate to good antibacterial and antifungal activities against the tested strains in comparison to reference drugs chloromycin, norfloxacin and fluconazole. Especially, 2,4-dichlorophenyl substituted benzotriazole derivative 6f displayed good antibacterial activity against MRSA with MIC value of 4 g/mL, which was 2-fold more potent than Chloromycin, and it also displayed 3-fold stronger antifungal activity (MIC = 4 g/mL) than fluconazole (MIC = 16 g/mL) against Beer yeast. The preliminary interactive investigations of compound 6f with calf thymus DNA revealed that compound 6f could effectively intercalate into DNA to form compound 6f–DNA complex which might block DNA replication to exert antimicrobial activities. Molecular docking experiments suggested that compound 6f projected into base-pairs of DNA hexamer duplex forming two hydrogen bonds with guanine of DNA. The theoretical calculations were in accordance with the experimental results.

  13. In vitro bioactivity and osteoblast response of porous NiTi synthesized by SHS using nanocrystalline Ni-Ti reaction agent.

    Science.gov (United States)

    Gu, Y W; Li, H; Tay, B Y; Lim, C S; Yong, M S; Khor, K A

    2006-08-01

    Porous NiTi with an average porosity of 55 vol % and a general pore size of 100-600 microm was synthesized by self-propagating high temperature synthesis (SHS) with the addition of mechanically alloyed nanocrystalline Ni-Ti as the reaction agent. The SHS of porous NiTi using elemental powders was also performed for comparison. To enhance the bioactivity of the metal surface, porous NiTi synthesized by nanocrystalline Ni-Ti was subjected to chemical treatment to form a layer of TiO(2) coating. The porous NiTi with TiO(2) coating was subsequently immersed in a simulated body fluid (SBF) to investigate its apatite forming ability. The effects of the addition of nanocrystalline Ni-Ti as reaction agent and the application of apatite coating on osteoblastic behavior were studied in primary cultures of human osteoblast cells. Results showed that the main phases in porous NiTi synthesized by elemental powders were NiTi, Ti(2)Ni, and unreacted free Ni. By using nanocrystalline Ni-Ti as reaction agent, the secondary intermetallic phase of Ti(2)Ni was significantly reduced and the free Ni was eliminated. TiO(2) coating with anatase phase was formed on the surface of porous NiTi after the chemical treatment. A layer consisting of nanocrystalline carbonate-containing apatite was formed on the surface of TiO(2) coating after soaking in SBF. The preliminary cell culture studies showed that the porous NiTi synthesized with the addition of nanocrystalline Ni-Ti attracted marked attachment and proliferation of the osteoblast cells. This gives the evidence of the potential biomedical applications of the porous NiTi.

  14. Bioactivity and structure-activity relationship of cinnamic acid esters and their derivatives as potential antifungal agents for plant protection.

    Science.gov (United States)

    Zhou, Kun; Chen, Dongdong; Li, Bin; Zhang, Bingyu; Miao, Fang; Zhou, Le

    2017-01-01

    A series of cinnamic acid esters and their derivatives were synthesized and evaluated for antifungal activities in vitro against four plant pathogenic fungi by using the mycelium growth rate method. Structure-activity relationship was derived also. Almost all of the compounds showed some inhibition activity on each of the fungi at 0.5 mM. Eight compounds showed the higher average activity with average EC50 values of 17.4-28.6 μg/mL for the fungi than kresoxim-methyl, a commercial fungicide standard, and ten compounds were much more active than commercial fungicide standards carbendazim against P. grisea or kresoxim-methyl against both P. grisea and Valsa mali. Compounds C1 and C2 showed the higher activity with average EC50 values of 17.4 and 18.5 μg/mL and great potential for development of new plant antifungal agents. The structure-activity relationship analysis showed that both the substitution pattern of the phenyl ring and the alkyl group in the alcohol moiety significantly influences the activity. There exists complexly comprehensive effect between the substituents on the phenyl ring and the alkyl group in the alcohol moiety on the activity. Thus, cinnamic acid esters showed great potential the development of new antifungal agents for plant protection due to high activity, natural compounds or natural compound framework, simple structure, easy preparation, low-cost and environmentally friendly.

  15. The bound conformation of microtubule-stabilizing agents: NMR insights into the bioactive 3D structure of discodermolide and dictyostatin.

    Science.gov (United States)

    Canales, Angeles; Matesanz, Ruth; Gardner, Nicola M; Andreu, José Manuel; Paterson, Ian; Díaz, J Fernando; Jiménez-Barbero, Jesús

    2008-01-01

    A protocol based on a combination of NMR experimental data with molecular mechanics calculations and docking procedures has been employed to determine the microtubule-bound conformation of two microtubule-stabilizing agents, discodermolide (DDM) and dictyostatin (DCT). The data indicate that tubulin in assembled microtubules recognizes DDM through a conformational selection process, with minor changes in the molecular skeleton between the major conformer in water solution and that bound to assembled microtubules. For DCT, the deduced bound geometry presents some key conformation differences around certain torsion angles, with respect to the major conformer in solution, and still displays mobility even when bound. The bound conformer of DCT resembles that of DDM and provides very similar contacts with the receptor. Competition experiments indicate that both molecules compete with the taxane-binding site. A model of the binding mode of DDM and DCT to tubulin is proposed.

  16. Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity

    Institute of Scientific and Technical Information of China (English)

    Wen-yuan YU; Li-xia YANG; Jian-shu XIE; Ling ZHOU; Xue-yuan JIANG; De-xu ZHU; Mutsumi MURAMATSU; Ming-wei WANG

    2008-01-01

    Aim: The aim of the present study was to design, synthesize, and evaluate novel antibacterial agents, derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide. Methods: A total of 44 derivatives of aryl-4-guanidin-omethylbenzoate (series A) and N-aryl-4-guanidinomethylbenzamide (series B) were synthesized and their antibacterial activities were assessed in vitro against a variety of Gram-positive and Gram-negative bacteria by an agar dilution method. Results: Twelve compounds showed potent bactericidal effects against a panel of Gram-positive germs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), vancomycin-intermediate Sta-phylococcus aureus (VISA), and methicillin-resistant coagulase-negative staphy-lococci (MRCNS), with minimum inhibitory concentrations (MIC) ranging be-tween 0.5 and 8 μg/mL, which were comparable to the MIC values of several marketed antibiotics. They exhibited weak or no activity on the Gram-negative bacteria tested. In addition, these compounds displayed high inhibitory activities towards oligopeptidase B of bacterial origin. Conclusion: In comparison with the previ-ously reported MIC values of several known antibiotics, the derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide showed com-parable in vitro bactericidal activities against VRE and VISA as linezolid. Their growth inhibitory effects on MRSA were similar to vancomycin, but were less potent than linezolid and vancomycin against MRCNS. This class of compounds may have the potential to be developed into narrow spectrum antibacterial agents against certain drug-resistant strains of bacteria.

  17. Characterization of the bioactive metabolites from a plant growth-promoting rhizobacteria and their exploitation as antimicrobial and plant growth-promoting agents.

    Science.gov (United States)

    George, Emrin; Kumar, S Nishanth; Jacob, Jubi; Bommasani, Bhaskara; Lankalapalli, Ravi S; Morang, P; Kumar, B S Dileep

    2015-05-01

    A plant growth-promoting bacterial strain, PM 105, isolated from a tea plantation soil from the North Eastern region of India was identified as Pseudomonas aeruginosa through classical and 16S ribosomal DNA (rDNA) gene sequencing. Further studies with this strain confirmed broad spectrum antifungal activity against ten human and plant pathogenic fungal pathogens viz. Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus tubingensis, Candida albicans, Colletotrichum gloeosporioides, Fusarium oxysporum, Pencillium expansum, Rhizoctonia solani, Trichophyton rubrum besides growth-promoting property in cowpea (Vigna unguiculata) and pigeon pea (Cajanus cajan). However, no antibacterial property was exhibited by this strain against the four test bacterial pathogens tested in agar overlay method. The crude bioactive metabolites produced by this strain were isolated with three different solvents that exhibited significant antimicrobial and plant growth-promoting activity. Chloroform extract recorded significant antimicrobial and plant growth-promoting activity. Three major compounds viz. 1-hydroxyphenazine, pyocyanin, and phenazine-1-carboxamide were purified and characterized from crude extracts of this strain by various spectral data. The purified compounds recorded prominent antimicrobial activity but failed to establish the plant growth promotion activity in test crop plants under gnotobiotic conditions. Pyocyanin recorded significant antimicrobial activity, and best activity was recorded against T. rubrum (29 mm), followed by P. expansum (28 mm). These results suggest the use of PM 105 as plant growth-promoting agent in crop plants after successful field trials.

  18. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    Science.gov (United States)

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

  19. Modulation of the multidrug efflux pump EmrD-3 from Vibrio cholerae by Allium sativum extract and the bioactive agent allyl sulfide plus synergistic enhancement of antimicrobial susceptibility by A. sativum extract.

    Science.gov (United States)

    Bruns, Merissa M; Kakarla, Prathusha; Floyd, Jared T; Mukherjee, Mun Mun; Ponce, Robert C; Garcia, John A; Ranaweera, Indrika; Sanford, Leslie M; Hernandez, Alberto J; Willmon, T Mark; Tolson, Grace L; Varela, Manuel F

    2017-04-21

    The causative agent of cholera, Vibrio cholerae, is a public health concern. Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies of severe cholera. We previously reported that the multidrug efflux pump EmrD-3 from V. cholerae confers resistance to multiple structurally distinct antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3 efflux pump modulation. The antibacterial activities of garlic Allium sativum, although poorly understood, predicts that a main bioactive component, allyl sulfide, modulates EmrD-3 efflux. Thus, we tested whether A. sativum extract acts in synergy with antimicrobials and that a main bioactive component allyl sulfide inhibits EmrD-3 efflux. We found that A. sativum extract and allyl sulfide inhibited ethidium bromide efflux in cells harboring EmrD-3 and that A. sativum lowered the MICs of multiple antibacterials. We conclude that A. sativum and allyl sulfide inhibit EmrD-3 and that A. sativum extract synergistically enhances antibacterial agents.

  20. Kinetics and Mechanism of Bioactivation via S-Oxygenation of Anti-Tubercular Agent Ethionamide by Peracetic Acid.

    Science.gov (United States)

    Chipiso, Kudzanai; Logan, Isabelle E; Eskew, Matthew W; Omondi, Benard; Simoyi, Reuben H

    2016-10-11

    The kinetics and mechanism of the oxidation of the important antitubercular agent, ethionamide, ETA (2-ethylthioisonicotinamide), by peracetic acid (PAA) have been studied. It is effectively a biphasic reaction with an initial rapid first phase of the reaction which is over in about 5 s and a second slower phase of the reaction which can run up to an hour. The first phase involves the addition of a single oxygen atom to ethionamide to form the S-oxide. The second phase involves further oxidation of the S-oxide to desulfurization of ETA to give 2-ethylisonicotinamide. In contrast to the stability of most organosulfur compounds, the S-oxide of ETA is relatively stable and can be isolated. In conditions of excess ETA, the stoichiometry of the reaction was strictly 1:1: CH3CO3H + Et(C5H4)C(═S)NH2 → CH3CO2H + Et(C5H4)C(═NH)SOH. In this oxidation, it was apparent that only the sulfur center was the reactive site. Though ETA was ultimately desulfurized, only the S-oxide was stable. Electrospray ionization (ESI) spectral analysis did not detect any substantial formation of the sulfinic and sulfonic acids. This suggests that cleavage of the carbon-sulfur bond occurs at the sulfenic acid stage, resulting in the formation of an unstable sulfur species that can react further to form more stable sulfur species. In this oxidation, no sulfate formation was observed. ESI spectral analysis data showed a final sulfur species in the form of a dimeric sulfur monoxide species, H3S2O2. We derived a bimolecular rate constant for the formation of the S-oxide of (3.08 ± 0.72) × 10(2) M(-1) s(-1). Oxidation of the S-oxide further to give 2-ethylisonicotinamide gave zero order kinetics.

  1. Recent progress in fungus-derived bioactive agents for targeting of signaling machinery in cancer cells

    Directory of Open Access Journals (Sweden)

    Lin X

    2015-03-01

    Full Text Available Xiukun Lin,1 Ammad Ahmad Farooqi,2 Muhammad Ismail2 1Department of Pharmacology, Capital Medical University, Beijing, People’s Republic of China; 2Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan Abstract: It is becoming increasingly understood that tumor cells may have different mutations and dependencies on diverse intracellular signaling cascades for survival or metastatic potential. Overexpression of oncogenes, inactivation of tumor suppressor genes, genetic/epigenetic mutations, genomic instability, and loss of apoptotic cell death are some of the mechanisms that have been widely investigated in molecular oncology. We partition this multicomponent review into the most recent evidence on the anticancer activity of fungal substances obtained from in vitro and xenografted models, and these fungal substances modulate expression of oncogenic and tumor suppressor miRNAs.  There are some outstanding questions regarding fungus-derived chemical-induced modulation of intracellular signaling networks in different cancer cell lines and preclinical models. Certain hints have emerged, emphasizing mechanisms via which apoptosis can be restored in TRAIL-resistant cancer cells. Reconceptualization of the knowledge obtained from these emerging areas of research will enable us to potentially identify natural agents with notable anticancer activity and minimal off-target effects. Integration of experimentally verified evidence obtained from cancer cell line gene expression with large-scale functional screening results and pharmacological sensitivity data will be helpful in identification of therapeutics with substantial efficacy. New tools and technologies will further deepen our understanding of the signaling networks that underlie the development of cancer, metastasis, and resistance to different therapeutics at both a personal and systems-wide level. Keywords: fungal products, cell signaling, cancer, apoptosis, miRNA, xenograft

  2. Macromolecular architectures for organic photovoltaics.

    Science.gov (United States)

    Popere, Bhooshan C; Della Pelle, Andrea M; Poe, Ambata; Thayumanavan, S

    2012-03-28

    Research in the field of organic photovoltaics has gained considerable momentum in the last two decades owing to the need for developing low-cost and efficient energy harvesting systems. Elegant molecular architectures have been designed, synthesized and employed as active materials for photovoltaic devices thereby leading to a better molecular structure-device property relationship understanding. In this perspective, we outline new macromolecular scaffolds that have been designed within the purview of each of the three fundamental processes involving light harvesting, charge separation and charge transport.

  3. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available BACKGROUND: Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins. METHODOLOGY/PRINCIPAL FINDINGS: As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l. CONCLUSIONS/SIGNIFICANCE: We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of

  4. Emergent Property in Macromolecular Motion

    Institute of Scientific and Technical Information of China (English)

    吴嘉麟

    2003-01-01

    In this paper, the model of inverse cascade fractal super-blocks along one direction (in the positive or negative) in the 3-dimensional space is developed to describe the self-similar motion in macromolecular system. Microscopically the cohesive and dispersed states of the motion blocks are co-existent states with vastly different probability of occurrence.Experimental results and theoretical analysis show that the microscopic cohesive state energy and dispersed state energy of each motion block are respectively equal to the macroscopic glassy state energy kT8 and molten state energy kTm of the system. This singularity unveils topologically the nonintegrability, mathematically the anholonomy, and macroscopically the emergent property. This singularity also reveals that the glass, viscoelastic and melt states are three distinct emergent properties of macromolecular motion from a macroscopic viewpoint. The fractal concept of excluded volume is introduced to depict the random motion at various scales in the system. The Hausdorff dimensions of the excluded volune and the motion blocks are both found equal to 3/2.

  5. Data Mining of Macromolecular Structures.

    Science.gov (United States)

    van Beusekom, Bart; Perrakis, Anastassis; Joosten, Robbie P

    2016-01-01

    The use of macromolecular structures is widespread for a variety of applications, from teaching protein structure principles all the way to ligand optimization in drug development. Applying data mining techniques on these experimentally determined structures requires a highly uniform, standardized structural data source. The Protein Data Bank (PDB) has evolved over the years toward becoming the standard resource for macromolecular structures. However, the process selecting the data most suitable for specific applications is still very much based on personal preferences and understanding of the experimental techniques used to obtain these models. In this chapter, we will first explain the challenges with data standardization, annotation, and uniformity in the PDB entries determined by X-ray crystallography. We then discuss the specific effect that crystallographic data quality and model optimization methods have on structural models and how validation tools can be used to make informed choices. We also discuss specific advantages of using the PDB_REDO databank as a resource for structural data. Finally, we will provide guidelines on how to select the most suitable protein structure models for detailed analysis and how to select a set of structure models suitable for data mining.

  6. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair......, and gene regulation, at both transcriptional and translational levels. Udgivelsesdato: 1999-Jul...

  7. Bioactive Peptides

    Directory of Open Access Journals (Sweden)

    Eric Banan-Mwine Daliri

    2017-04-01

    Full Text Available The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  8. Bioactive Peptides.

    Science.gov (United States)

    Daliri, Eric Banan-Mwine; Oh, Deog H; Lee, Byong H

    2017-04-26

    The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  9. Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics.

    Science.gov (United States)

    Lönn, Peter; Kacsinta, Apollo D; Cui, Xian-Shu; Hamil, Alexander S; Kaulich, Manuel; Gogoi, Khirud; Dowdy, Steven F

    2016-09-08

    Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

  10. Macromolecular Crowding Modulates Folding Mechanism of α/β Protein Apoflavodoxin

    Science.gov (United States)

    Homouz, D.; Stagg, L.; Wittungstafshede, P.; Cheung, M.

    2009-01-01

    Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.

  11. Analysis of Tagish Lake macromolecular organic material

    OpenAIRE

    Gilmour, I; Pearson, V. K.; Sephton, M.A.

    2001-01-01

    Macromolecular material is, by far, the major organic component of meteorites. Flash pyrolysis GCMS has been used to investigate this organic component in Tagish Lake. It is more condensed, less susbtituted than Murchson.

  12. Automated data collection for macromolecular crystallography.

    Science.gov (United States)

    Winter, Graeme; McAuley, Katherine E

    2011-09-01

    An overview, together with some practical advice, is presented of the current status of the automation of macromolecular crystallography (MX) data collection, with a focus on MX beamlines at Diamond Light Source, UK.

  13. Macromolecular crowding: Macromolecules friend or foe.

    Science.gov (United States)

    Mittal, Shruti; Chowhan, Rimpy Kaur; Singh, Laishram Rajendrakumar

    2015-09-01

    Cellular interior is known to be densely crowded due to the presence of soluble and insoluble macromolecules, which altogether occupy ~40% of the total cellular volume. This results in altered biological properties of macromolecules. Macromolecular crowding is observed to have both positive and negative effects on protein folding, structure, stability and function. Significant data has been accumulated so far on both the aspects. However, most of the review articles so far have focused on the positive aspect of macromolecular crowding and not much attention has been paid on the deleterious aspect of crowding on macromolecules. In order to have a complete knowledge of the effect of macromolecular crowding on proteins and enzymes, it is important to look into both the aspects of crowding to determine its precise role under physiological conditions. To fill the gap in the understanding of the effect of macromolecular crowding on proteins and enzymes, this review article focuses on the deleterious influence of crowding on macromolecules. Macromolecular crowding is not always good but also has several deleterious effects on various macromolecular properties. Taken together, the properties of biological macromolecules in vivo appears to be finely regulated by the nature and level of the intracellular crowdedness in order to perform their biological functions appropriately. The information provided here gives an understanding of the role played by the nature and level of cellular crowdedness in intensifying and/or alleviating the burden of various proteopathies. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Energy transfer in macromolecular arrays

    Science.gov (United States)

    Andrews, David L.; Jenkins, Robert D.

    2003-11-01

    Macromolecular systems comprised of many light-sensitive centres (the photosynthetic unit, dendrimers, and other highly symmetric multichromophore arrays) are important structures offering challenges to theoreticians and synthetic chemists alike. Here we outline novel photophysical interactions predicted and observed in such arrays. Using the tools of molecular quantum electrodynamics (QED) we present quantum amplitudes for a variety of higher-order resonance energy transfer (RET) schemes associated with well-known nonlinear optical effects such as two- and three-photon absorption. The initial analysis is extended to account for situations where the participant donor species are identical and exist in a highly symmetric environment, leading to the possible formation of excitons. It emerges from the QED theory that such excitons are closely associated with the higher-order RET processes. General results are interpreted by analyzing particular molecular architectures which offer interesting features such as rate enhancement or limitation and exciton pathway quenching. Applications in the areas of photosynthesis, molecular logic gates and low-intensity fluorescence energy transfer are predicted.

  15. Influence of protein crowder size on hydration structure and dynamics in macromolecular crowding

    Science.gov (United States)

    Wang, Po-hung; Yu, Isseki; Feig, Michael; Sugita, Yuji

    2017-03-01

    We investigate the effects of protein crowder sizes on hydration structure and dynamics in macromolecular crowded systems by all-atom MD simulations. The crowded systems consisting of only small proteins showed larger total surface areas than those of large proteins at the same volume fractions. As a result, more water molecules were trapped within the hydration shells, slowing down water diffusion. The simulation results suggest that the protein crowder size is another factor to determine the effect of macromolecular crowding and to explain the experimental kinetic data of proteins and DNAs in the presence of crowding agents.

  16. ARGET ATRP合成大分子偶联剂PMMA-b-PTMSPMA及其对玻璃表面的接枝%Synthesis of Macromolecular Coupling Agent PMMA-b-PTMSPMA by ARGET ATRP and Its Application in Modification of the Glass Surface

    Institute of Scientific and Technical Information of China (English)

    孙婷婷; 任强; 李坚

    2013-01-01

    以电子转移再生催化剂的原子转移自由基聚合(ARGET ATRP)成功合成了大分子硅烷偶联剂即聚甲基丙烯酸甲酯-b-3-甲基丙烯酰氧基丙基三甲氧基硅烷(PMMA-b-PTMSPMA).利用所制得的大分子偶联剂对玻璃表面进行了接枝改性,对改性后的玻璃表面形态及疏水性能进行了研究.结果表明,以CuBr2/PMDETA络合物为催化体系,溴化铜(CuBr2)用量为n(CuBr2)/n(单体)=5×10-4时,PMMA段以辛酸亚锡(Sn(EH)2)为还原剂,PTMSPMA段以铜(Cu)为还原剂,用ARGET ATRP两步法成功制备了嵌段共聚物PMMA-b-PTMSPMA.采用“接枝到(graft onto)”方法,在温和的条件下,在玻璃表面接枝上了大分子偶联剂.玻璃表面的接触角可从30°提高到65°,提高了玻璃表面的疏水性.%Macromolecular silane coupling agent,poly (methyl methacrylate-b-3-methacrylic acyloxy propyl trimethoxysilane) (PMMA-b-PTMSPMA) was successfully synthesized by electron transfer for atom transfer radical polymerization(ARGET ATRP).The structure and properties of block copolymer were characterized by 1H-NMR,GPC and TGA.The morphology and hydrophobic property of grafted glass were investigated.The results show that the block copolymer PMMA-b-PTMSPMA with designed molecular weight of 15000 was successfully synthesized by ARGET ATRP,using CuBr2/PMDETA complex as catalyst system (the catalyst content n (CuBr2) is 5 × 10-4 of n (monomer)).In synthesizing PMMA segment,Sn(EH)2 was used as the reducing agent and in preparing PTMSPMA segment copper was used as the reducing agent.Under mild conditions,the macromolecular coupling agent was grafted onto the surface of glass by the "graft onto" technique.The contact angle of the glass increases from 30° to 70° after the block copolymer grafted onto the glass surface,resulting in the improvement of hydrophobicity of glass surface.The AFM images show that the surface of glass is covered with the different size of aggregates of the block copolymer.

  17. 78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

    Science.gov (United States)

    2013-12-23

    ... macromolecular MRI contrast agents such as chelated Gd(III). These macromolecular imaging agents have clearance... Enhanced Delivery of a Therapeutic Agent With a Surrogate Tracer for Treating Cancer and Urological... Agents'', U.S. Provisional Patent Application 60/413,673 (filed September 24, 2002;...

  18. Porous bioactive materials

    Science.gov (United States)

    Zhang, Kai

    Bioactive materials chemically bond to tissues through the development of biologically active apatite. Porous structures in biomaterials are designed to enhance bioactivity, grow artificial tissues and achieve better integration with host tissues in the body. The goal of this research is to design, fabricate and characterize novel porous bioactive materials. 3D ordered macroporous bioactive glasses (3DOM-BGs, pore size: 200--1000 nm) were prepared using a sol-gel process and colloidal crystal templates. 3DOM-BGs are more bioactive and degradable than mesoporous (pore size simulated body fluid (SBF). Apatite formation and 3DOM-BG degradation rates increased with the decrease of soaking ratio. Apatite induction time in SBF increased with 3DOM-BG calcination temperature (600--800°C). Apatite formation and 3DOMBG degradation were slightly enhanced for a phosphate containing composition. Large 3DOM-BG particles formed less apatite and degraded less completely as compared with small particles. An increase in macropore size slowed down 3DOM-BG degradation and apatite formation processes. After heating the converted apatite at a temperature higher than 700°C, highly crystalline hydroxyapatite and a minor tri-calcium phosphate phase formed. 3DOM-BGs have potential applications as bone/periodontal fillers, and drugs and biological factors delivery agents. Anchoring artificial soft tissues (e.g., cartilage) to native bone presents a challenge. Porous polymer/bioactive glass composites are candidate materials for engineering artificial soft tissue/bone interfaces. Porous composites consisting of polymer matrices (e.g., polysulfone, polylactide, and polyurethane) and bioactive glass particles were prepared by polymer phase separation techniques adapted to include ceramic particles. Composites (thickness: 200--500 mum) have asymmetric structures with dense top layers and porous structures beneath. Porous structures consist of large pores (>100 mum) in a network of smaller (<10

  19. Effects of macromolecular crowding on genetic networks.

    Science.gov (United States)

    Morelli, Marco J; Allen, Rosalind J; Wolde, Pieter Rein ten

    2011-12-21

    The intracellular environment is crowded with proteins, DNA, and other macromolecules. Under physiological conditions, macromolecular crowding can alter both molecular diffusion and the equilibria of bimolecular reactions and therefore is likely to have a significant effect on the function of biochemical networks. We propose a simple way to model the effects of macromolecular crowding on biochemical networks via an appropriate scaling of bimolecular association and dissociation rates. We use this approach, in combination with kinetic Monte Carlo simulations, to analyze the effects of crowding on a constitutively expressed gene, a repressed gene, and a model for the bacteriophage λ genetic switch, in the presence and absence of nonspecific binding of transcription factors to genomic DNA. Our results show that the effects of crowding are mainly caused by the shift of association-dissociation equilibria rather than the slowing down of protein diffusion, and that macromolecular crowding can have relevant and counterintuitive effects on biochemical network performance.

  20. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair......Although proteins and nucleic acids consist of different chemical components, proteins can mimic structures and possibly also functions of nucleic acids. Recently, structural mimicry was observed between two elongation factors in bacterial protein biosynthesis leading to the introduction...

  1. Spectroscopic and molecular docking studies on N,N-di-tert-butoxycarbonyl (Boc)-2-amino pyridine: A potential bioactive agent for lung cancer treatment

    Science.gov (United States)

    Mohamed Asath, R.; Premkumar, R.; Mathavan, T.; Milton Franklin Benial, A.

    2017-09-01

    Potential energy surface scan was performed and the most stable molecular structure of the N,N-di-tert-butoxycarbonyl (Boc)-2-amino pyridine (DBAP) molecule was predicted. The most stable molecular structure of the molecule was optimized using B3LYP method with cc-pVTZ basis set. Anticancer activity of the DBAP molecule was evaluated by molecular docking analysis. The structural parameters and vibrational wavenumbers were calculated for the optimized molecular structure. The experimental and theoretical wavenumbers were assigned and compared. Ultraviolet-Visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated and Fukui function calculations were also carried out to investigate the reactive nature of the DBAP molecule. The natural bond orbital analysis was also performed to probe the intramolecular interactions and confirm the bioactivity of the DBAP molecule. The molecular docking analysis reveals the better inhibitory nature of the DBAP molecule against the epidermal growth factor receptor (EGFR) protein which causes lung cancer. Hence, the present study unveils the structural and bioactive nature of the title molecule. The DBAP molecule was identified as a potential inhibitor against the lung cancer which may be useful in further development of drug designing in the treatment of lung cancer.

  2. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents.

    Science.gov (United States)

    De Monte, Celeste; Bizzarri, Bruna; Gidaro, Maria Concetta; Carradori, Simone; Mollica, Adriano; Luisi, Grazia; Granese, Arianna; Alcaro, Stefano; Costa, Giosuè; Basilico, Nicoletta; Parapini, Silvia; Scaltrito, Maria Maddalena; Masia, Carla; Sisto, Francesca

    2015-12-01

    Crocus sativus L. is known in herbal medicine for the various pharmacological effects of its components, but no data are found in literature about its biological properties toward Helicobacter pylori, Plasmodium spp. and Leishmania spp. In this work, the potential anti-bacterial and anti-parasitic effects of crocin and safranal, two important bioactive components in C. sativus, were explored, and also some semi-synthetic derivatives of safranal were tested in order to establish which modifications in the chemical structure could improve the biological activity. According to our promising results, we virtually screened our compounds by means of molecular modeling studies against the main H. pylori enzymes in order to unravel their putative mechanism of action.

  3. Revealing the macromolecular targets of complex natural products

    Science.gov (United States)

    Reker, Daniel; Perna, Anna M.; Rodrigues, Tiago; Schneider, Petra; Reutlinger, Michael; Mönch, Bettina; Koeberle, Andreas; Lamers, Christina; Gabler, Matthias; Steinmetz, Heinrich; Müller, Rolf; Schubert-Zsilavecz, Manfred; Werz, Oliver; Schneider, Gisbert

    2014-12-01

    Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product ‘de-orphaning’.

  4. Bioactive constituents of Corni Fructus: The therapeutic use of morroniside, loganin, and 7-O-galloyl-D-sedoheptulose as renoprotective agents in type 2 diabetes.

    Science.gov (United States)

    Yokozawa, T; Kang, K S; Park, C H; Noh, J S; Yamabe, N; Shibahara, N; Tanaka, T

    2010-08-01

    Corni Fructus, the fruit of Cornus officinalis Sieb. et Zucc. (Cornaceae), is an important crude herb used in Chinese medicine to exhibit several biological activities, including hypoglycemic, antineoplastic, and antimicrobial effects, and to improve liver and kidney functions. We have been investigating the mechanism and bioactive constituents of Corni Fructus using diabetic animal models. Morroniside, loganin, and 7-O-galloyl-D-sedoheptulose, the main active compounds of Corni Fructus, exhibit the same lowering effects of elevated triglyceride, oxidative stress and advanced glycation endproduct (AGE) formation in the kidney of db/db mice. The effects of morroniside and 7-O-galloyl-D-sedoheptulose were mediated through modulation by renal sterol regulatory element binding proteins and nuclear factor-kappa B expression, but the effect of loganin was presumably mediated by hypoglycemic and antioxidant effects in the kidney, and also indirectly by the amelioration of metabolic disorders in other organs such as the liver. These findings led us to conclude that morroniside, loganin, and 7-O-galloyl-D-sedoheptulose would synergistically contribute to the inhibition of metabolic disorders (hyperglycemia and dyslipidemia), oxidative stress, inflammation, as well as AGE formation in the diabetic kidney.

  5. Statistics of Multiscale Fluctuations in Macromolecular Systems

    CERN Document Server

    Yukalov, V I

    2012-01-01

    An approach is suggested for treating multiscale fluctuations in macromolecular systems. The emphasis is on the statistical properties of such fluctuations. The approach is illustrated by a macromolecular system with mesoscopic fluctuations between the states of atomic orbitals. Strong-orbital and weak-orbital couplings fluctuationally arise, being multiscale in space and time. Statistical properties of the system are obtained by averaging over the multiscale fluctuations. The existence of such multiscale fluctuations causes phase transitions between strong-coupling and weak-coupling states. These transitions are connected with structure and size transformations of macromolecules. An approach for treating density and size multiscale fluctuations by means of classical statistical mechanics is also advanced.

  6. In situ macromolecular crystallography using microbeams.

    Science.gov (United States)

    Axford, Danny; Owen, Robin L; Aishima, Jun; Foadi, James; Morgan, Ann W; Robinson, James I; Nettleship, Joanne E; Owens, Raymond J; Moraes, Isabel; Fry, Elizabeth E; Grimes, Jonathan M; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S; Stuart, David I; Evans, Gwyndaf

    2012-05-01

    Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams.

  7. Growth and dissolution of macromolecular Markov chains

    CERN Document Server

    Gaspard, Pierre

    2016-01-01

    The kinetics and thermodynamics of free living copolymerization are studied for processes with rates depending on k monomeric units of the macromolecular chain behind the unit that is attached or detached. In this case, the sequence of monomeric units in the growing copolymer is a kth-order Markov chain. In the regime of steady growth, the statistical properties of the sequence are determined analytically in terms of the attachment and detachment rates. In this way, the mean growth velocity as well as the thermodynamic entropy production and the sequence disorder can be calculated systematically. These different properties are also investigated in the regime of depolymerization where the macromolecular chain is dissolved by the surrounding solution. In this regime, the entropy production is shown to satisfy Landauer's principle.

  8. Growth and Dissolution of Macromolecular Markov Chains

    Science.gov (United States)

    Gaspard, Pierre

    2016-07-01

    The kinetics and thermodynamics of free living copolymerization are studied for processes with rates depending on k monomeric units of the macromolecular chain behind the unit that is attached or detached. In this case, the sequence of monomeric units in the growing copolymer is a kth-order Markov chain. In the regime of steady growth, the statistical properties of the sequence are determined analytically in terms of the attachment and detachment rates. In this way, the mean growth velocity as well as the thermodynamic entropy production and the sequence disorder can be calculated systematically. These different properties are also investigated in the regime of depolymerization where the macromolecular chain is dissolved by the surrounding solution. In this regime, the entropy production is shown to satisfy Landauer's principle.

  9. Smoothing techniques for macromolecular global optimization

    Energy Technology Data Exchange (ETDEWEB)

    More, J.J.; Wu, Zhijun

    1995-09-01

    We study global optimization problems that arise in macromolecular modeling, and the solution of these problems via continuation and smoothing. Our results unify and extend the theory associated with the use of the Gaussian transform for smoothing. We show that the, Gaussian transform can be viewed as a special case of a generalized transform and that these generalized transforms share many of the properties of the Gaussian transform. We also show that the smoothing behavior of the generalized transform can be studied in terms of the Fourier transform and that these results indicate that the Gaussian transform has superior smoothing properties.

  10. Celebrating macromolecular crystallography: A personal perspective

    Directory of Open Access Journals (Sweden)

    Abad-Zapatero, Celerino

    2015-04-01

    Full Text Available The twentieth century has seen an enormous advance in the knowledge of the atomic structures that surround us. The discovery of the first crystal structures of simple inorganic salts by the Braggs in 1914, using the diffraction of X-rays by crystals, provided the critical elements to unveil the atomic structure of matter. Subsequent developments in the field leading to macromolecular crystallography are presented with a personal perspective, related to the cultural milieu of Spain in the late 1950’s. The journey of discovery of the author, as he developed professionally, is interwoven with the expansion of macromolecular crystallography from the first proteins (myoglobin, hemoglobin to the ‘coming of age’ of the field in 1971 and the discoveries that followed, culminating in the determination of the structure of the ribosomes at the turn of the century. A perspective is presented exploring the future of the field and also a reflection about the future generations of Spanish scientists.El siglo XX ha sido testigo del increíble avance que ha experimentado el conocimiento de la estructura atómica de la materia que nos rodea. El descubrimiento de las primeras estructuras atómicas de sales inorgánicas por los Bragg en 1914, empleando difracción de rayos X con cristales, proporcionó los elementos clave para alcanzar tal conocimiento. Posteriores desarrollos en este campo, que condujeron a la cristalografía macromolecular, se presentan aquí desde una perspectiva personal, relacionada con el contexto cultural de la España de la década de los 50. La experiencia del descubrimiento científico, durante mi desarrollo profesional, se integra en el desarrollo de la cristalografía macromolecular, desde las primeras proteínas (míoglobina y hemoglobina, hasta su madurez en 1971 que, con los posteriores descubrimientos, culmina con la determinación del la estructura del ribosoma. Asimismo, se explora el futuro de esta disciplina y se

  11. Multiscale macromolecular simulation: role of evolving ensembles.

    Science.gov (United States)

    Singharoy, A; Joshi, H; Ortoleva, P J

    2012-10-22

    Multiscale analysis provides an algorithm for the efficient simulation of macromolecular assemblies. This algorithm involves the coevolution of a quasiequilibrium probability density of atomic configurations and the Langevin dynamics of spatial coarse-grained variables denoted order parameters (OPs) characterizing nanoscale system features. In practice, implementation of the probability density involves the generation of constant OP ensembles of atomic configurations. Such ensembles are used to construct thermal forces and diffusion factors that mediate the stochastic OP dynamics. Generation of all-atom ensembles at every Langevin time step is computationally expensive. Here, multiscale computation for macromolecular systems is made more efficient by a method that self-consistently folds in ensembles of all-atom configurations constructed in an earlier step, history, of the Langevin evolution. This procedure accounts for the temporal evolution of these ensembles, accurately providing thermal forces and diffusions. It is shown that efficiency and accuracy of the OP-based simulations is increased via the integration of this historical information. Accuracy improves with the square root of the number of historical timesteps included in the calculation. As a result, CPU usage can be decreased by a factor of 3-8 without loss of accuracy. The algorithm is implemented into our existing force-field based multiscale simulation platform and demonstrated via the structural dynamics of viral capsomers.

  12. Macromolecular recognition in the Protein Data Bank

    Energy Technology Data Exchange (ETDEWEB)

    Janin, Joël, E-mail: joel.janin@ibbmc.u-psud.fr [Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France); Institut de Biochimie et Biologie Moléculaire et Cellulaire, UMR8619, Bâtiment 430, Université Paris-Sud, 91405 Orsay (France); Rodier, Francis [Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France); Chakrabarti, Pinak [Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054 (India); Bahadur, Ranjit P. [Institut de Biochimie et Biologie Moléculaire et Cellulaire, UMR8619, Bâtiment 430, Université Paris-Sud, 91405 Orsay (France); Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054 (India); Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France)

    2007-01-01

    X-ray structures in the PDB illustrate both the specific recognition of two polypeptide chains in protein–protein complexes and dimeric proteins and their nonspecific interaction at crystal contacts. Crystal structures deposited in the Protein Data Bank illustrate the diversity of biological macromolecular recognition: transient interactions in protein–protein and protein–DNA complexes and permanent assemblies in homodimeric proteins. The geometric and physical chemical properties of the macromolecular interfaces that may govern the stability and specificity of recognition are explored in complexes and homodimers compared with crystal-packing interactions. It is found that crystal-packing interfaces are usually much smaller; they bury fewer atoms and are less tightly packed than in specific assemblies. Standard-size interfaces burying 1200–2000 Å{sup 2} of protein surface occur in protease–inhibitor and antigen–antibody complexes that assemble with little or no conformation changes. Short-lived electron-transfer complexes have small interfaces; the larger size of the interfaces observed in complexes involved in signal transduction and homodimers correlates with the presence of conformation changes, often implicated in biological function. Results of the CAPRI (critical assessment of predicted interactions) blind prediction experiment show that docking algorithms efficiently and accurately predict the mode of assembly of proteins that do not change conformation when they associate. They perform less well in the presence of large conformation changes and the experiment stimulates the development of novel procedures that can handle such changes.

  13. Rotation-Induced Macromolecular Spooling of DNA

    Directory of Open Access Journals (Sweden)

    Tyler N. Shendruk

    2017-07-01

    Full Text Available Genetic information is stored in a linear sequence of base pairs; however, thermal fluctuations and complex DNA conformations such as folds and loops make it challenging to order genomic material for in vitro analysis. In this work, we discover that rotation-induced macromolecular spooling of DNA around a rotating microwire can monotonically order genomic bases, overcoming this challenge. We use single-molecule fluorescence microscopy to directly visualize long DNA strands deforming and elongating in shear flow near a rotating microwire, in agreement with numerical simulations. While untethered DNA is observed to elongate substantially, in agreement with our theory and numerical simulations, strong extension of DNA becomes possible by introducing tethering. For the case of tethered polymers, we show that increasing the rotation rate can deterministically spool a substantial portion of the chain into a fully stretched, single-file conformation. When applied to DNA, the fraction of genetic information sequentially ordered on the microwire surface will increase with the contour length, despite the increased entropy. This ability to handle long strands of DNA is in contrast to modern DNA sample preparation technologies for sequencing and mapping, which are typically restricted to comparatively short strands, resulting in challenges in reconstructing the genome. Thus, in addition to discovering new rotation-induced macromolecular dynamics, this work inspires new approaches to handling genomic-length DNA strands.

  14. Rotation-Induced Macromolecular Spooling of DNA

    Science.gov (United States)

    Shendruk, Tyler N.; Sean, David; Berard, Daniel J.; Wolf, Julian; Dragoman, Justin; Battat, Sophie; Slater, Gary W.; Leslie, Sabrina R.

    2017-07-01

    Genetic information is stored in a linear sequence of base pairs; however, thermal fluctuations and complex DNA conformations such as folds and loops make it challenging to order genomic material for in vitro analysis. In this work, we discover that rotation-induced macromolecular spooling of DNA around a rotating microwire can monotonically order genomic bases, overcoming this challenge. We use single-molecule fluorescence microscopy to directly visualize long DNA strands deforming and elongating in shear flow near a rotating microwire, in agreement with numerical simulations. While untethered DNA is observed to elongate substantially, in agreement with our theory and numerical simulations, strong extension of DNA becomes possible by introducing tethering. For the case of tethered polymers, we show that increasing the rotation rate can deterministically spool a substantial portion of the chain into a fully stretched, single-file conformation. When applied to DNA, the fraction of genetic information sequentially ordered on the microwire surface will increase with the contour length, despite the increased entropy. This ability to handle long strands of DNA is in contrast to modern DNA sample preparation technologies for sequencing and mapping, which are typically restricted to comparatively short strands, resulting in challenges in reconstructing the genome. Thus, in addition to discovering new rotation-induced macromolecular dynamics, this work inspires new approaches to handling genomic-length DNA strands.

  15. The role of macromolecular stability in desiccation tolerance

    NARCIS (Netherlands)

    Wolkers, W.F.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular st

  16. The role of macromolecular stability in desiccation tolerance.

    NARCIS (Netherlands)

    Wolkers, W.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular structures

  17. Macromolecular (pro)drugs with concurrent direct activity against the hepatitis C virus and inflammation.

    Science.gov (United States)

    Wohl, Benjamin M; Smith, Anton A A; Jensen, Bettina E B; Zelikin, Alexander N

    2014-12-28

    Macromolecular prodrugs (MPs) are a powerful tool to alleviate side-effects and improve the efficacy of the broad-spectrum antiviral agent ribavirin. In this work, we sought an understanding of what makes an optimal formulation within the macromolecular parameter space--nature of the polymer carrier, average molar mass, drug loading, or a good combination thereof. A panel of MPs based on biocompatible synthetic vinylic and (meth)acrylic polymers was tested in an anti-inflammatory assay with relevance to alleviating inflammation in the liver during hepatitis C infection. Pristine polymer carriers proved to have a pronounced anti-inflammatory activity, a notion which may prove significant in developing MPs for antiviral and anticancer treatments. With conjugated ribavirin, MPs revealed enhanced activity but also higher toxicity. Therapeutic windows and therapeutic indices were determined and discussed to reveal the most potent formulation and those with optimized safety. Polymers were also tested as inhibitors of replication of the hepatitis C viral RNA using a subgenomic viral replicon system. For the first time, negatively charged polymers are revealed to have an intracellular activity against hepatitis C virus replication. Concerted activity of the polymer and ribavirin afforded MPs which significantly increased the therapeutic index of ribavirin-based treatment. Taken together, the systematic investigation of the macromolecular space identified lead candidates with high efficacy and concurrent direct activity against the hepatitis C virus and inflammation.

  18. Macromolecular crowding for tailoring tissue-derived fibrillated matrices.

    Science.gov (United States)

    Magno, Valentina; Friedrichs, Jens; Weber, Heather M; Prewitz, Marina C; Tsurkan, Mikhail V; Werner, Carsten

    2017-06-01

    Tissue-derived fibrillated matrices can be instrumental for the in vitro reconstitution of multiphasic extracellular microenvironments. However, despite of several advantages, the obtained scaffolds so far offer a rather narrow range of materials characteristics only. In this work, we demonstrate how macromolecular crowding (MMC) - the supplementation of matrix reconstitution media with synthetic or natural macromolecules in ways to create excluded volume effects (EVE) - can be employed for tailoring important structural and biophysical characteristics of kidney-derived fibrillated matrices. Porcine kidneys were decellularized, ground and the obtained extracellular matrix (ECM) preparations were reconstituted under varied MMC conditions. We show that MMC strongly influences the fibrillogenesis kinetics and impacts the architecture and the elastic modulus of the reconstituted matrices, with diameters and relative alignment of fibrils increasing at elevated concentrations of the crowding agent Ficoll400, a nonionic synthetic polymer of sucrose. Furthermore, we demonstrate how MMC modulates the distribution of key ECM molecules within the reconstituted matrix scaffolds. As a proof of concept, we compared different variants of kidney-derived fibrillated matrices in cell culture experiments referring to specific requirements of kidney tissue engineering approaches. The results revealed that MMC-tailored matrices support the morphogenesis of human umbilical vein endothelial cells (HUVECs) into capillary networks and of murine kidney stem cells (KSCs) into highly branched aggregates. The established methodology is concluded to provide generally applicable new options for tailoring tissue-specific multiphasic matrices in vitro. Tissue-derived fibrillated matrices can be instrumental for the in vitro reconstitution of multiphasic extracellular microenvironments. However, despite of several advantages, the obtained scaffolds so far offer a rather narrow range of materials

  19. Bioactivation of particles

    Energy Technology Data Exchange (ETDEWEB)

    Pinaud, Fabien (Berkeley, CA); King, David (San Francisco, CA); Weiss, Shimon (Los Angeles, CA)

    2011-08-16

    Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.

  20. Advances on Bioactive Polysaccharides from Medicinal Plants.

    Science.gov (United States)

    Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

    2016-07-29

    In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

  1. Functional Sub-states by High-pressure Macromolecular Crystallography.

    Science.gov (United States)

    Dhaussy, Anne-Claire; Girard, Eric

    2015-01-01

    At the molecular level, high-pressure perturbation is of particular interest for biological studies as it allows trapping conformational substates. Moreover, within the context of high-pressure adaptation of deep-sea organisms, it allows to decipher the molecular determinants of piezophily. To provide an accurate description of structural changes produced by pressure in a macromolecular system, developments have been made to adapt macromolecular crystallography to high-pressure studies. The present chapter is an overview of results obtained so far using high-pressure macromolecular techniques, from nucleic acids to virus capsid through monomeric as well as multimeric proteins.

  2. Sequential recovery of macromolecular components of the nucleolus.

    Science.gov (United States)

    Bai, Baoyan; Laiho, Marikki

    2015-01-01

    The nucleolus is involved in a number of cellular processes of importance to cell physiology and pathology, including cell stress responses and malignancies. Studies of macromolecular composition of the nucleolus depend critically on the efficient extraction and accurate quantification of all macromolecular components (e.g., DNA, RNA, and protein). We have developed a TRIzol-based method that efficiently and simultaneously isolates these three macromolecular constituents from the same sample of purified nucleoli. The recovered and solubilized protein can be accurately quantified by the bicinchoninic acid assay and assessed by polyacrylamide gel electrophoresis or by mass spectrometry. We have successfully applied this approach to extract and quantify the responses of all three macromolecular components in nucleoli after drug treatments of HeLa cells, and conducted RNA-Seq analysis of the nucleolar RNA.

  3. An upper limit for macromolecular crowding effects

    Directory of Open Access Journals (Sweden)

    Miklos Andrew C

    2011-05-01

    Full Text Available Abstract Background Solutions containing high macromolecule concentrations are predicted to affect a number of protein properties compared to those properties in dilute solution. In cells, these macromolecular crowders have a large range of sizes and can occupy 30% or more of the available volume. We chose to study the stability and ps-ns internal dynamics of a globular protein whose radius is ~2 nm when crowded by a synthetic microgel composed of poly(N-isopropylacrylamide-co-acrylic acid with particle radii of ~300 nm. Results Our studies revealed no change in protein rotational or ps-ns backbone dynamics and only mild (~0.5 kcal/mol at 37°C, pH 5.4 stabilization at a volume occupancy of 70%, which approaches the occupancy of closely packing spheres. The lack of change in rotational dynamics indicates the absence of strong crowder-protein interactions. Conclusions Our observations are explained by the large size discrepancy between the protein and crowders and by the internal structure of the microgels, which provide interstitial spaces and internal pores where the protein can exist in a dilute solution-like environment. In summary, microgels that interact weakly with proteins do not strongly influence protein dynamics or stability because these large microgels constitute an upper size limit on crowding effects.

  4. Macromolecular components of tomato fruit pectin.

    Science.gov (United States)

    Fishman, M L; Gross, K C; Gillespie, D T; Sondey, S M

    1989-10-01

    Chelate and alkaline-soluble pectin extracted from cell walls of pericarp tissue from mature green, turning, and red ripe (Lycopersicon esculentum Mill.) fruit (cv. Rutgers), were studied by high-performance size-exclusion chromatography. Computer-aided curve fitting of the chromatograms to a series of Gaussian-shaped components revealed that pectin from all fractions was composed of a linear combination of five macromolecular-sized species. The relative sizes of these macromolecules as obtained from their radii of gyration were 1:2:4:8:16. Dialysis against 0.05 M NaCl induced partial dissociation of the biopolymers. Apparently, the weight fraction of smaller sized species increased at the expense of larger ones. Also, the dissociation produced low-molecular-weight fragments. Behavior in the presence of 0.05 M NaCl led to the conclusion that cell wall pectin acted as if it were an aggregated mosaic, held together at least partially through noncovalent interactions.

  5. The solvent component of macromolecular crystals

    Energy Technology Data Exchange (ETDEWEB)

    Weichenberger, Christian X. [European Academy of Bozen/Bolzano (EURAC), Viale Druso 1, Bozen/Bolzano, I-39100 Südtirol/Alto Adige (Italy); Afonine, Pavel V. [Lawrence Berkeley National Laboratory (LBNL), 1 Cyclotron Road, Mail Stop 64R0121, Berkeley, CA 94720 (United States); Kantardjieff, Katherine [California State University, San Marcos, CA 92078 (United States); Rupp, Bernhard, E-mail: br@hofkristallamt.org [k.-k. Hofkristallamt, 991 Audrey Place, Vista, CA 92084 (United States); Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck (Austria)

    2015-04-30

    On average, the mother liquor or solvent and its constituents occupy about 50% of a macromolecular crystal. Ordered as well as disordered solvent components need to be accurately accounted for in modelling and refinement, often with considerable complexity. The mother liquor from which a biomolecular crystal is grown will contain water, buffer molecules, native ligands and cofactors, crystallization precipitants and additives, various metal ions, and often small-molecule ligands or inhibitors. On average, about half the volume of a biomolecular crystal consists of this mother liquor, whose components form the disordered bulk solvent. Its scattering contributions can be exploited in initial phasing and must be included in crystal structure refinement as a bulk-solvent model. Concomitantly, distinct electron density originating from ordered solvent components must be correctly identified and represented as part of the atomic crystal structure model. Herein, are reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk-solvent density modification in phase improvement, (iii) bulk-solvent models and refinement of bulk-solvent contributions and (iv) modelling and validation of ordered solvent constituents. A brief summary is provided of current tools for bulk-solvent analysis and refinement, as well as of modelling, refinement and analysis of ordered solvent components, including small-molecule ligands.

  6. Bioactives from microalgal dinoflagellates.

    Science.gov (United States)

    Gallardo-Rodríguez, J; Sánchez-Mirón, A; García-Camacho, F; López-Rosales, L; Chisti, Y; Molina-Grima, E

    2012-01-01

    Dinoflagellate microalgae are an important source of marine biotoxins. Bioactives from dinoflagellates are attracting increasing attention because of their impact on the safety of seafood and potential uses in biomedical, toxicological and pharmacological research. Here we review the potential applications of dinoflagellate toxins and the methods for producing them. Only sparing quantities of dinoflagellate toxins are generally available and this hinders bioactivity characterization and evaluation in possible applications. Approaches to production of increased quantities of dinoflagellate bioactives are discussed. Although many dinoflagellates are fragile and grow slowly, controlled culture in bioreactors appears to be generally suitable for producing many of the metabolites of interest.

  7. Macromolecular networks and intelligence in microorganisms

    Directory of Open Access Journals (Sweden)

    Hans V Westerhoff

    2014-07-01

    Full Text Available Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of Information and Communication Technology (ICT: they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call intelligence. Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as human and brain out of the defining features of intelligence, all forms of life – from microbes to humans – exhibit some or all characteristics consistent with intelligence. We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo.

  8. Macromolecular networks and intelligence in microorganisms

    Science.gov (United States)

    Westerhoff, Hans V.; Brooks, Aaron N.; Simeonidis, Evangelos; García-Contreras, Rodolfo; He, Fei; Boogerd, Fred C.; Jackson, Victoria J.; Goncharuk, Valeri; Kolodkin, Alexey

    2014-01-01

    Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of information and communication technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call “intelligence.” Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as “human” and “brain” out of the defining features of “intelligence,” all forms of life – from microbes to humans – exhibit some or all characteristics consistent with “intelligence.” We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo. PMID:25101076

  9. Macromolecular Topography Leaps into the Digital Age

    Science.gov (United States)

    Lovelace, J.; Bellamy, H.; Snell, E. H.; Borgstahl, G.

    2003-01-01

    A low-cost, real-time digital topography system is under development which will replace x-ray film and nuclear emulsion plates. The imaging system is based on an inexpensive surveillance camera that offers a 1000x1000 array of 8 im square pixels, anti-blooming circuitry, and very quick read out. Currently, the system directly converts x-rays to an image with no phosphor. The system is small and light and can be easily adapted to work with other crystallographic equipment. Preliminary images have been acquired of cubic insulin at the NSLS x26c beam line. NSLS x26c was configured for unfocused monochromatic radiation. Six reflections were collected with stills spaced from 0.002 to 0.001 degrees apart across the entire oscillation range that the reflections were in diffracting condition. All of the reflections were rotated to the vertical to reduce Lorentz and beam related effects. This particular CCD is designed for short exposure applications (much less than 1 sec) and so has a relatively high dark current leading to noisy raw images. The images are processed to remove background and other system noise with a multi-step approach including the use of wavelets, histogram, and mean window filtering. After processing, animations were constructed with the corresponding reflection profile to show the diffraction of the crystal volume vs. the oscillation angle as well as composite images showing the parts of the crystal with the strongest diffraction for each reflection. The final goal is to correlate features seen in reflection profiles captured with fine phi slicing to those seen in the topography images. With this development macromolecular topography finally comes into the digital age.

  10. The effect of macromolecular crowding on the structure of the protein complex superoxide dismutase

    Science.gov (United States)

    Rajapaksha Mudalige, Ajith Rathnaweera

    % PEG did not change compared to the SOD structure in water. It therefore appears that under the conditions of our simulations MD could not describe the experimentally observed effects of macromolecular crowding. In a separate project, we measured the rate of diffusive transport in excised porcine corneal stroma using FCS for fluorescent labeled dextran molecules with hydrodynamic radii ranging from 1.3 to 34 nm. Dextran molecules diffuse more slowly in cornea as compared to buffer solution. The reduction in diffusion coefficient is modest however (67% smaller), and is uniform over the range of sizes that we measured. Diffusion coefficients measured parallel vs. perpendicular to the collagen lamellae were indistinguishable. This indicates that diffusion in the corneal stroma is not highly anisotropic. Delivery of therapeutic agents to the eye requires efficient transport through cellular and extracellular barriers. Our measurements bring important insights into how macromolecular and nanoparticle therapeutics might permeate through the eyes.

  11. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  12. Enhanced delivery of the RAPTA-C macromolecular chemotherapeutic by conjugation to degradable polymeric micelles.

    Science.gov (United States)

    Blunden, Bianca M; Lu, Hongxu; Stenzel, Martina H

    2013-12-09

    Macromolecular ruthenium complexes are a promising avenue to better and more selective chemotherapeutics. We have previously shown that RAPTA-C [RuCl2(p-cymene)(PTA)], with the water-soluble 1,3,5-phosphaadamantane (PTA) ligand, could be attached to a polymer moiety via nucleophilic substitution of an available iodide with an amide in the PTA ligand. To increase the cell uptake of this macromolecule, we designed an amphiphilic block copolymer capable of self-assembling into polymeric micelles. The block copolymer was prepared by ring-opening polymerization of d,l-lactide (3,6-dimethyl-1,4-dioxane-2,5-dione) using a RAFT agent with an additional hydroxyl functionality, followed by the RAFT copolymerization of 2-hydroxyethyl acrylate (HEA) and 2-chloroethyl methacrylate (CEMA). The Finkelstein reaction and reaction with PTA led to polymers that can readily react with the dimer of RuCl2(p-cymene) to create a macromolecular RAPTA-C drug. RAPTA-C conjugation, micellization, and subsequent cytotoxicity and cell uptake of these polymeric moieties was tested on ovarian cancer A2780, A2780cis, and Ovcar-3 cell lines. Confocal microscopy images confirmed cell uptake of the micelles into the lysosome of the cells, indicative of an endocytic pathway. On average, a 10-fold increase in toxicity was found for the macromolecular drugs when compared to the RAPTA-C molecule. Furthermore, the cell uptake of ruthenium was analyzed and a significant increase was found for the micelles compared to RAPTA-C. Notably, micelles prepared from the polymer containing fewer HEA units had the highest cytotoxicity, the best cell uptake of ruthenium and were highly effective in suppressing the colony-forming ability of cells.

  13. Macromolecular crystallography beamline X25 at the NSLS.

    Science.gov (United States)

    Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L; Dvorak, Joseph; Flaks, Leon; Lamarra, Steven; Myers, Stuart F; Orville, Allen M; Robinson, Howard H; Roessler, Christian G; Schneider, Dieter K; Shea-McCarthy, Grace; Skinner, John M; Skinner, Michael; Soares, Alexei S; Sweet, Robert M; Berman, Lonny E

    2014-05-01

    Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community.

  14. Chemical Blistering: Cellular and Macromolecular Components

    Science.gov (United States)

    1984-11-15

    cells in i Different species of keratin peptide can be visualized immunologically using monoclonal antibodies (14). .’n antibody which recognizes a...outlined below. b. Background Limited data are available on the various biochemical pathways involved in xenobiotic metabolism in keratinocytes...Alkylating Agents: A review, Cancer Res., 22:651-688. 6. Fox, M. and Scott, D. (1980) The Genetic Toxicology of Nitrogen and Sulphur Mustard. Mutation Res

  15. Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives.

    Science.gov (United States)

    Roberts, Joseph L; Moreau, Régis

    2016-08-10

    Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health-promoting activities that are attributed to the functional properties of their nutrients and non-essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach-derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti-obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non-essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits.

  16. The Differential Response of Proteins to Macromolecular Crowding

    Science.gov (United States)

    Candotti, Michela; Orozco, Modesto

    2016-01-01

    The habitat in which proteins exert their function contains up to 400 g/L of macromolecules, most of which are proteins. The repercussions of this dense environment on protein behavior are often overlooked or addressed using synthetic agents such as poly(ethylene glycol), whose ability to mimic protein crowders has not been demonstrated. Here we performed a comprehensive atomistic molecular dynamic analysis of the effect of protein crowders on the structure and dynamics of three proteins, namely an intrinsically disordered protein (ACTR), a molten globule conformation (NCBD), and a one-fold structure (IRF-3) protein. We found that crowding does not stabilize the native compact structure, and, in fact, often prevents structural collapse. Poly(ethylene glycol) PEG500 failed to reproduce many aspects of the physiologically-relevant protein crowders, thus indicating its unsuitability to mimic the cell interior. Instead, the impact of protein crowding on the structure and dynamics of a protein depends on its degree of disorder and results from two competing effects: the excluded volume, which favors compact states, and quinary interactions, which favor extended conformers. Such a viscous environment slows down protein flexibility and restricts the conformational landscape, often biasing it towards bioactive conformations but hindering biologically relevant protein-protein contacts. Overall, the protein crowders used here act as unspecific chaperons that modulate the protein conformational space, thus having relevant consequences for disordered proteins. PMID:27471851

  17. Marine Bioactives and Potential Application in Sports

    Directory of Open Access Journals (Sweden)

    Maria Alessandra Gammone

    2014-04-01

    Full Text Available An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP, such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB, macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  18. Marine bioactives and potential application in sports.

    Science.gov (United States)

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D'Orazio, Nicolantonio

    2014-04-30

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  19. Generating triangulated macromolecular surfaces by Euclidean Distance Transform.

    Directory of Open Access Journals (Sweden)

    Dong Xu

    Full Text Available Macromolecular surfaces are fundamental representations of their three-dimensional geometric shape. Accurate calculation of protein surfaces is of critical importance in the protein structural and functional studies including ligand-protein docking and virtual screening. In contrast to analytical or parametric representation of macromolecular surfaces, triangulated mesh surfaces have been proved to be easy to describe, visualize and manipulate by computer programs. Here, we develop a new algorithm of EDTSurf for generating three major macromolecular surfaces of van der Waals surface, solvent-accessible surface and molecular surface, using the technique of fast Euclidean Distance Transform (EDT. The triangulated surfaces are constructed directly from volumetric solids by a Vertex-Connected Marching Cube algorithm that forms triangles from grid points. Compared to the analytical result, the relative error of the surface calculations by EDTSurf is <2-4% depending on the grid resolution, which is 1.5-4 times lower than the methods in the literature; and yet, the algorithm is faster and costs less computer memory than the comparative methods. The improvements in both accuracy and speed of the macromolecular surface determination should make EDTSurf a useful tool for the detailed study of protein docking and structure predictions. Both source code and the executable program of EDTSurf are freely available at http://zhang.bioinformatics.ku.edu/EDTSurf.

  20. Two-center-multipole expansion method: application to macromolecular systems

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Yakubovich, Alexander V.; Solov'yov, Andrey V.;

    2007-01-01

    We propose a theoretical method for the calculation of the interaction energy between macromolecular systems at large distances. The method provides a linear scaling of the computing time with the system size and is considered as an alternative to the well-known fast multipole method. Its...

  1. Research progress of magnetic resonance imaging contrast agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Magnetic resonance imaging (MRI) is a clinical diagnostic modality, which has become popular in hospitals around the world. Approximately 30% of MRI exams include the use of contrast agents. The research progress of the paramagnetic resonance imaging contrast agents was described briefly. Three important approaches in the soluble paramagnetic resonance imaging contrast agents design including nonionic, tissue-specific and macromolecular contrast agents were investigated. In addition, the problems in the research and development in future were discussed.

  2. Syntheses of Macromolecular Ruthenium Compounds: A New Approach for the Search of Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Andreia Valente

    2014-03-01

    Full Text Available The continuous rising of the cancer patient death rate undoubtedly shows the pressure to find more potent and efficient drugs than those in clinical use. These agents only treat a narrow range of cancer conditions with limited success and are associated with serious side effects caused by the lack of selectivity. In this frame, innovative syntheses approaches can decisively contribute to the success of “smart compounds” that might be only selective and/or active towards the cancer cells, sparing the healthy ones. In this scope, ruthenium chemistry is a rising field for the search of proficient metallodrugs by the use of macromolecular ruthenium complexes (dendrimers and dendronized polymers, coordination-cage and protein conjugates, nanoparticles and polymer-“ruthenium-cyclopentadienyl” conjugates that can take advantage of the singularities of tumor cells (vs. healthy cells.

  3. In vitro bioactivity and antimicrobial tuning of bioactive glass nanoparticles added with neem (Azadirachta indica) leaf powder.

    Science.gov (United States)

    Prabhu, M; Ruby Priscilla, S; Kavitha, K; Manivasakan, P; Rajendran, V; Kulandaivelu, P

    2014-01-01

    Silica and phosphate based bioactive glass nanoparticles (58SiO2-33CaO-9P2O5) with doping of neem (Azadirachta indica) leaf powder and silver nanoparticles were prepared and characterised. Bioactive glass nanoparticles were produced using sol-gel technique. In vitro bioactivity of the prepared samples was investigated using simulated body fluid. X-ray diffraction (XRD) pattern of prepared glass particles reveals amorphous phase and spherical morphology with a particle size of less than 50 nm. When compared to neem doped glass, better bioactivity was attained in silver doped glass through formation of hydroxyapatite layer on the surface, which was confirmed through XRD, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) analysis. However, neem leaf powder doped bioactive glass nanoparticles show good antimicrobial activity against Staphylococcus aureus and Escherichia coli and less bioactivity compared with silver doped glass particles. In addition, the biocompatibility of the prepared nanocomposites reveals better results for neem doped and silver doped glasses at lower concentration. Therefore, neem doped bioactive glass may act as a potent antimicrobial agent for preventing microbial infection in tissue engineering applications.

  4. Applied bioactive polymeric materials

    CERN Document Server

    Carraher, Charles; Foster, Van

    1988-01-01

    The biological and biomedical applications of polymeric materials have increased greatly in the past few years. This book will detail some, but not all, of these recent developments. There would not be enough space in this book to cover, even lightly, all of the major advances that have occurred. Some earlier books and summaries are available by two of this book's Editors (Gebelein & Carraher) and these should be consul ted for additional information. The books are: "Bioactive Polymeric Systems" (Plenum, 1985); "Polymeric Materials In Medication" (Plenum, 1985); "Biological Acti vi ties of Polymers" (American Chemical Society, 1982). Of these three, "Bioacti ve Polymeric Systems" should be the most useful to a person who is new to this field because it only contains review articles written at an introductory level. The present book primarily consists of recent research results and applications, with only a few review or summary articles. Bioactive polymeric materials have existed from the creation of life...

  5. Bioactivities of chicken essence.

    Science.gov (United States)

    Li, Y F; He, R R; Tsoi, B; Kurihara, H

    2012-04-01

    The special flavor and health effects of chicken essence are being widely accepted by people. Scientific researches are revealing its truth as a tonic food in traditional health preservation. Chicken essence has been found to possess many bioactivities including relief of stress and fatigue, amelioration of anxiety, promotion of metabolisms and post-partum lactation, improvement on hyperglycemia and hypertension, enhancement of immune, and so on. These activities of chicken essence are suggested to be related with its active components, including proteins, dipeptides (such as carnosine and anserine), polypeptides, minerals, trace elements, and multiple amino acids, and so on. Underlying mechanisms responsible for the bioactivities of chicken essence are mainly related with anti-stress, anti-oxidant, and neural regulation effects. However, the mechanisms are complicated and may be mediated via the combined actions of many active components, more than the action of 1 or 2 components alone. © 2012 Institute of Food Technologists®

  6. Bioactive phytochemicals in flaxseed

    OpenAIRE

    Johnsson, Pernilla

    2009-01-01

    Flaxseed (Linum usitatissimum L.) is rich in health-promoting bioactive compounds. Among plant foods, flaxseed has the highest content of lignans, mainly in the form of secoisolariciresinol diglucoside (SDG). Flaxseed oil also has a very high concentration of the essential omega-3 fatty acid alpha-linolenic acid (ALA). This thesis presents studies on both SDG and ALA. An HPLC method for quantification of SDG in hydrolysed flaxseed extracts was developed and used to compare the SDG content in ...

  7. Stochastic reaction–diffusion algorithms for macromolecular crowding

    Science.gov (United States)

    Sturrock, Marc

    2016-06-01

    Compartment-based (lattice-based) reaction–diffusion algorithms are often used for studying complex stochastic spatio-temporal processes inside cells. In this paper the influence of macromolecular crowding on stochastic reaction–diffusion simulations is investigated. Reaction–diffusion processes are considered on two different kinds of compartmental lattice, a cubic lattice and a hexagonal close packed lattice, and solved using two different algorithms, the stochastic simulation algorithm and the spatiocyte algorithm (Arjunan and Tomita 2010 Syst. Synth. Biol. 4, 35–53). Obstacles (modelling macromolecular crowding) are shown to have substantial effects on the mean squared displacement and average number of molecules in the domain but the nature of these effects is dependent on the choice of lattice, with the cubic lattice being more susceptible to the effects of the obstacles. Finally, improvements for both algorithms are presented.

  8. Controlled architecture for improved macromolecular memory within polymer networks.

    Science.gov (United States)

    DiPasquale, Stephen A; Byrne, Mark E

    2016-08-01

    This brief review analyzes recent developments in the field of living/controlled polymerization and the potential of this technique for creating imprinted polymers with highly structured architecture with macromolecular memory. As a result, it is possible to engineer polymers at the molecular level with increased homogeneity relating to enhanced template binding and transport. Only recently has living/controlled polymerization been exploited to decrease heterogeneity and substantially improve the efficiency of the imprinting process for both highly and weakly crosslinked imprinted polymers. Living polymerization can be utilized to create imprinted networks that are vastly more efficient than similar polymers produced using conventional free radical polymerization, and these improvements increase the role that macromolecular memory can play in the design and engineering of new drug delivery and sensing platforms.

  9. Isotope labeling for NMR studies of macromolecular structure and interactions

    Energy Technology Data Exchange (ETDEWEB)

    Wright, P.E. [Scripps Research Institute, La Jolla, CA (United States)

    1994-12-01

    Implementation of biosynthetic methods for uniform or specific isotope labeling of proteins, coupled with the recent development of powerful heteronuclear multidimensional NMR methods, has led to a dramatic increase in the size and complexity of macromolecular systems that are now amenable to NMR structural analysis. In recent years, a new technology has emerged that combines uniform {sup 13}C, {sup 15}N labeling with heteronuclear multidimensional NMR methods to allow NMR structural studies of systems approaching 25 to 30 kDa in molecular weight. In addition, with the introduction of specific {sup 13}C and {sup 15}N labels into ligands, meaningful NMR studies of complexes of even higher molecular weight have become feasible. These advances usher in a new era in which the earlier, rather stringent molecular weight limitations have been greatly surpassed and NMR can begin to address many central biological problems that involve macromolecular structure, dynamics, and interactions.

  10. Temperature-dependent macromolecular X-ray crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Weik, Martin, E-mail: martin.weik@ibs.fr; Colletier, Jacques-Philippe [CEA, IBS, Laboratoire de Biophysique Moléculaire, F-38054 Grenoble (France); CNRS, UMR5075, F-38027 Grenoble (France); Université Joseph Fourier, F-38000 Grenoble (France)

    2010-04-01

    The dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed. X-ray crystallography provides structural details of biological macromolecules. Whereas routine data are collected close to 100 K in order to mitigate radiation damage, more exotic temperature-controlled experiments in a broader temperature range from 15 K to room temperature can provide both dynamical and structural insights. Here, the dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed. Experimental strategies of kinetic crystallography are discussed that have allowed the generation and trapping of macromolecular intermediate states by combining reaction initiation in the crystalline state with appropriate temperature profiles. A particular focus is on recruiting X-ray-induced changes for reaction initiation, thus unveiling useful aspects of radiation damage, which otherwise has to be minimized in macromolecular crystallography.

  11. Refinement of macromolecular structures against neutron data with SHELXL2013.

    Science.gov (United States)

    Gruene, Tim; Hahn, Hinrich W; Luebben, Anna V; Meilleur, Flora; Sheldrick, George M

    2014-02-01

    Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [Acta Cryst. (1991), A47, 392-400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures.

  12. The vibron dressing in α-helicoidal macromolecular chains

    Institute of Scientific and Technical Information of China (English)

    D.(C)evizovi(c); S.Galovi(c); A.Reshetnyak; Z.Ivi(c)

    2013-01-01

    We present a study of the physical properties of the vibrational excitation in α-helicoidal macromolecular chains,caused by the interaction with acoustical and optical phonon modes.The influence of the temperature and the basic system parameters on the vibron dressing have been analyzed by employing the simple mean-field approach based on the variational extension of the Lang-Firsov unitary transformation.The applied approach predicts a region in system parameter space where one has an abrupt transition from a partially dressed (light and mobile) to a fully dressed (immobile) vibron state.We found that the boundary of this region depends on system temperature and the type of bond among structural elements in the macromolecular chain.

  13. A macromolecular model for the endothelial surface layer

    Science.gov (United States)

    Harden, James; Danova-Okpetu, Darina; Grest, Gary

    2006-03-01

    The endothelial surface layer (ESL) is a micron-scale macromolecular lining of the luminal side of blood vessels composed of proteoglycans, glycoproteins, polysaccharides and associated plasma proteins all in dynamic equilibrium. It has numerous physiological roles including the regulation of blood flow and microvascular permeability, and active participation in mechanotransduction and stress regulation, coagulation, cell adhesion, and inflammatory response. The dynamic structure and the mechanical properties of the ESL are crucial for many of its physiological properties. We present a topological model for the ESL composed of three basic macromolecular elements: branched proteoglycans, linear polysaccharide chains, and small plasma proteins. The model was studied using non-equilibrium molecular dynamics simulations and compared with scaling theories for associating tethered polymers. We discuss the observed dynamical and mechanical properties of the ESL captured by this model, and the possible physical insight it provides into the physiological behavior of the ESL.

  14. A Strategy for the Development of Macromolecular Nonlinear Optical Materials

    Science.gov (United States)

    1990-01-01

    obsolete. SECURITY CLASSIFICATION OF THIS PAGE STRATEGY FOR THE DEVELOPMENT OF MACROMOLECULAR NONLINEAR OPTICAL MATERIALS Braja K. Mandala , Jan-Chan...materials is significantly different from the conventional inorganic NLO materials. The extent of second order (quadratic) NLO effect such as second...is a criterion of paramount importance for a large second order electro-optic effect in organic materials 8 ,9 . The most common approach to obtain

  15. Facilitating structure determination: workshop on robotics andautomation in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Ralston, Corie; Cork, C.W.; McDermott, G.; Earnest, T.N.

    2006-03-28

    As part of the annual Advanced Light Source (ALS) andStanford Synchrotron Radiation Laboratory (SSRL) Users' Meeting inOctober of this year, the macromolecular crystallography staff at bothsynchrotrons held a joint hands-on workshop to address automation issuesin crystal mounting and data collection at the beamline. This paperdescribes the ALS portion of the workshop, while the accompanying paperreviews the SSRL workshop.

  16. Single-particle cryo-electron microscopy of macromolecular assemblies

    OpenAIRE

    Cheng, Kimberley

    2009-01-01

    In this thesis, single-particle cryo-electron microscopy (cryo-EM) was used to study the structure of three macromolecular assemblies: the two hemocyanin isoforms from Rapana thomasiana, the Pyrococcus furiosus chaperonin, and the ribosome from Escherichia coli. Hemocyanins are large respiratory proteins in arthropods and molluscs. Most molluscan hemocyanins exist as two distinct isoforms composed of related polypeptides. In most species the two isoforms differ in terms of their oligomeric st...

  17. Bioactive glass in tissue engineering

    Science.gov (United States)

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  18. What Macromolecular Crowding Can Do to a Protein

    Science.gov (United States)

    Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

    2014-01-01

    The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

  19. REFMAC5 for the refinement of macromolecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Murshudov, Garib N., E-mail: garib@ysbl.york.ac.uk [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Skubák, Pavol [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Lebedev, Andrey A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Pannu, Navraj S. [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Steiner, Roberto A. [Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, London (United Kingdom); Nicholls, Robert A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Winn, Martyn D. [STFC Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Long, Fei; Vagin, Alexei A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom)

    2011-04-01

    The general principles behind the macromolecular crystal structure refinement program REFMAC5 are described. This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part of the CCP4 suite. REFMAC5 utilizes different likelihood functions depending on the diffraction data employed (amplitudes or intensities), the presence of twinning and the availability of SAD/SIRAS experimental diffraction data. To ensure chemical and structural integrity of the refined model, REFMAC5 offers several classes of restraints and choices of model parameterization. Reliable models at resolutions at least as low as 4 Å can be achieved thanks to low-resolution refinement tools such as secondary-structure restraints, restraints to known homologous structures, automatic global and local NCS restraints, ‘jelly-body’ restraints and the use of novel long-range restraints on atomic displacement parameters (ADPs) based on the Kullback–Leibler divergence. REFMAC5 additionally offers TLS parameterization and, when high-resolution data are available, fast refinement of anisotropic ADPs. Refinement in the presence of twinning is performed in a fully automated fashion. REFMAC5 is a flexible and highly optimized refinement package that is ideally suited for refinement across the entire resolution spectrum encountered in macromolecular crystallography.

  20. Macromolecular amplification of binding response in superaptamer hydrogels.

    Science.gov (United States)

    Bai, Wei; Gariano, Nicholas A; Spivak, David A

    2013-05-08

    It is becoming more important to detect ultralow concentrations of analytes for biomedical, environmental, and national security applications. Equally important is that new methods should be easy to use, inexpensive, portable, and if possible allow detection by the naked eye. By and large, detection of low concentrations of analytes cannot be achieved directly but requires signal amplification by catalysts, macromolecules, metal surfaces, or supramolecular aggregates. The rapidly progressing field of macromolecular signal amplification has been advanced using conjugated polymers, chirality in polymers, solvating polymers, and polymerization/depolymerization strategies. A new type of aptamer-based hydrogel with specific response to target proteins presented in this report demonstrates an additional category of macromolecular signal amplification. This superaptamer assembly provides the first example of using protein-specific aptamers to create volume-changing hydrogels with amplified response to the target protein. A remarkable aspect of these superaptamer hydrogels is that volume shrinking is visible to the naked eye down to femtomolar concentrations of protein. This extraordinary macromolecular amplification is attributed to a complex interplay between protein-aptamer supramolecular cross-links and the consequential reduction of excluded volume in the hydrogel. Specific recognition is even maintained in biological matrices such as urine and tears. Furthermore, the gels can be dried for long-term storage and regenerated for use without loss of activity. In practice, the ease of this biomarker detection method offers an alternative to traditional analytical techniques that require sophisticated instrumentation and highly trained personnel.

  1. Macromolecular Assemblage in the Design of a Synthetic AIDS Vaccine

    Science.gov (United States)

    Defoort, Jean-Philippe; Nardelli, Bernardetta; Huang, Wolin; Ho, David D.; Tam, James P.

    1992-05-01

    We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in liposome or micelle, was used to immunize mice and guinea pigs without any adjuvant and found to induce gp120-specific antibodies that neutralize virus infectivity in vitro, elicit cytokine production, and prime CD8^+ cytotoxic T lymphocytes in vivo. Our results show that the macromolecular assemblage approach bears immunological mimicry of the gp120 of HIV virus and may lead to useful vaccines against HIV infection.

  2. Human milk composition: nutrients and bioactive factors.

    Science.gov (United States)

    Ballard, Olivia; Morrow, Ardythe L

    2013-02-01

    This article provides an overview of the composition of human milk, its variation, and its clinical relevance. The composition of human milk is the biological norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules (eg, lactoferrin) are being investigated as novel therapeutic agents. Human milk changes in composition from colostrum to late lactation, within feeds, by gestational age, diurnally, and between mothers. Feeding infants with expressed human milk is increasing.

  3. Workshop on algorithms for macromolecular modeling. Final project report, June 1, 1994--May 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Leimkuhler, B.; Hermans, J.; Skeel, R.D.

    1995-07-01

    A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

  4. Macromolecular crowding and the steady-state kinetics of malate dehydrogenase.

    Science.gov (United States)

    Poggi, Christopher G; Slade, Kristin M

    2015-01-20

    To understand how macromolecular crowding affects enzyme activity, we quantified the Michaelis-Menten kinetics of mitochondrial malate dehydrogenase (MDH) in the presence of hen egg white (HEW), lysozyme, bovine serum albumin (BSA), gum arabic, poly(vinylpyrrolidone) (PVP), and dextrans of various molecular weights. Although crowding tended to decrease Km and Vmax values, the magnitude depended on the crowding agent, reaction direction, and isozyme (mitochondrial porcine heart or thermophlic TaqMDH from Thermus flavus). Crowding slowed oxaloacetate reduction more significantly than malate oxidation, which may suggest that mitochondrial enzymes have evolved to function optimally under the crowded constraints in which they are immersed. Since direct comparisons of neutral to charged crowders are underrepresented in the literature, we performed these studies and found that neutral crowding agents lowered Vmax values more than charged crowders of similar size. The exception was hen egg white, a mixture of charged proteins that caused the largest observed decreases in both Km and Vmax. Finally, the data provide insight about the mechanism by corroborating MDH subunit dependence.

  5. Anti-fouling bioactive surfaces.

    Science.gov (United States)

    Yu, Qian; Zhang, Yanxia; Wang, Hongwei; Brash, John; Chen, Hong

    2011-04-01

    Bioactive surfaces refer to surfaces with immobilized bioactive molecules aimed specifically at promoting or supporting particular interactions. Such surfaces are of great importance for various biomedical and biomaterials applications. In the past few years, considerable effort has been made to create bioactive surfaces by forming specific biomolecule-modified surfaces on a non-biofouling "base" or "background". Hydrophilic and bioinert polymers have been widely used as anti-fouling layers that resist non-specific protein interactions. They can also serve as "spacers" to effectively move the immobilized biomolecule away from the surface, thus enhancing its bioactivity. In this review we summarize several successful approaches for the design and preparation of bioactive surfaces based on different types of anti-fouling/spacer materials. Some perspectives on future research in this area are also presented.

  6. Bringing macromolecular machinery to life using 3D animation.

    Science.gov (United States)

    Iwasa, Janet H

    2015-04-01

    Over the past decade, there has been a rapid rise in the use of three-dimensional (3D) animation to depict molecular and cellular processes. Much of the growth in molecular animation has been in the educational arena, but increasingly, 3D animation software is finding its way into research laboratories. In this review, I will discuss a number of ways in which 3d animation software can play a valuable role in visualizing and communicating macromolecular structures and dynamics. I will also consider the challenges of using animation tools within the research sphere.

  7. BLOOD FLOW AND MACROMOLECULAR TRANSPORT IN CURVED BLOOD VESSELS

    Institute of Scientific and Technical Information of China (English)

    WEI Lan; WEN Gong-bi; TAN Wen-chang

    2006-01-01

    A numerical analysis of the steady/pulsatile flow and macromolecular (such as LDL and Albumin) transport in curved blood vessels was carried out. The computational results predict that the vortex of the secondary flow is time-dependent in the aortic arch.The concentration of macromolecule concentrates at the region of sharp curve, and the wall concentration at the outer part is higher than that at the inner part. Atherosclerosis and thrombosis are prone to develop in such regions with sharp flow.

  8. Role of solvent properties of aqueous media in macromolecular crowding effects.

    Science.gov (United States)

    Ferreira, Luisa A; Madeira, Pedro P; Breydo, Leonid; Reichardt, Christian; Uversky, Vladimir N; Zaslavsky, Boris Y

    2016-01-01

    Analysis of the macromolecular crowding effects in polymer solutions show that the excluded volume effect is not the only factor affecting the behavior of biomolecules in a crowded environment. The observed inconsistencies are commonly explained by the so-called soft interactions, such as electrostatic, hydrophobic, and van der Waals interactions, between the crowding agent and the protein, in addition to the hard nonspecific steric interactions. We suggest that the changes in the solvent properties of aqueous media induced by the crowding agents may be the root of these "soft" interactions. To check this hypothesis, the solvatochromic comparison method was used to determine the solvent dipolarity/polarizability, hydrogen-bond donor acidity, and hydrogen-bond acceptor basicity of aqueous solutions of different polymers (dextran, poly(ethylene glycol), Ficoll, Ucon, and polyvinylpyrrolidone) with the polymer concentration up to 40% typically used as crowding agents. Polymer-induced changes in these features were found to be polymer type and concentration specific, and, in case of polyethylene glycol (PEG), molecular mass specific. Similarly sized polymers PEG and Ucon producing different changes in the solvent properties of water in their solutions induced morphologically different α-synuclein aggregates. It is shown that the crowding effects of some polymers on protein refolding and stability reported in the literature can be quantitatively described in terms of the established solvent features of the media in these polymers solutions. These results indicate that the crowding agents do induce changes in solvent properties of aqueous media in crowded environment. Therefore, these changes should be taken into account for crowding effect analysis.

  9. Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca2+ Current Inhibitors for Hypotensive Agent Discovery

    Directory of Open Access Journals (Sweden)

    Hélène Carreyre

    2017-05-01

    Full Text Available Dodoneine (Ddn is one of the active compounds identified from Agelanthus dodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine’s vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III and L-type Ca2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.

  10. Identifying and visualizing macromolecular flexibility in structural biology

    Directory of Open Access Journals (Sweden)

    Martina Palamini

    2016-09-01

    Full Text Available Structural biology comprises a variety of tools to obtain atomic resolution data for the investigation of macromolecules. Conventional structural methodologies including crystallography, NMR and electron microscopy often do not provide sufficient details concerning flexibility and dynamics, even though these aspects are critical for the physiological functions of the systems under investigation. However, the increasing complexity of the molecules studied by structural biology (including large macromolecular assemblies, integral membrane proteins, intrinsically disordered systems, and folding intermediates continuously demands in-depth analyses of the roles of flexibility and conformational specificity involved in interactions with ligands and inhibitors. The intrinsic difficulties in capturing often subtle but critical molecular motions in biological systems have restrained the investigation of flexible molecules into a small niche of structural biology. Introduction of massive technological developments over the recent years, which include time-resolved studies, solution X-ray scattering, and new detectors for cryo-electron microscopy, have pushed the limits of structural investigation of flexible systems far beyond traditional approaches of NMR analysis. By integrating these modern methods with powerful biophysical and computational approaches such as generation of ensembles of molecular models and selective particle picking in electron microscopy, more feasible investigations of dynamic systems are now possible. Using some prominent examples from recent literature, we review how current structural biology methods can contribute useful data to accurately visualize flexibility in macromolecular structures and understand its important roles in regulation of biological processes.

  11. Enzymes as Green Catalysts for Precision Macromolecular Synthesis.

    Science.gov (United States)

    Shoda, Shin-ichiro; Uyama, Hiroshi; Kadokawa, Jun-ichi; Kimura, Shunsaku; Kobayashi, Shiro

    2016-02-24

    The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysaccharides and functionalized polyesters. The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin. These polymerizations are "green" with several respects; nontoxicity of enzyme, high catalyst efficiency, selective reactions under mild conditions using green solvents and renewable starting materials, and producing minimal byproducts. Thus, the enzymatic polymerization is desirable for the environment and contributes to "green polymer chemistry" for maintaining sustainable society.

  12. Critical review and perspective of macromolecularly imprinted polymers.

    Science.gov (United States)

    Kryscio, David R; Peppas, Nicholas A

    2012-02-01

    Molecular recognition is a fundamental and ubiquitous process that is the driving force behind life. Natural recognition elements - including antibodies, enzymes, nucleic acids, and cells - exploit non-covalent interactions to bind to their targets with exceptionally strong affinities. Due to this unparalleled proficiency, scientists have long sought to mimic natural recognition pathways. One promising approach is molecularly imprinted polymers (MIPs), which are fully synthetic systems formed via the crosslinking of organic polymers in the presence of a template molecule, which results in stereo-specific binding sites for this analyte of interest. Macromolecularly imprinted polymers, those synthesized in the presence of macromolecule templates (>1500 Da), are of particular importance because they open up the field for a whole new set of robust diagnostic tools. Although the specific recognition of small-molecular-weight analytes is now considered routine, extension of these efficacious procedures to the protein regime has, thus far, proved challenging. This paper reviews the main approaches employed, highlights studies of interest with an emphasis on recent work, and offers suggestions for future success in the field of macromolecularly imprinted polymers.

  13. The macromolecular crystallography facility at the advanced light source

    Science.gov (United States)

    Earnest, Thomas; Padmore, Howard; Cork, Carl; Behrsing, Rolf; Kim, Sung-Hou

    1996-10-01

    Synchrotron radiation offers several advantages over the use of rotating anode sources for biological crystallography, which allow for the collection of higher-resolution data, substantially more rapid data collection, phasing by multiwavelength anomalous diffraction (MAD) techniques, and time-resolved experiments using polychromatic radiation (Laue diffraction). The use of synchrotron radiation is often necessary to record useful data from crystals which diffract weakly or have very large unit cells. The high brightness and stability characteristics of the advanced light source (ALS) at Lawrence Berkeley National Laboratory, along with the low emittance and long straight sections to accommodate insertion devices present in third generation synchrotrons like the ALS, lead to several advantages in the field of macromolecular crystallography. We are presently constructing a macromolecular crystallography facility at the ALS which is optimized for user-friendliness and high-throughput data collection, with advanced capabilities for MAD and Laue experiments. The X-rays will be directed to three branchlines. A well-equipped support lab will be available for biochemistry, crystal mounting and sample storage, as well as computer hardware and software available, along with staff support, allowing for the complete processing of data on site.

  14. MMDB and VAST+: tracking structural similarities between macromolecular complexes.

    Science.gov (United States)

    Madej, Thomas; Lanczycki, Christopher J; Zhang, Dachuan; Thiessen, Paul A; Geer, Renata C; Marchler-Bauer, Aron; Bryant, Stephen H

    2014-01-01

    The computational detection of similarities between protein 3D structures has become an indispensable tool for the detection of homologous relationships, the classification of protein families and functional inference. Consequently, numerous algorithms have been developed that facilitate structure comparison, including rapid searches against a steadily growing collection of protein structures. To this end, NCBI's Molecular Modeling Database (MMDB), which is based on the Protein Data Bank (PDB), maintains a comprehensive and up-to-date archive of protein structure similarities computed with the Vector Alignment Search Tool (VAST). These similarities have been recorded on the level of single proteins and protein domains, comprising in excess of 1.5 billion pairwise alignments. Here we present VAST+, an extension to the existing VAST service, which summarizes and presents structural similarity on the level of biological assemblies or macromolecular complexes. VAST+ simplifies structure neighboring results and shows, for macromolecular complexes tracked in MMDB, lists of similar complexes ranked by the extent of similarity. VAST+ replaces the previous VAST service as the default presentation of structure neighboring data in NCBI's Entrez query and retrieval system. MMDB and VAST+ can be accessed via http://www.ncbi.nlm.nih.gov/Structure.

  15. Macromolecular Crowding Enhances Thermal Stability of Rabbit Muscle Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    ZHU Jiang; HE Huawei; LI Sen

    2008-01-01

    The effect of dextran on the conformation (or secondary structure) and thermal stability of creatine kinase (CK) was studied using the far-ultraviolet (UV) circular dichroism (CD) spectra.The results showed that lower concentrations of dextran (less than 60 g/L) induced formation of the secondary CK structures.However,the secondary structure content of CK decreased when the dextran concentrations exceeded 60 g/L.Thermally induced transition curves were measured for CK in the presence of different concentrations of dextran by far-UV CD.The thermal transition curves were fitted to a two-state model by a nonlinear,least-squares method to obtain the transition temperature of the unfolding transition.An increase in the tran- sition temperature was observed with the increase of the dextran concentration.These observations qualita-tively accord with predictions of a previously proposed model for the effect of intermolecular excluded volume (macromolecular crowding) on protein stability and conformation.These findings imply that the effects of macromolecular crowding can have an important influence on our understanding of how protein folding oc-curs in vivo.

  16. PRIGo: a new multi-axis goniometer for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Waltersperger, Sandro; Olieric, Vincent, E-mail: vincent.olieric@psi.ch; Pradervand, Claude [Paul Scherrer Institute, Villigen PSI (Switzerland); Glettig, Wayne [Centre Suisse d’Electronique et Microtechnique SA, Neuchâtel 2002 (Switzerland); Salathe, Marco; Fuchs, Martin R.; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias [Paul Scherrer Institute, Villigen PSI (Switzerland); Schulze-Briese, Clemens [Dectris Ltd, Baden 5400 (Switzerland); Wang, Meitian, E-mail: vincent.olieric@psi.ch [Paul Scherrer Institute, Villigen PSI (Switzerland)

    2015-05-09

    The design and performance of the new multi-axis goniometer PRIGo developed at the Swiss Light Source at Paul Scherrer Institute is described. The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0–90°), followed by a ϕ stage (0–360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  17. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2015-03-01

    Full Text Available Yi Liu,1 Hongyu Piao,1 Ying Gao,1 Caihong Xu,2 Ye Tian,1 Lihong Wang,1 Jinwen Liu,1 Bo Tang,1 Meijuan Zou,1 Gang Cheng1 1Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Food Science, Shenyang Normal University, Shenyang, Liaoning Province, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN38, an active metabolite of irinotecan (CPT-11, is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OHSN38 and chitosan-(C20-OHSN38 to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OHSN38 (CS-(10sSN38 and chitosan-(C20-OHSN38 (CS-(20sSN38 were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC0–24 of SN38 after intravenously administering CS-(10sSN38 and CS-(20sSN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P<0.01. A larger AUC0–24 of CS-(20sSN38 was observed when compared to CS-(10sSN38 (P<0.05. Both of the novel self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the differences between these macromolecular prodrug micelles with regards to enhancing the antitumor activity of SN38. CS-(20sSN38 exhibited better in vivo antitumor activity than CS-(10sSN38 at a dose of 2.5 mg/kg (P<0

  18. Developing a New Generation of Antimicrobial and Bioactive Dental Resins.

    Science.gov (United States)

    Cheng, L; Zhang, K; Zhang, N; Melo, M A S; Weir, M D; Zhou, X D; Bai, Y X; Reynolds, M A; Xu, H H K

    2017-07-01

    Dental caries is prevalent, and secondary caries causes restoration failures. This article reviews recent studies on developing a new generation of bioactive resins with anticaries properties. Extensive effects were made to develop new antimicrobial composites, bonding agents, and other resins containing quaternary ammonium methacrylates to suppress plaque buildup and bacterial acid production. The effects of alkyl chain length and charge density and the antimicrobial mechanisms for chlorhexidine, nano-silver, quaternary ammonium methacrylates, and protein-repellent agents were discussed. Synergistic effects of contact-killing and protein-repellent properties were shown to yield the greatest biofilm-inhibition effects. The combination of antimicrobial, protein-repellent, and calcium phosphate nanoparticle remineralization was suggested to provide maximal anticaries effects. In addition, for use orally, cytotoxicity and biocompatibility were important considerations for the new bioactive materials. Furthermore, rather than kill all bacteria, it would be more desirable to modulate the oral biofilm compositions via bioactive resins to suppress cariogenic/pathogenic species and promote benign species. For widespread clinical use of the new antimicrobial and therapeutic materials, whether they would induce bacterial drug resistance needs to be determined, which requires further study. Nonetheless, the new generation of bioactive anticaries resins with therapeutic and biofilm acid-inhibiting properties has the potential to substantially benefit oral health.

  19. Bioactive glasses: Frontiers and challenges

    Directory of Open Access Journals (Sweden)

    Larry L. Hench

    2015-11-01

    Full Text Available Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass-ceramics. In the 1980’s it was discovered that bioactive glasses could be used in particulate form to stimulate osteogenesis, which thereby led to the concept of regeneration of tissues. Later, it was discovered that the dissolution ions from the glasses behaved like growth factors, providing signals to the cells. This article summarizes the frontiers of knowledge crossed during four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglass®. The four eras are: a discovery; b clinical application; c tissue regeneration; and d innovation. Questions still to be answered for the fourth era are included to stimulate innovation in the field and exploration of new frontiers that can be the basis for a general theory of bioactive stimulation of regeneration of tissues and application to numerous clinical needs.

  20. Bioactive proteins from pipefishes

    Institute of Scientific and Technical Information of China (English)

    E. Rethna Priya; S. Ravichandran; R. Ezhilmathi

    2013-01-01

    Objective: To screen antimicrobial potence of some pipefish species collected from Tuticorin coastal environment.Methods:Antimicrobial activity of pipefishes in methanol extract was investigated against 10 bacterial and 10 fungal human pathogenic strains.Results:Among the tested strains, in Centriscus scutatus, pipefish showed maximum zone of inhibition against Vibrio cholerae (8 mm) and minimum in the sample of Hippichthys cyanospilos against Klebseilla pneumoniae (2 mm). In positive control, maximum zone of inhibition was recorded in Vibrio cholerae (9 mm) and minimum in Klebseilla pneumoniae, and Salmonella paratyphi (5 mm). Chemical investigation indicated the presence of peptides as evidenced by ninhydrin positive spots on thin layer chromatography and presence of peptide. In SDS PAGE, in Centriscus scutatus, four bands were detected in the gel that represented the presence of proteins in the range nearly 25.8-75 kDa. In Hippichthys cyanospilos, five bands were detected in the gel that represented the presence of proteins in the range nearly 20.5-78 kDa. The result of FT-IR spectrum revealed that the pipe fishes extracts compriseed to have peptide derivatives as their predominant chemical groups.Conclusions:It can be conclude that this present investigation suggests the tested pipe fishes will be a potential source of natural bioactive compounds.

  1. PROFESSOR TEJ PAL SINGH: THE LEGEND OF INDIAN MACROMOLECULAR CRYSTALLOGRAPHY

    Directory of Open Access Journals (Sweden)

    Md. Imtaiyaz Hassan

    2013-12-01

    Full Text Available Professor Tej Pal Singh, an internationally recognized Indian scientist par excellence, is one of the pioneers of Indian macromolecular crystallography. He is a person of significant and enduring accomplishments as a teacher, scientist, administrator and family man. He has developed various methods to crystallize wide varieties of proteins. He has successfully determined crystal structures of lactoferrin, phospholipase A2, lactoperoxidase, peptidoglycan recognition proteins, disintegrin, zinc-α2-glycoprotein and several others including various protein-ligand and protein-protein complexes. He has a remarkably high number of structural entries in protein data bank. He received most of the prestigious awards and honors by Indian Government. This article covers most of his research and other achievements which will be a source of inspiration for young scientific community, motivation for peers and joy for his fellow colleagues and friends.

  2. Identification of macromolecular complexes in cryoelectron tomograms of phantom cells

    Science.gov (United States)

    Frangakis, Achilleas S.; Böhm, Jochen; Förster, Friedrich; Nickell, Stephan; Nicastro, Daniela; Typke, Dieter; Hegerl, Reiner; Baumeister, Wolfgang

    2002-01-01

    Electron tomograms of intact frozen-hydrated cells are essentially three-dimensional images of the entire proteome of the cell, and they depict the whole network of macromolecular interactions. However, this information is not easily accessible because of the poor signal-to-noise ratio of the tomograms and the crowded nature of the cytoplasm. Here, we describe a template matching algorithm that is capable of detecting and identifying macromolecules in tomographic volumes in a fully automated manner. The algorithm is based on nonlinear cross correlation and incorporates elements of multivariate statistical analysis. Phantom cells, i.e., lipid vesicles filled with macromolecules, provide a realistic experimental scenario for an assessment of the fidelity of this approach. At the current resolution of ≈4 nm, macromolecules in the size range of 0.5–1 MDa can be identified with good fidelity. PMID:12391313

  3. Detecting stoichiometry of macromolecular complexes in live cells using FRET

    Science.gov (United States)

    Ben-Johny, Manu; Yue, Daniel N.; Yue, David T.

    2016-01-01

    The stoichiometry of macromolecular interactions is fundamental to cellular signalling yet challenging to detect from living cells. Fluorescence resonance energy transfer (FRET) is a powerful phenomenon for characterizing close-range interactions whereby a donor fluorophore transfers energy to a closely juxtaposed acceptor. Recognizing that FRET measured from the acceptor's perspective reports a related but distinct quantity versus the donor, we utilize the ratiometric comparison of the two to obtain the stoichiometry of a complex. Applying this principle to the long-standing controversy of calmodulin binding to ion channels, we find a surprising Ca2+-induced switch in calmodulin stoichiometry with Ca2+ channels—one calmodulin binds at basal cytosolic Ca2+ levels while two calmodulins interact following Ca2+ elevation. This feature is curiously absent for the related Na channels, also potently regulated by calmodulin. Overall, our assay adds to a burgeoning toolkit to pursue quantitative biochemistry of dynamic signalling complexes in living cells. PMID:27922011

  4. An analysis of fractal geometry of macromolecular gelation

    Institute of Scientific and Technical Information of China (English)

    左榘; 陈天红; 冉少峰; 何炳林; 董宝中; 生文君; 杨恒林

    1996-01-01

    With fractal geometry theory and based on experiments, an analysis of fractal geometry behavior of gelation of macromolecules was carried out. Using the cross-linking copolymerization of styrene-divinylbenzene (DVB) as an example, through the determinations of the evolution of the molecular weight, size and the dependence of scattering intensity on the angle of macromolecules by employing laser and synchrotron small angle X-ray scattering, respectively, this chemical reaction was described quantitatively, its fractal behavior was analyzed and the fractal dimension was also measured. By avoiding the complex theories on gelation, this approach is based on modern physical techniques and theories to perform the analysis of the behavior of fractal geometry of macromolecular gelation and thus is able to reveal the rules of this kind of complicated gelation more essentially and profoundly.

  5. Macromolecularly "Caged" Carbon Nanoparticles for Intracellular Trafficking via Switchable Photoluminescence.

    Science.gov (United States)

    Misra, Santosh K; Srivastava, Indrajit; Tripathi, Indu; Daza, Enrique; Ostadhossein, Fatemeh; Pan, Dipanjan

    2017-02-08

    Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counterionic macromolecular caging and decaging at the nanoscale. A negatively charged uncoated, "bare" CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant molecules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies. Results indicated for the first time that luminescence switchable CNPs can be synthesized for efficient intracellular tracking. This study further supports the origin of photoluminescence in CNP as a surface phenomenon correlated a function of characteristic charged macromolecules.

  6. On macromolecular refinement at subatomic resolution withinteratomic scatterers

    Energy Technology Data Exchange (ETDEWEB)

    Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.; Lunin, Vladimir Y.; Urzhumtsev, Alexandre

    2007-11-09

    A study of the accurate electron density distribution in molecular crystals at subatomic resolution, better than {approx} 1.0 {angstrom}, requires more detailed models than those based on independent spherical atoms. A tool conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8-1.0 {angstrom}, the number of experimental data is insufficient for the full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark datasets gave results comparable in quality with results of multipolar refinement and superior of those for conventional models. Applications to several datasets of both small- and macro-molecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

  7. Protein Coevolution and Isoexpression in Yeast Macromolecular Complexes

    Directory of Open Access Journals (Sweden)

    Laurence Ettwiller

    2007-01-01

    Full Text Available Previous studies in the yeast Saccharomyces cerevisiae have shown that genes encoding subunits of macromolecular complexes have similar evolutionary rates (K and expression levels (E. Besides, it is known that the expression of a gene is a strong predictor of its rate of evolution (i.e., E and K are correlated. Here we show that intracomplex variation of subunit expression correlates with intracomplex variation of their evolutionary rates (using two different measures of dispersion. However, a similar trend was observed for randomized complexes. Therefore, using a mathematical transformation, we created new variables capturing intracomplex variation of both E and K. The values of these new compound variables were smaller for real complexes than for randomized ones. This shows that proteins in complexes tend to have closer expressivities (E and K's simultaneously than in the randomly grouped genes. We speculate about the possible implications of this finding.

  8. [Progress in researches on synthetic antimicrobial macromolecular polymers].

    Science.gov (United States)

    Wei, Gang; Yang, Lihua; Chu, Liangyin

    2010-08-01

    Broad-spectrum antimicrobial peptides provide a new way to address the urgent growing problem of bacterial resistance. However, the limited natural resources and the high cost of extraction and purification of natural antimicrobial peptides can not meet the requirements of clinical application. In order to solve this problem, researchers have utilized two basic common structural features (amphiphilic and cationic) for designing and preparing synthetic antimicrobial macromolecular polymers. During the last decade, several kinds of amphiphilic polymers, including arylamide oligomers, phenylene ethynylenes, polymethacrylates, polynorbornenes as well as nylon-3 polymers have been synthesized. In this paper, the structures, antibacterial activities and selectivities of these polymers are reviewed, and the effects of molecular size, polarity and ratio of hydrophobic groups, positive charge density on antibacterial activity and selectivity are also summarized.

  9. Macromolecular Crystallization with Microfluidic Free-Interface Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Segelke, B

    2005-02-24

    Fluidigm released the Topaz 1.96 and 4.96 crystallization chips in the fall of 2004. Topaz 1.96 and 4.96 are the latest evolution of Fluidigm's microfluidics crystallization technologies that enable ultra low volume rapid screening for macromolecular crystallization. Topaz 1.96 and 4.96 are similar to each other but represent a major redesign of the Topaz system and have of substantially improved ease of automation and ease of use, improved efficiency and even further reduced amount of material needed. With the release of the new Topaz system, Fluidigm continues to set the standard in low volume crystallization screening which is having an increasing impact in the field of structural genomics, and structural biology more generally. In to the future we are likely to see further optimization and increased utility of the Topaz crystallization system, but we are also likely to see further innovation and the emergence of competing technologies.

  10. In-vacuum long-wavelength macromolecular crystallography.

    Science.gov (United States)

    Wagner, Armin; Duman, Ramona; Henderson, Keith; Mykhaylyk, Vitaliy

    2016-03-01

    Structure solution based on the weak anomalous signal from native (protein and DNA) crystals is increasingly being attempted as part of synchrotron experiments. Maximizing the measurable anomalous signal by collecting diffraction data at longer wavelengths presents a series of technical challenges caused by the increased absorption of X-rays and larger diffraction angles. A new beamline at Diamond Light Source has been built specifically for collecting data at wavelengths beyond the capability of other synchrotron macromolecular crystallography beamlines. Here, the theoretical considerations in support of the long-wavelength beamline are outlined and the in-vacuum design of the endstation is discussed, as well as other hardware features aimed at enhancing the accuracy of the diffraction data. The first commissioning results, representing the first in-vacuum protein structure solution, demonstrate the promising potential of the beamline.

  11. Extracting trends from two decades of microgravity macromolecular crystallization history

    Science.gov (United States)

    Judge, Russell A.; Snell, Edward H.; van der Woerd, Mark J.

    2005-01-01

    Since the 1980s hundreds of macromolecular crystal growth experiments have been performed in the reduced acceleration environment of an orbiting spacecraft. Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown. Similarly, many samples have shown no improvement or degradation in comparison to those grown on the ground. A complex series of interrelated factors affect these experiments and by building a comprehensive archive of the results it was aimed to identify factors that result in success and those that result in failure. Specifically, it was found that dedicated microgravity missions increase the chance of success when compared with those where crystallization took place as a parasitic aspect of the mission. It was also found that the chance of success could not be predicted based on any discernible property of the macromolecule available to us.

  12. Large-volume protein crystal growth for neutron macromolecular crystallography.

    Science.gov (United States)

    Ng, Joseph D; Baird, James K; Coates, Leighton; Garcia-Ruiz, Juan M; Hodge, Teresa A; Huang, Sijay

    2015-04-01

    Neutron macromolecular crystallography (NMC) is the prevailing method for the accurate determination of the positions of H atoms in macromolecules. As neutron sources are becoming more available to general users, finding means to optimize the growth of protein crystals to sizes suitable for NMC is extremely important. Historically, much has been learned about growing crystals for X-ray diffraction. However, owing to new-generation synchrotron X-ray facilities and sensitive detectors, protein crystal sizes as small as in the nano-range have become adequate for structure determination, lessening the necessity to grow large crystals. Here, some of the approaches, techniques and considerations for the growth of crystals to significant dimensions that are now relevant to NMC are revisited. These include experimental strategies utilizing solubility diagrams, ripening effects, classical crystallization techniques, microgravity and theoretical considerations.

  13. NATO Advanced Study Institute on Evolving Methods for Macromolecular Gystallography

    CERN Document Server

    Read, Randy J

    2007-01-01

    X-ray crystallography is the pre-eminent technique for visualizing the structures of macromolecules at atomic resolution. These structures are central to understanding the detailed mechanisms of biological processes, and to discovering novel therapeutics using a structure-based approach. As yet, structures are known for only a small fraction of the proteins encoded by human and pathogenic genomes. To counter the myriad modern threats of disease, there is an urgent need to determine the structures of the thousands of proteins whose structure and function remain unknown. This volume draws on the expertise of leaders in the field of macromolecular crystallography to illuminate the dramatic developments that are accelerating progress in structural biology. Their contributions span the range of techniques from crystallization through data collection, structure solution and analysis, and show how modern high-throughput methods are contributing to a deeper understanding of medical problems.

  14. Radiation damage to nucleoprotein complexes in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary [University of Oxford, South Parks Road, Oxford OX1 3QU (United Kingdom); Ravelli, Raimond B. G. [Maastricht University, PO Box 616, Maastricht 6200 MD (Netherlands); Carmichael, Ian [University of Notre Dame, Notre Dame, IN 46556 (United States); Kneale, Geoff; McGeehan, John E., E-mail: john.mcgeehan@port.ac.uk [University of Portsmouth, King Henry 1st Street, Portsmouth PO1 2DY (United Kingdom)

    2015-01-30

    Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N{sub 1}—C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses.

  15. The Effect of Attractive Interactions and Macromolecular Crowding on Crystallins Association.

    Directory of Open Access Journals (Sweden)

    Jiachen Wei

    Full Text Available In living systems proteins are typically found in crowded environments where their effective interactions strongly depend on the surrounding medium. Yet, their association and dissociation needs to be robustly controlled in order to enable biological function. Uncontrolled protein aggregation often causes disease. For instance, cataract is caused by the clustering of lens proteins, i.e., crystallins, resulting in enhanced light scattering and impaired vision or blindness. To investigate the molecular origins of cataract formation and to design efficient treatments, a better understanding of crystallin association in macromolecular crowded environment is needed. Here we present a theoretical study of simple coarse grained colloidal models to characterize the general features of how the association equilibrium of proteins depends on the magnitude of intermolecular attraction. By comparing the analytic results to the available experimental data on the osmotic pressure in crystallin solutions, we identify the effective parameters regimes applicable to crystallins. Moreover, the combination of two models allows us to predict that the number of binding sites on crystallin is small, i.e. one to three per protein, which is different from previous estimates. We further observe that the crowding factor is sensitive to the size asymmetry between the reactants and crowding agents, the shape of the protein clusters, and to small variations of intermolecular attraction. Our work may provide general guidelines on how to steer the protein interactions in order to control their association.

  16. New bioactive compounds from korean native mushrooms.

    Science.gov (United States)

    Kim, Seong-Eun; Hwang, Byung Soon; Song, Ja-Gyeong; Lee, Seung Woong; Lee, In-Kyoung; Yun, Bong-Sik

    2013-12-01

    Mushrooms are ubiquitous in nature and have high nutritional attributes. They have demonstrated diverse biological effects and therefore have been used in treatments of various diseases, including cancer, diabetes, bacterial and viral infections, and ulcer. In particular, polysaccharides, including β-glucan, are considered as the major constituents responsible for the biological activity of mushrooms. Although an overwhelming number of reports have been published on the importance of polysaccharides as immunomodulating agents, not all of the healing properties found in these mushrooms could be fully accounted for. Recently, many research groups have begun investigations on biologically active small-molecular weight compounds in wild mushrooms. In this mini-review, both structural diversity and biological activities of novel bioactive substances from Korean native mushrooms are described.

  17. NOVEL BIOACTIVE COMPOUNDS FROM MANGROVE DERIVED ACTINOMYCETES

    Directory of Open Access Journals (Sweden)

    Kumari Amrita

    2012-09-01

    Full Text Available Mangrove is most productive and unexplored ecosystem that approximately covers one fourth of world coastline with high diversity of thriving organism. Recently the rate of isolation of novel bioactive compounds from microorganism living in mangrove forest has tremendously increased which is reflected in significant hasten for exploration of mangrove actinomycetes. Actinomycetes are group of bacteria which are extremely interesting as active producers of many primary and secondary metabolites. Many survey reports has depicted that the biologically active compounds which have been obtained so far from microbes, 45 percent are produced by actinomycetes, 38 percent by fungi and 17 percent by unicellular bacteria. Actinomycetes from mangrove environment provide diverse and are potential rich source of antibiotics, anticancer, antifungal and antiviral agent, enzyme and enzyme inhibitor. Mangrove actinomycetes are a prolific but underexploited source for the discovery of novel secondary metabolites.

  18. Fluorescent Bioactive Corrole Grafted-Chitosan Films.

    Science.gov (United States)

    Barata, Joana F B; Pinto, Ricardo J B; Vaz Serra, Vanda I R C; Silvestre, Armando J D; Trindade, Tito; Neves, Maria Graça P M S; Cavaleiro, José A S; Daina, Sara; Sadocco, Patrizia; Freire, Carmen S R

    2016-04-11

    Transparent corrole grafted-chitosan films were prepared by chemical modification of chitosan with a corrole macrocycle, namely, 5,10,15-tris(pentafluorophenyl)corrole (TPFC), followed by solvent casting. The obtained films were characterized in terms of absorption spectra (UV-vis), FLIM (fluorescence lifetime imaging microscopy), structure (FTIR, XPS), thermal stability (TGA), thermomechanical properties (DMA), and antibacterial activity. The results showed that the chemical grafting of chitosan with corrole units did not affect its film-forming ability and that the grafting yield increased with the reaction time. The obtained transparent films presented fluorescence which increases with the amount of grafted corrole units. Additionally, all films showed bacteriostatic effect against S. aureus, as well as good thermomechanical properties and thermal stability. Considering these features, promising applications may be envisaged for these corrole-chitosan films, such as biosensors, bioimaging agents, and bioactive optical devices.

  19. Nocardiopsis species: a potential source of bioactive compounds.

    Science.gov (United States)

    Bennur, T; Ravi Kumar, A; Zinjarde, S S; Javdekar, V

    2016-01-01

    Members of the genus Nocardiopsis are an ecologically versatile and biotechnologically important group of Actinomycetes. Most of the isolates are halotolerant or halophilic and they prevail in soils, marine environments or hypersaline locations. To aid their survival under these conditions, they mainly produce extremozymes, compatible solutes, surfactants and bioactive compounds. The current review details the bioactive compounds obtained for this genus. Important antimicrobial agents obtained from this genus include polyketides, phenzines, quinoline alkaloids, terphenyls, proteins, thiopeptides and amines. Polyketides and peptides displaying potent anticancer activities are also significant. Tumour promoting agents, P-glycoprotein (P-gp) inhibitors, immunomodulators and protein kinase inhibitors are other relevant products obtained from Nocardiopsis species. Structurally, polyketides (synthesized by polyketide synthases) and peptides (made by nonribosomal peptide synthetases or cyclodipeptide synthases) are important compounds. Considered here are also toxins, anti photoaging and adipogenic agents produced by this genus. The gene clusters mediating the synthesis of bioactive compounds have been described. Commercially available products (Apoptolidins and K-252a) derived from this genus have also been described. This review highlights the significance of a single genus in producing an assortment of compounds with varied biological activities. On account of these features, the members of this genus have established a place for themselves and are of considerable value in producing compounds with profound bio-medical applications.

  20. The future of bioactive ceramics.

    Science.gov (United States)

    Hench, Larry L

    2015-02-01

    Two important worldwide needs must be satisfied in the future; (1) treatment of the deteriorating health of an aging population and, (2) decreasing healthcare costs to meet the needs of an increased population. The ethical and economic dilemma is how to achieve equality in quality of care while at the same time decreasing cost of care for an ever-expanding number of people. The limited lifetime of prosthetic devices made from first-generation nearly inert biomaterials requires new approaches to meet these two large needs. This paper advises an expanded emphasis on: (1) regeneration of tissues and (2) prevention of tissue deterioration to meet this growing need. Innovative use of bioactive ceramics with genetic control of in situ tissue responses offers the potential to achieve both tissue regeneration and prevention. Clinical success of use of bioactive glass for bone regeneration is evidence that this concept works. Likewise the use of micron sized bioactive glass powders in a dentifrice for re-mineralization of teeth provides evidence that prevention of tissue deterioration is also possible. This opinion paper outlines clinical needs that could be met by innovative use of bioactive glasses and ceramics in the near future; including: regeneration of skeletal tissues that is patient specific and genetic based, load-bearing bioactive glass-ceramics for skeletal and ligament and tendon repair, repair and regeneration of soft tissues, and rapid low-cost analysis of human cell-biomaterial interactions leading to patient specific diagnoses and treatments using molecularly tailored bioceramics.

  1. Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Shih, C.J., E-mail: cjshih@kmu.edu.tw [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chen, H.T. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Huang, L.F. [School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lu, P.S.; Chang, H.F. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, I.L., E-mail: 84004@cch.org.tw [Department of Orthopaedic Surgery, Chang-Hua Christian Hospital, Changhua 500, Taiwan (China)

    2010-06-15

    The main objective of the present study was to determine the effect of thermal treatment procedures (calcination temperature, heating rate and duration time) on the synthesis of SiO{sub 2}-CaO-P{sub 2}O{sub 5} mesoporous bioactive glass scaffolds. This is accomplished by thermogravimetric analyses, Fourier transform infrared (FTIR) absorption spectra, X-ray diffraction (XRD) and by analysis of nitrogen adsorption/desorption isotherms. In vitro bioactivity can also be assessed by the cytotoxic effect of the glasses on the NIH-3T3 cell line, and by characterization of MC-3T3-E1 cell attachment.

  2. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    . In particular, 3-15% of very low birth weight preterm infants suffer from the most servere form of intestinal inflammation, known as necrotizing enterocolitis (NEC). This disease is incurable with a high mortality rate of 15-30%. Mother’s breast milk consists of different bioactive constituents...... several steps of thermal processing, which are known to decrease/abolish bioactivity of milk constituents. This may explain for high NEC incidence in formula-fed preterm infants. We therefore in this PhD project investigated whether gentle thermal processing conditions increase the bioavailability...... of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  3. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    . In particular, 3-15% of very low birth weight preterm infants suffer from the most servere form of intestinal inflammation, known as necrotizing enterocolitis (NEC). This disease is incurable with a high mortality rate of 15-30%. Mother’s breast milk consists of different bioactive constituents...... several steps of thermal processing, which are known to decrease/abolish bioactivity of milk constituents. This may explain for high NEC incidence in formula-fed preterm infants. We therefore in this PhD project investigated whether gentle thermal processing conditions increase the bioavailability...... of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  4. NMR RELAXIVITY AND IMAGING OF NEUTRAL MACROMOLECULAR POLYESTER GADOLINIUM (Ⅲ) COMPLEXES

    Institute of Scientific and Technical Information of China (English)

    Kai-chao Yu; Hong-bing Hu; Mai-li Liu; Han-zhen Yuan; Chao-hui Ye; Ren-xi Zhuo

    1999-01-01

    Five neutral macromolecular polyester gadolinium (Ⅲ) complexes with pendant hydrophobic alkyl and aromatic functional groups were prepared. The longitudinal relaxation rates of these complexes were measured. One of these Gd (Ⅲ) complexes was chosen for the acute toxicity test and T1-weighted imaging measurement. Preliminary results showed that. compared with Gd-DTPA, the neutral macromolecular gadolinium (Ⅲ) complexes provide higher T1 relaxivity enhancement and longer function duration.

  5. Preparation and bioactivity of sol-gel macroporous bioactive glass

    Institute of Scientific and Technical Information of China (English)

    Zhihua Zhou; Jianming Ruan; Jianpeng Zou; Zhongcheng Zhou

    2008-01-01

    Bioactive glass is well known for its ability of bone regeneration, and sol-gel bioactive glass has many advantages com-pared with melt-derived bioactive glass. 3-D scaffold prepared by the sol-gel method is a promising substrate material for bone tissue engineering and large-scale bone repair. Porous sol-gel glass in the CaO-SiO2-P2O5 system with macropores larger than 100 μm was prepared by the addition of stearic acid as a pore former. The diameter of the pore created by the pore former varied from 100 to 300μm. The formation of a hydroxyapatite layer on the glass was analyzed by studying the surface of the porous glass by scanning elec-tron microscopy, energy dispersive spectroscopy, X-ray diffraction, and Raman spectra after they had been immersed in simulated body fluid (SBF) for some time, and the porous glass shows good bioactivity.

  6. Therapeutic potential of dairy bioactive peptides: A contemporary perspective.

    Science.gov (United States)

    Sultan, Saira; Huma, Nuzhat; Butt, Masood Sadiq; Aleem, Muhammad; Abbas, Munawar

    2016-02-06

    Dairy products are associated with numerous health benefits. These are a good source of nutrients such as carbohydrates, protein (bioactive peptides), lipids, minerals, and vitamins, which are essential for growth, development, and maintenance of the human body. Accordingly, dairy bioactive peptides are one of the targeted compounds present in different dairy products. Dairy bioactive compounds can be classified as antihypertensive, anti-oxidative, immmunomodulant, anti-mutagenic, antimicrobial, opoid, anti-thrombotic, anti-obesity, and mineral-binding agents, depending upon biological functions. These bioactive peptides can easily be produced by enzymatic hydrolysis, and during fermentation and gastrointestinal digestion. For this reason, fermented dairy products, such as yogurt, cheese, and sour milk, are gaining popularity worldwide, and are considered excellent source of dairy peptides. Furthermore, fermented and non-fermented dairy products are associated with lower risks of hypertension, coagulopathy, stroke, and cancer insurgences. The current review article is an attempt to disseminate general information about dairy peptides and their health claims to scientists, allied stakeholders, and, certainly, readers.

  7. A versatile microparticle-based immunoaggregation assay for macromolecular biomarker detection and quantification.

    Directory of Open Access Journals (Sweden)

    Haiyan Wu

    Full Text Available The rapid, sensitive and low-cost detection of macromolecular biomarkers is critical in clinical diagnostics, environmental monitoring, research, etc. Conventional assay methods usually require bulky, expensive and designated instruments and relative long assay time. For hospitals and laboratories that lack immediate access to analytical instruments, fast and low-cost assay methods for the detection of macromolecular biomarkers are urgently needed. In this work, we developed a versatile microparticle (MP-based immunoaggregation method for the detection and quantification of macromolecular biomarkers. Antibodies (Abs were firstly conjugated to MP through streptavidin-biotin interaction; the addition of macromolecular biomarkers caused the aggregation of Ab-MPs, which were subsequently detected by an optical microscope or optical particle sizer. The invisible nanometer-scale macromolecular biomarkers caused detectable change of micrometer-scale particle size distributions. Goat anti-rabbit immunoglobulin and human ferritin were used as model biomarkers to demonstrate MP-based immunoaggregation assay in PBS and 10% FBS to mimic real biomarker assay in the complex medium. It was found that both the number ratio and the volume ratio of Ab-MP aggregates caused by biomarker to all particles were directly correlated to the biomarker concentration. In addition, we found that the detection range could be tuned by adjusting the Ab-MP concentration. We envision that this novel MP-based immunoaggregation assay can be combined with multiple detection methods to detect and quantify macromolecular biomarkers at the nanogram per milliliter level.

  8. Bioactive glasses potential biomaterials for future therapy

    CERN Document Server

    Kaur, Gurbinder

    2017-01-01

    This book describes the history, origin and basic characteristics of bioactive materials. It includes a chapter dedicated to hydroxyapatite mineral, its formation and its bioactive properties. The authors address how cytotoxicity is a determining step for bioactivity. Applications of bioactive materials in the contexts of tissue regeneration, bone regeneration and cancer therapy are also covered. Silicate, metallic and mesoporous glasses are described, as well as the challenges and future prospects of research in this field.

  9. JBluIce-EPICS control system for macromolecular crystallography.

    Energy Technology Data Exchange (ETDEWEB)

    Stepanov, S.; Makarov, O.; Hilgart, M.; Pothineni, S.; Urakhchin, A.; Devarapalli, S.; Yoder, D.; Becker, M.; Ogata, C.; Sanishvili, R.; Nagarajan, V.; Smith, J. L.; Fischetti, R. F. (Biosciences Division); (Univ. of Michigan)

    2011-01-01

    The trio of macromolecular crystallography beamlines constructed by the General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) in Sector 23 of the Advanced Photon Source (APS) have been in growing demand owing to their outstanding beam quality and capacity to measure data from crystals of only a few micrometres in size. To take full advantage of the state-of-the-art mechanical and optical design of these beamlines, a significant effort has been devoted to designing fast, convenient, intuitive and robust beamline controls that could easily accommodate new beamline developments. The GM/CA-CAT beamline controls are based on the power of EPICS for distributed hardware control, the rich Java graphical user interface of Eclipse RCP and the task-oriented philosophy as well as the look and feel of the successful SSRL BluIce graphical user interface for crystallography. These beamline controls feature a minimum number of software layers, the wide use of plug-ins that can be written in any language and unified motion controls that allow on-the-fly scanning and optimization of any beamline component. This paper describes the ways in which BluIce was combined with EPICS and converted into the Java-based JBluIce, discusses the solutions aimed at streamlining and speeding up operations and gives an overview of the tools that are provided by this new open-source control system for facilitating crystallographic experiments, especially in the field of microcrystallography.

  10. Patch-clamp detection of macromolecular translocation along nuclear pores

    Directory of Open Access Journals (Sweden)

    Bustamante J.O.

    1998-01-01

    Full Text Available The present paper reviews the application of patch-clamp principles to the detection and measurement of macromolecular translocation along the nuclear pores. We demonstrate that the tight-seal 'gigaseal' between the pipette tip and the nuclear membrane is possible in the presence of fully operational nuclear pores. We show that the ability to form a gigaseal in nucleus-attached configurations does not mean that only the activity of channels from the outer membrane of the nuclear envelope can be detected. Instead, we show that, in the presence of fully operational nuclear pores, it is likely that the large-conductance ion channel activity recorded derives from the nuclear pores. We conclude the technical section with the suggestion that the best way to demonstrate that the nuclear pores are responsible for ion channel activity is by showing with fluorescence microscopy the nuclear translocation of ions and small molecules and the exclusion of the same from the cisterna enclosed by the two membranes of the envelope. Since transcription factors and mRNAs, two major groups of nuclear macromolecules, use nuclear pores to enter and exit the nucleus and play essential roles in the control of gene activity and expression, this review should be useful to cell and molecular biologists interested in understanding how patch-clamp can be used to quantitate the translocation of such macromolecules into and out of the nucleus

  11. Timely deposition of macromolecular structures is necessary for peer review

    Energy Technology Data Exchange (ETDEWEB)

    Joosten, Robbie P. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Soueidan, Hayssam; Wessels, Lodewyk F. A. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam (Netherlands); Perrakis, Anastassis, E-mail: a.perrakis@nki.nl [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2013-12-01

    Deposition of crystallographic structures should be concurrent with or prior to manuscript submission for peer review, enabling validation and increasing reliability of the PDB. Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature.

  12. Synchrotron radiation macromolecular crystallography: science and spin-offs

    Directory of Open Access Journals (Sweden)

    John R. Helliwell

    2015-03-01

    Full Text Available A current overview of synchrotron radiation (SR in macromolecular crystallography (MX instrumentation, methods and applications is presented. Automation has been and remains a central development in the last decade, as have the rise of remote access and of industrial service provision. Results include a high number of Protein Data Bank depositions, with an increasing emphasis on the successful use of microcrystals. One future emphasis involves pushing the frontiers of using higher and lower photon energies. With the advent of X-ray free-electron lasers, closely linked to SR developments, the use of ever smaller samples such as nanocrystals, nanoclusters and single molecules is anticipated, as well as the opening up of femtosecond time-resolved diffraction structural studies. At SR sources, a very high-throughput assessment for the best crystal samples and the ability to tackle just a few micron and sub-micron crystals will become widespread. With higher speeds and larger detectors, diffraction data volumes are becoming long-term storage and archiving issues; the implications for today and the future are discussed. Together with the rise of the storage ring to its current pre-eminence in MX data provision, the growing tendency of central facility sites to offer other centralized facilities complementary to crystallography, such as cryo-electron microscopy and NMR, is a welcome development.

  13. New concepts and applications in the macromolecular chemistry of fullerenes.

    Science.gov (United States)

    Giacalone, Francesco; Martín, Nazario

    2010-10-08

    A new classification on the different types of fullerene-containing polymers is presented according to their different properties and applications they exhibit in a variety of fields. Because of their interest and novelty, water-soluble and biodegradable C(60)-polymers are discussed first, followed by polyfullerene-based membranes where unprecedented supramolecular structures are presented. Next are compounds that involve hybrid materials formed from fullerenes and other components such as silica, DNA, and carbon nanotubes (CNTs) where the most recent advances have been achieved. A most relevant topic is still that of C(60)-based donor-acceptor (D-A) polymers. Since their application in photovoltaics D-A polymers are among the most realistic applications of fullerenes in the so-called molecular electronics. The most relevant aspects in these covalently connected fullerene/polymer hybrids as well as new concepts to improve energy conversion efficiencies are presented.The last topics disccused relate to supramolecular aspects that are in involved in C(60)-polymer systems and in the self-assembly of C(60)-macromolecular structures, which open a new scenario for organizing, by means of non-covalent interactions, new supramolecular structures at the nano- and micrometric scale, in which the combination of the hydrofobicity of fullerenes with the versatility of the noncovalent chemistry afford new and spectacular superstructures.

  14. Macromolecular metallurgy of binary mesocrystals via designed multiblock terpolymers.

    Science.gov (United States)

    Xie, Nan; Liu, Meijiao; Deng, Hanlin; Li, Weihua; Qiu, Feng; Shi, An-Chang

    2014-02-26

    Self-assembling block copolymers provide access to the fabrication of various ordered phases. In particular, the ordered spherical phases can be used to engineer soft mesocrystals with domain size at the 5-100 nm scales. Simple block copolymers, such as diblock copolymers, form a limited number of mesocrystals. However multiblock copolymers are capable to form more complex mesocrystals. We demonstrate that designed B1AB2CB3 multiblock terpolymers, in which the A- and C-blocks form spherical domains and the packing of these spheres can be controlled by changing the lengths of the middle and terminal B-blocks, self-assemble into various binary mesocrystals with space group symmetries of a large number of binary ionic crystals, including NaCl, CsCl, ZnS, α-BN, AlB2, CaF2, TiO2, ReO3, Li3Bi, Nb3Sn(A15), and α-Al2O3. This approach can be generalized to other terpolymers as well as to tetrapolymers to obtain ternary mesocrystals. Our study provides a new concept of macromolecular metallurgy for producing crystal phases in a mesoscale and thus makes multiblock copolymers a robust platform for the engineering of functional materials.

  15. Macromolecular Powder Diffraction: Ready for genuine biological problems.

    Science.gov (United States)

    Karavassili, Fotini; Margiolaki, Irene

    2016-01-01

    Knowledge of 3D structures of biological molecules plays a major role in both understanding important processes of life and developing pharmaceuticals. Among several methods available for structure determination, macromolecular X-ray powder diffraction (XRPD) has transformed over the past decade from an impossible dream to a respectable method. XRPD can be employed in biosciences for various purposes such as observing phase transitions, characterizing bulk pharmaceuticals, determining structures via the molecular replacement method, detecting ligands in protein-ligand complexes, as well as combining micro-sized single crystal crystallographic data and powder diffraction data. Studies using synchrotron and laboratory sources in some standard configuration setups are reported in this review, including their respective advantages and disadvantages. Methods presented here provide an alternative, complementary set of tools to resolve structural problems. A variety of already existing software packages for powder diffraction data processing and analysis, some of which have been adapted to large unit cell studies, are briefly described. This review aims to provide necessary elements of theory and current methods, along with practical explanations, available software packages and highlighted case studies.

  16. Canadian macromolecular crystallography facility: a suite of fully automated beamlines.

    Science.gov (United States)

    Grochulski, Pawel; Fodje, Michel; Labiuk, Shaunivan; Gorin, James; Janzen, Kathryn; Berg, Russ

    2012-06-01

    The Canadian light source is a 2.9 GeV national synchrotron radiation facility located on the University of Saskatchewan campus in Saskatoon. The small-gap in-vacuum undulator illuminated beamline, 08ID-1, together with the bending magnet beamline, 08B1-1, constitute the Canadian Macromolecular Crystallography Facility (CMCF). The CMCF provides service to more than 50 Principal Investigators in Canada and the United States. Up to 25% of the beam time is devoted to commercial users and the general user program is guaranteed up to 55% of the useful beam time through a peer-review process. CMCF staff provides "Mail-In" crystallography service to users with the highest scored proposals. Both beamlines are equipped with very robust end-stations including on-axis visualization systems, Rayonix 300 CCD series detectors and Stanford-type robotic sample auto-mounters. MxDC, an in-house developed beamline control system, is integrated with a data processing module, AutoProcess, allowing full automation of data collection and data processing with minimal human intervention. Sample management and remote monitoring of experiments is enabled through interaction with a Laboratory Information Management System developed at the facility.

  17. Immunological Regulation by Bioactive Lipids.

    Science.gov (United States)

    Taketomi, Yoshitaka; Murakami, Makoto

    2017-01-01

     Mast cells originate from hematopoietic stem cells and undergo terminal maturation in the extravascular tissues, in which they are ultimately resident. Mast maturation, phenotype, and function are dictated by the local microenvironment, which has a significant influence on the ability of mast cells to recognize and respond to stimuli. Activation of mast cells can lead to the release of three distinct classes of mediators, including preformed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo-synthesized bioactive lipid mediators. It is currently recognized that bioactive lipids such as arachidonic acid metabolites (prostaglandins and leukotrienes) released from mast cells modulate innate and adaptive immune responses both directly and indirectly through communication with other microenvironmental immune cells or stroma cells. Moreover, mast cells express a variety of lipid receptors and, if activated by bioactive lipids such as arachidonic acid, ω3 fatty acids, lysophospholipids, and their metabolites, can alter the release and production of other mediators including histamine, cytokines, and chemokines, and thereby alter homeostatic or pathophysiological responses. This review focuses on newly identified functional aspects of bioactive lipids with regard to their immune regulation and functional outcomes in both homeostasis and allergic disease.

  18. TRIAZOLE: A POTENTIAL BIOACTIVE AGENT (SYNTHESIS AND BIOLOGICAL ACTIVITY)

    OpenAIRE

    Pandeya Surendra Nath; Pathak Ashish; Mishra Rupesh

    2011-01-01

    Azoles belong to very important class of Antimicrobial drugs. Triazole is very important Azole which exists in two isomeric forms namely 1, 2, 3-Triazole and 1, 2, 4-Triazole. This Review Article covers the Different approaches to synthesize Triazoles having different substitution and their different biological activity. This Review article can be useful to synthesize new compounds having Triazole nucleolus.

  19. Anaerobes as Sources of Bioactive Compounds and Health Promoting Tools.

    Science.gov (United States)

    Mamo, Gashaw

    Aerobic microorganisms have been sources of medicinal agents for several decades and an impressive variety of drugs have been isolated from their cultures, studied and formulated to treat or prevent diseases. On the other hand, anaerobes, which are believed to be the oldest life forms on earth and evolved remarkably diverse physiological functions, have largely been neglected as sources of bioactive compounds. However, results obtained from the limited research done so far show that anaerobes are capable of producing a range of interesting bioactive compounds that can promote human health. In fact, some of these bioactive compounds are found to be novel in their structure and/or mode of action.Anaerobes play health-promoting roles through their bioactive products as well as application of whole cells. The bioactive compounds produced by these microorganisms include antimicrobial agents and substances such as immunomodulators and vitamins. Bacteriocins produced by anaerobes have been in use as preservatives for about 40 years. Because these substances are effective at low concentrations, encounter relatively less resistance from bacteria and are safe to use, there is a growing interest in these antimicrobial agents. Moreover, several antibiotics have been reported from the cultures of anaerobes. Closthioamide and andrimid produced by Clostridium cellulolyticum and Pantoea agglomerans, respectively, are examples of novel antibiotics of anaerobe origin. The discovery of such novel bioactive compounds is expected to encourage further studies which can potentially lead to tapping of the antibiotic production potential of this fascinating group of microorganisms.Anaerobes are widely used in preparation of fermented foods and beverages. During the fermentation processes, these organisms produce a number of bioactive compounds including anticancer, antihypertensive and antioxidant substances. The well-known health promoting effect of fermented food is mostly due to these

  20. Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Michael T. Puccinelli

    2017-07-01

    Full Text Available Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS, a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent.

  1. Review: Mycoendophytes in medicinal plants: Diversity and bioactivities

    Directory of Open Access Journals (Sweden)

    MUDASIR DAR

    2012-07-01

    Full Text Available Rai M, Gade A, Rathod D, Dar M, Varma A. 2012. Review: Mycoendophytes in medicinal plants: Diversity and bioactivities. Nusantara Bioscience 4: 86-96. Endophytes are microorganisms that reside in internal tissues of living plants without causing any negative effect. These offer tremendous potential for the exploitation of novel and eco-friendly secondary metabolites used in medicine, the pharmaceutical industry and agriculture. The present review is focused on diversity of endophytes, current national and international bioactive secondary metabolite scenario and future prospects. Endophytic fungi as novel source of potentially useful medicinal compounds are discussed along with the need to search for new and more effective agents from endophytes to combat disease problems.

  2. Azadirachta indica Mediated Bioactive Lyocell Yarn: Chemical and Colour Characterization

    Directory of Open Access Journals (Sweden)

    B. H. Patel

    2014-01-01

    Full Text Available The study deals with preparing aesthetic textiles using methanolic extract of Azadirachta indica leaves. The extract with metallic and natural mordents was utilized to create various shades on lyocell yarn using exhaust technique of dyeing. Aesthetic values of dyed yarns were analyzed in terms of colourimetric parameters, that is, CIE L*  a*  b* and colour fastness. The attachment of Azadirachta indica compounds has been confirmed by using infrared spectroscopy (IR analysis. The dyed samples exhibit moderate to good fastness properties. The study showed that lyocell yarn treated at 15% (owf methanolic extract of Azadirachta indica leaves can be utilized as effective bioactive textiles. Azadirachta indica is an alternative to synthetic antimicrobial agents. This bioactive yarn can be used in fashion as well as in medicinal industry.

  3. DOMMINO 2.0: integrating structurally resolved protein-, RNA-, and DNA-mediated macromolecular interactions.

    Science.gov (United States)

    Kuang, Xingyan; Dhroso, Andi; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

    2016-01-01

    Macromolecular interactions are formed between proteins, DNA and RNA molecules. Being a principle building block in macromolecular assemblies and pathways, the interactions underlie most of cellular functions. Malfunctioning of macromolecular interactions is also linked to a number of diseases. Structural knowledge of the macromolecular interaction allows one to understand the interaction's mechanism, determine its functional implications and characterize the effects of genetic variations, such as single nucleotide polymorphisms, on the interaction. Unfortunately, until now the interactions mediated by different types of macromolecules, e.g. protein-protein interactions or protein-DNA interactions, are collected into individual and unrelated structural databases. This presents a significant obstacle in the analysis of macromolecular interactions. For instance, the homogeneous structural interaction databases prevent scientists from studying structural interactions of different types but occurring in the same macromolecular complex. Here, we introduce DOMMINO 2.0, a structural Database Of Macro-Molecular INteractiOns. Compared to DOMMINO 1.0, a comprehensive database on protein-protein interactions, DOMMINO 2.0 includes the interactions between all three basic types of macromolecules extracted from PDB files. DOMMINO 2.0 is automatically updated on a weekly basis. It currently includes ∼1,040,000 interactions between two polypeptide subunits (e.g. domains, peptides, termini and interdomain linkers), ∼43,000 RNA-mediated interactions, and ∼12,000 DNA-mediated interactions. All protein structures in the database are annotated using SCOP and SUPERFAMILY family annotation. As a result, protein-mediated interactions involving protein domains, interdomain linkers, C- and N- termini, and peptides are identified. Our database provides an intuitive web interface, allowing one to investigate interactions at three different resolution levels: whole subunit network

  4. Non-contact luminescence lifetime cryothermometry for macromolecular crystallography.

    Science.gov (United States)

    Mykhaylyk, V B; Wagner, A; Kraus, H

    2017-05-01

    Temperature is a very important parameter when aiming to minimize radiation damage to biological samples during experiments that utilize intense ionizing radiation. A novel technique for remote, non-contact, in situ monitoring of the protein crystal temperature has been developed for the new I23 beamline at the Diamond Light Source, a facility dedicated to macromolecular crystallography (MX) with long-wavelength X-rays. The temperature is derived from the temperature-dependent decay time constant of luminescence from a minuscule scintillation sensor (luminescence lifetime thermometry is presented, the features of the detection method and the choice of temperature sensor are discussed, and it is demonstrated how the temperature monitoring system was integrated within the viewing system of the endstation used for the visualization of protein crystals. The thermometry system was characterized using a Bi4Ge3O12 crystal scintillator that exhibits good responsivity of the decay time constant as a function of temperature over a wide range (8-270 K). The scintillation sensor was calibrated and the uncertainty of the temperature measurements over the primary operation temperature range of the beamline (30-150 K) was assessed to be ±1.6 K. It has been shown that the temperature of the sample holder, measured using the luminescence sensor, agrees well with the expected value. The technique was applied to characterize the thermal performance of different sample mounts that have been used in MX experiments at the I23 beamline. The thickness of the mount is shown to have the greatest impact upon the temperature distribution across the sample mount. Altogether, these tests and findings demonstrate the usefulness of the thermometry system in highlighting the challenges that remain to be addressed for the in-vacuum MX experiment to become a reliable and indispensable tool for structural biology.

  5. A Compact X-Ray System for Macromolecular Crystallography. 5

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for macromolecular crystallography that combines a microfocus x-ray generator (40 gm FWHM spot size at a power level of 46.5Watts) and a 5.5 mm focal distance polycapillary optic. The Cu K(sub alpha) X-ray flux produced by this optimized system is 7.0 times above the X-ray flux previously reported. The X-ray flux from the microfocus system is also 3.2 times higher than that produced by the rotating anode generator equipped with a long focal distance graded multilayer monochromator (Green optic; CMF24-48-Cu6) and 30% less than that produced by the rotating anode generator with the newest design of graded multilayer monochromator (Blue optic; CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 Watts, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42,540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym) 5.0% for the data extending to 1.7A, and 4.8% for the complete set of data to 1.85A. The amplitudes of the reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  6. A Compact X-Ray System for Macromolecular Crystallography

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Gibson, Walter; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for a macromolecular crystallography that combines a microfocus x-ray generator (40 micrometer full width at half maximum spot size at a power level of 46.5 W) and a collimating polycapillary optic. The Cu Ka lpha x-ray flux produced by this optimized system through a 500,um diam orifice is 7.0 times greater than the x-ray flux previously reported by Gubarev et al. [M. Gubarev et al., J. Appl. Crystallogr. 33, 882 (2000)]. The x-ray flux from the microfocus system is also 2.6 times higher than that produced by a rotating anode generator equipped with a graded multilayer monochromator (green optic, Osmic Inc. CMF24-48-Cu6) and 40% less than that produced by a rotating anode generator with the newest design of graded multilayer monochromator (blue optic, Osmic, Inc. CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 W, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42 540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym)=5.0% for data extending to 1.70 A, and 4.8% for the complete set of data to 1.85 A. The amplitudes of the observed reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  7. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  8. Classification and basic properties of contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Geraldes, Carlos F G C; Laurent, Sophie

    2009-01-01

    A comprehensive classification of contrast agents currently used or under development for magnetic resonance imaging (MRI) is presented. Agents based on small chelates, macromolecular systems, iron oxides and other nanosystems, as well as responsive, chemical exchange saturation transfer (CEST) and hyperpolarization agents are covered in order to discuss the various possibilities of using MRI as a molecular imaging technique. The classification includes composition, magnetic properties, biodistribution and imaging applications. Chemical compositions of various classes of MRI contrast agents are tabulated, and their magnetic status including diamagnetic, paramagnetic and superparamagnetic are outlined. Classification according to biodistribution covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting strategies of molecular, macromolecular and particulate carriers are also illustrated.

  9. Characterization of cereulide synthetase, a toxin-producing macromolecular machine.

    Directory of Open Access Journals (Sweden)

    Diego A Alonzo

    Full Text Available Cereulide synthetase is a two-protein nonribosomal peptide synthetase system that produces a potent emetic toxin in virulent strains of Bacillus cereus. The toxin cereulide is a depsipeptide, as it consists of alternating aminoacyl and hydroxyacyl residues. The hydroxyacyl residues are derived from keto acid substrates, which cereulide synthetase selects and stereospecifically reduces with imbedded ketoreductase domains before incorporating them into the growing depsipeptide chain. We present an in vitro biochemical characterization of cereulide synthetase. We investigate the kinetics and side chain specificity of α-keto acid selection, evaluate the requirement of an MbtH-like protein for adenylation domain activity, assay the effectiveness of vinylsulfonamide inhibitors on ester-adding modules, perform NADPH turnover experiments and evaluate in vitro depsipeptide biosynthesis. This work also provides biochemical insight into depsipeptide-synthesizing nonribosomal peptide synthetases responsible for other bioactive molecules such as valinomycin, antimycin and kutzneride.

  10. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography

    Directory of Open Access Journals (Sweden)

    Julian C.-H. Chen

    2017-01-01

    Full Text Available The Protein Crystallography Station (PCS, located at the Los Alamos Neutron Scattering Center (LANSCE, was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER for 13 years (2002–2014. The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallography in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  11. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography.

    Science.gov (United States)

    Chen, Julian C-H; Unkefer, Clifford J

    2017-01-01

    The Protein Crystallography Station (PCS), located at the Los Alamos Neutron Scattering Center (LANSCE), was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER) for 13 years (2002-2014). The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallo-graphy in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  12. Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

    Science.gov (United States)

    Marín-Yaseli, Margarita R; Cid, Cristina; Yagüe, Ana I; Ruiz-Bermejo, Marta

    2017-02-01

    Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed.

  13. The Occurrence of Bioactive Micromonosporae in Aquatic Habitats of the Sunshine Coast in Australia

    Directory of Open Access Journals (Sweden)

    D. Ipek Kurtböke

    2008-06-01

    Full Text Available Screening strategies based on the ecological knowledge of antibiotic producing microorganisms and their roles in the natural environment are being increasingly employed in the search for novel antibiotic agents. Micromonosporae are common inhabitants of aquatic habitats and have proved to be a continuing source of novel bioactive compounds including antibacterial and antitumor agents. The ecological distribution and frequency of bioactive micromonosporae in Sunshine Coast region aquatic habitats were studied through a range of selective isolation procedures designed to negatively select against the isolation of unwanted microbial taxa commonly associated with marine environments. It was revealed that bioactive compound producing species of micromonosporae were present in the aquatic habitats of the Sunshine Coast region in Australia.

  14. Synthesis and characterization of miktoarm star copolymer of styrene and butadiene using multifunctional macromolecular initiator

    Institute of Scientific and Technical Information of China (English)

    Hai Yan Zhang; Xing Ying Zhang

    2009-01-01

    A new kind of multifunctional macromolecular initiator with Sn-C bonds and polydiene arms was synthesized by living anionic polymerization.At first,polydiene-stannum chloride(PD-SnCl3)was prepared by the reaction of n-butyl-Li(n-BuLi),stannic chloride(SnCl4)and diene.Then PD-SnCl3 was used to react with the dilithium initiator to prepare the multifunctional organic macromolecular initiators.The result suggested that the initiators had a remarkable yield by GPC,nearly 90%.By using these multifunctional macromolecular initiators,styrene and butadiene were effectively polymerized via anionic polymerization,which gave birth to novel miktoarm star copolymers.The relative molecular weight and polydispersity index,microstructure contents,copolymerization components,glass transition temperature(Tg)and morphology of the miktoarm star copolymers were investigated by GPC-UV,1H NMR,DSC and TEM,respectively.

  15. Use of Site-Specifically Tethered Chemical Nucleases to Study Macromolecular Reactions

    Directory of Open Access Journals (Sweden)

    Mukherjee Srabani

    2003-01-01

    Full Text Available During a complex macromolecular reaction multiple changes in molecular conformation and interactions with ligands may occur. X-ray crystallography may provide only a limited set of snapshots of these changes. Solution methods can augment such structural information to provide a more complete picture of a macromolecular reaction. We analyzed the changes in protein conformation and protein:nucleic acid interactions which occur during transcription initiation by using a chemical nuclease tethered to cysteines introduced site-specifically into the RNA polymerase of bacteriophage T7 (T7 RNAP. Changes in cleavage patterns as the polymerase steps through transcription reveal a series of structural transitions which mediate transcription initiation. Cleavage by tethered chemical nucleases is seen to be a powerful method for revealing the conformational dynamics of macromolecular reactions, and has certain advantages over cross-linking or energy transfer approaches.

  16. Macromolecular Hydrogen Sulfide Donors Trigger Spatiotemporally Confined Changes in Cell Signaling.

    Science.gov (United States)

    Ercole, Francesca; Mansfeld, Friederike M; Kavallaris, Maria; Whittaker, Michael R; Quinn, John F; Halls, Michelle L; Davis, Thomas P

    2016-01-11

    Hydrogen sulfide (H2S) is involved in a myriad of cell signaling processes that trigger physiological events ranging from vasodilation to cell proliferation. Moreover, disturbances to H2S signaling have been associated with numerous pathologies. As such, the ability to release H2S in a cellular environment and stimulate signaling events is of considerable interest. Herein we report the synthesis of macromolecular H2S donors capable of stimulating cell signaling pathways in both the cytosol and at the cell membrane. Specifically, copolymers having pendent oligo(ethylene glycol) and benzonitrile groups were synthesized, and the benzonitrile groups were subsequently transformed into primary aryl thioamide groups via thionation using sodium hydrosulfide. These thioamide moieties could be incorporated into a hydrophilic copolymer or a block copolymer (i.e., into either the hydrophilic or hydrophobic domain). An electrochemical sensor was used to demonstrate release of H2S under simulated physiological conditions. Subsequent treatment of HEK293 cells with a macromolecular H2S donor elicited a slow and sustained increase in cytosolic ERK signaling, as monitored using a FRET-based biosensor. The macromolecular donor was also shown to induce a small, fast and sustained increase in plasma membrane-localized PKC activity immediately following addition to cells. Studies using an H2S-selective fluorescent probe in live cells confirmed release of H2S from the macromolecular donor over physiologically relevant time scales consistent with the signaling observations. Taken together, these results demonstrate that by using macromolecular H2S donors it is possible to trigger spatiotemporally confined cell signaling events. Moreover, the localized nature of the observed signaling suggests that macromolecular donor design may provide an approach for selectively stimulating certain cellular biochemical pathways.

  17. Bioactive phytoconstituents and plant extracts from genus Heliotropium

    Directory of Open Access Journals (Sweden)

    Naveen Goyal

    2014-01-01

    Full Text Available Heliotropium is a genus of herbs and rarely shrubs of family Boraginaceae. Heliotropium species have been used in folk medicine for the treatment of gout, rheumatism and as antiseptic, febrifuge, cholagogue, anti-inflammatory and healing agents. The alkaloids mainly pyrrolizidine alkaloids are the main constituents of Heliotropium species, which are responsible for several biological activities viz. anti-tumoural, anti-microbial, and anti-viral effects. Phenolic compounds, terpenoids, and quinones have also been reported in this genus. The present review summarizes the various biological studies done on the extracts and bioactive phytoconstituents from the plants of the genus Heliotropium over the past few decades.

  18. Hierarchical Structures and Shaped Particles of Bioactive Glass and Its In Vitro Bioactivity

    Directory of Open Access Journals (Sweden)

    U. Boonyang

    2013-01-01

    Full Text Available In this study, bioactive glass particles with controllable structure and porosity were prepared using dual-templating methods. Block copolymers used as one template component produced mesopores in the calcined samples. Polymer colloidal crystals as the other template component yielded either three-dimensionally ordered macroporous (3DOM products or shaped bioactive glass nanoparticles. The in vitro bioactivity of these bioactive glasses was studied by soaking the samples in simulated body fluid (SBF at body temperature (37°C for varying lengths of time and monitoring the formation of bone-like apatite on the surface of the bioactive glass. A considerable bioactivity was found that all of bioactive glass samples have the ability to induce the formation of an apatite layer on its surface when in contact with SBF. The development of bone-like apatite is faster for 3DOM bioactive glasses than for nanoparticles.

  19. Bioactive Phenols in Small Fruits and Berries

    OpenAIRE

    Guiné, R. P. F.

    2016-01-01

    Bioactive compounds are extra nutritional constituents occurring naturally in plant foods in small amounts, however in quantities enough to produce bioactive effects. Among bioactive compounds the phenolic compounds are a very large set of molecules, which include several groups such as for example flavonoids, phenolic acids or tannins. Small fruits and berries include a wide diversity of fruits, like grapes, strawberries, blackberries, blueberries, raspberries, cherries, hardi kiwi, gooseber...

  20. The Joint Structural Biology Group beam lines at the ESRF: Modern macromolecular crystallography

    CERN Document Server

    Mitchell, E P

    2001-01-01

    Macromolecular crystallography has evolved considerably over the last decade. Data sets in under an hour are now possible on high throughput beam lines leading to electron density and, possibly, initial models calculated on-site. There are five beam lines currently dedicated to macromolecular crystallography: the ID14 complex and BM-14 (soon to be superseded by ID-29). These lines handle over five hundred projects every six months and demand is increasing. Automated sample handling, alignment and data management protocols will be required to work efficiently with this demanding load. Projects developing these themes are underway within the JSBG.

  1. Aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes as revealed by microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu University, Matsumoto (Japan). Dept. of Anatomy and Cell Biology

    2007-07-01

    This mini-review reports aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes. We have observed the macromolecular synthesis, such as DNA, RNA and proteins, in the mitochondria of various mammalian cells by means of electron microscopic radioautography technique developed in our laboratory. The number of mitochondria per cell, number of labeled mitochondria per cell with 3H-thymidine, 3H-uridine and 3H-leucine, precursors for DNA, RNA and proteins, respectively, were counted and the labeling indices at various ages, from fetal to postnatal early days and several months to 1 and 2 years in senescence, were calculated, which showed variations due to aging. (author)

  2. THE STEADY/PULSATILE FLOW AND MACROMOLECULAR TRANSPORT IN T-BIFURCATION BLOOD VESSELS

    Institute of Scientific and Technical Information of China (English)

    李丁; 温功碧

    2003-01-01

    A numerical analysis of the steady and pulsatile, macromolecular( such as lowdensity lipopotein ( LDL ), Albumin ) transport in T-bifurcation was proposed. Theinfluence of Reynolds number and mass flow ratio etc. parameters on the velocity field andmass transport were calculated. The computational results predict that the blood flow factorsaffect the macromolecular distribution and the transport across the wall, it shows thathemodynamic play an important role in the process of atherosclerosis . The LDL and Albuminconcentration on the wall varies most greatly in flow bifurcation area where the wall shearstress varies greatly at the branching vessel and the atherosclerosis often appears there.

  3. Accounting for large amplitude protein deformation during in silico macromolecular docking.

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-02-22

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  4. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-01-01

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success. PMID:21541061

  5. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Directory of Open Access Journals (Sweden)

    Chantal Prévost

    2011-02-01

    Full Text Available Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA.We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  6. Phase Sensitive X-Ray Diffraction Imaging of Defects in Biological Macromolecular Crystals

    Science.gov (United States)

    Hu, Z. W.; Lai, B.; Chu, Y. S.; Cai, Z.; Mancini, D. C.; Thomas, B. R.; Chernov, A. A.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Characterization of defects and/or disorder in biological macromolecular crystals presents much greater challenges than in conventional small-molecule crystals. The lack of sufficient contrast of defects is often a limiting factor in x-ray diffraction topography of protein crystals. This has seriously hampered efforts to understand mechanisms and origins of formation of imperfections, and the role of defects as essential entities in the bulk of macromolecular crystals. In this report, we employ a phase sensitive x-ray diffraction imaging approach for augmenting the contrast of defects in protein crystals.

  7. Poly(isophthalic acid)(ethylene oxide) as a Macromolecular Modulator for Metal-Organic Polyhedra.

    Science.gov (United States)

    Chen, Teng-Hao; Wang, Le; Trueblood, Jonathan V; Grassian, Vicki H; Cohen, Seth M

    2016-08-03

    A new strategy was developed by using a polymer ligand, poly(isophthalic acid)(ethylene oxide), to modulate the growth of metal-organic polyhedra (MOP) crystals. This macromolecular modulator can effectively control the crystal habit of several different Cu24L24 (L = isophthalic acid derivatives) MOPs. The polymer also directed the formation of MOP structures under reaction conditions that only produce metal-organic frameworks in the absence of modulator. Moreover, the polymer also enabled the deposition of MOP crystals on glass surfaces. This macromolecular modulator strategy provides an innovative approach to control the morphology and assembly of MOP particles.

  8. Effect of macromolecular crowding on the rate of diffusion-limited enzymatic reaction

    Indian Academy of Sciences (India)

    Manish Agrawal; S B Santra; Rajat Anand; Rajaram Swaminathan

    2008-08-01

    The cytoplasm of a living cell is crowded with several macromolecules of different shapes and sizes. Molecular diffusion in such a medium becomes anomalous due to the presence of macromolecules and diffusivity is expected to decrease with increase in macromolecular crowding. Moreover, many cellular processes are dependent on molecular diffusion in the cell cytosol. The enzymatic reaction rate has been shown to be affected by the presence of such macromolecules. A simple numerical model is proposed here based on percolation and diffusion in disordered systems to study the effect of macromolecular crowding on the enzymatic reaction rates. The model qualitatively explains some of the experimental observations.

  9. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Science.gov (United States)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  10. Bioactive Triterpenes from the Fungus Piptoporus betulinus

    National Research Council Canada - National Science Library

    Zeyad Alresly; Ulrike Lindequist; Michael Lalk; Andrea Porzel; Norbert Arnold; Ludger AWessjohann

    2016-01-01

      Phytochemical investigation of the ethyl acetate extract of the fruiting bodies from the basidiomycete Piptoporus betulinus led to the isolation of a new bioactive lanostane triterpene identified...

  11. Bioactive glasses materials, properties and applications

    CERN Document Server

    Ylänen, Heimo

    2011-01-01

    Due to their biocompatibility and bioactivity, bioactive glasses are used as highly effective implant materials throughout the human body to replace or repair damaged tissue. As a result, they have been in continuous use since shortly after their invention in the late 1960s and are the subject of extensive research worldwide.Bioactive glasses provides readers with a detailed review of the current status of this unique material, its properties, technologies and applications. Chapters in part one deal with the materials and mechanical properties of bioactive glass, examining topics such

  12. Burchellin: study of bioactivity against Aedes aegypti.

    Science.gov (United States)

    Narciso, Juliana Oliveira Abreu; Soares, Renata Oliveira de Araújo; Reis dos Santos Mallet, Jacenir; Guimarães, Anthony Érico; de Oliveira Chaves, Maria Célia; Barbosa-Filho, José Maria; Maleck, Marise

    2014-04-08

    The dengue mosquito Aedes aegypti Linnaeus, 1762 is a widespread insect pest of serious medical importance. Since no effective vaccine is available for treating dengue, the eradication or control of the main mosquito vector is regarded as essential. Since conventional insecticides have limited success, plants may be an alternative source of larvicidal agents, since they contain a rich source of bioactive chemicals. The aim of this study was to evaluate the larvicidal activity of the neolignan burchellin isolated from Ocotea cymbarum (Lauraceae), a plant from the Amazon region, against third instar larvae of A. aegypti. Burchellin obtained from O. cymbarum was analyzed. The inhibitory activity against A. aegypti eggs and larvae and histological changes in the digestive system of treated L3 larvae were evaluated. In addition, nitric oxide synthase activity and nitric oxide levels were determined, and cytotoxicity bioassays performed. The data showed that burchellin interfered with the development cycle of the mosquito, where its strongest toxic effect was 100% mortality in larvae (L3) at concentrations ≥ 30 ppm. This compound did not show target cell toxicity in peritoneal macrophages from BALB/c mice, and proved to have molecular stability when dissolved in water. The L3 and L4 larvae treated with the compound showed cellular destruction and disorganization, cell spacing, and vacuolization of epithelial cells in small regions of the midgut. The neolignan burchellin proved to be a strong candidate for a natural, safe and stable phytolarvicidal to be used in population control of A. aegypti.

  13. Bioactive Egg Components and Inflammation.

    Science.gov (United States)

    Andersen, Catherine J

    2015-09-16

    Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk.

  14. Bioactive Egg Components and Inflammation

    Directory of Open Access Journals (Sweden)

    Catherine J. Andersen

    2015-09-01

    Full Text Available Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk.

  15. Bioactive Components in Fish Venoms

    Science.gov (United States)

    Ziegman, Rebekah; Alewood, Paul

    2015-01-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  16. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

      In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular crow

  17. A kinetic type extended model for dense gases and macromolecular fluids

    Directory of Open Access Journals (Sweden)

    M. Cristina Carrisi

    2005-05-01

    Full Text Available Extended thermodynamics is an important theory which is appreciated from mathematicians and physicists. Following its ideas and considering the macroscopic approach with suggestions from the kinetic one, we find in this paper, the solution of an interesting model: the model for dense gases and macromolecular fluids.

  18. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DEFF Research Database (Denmark)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    2017-01-01

    Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many...

  19. Isolation and chemical characterization of resistant macromolecular constituents in microalgae and marine sediments

    NARCIS (Netherlands)

    Gelin, F.

    1996-01-01

    The recognition of novel, insoluble and non-hydrolysable macromolecular constituents in protective tissues of fresh-water algae and higher plants has had a major impact on our understanding of the origin and fate of sedimentary organic matter (OM) in terrestrial and lacustrine deposits. The investig

  20. Researches, Publications and Achievements 2007-2011, Department of Macromolecular Science and Engineering

    OpenAIRE

    All teaching staffs at Department of Macromolecular Science and Engineering (19 members)

    2012-01-01

    Recent researches, publications and achievements are presented, which were made during these five years (2007-2011) by 19 members at Department of Macromolecular Science and Engineering. Listed publications include original papers, books, reviews and reports. Achievements such as invited lectures, patents, funds and financial supports, and awards are also listed.

  1. Synergy of DNA-bending nucleoid proteins and macromolecular crowd-condensing DNA

    NARCIS (Netherlands)

    Bessa Ramos, E.; Wintraecken, C.H.J.M.; Geerling, A.C.M.; Vries, de R.J.

    2007-01-01

    Many prokaryotic nucleoid proteins bend DNA and form extended helical protein-DNA fibers rather than condensed structures. On the other hand, it is known that such proteins (such as bacterial HU) strongly promote DNA condensation by macromolecular crowding. Using theoretical arguments, we show that

  2. The Postgraduate Study of Macromolecular Sciences at the University of Zagreb (1971-1980

    Directory of Open Access Journals (Sweden)

    Kunst, B.

    2008-07-01

    Full Text Available The postgraduate study of macromolecular sciences (PSMS was established at the University of Zagreb in 1971 as a university study in the time of expressed interdisciplinary permeation of natural sciences - physics, chemistry and biology, and application of their achievements in technologicaldisciplines. PSMS was established by a group of prominent university professors from the schools of Science, Chemical Technology, Pharmacy and Medicine, as well as from the Institute of Biology. The study comprised basic fields of macromolecular sciences: organic chemistry of synthetic macromolecules, physical chemistry of macromolecules, physics of macromolecules, biological macromolecules and polymer engineering with polymer application and processing, and teaching was performed in 29 lecture courses lead by 30 professors with their collaborators. PSMS ceased to exist with the change of legislation in Croatia in 1980, when the attitude prevailed to render back postgraduate studies to the university schools. During 9 years of existence of PSMS the MSci grade was awarded to 37 macromolecular experts. It was assessed that the PSMS some thirty years ago was an important example of modern postgraduate education as compared with the international postgraduate development. In concordance with the recent introduction of similar interdisciplinary studies in macromolecular sciences elsewhere in the world, the establishment of a modern interdisciplinary study in the field would be of importance for further development of these sciences in Croatia.

  3. Hydropyrolysis: A new technique for the analysis of macromolecular material in meteorites

    Science.gov (United States)

    Sephton, Mark A.; Love, Gordon D.; Meredith, Will; Snape, Colin E.; Sun, Cheng-Gong; Watson, Jonathan S.

    2005-10-01

    The carbonaceous chondrite meteorites are fragments of asteroids that have remained relatively unprocessed since the formation of the Solar System 4.56 billion years ago. The major organic component in these meteorites is a macromolecular phase that is resistant to solvent extraction. The information contained within macromolecular material can be accessed by degradative techniques such as pyrolysis. Hydropyrolysis refers to pyrolysis assisted by high hydrogen gas pressures and a dispersed sulphided molybdenum catalyst. Hydropyrolysis of the Murchison macromolecular material successfully releases much greater quantities of hydrocarbons than traditional pyrolysis techniques (twofold greater than hydrous pyrolysis) including significant amounts of high molecular weight polyaromatic hydrocarbons (PAH) such as phenanthrene, carbazole, fluoranthene, pyrene, chrysene, perylene, benzoperylene and coronene units with varying degrees of alkylation. When hydropyrolysis products are collected using a silica trap immersed in liquid nitrogen, the technique enables the solubilisation and retention of compounds with a wide range of volatilities (i.e. benzene to coronene). This report describes the hydropyrolysis method and the information it can provide about meteorite macromolecular material constitution.

  4. Asphalts and asphaltenes: Macromolecular structure, precipitation properties, and flow in porous media

    Science.gov (United States)

    Rassamdana, Hossein

    Depending on rock and fluid properties, more than 50% of reservoir oil in place is normally produced by enhanced oil recovery (EOR) methods. Among the EOR techniques, miscible flooding is one of the most efficient and widely-used methods. However, this method can suffer from the formation and precipitation of asphalt aggregates. In addition, asphalt deposition is also a major hindrance to heavy oil production, and even primary recovery operations. Asphalt deposition can alter the reservoir rock properties, fluid saturation distribution, fluid flow properties, and eventually the ultimate oil recovery. The shortage of studies on the macromolecular structure and growth mechanisms of asphalt particles is the main reason for the unsuccessful modeling of their precipitation properties. The equivocal behavior of asphalt under some specific conditions could be the other reason. In this research we look at the problem of asphalt formation, flow, and precipitation from three different angles. We analyze extensive small-angle X-ray and neutron scattering data, precipitation data, and molecular weight distribution measurements, and show that they all suggest conclusively that asphalts and asphaltenes are fractal aggregates, and their growth mechanisms are diffusion-limited particle (DLP) and diffusion-limited cluster-cluster (DLCC) aggregation processes. These results lead us to development of a scaling equation of state for predicting asphalt precipitation properties, such as its onset and amount of precipitation. Another result of our study is an analytical equation for modeling the molecular weight distribution of asphalt and asphaltene aggregates. In addition, asphalt phase behavior in miscible and immiscible injections is studied. The effect of the governing thermodynamic factors, such as the pressure, temperature, and composition of the oil and precipitation agents, on the asphalt aggregation and disaggregation processes are investigated. Finally, a model is developed to

  5. Bioactive Glasses in Dentistry: A Review

    Directory of Open Access Journals (Sweden)

    Abbasi Z

    2015-03-01

    Full Text Available Bioactive glasses are silicate-based and can form a strong chemical bond with the tissues. These biomaterials are highly biocompatible and can form a hydroxyapatite layer when implanted in the body or soaked in the simulated body fluid. Due to several disadvantages, conventional glass processing method including melting of glass components, is replaced by sol-gel method with a large number of benefits such as low processing temperature, higher purity and homogeneity and therefore better control of bioactivity. Bioactive glasses have a wide range of applications, particularly in dentistry. These glasses can be used as particulates or monolithic shapes and porous or dense constructs in different applications such as remineralization or hypersensitivity treatment. Some properties of bioactive glasses such as antibacterial properties can be promoted by adding different elements into the glass. Bioactive glasses can also be used to modify different biocompatible materials that need to be bioactive. This study reviews the significant developments of bioactive glasses in clinical application, especially dentistry. Furthermore, we will discuss the field of bioactive glasses from beginning to the current developments, which includes processing methods, applications, and properties of these glasses.

  6. Bioactive berry compounds-novel tools against human pathogens.

    Science.gov (United States)

    Puupponen-Pimiä, Riitta; Nohynek, Liisa; Alakomi, Hanna-Leena; Oksman-Caldentey, Kirsi-Marja

    2005-04-01

    Berry fruits are rich sources of bioactive compounds, such as phenolics and organic acids, which have antimicrobial activities against human pathogens. Among different berries and berry phenolics, cranberry, cloudberry, raspberry, strawberry and bilberry especially possess clear antimicrobial effects against, e.g. Salmonella and Staphylococcus. Complex phenolic polymers, like ellagitannins, are strong antibacterial agents present in cloudberry and raspberry. Several mechanisms of action in the growth inhibition of bacteria are involved, such as destabilisation of cytoplasmic membrane, permeabilisation of plasma membrane, inhibition of extracellular microbial enzymes, direct actions on microbial metabolism and deprivation of the substrates required for microbial growth. Antimicrobial activity of berries may also be related to antiadherence of bacteria to epithelial cells, which is a prerequisite for colonisation and infection of many pathogens. Antimicrobial berry compounds may have important applications in the future as natural antimicrobial agents for food industry as well as for medicine. Some of the novel approaches are discussed.

  7. Laser cladding of bioactive glass coatings.

    Science.gov (United States)

    Comesaña, R; Quintero, F; Lusquiños, F; Pascual, M J; Boutinguiza, M; Durán, A; Pou, J

    2010-03-01

    Laser cladding by powder injection has been used to produce bioactive glass coatings on titanium alloy (Ti6Al4V) substrates. Bioactive glass compositions alternative to 45S5 Bioglass were demonstrated to exhibit a gradual wetting angle-temperature evolution and therefore a more homogeneous deposition of the coating over the substrate was achieved. Among the different compositions studied, the S520 bioactive glass showed smoother wetting angle-temperature behavior and was successfully used as precursor material to produce bioactive coatings. Coatings processed using a Nd:YAG laser presented calcium silicate crystallization at the surface, with a uniform composition along the coating cross-section, and no significant dilution of the titanium alloy was observed. These coatings maintain similar bioactivity to that of the precursor material as demonstrated by immersion in simulated body fluid. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Bioprospecting for bioactives from seaweeds: potential, obstacles and alternatives

    Directory of Open Access Journals (Sweden)

    Renato C. Pereira

    2012-08-01

    Full Text Available Seaweeds are potential sources of high biotechnological interest due to production of a great diversity of compounds exhibiting a broad spectrum of biological activities. On the other hand, there is an urgent need for management options for a sustainable approach to the use of marine organisms as a source of bioactive compounds. This review discusses the bioprospection for bioactive seaweed compounds as pharmaceuticals and antifouling agents, encompassing their potential and possible obstacles and alternatives. In spite of their potential, research on pharmaceuticals and antifouling agents from seaweeds includes mainly the search for molecules that exhibit these biological activities, but lacks of consideration of fundamental and limiting aspects such as the development of alternatives to sustainable supply. However, for the complete development of pharmaceuticals and antifouling compounds in Brazil, marine bioprospection should be more comprehensive, associating the search for molecules with an analysis of their supply. In this way, it is possible to promote sustainable development and conservation of biodiversity, as well as to assert the economic development of Brazil.

  9. Surface modification of bioactive glasses and preparation of PDLLA/bioactive glass composite films.

    Science.gov (United States)

    Gao, Yuan; Chang, Jiang

    2009-08-01

    In order to improve the homogeneous dispersion of particles in the polymeric matrix, 45S5, mesoporous 58S, and 58S bioactive glasses were surface modified by esterification reactions with dodecyl alcohol at reflux temperature of 260 degrees C (named as m-45S5, m-mesoporous 58S, and m-58S, respectively). The modified particles showed better hydrophobicity and longer time of suspension in organic matrix. The PDLLA/bioactive glass composite films were fabricated using surface modified bioactive glass particles through solvent casting-evaporation method. Surface morphology, mechanical property, and bioactivity were investigated. The results revealed that the inorganic particle distribution and tensile strength of the composite films with modified bioactive glass particles were significantly improved while great bioactive properties were maintained. Scanning electron microscopy (SEM) observation illustrated that the modified bioactive glass particles were homogeneously dispersed in the PDLLA matrix. The maximum tensile strengths of composite films with modified bioactive glass particles were higher than that of composite films with unmodified bioactive glass particles. The bioactivity of the composite films were evaluated by being soaked in the simulated body fluid (SBF) and the SEM observation of the films suggested that the modified composite films were still bioactive in that they could induce the formation of HAp on its surface and the distribution of HAp was even more homogeneous on the film. The results mentioned above indicated that the surface modification of bioactive glasses with dodecyl alcohol was an effective method to prepare PDLLA/bioactive glass composites with enhanced properties. By studying the comparisons of modification effects among the three types of bioactive glasses, we could get the conclusion that the size and morphology of the inorganic particles would greatly affect the modification effects and the properties of composites.

  10. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução Cancer and cell cicle-specific and cell cicle nonspecific anticancer DNA-interactive agents: an introduction

    OpenAIRE

    Vera Lúcia de Almeida; Andrei Leitão; Luisa del Carmen Barrett Reina; Carlos Alberto Montanari; Claudio Luis Donnici; Míriam Teresa Paz Lopes

    2005-01-01

    The chemotherapy agents against cancer may be classified as "cell cycle-specific" or "cell cycle-nonspecific". Nevertheless, several of them have their biological activity related to any kind of action on DNA such as: antimetabolic agents (DNA synthesis inhibition), inherently reactive agents (DNA alkylating electrophilic traps for macromolecular nucleophiles from DNA through inter-strand cross-linking - ISC - alkylation) and intercalating agents (drug-DNA interactions inherent to the binding...

  11. Bioactive proteins against pathogenic and spoilage bacteria

    Directory of Open Access Journals (Sweden)

    Mahmoud Z. Sitohy

    2014-10-01

    Full Text Available Background: It is likely that both human nutrition and the nutrition of livestock are benefited by the presence of bioactive proteins within their respective diet regimes. Bioactive proteins have been defined as specific protein fragments that positively impact bodily functions or conditions and may, ultimately, influence overall human health. The ingestion of bioactive proteins may have an effect on the major body systems—namely, the cardiovascular, digestive, immune and nervous systems. According to their functional properties, bioactive proteins may be classified as antimicrobial, antithrombotic, antihypertensive, opioid, immune-modulatory, mineral binding and anti-oxidative. There are many examples of biologically active food proteins and active peptides that can be obtained from various food protein sources. They have a physiological significance beyond the pure nutritional requirements; in other wordsthey have the acquisition of nitrogen for normal growth and maintenance. Objective: This study aims to specify and characterize the extent and mode of action of bioactive proteins in their native form, (glycinin, glycinin basic sub-unit and β-conglycinin against specific main pathogens (Listeria monocytogenes, Escherichia coli O157:H7 and Salmonella enterica serovar Enteritidis. We will be using standard media while identifying the main constituents responsible for this action. Methods: Glycinin, basic sub-unit and β-conglycinin were isolated from soybean protein and tested for their antimicrobial action against pathogenic and spoilage bacteria, They were thencompared to the properties of penicillin. Methylated soybean protein and also methylated chickpea protein (MSP and MCP, with isoelectric points around pI 8, were prepared by esterifying. 83 % of their free carboxyl groups and their interactions with Gram positive and Gram negative bacteria were examined. Results: The three divisions of cationic proteins exhibited antibacterial

  12. Lipoic Acid Gold Nanoparticles Functionalized with Organic Compounds as Bioactive Materials

    Science.gov (United States)

    Turcu, Ioana; Zarafu, Irina; Popa, Marcela; Chifiriuc, Mariana Carmen; Bleotu, Coralia; Culita, Daniela; Ghica, Corneliu; Ionita, Petre

    2017-01-01

    Water soluble gold nanoparticles protected by lipoic acid were obtained and further functionalized by standard coupling reaction with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether. Derivatives of lipoic acid with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether were also obtained and characterized. All these were tested for their antimicrobial activity, as well as for their influence on mammalian cell viability and cellular cycle. In all cases a decreased antimicrobial activity of the obtained bioactive nanoparticles was observed as compared with the organic compounds, proving that a possible inactivation of the bioactive groups could occur during functionalization. However, both the gold nanoparticles as well as the functionalized bioactive nanosystems proved to be biocompatible at concentrations lower than 50 µg/mL, as revealed by the cellular viability and cell cycle assay, demonstrating their potential for the development of novel antimicrobial agents.

  13. Fabrication of hydrogel based nanocomposite scaffold containing bioactive glass nanoparticles for myocardial tissue engineering.

    Science.gov (United States)

    Barabadi, Zahra; Azami, Mahmoud; Sharifi, Esmaeel; Karimi, Roya; Lotfibakhshaiesh, Nasrin; Roozafzoon, Reza; Joghataei, Mohammad Taghi; Ai, Jafar

    2016-12-01

    Selecting suitable cell sources and angiogenesis induction are two important issues in myocardial tissue engineering. Human endometrial stromal cells (EnSCs) have been introduced as an abundant and easily available resource in regenerative medicine. Bioactive glass is an agent that induces angiogenesis and has been studied in some experiments. The aim of this study was to investigate in vitro differentiation capacity of endometrial stem cells into cardiomyocyte lineage and to evaluate capability of bioactive glass nanoparticles toward EnSCs differentiation into endothelial lineage and angiogenesis on hydrogel scaffold. Our findings suggests that endometrial stem cells could be programmed into cardiomyocyte linage and considered a suitable cell source for myocardial regeneration. This experiment also revealed that inclusion of bioactive glass nanoparticles in hydrogel scaffold could improve angiogenesis through differentiating EnSCs toward endothelial lineage and increasing level of vascular endothelial growth factor secretion. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Thiocarbamates from Moringa oleifera Seeds Bioactive against Virulent and Multidrug-Resistant Vibrio Species

    Science.gov (United States)

    de Sousa, Oscarina Viana; Hofer, Ernesto; Mafezoli, Jair; Barbosa, Francisco Geraldo

    2017-01-01

    Prospect of antibacterial agents may provide an alternative therapy for diseases caused by multidrug-resistant bacteria. This study aimed to evaluate the in vitro bioactivity of Moringa oleifera seed extracts against 100 vibrios isolated from the marine shrimp Litopenaeus vannamei. Ethanol extracts at low (MOS-E) and hot (MOS-ES) temperature are shown to be bioactive against 92% and 90% of the strains, respectively. The most efficient Minimum Inhibitory Concentration (MIC) levels of MOS-E and MOS-ES against a high percentage of strains were 32 µg mL−1. Bioguided screening of bioactive compounds showed that the ethyl acetate fraction from both extracts was the only one that showed antibacterial activity. Vibriocidal substances, niazirine and niazimicine, were isolated from the aforementioned fraction through chromatographic fractionation. PMID:28770224

  15. Yolk shell nanocomposite particles as bioactive bone fillers and growth factor carriers.

    Science.gov (United States)

    Shi, Pujiang; Abbah, Sunny A; Chuah, Yon Jin; Li, Jun; Zhang, Yong; He, Pengfei; Wong, Hee Kit; Goh, James C H

    2017-09-20

    The efficient delivery of bioactive molecules via rationally designed nanoparticles is an important focus in regenerative medicine. The yolk shell nanocomposite particles described herein are composed of silk fibroin movable cores formed within voided calcium carbonate shells to load and control the release of labile cytokines. These particles are excellent carrier vehicles of potent molecules as they sustained the release of bioactive Bone Morphogenetic Protein 2 (BMP-2) for more than 28 days in vitro. Implantation into bone defects in rabbits corroborates the in vitro results and also reveals that upon contact with phosphate containing body fluids, implanted yolk shell particles agglomerate and transform into a filler that adapts to defect contour to further act as an absorbable hemostatic agent. Taken together, the fabrication of these yolk shell particle-based "bone fillers" could expand the horizon for the development of newer generations of advanced bioactive materials in tissue regeneration applications.

  16. A novel sol-gel derived bioactive glass featuring antibacterial properties

    Energy Technology Data Exchange (ETDEWEB)

    Bellantone, M.; Coleman, N.J.; Hench, L.L. [Imperial Coll. of Science, Technology and Medicine, London (United Kingdom). Dept. of Materials

    2001-07-01

    Antibacterial effects are highly desirable in biomaterials for dental, orthopaedic, and tissue engineering applications. The study herein reports on the bacteriostatic properties of a new composition of bioactive glass derived by the sol-gel process. Ag{sub 2}O was incorporated into the SiO{sub 2}-CaO-P{sub 2}O{sub 5} system. Leaching of the Ag{sup +} ion from the glass conferred strong bacteriostatic properties to the system. In vitro antibacterial tests on gram (+) and gram (-) bacteria showed that in the presence of bioactive glass no significant alteration of the cell concentration occurs. Conversely, the novel silver-doped bioactive glass causes a dramatic decrease of cell population for each of the bacteria under investigation. Unlike antibiotics the silver ion does not cause bacterial resistance. This property, together with its broad spectrum of action, makes silver an exceptionally versatile in situ antibacterial agent. (orig.)

  17. Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

    A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

  18. Bioactivity of fungal endophytes as a function of endophyte taxonomy and the taxonomy and distribution of their host plants.

    Science.gov (United States)

    Higginbotham, Sarah J; Arnold, A Elizabeth; Ibañez, Alicia; Spadafora, Carmenza; Coley, Phyllis D; Kursar, Thomas A

    2013-01-01

    Fungal endophytes--fungi that grow within plant tissues without causing immediate signs of disease--are abundant and diverse producers of bioactive secondary metabolites. Endophytes associated with leaves of tropical plants are an especially exciting and relatively untapped source of novel compounds. However, one major challenge in drug discovery lies in developing strategies to efficiently recover highly bioactive strains. As part of a 15-year drug discovery project, foliar endophytes were isolated from 3198 plant samples (51 orders, 105 families and at least 232 genera of angiosperms and ferns) collected in nine geographically distinct regions of Panama. Extracts from culture supernatants of >2700 isolates were tested for bioactivity (in vitro percent inhibition of growth, % IG) against a human breast cancer cell line (MCF-7) and the causative agents of malaria, leishmaniasis, and Chagas' disease. Overall, 32.7% of endophyte isolates were highly active in at least one bioassay, including representatives of diverse fungal lineages, host lineages, and collection sites. Up to 17% of isolates tested per assay were highly active. Most bioactive strains were active in only one assay. Fungal lineages differed in the incidence and degree of bioactivity, as did fungi from particular plant taxa, and greater bioactivity was observed in endophytes isolated from plants in cloud forests vs. lowland forests. Our results suggest that using host taxonomy and forest type to tailor plant collections, and selecting endophytes from specific orders or families for cultivation, will markedly increase the efficiency and efficacy of discovering bioactive metabolites for particular pharmaceutical targets.

  19. Bioactivity of fungal endophytes as a function of endophyte taxonomy and the taxonomy and distribution of their host plants.

    Directory of Open Access Journals (Sweden)

    Sarah J Higginbotham

    Full Text Available Fungal endophytes--fungi that grow within plant tissues without causing immediate signs of disease--are abundant and diverse producers of bioactive secondary metabolites. Endophytes associated with leaves of tropical plants are an especially exciting and relatively untapped source of novel compounds. However, one major challenge in drug discovery lies in developing strategies to efficiently recover highly bioactive strains. As part of a 15-year drug discovery project, foliar endophytes were isolated from 3198 plant samples (51 orders, 105 families and at least 232 genera of angiosperms and ferns collected in nine geographically distinct regions of Panama. Extracts from culture supernatants of >2700 isolates were tested for bioactivity (in vitro percent inhibition of growth, % IG against a human breast cancer cell line (MCF-7 and the causative agents of malaria, leishmaniasis, and Chagas' disease. Overall, 32.7% of endophyte isolates were highly active in at least one bioassay, including representatives of diverse fungal lineages, host lineages, and collection sites. Up to 17% of isolates tested per assay were highly active. Most bioactive strains were active in only one assay. Fungal lineages differed in the incidence and degree of bioactivity, as did fungi from particular plant taxa, and greater bioactivity was observed in endophytes isolated from plants in cloud forests vs. lowland forests. Our results suggest that using host taxonomy and forest type to tailor plant collections, and selecting endophytes from specific orders or families for cultivation, will markedly increase the efficiency and efficacy of discovering bioactive metabolites for particular pharmaceutical targets.

  20. Planctomycetes as novel source of bioactive molecules

    Directory of Open Access Journals (Sweden)

    Ana Patrícia Graça

    2016-08-01

    Full Text Available Marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. Of particular importance are organisms like sponges and macroalgae and their associated microbiome. Planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the Actinobacteria. Furthermore, genome mining revealed the presence of secondary metabolite pathway genes or clusters in 13 analyzed Planctomycetes genomes.In order to assess the antimicrobial production of a large and diverse collection of Planctomycetes isolated from macroalgae from the Portuguese coast, molecular and bioactivity assays were performed in 40 bacteria from several taxa. Two genes commonly associated with the production of bioactive compounds, nonribosomal peptide synthetases (NRPS and polyketide synthases (PKS genes were screened. Molecular analysis revealed that 95 % of the planctomycetes potentially have one or both secondary bioactive genes; 85 % amplified with PKS-I primers and 55 % with NRPS primers. Some of the amplified genes were confirmed to be involved in secondary metabolite pathways. Using bioinformatic tools their biosynthetic pathways were predicted. The secondary metabolite genomic potential of strains LF1, UC8 and FC18 was assessed using in silico analysis of their genomes. Aqueous and organic extracts of the Planctomycetes were evaluated for their antimicrobial activity against an environmental Escherichia coli, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633 and a clinical isolate of Candida albicans. The screening assays showed a high number of planctomycetes with bioactive extracts revealing antifungal (43 % and antibacterial (54 % activity against C. albicans and B. subtilis, respectively

  1. Bioactivities and Health Benefits of Wild Fruits.

    Science.gov (United States)

    Li, Ya; Zhang, Jiao-Jiao; Xu, Dong-Ping; Zhou, Tong; Zhou, Yue; Li, Sha; Li, Hua-Bin

    2016-08-04

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

  2. Comparison of Calcium Hydroxide and Bioactive Glass after Direct Pulp Capping in Primary Teeth

    Directory of Open Access Journals (Sweden)

    R. Haghgoo

    2007-12-01

    Full Text Available Objective: Bioactive glass is often used as a filler material for repair of dental bone defects.In different studies osteogenic potential of this material was proved, but its dentinogenesisproperty is in doubt. The purpose of this study was to evaluate the histological pulp responses of Calcium hydroxide and Bioactive glass placed directly on exposed pulp tissues.Materials and Methods: Twenty teeth to be extracted due to orthodontic reasons were selected. These teeth were divided into two groups and treated with direct pulp capping.Calcium hydroxide was used for 10 teeth and Bioactive glass for 10 teeth. After 60 daysthe teeth were extracted and prepared for histological evaluation. Finally the data was analyzed with exact Fisher test.Results: All teeth treated with Calcium hydroxide showed inflammation. Internal resorption was seen in six teeth, abscess in five teeth and dentinal bridge in two teeth. Inflammationwas seen in three Bioactive glass samples and dentinal bridge in seven teeth, but internal resorption and abscess were not seen.Conclusion: Bioactive glass appears to be superior to Calcium hydroxide as a pulp capping agent in primary teeth.

  3. Bioactivity of bioresorbable composite based on bioactive glass and poly-L-lactide

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhi-hua; RUAN Jian-ming; ZOU Jian-peng; ZHOU Zhong-cheng; SHEN Xiong-jun

    2007-01-01

    Bioactive and bioresorbable composite was fabricated by a solvent evaporation technique using poly-L-lactide(PLLA) and bioactive glass (average particle size: 6.8 μm). Bioactive glass granules are homogeneously distributed in the composite with microcrack structure. The formation of hydroxyapatite(HA) on the composite in simulated body fluid(SBF) was analyzed by scanning electron microscopy(SEM), energy dispersive spectroscopy(EDS), X-ray diffraction(XRD), and Raman spectra. Rod-like HA crystals deposit on the surface of PLLA/bioactive glass composite after soaking for 3 d. Both rod-like crystals and HA layer form on the surface for 14 d in SBF. The high bioactivity of PLLA/bioactive glass composite indicates the potential of materials for integration with bone.

  4. Sol-gel derived porous bioactive nanocomposites: Synthesis and in vitro bioactivity

    Science.gov (United States)

    Shankhwar, Nisha; Kothiyal, G. P.; Srinivasan, A.

    2013-06-01

    Porous bioactive composites consisting of SiO2-CaO-Na2O-P2O5 bioactive glass-ceramic and synthetic water soluble polymer Polyvinylpyrrolidone [PVP (C6H9NO)n, MW˜40000 g/mol] have been synthesized by sol-gel route. As-prepared polymeric composites were characterized by X-ray diffraction (XRD) technique. Two major bone mineral phases, viz., hydroxyapatite [Ca10(PO4)6(OH)2] and wollastonite [calcium silicate (CaSiO3)] have been identified in the XRD patterns of the composites. Presence of these bone minerals indicates the bioactive nature of the composites. In vitro bioactivity tests confirm bioactivity in the porous composites. The flexibility offered by these bioactive polymer composites is advantageous for its application as implant material.

  5. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    Science.gov (United States)

    Hayes, Maria; Tiwari, Brijesh K

    2015-09-17

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  6. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities

    Directory of Open Access Journals (Sweden)

    Maria Hayes

    2015-09-01

    Full Text Available Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  7. Assessment of nickel oxide substituted bioactive glass-ceramic on in vitro bioactivity and mechanical properties

    Energy Technology Data Exchange (ETDEWEB)

    Kumar Vyas, V.; Sampath Kumar, A.; Ali, A.; Prasad, S.; Srivastava, P.; Prasanna Mallick, S.; Ershad, Md.; Prasad Singh, S.; Pyare, R.

    2016-07-01

    Many type of oxide substituted glass-ceramics like strontium, cobalt, barium and titanium have shown bioactivity with improved mechanical properties. The present work reports the in vitro bioactivity and mechanical properties of nickel oxide substituted in bioactive glass-ceramic and results were compared with 45S5 bioactive glass-ceramic. Bioactive glass ceramics were processed through controlled crystallization of their respective bioactive glasses. The formed crystalline phases in bioactive glass-ceramics were identified using X-ray diffraction (XRD) analysis. The formation of HA layer was assessed by immersing them in the simulated body fluid (SBF) for different soaking periods. The formation of hydroxyapatite was confirmed by FTIR spectrometry, SEM and pH measurement. Densities and mechanical properties of the samples were found to increase considerably with an increasing the concentration of nickel oxide. A decrease in glass transition temperature (Tg) with NiO addition showed that the nickel oxide had acted as an intermediate in smaller quantities in the bioactive glass. The cell culture studies demonstrated that the samples containing low concentration of NiO from 0 to 1.65mol% were non-cytotoxic against osteoblast cells. Finally, this investigation clearly concluded that NiO doped bioactive glass would be potential biomaterials for biomedical applications. (Author)

  8. Advances in electron microscopy: A qualitative view of instrumentation development for macromolecular imaging and tomography.

    Science.gov (United States)

    Schröder, Rasmus R

    2015-09-01

    Macromolecular imaging and tomography of ice embedded samples has developed into a mature imaging technology, in structural biology today widely referred to simply as cryo electron microscopy.(1) While the pioneers of the technique struggled with ill-suited instruments, state-of-the-art cryo microscopes are now readily available and an increasing number of groups are producing excellent high-resolution structural data of macromolecular complexes, of cellular organelles, or the morphology of whole cells. Instrumentation developers, however, are offering yet more novel electron optical devices, such as energy filters and monochromators, aberration correctors or physical phase plates. Here we discuss how current instrumentation has already changed cryo EM, and how newly available instrumentation - often developed in other fields of electron microscopy - may further develop the use and applicability of cryo EM to the imaging of single isolated macromolecules of smaller size or molecules embedded in a crowded cellular environment.

  9. Optimal cytoplasmatic density and flux balance model under macromolecular crowding effects.

    Science.gov (United States)

    Vazquez, Alexei

    2010-05-21

    Macromolecules occupy between 34% and 44% of the cell cytoplasm, about half the maximum packing density of spheres in three dimension. Yet, there is no clear understanding of what is special about this value. To address this fundamental question we investigate the effect of macromolecular crowding on cell metabolism. We develop a cell scale flux balance model capturing the main features of cell metabolism at different nutrient uptakes and macromolecular densities. Using this model we show there are two metabolic regimes at low and high nutrient uptakes. The latter regime is characterized by an optimal cytoplasmatic density where the increase of reaction rates by confinement and the decrease by diffusion slow-down balance. More important, the predicted optimal density is in the range of the experimentally determined density of Escherichia coli.

  10. Macromolecular crowding increases binding of DNA polymerase to DNA: an adaptive effect

    Energy Technology Data Exchange (ETDEWEB)

    Zimmerman, S.B.; Harrison, B.

    1987-05-01

    Macromolecular crowding extends the range of ionic conditions supporting high DNA polymerase reaction rates. Reactions tested were nick translation and gap-filling by DNA polymerase I of E. coli, nuclease and polymerase activities of the large fragment of that polymerase, and polymerization by the T4 DNA polymerase. For all of these reactions, high concentrations of nonspecific polymers increased enzymatic activity under otherwise inhibitory conditions resulting from relatively high ionic strength. The primary mechanism of the polymer effect seems to be to increase the binding of polymerase to DNA. They suggest that this effect of protein-DNA complexes is only one example of a general metabolic buffering action of crowded solutions on a variety of macromolecular interactions.

  11. The macromolecular crystallography beamline I911-3 at the MAX IV laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Ursby, Thomas, E-mail: thomas.ursby@maxlab.lu.se; Unge, Johan; Appio, Roberto [Lund University, POB 118, Lund SE-221 00 (Sweden); Logan, Derek T. [Lund University, POB 124, Lund SE-221 00 (Sweden); Fredslund, Folmer; Svensson, Christer; Larsson, Krister; Labrador, Ana [Lund University, POB 118, Lund SE-221 00 (Sweden); Thunnissen, Marjolein M. G. M. [Lund University, POB 124, Lund SE-221 00 (Sweden)

    2013-07-01

    The updated macromolecular crystallography beamline I911-3 at the MAX II storage ring is described. The macromolecular crystallography beamline I911-3, part of the Cassiopeia/I911 suite of beamlines, is based on a superconducting wiggler at the MAX II ring of the MAX IV Laboratory in Lund, Sweden. The beamline is energy-tunable within a range between 6 and 18 keV. I911-3 opened for users in 2005. In 2010–2011 the experimental station was completely rebuilt and refurbished such that it has become a state-of-the-art experimental station with better possibilities for rapid throughput, crystal screening and work with smaller samples. This paper describes the complete I911-3 beamline and how it is embedded in the Cassiopeia suite of beamlines.

  12. Romp: The Method of Choice for Precise Macromolecular Engineering and Synthesis of Smart Materials

    Science.gov (United States)

    Khosravi, Ezat; Castle, Thomas C.; Kujawa, Margaret; Leejarkpai, Jan; Hutchings, Lian R.; Hine, Peter J.

    The recent advances in olefin metathesis highlight the impact of Ring Opening Metathesis Polymerisation (ROMP) as a powerful technique for macromolecular engineering and synthesis of smart materials with well-defined structures. ROMP has attracted a considerable research attention recently particularly by industry largely due to the development of well-defined metal complexes as initiators and also because of the award of the Noble Prize for Chemistry in 2005 to three scientists (Chauvin, Grubbs, Schrock) for their contributions in this area. This chapter discusses several interesting examples in order to demonstrate that ROMP is a power tool in macromolecular engineering and that it allows the design and synthesis of polymers with novel topologies.

  13. Long-Wavelength X-Ray Diffraction and Its Applications in Macromolecular Crystallography.

    Science.gov (United States)

    Weiss, Manfred S

    2017-01-01

    For many years, diffraction experiments in macromolecular crystallography at X-ray wavelengths longer than that of Cu-K α (1.54 Å) have been largely underappreciated. Effects caused by increased X-ray absorption result in the fact that these experiments are more difficult than the standard diffraction experiments at short wavelengths. However, due to the also increased anomalous scattering of many biologically relevant atoms, important additional structural information can be obtained. This information, in turn, can be used for phase determination, for substructure identification, in molecular replacement approaches, as well as in structure refinement. This chapter reviews the possibilities and the difficulties associated with such experiments, and it provides a short description of two macromolecular crystallography synchrotron beam lines dedicated to long-wavelength X-ray diffraction experiments.

  14. 3DEM Loupe: Analysis of macromolecular dynamics using structures from electron microscopy.

    Science.gov (United States)

    Nogales-Cadenas, R; Jonic, S; Tama, F; Arteni, A A; Tabas-Madrid, D; Vázquez, M; Pascual-Montano, A; Sorzano, C O S

    2013-07-01

    Electron microscopy (EM) provides access to structural information of macromolecular complexes in the 3-20 Å resolution range. Normal mode analysis has been extensively used with atomic resolution structures and successfully applied to EM structures. The major application of normal modes is the identification of possible conformational changes in proteins. The analysis can throw light on the mechanism following ligand binding, protein-protein interactions, channel opening and other functional macromolecular movements. In this article, we present a new web server, 3DEM Loupe, which allows normal mode analysis of any uploaded EM volume using a user-friendly interface and an intuitive workflow. Results can be fully explored in 3D through animations and movies generated by the server. The application is freely available at http://3demloupe.cnb.csic.es.

  15. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Foadi, James [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Aller, Pierre [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Alguel, Yilmaz; Cameron, Alex [Imperial College, London SW7 2AZ (United Kingdom); Axford, Danny; Owen, Robin L. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Armour, Wes [Oxford e-Research Centre (OeRC), Keble Road, Oxford OX1 3QG (United Kingdom); Waterman, David G. [Research Complex at Harwell (RCaH), Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0FA (United Kingdom); Iwata, So [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Evans, Gwyndaf, E-mail: gwyndaf.evans@diamond.ac.uk [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2013-08-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  16. STUDIES ON PAN MACROMOLECULAR SEMICONDUCTING FIBER 1. PREPARATION OF PAN CONDUCTING FIBER TREATED BY STANNIC CHLORIDE AND ITS SEMICONDUCTING BEHAVIOUR

    Institute of Scientific and Technical Information of China (English)

    WANG Dexi; CUI Dayuan; LUO Boliang; WANG Xiugang; WU Renjie

    1984-01-01

    The PAN fiber treated by Lewis acid (e.g. stannic chloride) could be transformed into a macromolecular conducting fiber by further thermal treatment. Depending on thermal treatment condition the resistance of the fiber varied from 103 to 1012 Ω and kept stable after hydrolysis. The fiber has enough strength to be processed by various means. This is a new kind of macromolecular semiconducting fiber having some characteristics similar to those of organic semiconductors.

  17. STUDY ON HYDROLYSIS OF MACROMOLECULAR GELATIN WITH ENZYMES IN COMBINATION MODE

    Institute of Scientific and Technical Information of China (English)

    Ya-qin Huang; Rui Guan; Ming-zhi Huang

    2004-01-01

    The enzymatic hydrolysis of macromolecular gelatin with AS1.398 neutral protease, bromelain and their combinations was studied by estimating the molecular weights of their hydrolytic products. It was discovered that the products hydrolyzed by using combination enzymes had lower molecular weight than those obtained by using single ones,and the kind of enzymes, their combination mode and addition sequence are effective ways to control the molecular weights of gelatin hydrolyzates.

  18. Porphyrin-Cored Polymer Nanoparticles: Macromolecular Models for Heme Iron Coordination.

    Science.gov (United States)

    Rodriguez, Kyle J; Hanlon, Ashley M; Lyon, Christopher K; Cole, Justin P; Tuten, Bryan T; Tooley, Christian A; Berda, Erik B; Pazicni, Samuel

    2016-10-03

    Porphyrin-cored polymer nanoparticles (PCPNs) were synthesized and characterized to investigate their utility as heme protein models. Created using collapsible heme-centered star polymers containing photodimerizable anthracene units, these systems afford model heme cofactors buried within hydrophobic, macromolecular environments. Spectroscopic interrogations demonstrate that PCPNs display redox and ligand-binding reactivity similar to that of native systems and thus are potential candidates for modeling biological heme iron coordination.

  19. CplexA: a Mathematica package to study macromolecular-assembly control of gene expression

    OpenAIRE

    Vilar, J. M. G.; Saiz, L

    2010-01-01

    Summary: Macromolecular assembly vertebrates essential cellular processes, such as gene regulation and signal transduction. A major challenge for conventional computational methods to study these processes is tackling the exponential increase of the number of configurational states with the number of components. CplexA is a Mathematica package that uses functional programming to efficiently compute probabilities and average properties over such exponentially large number of states from the en...

  20. Controlling Macromolecular Topology with Genetically Encoded SpyTag-SpyCatcher Chemistry

    OpenAIRE

    Zhang, Wen-Bin; Sun, Fei; Tirrell, David A.; Arnold, Frances H.

    2013-01-01

    Control of molecular topology constitutes a fundamental challenge in macromolecular chemistry. Here we describe the synthesis and characterization of artificial elastin-like proteins (ELPs) with unconventional nonlinear topologies including circular, tadpole, star, and H-shaped proteins using genetically encoded SpyTag–SpyCatcher chemistry. SpyTag is a short polypeptide that binds its protein partner SpyCatcher and forms isopeptide bonds under physiological conditions. Sequences encoding SpyT...

  1. Going viral: designing bioactive surfaces with bacteriophage.

    Science.gov (United States)

    Hosseinidoust, Zeinab; Olsson, Adam L J; Tufenkji, Nathalie

    2014-12-01

    Bacteriophage-functionalized bioactive surfaces are functional materials that can be used as antimicrobial surfaces in medical applications (e.g., indwelling medical devices or wound dressings) or as biosensors for bacterial capture and detection. Despite offering immense potential, designing efficient phage-functionalized bioactive surfaces is hampered by a number of challenges. This review offers an overview of the current state of knowledge in this field and presents a critical perspective of the technological promises and challenges.

  2. Bioactivities and Health Benefits of Wild Fruits

    OpenAIRE

    Ya Li; Jiao-Jiao Zhang; Dong-Ping Xu; Tong Zhou; Yue. Zhou; Sha Li; Hua-Bin Li

    2016-01-01

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we rev...

  3. Microencapsulation of bioactives for food applications

    OpenAIRE

    Dias, Maria Inês; Isabel C. F. R. Ferreira; Barreiro, M.F.

    2015-01-01

    Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this co...

  4. Biomolecule immobilization techniques for bioactive paper fabrication.

    Science.gov (United States)

    Kong, Fanzhi; Hu, Yim Fun

    2012-04-01

    Research into paper-based sensors or functional materials that can perform analytical functions with active recognition capabilities is rapidly expanding, and significant research effort has been made into the design and fabrication of bioactive paper at the biosensor level to detect potential health hazards. A key step in the fabrication of bioactive paper is the design of the experimental and operational procedures for the immobilization of biomolecules such as antibodies, enzymes, phages, cells, proteins, synthetic polymers and DNA aptamers on a suitably prepared paper membrane. The immobilization methods are concisely categorized into physical absorption, bioactive ink entrapment, bioaffinity attachment and covalent chemical bonding immobilization. Each method has individual immobilization characteristics. Although every biomolecule-paper combination has to be optimized before use, the bioactive ink entrapment method is the most commonly used approach owing to its general applicability and biocompatibility. Currently, there are four common applications of bioactive paper: (1) paper-based bioassay or paper-based analytical devices for sample conditioning; (2) counterfeiting and countertempering in the packaging and construction industries; (3) pathogen detection for food and water quality monitoring; and (4) deactivation of pathogenic bacteria using antimicrobial paper. This article reviews and compares the different biomolecule immobilization techniques and discusses current trends. Current, emerging and future applications of bioactive paper are also discussed.

  5. In Vitro and In Vivo Evaluation of Microparticulate Drug Delivery Systems Composed of Macromolecular Prodrugs

    Directory of Open Access Journals (Sweden)

    Yoshiharu Machida

    2008-08-01

    Full Text Available Macromolecular prodrugs are very useful systems for achieving controlled drug release and drug targeting. In particular, various macromolecule-antitumor drug conjugates enhance the effectiveness and improve the toxic side effects. Also, polymeric micro- and nanoparticles have been actively examined and their in vivo behaviors elucidated, and it has been realized that their particle characteristics are very useful to control drug behavior. Recently, researches based on the combination of the concepts of macromolecular prodrugs and micro- or nanoparticles have been reported, although they are limited. Macromolecular prodrugs enable drugs to be released at a certain controlled release rate based on the features of the macromolecule-drug linkage. Micro- and nanoparticles can control in vivo behavior based on their size, surface charge and surface structure. These merits are expected for systems produced by the combination of each concept. In this review, several micro- or nanoparticles composed of macromolecule-drug conjugates are described for their preparation, in vitro properties and/or in vivo behavior.

  6. Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics

    Science.gov (United States)

    Moffatt, Ryan; Ma, Buyong; Nussinov, Ruth

    2016-01-01

    Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts. PMID:27124275

  7. Implementation of remote monitoring and diffraction evaluation systems at the Photon Factory macromolecular crystallography beamlines

    Science.gov (United States)

    Yamada, Yusuke; pHonda, Nobuo; Matsugaki, Naohiro; Igarashi, Noriyuki; Hiraki, Masahiko; Wakatsuki, Soichi

    2008-01-01

    Owing to recent advances in high-throughput technology in macromolecular crystallography beamlines, such as high-brilliant X-ray sources, high-speed readout detectors and robotics, the number of samples that can be examined in a single visit to the beamline has increased dramatically. In order to make these experiments more efficient, two functions, remote monitoring and diffraction image evaluation, have been implemented in the macromolecular crystallography beamlines at the Photon Factory (PF). Remote monitoring allows scientists to participate in the experiment by watching from their laboratories, without having to come to the beamline. Diffraction image evaluation makes experiments easier, especially when using the sample exchange robot. To implement these two functions, two independent clients have been developed that work specifically for remote monitoring and diffraction image evaluation. In the macromolecular crystallography beamlines at PF, beamline control is performed using STARS (simple transmission and retrieval system). The system adopts a client–server style in which client programs communicate with each other through a server process using the STARS protocol. This is an advantage of the extension of the system; implementation of these new functions required few modifications of the existing system. PMID:18421163

  8. Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics.

    Directory of Open Access Journals (Sweden)

    Tatiana Maximova

    2016-04-01

    Full Text Available Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts.

  9. Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.

    Science.gov (United States)

    Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

    2013-11-01

    The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation.

  10. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução

    OpenAIRE

    Almeida,Vera Lúcia; Leitão,Andrei; Reina,Luisa del Carmen Barrett; Montanari,Carlos Alberto; Donnici,Claudio Luis; Lopes,Míriam Teresa Paz

    2005-01-01

    The chemotherapy agents against cancer may be classified as "cell cycle-specific" or "cell cycle-nonspecific". Nevertheless, several of them have their biological activity related to any kind of action on DNA such as: antimetabolic agents (DNA synthesis inhibition), inherently reactive agents (DNA alkylating electrophilic traps for macromolecular nucleophiles from DNA through inter-strand cross-linking - ISC - alkylation) and intercalating agents (drug-DNA interactions inherent to the binding...

  11. Marine actinomycetes: an ongoing source of novel bioactive metabolites.

    Science.gov (United States)

    Subramani, Ramesh; Aalbersberg, William

    2012-12-20

    Actinomycetes are virtually unlimited sources of novel compounds with many therapeutic applications and hold a prominent position due to their diversity and proven ability to produce novel bioactive compounds. There are more than 22,000 known microbial secondary metabolites, 70% of which are produced by actinomycetes, 20% from fungi, 7% from Bacillus spp. and 1-2% by other bacteria. Among the actinomycetes, streptomycetes group are considered economically important because out of the approximately more than 10,000 known antibiotics, 50-55% are produced by this genus. The ecological role of actinomycetes in the marine ecosystem is largely neglected and various assumptions meant there was little incentive to isolate marine strains for search and discovery of new drugs. The search for and discovery of rare and new actinomycetes is of significant interest to drug discovery due to a growing need for the development of new and potent therapeutic agents. Modern molecular technologies are adding strength to the target-directed search for detection and isolation of bioactive actinomycetes, and continued development of improved cultivation methods and molecular technologies for accessing the marine environment promises to provide access to this significant new source of chemical diversity with novel/rare actinomycetes including new species of previously reported actinomycetes. Copyright © 2012 Elsevier GmbH. All rights reserved.

  12. Investigation of ethosomes as surrogate carriers for bioactives

    Directory of Open Access Journals (Sweden)

    Devina Verma

    2016-01-01

    Full Text Available Background: Ethosomal vesicular system delivering a bioactive phytochemical, chrysin, was developed for transdermal delivery to increase its permeability and penetrability. Materials and Methods: Ethosomal system was optimized by keeping lecithin and ethanol concentration as independent variable while size and size distribution were taken as dependent variables. The optimized formulation was then subjected to various in vitro characterization parameters. Results: Ethosomal vesicle with an optimum size and polydispersity index of 134 ± 35 nm and 0.153, respectively, and entrapment efficiency of 80.05 ± 2.6% was considered as optimized and subjected to characterization. The scanning electron microscopy and transmission electron microscopy showed spherical entities with uniform surface whereas in vitro permeation and retention study showed the sustained mode of drug release and better skin retention as compared to hydroethanolic solution of the drug. The confocal laser scanning microscopy study reiterated high penetrability of vesicles into the skin. Histopathological and Fourier transform infrared spectroscopy analysis revealed its mechanism of penetration. Conclusion : The study thus demonstrated the ability of the ethosomal vesicles as surrogate carriers for delivery of bioactive agents through the skin for better amelioration of skin inflammation and other diseases.

  13. [Uricosuric agent].

    Science.gov (United States)

    Ohno, Iwao

    2008-04-01

    Urate lowering treatment is indicated in patients with recurrent acute attacks, tophi, gouty arthropathy, radiographic changes of gout, multiple joint involvement, or associated uric acid nephrolithiasis. Uricosuric agents like benzbromarone and probenecid are very useful to treat hyperuricemia as well as allopurinol (xanthine oxidase inhibitor). Uricosuric agents act the urate lowering effect through blocking the URAT1, an urate transporter, in brush border of renal proximal tubular cells. In order to avoid the nephrotoxicity and urolithiasis due to increasing of urinary urate excretion by using uricosuric agents, the proper urinary tract management (enough urine volume and correction of aciduria) should be performed.

  14. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance

    OpenAIRE

    Nishant A. Dafale; Uttam P. Semwal; Rupak K. Rajput; Singh, G. N.

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Resistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the pote...

  15. GC/MS DETERMINATION OF BIOACTIVE COMPONENTS OF PLEUROTUS OSTREATUS

    Directory of Open Access Journals (Sweden)

    V.Priya

    2012-03-01

    Full Text Available In this study, the bioactive components of Pleurotus ostreatus have been evaluated using GC/MS. The chemical compositions of the hydroalcholic extract of Pleurotus ostreatus were investigated using Perkin-Elmer Chromatography–Mass Spectrometry, while the mass spectra of the compounds found in the extract was matched with the National Institute of Standards and Technology (NIST library. GC/MS analysis of hydroalcholic extract of Pleurotus ostreatus revealed the existence of Cholestane-3,7,1,25-tetrol tetraacetate,(3a,5a,7a,12 a-55.20, 9,12-Octadecadienoic acid,methyl ester(E,E-18.55,14,17- Octadecadienoic acid,methyl ester(E,E-5.59,Pentadecanoic acid, ethyl ester-3.84.. The results of this study offer a platform for using Pleurotus ostreatus as herbal alternative for the current synthetic antimicrobial agents.

  16. Vasoactive Agents

    OpenAIRE

    Husedzinovic, Ino; Bradic, Nikola; Goranovic, Tanja

    2006-01-01

    This article is a short review of vasoactive drugs which are in use in todays clinical practice. In the past century, development of vasoactive drugs went through several phases. All of these drugs are today divided into several groups, depending on their place of action, pharmacological pathways and/or effects on target organ or organ system. Hence, many different agents are today in clinical practice, we have shown comparison between them. These agents provide new directions in the treatmen...

  17. The effect of macromolecular crowding on the electrostatic component of barnase-barstar binding: a computational, implicit solvent-based study.

    Directory of Open Access Journals (Sweden)

    Helena W Qi

    Full Text Available Macromolecular crowding within the cell can impact both protein folding and binding. Earlier models of cellular crowding focused on the excluded volume, entropic effect of crowding agents, which generally favors compact protein states. Recently, other effects of crowding have been explored, including enthalpically-related crowder-protein interactions and changes in solvation properties. In this work, we explore the effects of macromolecular crowding on the electrostatic desolvation and solvent-screened interaction components of protein-protein binding. Our simple model enables us to focus exclusively on the electrostatic effects of water depletion on protein binding due to crowding, providing us with the ability to systematically analyze and quantify these potentially intuitive effects. We use the barnase-barstar complex as a model system and randomly placed, uncharged spheres within implicit solvent to model crowding in an aqueous environment. On average, we find that the desolvation free energy penalties incurred by partners upon binding are lowered in a crowded environment and solvent-screened interactions are amplified. At a constant crowder density (fraction of total available volume occupied by crowders, this effect generally increases as the radius of model crowders decreases, but the strength and nature of this trend can depend on the water probe radius used to generate the molecular surface in the continuum model. In general, there is huge variation in desolvation penalties as a function of the random crowder positions. Results with explicit model crowders can be qualitatively similar to those using a lowered "effective" solvent dielectric to account for crowding, although the "best" effective dielectric constant will likely depend on multiple system properties. Taken together, this work systematically demonstrates, quantifies, and analyzes qualitative intuition-based insights into the effects of water depletion due to crowding on the

  18. Silicon Utilizing Microbial Bioactivities in the Biosphere

    Science.gov (United States)

    Sen, M. M.; Das, S.

    2012-12-01

    potential as a source of biomass for the production of biofuels, due to their high growth rates and high cellular lipid content. Petroleum pollutant degradation can also be done by these organisms-Achanthes minutissima has degradable effects involving petroleum hydocarbons. Stephanopyxis turris a silicon utilizing organism releases a blend of chlorinated C8 hydrocarbons. This adds a fundamentally new pathway to the limited set of halogenating enzymatic activities known from nature. Many silicon utilizing organisms can produce PUFA from saturated fatty acids which ultimately produce many important bioactive chemicals like hormosirene, finaverrene, heptadienal, dietyopterene, cystophorene, decadienal. Trienoic acid, octadiene and many other important agents. Similarly terpenoid biosynthetic pathway is activated by them with formation of diterpenoids, sesterpenoids, triterpenoids and sterols.

  19. Microencapsulation of bioactives for food applications.

    Science.gov (United States)

    Dias, Maria Inês; Ferreira, Isabel C F R; Barreiro, Maria Filomena

    2015-04-01

    Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this context, microencapsulation emerges as a potential approach to overcome these problems and, additionally, to provide controlled or targeted delivery or release. This work intends to contribute to the field of functional food development by performing a comprehensive review on the microencapsulation methods and materials, the bioactives used (extracts and isolated compounds) and the final application development. Although several studies dealing with microencapsulation of bioactives exist, they are mainly focused on the process development and the majority lack proof of concept for final applications. These factors, together with the lack of regulation, in Europe and in the United States, delay the development of new functional foods and, consequently, their market entry. In conclusion, the potential of microencapsulation to protect bioactive compounds ensuring their bioavailability is shown, but further studies are required, considering both its applicability and incentives by regulatory agencies.

  20. Bioactive glass-ceramics coatings on alumina

    Energy Technology Data Exchange (ETDEWEB)

    Vitale Brovarone, C.; Verne, E.; Lupo, F. [Politecnico di Torino (Italy). Materials Science and Chemical Eng. Dept.; Moisescu, C. [Jena Univ. (Germany). Otto-Schott-Inst. fuer Glaschemie; Zanardi, L.; Bosetti, M.; Cannas, M. [Eastern Piemont Univ., Novara (Italy). Medical Science Dept.

    2001-07-01

    In this work, aiming to combine the mechanical performances of alumina with the surface properties of a bioactive material, we coated full density alumina substrates by a bioactive glass-ceramic GC. This latter was specially tailored, in term of costituents and specific quantity to have a thermal expansion coefficient close to that of alumina (8.5-9{sup *}10{sup -6}/ C) which is lower than most of the bioactive glasses and glass-ceramics already in use. In this way, we sought to avoid, as much as possible, the crack formation and propagation due to residual stresses generated by the thermal expansion coefficients mismatch. Furthermore, the high reactivity of alumina toward the glass-ceramic was carefully controlled to avoid deep compositional modification of the GC that will negatively affect its bioactivity. At this purpose, an intermediate layer of an appropriate glass G was coated prior to coat the bioactive glass-ceramic. On the materials obtained, preliminary biological tests have been done to evaluate glass-ceramic biocompatibility respect to alumina. (orig.)

  1. Milk proteins as precursors of bioactive peptides

    Directory of Open Access Journals (Sweden)

    Marta Dziuba

    2009-03-01

    Full Text Available Milk proteins, a source of bioactive peptides, are the subject of numerous research studies aiming to, among others, evaluate their properties as precursors of biologically active peptides. Physiologically active peptides released from their precursors may interact with selected receptors and affect the overall condition and health of humans. By relying on the BIOPEP database of proteins and bioactive peptides, developed by the Department of Food Biochemistry at the University of Warmia and Mazury in Olsztyn (www.uwm.edu.pl/biochemia, the profiles of potential activity of milk proteins were determined and the function of those proteins as bioactive peptide precursors was evaluated based on a quantitative criterion, i.e. the occurrence frequency of bioactive fragments (A. The study revealed that milk proteins are mainly a source of peptides with the following types of activity: antihypertensive (Amax = 0.225, immunomodulating (0.024, smooth muscle contracting (0.011, antioxidative (0.029, dipeptidyl peptidase IV inhibitors (0.148, opioid (0.073, opioid antagonistic (0.053, bonding and transporting metals and metal ions (0.024, antibacterial and antiviral (0.024, and antithrombotic (0.029. The enzymes capable of releasing bioactive peptides from precursor proteins were determined for every type of activity. The results of the experiment indicate that milk proteins such as lactoferrin, α-lactalbumin, β-casein and κ-casein hydrolysed by trypsin can be a relatively abundant source of biologically active peptides.

  2. [Inotropic agents].

    Science.gov (United States)

    Sasayama, Shigetake

    2003-05-01

    Depression of myocardial contractility plays an important role in the development of heart failure and many inotropic agents were developed to improve the contractile function of the failing heart. Agents that increase cyclic AMP, either by increasing its synthesis or reducing its degradation, exerted dramatic short-term hemodynamic benefits, but these acute effects were not extrapolated into long-term improvement of the clinical outcome of heart failure patients. Administration of these agents to an energy starved failing heart would be expected to increase myocardial energy use and could accelerate disease progression. The role of digitalis in the management of heart failure has been controversial, however, the recent large scale clinical trial has ironically proved that digoxin reduced the rate of hospitalization both overall and for worsening heart failure. More recently, attention was paid to other inotropic agents that have a complex and diversified mechanism. These agents have some phosphodiesterase-inhibitory action but also possess additional effects, including cytokine inhibitors, immunomodulators, or calcium sensitizers. In the Western Societies these agents were again shown to increase mortality of patients with severe heart failure in a dose dependent manner with the long-term administration. However, it may not be the case in the Japanese population in whom mortality is relatively low. Chronic treatment with inotropic agent may be justified in Japanese, as it allows optimal care in the context of relief of symptoms and an improved quality of life. Therefore, each racial group should obtain specific evidence aimed at developing its own guidelines for therapy rather than translating major guidelines developed for other populations.

  3. Bioactive sterols from marine resources and their potential benefits for human health.

    Science.gov (United States)

    Kim, Se-Kwon; Van Ta, Quang

    2012-01-01

    Bioactive agents from marine resources have shown their valuable health beneficial effects. Therefore, increase knowledge on novel functional ingredients with biological activities from marine animal and microbe has gained much attention. Sterols are recognized as potential in development functional food ingredients and pharmaceutical agents. Marine resources, with a great diversity, can be a very interesting natural resource of sterols. This chapter focuses on biological activities of marine animal and microbe sterols with potential health beneficial applications in functional foods and pharmaceuticals. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Aquasomes: Self-assembled systems for the delivery of bioactive molecules

    Directory of Open Access Journals (Sweden)

    Neha Narang

    2012-01-01

    Full Text Available Nanocarriers increase the therapeutic efficacy of the pharmaceutically active agents as they can regulate their release, improve their stability and prolong circulation time by protecting the drug from phagocytosis and premature degradation. These delivery vehicles have the potential to augment the pharmacodynamic and pharmacokinetic profiles of drug molecules, thereby enhancing the therapeutic efficacy of the pharmaceutical agents. Nanoparticles which are fabricated from ceramics consist of a hydroxyapatite core whose surface is noncovalently modified by oligosaccharide on which bioactive material/drug can be absorbed, are known as "aquasomes." This review involves properties, advantages, preparation methods, evaluation, and applications of aquasomes.

  5. Interaction between cationic agents and small interfering RNA and DNA molecules

    Science.gov (United States)

    Unksov, I. N.; Slita, A. V.; Petrova, A. V.; Pereviazko, I.; Bakulev, V. M.; Rolich, V. I.; Bondarenko, A. B.; Kasyanenko, N. A.

    2016-11-01

    Azobenzene containing surfactant AzoTAB was used for investigation of binding in cationic- agent + nucleic acid in NaCl salt aqueous solutions. Two nucleic acids, macromolecular DNA and small interfering RNA, were examined upon the interaction with the surfactant. For DNA the interaction was studied using spectral methods and the methods of viscometry and flow birefringence measurement. For siRNA the possibility of surfactant-based delivery was checked in vitro.

  6. Sunscreening Agents

    Science.gov (United States)

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  7. PREPARATION AND CATALYTIC ACTIVITY OF BIOACTIVE FIBERS

    Institute of Scientific and Technical Information of China (English)

    Yu-yuan Yao; Wen-xing Chen; Bao-yan Zhao; Shen-shui Lü

    2006-01-01

    Two kinds of water-soluble metallophthalocyanines, binuclear cobalt phthalocyanine (Co2Pc2) and binuclear ferric phthalocyanine (Fe2Pc2), were synthesized through phenylanhydride-urea route and characterized by elemental analysis and FT-IR spectra. Binuclear metallophthalocyanine derivatives (Mt2Pc2) were immobilized on silk fibers and modified viscose fibers to construct bioactive fibers of mimic enzyme. Mt2Pc2 was used as the active center ofbioactive fibers, viscose and silk fibers as the microenvironments. The catalytic oxidation ability of bioactive fibers on the malodors of methanthiol and hydrogen sulfide was investigated at room temperature. The experimental results indicated that the catalytic activity of such bioactive fibers was closely correlative to the types ofbioactive fibers and substrates.

  8. Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses.

    Science.gov (United States)

    Arepalli, Sampath Kumar; Tripathi, Himanshu; Hira, Sumit Kumar; Manna, Partha Pratim; Pyare, Ram; S P Singh

    2016-12-01

    Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO2 in Na2O-CaO-SrO-P2O5-SiO2 system. This work demonstrates that the substitution of SrO for SiO2 has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO2. The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Science.gov (United States)

    Ó Conchúir, Shane; Barlow, Kyle A; Pache, Roland A; Ollikainen, Noah; Kundert, Kale; O'Meara, Matthew J; Smith, Colin A; Kortemme, Tanja

    2015-01-01

    The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks) to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  10. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Directory of Open Access Journals (Sweden)

    Shane Ó Conchúir

    Full Text Available The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  11. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Coquel

    2013-04-01

    Full Text Available Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian. Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on

  12. D3, the new diffractometer for the macromolecular crystallography beamlines of the Swiss Light Source

    Energy Technology Data Exchange (ETDEWEB)

    Fuchs, Martin R., E-mail: mfuchs@bnl.gov [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Brookhaven National Laboratory, Mail Stop 745, Upton, NY 11973 (United States); Pradervand, Claude; Thominet, Vincent; Schneider, Roman; Panepucci, Ezequiel; Grunder, Marcel; Gabadinho, Jose; Dworkowski, Florian S. N.; Tomizaki, Takashi; Schneider, Jörg; Mayer, Aline; Curtin, Adrian; Olieric, Vincent; Frommherz, Uli; Kotrle, Goran; Welte, Jörg; Wang, Xinyu; Maag, Stephan [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Schulze-Briese, Clemens [DECTRIS Ltd, Neuenhoferstrasse 107, 5400 Baden (Switzerland); Wang, Meitian [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland)

    2014-02-04

    A new diffractometer for microcrystallography has been developed for the three macromolecular crystallography beamlines of the Swiss Light Source. A new diffractometer for microcrystallography has been developed for the three macromolecular crystallography beamlines of the Swiss Light Source. Building upon and critically extending previous developments realised for the high-resolution endstations of the two undulator beamlines X06SA and X10SA, as well as the super-bend dipole beamline X06DA, the new diffractometer was designed to the following core design goals. (i) Redesign of the goniometer to a sub-micrometer peak-to-peak cylinder of confusion for the horizontal single axis. Crystal sizes down to at least 5 µm and advanced sample-rastering and scanning modes are supported. In addition, it can accommodate the new multi-axis goniometer PRIGo (Parallel Robotics Inspired Goniometer). (ii) A rapid-change beam-shaping element system with aperture sizes down to a minimum of 10 µm for microcrystallography measurements. (iii) Integration of the on-axis microspectrophotometer MS3 for microscopic sample imaging with 1 µm image resolution. Its multi-mode optical spectroscopy module is always online and supports in situ UV/Vis absorption, fluorescence and Raman spectroscopy. (iv) High stability of the sample environment by a mineral cast support construction and by close containment of the cryo-stream. Further features are the support for in situ crystallization plate screening and a minimal achievable detector distance of 120 mm for the Pilatus 6M, 2M and the macromolecular crystallography group’s planned future area detector Eiger 16M.

  13. Optimized beamline design for macromolecular crystallography at the Cornell High Energy Synchrotron Source (CHESS) (abstract)

    Science.gov (United States)

    Schildkamp, Wilfried; Bilderback, Donald; Moffat, Keith

    1989-07-01

    The A1 station on the CHESS wiggler beamline has been the workhorse for most macromolecular crystallographic experiments. This station is equipped with a fixed energy focusing germanium (111) monochromator and a focusing total reflection mirror. Our macromolecular crystallographers made full use of the high flux of more than 1012 photons/s/mm2 and the stable beam conditions, both in position and energy resolution. As a result, the A1 station was heavily oversubscribed. CHESS is presently expanding its capabilities and a new diffraction station for macromolecular crystallography is under construction. This beamline will be powered by a 24-pole hybrid permanent magnet wiggler with a critical energy of 25 keV. A focusing monochromator, which handles a specific heat load of 10 W/mm2, will have a range of tunability which covers all relevant absorption edges from 7 to 15 keV using a Ge(111) crystal. The energy resolution and the focusing properties remain constant within a factor of 2 over the entire tunability range. We expect a brilliance of about 1013 photons/s/mm2/mrad2/0.1% bandpass. The diffraction station will be equipped with an oscillation camera which can be used with x-ray film of 5×5 or 8×10 in. size or alternatively with Kodak storage phosphors. A wide variety of clamp-on accessories, like crystal coolers, fast shutters, helium pathways, polarimeter, etc. are available. The station will contain a beampipe system, which can also be used for small angle scattering experiments with sample-to-detector distances of up to 3000 mm. The entire diffraction station, its control area, a biological preparation area, and a darkroom are to be embedded in a biological safety containment of the level BL3. This will allow diffraction studies of virulent strains of viruses and other biohazards, which could not previously be studied at synchrotron radiation sources before without causing major disruption to the normal laboratory procedure.

  14. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

    Science.gov (United States)

    Coquel, Anne-Sophie; Jacob, Jean-Pascal; Primet, Mael; Demarez, Alice; Dimiccoli, Mariella; Julou, Thomas; Moisan, Lionel; Lindner, Ariel B; Berry, Hugues

    2013-04-01

    Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular

  15. Mobile Agents

    Science.gov (United States)

    Satoh, Ichiro

    Mobile agents are autonomous programs that can travel from computer to computer in a network, at times and to places of their own choosing. The state of the running program is saved, by being transmitted to the destination. The program is resumed at the destination continuing its processing with the saved state. They can provide a convenient, efficient, and robust framework for implementing distributed applications and smart environments for several reasons, including improvements to the latency and bandwidth of client-server applications and reducing vulnerability to network disconnection. In fact, mobile agents have several advantages in the development of various services in smart environments in addition to distributed applications.

  16. The "macromolecular tourist": universal temperature dependence of thermal diffusion in aqueous colloidal suspensions.

    Science.gov (United States)

    Iacopini, S; Rusconi, R; Piazza, R

    2006-01-01

    By performing measurements on a large class of macromolecular and colloidal systems, we show that thermophoresis (particle drift induced by thermal gradients) in aqueous solvents displays a distinctive universal dependence on temperature. For systems of particles interacting via temperature-independent forces, this behavior is strictly related to the solvent thermal expansivity, while an additional, T-independent term is needed to account for the behavior of "thermophilic" (migrating to the warmth) particles. The former relation between thermophoresis and thermal expansion may be exploited to envisage other fruitful studies of colloidal diffusion in inhomogeneous fluids.

  17. Simulation of macromolecular liquids with the adaptive resolution molecular dynamics technique

    Science.gov (United States)

    Peters, J. H.; Klein, R.; Delle Site, L.

    2016-08-01

    We extend the application of the adaptive resolution technique (AdResS) to liquid systems composed of alkane chains of different lengths. The aim of the study is to develop and test the modifications of AdResS required in order to handle the change of representation of large molecules. The robustness of the approach is shown by calculating several relevant structural properties and comparing them with the results of full atomistic simulations. The extended scheme represents a robust prototype for the simulation of macromolecular systems of interest in several fields, from material science to biophysics.

  18. INFLUENCE OF THE SOLVENT SWELLING ON MACROMOLECULAR CHOLESTERIC LIQUID CRYSTALLINE STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    Jia Zeng; Yong Huang

    1999-01-01

    Ethyl-cyanoethyl cellulose [(E-CE)C]/cross-linked polyacrylic acid [PAA] molecular composites with cholesteric order were prepared. It was found that the macromolecular cholesteric structure was changed with the swelling of PAA in the composites. The selective reflection of the cholesteric phase shifted to the longer wavelength and the X-ray diffraction angle shifted to the high angle direction during swelling, which suggested that the cholesteric pitch and the number of the layers of ordered (E-CE)C chains in the cholesteric phase were increased.

  19. A vibrating membrane bioreactor (VMBR): Macromolecular transmission-influence of extracellular polymeric substances

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2009-01-01

    The vibrating membrane bioreactor (VMBR) system facilitates the possibility of conducting a separation of macromolecules (BSA) from larger biological components (yeast cells) with a relatively high and stable macromolecular transmission at sub-critical flux. This is not possible to achieve...... for a static non-vibrating membrane module. A BSA transmission of 74% has been measured in the separation of 4g/L BSA from 8 g/L dry weight yeast cells in suspension at sub-critical flux (20L/(m(2) h)). However, this transmission is lower than the 85% BSA transmission measured for at pure 4g/L BSA solution...

  20. Chirality as a physical aspect of structure formation in biological macromolecular systems

    Science.gov (United States)

    Malyshko, E. V.; Tverdislov, V. A.

    2016-08-01

    A novel regularity of hierarchical structures is found in the formation of chiral biological macromolecular systems. The formation of structures with alternating chirality (helical structures) serves as an instrument of stratification. The ability of a carbon atom to form chiral compounds is an important factor that determined the carbon basis of living systems on the Earth as well as their development through a series of chiral bifurcations. In the course of biological evolution, the helical structures became basic elements of the molecular machines in the cell. The discreteness of structural levels allowed the mechanical degrees of freedom formation in the molecular machines in the cell.

  1. Milk derived bioactive peptides and their impact on human health – A review

    Directory of Open Access Journals (Sweden)

    D.P. Mohanty

    2016-09-01

    Full Text Available Milk-derived bioactive peptides have been identified as potential ingredients of health-promoting functional foods. These bioactive peptides are targeted at diet-related chronic diseases especially the non-communicable diseases viz., obesity, cardiovascular diseases and diabetes. Peptides derived from the milk of cow, goat, sheep, buffalo and camel exert multifunctional properties, including anti-microbial, immune modulatory, anti-oxidant, inhibitory effect on enzymes, anti-thrombotic, and antagonistic activities against various toxic agents. Majority of those regulate immunological, gastrointestinal, hormonal and neurological responses, thereby playing a vital role in the prevention of cancer, osteoporosis, hypertension and other disorders as discussed in this review. For the commercial production of such novel bioactive peptides large scale technologies based on membrane separation and ion exchange chromatography methods have been developed. Separation and identification of those peptides and their pharmacodynamic parameters are necessary to transfer their potent functional properties into food applications. The present review summarizes the preliminary classes of bioactive milk-derived peptides along with their physiological functions, general characteristics and potential applications in health-care.

  2. Preparation and biocompatibility of poly (methyl methacrylate reinforced with bioactive particles

    Directory of Open Access Journals (Sweden)

    Pereira Marivalda de Magalhães

    2003-01-01

    Full Text Available Calcium phosphates and bioactive glasses have been used in many biomedical applications for more than 30 years due basically to their bioactive behavior. However, ceramics are too brittle for applications that require high levels of toughness and easy processability. In this work, a biphasic calcium phosphate (BCP and a bioactive glass composition (BG were combined with polymers to produce composites with tailorable properties and processability. The BCP particles were synthesized by a precipitation technique. The BG particles were produced by sol-gel processing. The BCP particles were treated with a silane agent to improve the compatibility between particles and the polymer matrix. Dense samples were produced by hot pressing (200 °C a mixture of 30 wt.% of particles in poly (methyl methacrylate. The samples produced were characterized by X-ray diffraction, infrared spectroscopy and scanning electron microscopy. Mechanical properties were evaluated by a three point bending test. Samples were also submitted to in vitro bioactivity test and in vivo toxicity test. Results showed that the production of the composites was successfully achieved, yielding materials with particles well dispersed within the matrices. Evaluation of the in vivo inflammatory response showed low activity levels for all composites although composites with silane treated BCP particles led to milder inflammatory responses than composites with non-treated particles.

  3. Milk derived bioactive peptides and their impact on human health - A review.

    Science.gov (United States)

    Mohanty, D P; Mohapatra, S; Misra, S; Sahu, P S

    2016-09-01

    Milk-derived bioactive peptides have been identified as potential ingredients of health-promoting functional foods. These bioactive peptides are targeted at diet-related chronic diseases especially the non-communicable diseases viz., obesity, cardiovascular diseases and diabetes. Peptides derived from the milk of cow, goat, sheep, buffalo and camel exert multifunctional properties, including anti-microbial, immune modulatory, anti-oxidant, inhibitory effect on enzymes, anti-thrombotic, and antagonistic activities against various toxic agents. Majority of those regulate immunological, gastrointestinal, hormonal and neurological responses, thereby playing a vital role in the prevention of cancer, osteoporosis, hypertension and other disorders as discussed in this review. For the commercial production of such novel bioactive peptides large scale technologies based on membrane separation and ion exchange chromatography methods have been developed. Separation and identification of those peptides and their pharmacodynamic parameters are necessary to transfer their potent functional properties into food applications. The present review summarizes the preliminary classes of bioactive milk-derived peptides along with their physiological functions, general characteristics and potential applications in health-care.

  4. Characterization and bioactivities of a novel polysaccharide obtained from Gracilariopsis lemaneiformis

    Directory of Open Access Journals (Sweden)

    CHEN-SHAN SHI

    Full Text Available ABSTRACT Gracilariopsis lemaneiformis is a type of red alga that contains seaweed polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis lemaneiformis was isolated from Gracilariopsis lemaneiformis. Structural analysis showed that GCP shows triple helical chain conformation when dissolved in water and has many branches and long side chains. Also, 1→3 linkage is the major linkage and the sugar structures are galactopyranose configurations linked by β-type glycosidic linkages. Two macromolecular substance fractions (GCP-1 and GCP-2 were purified by DEAE Sepharose Fast Flow column chromatography. Moreover, a splenocyte damage assay and splenocyte proliferation assay were used to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest protection rate, that is, 92.8%, which significantly enhanced the splenocyte proliferation, and GCP showed the highest proliferation rate, 9.30%. The results suggested that this type of novel non-agar polysaccharide displayed remarkable antioxidant and immunomodulatory activities and early alkali treatment could decrease the activities. It may represent a potential material for health food and clinical medicines.

  5. Sequence-defined bioactive macrocycles via an acid-catalysed cascade reaction

    Science.gov (United States)

    Porel, Mintu; Thornlow, Dana N.; Phan, Ngoc N.; Alabi, Christopher A.

    2016-06-01

    Synthetic macrocycles derived from sequence-defined oligomers are a unique structural class whose ring size, sequence and structure can be tuned via precise organization of the primary sequence. Similar to peptides and other peptidomimetics, these well-defined synthetic macromolecules become pharmacologically relevant when bioactive side chains are incorporated into their primary sequence. In this article, we report the synthesis of oligothioetheramide (oligoTEA) macrocycles via a one-pot acid-catalysed cascade reaction. The versatility of the cyclization chemistry and modularity of the assembly process was demonstrated via the synthesis of >20 diverse oligoTEA macrocycles. Structural characterization via NMR spectroscopy revealed the presence of conformational isomers, which enabled the determination of local chain dynamics within the macromolecular structure. Finally, we demonstrate the biological activity of oligoTEA macrocycles designed to mimic facially amphiphilic antimicrobial peptides. The preliminary results indicate that macrocyclic oligoTEAs with just two-to-three cationic charge centres can elicit potent antibacterial activity against Gram-positive and Gram-negative bacteria.

  6. Hierarchically Nanoporous Bioactive Glasses for High Efficiency Immobilization of Enzymes

    DEFF Research Database (Denmark)

    He, W.; Min, D.D.; Zhang, X.D.

    2014-01-01

    Bioactive glasses with hierarchical nanoporosity and structures have been heavily involved in immobilization of enzymes. Because of meticulous design and ingenious hierarchical nanostructuration of porosities from yeast cell biotemplates, hierarchically nanostructured porous bioactive glasses can...

  7. Antibiotic Agents

    Science.gov (United States)

    ... agents. A recent survey reported that 76% of liquid soaps from 10 states in the US contained triclosan ... regulated depends upon its intended use and its effectiveness. The US Food and Drug Administration (FDA) regulates antibacterial soaps and antibacterial substances that will either be used ...

  8. Protein co-assembly for the delivery of bioactives.

    OpenAIRE

    Miranda-Tavares, Guilherme; Croguennec, Thomas; Hamon, Pascaline; Peres de sa Peixoto Junior, Paulo; De Carvahlo, Antonio Fernandes; Bouhallab, Said

    2015-01-01

    Introduction Protection and target delivery of food bioactives are main concerns when the manufacture of food products with health-benefit assets is involved. Natural delivery systems for bioactives for instance casein micelle for calcium phosphate are only encountered in some food products and allow the protection and control release of a limited number of bioactives. For this reason, the design of new devices that allow the encapsulation of any types of bioactives is required. Since a large...

  9. Encapsulation for preservation of functionality and targeted delivery of bioactive food components

    NARCIS (Netherlands)

    de Vos, Paul; Faas, Marijke M.; Spasojevic, Milica; Sikkema, Jan

    There has been a tremendous increase in the number of food products containing bioactive components with a health promoting or disease preventing effect. Bioactive food components can be divided into bioactive molecules and bioactive living cells (probiotics). Both bioactive molecules and bioactive

  10. Encapsulation for preservation of functionality and targeted delivery of bioactive food components

    NARCIS (Netherlands)

    de Vos, Paul; Faas, Marijke M.; Spasojevic, Milica; Sikkema, Jan

    2010-01-01

    There has been a tremendous increase in the number of food products containing bioactive components with a health promoting or disease preventing effect. Bioactive food components can be divided into bioactive molecules and bioactive living cells (probiotics). Both bioactive molecules and bioactive

  11. Macromolecular liquids

    Energy Technology Data Exchange (ETDEWEB)

    Safinya, C.R.; Safran, S.A. (Exxon Research and Engineering Co., Annandale, NJ (US)); Pincus, P.A. (Univ. of California at Santa Barbara, Santa Barbara, CA (US))

    1990-01-01

    Liquids include a broad range of material systems which are of high scientific and technological interest. Generally speaking, these are partially ordered or disordered phases where the individual molecular species have organized themselves on length scales which are larger than simple fluids, typically between 10 Angstroms and several microns. The specific systems reported on in this book include membranes, microemulsions, micelles, liquid crystals, colloidal suspensions, and polymers. They have a major impact on a broad spectrum of technological industries such as displays, plastics, soap and detergents, chemicals and petroleum, and pharmaceuticals.

  12. Five new bioactive compounds from Chenopodium ambrosioides.

    Science.gov (United States)

    Song, Kun; Zhang, Jian; Zhang, Peng; Wang, Hong-Qing; Liu, Chao; Li, Bao-Ming; Kang, Jie; Chen, Ruo-Yun

    2015-05-01

    Five new bioactive compounds, chenopodiumamines A-D (1-4) and chenopodiumoside A (5), were isolated from the ethanol extract of Chenopodium ambrosioides. The structures of these compounds were elucidated by various spectroscopic means (UV, IR, HR-ESI-MS, 1D and 2D NMR). Compounds 1-3 had moderate antioxidant and anti-inflammatory activities.

  13. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van

    2000-01-01

    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  14. Bioactive polymeric scaffolds for tissue engineering

    Directory of Open Access Journals (Sweden)

    Scott Stratton

    2016-12-01

    Full Text Available A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

  15. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van

    2000-01-01

    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  16. Bioactive compounds in whole grain wheat

    NARCIS (Netherlands)

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much

  17. Bioactive motifs of agouti signal protein.

    Science.gov (United States)

    Virador, V M; Santis, C; Furumura, M; Kalbacher, H; Hearing, V J

    2000-08-25

    The switch between the synthesis of eu- and pheomelanins is modulated by the interaction of two paracrine signaling molecules, alpha-melanocyte stimulating hormone (MSH) and agouti signal protein (ASP), which interact with melanocytes via the MSH receptor (MC1R). Comparison of the primary sequence of ASP with the known MSH pharmacophore provides no suggestion about the putative bioactive domain(s) of ASP. To identify such bioactive motif(s), we synthesized 15-mer peptides that spanned the primary sequence of ASP and determined their effects on the melanogenic activities of murine melanocytes. Northern and Western blotting were used, together with chemical analysis of melanins and enzymatic assays, to identify three distinct bioactive regions of ASP that down-regulate eumelanogenesis. The decrease in eumelanin production was mediated by down-regulation of mRNA levels for tyrosinase and other melanogenic enzymes, as occurs in vivo, and these effects were comparable to those elicited by intact recombinant ASP. Shorter peptides in those motifs were synthesized and their effects on melanogenesis were further investigated. The amino acid arginine, which is present in the MSH peptide pharmacophore (HFRW), is also in the most active domain of ASP (KVARP). Our data suggest that lysines and an arginine (in motifs such as KxxxxKxxR or KxxRxxxxK) are important for the bioactivity of ASP. Identification of the specific ASP epitope that interacts with the MC1R has potential pharmacological applications in treating dysfunctions of skin pigmentation.

  18. Bioactive compounds in whole grain wheat

    NARCIS (Netherlands)

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much i

  19. Bioactive compounds in whole grain wheat

    NARCIS (Netherlands)

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much i

  20. Bioactive alkaloids in vertically transmitted fungal endophytes

    Science.gov (United States)

    Plants form mutualistic symbioses with a variety of microorganisms, including endophytic fungi that live inside the plant and cause no symptoms of infection. Some endophytic fungi form defensive mutualisms based on the production of bioactive metabolites that protect the plant from herbivores in exc...

  1. Citrus Limonoids: Analysis, Bioactivity, and Biomedical Prospects

    Science.gov (United States)

    This publication is a review of the chemistry, biochemistry and bioactivity of limonoids occurring in citrus. The review chronologically relates the evolution of research in citrus limonoids beginning with their association with bitterness development in citrus juices. The chemical and biochemical...

  2. Bioactive Terpenes from Marine-Derived Fungi

    Directory of Open Access Journals (Sweden)

    Ahmed M. Elissawy

    2015-04-01

    Full Text Available Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

  3. Bioactive terpenes from marine-derived fungi.

    Science.gov (United States)

    Elissawy, Ahmed M; El-Shazly, Mohamed; Ebada, Sherif S; Singab, AbdelNasser B; Proksch, Peter

    2015-04-03

    Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years' reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

  4. Preparation and bioactive properties of nano bioactive glass and segmented polyurethane composites.

    Science.gov (United States)

    Aguilar-Pérez, Fernando J; Vargas-Coronado, Rossana F; Cervantes-Uc, Jose M; Cauich-Rodríguez, Juan V; Covarrubias, Cristian; Pedram-Yazdani, Merhdad

    2016-04-01

    Composites of glutamine-based segmented polyurethanes with 5 to 25 wt.% bioactive glass nanoparticles were prepared, characterized, and their mineralization potential was evaluated in simulated body fluid. Biocompatibility with dental pulp stem cells was assessed by MTS to an extended range of compositions (1 to 25 wt.% of bioactive glass nanoparticles). Physicochemical characterization showed that composites retained many of the matrix properties, i.e. those corresponding to semicrystalline elastomeric polymers as they exhibited a glass transition temperature (Tg) between -41 and -36℃ and a melting temperature (Tm) between 46 and 49℃ in agreement with X-ray reflections at 23.6° and 21.3°. However, with bioactive glass nanoparticles addition, tensile strength and strain were reduced from 22.2 to 12.2 MPa and 667.2 to 457.8%, respectively with 25 wt.% of bioactive glass nanoparticles. Although Fourier transform infrared spectroscopy did not show evidence of mineralization after conditioning of these composites in simulated body fluid, X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray microanalysis showed the formation of an apatite layer on the surface which increased with higher bioactive glass concentrations and longer conditioning time. Dental pulp stem cells proliferation at day 5 was improved in bioactive glass nanoparticles composites containing lower amounts of the filler (1-2.5 wt.%) but it was compromised at day 9 in composites containing high contents of nBG (5, 15, 25 wt.%). However, Runx2 gene expression was particularly upregulated for the dental pulp stem cells cultured with composites loaded with 15 and 25 wt.% of bioactive glass nanoparticles. In conclusion, low content bioactive glass nanoparticles and segmented polyurethanes composites deserve further investigation for applications such as guided bone regeneration membranes, where osteoconductivity is desirable but not a demanding mechanical performance.

  5. Fast Method for Computing Chemical Potentials and Liquid-Liquid Phase Equilibria of Macromolecular Solutions.

    Science.gov (United States)

    Qin, Sanbo; Zhou, Huan-Xiang

    2016-08-25

    Chemical potential is a fundamental property for determining thermodynamic equilibria involving exchange of molecules, such as between two phases of molecular systems. Previously, we developed the fast Fourier transform (FFT)-based method for Modeling Atomistic Protein-crowder interactions (FMAP) to calculate excess chemical potentials according to the Widom insertion. Intermolecular interaction energies were expressed as correlation functions and evaluated via FFT. Here, we extend this method to calculate liquid-liquid phase equilibria of macromolecular solutions. Chemical potentials are calculated by FMAP over a wide range of molecular densities, and the condition for coexistence of low- and high-density phases is determined by the Maxwell equal-area rule. When benchmarked on Lennard-Jones fluids, our method produces an accurate phase diagram at 18% of the computational cost of the current best method. Importantly, the gain in computational speed increases dramatically as the molecules become more complex, leading to many orders of magnitude in speed up for atomistically represented proteins. We demonstrate the power of FMAP by reporting the first results for the liquid-liquid coexistence curve of γII-crystallin represented at the all-atom level. Our method may thus open the door to accurate determination of phase equilibria for macromolecular mixtures such as protein-protein mixtures and protein-RNA mixtures, that are known to undergo liquid-liquid phase separation, both in vitro and in vivo.

  6. A NEW UNSTEADY THREE DIMENSIONAL MODEL FOR MACROMOLECULAR TRANSPORT AND WATER FILTRATION ACROSS THE ARTERIAL WALL

    Institute of Scientific and Technical Information of China (English)

    黄浩; 温功碧

    2001-01-01

    A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mitosis of endothelial cell of the arterial wall, the macromolecular transport happens surrounding the leaky cells. The arterial wall was divided into four layers: the endothelial layer, the subendothelial intima, the internal elastic lamina and the media for the convenience of research. The time-dependent concentration growth,the effect of the shape of endothelial cell and the effect of physiological parameters were analyzed. The analytical solution of velocity field and pressure field of water flow across the arterial wall were obtained; and concentration distribution of three macromolecules ; LDL,HRP and Albumin, were calculated with numerical simulation method. The new theory predicts, the maximum and distribution areas of time dependent concentration with round shape endothelial cell are both larger than that with ellipse-shape endothelial cell. The model also predicts the concentration growth is much alike that of a two-dimensional model and it shows that the concentration reaches its peak at the leaky junction where atherosclerotic formation frequently occurs and falls down rapidly in a limited area beginning from its earlier time growth to the state when macromolecular transfer approaches steadily. These predictions of the new model are in agreement with the experimental observation for the growth and concentration distribution of LDL and Albumin.

  7. A brief history of macromolecular crystallography, illustrated by a family tree and its Nobel fruits.

    Science.gov (United States)

    Jaskolski, Mariusz; Dauter, Zbigniew; Wlodawer, Alexander

    2014-09-01

    As a contribution to the celebration of the year 2014, declared by the United Nations to be 'The International Year of Crystallography', the FEBS Journal is dedicating this issue to papers showcasing the intimate union between macromolecular crystallography and structural biology, both in historical perspective and in current research. Instead of a formal editorial piece, by way of introduction, this review discusses the most important, often iconic, achievements of crystallographers that led to major advances in our understanding of the structure and function of biological macromolecules. We identified at least 42 scientists who received Nobel Prizes in Physics, Chemistry or Medicine for their contributions that included the use of X-rays or neutrons and crystallography, including 24 who made seminal discoveries in macromolecular sciences. Our spotlight is mostly, but not only, on the recipients of this most prestigious scientific honor, presented in approximately chronological order. As a summary of the review, we attempt to construct a genealogy tree of the principal lineages of protein crystallography, leading from the founding members to the present generation. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  8. Force interacts with macromolecular structure in activation of TGF-β.

    Science.gov (United States)

    Dong, Xianchi; Zhao, Bo; Iacob, Roxana E; Zhu, Jianghai; Koksal, Adem C; Lu, Chafen; Engen, John R; Springer, Timothy A

    2017-02-02

    Integrins are adhesion receptors that transmit force across the plasma membrane between extracellular ligands and the actin cytoskeleton. In activation of the transforming growth factor-β1 precursor (pro-TGF-β1), integrins bind to the prodomain, apply force, and release the TGF-β growth factor. However, we know little about how integrins bind macromolecular ligands in the extracellular matrix or transmit force to them. Here we show how integrin αVβ6 binds pro-TGF-β1 in an orientation biologically relevant for force-dependent release of TGF-β from latency. The conformation of the prodomain integrin-binding motif differs in the presence and absence of integrin binding; differences extend well outside the interface and illustrate how integrins can remodel extracellular matrix. Remodelled residues outside the interface stabilize the integrin-bound conformation, adopt a conformation similar to earlier-evolving family members, and show how macromolecular components outside the binding motif contribute to integrin recognition. Regions in and outside the highly interdigitated interface stabilize a specific integrin/pro-TGF-β orientation that defines the pathway through these macromolecules which actin-cytoskeleton-generated tensile force takes when applied through the integrin β-subunit. Simulations of force-dependent activation of TGF-β demonstrate evolutionary specializations for force application through the TGF-β prodomain and through the β- and not α-subunit of the integrin.

  9. Resolving macromolecular structures from electron cryo-tomography data using subtomogram averaging in RELION.

    Science.gov (United States)

    Bharat, Tanmay A M; Scheres, Sjors H W

    2016-11-01

    Electron cryo-tomography (cryo-ET) is a technique that is used to produce 3D pictures (tomograms) of complex objects such as asymmetric viruses, cellular organelles or whole cells from a series of tilted electron cryo-microscopy (cryo-EM) images. Averaging of macromolecular complexes found within tomograms is known as subtomogram averaging, and this technique allows structure determination of macromolecular complexes in situ. Subtomogram averaging is also gaining in popularity for the calculation of initial models for single-particle analysis. We describe herein a protocol for subtomogram averaging from cryo-ET data using the RELION software (http://www2.mrc-lmb.cam.ac.uk/relion). RELION was originally developed for cryo-EM single-particle analysis, and the subtomogram averaging approach presented in this protocol has been implemented in the existing workflow for single-particle analysis so that users may conveniently tap into existing capabilities of the RELION software. We describe how to calculate 3D models for the contrast transfer function (CTF) that describe the transfer of information in the imaging process, and we illustrate the results of classification and subtomogram averaging refinement for cryo-ET data of purified hepatitis B capsid particles and Saccharomyces cerevisiae 80S ribosomes. Using the steps described in this protocol, along with the troubleshooting and optimization guidelines, high-resolution maps can be obtained in which secondary structure elements are resolved subtomogram.

  10. Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction

    Science.gov (United States)

    Wakabayashi, Ayako; Kumagai, Yoshihiro; Watari, Eiji; Shimizu, Masumi; Utsuyama, Masanori; Hirokawa, Katsuiku; Takahashi, Hidemi

    2006-01-01

    Oral administration of a certain dose of antigen can generally induce immunological tolerance against the same antigen. In this study, we showed the temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral blood of mice after the oral administration of OVA. Furthermore, we detected 45 000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based on this observation, we examined whether the injection of intact OVA into the portal or peripheral vein induces immunological tolerance against OVA. We found that the intravenous injection of intact OVA did not induce immunological tolerance but rather enhanced OVA-specific antibody production in some subclasses, suggesting that OVA antigens via the gastrointestinal tract but not intact OVA may contribute to establish immunological tolerance against OVA. Therefore, we examined the effects of digesting intact OVA in the gastrointestinal tract on the induction of oral tolerance. When mice were orally administered or injected into various gastrointestinal organs, such as the stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA-specific antibody production and delayed-type hypersensitivity (DTH) response were significantly enhanced in mice injected into the ileum or colon, compared with orally administered mice. These results suggest that although macromolecular OVA antigens are detected after oral administration of OVA in tolerant-mouse serum, injection of intact OVA cannot contribute to tolerance induction. Therefore, some modification of macromolecular OVA in the gastrointestinal tract and ingestion may be essential for oral tolerance induction. PMID:16796692

  11. Assessing physio-macromolecular effects of lactic acid on Zygosaccharomyces bailii cells during microaerobic fermentation.

    Science.gov (United States)

    Kuanyshev, Nurzhan; Ami, Diletta; Signori, Lorenzo; Porro, Danilo; Morrissey, John P; Branduardi, Paola

    2016-08-01

    The ability of Zygosaccharomyces bailii to grow at low pH and in the presence of considerable amounts of weak organic acids, at lethal condition for Saccharomyces cerevisiae, increased the interest in the biotechnological potential of the yeast. To understand the mechanism of tolerance and growth effect of weak acids on Z. bailii, we evaluated the physiological and macromolecular changes of the yeast exposed to sub lethal concentrations of lactic acid. Lactic acid represents one of the important commodity chemical which can be produced by microbial fermentation. We assessed physiological effect of lactic acid by bioreactor fermentation using synthetic media at low pH in the presence of lactic acid. Samples collected from bioreactors were stained with propidium iodide (PI) which revealed that, despite lactic acid negatively influence the growth rate, the number of PI positive cells is similar to that of the control. Moreover, we have performed Fourier Transform Infra-Red (FTIR) microspectroscopy analysis on intact cells of the same samples. This technique has been never applied before to study Z. bailii under this condition. The analyses revealed lactic acid induced macromolecular changes in the overall cellular protein secondary structures, and alterations of cell wall and membrane physico-chemical properties.

  12. Influence of macromolecular architecture on necking in polymer extrusion film casting process

    Energy Technology Data Exchange (ETDEWEB)

    Pol, Harshawardhan; Banik, Sourya; Azad, Lal Busher; Doshi, Pankaj; Lele, Ashish [CSIR-National Chemical Laboratory, Pune, Maharashtra (India); Thete, Sumeet [Purdue University, West Lafayette, Indiana (United States)

    2015-05-22

    Extrusion film casting (EFC) is an important polymer processing technique that is used to produce several thousand tons of polymer films/coatings on an industrial scale. In this research, we are interested in understanding quantitatively how macromolecular chain architecture (for example long chain branching (LCB) or molecular weight distribution (MWD or PDI)) influences the necking and thickness distribution of extrusion cast films. We have used different polymer resins of linear and branched molecular architecture to produce extrusion cast films under controlled experimental conditions. The necking profiles of the films were imaged and the velocity profiles during EFC were monitored using particle tracking velocimetry (PTV) technique. Additionally, the temperature profiles were captured using an IR thermography and thickness profiles were calculated. The experimental results are compared with predictions of one-dimensional flow model of Silagy et al{sup 1} wherein the polymer resin rheology is modeled using molecular constitutive equations such as the Rolie-Poly (RP) and extended Pom Pom (XPP). We demonstrate that the 1-D flow model containing the molecular constitutive equations provides new insights into the role of macromolecular chain architecture on film necking.{sup 1}D. Silagy, Y. Demay, and J-F. Agassant, Polym. Eng. Sci., 36, 2614 (1996)

  13. X-ray Diffraction of Cotton Treated with Neutralized Vegetable Oil-based Macromolecular Crosslinkers

    Directory of Open Access Journals (Sweden)

    James W. Rawlins, Ph.D.

    2010-03-01

    Full Text Available Maleinized soybean oil (MSO has been investigated as a flexible, macromolecular crosslinker for cotton fabrics. The ability of MSO to penetrate crystalline cellulose and crosslink aligned cellulose chains upon cure has been in question. This study compares the penetration capability of MSO to dimethyloldihydroxyethyleneurea (DMDHEU, which is the commercial standard for durable press finishing and is an efficient cellulose crosslinker. X-ray diffraction was employed to characterize changes in the crystalline morphology upon heating un-mercerized cotton fabrics treated with aqueous DMDHEU and soybean oil derivatives. Displacement of characteristic interplanar spacings and the genesis/elimination of diffraction intensities from quintessential planes were evidence of structural modification. The penetration of ammonia neutralized MSO (acid value 230.00 mg KOH/g into the microstructure of cotton cellulose is similar to that of DMDHEU in terms of expanding the interplanar spacings of characteristic planes. Moreover, polymorphism of cotton and mercerized cotton occurred upon treatment with aqueous solutions of MSO. These findings suggest that macromolecular reagents can diffuse into cellulose fibrils if they are sufficiently hydrated or enshrouded by more favored penetrants.

  14. MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments.

    Science.gov (United States)

    Gabadinho, José; Beteva, Antonia; Guijarro, Matias; Rey-Bakaikoa, Vicente; Spruce, Darren; Bowler, Matthew W; Brockhauser, Sandor; Flot, David; Gordon, Elspeth J; Hall, David R; Lavault, Bernard; McCarthy, Andrew A; McCarthy, Joanne; Mitchell, Edward; Monaco, Stéphanie; Mueller-Dieckmann, Christoph; Nurizzo, Didier; Ravelli, Raimond B G; Thibault, Xavier; Walsh, Martin A; Leonard, Gordon A; McSweeney, Sean M

    2010-09-01

    The design and features of a beamline control software system for macromolecular crystallography (MX) experiments developed at the European Synchrotron Radiation Facility (ESRF) are described. This system, MxCuBE, allows users to easily and simply interact with beamline hardware components and provides automated routines for common tasks in the operation of a synchrotron beamline dedicated to experiments in MX. Additional functionality is provided through intuitive interfaces that enable the assessment of the diffraction characteristics of samples, experiment planning, automatic data collection and the on-line collection and analysis of X-ray emission spectra. The software can be run in a tandem client-server mode that allows for remote control and relevant experimental parameters and results are automatically logged in a relational database, ISPyB. MxCuBE is modular, flexible and extensible and is currently deployed on eight macromolecular crystallography beamlines at the ESRF. Additionally, the software is installed at MAX-lab beamline I911-3 and at BESSY beamline BL14.1.

  15. Translational diffusion of macromolecular assemblies measured using transverse-relaxation-optimized pulsed field gradient NMR.

    Science.gov (United States)

    Horst, Reto; Horwich, Arthur L; Wüthrich, Kurt

    2011-10-19

    In structural biology, pulsed field gradient (PFG) NMR spectroscopy for the characterization of size and hydrodynamic parameters of macromolecular solutes has the advantage over other techniques that the measurements can be recorded with identical solution conditions as used for NMR structure determination or for crystallization trials. This paper describes two transverse-relaxation-optimized (TRO) (15)N-filtered PFG stimulated-echo (STE) experiments for studies of macromolecular translational diffusion in solution, (1)H-TRO-STE and (15)N-TRO-STE, which include CRINEPT and TROSY elements. Measurements with mixed micelles of the Escherichia coli outer membrane protein X (OmpX) and the detergent Fos-10 were used for a systematic comparison of (1)H-TRO-STE and (15)N-TRO-STE with conventional (15)N-filtered STE experimental schemes. The results provide an extended platform for evaluating the NMR experiments available for diffusion measurements in structural biology projects involving molecular particles with different size ranges. An initial application of the (15)N-TRO-STE experiment with very long diffusion delays showed that the tedradecamer structure of the 800 kDa Thermus thermophilus chaperonin GroEL is preserved in aqueous solution over the temperature range 25-60 °C.

  16. Translational diffusion of macromolecular assemblies measured using transverse relaxation-optimized PFG-NMR

    Science.gov (United States)

    Horst, Reto; Horwich, Arthur L.

    2012-01-01

    In structural biology, pulsed field gradient (PFG) NMR for characterization of size and hydrodynamic parameters of macromolecular solutes has the advantage over other techniques that the measurements can be recorded with identical solution conditions as used for NMR structure determination or for crystallization trials. This paper describes two transverse relaxation-optimized (TRO) 15N-filtered PFG stimulated-echo (STE) experiments for studies of macromolecular translational diffusion in solution, 1H-TRO-STE and 15N-TRO-STE, which include CRINEPT and TROSY elements. Measurements with mixed micelles of the Escherichia coli outer membrane protein X (OmpX) and the detergent Fos-10 were used for a systematic comparison of 1H-TRO-STE and 15N-TRO-STE with conventional 15N-filtered STE experimental schemes. The results provide an extended platform for evaluating the NMR experiments available for diffusion measurements in structural biology projects with molecular particles of different size ranges. An initial application of the 15N-TRO-STE experiment with very long diffusion delays showed that the tedradecamer structure of the 800 kDa Thermus thermophilus chaperonin GroEL is preserved in aqueous solution over the temperature range 25–60°C. PMID:21919531

  17. Macromolecular Crowding Studies of Amino Acids Using NMR Diffusion Measurements and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Amninder S Virk

    2015-02-01

    Full Text Available Molecular crowding occurs when the total concentration of macromolecular species in a solution is so high that a considerable proportion of the volume is physically occupied and therefore not accessible to other molecules. This results in significant changes in the solution properties of the molecules in such systems. Macromolecular crowding is ubiquitous in biological systems due to the generally high intracellular protein concentrations. The major hindrance to understanding crowding is the lack of direct comparison of experimental data with theoretical or simulated data. Self-diffusion is sensitive to changes in the molecular weight and shape of the diffusing species, and the available diffusion space (i.e., diffusive obstruction. Consequently, diffusion measurements are a direct means for probing crowded systems including the self-association of molecules. In this work, nuclear magnetic resonance measurements of the self-diffusion of four amino acids (glycine, alanine, valine and phenylalanine up to their solubility limit in water were compared directly with molecular dynamics simulations. The experimental data were then analyzed using various models of aggregation and obstruction. Both experimental and simulated data revealed that the diffusion of both water and the amino acids were sensitive to the amino acid concentration. The direct comparison of the simulated and experimental data afforded greater insights into the aggregation and obstruction properties of each amino acid.

  18. Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

    Directory of Open Access Journals (Sweden)

    Iborra Francisco J

    2007-04-01

    Full Text Available Abstract Background The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. Results The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin scattered within domains rich in fast components (protein/RNA. Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. Conclusion I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon.

  19. MX1: a bending-magnet crystallography beamline serving both chemical and macromolecular crystallography communities at the Australian Synchrotron

    Energy Technology Data Exchange (ETDEWEB)

    Cowieson, Nathan Philip; Aragao, David; Clift, Mark; Ericsson, Daniel J.; Gee, Christine; Harrop, Stephen J.; Mudie, Nathan; Panjikar, Santosh; Price, Jason R.; Riboldi-Tunnicliffe, Alan; Williamson, Rachel; Caradoc-Davies, Tom, E-mail: tom.caradoc-davies@synchrotron.org.au [Australian Synchrotron, 800 Blackburn Road, Clayton, Victoria 3168 (Australia)

    2015-01-01

    The macromolecular crystallography beamline MX1 at the Australian Synchrotron is described. MX1 is a bending-magnet crystallography beamline at the 3 GeV Australian Synchrotron. The beamline delivers hard X-rays in the energy range from 8 to 18 keV to a focal spot at the sample position of 120 µm FWHM. The beamline endstation and ancillary equipment facilitate local and remote access for both chemical and biological macromolecular crystallography. Here, the design of the beamline and endstation are discussed. The beamline has enjoyed a full user program for the last seven years and scientific highlights from the user program are also presented.

  20. Potential Bioactive Compounds from Seaweed for Diabetes Management

    Directory of Open Access Journals (Sweden)

    Yusrizam Sharifuddin

    2015-08-01

    Full Text Available Diabetes mellitus is a group of metabolic disorders of the endocrine system characterised by hyperglycaemia. Type II diabetes mellitus (T2DM constitutes the majority of diabetes cases around the world and are due to unhealthy diet, sedentary lifestyle, as well as rise of obesity in the population, which warrants the search for new preventive and treatment strategies. Improved comprehension of T2DM pathophysiology provided various new agents and approaches against T2DM including via nutritional and lifestyle interventions. Seaweeds are rich in dietary fibres, unsaturated fatty acids, and polyphenolic compounds. Many of these seaweed compositions have been reported to be beneficial to human health including in managing diabetes. In this review, we discussed the diversity of seaweed composition and bioactive compounds which are potentially useful in preventing or managing T2DM by targeting various pharmacologically relevant routes including inhibition of enzymes such as α-glucosidase, α-amylase, lipase, aldose reductase, protein tyrosine phosphatase 1B (PTP1B and dipeptidyl-peptidase-4 (DPP-4. Other mechanisms of action identified, such as anti-inflammatory, induction of hepatic antioxidant enzymes’ activities, stimulation of glucose transport and incretin hormones release, as well as β-cell cytoprotection, were also discussed by taking into consideration numerous in vitro, in vivo, and human studies involving seaweed and seaweed-derived agents.

  1. Potential Bioactive Compounds from Seaweed for Diabetes Management.

    Science.gov (United States)

    Sharifuddin, Yusrizam; Chin, Yao-Xian; Lim, Phaik-Eem; Phang, Siew-Moi

    2015-08-21

    Diabetes mellitus is a group of metabolic disorders of the endocrine system characterised by hyperglycaemia. Type II diabetes mellitus (T2DM) constitutes the majority of diabetes cases around the world and are due to unhealthy diet, sedentary lifestyle, as well as rise of obesity in the population, which warrants the search for new preventive and treatment strategies. Improved comprehension of T2DM pathophysiology provided various new agents and approaches against T2DM including via nutritional and lifestyle interventions. Seaweeds are rich in dietary fibres, unsaturated fatty acids, and polyphenolic compounds. Many of these seaweed compositions have been reported to be beneficial to human health including in managing diabetes. In this review, we discussed the diversity of seaweed composition and bioactive compounds which are potentially useful in preventing or managing T2DM by targeting various pharmacologically relevant routes including inhibition of enzymes such as α-glucosidase, α-amylase, lipase, aldose reductase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl-peptidase-4 (DPP-4). Other mechanisms of action identified, such as anti-inflammatory, induction of hepatic antioxidant enzymes' activities, stimulation of glucose transport and incretin hormones release, as well as β-cell cytoprotection, were also discussed by taking into consideration numerous in vitro, in vivo, and human studies involving seaweed and seaweed-derived agents.

  2. Recent progress in the development of synthetic hybrids of natural or unnatural bioactive compounds for medicinal chemistry.

    Science.gov (United States)

    Tsogoeva, Svetlana B

    2010-08-01

    The present mini-review highlights the recent developments on different classes of synthetic hybrids of natural and/or unnatural bioactive compounds, the utilization of which is very promising, as distinct features of each component can be hybridized and their properties leveraged. Particular stress is put on the respective mode of action and the corresponding rationale behind covalent combinations of various bioactive agents to increase their therapeutic potential, facilitate their administration, to reduce harmful side effects and/or to overcome the problem of multi-drug resistance. This rather recent approach has already found applications in the development of new anti-cancer, anti-Alzheimer, anti-malaria, anti-microbial therapeutics and other novel compounds with unprecedented bioactivity.

  3. Radioprotective Agents

    Science.gov (United States)

    1982-01-01

    claimed to be effective are gallic acid derivatives, eg, sodium gallate 12053-21-61 (295-297) and propyl gallate 1121-79-91 (298). p...inhibition of a-adrenergic receptors can be achieved through the use of the antiradiation agents 2-(5-aminopentylamino)ethanephos- phorothioic acid ...tissue was ap- preciated immediately as a potential medical set, and they were put to use en- thusiastically. Early workers did notice an erythematous

  4. STUDY ON THE CATALYTIC ABILITY OF BIOACTIVE FIBERS

    Institute of Scientific and Technical Information of China (English)

    YAO Yuyuan; CHEN Wenxing

    2006-01-01

    Two kinds of water-soluble metallophthalocyanines (Mt2Pc2), binuclear cobalt phthalocyanine (Co2Pc2) and binuclear ferric phthalocyanine (Fe2Pc2), were supported on silk fibers and modified viscose fibers to construct bioactive fibers of mimic enzyme, Mt2Pc2 used as the active center of bioactive fibers, viscose and silk fibers as the microenvironments. The catalytic oxidation ability of bioactive fibers on the malodors of methanthiol and hydrogen sulfide was investigated at room temperature. The experimental results demonstrated that the catalytic activity of such bioactive fibers was tightly correlative to the types of bioactive fibers and substrates.

  5. Cotton-wool-like bioactive glasses for bone regeneration.

    Science.gov (United States)

    Poologasundarampillai, G; Wang, D; Li, S; Nakamura, J; Bradley, R; Lee, P D; Stevens, M M; McPhail, D S; Kasuga, T; Jones, J R

    2014-08-01

    Inorganic sol-gel solutions were electrospun to produce the first bioactive three-dimensional (3-D) scaffolds for bone tissue regeneration with a structure like cotton-wool (or cotton candy). This flexible 3-D fibrous structure is ideal for packing into complex defects. It also has large inter-fiber spaces to promote vascularization, penetration of cells and transport of nutrients throughout the scaffold. The 3-D fibrous structure was obtained by electrospinning, where the applied electric field and the instabilities exert tremendous force on the spinning jet, which is required to be viscoelastic to prevent jet break up. Previously, polymer binding agents were used with inorganic solutions to produce electrospun composite two-dimensional fibermats, requiring calcination to remove the polymer. This study presents novel reaction and processing conditions for producing a viscoelastic inorganic sol-gel solution that results in fibers by the entanglement of the intermolecularly overlapped nanosilica species in the solution, eliminating the need for a binder. Three-dimensional cotton-wool-like structures were only produced when solutions containing calcium nitrate were used, suggesting that the charge of the Ca(2+) ions had a significant effect. The resulting bioactive silica fibers had a narrow diameter range of 0.5-2μm and were nanoporous. A hydroxycarbonate apatite layer was formed on the fibers within the first 12h of soaking in simulated body fluid. MC3T3-E1 preosteoblast cells cultured on the fibers showed no adverse cytotoxic effect and they were observed to attach to and spread in the material.

  6. Effects of temperature, light and incubation period on production, germination and bioactivity of Trichoderma atroviride.

    Science.gov (United States)

    Daryaei, A; Jones, E E; Ghazalibiglar, H; Glare, T R; Falloon, R E

    2016-04-01

    The goal was to determine the effect of temperature, light and incubation period on production, germination and bioactivity of Trichoderma atroviride LU132 against Rhizoctonia solani. The incubation temperatures of 20, 25 or 30°C were assessed on the production of T. atroviride conidia under constant light over a 25 and 50 days periods. The resulting conidia were also studied for germination and bioactivity. Conidium production was maximum at 25°C after 20 days. The second peak of conidium production occurred at 45-50 days. Incubation at 25°C after 15 days showed optimum production of T. atroviride LU132. Conidia produced at 30°C gave the greatest germination and bioactivity in comparison with incubation at 20 or 25°C. This study indicates that the temperature at which conidia of T. atroviride are produced affects germination and bioactivity. Formulations based on production of the high conidia yield may not result in optimal bioactivity and there is a trade-off between quantity and quality of T. atroviride LU132 conidia. Conidium production was shown to be a continuous process, and increased under a dark/light regime. This is the first report of bimodal conidium production in a Trichoderma biological control agent (BCA), which is likely to be on 20 days cycle, and is dependent on colony age rather than abiotic factors. Conidia produced after 15 days are likely to be the most suitable for use in commercial production of this strain as a BCA. Most studies on Trichoderma-based BCA have only shown the effect of culture conditions on the high conidia yield regardless of conidium quality. This study is the first report on conidium quality affected by principal culture conditions for Trichoderma biological control formulations. © 2016 The Society for Applied Microbiology.

  7. Potential anticancer properties of bioactive compounds of Gymnema sylvestre and its biofunctionalized silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Arunachalam KD

    2014-12-01

    Full Text Available Kantha Deivi Arunachalam,1 Lilly Baptista Arun,1 Sathesh Kumar Annamalai,1 Aarrthy M Arunachalam2 1Center for Environmental Nuclear Research, SRM University, Potheri, Tamil Nadu, India; 2Division of Educational Services, Kaplan University (Medical, Washington DC, USA Background: Gymnema sylvestre is an ethno-pharmacologically important medicinal plant used in many polyherbal formulations for its potential health benefits. Silver nanoparticles (SNPs were biofunctionalized using aqueous leaf extracts of G. sylvestre. The anticancer properties of the bioactive compounds and the biofunctionalized SNPs were compared using the HT29 human adenoma colon cancer cell line.Methods: The preliminary phytochemical screening for bioactive compounds from aqueous extracts revealed the presence of alkaloids, triterpenes, flavonoids, steroids, and saponins. Biofunctionalized SNPs were synthesized using silver nitrate and characterized by ultraviolet–visible spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, and X-ray diffraction for size and shape. The characterized biofunctionalized G. sylvestre were tested for its in vitro anticancer activity against HT29 human colon adenocarcinoma cells.Results: The biofunctionlized G. sylvestre SNPs showed the surface plasmon resonance band at 430 nm. The scanning electron microscopy images showed the presence of spherical nanoparticles of various sizes, which were further determined using the Scherrer equation. In vitro cytotoxic activity of the biofunctionalized green-synthesized SNPs (GSNPs indicated that the sensitivity of HT29 human colon adenocarcinoma cells for cytotoxic drugs is higher than that of Vero cell line for the same cytotoxic agents and also higher than the bioactive compound of the aqueous extract.Conclusion: Our results show that the anticancer properties of the bioactive compounds of G. sylvestre can be enhanced through

  8. Recent Researches of Bioactive Metabolites in Marine Organisms-associated Microor-ganisms

    Institute of Scientific and Technical Information of China (English)

    GU Qianqun; LU Jia; CUI Chengbin; ZHU Tianjiao; FANG Yuchun; LIU Hongbing; ZHU Weiming

    2004-01-01

    Recent researches have shown that some compounds isolated from marine organisms have striking structural similarities with the metabolites from known microorganisms. It is inferred from the researches that the symbiotic or associated marine microorganisms may be the true sources of those compounds or at least involved in the biosynthesizing process. This view has been further evidenced by the researches for many sponges and sponge-associated microorganisms. Importantly, growing evidence has highlighted that the symbiotic or associated marine microorganisms live in the microenvironment within the hosts, and they also produce secondary metabolites which are new and original in structure and unique in activity. All these suggest that the microorganisms associated with marine organisms are the sources with very high potential to be new natural bioactive agents. This article reviews briefly the research advances in the study of new bioactive metabolites from marine organisms-associated microorganisms since 2000.

  9. Bioactivity, mechanism of action, and cytotoxicity of copper-based nanoparticles: a review.

    Science.gov (United States)

    Ingle, Avinash P; Duran, Nelson; Rai, Mahendra

    2014-02-01

    Nanotechnology is an emerging branch of science, which has potential to solve many problems in different fields. The union of nanotechnology with other fields of sciences including physics, chemistry, and biology has brought the concept of synthesis of nanoparticles from their respective metals. Till date, many types of nanoparticles have been synthesized and being used in different fields for various applications. Moreover, copper nanoparticles attract biologists because of their significant and broad-spectrum bioactivity. Due to the large surface area to volume ratio, copper nanoparticles have been used as potential antimicrobial agent in many biomedical applications. But the excess use of any metal nanoparticles increase the chance of toxicity to humans, other living beings, and environment. In this article, we have critically reviewed the bioactivities and cytotoxicity of copper nanoparticles. We have also focused on possible mechanism involved in its interaction with microbes.

  10. Bioactive cotton fabrics containing chitosan and biologically active substances extracted from plants.

    Science.gov (United States)

    Mocanu, G; Nichifor, M; Mihai, D; Oproiu, L C

    2013-01-01

    The paper studies the obtaining of bioactive textiles using chitosan-coated fabrics, in which biologically active substances contained by Viola Tricolor (VT) - an extract of three Viola species (Violaceae) - were immobilized. Chitosan was applied on cotton fabric or on chemically modified cotton (having reactive -CHO or carboxymethyl groups), as tripolyphosphate (TPP) crosslinked fine particles, or by use of glutaraldehyde crosslinking agent. The amount of VT retained on the fabrics was found to depend on the procedure of chitosan application on the cotton. The obtained bioactive textiles are expected to have antioxidant activity due to the biologically active substances from VT; they can be used for obtaining clothes for people with allergies or other skin problems, assuring a controlled release of biomolecules. The study focuses on the in vitro release of VT retained on the fabrics, as well as on its antioxidant activity.

  11. Influence of barium substitution on bioactivity, thermal and physico-mechanical properties of bioactive glass

    Energy Technology Data Exchange (ETDEWEB)

    Arepalli, Sampath Kumar, E-mail: askumar.rs.cer11@iitbhu.ac.in; Tripathi, Himanshu; Vyas, Vikash Kumar; Jain, Shubham; Suman, Shyam Kumar; Pyare, Ram; Singh, S.P., E-mail: spsinghceram@gmail.com

    2015-04-01

    Barium with low concentration in the glasses acts as a muscle stimulant and is found in human teeth. We have made a primary study by substituting barium in the bioactive glass. The chemical composition containing (46.1 − X) SiO{sub 2−}–24.3 Na{sub 2}O–26.9 CaO–2.6 P{sub 2}O{sub 5}, where X = 0, 0.4, 0.8, 1.2 and 1.6 mol% of BaO was chosen and melted in an electric furnace at 1400 ± 5 °C. The glasses were characterized to determine their use in biomedical applications. The nucleation and crystallization regimes were determined by DTA and the controlled crystallization was carried out by suitable heat treatment. The crystalline phase formed was identified by using XRD technique. Bioactivity of these glasses was assessed by immersion in simulated body fluid (SBF) for various time periods. The formation of hydroxy carbonate apatite (HCA) layer was identified by FTIR spectrometry, scanning electron microscope (SEM) and XRD which showed the presence of HCA as the main phase in all tested bioactive glass samples. Flexural strength and densities of bioactive glasses have been measured and found to increase with increasing the barium content. The human blood compatibility of the samples was evaluated and found to be pertinent. - Highlights: • In vitro bioactivity of soda-lime–baria-phospho-silicate glass was investigated. • HCA formed on surface of glasses was confirmed by XRD, SEM and FTIR spectrometry. • Mechanical properties of glasses were found to increase with barium addition. • Hemolysis showed that 1.2 mol% BaO bioactive glass exhibited better biocompatibility. • Barium substituted bioactive glasses can be used as bone implants.

  12. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  13. Probing the Interplay of Size, Shape, and Solution Environment in Macromolecular Diffusion Using a Simple Refraction Experiment

    Science.gov (United States)

    Mankidy, Bijith D.; Coutinho, Cecil A.; Gupta, Vinay K.

    2010-01-01

    The diffusion coefficient of polymers is a critical parameter in biomedicine, catalysis, chemical separations, nanotechnology, and other industrial applications. Here, measurement of macromolecular diffusion in solutions is described using a visually instructive, undergraduate-level optical refraction experiment based on Weiner's method. To…

  14. Macromolecular crowding meets oxygen tension in human mesenchymal stem cell culture - A step closer to physiologically relevant in vitro organogenesis

    Science.gov (United States)

    Cigognini, Daniela; Gaspar, Diana; Kumar, Pramod; Satyam, Abhigyan; Alagesan, Senthilkumar; Sanz-Nogués, Clara; Griffin, Matthew; O’Brien, Timothy; Pandit, Abhay; Zeugolis, Dimitrios I.

    2016-01-01

    Modular tissue engineering is based on the cells’ innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes. PMID:27478033

  15. Errors in macromolecular synthesis after stress : a study of the possible protective role of the small heat shock proteins

    NARCIS (Netherlands)

    Marin Vinader, L.

    2006-01-01

    The general goal of this thesis was to gain insight in what small heat shock proteins (sHsps) do with respect to macromolecular synthesis during a stressful situation in the cell. It is known that after a non-lethal heat shock, cells are better protected against a subsequent more severe heat shock,

  16. An optimal strategy for X-ray data collection on macromolecular crystals with position-sensitive detectors

    NARCIS (Netherlands)

    Vicković, Ivan; Kalk, Kor H.; Drenth, Jan; Dijkstra, Bauke W.

    1994-01-01

    X-ray data collection on macromolecular crystals is preferably done with minimum exposure time and high completeness. A Fortran procedure - DCS - has been written in the environment of the MADNES program to predict the completeness of data before the start of actual data collection. In addition, the

  17. Probing the Interplay of Size, Shape, and Solution Environment in Macromolecular Diffusion Using a Simple Refraction Experiment

    Science.gov (United States)

    Mankidy, Bijith D.; Coutinho, Cecil A.; Gupta, Vinay K.

    2010-01-01

    The diffusion coefficient of polymers is a critical parameter in biomedicine, catalysis, chemical separations, nanotechnology, and other industrial applications. Here, measurement of macromolecular diffusion in solutions is described using a visually instructive, undergraduate-level optical refraction experiment based on Weiner's method. To…

  18. Macromolecular crowding meets oxygen tension in human mesenchymal stem cell culture - A step closer to physiologically relevant in vitro organogenesis

    Science.gov (United States)

    Cigognini, Daniela; Gaspar, Diana; Kumar, Pramod; Satyam, Abhigyan; Alagesan, Senthilkumar; Sanz-Nogués, Clara; Griffin, Matthew; O'Brien, Timothy; Pandit, Abhay; Zeugolis, Dimitrios I.

    2016-08-01

    Modular tissue engineering is based on the cells’ innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes.

  19. Proceedings of a one-week course on exploiting anomalous scattering in macromolecular structure determination (EMBO'07)

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, M.S.; Shepard, W.; Dauter, Z.; Leslie, A.; Diederichs, K.; Evans, G.; Svensson, O.; Schneider, T.; Bricogne, G.; Dauter, Z.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Leslie, A.; Kabsch, W.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Read, R.; Panjikar, S.; Pannu, N.S.; Dauter, Z.; Weiss, M.S.; McSweeney, S

    2007-07-01

    This course, which was directed to young scientists, illustrated both theoretical and practical aspects of macromolecular crystal structure solution using synchrotron radiation. Some software dedicated to data collection, processing and analysis were presented. This document gathers only the slides of the presentations.

  20. Lipase-catalyzed Regioselective Synthesis of Vinyl Ester Derivatives of Thiamphenicol: Novel Thiamphenicol Monomers for Preparation of Macromolecular Antibiotic

    Institute of Scientific and Technical Information of China (English)

    Yu Zhen SHI; Zhi Chun CHEN; Na WANG; Qi WU; Xian Fu LIN

    2005-01-01

    Three polymerizable vinyl thiamphenicol esters with different acyl donor carbon chain length (C4, C6, C10) were regioselectivly synthesized by Lipozyme(R) (immobilized from mucor miehei) in acetone at 50 ℃ for 12 h to give 73%, 81%, 63% yield, respectively. The products were valuable monomers for preparation of macromolecular antibiotic.

  1. Force Spectroscopy of Individual Stimulus-Responsive Poly(ferrocenyldimethylsilane) Chains: Towards a Redox-Driven Macromolecular Motor

    NARCIS (Netherlands)

    Zou, Shan; Hempenius, Mark A.; Schönherr, Holger; Vancso, G. Julius

    2006-01-01

    Progress in the development of a redox-driven macromolecular motor and the characterization of its redox-mechanical cycle using electrochemical AFM-based single-molecule force spectroscopy (SMFS) is described. The elasticities of individual neutral and oxidized poly(ferrocenyldimethylsilane) (PFS) m

  2. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

    Science.gov (United States)

    Foffi, G; Pastore, A; Piazza, F; Temussi, P A

    2013-08-02

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). [Formula: see text] Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international

  3. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012)

    Science.gov (United States)

    Foffi, G.; Pastore, A.; Piazza, F.; Temussi, P. A.

    2013-08-01

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). Figure 1. Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference

  4. Polyphenols from wolfberry and their bioactivities.

    Science.gov (United States)

    Zhou, Zheng-Qun; Xiao, Jia; Fan, Hong-Xia; Yu, Yang; He, Rong-Rong; Feng, Xiao-Lin; Kurihara, Hiroshi; So, Kwok-Fai; Yao, Xin-Sheng; Gao, Hao

    2017-01-01

    Nine new phenylpropanoids, one new coumarin, and 43 known polyphenols were isolated from wolfberry. Their structures were determined by spectroscopic analyses, chemical methods, and comparison of NMR data. Polyphenols, an important type of natural products, are notable constituents in wolfberry. 53 polyphenols, including 28 phenylpropanoids, four coumarins, eight lignans, five flavonoids, three isoflavonoids, two chlorogenic acid derivatives, and three other constituents, were identified from wolfberry. Lignans and isoflavonoids were firstly reported from wolfberry. 22 known polyphenols were the first isolates from the genus Lycium. This research presents a systematic study on wolfberry polyphenols, including their bioactivities. All these compounds exhibited oxygen radical absorbance capacity (ORAC), and some compounds displayed DPPH radical scavenging activity. One compound had acetylcholinesterase inhibitory activity. The discovery of new polyphenols and their bioactivities is beneficial for understanding the scientific basis of the effects of wolfberry.

  5. Bioactivity of mica/apatite glass ceramics

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The bioactivity of mica/apatite glass ceramic composites, including the in vitro behavior in simulated body fluid and the histological appearance of the interface between the mica/apatite glass ceramics and the rabbit mandible defect in vivo under a dynamic condition. The results show that biological apatite layer forms on the surface of the mica/apatite glass ceramics after 1 d of immersion in the simulated body fluid, and becomes dense after 14 d. In vivo tests indicate that bone formation occurs after implantation for 14 d, and strong bonding of bone to the implant occurs after 42 d. No aseptic loosening occurs during 42 d of implantation. The finding shows that mica/apatite glass ceramics have good bioactivity and osteoconductivity for constructing bone graft, and can be promising for biomedical application.

  6. Bioactive lipids in kidney physiology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Daria Sałata

    2014-01-01

    Full Text Available Lipids not only have structural functions, but also play an important role as signaling and regulatory molecules and participate in many cellular processes such as proliferation, differentiation, migration, and apoptosis. Bioactive lipids act both as extracellular mediators, which are associated with receptors on the surface of cells, and intracellular mediators triggering different signal pathways. They are present and active in physiological conditions, and are also involved in the pathogenesis of inflammation, asthma, cancer, diabetes, and hypertension. Bioactive lipids such as derivatives of arachidonic acid and sphingolipids have an important role in renal development, physiology and in many renal diseases. Some of them are potential indicators of kidney damage degree and/or function of the transplanted kidneys.

  7. Bioactive foods and ingredients for health.

    Science.gov (United States)

    Weaver, Connie M

    2014-05-01

    Bioactive compounds in foods have been gaining interest, and processes to consider them for public health recommendations are being discussed. However, the evidence base is difficult to assemble. It is difficult to demonstrate causality, and there often is not a single compound-single effect relation. Furthermore, health benefits may be due to metabolites produced by the host or gut microbiome rather than the food constituent per se. Properties that can be measured in a food may not translate to in vivo health effects. Compounds that are being pursued may increase gut microbial diversity, improve endothelial function, improve cognitive function, reduce bone loss, and so forth. A new type of bioactive component is emerging from epigenetic modifications by our diet, including microRNA transfer from our diet, which can regulate expression of human genes. Policy processes are needed to establish the level of evidence needed to determine dietary advice and policy recommendations and to set research agendas.

  8. Secondary metabolites and bioactivities of Myrtus communis

    OpenAIRE

    Mahmoud I Nassar; Aboutabl, El-Sayed A.; Rania F. Ahmed; EL-Khrisy, Ezzel-Din A.; Khaled M Ibrahim; Sleem, Amany A.

    2010-01-01

    Background: Myrtus species are characterized by the presence of phenolic acids, flavonoids, tannins, volatile oils and fatty acids. They are remedies for variety of ailments. This study therefore investigated medicinal effects of Myrtus communis L. Methods: Bioactivity studies of Myrtus communis L. leaves were carried out on volatile oil, 7% methanol and aqueous extracts and the isolated compounds myricetin 3-O-β-glucopyranoside, myricetin 3-O-∝-rhamnopyranoside and gallic acid. Results: Dete...

  9. Bioactive compounds in whole grain wheat

    OpenAIRE

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much in their content. The external fractions of the grain, the bran and specially the aleurone, are the richest. We observed that processing the bran in whole-grain breads increased three times the leve...

  10. Pinocembrine: a bioactive flavanone from Teloxys graveolens.

    Science.gov (United States)

    Del Rayo Camacho, M; Sanchez, B; Quiroz, H; Contreras, J L; Mata, R

    1991-03-01

    Bioactivity directed fractionation of the acetone extract of Teloxys graveolens (Willd.) Weber (Chenopodiaceae), using the brine shrimp lethality test, led to the isolation of 5,7-dihydroxyflavanone (pinocembrine) (LC50 = 4.25 micrograms/ml) as the only active compound. Pinocembrine also exhibited fasciolicide, ovicide and larvicide activities on newly excysted Fasciola hepatica, on infective eggs of Ascaridi galli and on stage three larvae of Stomoxys calcitrans, respectively.

  11. Fluoride-containing bioactive glasses: Glass design, structure, bioactivity, cellular interactions, and recent developments.

    Science.gov (United States)

    Shah, Furqan A

    2016-01-01

    Bioactive glasses (BGs) are known to bond to both hard and soft tissues. Upon exposure to an aqueous environment, BG undergoes ion exchange, hydrolysis, selective dissolution and precipitation of an apatite layer on their surface, which elicits an interfacial biological response resulting in bioactive fixation, inhibiting further dissolution of the glass, and preventing complete resorption of the material. Fluorine is considered one of the most effective in-vivo bone anabolic factors. In low concentrations, fluoride ions (F(-)) increase bone mass and mineral density, improve the resistance of the apatite structure to acid attack, and have well documented antibacterial properties. F(-) ions may be incorporated into the glass in the form of calcium fluoride (CaF2) either by part-substitution of network modifier oxides, or by maintaining the ratios of the other constituents relatively constant. Fluoride-containing bioactive glasses (FBGs) enhance and control osteoblast proliferation, differentiation and mineralisation. And with their ability to release fluoride locally, FBGs make interesting candidates for various clinical applications, dentinal tubule occlusion in the treatment of dentin hypersensitivity. This paper reviews the chemistry of FBGs and the influence of F(-) incorporation on the thermal properties, bioactivity, and cytotoxicity; and novel glass compositions for improved mechanical properties, processing, and bioactive potential. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Promiscuity progression of bioactive compounds over time.

    Science.gov (United States)

    Hu, Ye; Jasial, Swarit; Bajorath, Jürgen

    2015-01-01

    In the context of polypharmacology, compound promiscuity is rationalized as the ability of small molecules to specifically interact with multiple targets. To study promiscuity progression of bioactive compounds in detail, nearly 1 million compounds and more than 5.2 million activity records were analyzed. Compound sets were assembled by applying different data confidence criteria and selecting compounds with activity histories over many years. On the basis of release dates, compounds and activity records were organized on a time course, which ultimately enabled monitoring data growth and promiscuity progression over nearly 40 years, beginning in 1976. Surprisingly low degrees of promiscuity were consistently detected for all compound sets and there were only small increases in promiscuity over time. In fact, most compounds had a constant degree of promiscuity, including compounds with an activity history of 10 or 20 years. Moreover, during periods of massive data growth, beginning in 2007, promiscuity degrees also remained constant or displayed only minor increases, depending on the activity data confidence levels. Considering high-confidence data, bioactive compounds currently interact with 1.5 targets on average, regardless of their origins, and display essentially constant degrees of promiscuity over time. Taken together, our findings provide expectation values for promiscuity progression and magnitudes among bioactive compounds as activity data further grow.

  13. Bioactive lipids naturally occurring in bovine milk.

    Science.gov (United States)

    Molkentin, J

    1999-06-01

    Bioactive properties of food components increasingly gain in importance in the modern diet. Bovine milk fat (BMF) exhibits bioactive substances mainly in the class of fatty acids. Currently, most interest is addressed to trans fatty acids (TFA) and particularly conjugated linoleic acids (CLA) with BMF being the main source of CLA in food. Whereas saturated fatty acids (C12-C16) and TFA are reported to be positively correlated (negatively for oleic acid) with atherosclerosis and coronary heart disease, CLA are regarded as potent anticarcinogens. Also butyric acid (C4) as well as some phospholipids and either lipids present in BMF are thought to have anticarcinogenic properties. Furthermore, BMF contains the essential fatty acids C18:2 n-6 and C18:3 n-3 that have many and diverse functions in human metabolism and, thus, control a variety of biochemical and physiological processes. Altogether, BMF contains approximately 75 wt% of bioactive substances. However, the overall impact on human health can hardly be assessed.

  14. Nanotech: propensity in foods and bioactives.

    Science.gov (United States)

    Kuan, Chiu-Yin; Yee-Fung, Wai; Yuen, Kah-Hay; Liong, Min-Tze

    2012-01-01

    Nanotechnology is seeing higher propensity in various industries, including food and bioactives. New nanomaterials are constantly being developed from both natural biodegradable polymers of plant and animal origins such as polysaccharides and derivatives, peptides and proteins, lipids and fats, and biocompatible synthetic biopolyester polymers such as polylactic acid (PLA), polyhydroxyalkonoates (PHA), and polycaprolactone (PCL). Applications in food industries include molecular synthesis of new functional food compounds, innovative food packaging, food safety, and security monitoring. The relevance of bioactives includes targeted delivery systems with improved bioavailability using nanostructure vehicles such as association colloids, lipid based nanoencapsulator, nanoemulsions, biopolymeric nanoparticles, nanolaminates, and nanofibers. The extensive use of nanotechnology has led to the need for parallel safety assessment and regulations to protect public health and adverse effects to the environment. This review covers the use of biopolymers in the production of nanomaterials and the propensity of nanotechnology in food and bioactives. The exposure routes of nanoparticles, safety challenges, and measures undertaken to ensure optimal benefits that outweigh detriments are also discussed.

  15. Minimum information about a bioactive entity (MIABE).

    Science.gov (United States)

    Orchard, Sandra; Al-Lazikani, Bissan; Bryant, Steve; Clark, Dominic; Calder, Elizabeth; Dix, Ian; Engkvist, Ola; Forster, Mark; Gaulton, Anna; Gilson, Michael; Glen, Robert; Grigorov, Martin; Hammond-Kosack, Kim; Harland, Lee; Hopkins, Andrew; Larminie, Christopher; Lynch, Nick; Mann, Romeena K; Murray-Rust, Peter; Lo Piparo, Elena; Southan, Christopher; Steinbeck, Christoph; Wishart, David; Hermjakob, Henning; Overington, John; Thornton, Janet

    2011-08-31

    Bioactive molecules such as drugs, pesticides and food additives are produced in large numbers by many commercial and academic groups around the world. Enormous quantities of data are generated on the biological properties and quality of these molecules. Access to such data - both on licensed and commercially available compounds, and also on those that fail during development - is crucial for understanding how improved molecules could be developed. For example, computational analysis of aggregated data on molecules that are investigated in drug discovery programmes has led to a greater understanding of the properties of successful drugs. However, the information required to perform these analyses is rarely published, and when it is made available it is often missing crucial data or is in a format that is inappropriate for efficient data-mining. Here, we propose a solution: the definition of reporting guidelines for bioactive entities - the Minimum Information About a Bioactive Entity (MIABE) - which has been developed by representatives of pharmaceutical companies, data resource providers and academic groups.

  16. A mixed method for measuring low-frequency acoustic properties of macromolecular materials

    Institute of Scientific and Technical Information of China (English)

    LIU; Hongwei; YAO; Lei; ZHAO; Hong; ZHANG; Jichuan; XUE; Zhaohong

    2006-01-01

    A mixed method for measuring low-frequency acoustic properties of macromolecular materials is presented.The dynamic mechanical parameters of materials are first measured by using Dynamic Mechanical Thermal Apparatus(DMTA) at low frequencies,usually less than 100 Hz; then based on the Principles of Time-Temperature Super position (TTS),these parameters are extended to the frequency range that acousticians are concerned about,usually from hundreds to thousands of hertz; finally the extended dynamic mechanical parameters are transformed into acoustic parameters with the help of acoustic measurement and inverse analysis.To test the feasibility and accuracy,we measure a kind of rubber sample in DMTA and acquire the basic acoustic parameters of the sample by using this method.While applying the basic parameters to calculating characteristics of the sample in acoustic pipe,a reasonable agreement of sound absorption coefficients is obtained between the calculations and measurements in the acoustic pipe.

  17. Site-selective electroless nickel plating on patterned thin films of macromolecular metal complexes.

    Science.gov (United States)

    Kimura, Mutsumi; Yamagiwa, Hiroki; Asakawa, Daisuke; Noguchi, Makoto; Kurashina, Tadashi; Fukawa, Tadashi; Shirai, Hirofusa

    2010-12-01

    We demonstrate a simple route to depositing nickel layer patterns using photocross-linked polymer thin films containing palladium catalysts, which can be used as adhesive interlayers for fabrication of nickel patterns on glass and plastic substrates. Electroless nickel patterns can be obtained in three steps: (i) the pattern formation of partially quaterized poly(vinyl pyridine) by UV irradiation, (ii) the formation of macromolecular metal complex with palladium, and (iii) the nickel metallization using electroless plating bath. Metallization is site-selective and allows for a high resolution. And the resulting nickel layered structure shows good adhesion with glass and plastic substrates. The direct patterning of metallic layers onto insulating substrates indicates a great potential for fabricating micro/nano devices.

  18. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    Science.gov (United States)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.; Thiele, Ines; Palsson, Bernhard O.; Saunders, Michael A.

    2017-01-01

    Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many orders of magnitude. Data values also have greatly varying magnitudes. Standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME models have 70,000 constraints and variables and will grow larger). We have developed a quadruple-precision version of our linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data.

  19. Phenix - a comprehensive python-based system for macromolecular structure solution

    Energy Technology Data Exchange (ETDEWEB)

    Terwilliger, Thomas C [Los Alamos National Laboratory; Hung, Li - Wei [Los Alamos National Laboratory; Adams, Paul D [UC BERKELEY; Afonine, Pavel V [UC BERKELEY; Bunkoczi, Gabor [UNIV OF CAMBRIDGE; Chen, Vincent B [DUKE UNIV; Davis, Ian [DUKE UNIV; Echols, Nathaniel [LBNL; Headd, Jeffrey J [DUKE UNIV; Grosse Kunstleve, Ralf W [LBNL; Mccoy, Airlie J [UNIV OF CAMBRIDGE; Moriarty, Nigel W [LBNL; Oeffner, Robert [UNIV OF CAMBRIDGE; Read, Randy J [UNIV OF CAMBRIDGE; Richardson, David C [DUKE UNIV; Richardson, Jane S [DUKE UNIV; Zwarta, Peter H [LBNL

    2009-01-01

    Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages, and the repeated use of interactive three-dimensional graphics. Phenix has been developed to provide a comprehensive system for crystallographic structure solution with an emphasis on automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand, and finally the development of a framework that allows a tight integration between the algorithms.

  20. Recent Major Improvements to the ALS Sector 5 MacromolecularCrystallography Beamlines

    Energy Technology Data Exchange (ETDEWEB)

    Morton, Simon A.; Glossinger, James; Smith-Baumann, Alexis; McKean, John P.; Trame, Christine; Dickert, Jeff; Rozales, Anthony; Dauz,Azer; Taylor, John; Zwart, Petrus; Duarte, Robert; Padmore, Howard; McDermott, Gerry; Adams, Paul

    2007-07-01

    Although the Advanced Light Source (ALS) was initially conceived primarily as a low energy (1.9GeV) 3rd generation source of VUV and soft x-ray radiation it was realized very early in the development of the facility that a multipole wiggler source coupled with high quality, (brightness preserving), optics would result in a beamline whose performance across the optimal energy range (5-15keV) for macromolecular crystallography (MX) would be comparable to, or even exceed, that of many existing crystallography beamlines at higher energy facilities. Hence, starting in 1996, a suite of three beamlines, branching off a single wiggler source, was constructed, which together formed the ALS Macromolecular Crystallography Facility. From the outset this facility was designed to cater equally to the needs of both academic and industrial users with a heavy emphasis placed on the development and introduction of high throughput crystallographic tools, techniques, and facilities--such as large area CCD detectors, robotic sample handling and automounting facilities, a service crystallography program, and a tightly integrated, centralized, and highly automated beamline control environment for users. This facility was immediately successful, with the primary Multiwavelength Anomalous Diffraction beamline (5.0.2) in particular rapidly becoming one of the foremost crystallographic facilities in the US--responsible for structures such as the 70S ribosome. This success in-turn triggered enormous growth of the ALS macromolecular crystallography community and spurred the development of five additional ALS MX beamlines all utilizing the newly developed superconducting bending magnets ('superbends') as sources. However in the years since the original Sector 5.0 beamlines were built the performance demands of macromolecular crystallography users have become ever more exacting; with growing emphasis placed on studying larger complexes, more difficult structures, weakly diffracting or

  1. Dependence of Protein Folding Stability and Dynamics on the Density and Composition of Macromolecular Crowders

    Science.gov (United States)

    Mittal, Jeetain; Best, Robert B.

    2010-01-01

    We investigate the effect of macromolecular crowding on protein folding, using purely repulsive crowding particles and a self-organizing polymer model of protein folding. We find that the variation in folding stability with crowder size for typical α-, β-, and α/β-proteins is well described by an adaptation of the scaled particle theory. The native state, the transition state, and the unfolded protein are treated as effective hard spheres, with the folded and transition state radii independent of the size and concentration of the crowders. Remarkably, we find that, as the effective unfolded state radius is very weakly dependent on the crowder concentration, it can also be approximated by a single size. The same model predicts the effect of crowding on the folding barrier and therefore refolding rates with no adjustable parameters. A simple extension of the scaled-particle theory model, assuming additivity, can also describe the behavior of mixtures of crowding particles. PMID:20338853

  2. Integration and global analysis of isothermal titration calorimetry data for studying macromolecular interactions.

    Science.gov (United States)

    Brautigam, Chad A; Zhao, Huaying; Vargas, Carolyn; Keller, Sandro; Schuck, Peter

    2016-05-01

    Isothermal titration calorimetry (ITC) is a powerful and widely used method to measure the energetics of macromolecular interactions by recording a thermogram of differential heating power during a titration. However, traditional ITC analysis is limited by stochastic thermogram noise and by the limited information content of a single titration experiment. Here we present a protocol for bias-free thermogram integration based on automated shape analysis of the injection peaks, followed by combination of isotherms from different calorimetric titration experiments into a global analysis, statistical analysis of binding parameters and graphical presentation of the results. This is performed using the integrated public-domain software packages NITPIC, SEDPHAT and GUSSI. The recently developed low-noise thermogram integration approach and global analysis allow for more precise parameter estimates and more reliable quantification of multisite and multicomponent cooperative and competitive interactions. Titration experiments typically take 1-2.5 h each, and global analysis usually takes 10-20 min.

  3. C1 Polymerization: a unique tool towards polyethylene-based complex macromolecular architectures

    KAUST Repository

    Wang, De

    2017-05-09

    The recent developments in organoborane initiated C1 polymerization (chain grows by one atom at a time) of ylides opens unique horizons towards well-defined/perfectly linear polymethylenes (equivalent to polyethylenes, PE) and PE-based complex macromolecular architectures. The general mechanism of C1 polymerization (polyhomologation) involves the formation of a Lewis complex between a methylide (monomer) and a borane (initiator), followed by migration/insertion of a methylene into the initiator and after oxidation/hydrolysis to afford OH-terminated polyethylenes. This review summarizes efforts towards conventional and newly discovered borane-initiators and ylides (monomers), as well as a combination of polyhomologation with other polymerization methods. Initial efforts dealing with C3 polymerization and the synthesis of the first C1/C3 copolymers are also given. Finally, some thoughts for the future of these polymerizations are presented.

  4. Mix and Inject: Reaction Initiation by Diffusion for Time-Resolved Macromolecular Crystallography

    Directory of Open Access Journals (Sweden)

    Marius Schmidt

    2013-01-01

    Full Text Available Time-resolved macromolecular crystallography unifies structure determination with chemical kinetics, since the structures of transient states and chemical and kinetic mechanisms can be determined simultaneously from the same data. To start a reaction in an enzyme, typically, an initially inactive substrate present in the crystal is activated. This has particular disadvantages that are circumvented when active substrate is directly provided by diffusion. However, then it is prohibitive to use macroscopic crystals because diffusion times become too long. With small micro- and nanocrystals diffusion times are adequately short for most enzymes and the reaction can be swiftly initiated. We demonstrate here that a time-resolved crystallographic experiment becomes feasible by mixing substrate with enzyme nanocrystals which are subsequently injected into the X-ray beam of a pulsed X-ray source.

  5. Phase behaviour of macromolecular liquid crystalline materials. Computational studies at the molecular level

    CERN Document Server

    Stimson, L M

    2003-01-01

    Molecular simulations provide an increasingly useful insight into the static and dynamic characteristics of materials. In this thesis molecular simulations of macro-molecular liquid crystalline materials are reported. The first liquid crystalline material that has been investigated is a side chain liquid crystal polymer (SCLCP). In this study semi-atomistic molecular dynamics simulations have been conducted at a range of temperatures and an aligning potential has been applied to mimic the effect of a magnetic field. In cooling the SCLCP from an isotropic melt, microphase separation was observed yielding a domain structure. The application of a magnetic field to this structure aligns the domains producing a stable smectic mesophase. This is the first study in which mesophases have been observed using an off-lattice model of a SCLCP. The second material that has been investigated is a dendrimer with terminal mesogenic functionalization. Here, a multi-scale approach has been taken with Monte Carlo studies of a s...

  6. Phase transitions of macromolecular microsphere composite hydrogels based on the stochastic Cahn–Hilliard equation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiao, E-mail: lixiao1228@163.com; Ji, Guanghua, E-mail: ghji@bnu.edu.cn; Zhang, Hui, E-mail: hzhang@bnu.edu.cn

    2015-02-15

    We use the stochastic Cahn–Hilliard equation to simulate the phase transitions of the macromolecular microsphere composite (MMC) hydrogels under a random disturbance. Based on the Flory–Huggins lattice model and the Boltzmann entropy theorem, we develop a reticular free energy suit for the network structure of MMC hydrogels. Taking the random factor into account, with the time-dependent Ginzburg-Landau (TDGL) mesoscopic simulation method, we set up a stochastic Cahn–Hilliard equation, designated herein as the MMC-TDGL equation. The stochastic term in the equation is constructed appropriately to satisfy the fluctuation-dissipation theorem and is discretized on a spatial grid for the simulation. A semi-implicit difference scheme is adopted to numerically solve the MMC-TDGL equation. Some numerical experiments are performed with different parameters. The results are consistent with the physical phenomenon, which verifies the good simulation of the stochastic term.

  7. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species

    KAUST Repository

    Rossner, Christian

    2016-09-26

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer is synthesized to study its localization within PlSNs by analyzing the elemental distribution of chlorine. The functionalized nanohybrid structures are analyzed by scanning transmission electron microscopy, electron energy loss spectroscopy, and spectrum imaging. The results show that the RAFT (reversible addition-fragmentation chain transfer) polymers\\' sulfur containing end groups are colocalized at the gold cores, both within nanohybrids of simple core-shell morphology and within higher order PlSNs, providing microscopic evidence for the affinity of the RAFT group toward gold surfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA., Weinheim.

  8. PURY: a database of geometric restraints of hetero compounds for refinement in complexes with macromolecular structures.

    Science.gov (United States)

    Andrejasic, Miha; Praaenikar, Jure; Turk, Dusan

    2008-11-01

    The number and variety of macromolecular structures in complex with ;hetero' ligands is growing. The need for rapid delivery of correct geometric parameters for their refinement, which is often crucial for understanding the biological relevance of the structure, is growing correspondingly. The current standard for describing protein structures is the Engh-Huber parameter set. It is an expert data set resulting from selection and analysis of the crystal structures gathered in the Cambridge Structural Database (CSD). Clearly, such a manual approach cannot be applied to the vast and ever-growing number of chemical compounds. Therefore, a database, named PURY, of geometric parameters of chemical compounds has been developed, together with a server that accesses it. PURY is a compilation of the whole CSD. It contains lists of atom classes and bonds connecting them, as well as angle, chirality, planarity and conformation parameters. The current compilation is based on CSD 5.28 and contains 1978 atom classes and 32,702 bonding, 237,068 angle, 201,860 dihedral and 64,193 improper geometric restraints. Analysis has confirmed that the restraints from the PURY database are suitable for use in macromolecular crystal structure refinement and should be of value to the crystallographic community. The database can be accessed through the web server http://pury.ijs.si/, which creates topology and parameter files from deposited coordinates in suitable forms for the refinement programs MAIN, CNS and REFMAC. In the near future, the server will move to the CSD website http://pury.ccdc.cam.ac.uk/.

  9. A 3D image filter for parameter-free segmentation of macromolecular structures from electron tomograms.

    Directory of Open Access Journals (Sweden)

    Rubbiya A Ali

    Full Text Available 3D image reconstruction of large cellular volumes by electron tomography (ET at high (≤ 5 nm resolution can now routinely resolve organellar and compartmental membrane structures, protein coats, cytoskeletal filaments, and macromolecules. However, current image analysis methods for identifying in situ macromolecular structures within the crowded 3D ultrastructural landscape of a cell remain labor-intensive, time-consuming, and prone to user-bias and/or error. This paper demonstrates the development and application of a parameter-free, 3D implementation of the bilateral edge-detection (BLE algorithm for the rapid and accurate segmentation of cellular tomograms. The performance of the 3D BLE filter has been tested on a range of synthetic and real biological data sets and validated against current leading filters-the pseudo 3D recursive and Canny filters. The performance of the 3D BLE filter was found to be comparable to or better than that of both the 3D recursive and Canny filters while offering the significant advantage that it requires no parameter input or optimisation. Edge widths as little as 2 pixels are reproducibly detected with signal intensity and grey scale values as low as 0.72% above the mean of the background noise. The 3D BLE thus provides an efficient method for the automated segmentation of complex cellular structures across multiple scales for further downstream processing, such as cellular annotation and sub-tomogram averaging, and provides a valuable tool for the accurate and high-throughput identification and annotation of 3D structural complexity at the subcellular level, as well as for mapping the spatial and temporal rearrangement of macromolecular assemblies in situ within cellular tomograms.

  10. A 3D image filter for parameter-free segmentation of macromolecular structures from electron tomograms.

    Science.gov (United States)

    Ali, Rubbiya A; Landsberg, Michael J; Knauth, Emily; Morgan, Garry P; Marsh, Brad J; Hankamer, Ben

    2012-01-01

    3D image reconstruction of large cellular volumes by electron tomography (ET) at high (≤ 5 nm) resolution can now routinely resolve organellar and compartmental membrane structures, protein coats, cytoskeletal filaments, and macromolecules. However, current image analysis methods for identifying in situ macromolecular structures within the crowded 3D ultrastructural landscape of a cell remain labor-intensive, time-consuming, and prone to user-bias and/or error. This paper demonstrates the development and application of a parameter-free, 3D implementation of the bilateral edge-detection (BLE) algorithm for the rapid and accurate segmentation of cellular tomograms. The performance of the 3D BLE filter has been tested on a range of synthetic and real biological data sets and validated against current leading filters-the pseudo 3D recursive and Canny filters. The performance of the 3D BLE filter was found to be comparable to or better than that of both the 3D recursive and Canny filters while offering the significant advantage that it requires no parameter input or optimisation. Edge widths as little as 2 pixels are reproducibly detected with signal intensity and grey scale values as low as 0.72% above the mean of the background noise. The 3D BLE thus provides an efficient method for the automated segmentation of complex cellular structures across multiple scales for further downstream processing, such as cellular annotation and sub-tomogram averaging, and provides a valuable tool for the accurate and high-throughput identification and annotation of 3D structural complexity at the subcellular level, as well as for mapping the spatial and temporal rearrangement of macromolecular assemblies in situ within cellular tomograms.

  11. Transition modes in Ising networks: an approximate theory for macromolecular recognition.

    Science.gov (United States)

    Keating, S; Di Cera, E

    1993-07-01

    For a statistical lattice, or Ising network, composed of N identical units existing in two possible states, 0 and 1, and interacting according to a given geometry, a set of values can be found for the mean free energy of the 0-->1 transition of a single unit. Each value defines a transition mode in an ensemble of nu N = 3N - 2N possible values and reflects the role played by intermediate states in shaping the energetics of the system as a whole. The distribution of transition modes has a number of intriguing properties. Some of them apply quite generally to any Ising network, regardless of its dimension, while others are specific for each interaction geometry and dimensional embedding and bear on fundamental aspects of analytical number theory. The landscape of transition modes encapsulates all of the important thermodynamic properties of the network. The free energy terms defining the partition function of the system can be derived from the modes by simple transformations. Classical mean-field expressions can be obtained from consideration of the properties of transition modes in a rather straightforward way. The results obtained in the analysis of the transition mode distributions have been used to develop an approximate treatment of the problem of macromolecular recognition. This phenomenon is modeled as a cooperative process that involves a number of recognition subsites across an interface generated by the binding of two macromolecular components. The distribution of allowed binding free energies for the system is shown to be a superposition of Gaussian terms with mean and variance determined a priori by the theory. Application to the analysis of the biologically interaction of thrombin with hirudin has provided some useful information on basic aspects of the interaction, such as the number of recognition subsites involved and the energy balance for binding and cooperative coupling among them. Our results agree quite well with information derived independently

  12. Bioactive glasses and glass-ceramics

    Directory of Open Access Journals (Sweden)

    de Aza, P. N.

    2007-04-01

    Full Text Available Since the late 1960´s, a great interest in the use of bioceramic materials for biomedical applications has been developed. In a previous paper, the authors reviewed crystalline bioceramic materials “sensus stricto”, it is to say, those ceramic materials, constituted for non-metallic inorganic compounds, crystallines and consolidates by thermal treatment of powders at high temperature. In the present review, the authors deal with those called bioactive glasses and glassceramics. Although all of them are also obtained by thermal treatment at high temperature, the first are amorphous and the second are obtained by devitrification of a glass, although the vitreous phase normally prevails on the crystalline phases. After an introduction to the concept of bioactive materials, a short historical review of the bioactive glasses development is made. Its preparation, reactivity in physiological media, mechanism of bonding to living tissues and mechanical strength of the bone-implant interface is also reported. Next, the concept of glass-ceramic and the way of its preparation are exposed. The composition, physicochemical properties and biological behaviour of the principal types of bioactive glasses and glass-ceramic materials: Bioglass®, Ceravital®, Cerabone®, Ilmaplant® and Bioverit® are also reviewed. Finally, a short review on the bioactive-glass coatings and bioactive-composites and most common uses of bioactive-glasses and glass-ceramics are carried out too.

    Desde finales de los años sesenta, se ha despertado un gran interés por el uso de los materiales biocerámicos para aplicaciones biomédicas. En un trabajo previo, los autores hicieron una revisión de los denominados materiales biocerámicos cristalinos en sentido estricto, es decir, de aquellos materiales, constituidos por compuestos inorgánicos no metálicos, cristalinos y consolidados mediante tratamientos térmicos a altas temperaturas. En el presente trabajo, los autores

  13. Physicochemical properties and bioactivity of freeze-cast chitosan nanocomposite scaffolds reinforced with bioactive glass

    Energy Technology Data Exchange (ETDEWEB)

    Pourhaghgouy, Masoud, E-mail: m.pourhaghgouy@merc.ac.ir [Department of Nanotechnology & Advanced Materials, Materials & Energy Research Center, Karaj, P.O. Box: 13145-1659 (Iran, Islamic Republic of); Zamanian, Ali, E-mail: a-zamanian@merc.ac.ir [Department of Nanotechnology & Advanced Materials, Materials & Energy Research Center, Karaj, P.O. Box: 13145-1659 (Iran, Islamic Republic of); Shahrezaee, Mostafa, E-mail: moshahrezaee@yahoo.com [Department of Orthopedic Surgery, AJA University of Medical Sciences, Tehran (Iran, Islamic Republic of); Masouleh, Milad Pourbaghi, E-mail: miladpourbaghi@gmail.com [Department of Nanotechnology & Advanced Materials, Materials & Energy Research Center, Karaj, P.O. Box: 13145-1659 (Iran, Islamic Republic of)

    2016-01-01

    Chitosan based nanocomposite scaffolds were prepared by freeze casting method through blending constant chitosan concentration with different portions of synthesized bioactive glass nanoparticles (BGNPs). Transmission Electron Microscopy (TEM) image showed that the particles size of bioactive glass (64SiO{sub 2}.28CaO.8P{sub 2}O{sub 5}) prepared by sol–gel method was approximately less than 20 nm. Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Diffraction (XRD) analysis showed proper interfacial bonding between BGNPs and chitosan polymers. Scanning Electron Microscopy (SEM) images depicted a unidirectional structure with homogenous distribution of BGNPs among chitosan matrix associated with the absence of pure chitosan scaffold's wall pores after addition of only 10 wt.% BGNPs. As the BGNP content increased from 0 to 50 wt.%, the compressive strength and compressive module values increased from 0.034 to 0.419 MPa and 0.41 to 10.77 MPa, respectively. Biodegradation study showed that increase in BGNP content leads to growth of weight loss amount. The in vitro biomineralization studies confirmed the bioactive nature of all nanocomposites. Amount of 30 wt.% BGNPs represented the best concentration for absorption capacity and bioactivity behaviors. - Highlights: • Particle size of synthesized bioactive glass was approximately less than 20 nm. • Increase in BGNP content did not change the pore channels size. • Addition of 10 wt.% of BGNP led to absence of the pores located on chitosan walls. • Mechanical properties of chitosan scaffold significantly improved by addition of BGNPs. • Chi-BGNPs30 scaffold indicated acceptable absorption capacity and bioactivity behavior.

  14. Bioactivity and properties of a dental adhesive functionalized with polyhedral oligomeric silsesquioxanes (POSS) and bioactive glass.

    Science.gov (United States)

    Rizk, Marta; Hohlfeld, Lisa; Thanh, Loan Tao; Biehl, Ralf; Lühmann, Nicole; Mohn, Dirk; Wiegand, Annette

    2017-09-01

    This study aimed to analyze the effect of infiltrating a commercial adhesive with nanosized bioactive glass (BG-Bi) particles or methacryl-functionalized polyhedral oligomeric silsesquioxanes (POSS) on material properties and bioactivity. An acetone-based dental adhesive (Solobond Plus adhesive, VOCO GmbH, Cuxhaven, Germany) was infiltrated with nanosized bioactive glass particles (0.1 or 1wt%), or with monofunctional or multifunctional POSS particles (10 or 20wt%). Unfilled adhesive served as control. Dispersion and hydrodynamic radius of the nanoparticles were studied by dynamic light scattering. Set specimens were immersed for 28days in artificial saliva at 37°C, and surfaces were mapped for the formation of calcium phospate (Ca/P) precipitates (scanning electron microscopy/energy-dispersive X-ray spectroscopy). Viscosity (rheometry) and the structural characteristic of the networks were studied, such as degree of conversion (FTIR spectroscopy), sol fraction and water sorption. POSS particles showed a good dispersion of the particles for both types of particles being smaller than 3nm, while the bioactive glass particles had a strong tendency to agglomerate. All nanoparticles induced the formation of Ca/P precipitates. The viscosity of the adhesive was not or only slightly increased by POSS particle addition but strongly increased by the bioactive glass particles. The degree of conversion, water sorption and sol fraction showed a maintained or improved network structure and properties when filled with BG-Bi and multifunctional POSS, however, less polymerization was found when loading a monofunctional POSS. Multifunctional POSS may be incorporated into dental adhesives to provide a bioactive potential without changing material properties adversely. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  15. Bioactive glass coupling with natural polyphenols: Surface modification, bioactivity and anti-oxidant ability

    Energy Technology Data Exchange (ETDEWEB)

    Cazzola, Martina [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Corazzari, Ingrid [Università degli Studi di Torino, Department of Chemistry, Via Pietro Giuria 7, Torino 10125 (Italy); Centro Interdipartimentale “G. Scansetti” per lo studio degli amianti e di altri particolati nocivi, Via Pietro Giuria 9, 10125 Torino (Italy); Prenesti, Enrico [Università degli Studi di Torino, Department of Chemistry, Via Pietro Giuria 7, Torino 10125 (Italy); Bertone, Elisa [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Vernè, Enrica, E-mail: enrica.verne@polito.it [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Ferraris, Sara [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy)

    2016-03-30

    Graphical abstract: - Highlights: • Surface functionalization of bioactive glass with biomolecules has been optimized. • Biomolecules are present and active on the glass surface after functionalization. • Biomolecules affect deposition kinetics and morphology of hydroxyapatite. • Free radical scavenging activity is seen for the first time on bioactive glasses. - Abstract: Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H{sub 2}O{sub 2} highlighting scavenging activity of the bioactive glass.

  16. Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Aida Rodriguez-Garcia

    2017-08-01

    Full Text Available Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer.

  17. The Correlation of Pore Size and Bioactivity of Spray-Pyrolyzed Mesoporous Bioactive Glasses

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chou

    2017-05-01

    Full Text Available SiO2–CaO–P2O5-based mesoporous bioactive glasses (MBGs were synthesized by spray pyrolysis in this study. Three commonly used non-ionic tri-block copolymers (L121, P123, and F127 with various lengths of hydrophilic chains were applied as structural templates to achieve different pore sizes. A mesoporous structure was observed in each as-prepared specimen, and the results showed that the L121-treated MBG had the largest pore size. The results of bioactivity tests indicated that the growth of hydroxyapatite is related to the pore size of the materials.

  18. Streptococcus thermophilus APC151 strain is suitable for the manufacture of naturally GABA-enriched bioactive yogurt

    OpenAIRE

    Linares, Daniel M.; O'Callaghan, Tom F.; O'Connor, Paula M.; Ross, R. Paul; Stanton, Catherine

    2016-01-01

    Consumer interest in health-promoting food products is a major driving force for the increasing global demand of functional (probiotic) dairy foods. Yogurt is considered the ideal medium for delivery of beneficial functional ingredients. Gamma-amino-butyric acid has potential as a bioactive ingredient in functional foods due to its health-promoting properties as an anti-stress, anti-hypertensive, and anti-diabetic agent. Here, we report the use of a novel Streptococcus thermophilus strain, is...

  19. Mannich reaction: A versatile and convenient approach to bioactive skeletons

    Indian Academy of Sciences (India)

    Selva Ganesan Subramaniapillai

    2013-05-01

    This review gives an insight into the recent applications of Mannich reaction and its variants in the construction of bioactive molecules. Emphasis is given to the Mannich reaction that provides bioactive molecules and/or modifies the property of an existing bioactive molecule. The role of Mannich reaction in the construction of antimalarial, antitumour, antimicrobial, antitubercular, antiinflammatory and anticonvulsant molecules and also the significance of aminoalkyl Mannich side chain on the biological property of molecules is discussed here.

  20. Beebread from Apis mellifera and Apis dorsata. Comparative Chemical Composition and Bioactivity

    Directory of Open Access Journals (Sweden)

    Otilia BOBIS

    2017-05-01

    Full Text Available Beebread is a valuable bee product, both for bee nutrition and for humans. The high nutritional and bioactive properties of beebread were evaluated by chemical composition analysis of beebread from Apis mellifera and Apis dorsata. Bee bread harvested from Romania and India, coming from Apis mellifera and Apis dorsata bees, were evaluated for their chemical composition. Analyses were made in APHIS Laboratory from USAMV Cluj, using validated methods for bee products. Lipids were determined by the Soxhlet extraction method, total protein content was determined by Kjehldahl method, sugar spectrum was determined by high performance liquid chromatography with refractive index detection (HPLC-IR. Water content of beebread samples were situated between 11.45 and 16.46%, total protein content between 16.84 and 19.19% and total lipids between 6.36 and 13.47%.  Beebread has high bioactive properties which can be expressed as antioxidant and/or antibacterial activity. Chemical composition and bioactive properties of beebread is influenced by floral origin of the pollen which the bees collect and place in combs for fermentation. Also the climatic conditions have an important role in developing different fermentation compounds, that may act as antioxidants or antibacterial agents.

  1. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance$

    Institute of Scientific and Technical Information of China (English)

    Nishant A. Dafale n; Uttam P. Semwal; Rupak K. Rajput; G.N. Singh

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Re-sistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the potency of antibiotics. HPLC method is commonly used for the quantification of potency of antibiotics, but unable to determine the bioactivity; whereas microbiological assay estimates both potency and bioactivity of antibiotics. Additionally, bioassay is used to estimate the effective dose against antibiotic resistant microbes. Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutation prevention concentration (MPC) and critical concentration (Ccr) which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

  2. Eco-taxonomic insights into actinomycete symbionts of termites for discovery of novel bioactive compounds.

    Science.gov (United States)

    Kurtböke, D Ipek; French, John R J; Hayes, R Andrew; Quinn, Ronald J

    2015-01-01

    Termites play a major role in foraging and degradation of plant biomass as well as cultivating bioactive microorganisms for their defense. Current advances in "omics" sciences are revealing insights into function-related presence of these symbionts, and their related biosynthetic activities and genes identified in gut symbiotic bacteria might offer a significant potential for biotechnology and biodiscovery. Actinomycetes have been the major producers of bioactive compounds with an extraordinary range of biological activities. These metabolites have been in use as anticancer agents, immune suppressants, and most notably, as antibiotics. Insect-associated actinomycetes have also been reported to produce a range of antibiotics such as dentigerumycin and mycangimycin. Advances in genomics targeting a single species of the unculturable microbial members are currently aiding an improved understanding of the symbiotic interrelationships among the gut microorganisms as well as revealing the taxonomical identity and functions of the complex multilayered symbiotic actinofloral layers. If combined with target-directed approaches, these molecular advances can provide guidance towards the design of highly selective culturing methods to generate further information related to the physiology and growth requirements of these bioactive actinomycetes associated with the termite guts. This chapter provides an overview on the termite gut symbiotic actinoflora in the light of current advances in the "omics" science, with examples of their detection and selective isolation from the guts of the Sunshine Coast regional termite Coptotermes lacteus in Queensland, Australia.

  3. Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates.

    Science.gov (United States)

    Ebada, Sherif S; Edrada, Ru Angelie; Lin, Wenhan; Proksch, Peter

    2008-01-01

    In the past few decades, marine natural products bioprospecting has yielded a considerable number of drug candidates. Two marine natural products have recently been admitted as new drugs: Prialt (also known as ziconotide) as a potent analgesic for severe chronic pain and Yondelis (known also as trabectedin or E-743) as antitumor agent for the treatment of advanced soft tissue sarcoma. In this protocol, methods for bioactivity-guided isolation, purification and identification of secondary metabolites from marine invertebrates such as sponges, tunicates, soft corals and crinoids are discussed. To achieve this goal, solvent extraction of usually freeze-dried sample of marine organisms is performed. Next, the extract obtained is fractionated by liquid-liquid partitioning followed by various chromatographic separation techniques including thin layer chromatography, vacuum liquid chromatography, column chromatography (CC) and preparative high-performance reversed-phase liquid chromatography. Isolation of bioactive secondary metabolites is usually monitored by bioactivity assays, e.g., antioxidant (2,2-diphenyl-1-picryl hydrazyl) and cytotoxicity (microculture tetrazolium) activities that ultimately yield the active principles. Special care should be taken when performing isolation procedures adapted to the physical and chemical characteristics of the compounds isolated, particularly their lipo- or hydrophilic characters. Examples of isolation of compounds of different polarities from extracts of various marine invertebrates will be presented in this protocol. Structure elucidation is achieved using recent spectroscopic techniques, especially 2D NMR and mass spectrometry analysis.

  4. Comparison of the Remineralizing Effects of Sodium Fluoride and Bioactive Glass Using Bioerodible Gel Systems

    Directory of Open Access Journals (Sweden)

    Attiguppe Ramashetty Prabhakar

    2009-12-01

    Full Text Available Background and aims. A carious lesion is the accumulation of numerous episodes of de- and remineralization, rather than a unidirectional demineralization process. Tooth destruction can be arrested or reversed by the frequent delivery of fluoride or calcium/phosphorous ions to the tooth surface. The present study compared and evaluated the remineralization potential of sodium fluoride and bioactive glass delivered through a bioerodible gel system. Materials and methods. Longitudinal sections of artificial carious lesions, created at the gingivofacial surface of 64 primary maxillary incisors were photographed under a polarized light microscope and quantified for demineralization. The sections were repositioned into the tooth form and randomly mounted in sets of four that simulated an arch form. The teeth were divided into 4 groups: 1 sodium fluoride films, 2 bioactive glass films, 3 control films placed interproximally and 4 nontreatment group. Following exposure to artificial saliva for 30 days, the lesions were again photographed and quantified as above. The recorded values were statistically analyzed using Student’s paired t-test for intragroup comparison, one-way ANOVA and Post-Hoc Tukey’s test for pairwise comparison. Results. The sodium fluoride and bioactive gel groups showed significant remineralization compared with the control groups (P < 0.001. Conclusion. Bioerodible gel films can be used to deliver remineralizing agents to enhance remineralization.

  5. History and trends of bioactive glass-ceramics.

    Science.gov (United States)

    Montazerian, Maziar; Dutra Zanotto, Edgar

    2016-05-01

    The interest around bioactive glass-ceramics (GCs) has grown significantly over the last two decades due to their appropriate biochemical and mechanical properties. The intense research effort in this field has led to some new commercial products for biomedical applications. This review article begins with the basic concepts of GC processing and development via controlled heat treatments of monolithic pieces or sinter-crystallization of powdered glasses. We then go on to describe the processing, properties, and applications of some commercial bioactive GCs and discuss selected valuable reported researches on several promising types of bioactive GCs. The article finishes with a section on open relevant research directions for bioactive GC development.

  6. Bioactive Peptides from Muscle Sources: Meat and Fish

    Directory of Open Access Journals (Sweden)

    Catherine Stanton

    2011-08-01

    Full Text Available Bioactive peptides have been identified in a range of foods, including plant, milk and muscle, e.g., beef, chicken, pork and fish muscle proteins. Bioactive peptides from food proteins offer major potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an outline of the bioactive peptides identified in the muscle protein of meat to date, with a focus on muscle protein from domestic animals and fish. The majority of research on bioactives from meat sources has focused on angiotensin-1-converting enzyme (ACE inhibitory and antioxidant peptides.

  7. Microencapsulation for the improved delivery of bioactive compounds into foods.

    Science.gov (United States)

    Champagne, Claude P; Fustier, Patrick

    2007-04-01

    The development of functional foods through the addition of bioactive compounds holds many technological challenges. Microencapsulation is a useful tool to improve the delivery of bioactive compounds into foods, particularly probiotics, minerals, vitamins, phytosterols, lutein, fatty acids, lycopene and antioxidants. Several microencapsulation technologies have been developed for use in the food industry and show promise for the production of functional foods. Moreover, these technologies could promote the successful delivery of bioactive ingredients to the gastrointestinal tract. Future research is likely to focus on aspects of delivery and the potential use of co-encapsulation methodologies, where two or more bioactive ingredients can be combined to have a synergistic effect.

  8. Bioactive Hierarchical Structures for Genetic Control of Bone Morphogenesis

    Directory of Open Access Journals (Sweden)

    Pilar Sepulveda

    2002-09-01

    Full Text Available For thirty years it has been known that certain compositions of Na2O-CaO-P2O5-SiO 2 glasses will form a mechanically strong, chemical bond to bone. These materials have become known as bioactive glasses and the process of bonding is called bioactive fixation. Bioactive glasses are widely used clinically in the repair of bone defects. Recent research at the Imperial College Tissue Engineering Centre has now established that there is a genetic control of the cellular response to bioactive materials. Seven families of genes are up-regulated when primary human osteoblasts are exposed to the ionic dissolution products of bioactive glasses. The gene expression occurs very rapidly, within two days, and includes enhanced expression of cell cycle regulators. The consequence is rapid differentiation of the osteoblasts into a mature phenotype and formation of large three-dimensional bone nodules within six days in vitro. These cell culture results correlate with extensive human clinical results using the same bioactive material. The new genetic theory of bioactive materials provides a scientific foundation for molecular design of new generation of resorbable bioactive materials for tissue engineering and in situ tissue regeneration and repair. Application of this theory to the synthesis of bioactive foams for tissue engineering of bone is described.

  9. Quorum Quenching Agents: Resources for Antivirulence Therapy

    Directory of Open Access Journals (Sweden)

    Kaihao Tang

    2014-05-01

    Full Text Available The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy.

  10. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF.

    Directory of Open Access Journals (Sweden)

    Yonghua He

    Full Text Available Necrotizing enterocolitis (NEC is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF, typically found in bodily fluids, such as amniotic fluid, salvia and mother's breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N' terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform.

  11. Bioactive heterocycles containing endocyclic N-hydroxy groups.

    Science.gov (United States)

    Rani, Reshma; Granchi, Carlotta

    2015-06-05

    Drug-likeness rules consider N-O single bonds as "structural alerts" which should not be present in a perspective drug candidate. In most cases this concern is correct, since it is known that N-hydroxy metabolites of branded drugs produce reactive species that cause serious side effects. However, this dangerous reactivity of the N-OH species generally takes place when the nitrogen atom is not comprised in a cyclic moiety. In fact, the same type of metabolic behavior should not be expected when the nitrogen atom is included in the ring of an aromatic heterocyclic scaffold. Nevertheless, heterocycles bearing endocyclic N-hydroxy portions have so far been poorly studied as chemical classes that may provide new therapeutic agents. This review provides an overview of N-OH-containing heterocycles with reported bioactivities that may be considered as therapeutically relevant and, therefore, may extend the chemical space available for the future development of novel pharmaceuticals. A systematic treatment of the various chemical classes belonging to this particular family of molecules is described along with a discussion of the biological activities associated to the most important examples.

  12. Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity.

    Science.gov (United States)

    Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

    2013-07-21

    Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

  13. Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity

    Science.gov (United States)

    Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

    2013-06-01

    Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

  14. Characterization of the bioactive and mechanical behavior of dental ceramic/sol-gel derived bioactive glass mixtures.

    Science.gov (United States)

    Abbasi, Zahra; Bahrololoum, Mohammad E; Bagheri, Rafat; Shariat, Mohammad H

    2016-02-01

    Dental ceramics can be modified by bioactive glasses in order to develop apatite layer on their surface. One of the benefits of such modification is to prolong the lifetime of the fixed dental prosthesis by preventing the formation of secondary caries. Dental ceramic/sol-gel derived bioactive glass mixture is one of the options for this modification. In the current study, mixtures of dental ceramic/bioactive glass with different compositions were successfully produced. To evaluate their bioactive behavior, prepared samples were immersed in a simulated body fluid at various time intervals. The prepared and soaked specimens were characterized using Fourier transform infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. Since bioactive glasses have deleterious effects on the mechanical properties of dental ceramics, 3-point bending tests were used to evaluate the flexural strength, flexural strain, tangent modulus of elasticity and Weibull modulus of the specimens in order to find the optimal relationship between mechanical and bioactive properties.

  15. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

    Science.gov (United States)

    Shirode, Amit B; Bharali, Dhruba J; Nallanthighal, Sameera; Coon, Justin K; Mousa, Shaker A; Reliene, Ramune

    2015-01-01

    Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs loaded with pomegranate extract (PE) or individual polyphenols such as PU or EA. Monodispersed, spherical 150-200 nm average diameter NPs were prepared by the double emulsion-solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA-PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer.

  16. COMPARISON OF BIOACTIVE INGREDIENTS IN OCIMUM SPECIES

    Directory of Open Access Journals (Sweden)

    R.Caroline Jeba

    2013-08-01

    Full Text Available With the increasing demand for health care approaches, resurgence of herbal medicines has taken up great dimensions in changing the health care scenario across the globe. However, identification of the correct species of therapeutic importance is of utmost necessity to deliver quality products to the global market. Hence, modern approach in the standardization of single herbal preparations employing sophisticated techniques is the need of the hour. The evaluation of a product in its entirety, so-called “fingerprinting” can be accomplished by appropriate methods, which may include HPLC, GC-MS, HPTLC-densitometry, FT-NIR, high-field NMR or a combination of these techniques. Using chemical fingerprinting, plants can be demarcated on the basis of their species, strain and geographical origin. Chemical fingerprinting of plants, through chromatographic fingerprinting is highly informative which includes its use as an absolute indicator of the chemical characteristics of plants. Adulterants can be distinguished even in processed samples, enabling the authentication of the drug. Herein, in the present study two varieties of Ocimum species with green and purple coloured leaves collected from Tirunelvelli district commonly known as “Tulasi” in Tamil or “Holy Basil” in English and widely used in both ayurvedic and siddha drugs was subjected to chemical fingerprinting using HPTLC and GC. Moreover, the secondary metabolities such as polyphenols, tannins, and flavonoids were quantified to check the potency of the crude drug material. The bioactive molecule such as eugenol was found to be varying in both the species and the purple variety was found to contain more of the bioactive molecules. The fingerprinting of chemical profile as well as the quantification of the bioactive molecules in the two varieties of Ocimum species exemplified that fingerprinting using analytical techniques are comprehensive and more informative to identify and

  17. Bioactive glass coupling with natural polyphenols: Surface modification, bioactivity and anti-oxidant ability

    Science.gov (United States)

    Cazzola, Martina; Corazzari, Ingrid; Prenesti, Enrico; Bertone, Elisa; Vernè, Enrica; Ferraris, Sara

    2016-03-01

    Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H2O2 highlighting scavenging activity of the bioactive glass.

  18. In vitro bioactivity and cytocompatibility of porous scaffolds of bioactive borosilicate glasses

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin; FU HaiLuo; LIU Xin; YAO AiHua; WANG DePing; HUANG WenHai; ZHAO Ying; JIANG XinQuan

    2009-01-01

    The bioactive borosilicate scaffolds (R2O-RO-B2O3-SiO2-P2O5) with four different contents of borate were fabricated by replication technique. The bioactivity,degradability and the cytotoxicity of the scaffolds were studied in this paper. The porosity of the scaffolds was found to be 73%-80%,and the pore size was in the range of 200-300 μm. The porous scaffolds immersed in 0.02 mol. L-1 K2HPO4 solution were transformed into hydroxyapatite. And it is notable that the D-AIk-2B,D-AIk-3B-scaffolds were covered by hydroxyapatite layers after 7 h-immersion,which proved their high bioactivity. In the cell adhesion test,cells could be seen growing well on the scaffolds,showing stretched morphology and obvious pseudopodia,and only the high cumulative concentration of B ions released from the D-AIk-3B-scaffold samples had an inhibition effect on cell proliferation. But the inhibition effect could be alleviated by diluting the extract solution to a certain concentration (dilution ratio:1:8). Therefore,after suitable pretreatment,the porous borosilicate bioactive glass scaffold can be e desirable candidate for bone tissue engineering.

  19. LASER-INDUCED BIOACTIVITY IN DENTAL PORCELAIN MODIFIED BY BIOACTIVE GLASS

    Directory of Open Access Journals (Sweden)

    ANASTASIA BEKETOVA

    2012-12-01

    Full Text Available The aim of this study was to investigate the impact of laser-liquid-solid interaction method in the bioactivity of dental porcelain modified by bioactive glass. Forty sol-gel derived specimens were immersed in Dulbecco's Modified Eagle's Medium, 31 and 9 specimens of which were treated with Er:YAG and Nd:YAG laser respectively. Untreated specimens served as controls. Incubation of specimens followed. Bioactivity was evaluated, using Fourier Transform Infrared spectroscopy (FTIR, Scanning Electron Microscopy (SEM/Energy Dispersive Spectroscopy (EDS and Transmission Electron Microscopy (TEM. FTIR detected peaks associated with hydroxyapatite on 1 Nd:YAG- and 4 Er:YAG-treated specimens. SEM analysis revealed that Er:YAG-treated specimens were covered by granular hydroxyapatite layer, while Nd:YAG treated specimen presented growth of flake-like hydroxyapatite. TEM confirmed the results. The untreated controls presented delayed bioactivity. In conclusion, Nd:YAG and Er:YAG laser treatment of the material, under certain fluencies, accelerates hydroxyapatite formation. Nd:YAG laser treatment of specific parameters causes the precipitation of flake-like hydroxyapatite in nano-scale.

  20. Composite bone cements loaded with a bioactive and ferrimagnetic glass-ceramic: Leaching, bioactivity and cytocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Verné, Enrica, E-mail: enrica.verne@polito.it [Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, C. so Duca degli Abruzzi 24, 10129 Torino (Italy); Bruno, Matteo [Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, C. so Duca degli Abruzzi 24, 10129 Torino (Italy); Miola, Marta [Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, C. so Duca degli Abruzzi 24, 10129 Torino (Italy); Department of Health Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Via Solaroli 17, 28100 Novara (Italy); Maina, Giovanni; Bianco, Carlotta [Traumatology Orthopedics and Occupational Medicine Dept., Università di Torino, Via G. Zuretti 29, 10126 Torino (Italy); Cochis, Andrea [Department of Health Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Via Solaroli 17, 28100 Novara (Italy); Rimondini, Lia [Department of Health Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Via Solaroli 17, 28100 Novara (Italy); Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali, Via G. Giusti, 9, 50121 Firenze (Italy)

    2015-08-01

    In this work, composite bone cements, based on a commercial polymethylmethacrylate matrix (Palamed®) loaded with ferrimagnetic bioactive glass-ceramic particles (SC45), were produced and characterized in vitro. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO{sub 2}–Na{sub 2}O–CaO–P{sub 2}O{sub 5}–FeO–Fe{sub 2}O{sub 3} and contains magnetite (Fe{sub 3}O{sub 4}) crystals into a residual amorphous bioactive phase. Three different formulations (containing 10, 15 and 20 wt.% of glass-ceramic particles respectively) have been investigated. These materials are intended to be applied as bone fillers for the hyperthermic treatment of bone tumors. The morphological, compositional, calorimetric and mechanical properties of each formulation have been already discussed in a previous paper. The in vitro properties of the composite bone cements described in the present paper are related to iron ion leaching test (by graphite furnace atomic absorption spectrometer), bioactivity (i.e. the ability to stimulate the formation of a hydroxyapatite – HAp – layer on their surface after soaking in simulated body fluid SBF) and cytocompatibility toward human osteosarcoma cells (ATCC CRL-1427, Mg63). Morphological and chemical characterizations by scanning electron microscopy and energy dispersion spectrometry have been performed on the composite samples after each test. The iron release was negligible and all the tested samples showed the growth of HAp on their surface after 28 days of immersion in a simulated body fluid (SBF). Cells showed good viability, morphology, adhesion, density and the ability to develop bridge-like structures on all investigated samples. A synergistic effect between bioactivity and cell mineralization was also evidenced. - Highlights: • An in vitro biological characterization was carried out on ferromagnetic and bioactive composite cements. • No release of iron was revealed in the physiological solution. • Bioactivity tests

  1. In vitro analysis of PDZ-dependent CFTR macromolecular signaling complexes.

    Science.gov (United States)

    Wu, Yanning; Wang, Shuo; Li, Chunying

    2012-08-13

    has been shown to be of functional significance, suggesting that PDZ scaffold proteins may facilitate formation of CFTR macromolecular signaling complexes for specific/selective and efficient signaling in cells(16-18). Multiple biochemical assays have been developed to study CFTR-involving protein interactions, such as co-immunoprecipitation, pull-down assay, pair-wise binding assay, colorimetric pair-wise binding assay, and macromolecular complex assembly assay(16-19,28,29). Here we focus on the detailed procedures of assembling a PDZ motif-dependent CFTR-containing macromolecular complex in vitro, which is used extensively by our laboratory to study protein-protein or domain-domain interactions involving CFTR(16-19,28,29).

  2. Patents on Therapeutic and Cosmetic Applications of Bioactives of Crocus Sativus L. and their Production through Synthetic Biology Methods: A Review.

    Science.gov (United States)

    Dawalbhakta, Mitali; Telang, Manasi

    2017-01-01

    Saffron (Crocus sativus L.) has a long history of use as a food additive and a traditional medicine for treating a number of disorders. Prominent bioactives of saffron are crocin, crocetin and safranal. The aim of this study was to carry out an extensive patent search to collect information on saffron bioactives and their derivatives as therapeutic and cosmeceutical agents. All patents related to the area of interest published globally till date have been reviewed. Moreover, a recent synthetic biology approach to cost effective and consistent production of saffron bioactives has been highlighted. A patent search strategy was designed based on keywords and concepts related to Crocus sativus L. and its bioactives- safranal, crocin and crocetin in combination with different patent classification codes relevant to the technology areas. This search strategy was employed to retrieve patents from various patent databases. The patents which focused on therapeutic or cosmetic applications and claimed compositions comprising crocin, crocetin or safranal as the main active component were selected and analysed. Maximum patenting activity was noticed towards the use of these bioactives in the treatment of neurological disorders followed by multiple uses of the same compound, use in treatment of metabolic disorders and use as cosmeceuticals. Interestingly, there were no patent records related to use of these bioactives in treating infectious disorders. Our patent analysis points out the populous and less explored uses of saffron bioactives and areas where there is further scope for research and growth. Recently developed synthetic biology approach is contributory in improving availability, consistency and cost effectiveness of saffron bioactives. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Multilayer bioactive glass/zirconium titanate thin films in bone tissue engineering and regenerative dentistry

    Directory of Open Access Journals (Sweden)

    Mozafari M

    2013-04-01

    Full Text Available Masoud Mozafari,1,2 Erfan Salahinejad,1,3 Vahid Shabafrooz,1 Mostafa Yazdimamaghani,1 Daryoosh Vashaee,4 Lobat Tayebi1,5 1Helmerich Advanced Technology Research Center, School of Materials Science and Engineering, Oklahoma State University, Tulsa, OK, USA; 2Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence, Amirkabir University of Technology, Tehran, Iran; 3Department of Materials Science and Engineering, School of Engineering, Shiraz University, Shiraz, Iran; 4Helmerich Advanced Technology Research Center, School of Electrical and Computer Engineering, Oklahoma State University, Tulsa, OK, USA; 5School of Chemical Engineering, Oklahoma State University, Tulsa, OK, USA Abstract: Surface modification, particularly coatings deposition, is beneficial to tissue-engineering applications. In this work, bioactive glass/zirconium titanate composite thin films were prepared by a sol-gel spin-coating method. The surface features of the coatings were studied by scanning electron microscopy, atomic force microscopy, and spectroscopic reflection analyses. The results show that uniform and sound multilayer thin films were successfully prepared through the optimization of the process variables and the application of carboxymethyl cellulose as a dispersing agent. Also, it was found that the thickness and roughness of the multilayer coatings increase nonlinearly with increasing the number of the layers. This new class of nanocomposite coatings, comprising the bioactive and inert components, is expected not only to enhance bioactivity and biocompatibility, but also to protect the surface of metallic implants against wear and corrosion. Keywords: bioactive glass, zirconium titanate, spin-coating, microstructural properties, bone/dental applications, tissue engineering

  4. Fluoride-containing bioactive glasses: Glass design, structure, bioactivity, cellular interactions, and recent developments

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Furqan A., E-mail: furqan.ali.shah@biomaterials.gu.se

    2016-01-01

    Bioactive glasses (BGs) are known to bond to both hard and soft tissues. Upon exposure to an aqueous environment, BG undergoes ion exchange, hydrolysis, selective dissolution and precipitation of an apatite layer on their surface, which elicits an interfacial biological response resulting in bioactive fixation, inhibiting further dissolution of the glass, and preventing complete resorption of the material. Fluorine is considered one of the most effective in-vivo bone anabolic factors. In low concentrations, fluoride ions (F{sup −}) increase bone mass and mineral density, improve the resistance of the apatite structure to acid attack, and have well documented antibacterial properties. F{sup −} ions may be incorporated into the glass in the form of calcium fluoride (CaF{sub 2}) either by part-substitution of network modifier oxides, or by maintaining the ratios of the other constituents relatively constant. Fluoride-containing bioactive glasses (FBGs) enhance and control osteoblast proliferation, differentiation and mineralisation. And with their ability to release fluoride locally, FBGs make interesting candidates for various clinical applications, dentinal tubule occlusion in the treatment of dentin hypersensitivity. This paper reviews the chemistry of FBGs and the influence of F{sup −} incorporation on the thermal properties, bioactivity, and cytotoxicity; and novel glass compositions for improved mechanical properties, processing, and bioactive potential. - Highlights: • Fluoride ions form charged CaF{sup +} species rather than Si–F bonds. • Fluoride incorporation lowers glass transition and crystallisation temperatures. • Oxynitride and oxyfluoronitride glasses with superior mechanical properties • Mixed-alkali and alkali-free compositions with better processing characteristics.

  5. Fabrication and bioactivity behavior of HA/bioactive glass composites in the presence of calcium hexaboride

    Energy Technology Data Exchange (ETDEWEB)

    El-Bassyouni, Gehan T.; Beherei, Hanan H. [Biomaterials Dept., National Research Centre (NRC), Dokki, Cairo (Egypt); Mohamed, Khaled R., E-mail: kh_rezk1966@yahoo.com [Biomaterials Dept., National Research Centre (NRC), Dokki, Cairo (Egypt); Kenawy, Sayed H. [Ceramics Dept., National Research Centre (NRC), Dokki, Cairo (Egypt)

    2016-06-01

    In the current study, composites were prepared using both the synthesized nano-sized hydroxyapatite (HA), bioactive glass (BG) powders (obtained by the traditional melt-quenching route) together with the purchased nano-sized calcium hexaboride (CB) with different ratios and were fired at 1250 °C. The structure and composition of the solid reaction products were analyzed using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy; scanning electron microscope (SEM) coupled with energy dispersive spectroscopy (EDS), transmission electron microscope (TEM) techniques and compressive strength. The mechanical testing was to designate the role of the CB in improving the mechanical property of the prepared composites. In vitro bioactivity of the prepared composites was assessed by soaking in the simulated body fluid (SBF) at 37 ± 0.5 °°C for 10 days. The effect of different ratios of the three components (CB, HA & BG) on the bioactivity properties was assessed to explore the possibility of enhancing such property to perform in vitro imitations of in vivo conditions in the future. It can be pointed out that the Si-HA content in the composition showed outstanding in vitro bioactivity than pure hydroxyapatite which could be attributed to the excellent bioactivity of the synthesized composites. - Highlights: • The prepared of nano-composites containing CB, HA and BG powders were achieved. • The addition of CB powder enhanced the compressive strength for all the composites. • The composites containing high BG and CB contents improved formation of bone-like apatite layer.

  6. Solid-state NMR in macromolecular systems: insights on how molecular entities move.

    Science.gov (United States)

    Hansen, Michael Ryan; Graf, Robert; Spiess, Hans Wolfgang

    2013-09-17

    The function of synthetic and natural macromolecularsystems critically depends on the packing and dynamics of the individual components of a given system. Not only can solid-state NMR provide structural information with atomic resolution, but it can also provide a way to characterize the amplitude and time scales of motions over broad ranges of length and time. These movements include molecular dynamics, rotational and translational motions of the building blocks, and also the motion of the functional species themselves, such as protons or ions. This Account examines solid-state NMR methods for correlating dynamics and function in a variety of chemical systems. In the early days, scientists thought that the rotationalmotions reflected the geometry of the moving entities. They described these phenomena as jumps about well-defined axes, such as phenyl flips, even in amorphous polymers. Later, they realized that conformational transitions in macromolecules happen in a much more complex way. Because the individual entities do not rotate around well-defined axes, they require much less space. Only recently researchers have appreciated the relative importance of large angle fluctuations of polymers over rotational jumps. Researchers have long considered that cooperative motions might be at work, yet only recently they have clearly detected these motions by NMR in macromolecular and supramolecular systems. In correlations of dynamics and function, local motions do not always provide the mechanism of long-range transport. This idea holds true in ion conduction but also applies to chain transport in polymer melts and semicrystalline polymers. Similar chain motions and ion transport likewise occur in functional biopolymers, systems where solid-state NMR studies are also performed. In polymer science, researchers have appreciated the unique information on molecular dynamics available from advanced solid-state NMR at times, where their colleagues in the biomacromolecular

  7. Macromolecular composition of terrestrial and marine organic matter in sediments across the East Siberian Arctic Shelf

    Science.gov (United States)

    Sparkes, Robert B.; Doğrul Selver, Ayça; Gustafsson, Örjan; Semiletov, Igor P.; Haghipour, Negar; Wacker, Lukas; Eglinton, Timothy I.; Talbot, Helen M.; van Dongen, Bart E.

    2016-10-01

    Mobilisation of terrestrial organic carbon (terrOC) from permafrost environments in eastern Siberia has the potential to deliver significant amounts of carbon to the Arctic Ocean, via both fluvial and coastal erosion. Eroded terrOC can be degraded during offshore transport or deposited across the wide East Siberian Arctic Shelf (ESAS). Most studies of terrOC on the ESAS have concentrated on solvent-extractable organic matter, but this represents only a small proportion of the total terrOC load. In this study we have used pyrolysis-gas chromatography-mass spectrometry (py-GCMS) to study all major groups of macromolecular components of the terrOC; this is the first time that this technique has been applied to the ESAS. This has shown that there is a strong offshore trend from terrestrial phenols, aromatics and cyclopentenones to marine pyridines. There is good agreement between proportion phenols measured using py-GCMS and independent quantification of lignin phenol concentrations (r2 = 0.67, p < 0.01, n = 24). Furfurals, thought to represent carbohydrates, show no offshore trend and are likely found in both marine and terrestrial organic matter. We have also collected new radiocarbon data for bulk OC (14COC) which, when coupled with previous measurements, allows us to produce the most comprehensive 14COC map of the ESAS to date. Combining the 14COC and py-GCMS data suggests that the aromatics group of compounds is likely sourced from old, aged terrOC, in contrast to the phenols group, which is likely sourced from modern woody material. We propose that an index of the relative proportions of phenols and pyridines can be used as a novel terrestrial vs. marine proxy measurement for macromolecular organic matter. Principal component analysis found that various terrestrial vs. marine proxies show different patterns across the ESAS, and it shows that multiple river-ocean transects of surface sediments transition from river-dominated to coastal-erosion-dominated to marine

  8. Chemiluminescence-imaging detection of DNA on a solid-phase membrane by using a peroxidase-labeled macromolecular probe.

    Science.gov (United States)

    Azam, Md Golam; Yamasuji, Mutsumi; Krawczyk, Tomasz; Shibata, Takayuki; Kabashima, Tsutomu; Kai, Masaaki

    2015-07-01

    We have developed a novel method for sensitive chemiluminescence (CL)-imaging detection of DNA by using a macromolecular probe synthesized by attaching multiple molecules of horseradish peroxidase (HRP) and biotin in dextran backbone. The probe formed a macromolecular assembly by binding to streptavidin which specifically recognized biotinylated complementary DNA, which was hybridized to a target DNA on a solid-phase membrane. This methodology was applied to CL-imaging detection of a synthetic telomere DNA (TTAGGG)10 and human telomere DNA by using the CL probe comprising of dextranT2000 (MW=ca. 2000kDa) bonded to approximately 42 molecules of HRP and 210 molecules of biotin. The human telomere DNA in a small number of buccal mucous cells (ca. 70 cell numbers) of cheek tissue was quantitatively determined by the proposed CL detection method that afforded approximately 10 times higher sensitivity than that of the conventional CL method using commercially available HRP-avidin probe.

  9. Distribution and enzymatic activity of heterotrophic bacteria decomposing selected macromolecular compounds in a Baltic Sea sandy beach

    Science.gov (United States)

    Podgórska, B.; Mudryk, Z. J.

    2003-03-01

    The potential capability to decompose macromolecular compounds, and the level of extracellular enzyme activities were determined in heterotrophic bacteria isolated from a sandy beach in Sopot on the Southern Baltic Sea coast. Individual isolates were capable of hydrolysing a wide spectrum of organic macromolecular compounds. Lipids, gelatine, and DNA were hydrolyzed most efficiently. Only a very small percentage of strains were able to decompose cellulose, and no pectinolytic bacteria were found. Except for starch-hydrolysis, no significant differences in the intensity of organic compound decomposition were recorded between horizontal and vertical profiles of the studied beach. Of all the studied extracellular enzymes, alkaline phosphatase, esterase lipase, and leucine acrylaminidase were most active; in contrast, the activity α-fucosidase, α-galactosidase and β-glucouronidase was the weakest. The level of extracellular enzyme activity was similar in both sand layers.

  10. On the vibron dressing in the one-dimensional macromolecular chains caused by the interaction with acoustic phonon modes

    CERN Document Server

    Cevizovic, Dalibor; Galovic, Slobodanka; Ivic, Zoran

    2012-01-01

    We present a study of the physical properties of the vibrational excitation in the one-dimensional macromolecular chains, caused by the interaction with acoustical phonon modes. The influence of the temperature and the basic system parameters on the vibron dressing has been analyzed by employing the simple mean--field approach based on the variational extension of the Lang--Firsov unitary transformation. Applied approach predicts a region in system parameter space where it is possible of the coexistence of the partially dressed (light and mobile) and fully dressed (immobile) vibron states. We found that the boundary of this region depends on system temperature and type of bond among structure elements in macromolecular chain.

  11. Cobalt Derivatives as Promising Therapeutic Agents

    Science.gov (United States)

    Heffern, Marie C.; Yamamoto, Natsuho; Holbrook, Robert J.; Eckermann, Amanda L.; Meade, Thomas J.

    2013-01-01

    Inorganic complexes are versatile platforms for the development of potent and selective pharmaceutical agents. Cobalt possesses a diverse array of properties that can be manipulated to yield promising drug candidates. Investigations into the mechanism of cobalt therapeutic agents can provide valuable insight into the physicochemical properties that can be harnessed for drug development. This review presents examples of bioactive cobalt complexes with special attention to their mechanisms of action. Specifically, cobalt complexes that elicit biological effects through protein inhibition, modification of drug activity, and bioreductive activation are discussed. Insights gained from these examples reveal features of cobalt that can be rationally tuned to produce therapeutics with high specificity and improved efficacy for the biomolecule or pathway of interest. PMID:23270779

  12. Bioactive borate glass coatings for titanium alloys.

    Science.gov (United States)

    Peddi, Laxmikanth; Brow, Richard K; Brown, Roger F

    2008-09-01

    Bioactive borate glass coatings have been developed for titanium and titanium alloys. Glasses from the Na(2)O-CaO-B(2)O(3) system, modified by additions of SiO(2), Al(2)O(3), and P(2)O(5), were characterized and compositions with thermal expansion matches to titanium were identified. Infrared and X-ray diffraction analyses indicate that a hydroxyapatite surface layer forms on the borate glasses after exposure to a simulated body fluid for 2 weeks at 37 degrees C; similar layers form on 45S5 Bioglass((R)) exposed to the same conditions. Assays with MC3T3-E1 pre-osteoblastic cells show the borate glasses exhibit in vitro biocompatibility similar to that of the 45S5 Bioglass((R)). An enameling technique was developed to form adherent borate glass coatings on Ti6Al4V alloy, with adhesive strengths of 36 +/- 2 MPa on polished substrates. The results show these new borate glasses to be promising candidates for forming bioactive coatings on titanium substrates.

  13. Processing of apple pomace for bioactive molecules.

    Science.gov (United States)

    Bhushan, Shashi; Kalia, Kalpana; Sharma, Madhu; Singh, Bikram; Ahuja, P S

    2008-01-01

    The growth of horticulture industries worldwide has generated huge quantities of fruit wastes (25%-40% of the total fruits processed). These residues are generally a good source of carbohydrates, especially cell wall polysaccharides and other functionally important bioactive molecules such as proteins, vitamins, minerals and natural antioxidants. "Apple pomace" is a left-over solid biomass with a high moisture content, obtained as a by-product during the processing of apple fruits for juice, cider or wine preparation. Owing to the high carbohydrate content, apple pomace is used as a substrate in a number of microbial processes for the production of organic acids, enzymes, single cell protein, ethanol, low alcoholic drinks and pigments. Recent research trends reveal that there is an increase in the utilization of apple pomace as a food processing residue for the extraction of value added products such as dietary fibre, protein, natural antioxidants, biopolymers, pigments and compounds with unique properties. However, the central dogma is still the stability, safety and economic feasibility of the process(s)/product(s) developed. This review is mainly focused on assessing recent research developments in extraction, isolation and characterization of bioactive molecules from apple pomace, along with their commercial utilization, in food fortification.

  14. Quantification and bioaccessibility of california pistachio bioactives.

    Science.gov (United States)

    Liu, Yuntao; Blumberg, Jeffrey B; Chen, C-Y Oliver

    2014-02-19

    The content of carotenoids, chlorophylls, phenolics, and tocols in pistachios ( Pistacia vera L.) has not been methodically quantified. The objective of this study was to first optimize extraction protocols for lipophilic nutrients and then quantify the content of two phenolic acids, nine flavonoids, four carotenoids, two chlorophylls, and three tocols in the skin, nutmeat, and whole nut of California pistachios. The dominant bioactives in whole pistachios are lutein [42.35 μg/g fresh weight (FW)], chlorophyll a (142.24 μg/g FW), γ-tocopherol (182.20 μg/g FW), flavan-3-ols (catechins) (199.18 μg/g FW), luteolin (217.89 μg/g FW), myricetin (135.18 μg/g FW), and cyanidin-3-galactose (38.34 μg/g FW) in each nutrient class. Most phenolics are present in the skin, while the lipophilic nutrients are dominantly present in the nutmeat. Digestion with a gastrointestinal mimic showed pistachio matrices. In conclusion, 9 lipophilic and 11 hydrophilic bioactives in pistachios are systematically quantified.

  15. Exploring marine resources for bioactive compounds.

    Science.gov (United States)

    Kiuru, Paula; DʼAuria, M Valeria; Muller, Christian D; Tammela, Päivi; Vuorela, Heikki; Yli-Kauhaluoma, Jari

    2014-09-01

    Biodiversity in the seas is only partly explored, although marine organisms are excellent sources for many industrial products. Through close co-operation between industrial and academic partners, it is possible to successfully collect, isolate and classify marine organisms, such as bacteria, fungi, micro- and macroalgae, cyanobacteria, and marine invertebrates from the oceans and seas globally. Extracts and purified compounds of these organisms can be studied for several therapeutically and industrially significant biological activities, including anticancer, anti-inflammatory, antiviral, antibacterial, and anticoagulant activities by applying a wide variety of screening tools, as well as for ion channel/receptor modulation and plant growth regulation. Chromatographic isolation of bioactive compounds will be followed by structural determination. Sustainable cultivation methods for promising organisms and biotechnological processes for selected compounds can be developed, as well as biosensors for monitoring the target compounds. The (semi)synthetic modification of marine-based bioactive compounds produces their new derivatives, structural analogs and mimetics that could serve as hit or lead compounds and be used to expand compound libraries based on marine natural products. The research innovations can be targeted for industrial product development in order to improve the growth and productivity of marine biotechnology. Marine research aims at a better understanding of environmentally conscious sourcing of marine biotechnology products and increased public awareness of marine biodiversity. Marine research is expected to offer novel marine-based lead compounds for industries and strengthen their product portfolios related to pharmaceutical, nutraceutical, cosmetic, agrochemical, food processing, material and biosensor applications.

  16. Bioactive Polymeric Materials for Tissue Repair

    Directory of Open Access Journals (Sweden)

    Diane R. Bienek

    2017-01-01

    Full Text Available Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP’s dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material’s critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field.

  17. Bioactivation of biomorphous silicon carbide bone implants.

    Science.gov (United States)

    Will, Julia; Hoppe, Alexander; Müller, Frank A; Raya, Carmen T; Fernández, Julián M; Greil, Peter

    2010-12-01

    Wood-derived silicon carbide (SiC) offers a specific biomorphous microstructure similar to the cellular pore microstructure of bone. Compared with bioactive ceramics such as calcium phosphate, however, silicon carbide is considered not to induce spontaneous interface bonding to living bone. Bioactivation by chemical treatment of biomorphous silicon carbide was investigated in order to accelerate osseointegration and improve bone bonding ability. Biomorphous SiC was processed from sipo (Entrandrophragma utile) wood by heating in an inert atmosphere and infiltrating the resulting carbon replica with liquid silicon melt at 1450°C. After removing excess silicon by leaching in HF/HNO₃ the biomorphous preform consisted of β-SiC with a small amount (approximately 6wt.%) of unreacted carbon. The preform was again leached in HCl/HNO₃ and finally exposed to CaCl₂ solution. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared analyses proved that oxidation of the residual carbon at the surface induced formation of carboxyl [COO⁻] groups, which triggered adsorption of Ca(2+), as confirmed by XPS and inductively coupled plasma optical emission spectroscopy measurements. A local increase in Ca(2+) concentration stimulated in vitro precipitation of Ca₅(PO₄)₃OH (HAP) on the silicon carbide preform surface during exposure to simulated body fluid, which indicates a significantly increased bone bonding activity compared with SiC.

  18. Bioactive Peptides in Animal Food Products

    Directory of Open Access Journals (Sweden)

    Marzia Albenzio

    2017-05-01

    Full Text Available Proteins of animal origin represent physiologically active components in the human diet; they exert a direct action or constitute a substrate for enzymatic hydrolysis upon food processing and consumption. Bioactive peptides may descend from the hydrolysis by digestive enzymes, enzymes endogenous to raw food materials, and enzymes from microorganisms added during food processing. Milk proteins have different polymorphisms for each dairy species that influence the amount and the biochemical characteristics (e.g., amino acid chain, phosphorylation, and glycosylation of the protein. Milk from other species alternative to cow has been exploited for their role in children with cow milk allergy and in some infant pathologies, such as epilepsy, by monitoring the immune status. Different mechanisms concur for bioactive peptides generation from meat and meat products, and their functionality and application as functional ingredients have proven effects on consumer health. Animal food proteins are currently the main source of a range of biologically-active peptides which have gained special interest because they may also influence numerous physiological responses in the organism. The addition of probiotics to animal food products represent a strategy for the increase of molecules with health and functional properties.

  19. MOBILE AGENT: EMERGING TECHNOLOGY

    OpenAIRE

    RAJGURU P. V. DR. DESHMUKH S. D

    2011-01-01

    Mobile agent technology has been promoted as an emerging technology that makes it much easier to design, implement, and maintain distributed systems, introduction to basic concepts of mobile agents like agent mobility, agent types and places and agent communication. Then benefits of the usage of mobile agents are summarized and illustrated by selected applications. The next section lists requirements and desirable properties for mobile agent languages and systems. We study the main features, ...

  20. 08B1-1: an automated beamline for macromolecular crystallography experiments at the Canadian Light Source.

    Science.gov (United States)

    Fodje, Michel; Grochulski, Pawel; Janzen, Kathryn; Labiuk, Shaunivan; Gorin, James; Berg, Russ

    2014-05-01

    Beamline 08B1-1 is a recently commissioned bending-magnet beamline at the Canadian Light Source. The beamline is designed for automation and remote access. Together with the undulator-based beamline 08ID-1, they constitute the Canadian Macromolecular Crystallography Facility. This paper describes the design, specifications, hardware and software of beamline 08B1-1. A few scientific results using data obtained at the beamline will be highlighted.

  1. A facile metal-free "grafting-from" route from acrylamide-based substrate toward complex macromolecular combs

    KAUST Repository

    Zhao, Junpeng

    2013-01-01

    High-molecular-weight poly(N,N-dimethylacrylamide-co-acrylamide) was used as a model functional substrate to investigate phosphazene base (t-BuP 4)-promoted metal-free anionic graft polymerization utilizing primary amide moieties as initiating sites. The (co)polymerization of epoxides was proven to be effective, leading to macromolecular combs with side chains being single- or double-graft homopolymer, block copolymer and statistical copolymer. © 2013 The Royal Society of Chemistry.

  2. Contrast-enhanced peripheral MRA. Technique and contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Yousef W. [Dept. of Radiology, Copenhagen Univ. Hospital Bispebjerg, Bispebjerg (Denmark)], e-mail: ywnielsen@gmail.com; Thomsen, Henrik S. [Dept. of Diagnostic Radiology, Copenhagen Univ. Hospital Herlev, Herlev (Denmark)

    2012-09-15

    In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast agents. Peripheral CE-MRA is defined as an MR angiogram of the arteries from the aortic bifurcation to the feet. Advantages of CE-MRA include minimal invasiveness and lack of ionizing radiation. The basic technique employed for peripheral CE-MRA is the bolus-chase method. With this method a paramagnetic MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic field strength of the MRI system, receiver coil configuration, use of parallel imaging, contrast bolus timing technique, and k-space filling strategies. Furthermore, it is possible to optimize peripheral CE-MRA using venous compression techniques, hybrid scan protocols, time-resolved imaging, and steady-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Using optimized technique and a stable MRI contrast agent, peripheral CE-MRA is a safe procedure with diagnostic accuracy close to that of conventional catheter X

  3. Bioactivity and chemical ecology of some intertidal animals

    Digital Repository Service at National Institute of Oceanography (India)

    Parulekar, A.H.; Shirwaikar, P.

    stream_size 7 stream_content_type text/plain stream_name Bioactive_Com_Mar_Org_1991_29.pdf.txt stream_source_info Bioactive_Com_Mar_Org_1991_29.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 ...

  4. Bioactive compounds: Safety and efficacy (Consensus Meeting - Part II)

    NARCIS (Netherlands)

    Biesalski, H.K.; Dragsted, L.O.; Elmadfa, I.; Grossklaus, R.; Müller, M.R.; Schrenk, D.; Walter, P.; Weber, P.

    2009-01-01

    The efficacy and safety of bioactive compounds depend on a few known and unknown parameters. What is a physiologic dose and how can that dose be defined in cases of bioactive compounds with a poor knowledge of supply and distribution? What safety sets are needed? How can individual aspects such as p

  5. A decade of user operation on the macromolecular crystallography MAD beamline ID14-4 at the ESRF.

    Science.gov (United States)

    McCarthy, Andrew A; Brockhauser, Sandor; Nurizzo, Didier; Theveneau, Pascal; Mairs, Trevor; Spruce, Darren; Guijarro, Matias; Lesourd, Marc; Ravelli, Raimond B G; McSweeney, Sean

    2009-11-01

    ID14-4 at the ESRF is the first tunable undulator-based macromolecular crystallography beamline that can celebrate a decade of user service. During this time ID14-4 has not only been instrumental in the determination of the structures of biologically important molecules but has also contributed significantly to the development of various instruments, novel data collection schemes and pioneering radiation damage studies on biological samples. Here, the evolution of ID14-4 over the last decade is presented, and some of the major improvements that were carried out in order to maintain its status as one of the most productive macromolecular crystallography beamlines are highlighted. The experimental hutch has been upgraded to accommodate a high-precision diffractometer, a sample changer and a large CCD detector. More recently, the optical hutch has been refurbished in order to improve the X-ray beam quality on ID14-4 and to incorporate the most modern and robust optical elements used at other ESRF beamlines. These new optical elements will be described and their effect on beam stability discussed. These studies may be useful in the design, construction and maintenance of future X-ray beamlines for macromolecular crystallography and indeed other applications, such as those planned for the ESRF upgrade.

  6. A decade of user operation on the macromolecular crystallography MAD beamline ID14-4 at the ESRF

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, Andrew A., E-mail: andrewmc@embl.fr; Brockhauser, Sandor [European Molecular Biology Laboratory, 6 rue Jules Horowitz, BP 181, 38042 Grenoble (France); Unit of Virus Host Cell Interactions, UJF-EMBL-CNRS, UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9 (France); Nurizzo, Didier; Theveneau, Pascal; Mairs, Trevor; Spruce, Darren; Guijarro, Matias; Lesourd, Marc [European Synchrotron Radiation Facility, 6 rue Jules Horowitz, BP 220, 38042 Grenoble (France); Ravelli, Raimond B. G. [European Molecular Biology Laboratory, 6 rue Jules Horowitz, BP 181, 38042 Grenoble (France); McSweeney, Sean [European Synchrotron Radiation Facility, 6 rue Jules Horowitz, BP 220, 38042 Grenoble (France)

    2009-11-01

    The improvement of the X-ray beam quality achieved on ID14-4 by the installation of new X-ray optical elements is described. ID14-4 at the ESRF is the first tunable undulator-based macromolecular crystallography beamline that can celebrate a decade of user service. During this time ID14-4 has not only been instrumental in the determination of the structures of biologically important molecules but has also contributed significantly to the development of various instruments, novel data collection schemes and pioneering radiation damage studies on biological samples. Here, the evolution of ID14-4 over the last decade is presented, and some of the major improvements that were carried out in order to maintain its status as one of the most productive macromolecular crystallography beamlines are highlighted. The experimental hutch has been upgraded to accommodate a high-precision diffractometer, a sample changer and a large CCD detector. More recently, the optical hutch has been refurbished in order to improve the X-ray beam quality on ID14-4 and to incorporate the most modern and robust optical elements used at other ESRF beamlines. These new optical elements will be described and their effect on beam stability discussed. These studies may be useful in the design, construction and maintenance of future X-ray beamlines for macromolecular crystallography and indeed other applications, such as those planned for the ESRF upgrade.

  7. Cysteine amide adduct formation from carboxylic acid drugs via UGT-mediated bioactivation in human liver microsomes.

    Science.gov (United States)

    Harada, H; Toyoda, Y; Endo, T; Kobayashi, M

    2015-10-01

    Although chemical trapping has been widely used to evaluate cytochrome P450-mediated drug bioactivation, thus far, only a few in vitro-trapping studies have been performed on UDP-glucuronosyltransferase (UGT)-mediated drug bioactivation. In this study, we used cysteine (Cys) as trapping agent to gain new insights into the UGT-mediated bioactivation involving acyl glucuronides of carboxylic acid drugs. Diclofenac, ketoprofen and ibuprofen were incubated in human liver microsomes with UDPGA and Cys, followed by analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The N-acyl-Cys amide adduct of diclofenac was characterized by mass analysis and was detectable even in photodiode array analysis. Our data indicated that the formation of such adducts reflects the reactivity of the corresponding acyl glucuronides. In addition, it was suggested that the adduct formation requires an N-terminal Cys moiety with both a free amine and a free thiol group, from the results using various cysteine derivatives. We propose that the S-acyl-Cys thioester adduct can form via transacylation of an acyl glucuronide and can then form to an N-acyl-Cys amide adduct through intramolecular S- to N-acyl rearrangement. This series of the reactions has important implications as a possible bioactivation mechanism for covalent binding of carboxylic acid drugs to macromolecules.

  8. Nutritional and biochemical properties of human milk: II. Lipids, micronutrients, and bioactive factors.

    Science.gov (United States)

    Rodriguez-Palmero, M; Koletzko, B; Kunz, C; Jensen, R

    1999-06-01

    Human milk lipids contain preformed LCPUFA in considerable amounts, which serve as precursors for the formation of prostaglandins, prostacyclins, and other lipid mediators, as well as essential components in membrane-rich tissues (such as the brain and the retina), thus affecting functional outcomes. Besides a balanced nutrient composition and a number of conditionally essential nutrients, human milk provides different types and classes of bioactive factors, such as enzymes, hormones, and growth factors, many of which appear to have a role in supporting infantile growth and development. The bioactive agents include antimicrobial factors (e.g., secretory IgA, oligosaccharides, FA); anti-inflammatory agents; transporters (e.g., lactoferrin); and digestive enzymes (e.g., BSSL). Several nonpeptide hormones (thyroid hormones, cortisol, progesterone, pregnanediol, estrogens, and artificial contraceptive) and peptide hormones and growth factors (erythropoietin, hHG, gonadotropin-releasing hormone, epidermal growth factor insulin, insulin-like growth factor-I, nerve growth factor, transforming growth factor-alpha, gastrointestinal regulatory peptides and thyroid-parathyroid hormones) have been isolated and quantitated in human milk. Some of these components are also involved in the maturation of the gastrointestinal tract of the infant. In addition to the passive benefits provided by human milk, several data support the hypothesis that breastfeeding promotes the development of the infant's own immune system, which might confer long-term benefits for the newborn infant. The risk of IDDM, Crohn's disease, and atopic disease is lower in individuals who had been breastfed during infancy. Areas of major interest in human milk research include the study of human milk synthesis and the contributions of dietary composition and maternal metabolism to human milk composition, infantile utilization of human milk components, and the study of bioactive components, such as

  9. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

    Science.gov (United States)

    García-Suástegui, W. A.; Ramos-Chávez, L. A.; Rubio-Osornio, M.; Calvillo-Velasco, M.; Atzin-Méndez, J. A.; Guevara, J.

    2017-01-01

    Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism. PMID:28163821

  10. Bioactivity studies of calcium magnesium silicate prepared from eggshell waste by sol–gel combustion synthesis

    Directory of Open Access Journals (Sweden)

    Rajan Choudhary

    2015-06-01

    Full Text Available The present study focused on the synthesis of calcium magnesium silicate (akermanite, Ca2MgSi2O7 using eggshell biowaste (as calcium source, magnesium nitrate and tetraethyl orthosilicate (TEOS as starting materials. Sol–gel combustion method was adopted to obtain calcium magnesium silicate. Citric acid was used as a fuel (reducing agent and nitrate ions present in the metal nitrates acts as an oxidizing agent during combustion process. The characterization of synthesized calcium magnesium silicate was carried out by powder X-ray diffraction (XRD, Fourier transform infrared (FTIR and scanning electron microscopy (SEM techniques. Calcium magnesium silicate crystallite size was observed in nano regime which can effectively mimic natural bone apatite composition. In-vitro bioactivity was investigated by immersing calcium magnesium silicate pellet in simulated body fluid (SBF for three weeks. Results show effective deposition of crystallized hydroxyapatite (HAP layer on its surface and predicting its possibilities for applications in hard tissue regeneration.

  11. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

    Directory of Open Access Journals (Sweden)

    W. A. García-Suástegui

    2017-01-01

    Full Text Available Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.

  12. Temperature sensitivity of soil microbial communities: An application of macromolecular rate theory to microbial respiration

    Science.gov (United States)

    Alster, Charlotte J.; Koyama, Akihiro; Johnson, Nels G.; Wallenstein, Matthew D.; Fischer, Joseph C.

    2016-06-01

    There is compelling evidence that microbial communities vary widely in their temperature sensitivity and may adapt to warming through time. To date, this sensitivity has been largely characterized using a range of models relying on versions of the Arrhenius equation, which predicts an exponential increase in reaction rate with temperature. However, there is growing evidence from laboratory and field studies that observe nonmonotonic responses of reaction rates to variation in temperature, indicating that Arrhenius is not an appropriate model for quantitatively characterizing temperature sensitivity. Recently, Hobbs et al. (2013) developed macromolecular rate theory (MMRT), which incorporates thermodynamic temperature optima as arising from heat capacity differences between isoenzymes. We applied MMRT to measurements of respiration from soils incubated at different temperatures. These soils were collected from three grassland sites across the U.S. Great Plains and reciprocally transplanted, allowing us to isolate the effects of microbial community type from edaphic factors. We found that microbial community type explained roughly 30% of the variation in the CO2 production rate from the labile C pool but that temperature and soil type were most important in explaining variation in labile and recalcitrant C pool size. For six out of the nine soil × inoculum combinations, MMRT was superior to Arrhenius. The MMRT analysis revealed that microbial communities have distinct heat capacity values and temperature sensitivities sometimes independent of soil type. These results challenge the current paradigm for modeling temperature sensitivity of soil C pools and understanding of microbial enzyme dynamics.

  13. Interaction of wall shear stress magnitude and gradient in the prediction of arterial macromolecular permeability.

    Science.gov (United States)

    LaMack, Jeffrey A; Himburg, Heather A; Li, Xue-Mei; Friedman, Morton H

    2005-04-01

    Large spatial shear stress gradients have anecdotally been associated with early atherosclerotic lesion susceptibility in vivo and have been proposed as promoters of endothelial cell dysfunction in vitro. Here, experiments are presented in which several measures of the fluid dynamic shear stress, including its gradient, at the walls of in vivo porcine iliac arteries, are correlated against the transendothelial macromolecular permeability of the vessels. The fluid dynamic measurements are based on postmortem vascular casts, and permeability is measured from Evans blue dye (EBD) uptake. Time-averaged wall shear stress (WSS), as well as a new parameter termed maximum gradient stress (MGS) that describes the spatial shear stress gradient due to flow acceleration at a given point, are mapped for each artery and compared on a point-by-point basis to the corresponding EBD patterns. While there was no apparent relation between MGS and EBD uptake, a composite parameter, WSS(-0.11) MGS(0.044), was highly correlated with permeability. Notwithstanding the small exponents, the parameter varied widely within the region of interest. The results suggest that sites exposed to low wall shear stresses are more likely to exhibit elevated permeability, and that this increase is exacerbated in the presence of large spatial shear stress gradients.

  14. Effect of the macromolecular architecture of biodegradable polyurethanes on the controlled delivery of ocular drugs.

    Science.gov (United States)

    da Silva, Gisele Rodrigues; da Silva Cunha, Armando; Ayres, Eliane; Oréfice, Rodrigo L

    2009-02-01

    Controlled delivery of drugs is a major issue in the treatment of ocular diseases, such as in the treatment of uveitis. In this study, dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, was incorporated into biodegradable polyurethanes (PU) having different macromolecular architectures. The biodegradable polyurethanes were obtained by preparing PU aqueous dispersions having poly(caprolactone) and/or poly(ethylene glycol) as soft segments. The drug was incorporated into the polymer by dissolving it in the PU aqueous dispersion. FTIR results showed the presence of the drug in the polymer with its original chemical structure. Small angle X-ray scattering (SAXS) results were explored to show that the incorporation of dexamethasone acetate led to the modification of the nanostructure of the polyurethane having only poly(caprolactone) as the soft segment, while the drug did not change significantly the microphase separated structure of PU having both poly(caprolactone) and poly(ethylene glycol) as soft segments. The evaluation of the release of the drug in vitro demonstrated that the obtained biodegradable polyurethanes were well succeeded in delivering dexamethasone acetate at an almost constant rate for 53 weeks. The presence of poly(ethylene glycol) together with poly(caprolactone) as soft segment in biodegradable PU was able to increase the rate of dexamethasone acetate release when compared to the rate of drug release from PU having only poly(caprolactone).

  15. Influence of temperature and macromolecular mobility on sorption of TCE on humic acid coated mineral surfaces.

    Science.gov (United States)

    Bell, Katherine Young; LeBoeuf, Eugene J

    2013-01-01

    This study demonstrates differences in sorptive capacity of volatile organic compound (VOC) trichloroethylene (TCE) onto natural organic matter (NOM) coated and uncoated mineral surfaces above and below the NOM glass transition temperature. TCE sorption isotherms for dry NOM-mineral systems below the NOM glass transition temperature (T(g)) demonstrated sorption behavior characteristic of micropore filling, with sorption capacities reduced relative to uncoated mineral matrices. Such differences were not entirely associated with differences in surface areas of the coated and uncoated mineral matrices, but were likely associated with either a blockage of pore space available to the VOC or a kinetic limitation that does not allow the VOC access to the internal porosity of the model soil within the time periods of the experiment. TCE sorption in dry NOM-mineral matrices above the T(g), however, was described in terms of sorption within a more fluid, macromolecular dissolution medium that does not hinder access to mineral surfaces. Such observations have potential important implications for modeling the fate and transport of VOCs in soils and sediment systems.

  16. IMAGINE: first neutron protein structure and new capabilities for neutron macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Munshi, Parthapratim [ORNL; Myles, Dean A A [ORNL; Robertson, Lee [ORNL; Stoica, Alexandru Dan [ORNL; Crow, Lowell [ORNL; Kovalevskyi, Andrii Y [ORNL; Koritsanszky, Tibor S [ORNL; Chakoumakos, Bryan C [ORNL; Blessing, Robert [Hauptman-Woodward Medical Research Institute; Meilleur, Flora [ORNL

    2013-01-01

    We report the first high resolution neutron protein structure of perdeuterated rubredoxin from Pyrococcus furiosus (PfRd) determined using the new IMAGINE macromolecular neutron crystallography instrument at the Oak Ridge National Laboratory. Neutron diffraction data extending to 1.65 resolution were collected from a relatively small 0.7 mm3 PfRd crystal using 2.5 days (60 h) of beam time. The refined structure contains 371 out of 391, or 95%, of the deuterium atoms of the protein, and 58 solvent molecules. The IMAGINE instrument is designed to provide neutron data at or near atomic resolutions (1.5 ) from crystals with volume < 1.0 mm3 and with unit cell edges < 100 . Beam line features include elliptical focusing mirrors that deliver 3x107 n s-1 cm-2 into a 3.5 x 2.0 mm2 focal spot at the sample position, and variable short and long wavelength cutoff optics that provide automated exchange between multiple wavelength configurations ( min=2.0 , 2.8 , 3.3 - max =3.0 , 4.0 , 4.5 , ~20 ). Notably, the crystal used to collect this PfRd data is 5-10 times smaller than has been previously reported.

  17. Enzyme activity determination on macromolecular substrates by isothermal titration calorimetry: application to mesophilic and psychrophilic chitinases.

    Science.gov (United States)

    Lonhienne, T; Baise, E; Feller, G; Bouriotis, V; Gerday, C

    2001-02-09

    Isothermal titration calorimetry has been applied to the determination of the kinetic parameters of chitinases (EC 3.2.1.14) by monitoring the heat released during the hydrolysis of chitin glycosidic bonds. Experiments were carried out using two different macromolecular substrates: a soluble polymer of N-acetylglucosamine and the insoluble chitin from crab shells. Different experimental temperatures were used in order to compare the thermodependence of the activity of two chitinases from the psychrophile Arthrobacter sp. TAD20 and of chitinase A from the mesophile Serratia marcescens. The method allowed to determine unequivocally the catalytic rate constant k(cat), the activation energy (E(a)) and the thermodynamic activation parameters (DeltaG(#), DeltaH(#), DeltaS(#)) of the chitinolytic reaction on the soluble substrate. The catalytic activity has also been determined on insoluble chitin, which displays an effect of substrate saturation by chitinases. On both substrates, the thermodependence of the activity of the psychrophilic chitinases was lower than that observed with the mesophilic counterpart.

  18. Chemical composition and structural features of the macromolecular components of plantation Acacia mangium wood.

    Science.gov (United States)

    Pinto, Paula C; Evtuguin, Dmitry V; Pascoal Neto, Carlos

    2005-10-05

    The wood of Acacia mangium, a prominent fast-growing plantation species used in the pulp-and-paper industry and, so far, poorly investigated for its chemical structure, was submitted to a detailed characterization of its main macromolecular components. Lignin (28% wood weight) isolated by mild acidolysis and characterized by permanganate oxidation, 1H and 13C NMR, and GPC, showed a very low content of syringylpropane-derived units (S:G:H of 48:49:3), a high degree of condensation, a low content of beta-O-4 ( approximately 0.40-0.43 per C6) structures, and a Mw of 2230. Glucuronoxylan (14% wood weight) isolated by alkaline (KOH) or by dimethyl sulfoxide extraction was characterized by methylation analysis, 1H NMR, and GPC. About 10% of the xylopyranose (Xylp) units constituting the linear backbone were substituted at O-2 with 4-O-methylglucuronic acid residues. Almost half of the Xylp units (45%) were O-2 (18%), O-3 (24%) or O-2,3 (3%) acetylated. X-ray diffraction analysis of cellulose (46% wood weight), isolated according to the Kürschner-Hoffer method, showed a degree of crystallinity of 67.6%.

  19. Synthesis and Self-Assembly of Amphiphilic Triblock Terpolymers with Complex Macromolecular Architecture

    KAUST Repository

    Polymeropoulos, George

    2015-11-25

    Two star triblock terpolymers (PS-b-P2VP-b-PEO)3 and one dendritic-like terpolymer [PS-b-P2VP-b-(PEO)2]3 of PS (polystyrene), P2VP (poly(2-vinylpyridine)), and PEO (poly(ethylene oxide)), never reported before, were synthesized by combining atom transfer radical and anionic polymerizations. The synthesis involves the transformation of the -Br groups of the previously reported Br-terminated 3-arm star diblock copolymers to one or two -OH groups, followed by anionic polymerization of ethylene oxide to afford the star or dendritic structure, respectively. The well-defined structure of the terpolymers was confirmed by static light scattering, size exclusion chromatography, and NMR spectroscopy. The self-assembly in solution and the morphology in bulk of the terpolymers, studied by dynamic light scattering and transmission electron microscopy, respectively, reveal new insights in the phase separation of these materials with complex macromolecular architecture. © 2015 American Chemical Society.

  20. Using support vector machines to improve elemental ion identification in macromolecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Morshed, Nader [University of California, Berkeley, CA 94720 (United States); Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Echols, Nathaniel, E-mail: nechols@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Adams, Paul D., E-mail: nechols@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); University of California, Berkeley, CA 94720 (United States)

    2015-05-01

    A method to automatically identify possible elemental ions in X-ray crystal structures has been extended to use support vector machine (SVM) classifiers trained on selected structures in the PDB, with significantly improved sensitivity over manually encoded heuristics. In the process of macromolecular model building, crystallographers must examine electron density for isolated atoms and differentiate sites containing structured solvent molecules from those containing elemental ions. This task requires specific knowledge of metal-binding chemistry and scattering properties and is prone to error. A method has previously been described to identify ions based on manually chosen criteria for a number of elements. Here, the use of support vector machines (SVMs) to automatically classify isolated atoms as either solvent or one of various ions is described. Two data sets of protein crystal structures, one containing manually curated structures deposited with anomalous diffraction data and another with automatically filtered, high-resolution structures, were constructed. On the manually curated data set, an SVM classifier was able to distinguish calcium from manganese, zinc, iron and nickel, as well as all five of these ions from water molecules, with a high degree of accuracy. Additionally, SVMs trained on the automatically curated set of high-resolution structures were able to successfully classify most common elemental ions in an independent validation test set. This method is readily extensible to other elemental ions and can also be used in conjunction with previous methods based on a priori expectations of the chemical environment and X-ray scattering.

  1. Visualization of X-ray Beam Using CdWO4 Crystal for Macromolecular Crystallography

    Directory of Open Access Journals (Sweden)

    Kazimierz J. Gofron

    2011-12-01

    Full Text Available In synchrotron diffraction experiments, it is typically assumed that the X-ray beam at the sample position is uniform, stable and has dimensions that are controlled by the focus and slits settings. As might be expected, this process is much more complex. We present here an investigation of the properties of a synchrotron X-ray beam at the sample position. The X-ray beam is visualized with a single crystal scintillator that converts X-ray photons into visible light photons, which can be imaged using Structure Biology Center (SBC on-axis and off-axis microscope optics. The X-ray penetration is dependent on the composition of the scintillator (especially the effective Z, and X-ray energy. Several scintillators have been used to visualize X-ray beams. Here we compare CdWO4, PbWO4, Bi4Ge3O12, Y3Al5O12:Ce (YAG:Ce, and Gd2O2S:Tb (phosphor. We determined that scintillator crystals made of CdWO4 and similar high-Z materials are best suited for the energy range (7–20 keV and are most suitable for beam visualization for macromolecular crystallography applications. These scintillators show excellent absorption, optical, and mechanical properties.

  2. FitEM2EM--tools for low resolution study of macromolecular assembly and dynamics.

    Directory of Open Access Journals (Sweden)

    Ziv Frankenstein

    Full Text Available Studies of the structure and dynamics of macromolecular assemblies often involve comparison of low resolution models obtained using different techniques such as electron microscopy or atomic force microscopy. We present new computational tools for comparing (matching and docking of low resolution structures, based on shape complementarity. The matched or docked objects are represented by three dimensional grids where the value of each grid point depends on its position with regard to the interior, surface or exterior of the object. The grids are correlated using fast Fourier transformations producing either matches of related objects or docking models depending on the details of the grid representations. The procedures incorporate thickening and smoothing of the surfaces of the objects which effectively compensates for differences in the resolution of the matched/docked objects, circumventing the need for resolution modification. The presented matching tool FitEM2EMin successfully fitted electron microscopy structures obtained at different resolutions, different conformers of the same structure and partial structures, ranking correct matches at the top in every case. The differences between the grid representations of the matched objects can be used to study conformation differences or to characterize the size and shape of substructures. The presented low-to-low docking tool FitEM2EMout ranked the expected models at the top.

  3. Involvement of lysosomes in the uptake of macromolecular material by bloodstream forms of Trypanosoma brucei.

    Science.gov (United States)

    Opperdoes, F R; Van Roy, J

    1982-09-01

    To investigate whether the lysosomes of Trypanosoma brucei are capable of uptake of macromolecules after internalization by the cell, we used Triton WR-1339, a non-digestible macromolecular compound, which is known to cause a marked decrease in the density of hepatic lysosomes due to massive intralysosomal storage. Intraperitoneal administration of 0.4 g/kg Triton WR-1339 to rats infected with T. brucei led to the development of a large vacuole in the trypanosomes between nucleus and kinetoplast within 22 h. Higher doses (2 g/kg) led to the disappearance of the trypanosomes from the blood and resulted in permanent cures (greater than 100 days). Lysosomes isolated from the trypanosomes of animals treated with a sub-curative dose showed a decrease in equilibrium density of 0.03 g/cm3 in sucrose gradients. These lysosomes were partly damaged as evidenced by a reduction in latency and an increase in the non-sedimentable part of lysosomal enzymes. We conclude that acid proteinase and alpha-mannosidase-containing organelles of T. brucei take up exogenous macromolecules and must therefore be considered as true lysosomes and that Triton WR-1339 acts in T. brucei as a true lysosomotropic drug. Its trypanocidal action probably results from an interference with lysosomal function.

  4. Large area high-resolution CCD-based X-ray detector for macromolecular crystallography

    CERN Document Server

    Pokric, M; Jorden, A R; Cox, M P; Marshall, A; Long, P G; Moon, K; Jerram, P A; Pool, P; Nave, C; Derbyshire, G E; Helliwell, J R

    2002-01-01

    An X-ray detector system for macromolecular crystallography based on a large area charge-coupled device (CCD) sensor has been developed as part of a large research and development programme for advanced X-ray sensor technology, funded by industry and the Particle Physics and Astronomy Research Council (PPARC) in the UK. The prototype detector consists of two large area three-sides buttable charge-coupled devices (CCD 46-62 EEV), where the single CCD area is 55.3 mmx41.5 mm. Overall detector imaging area is easily extendable to 85 mmx110 mm. The detector consists of an optically coupled X-ray sensitive phosphor, skewed fibre-optic studs and CCDs. The crystallographic measurement requirements at synchrotron sources are met through a high spatial resolution (2048x1536 pixel array), high dynamic range (approx 10 sup 5), a fast readout (approx 1 s), low noise (<10e sup -) and much reduced parallax error. Additionally, the prototype detector system has been optimised by increasing its efficiency at low X-ray ene...

  5. Proteinase K activity determination with β-galactosidase as sensitive macromolecular substrate.

    Science.gov (United States)

    Ghéczy, Nicolas; Küchler, Andreas; Walde, Peter

    2016-11-15

    Proteinase K from Engyodontium album (proK) is a relatively unspecific serine endopeptidase which is known to attack proteins yet in their native states. If the attacked protein is an enzyme, even a partial hydrolysis by proK may lead to an inactivation of the enzyme, which can be monitored by measuring the loss of catalytic activity of the attacked enzyme. E. coli β-galactosidase (β-Gal) was used in this work as such enzyme. It was found to be a convenient and sensitive macromolecular model substrate for comparing the "native protein-attacking ability" of free and immobilized proK at pH = 7.0 and 23 °C. The β-Gal activity was measured spectrophotometrically with o-nitrophenyl-β-galactopyranoside. Reproducible proK determinations were possible for as little as 4.3 ng proK by using a proK analyte solution of 10 nM. Compared to free proK, immobilized proK was much less efficient in inactivating β-Gal, most likely due to a decreased mobility of immobilized proK and a restricted accessibility of β-Gal to the active site of proK. Worth noting is, that under conditions at which β-Gal was completely inactivated by proK, the activity of hen egg lysozyme, horseradish peroxidase, or Aspergillus sp. glucose oxidase remained unaltered.

  6. Visualization of X-ray Beam Using CdWO4 Crystal for Macromolecular Crystallography

    Directory of Open Access Journals (Sweden)

    Kazimierz J. Gofron

    2011-12-01

    Full Text Available In synchrotron diffraction experiments, it is typically assumed that the X-ray beam at the sample position is uniform, stable and has dimensions that are controlled by the focus and slits settings. As might be expected, this process is much more complex. We present here an investigation of the properties of a synchrotron X-ray beam at the sample position. The X-ray beam is visualized with a single crystal scintillator that converts X-ray photons into visible light photons, which can be imaged using Structure Biology Center (SBC on-axis and off-axis microscope optics. The X-ray penetration is dependent on the composition of the scintillator (especially the effective Z, and X-ray energy. Several scintillators have been used to visualize X-ray beams. Here we compare CdWO4, PbWO4, Bi4Ge3O12, Y3Al5O12:Ce (YAG:Ce, and Gd2O2S:Tb (phosphor. We determined that scintillator crystals made of CdWO4 and similar high-Z materials are best suited for the energy range (7–20 keV and are most suitable for beam visualization for macromolecular crystallography applications. These scintillators show excellent absorption, optical, and mechanical properties.

  7. A graph theoretical approach for assessing bio-macromolecular complex structural stability.

    Science.gov (United States)

    Del Carpio, Carlos Adriel; Iulian Florea, Mihai; Suzuki, Ai; Tsuboi, Hideyuki; Hatakeyama, Nozomu; Endou, Akira; Takaba, Hiromitsu; Ichiishi, Eiichiro; Miyamoto, Akira

    2009-11-01

    Fast and proper assessment of bio macro-molecular complex structural rigidity as a measure of structural stability can be useful in systematic studies to predict molecular function, and can also enable the design of rapid scoring functions to rank automatically generated bio-molecular complexes. Based on the graph theoretical approach of Jacobs et al. [Jacobs DJ, Rader AJ, Kuhn LA, Thorpe MF (2001) Protein flexibility predictions using graph theory. Proteins: Struct Funct Genet 44:150-165] for expressing molecular flexibility, we propose a new scheme to analyze the structural stability of bio-molecular complexes. This analysis is performed in terms of the identification in interacting subunits of clusters of flappy amino acids (those constituting regions of potential internal motion) that undergo an increase in rigidity at complex formation. Gains in structural rigidity of the interacting subunits upon bio-molecular complex formation can be evaluated by expansion of the network of intra-molecular inter-atomic interactions to include inter-molecular inter-atomic interaction terms. We propose two indices for quantifying this change: one local, which can express localized (at the amino acid level) structural rigidity, the other global to express overall structural stability for the complex. The new system is validated with a series of protein complex structures reported in the protein data bank. Finally, the indices are used as scoring coefficients to rank automatically generated protein complex decoys.

  8. The status of the macromolecular crystallography beamlines at the European Synchrotron Radiation Facility

    Science.gov (United States)

    Mueller-Dieckmann, Christoph; Bowler, Matthew W.; Carpentier, Philippe; Flot, David; McCarthy, Andrew A.; Nanao, Max H.; Nurizzo, Didier; Pernot, Petra; Popov, Alexander; Round, Adam; Royant, Antoine; de Sanctis, Daniele; von Stetten, David; Leonard, Gordon A.

    2015-04-01

    The European Synchrotron Radiation Facility (ESRF) is the oldest and most powerful 3rd generation synchrotron in Europe, providing X-rays to more than 40 experimental stations welcoming several thousand researchers per year. A major success story has been the ESRF's facilities for macromolecular crystallography (MX). These are grouped around 3 straight sections: On ID23 canted undulators accommodate ID23-1, a mini-focus tuneable energy end station and ID23-2, the world's first micro-focus beamline dedicated to MX; ID29 houses a single, mini-focus, tuneable energy end station; ID30 will provide three end stations for MX due in operation from mid-2014 to early 2015. Here, one branch of a canted X-ray source feeds two fixed-energy end stations (MASSIF-1, MASSIF-3). The second feeds ID30B, a variable focus, tuneable energy beamline. MASSIF-1 is optimised for automatic high-throughput experiments requiring a relatively large beam size at the sample position, MASSIF-3 is a high-intensity, micro-focus facility designed to complement ID23-2. All end stations are highly automated, equipped with sample mounting robots and large area, fast-readout photon-counting detectors. Experiment control and tracking is achieved via a combination of the MXCuBE2 graphical user interface and the ISPyB database, the former allowing user-friendly control of all beamline components, the latter providing data tracking before, after and during experiments.

  9. SCIENTIFIC PRINCIPLES FOR MODIFICATION OF WATER-SOLUBLE POLYMERS. FORMATION OF MACROMOLECULAR COMPLEXES

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    The study of nanosecond dynamics of macromolecules with the luminescent methods make it possible to investigate the formation and functioning of polymeric complexes, polymeric conjugates and macromolecular metal complexes, which are widely used for solving many practical tasks. The nanosecond dynamics of macromolecules are a highly sensitive indicator of interpolymer complexes (IPC) formation. It enables us to solve the problems of studying IPC formation and stability and to investigate the interpolymer reactions of exchange and substitution. The investigation of changes in the rotational mobility of globular protein molecules as a whole makes it possible to determine the complex composition and its stability, and to control the course of polymer-protein conjugate formstion reaction. The nanosecond dynamics of polymers interacting with surfacants' ions (S)are the sensitive indicator of the S-polymer complex formation. A method for determining the equilibrium constants of the S-polymer complex formation was developed on the basis of the study of polymer chains mobility. It is established that nanosecond dynamics influences the course of chemical reactions in polymer chains. Moreover, the marked effect of the nanosecond dynamics is also revealed in the study of photophysical processes (the formation of excimers and energy migration of electron excitation) in polymers with photoactive groups. It was found that the efficiency of both processes increases with increasing the mobility of side chains, the carriers of photoactive groups.

  10. Macromolecular scaffolding: the relationship between nanoscale architecture and function in multichromophoric arrays for organic electronics.

    Science.gov (United States)

    Palermo, Vincenzo; Schwartz, Erik; Finlayson, Chris E; Liscio, Andrea; Otten, Matthijs B J; Trapani, Sara; Müllen, Klaus; Beljonne, David; Friend, Richard H; Nolte, Roeland J M; Rowan, Alan E; Samorì, Paolo

    2010-02-23

    The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

  11. A test of macromolecular crystallization in microgravity: large well ordered insulin crystals.

    Science.gov (United States)

    Borgstahl, G E; Vahedi-Faridi, A; Lovelace, J; Bellamy, H D; Snell, E H

    2001-08-01

    Crystals of insulin grown in microgravity on Space Shuttle Mission STS-95 were extremely well ordered and unusually large (many >2 mm). The physical characteristics of six microgravity and six earth-grown crystals were examined by X-ray analysis employing superfine phi slicing and unfocused synchrotron radiation. This experimental setup allowed hundreds of reflections to be precisely examined from each crystal in a short period of time. The microgravity crystals were on average 34 times larger, had sevenfold lower mosaicity, had 54-fold higher reflection peak heights and diffracted to significantly higher resolution than their earth-grown counterparts. A single mosaic domain model could account for the observed reflection profiles in microgravity crystals, whereas data from earth crystals required a model with multiple mosaic domains. This statistically significant and unbiased characterization indicates that the microgravity environment was useful for the improvement of crystal growth and the resultant diffraction quality in insulin crystals and may be similarly useful for macromolecular crystals in general.

  12. Characterization of PEG-Like Macromolecular Coatings on Plasma Modified NiTi Alloy

    Science.gov (United States)

    Yang, Jun; Gao, Jiacheng; Chang, Peng; Wang, Jianhua

    2008-04-01

    A poly (ethylene glycol) (PEG-like) coating was developed to improve the biocompatibility of Nickel-Titanium (NiTi) alloy implants. The PEG-like macromolecular coatings were deposited on NiTi substrates at a room temperature of 298 K through a ECR (electron-cyclotron resonance) cold-plasma enhanced chemical vapor deposition method using tetraglyme (CH3-O-(CH2-CH2-O)4-CH3) as a precursor. A power supply with a frequency of 2.45 GHz was applied to ignite the plasma with Ar(argon) used as the carrier gas. Based on the atomic force microscopy (AFM) studies, a thin smooth coating on NiTi substrates with highly amorphous functional groups on the modified NiTi surfaces were mainly the same accumulated stoichiometric ratio of C and O with PEG. The vitro studies showed that platelet-rich plasma (PRP) adsorption on the modified NiTi alloy surface was significantly reduced. This study indicated that plasma surface modification changes the surface components of NiTi alloy and subsequently improves its biocompatibility.

  13. Characterization of PEG-Like Macromolecular Coatings on Plasma Modified NiTi Alloy

    Institute of Scientific and Technical Information of China (English)

    YANG Jun; GAO Jiacheng; CHANG Peng; WANG Jianhua

    2008-01-01

    A poly(ethylene glycol) (PEG-like) coating was developed to improve the biocompatibility of Nickel-Titanium (NiTi) alloy implants. The PEG-like macromolecular coatings were deposited on NiTi substrates at a room temperature of 298 K through a ECR (electron-cyclotron resonance) cold-plasma .enhanced chemical vapor deposition method using tetraglyme (CH3-O(CH2-CH2-O)4-CH3) as a precursor. A power supply with a frequency of 2.45 GHz was applied to ignite the plasma with Ar(argon) used as the carrier gas. Based on the atomic force microscopy (AFM) studies, a thin smooth coating on NiTi substrates with highly amorphous functional groups on the modified NiTi surfaces were mainly the same accumulated stoichiometric ratio of C and O with PEG. The vitro studies showed that platelet-rich plasma (PRP) adsorption on the modified NiTi alloy surface was significantly reduced. This study indicated that plasma surface modification changes the surface components of NiTi alloy and subsequently improves its biocompatibility.

  14. Macromolecular depletion modulates the binding of red blood cells to activated endothelial cells.

    Science.gov (United States)

    Yang, Yang; Koo, Stephanie; Lin, Cheryl Shuyi; Neu, Björn

    2010-09-01

    Adhesion of red blood cells (RBCs) to endothelial cells (ECs) is usually insignificant but an enhanced adhesion has been observed in various diseases associated with vascular complications. This abnormal adhesion under pathological conditions such as sickle cell disease has been correlated with increased levels of various plasma proteins but the detailed underlying mechanism(s) remains unclear. Usually it is assumed that the proadhesive effects of plasma proteins originate from ligand interactions cross-linking receptors on adjacent cells, but explicit results detailing binding sites or receptors for some proteins (e.g., fibrinogen) on either RBC or EC surfaces that would support this model are missing. In this study, the authors tested whether there is an alternative mechanism. Their results demonstrate that dextran 2 MDa promotes the adhesion of normal RBCs to thrombin-activated ECs and that this effect becomes more pronounced with increasing thrombin concentration or with prolonged thrombin incubation time. It is concluded that depletion interaction originating from nonadsorbing macromolecules (i.e., dextran) can modulate the adhesion of red blood cells to thrombin-activated EC. This study thereby suggests macromolecular depletion as an alternative mechanism for the adhesion-promoting effects of nonadsorbing plasma proteins. These findings should not only aid in getting a better understanding of diseases associated with vascular complications but should also have many potential applications in biomedical or biotechnological areas that require the control of cell-cell or cell surface interactions.

  15. RoboDiff: combining a sample changer and goniometer for highly automated macromolecular crystallography experiments

    Science.gov (United States)

    Nurizzo, Didier; Bowler, Matthew W.; Caserotto, Hugo; Dobias, Fabien; Giraud, Thierry; Surr, John; Guichard, Nicolas; Papp, Gergely; Guijarro, Matias; Mueller-Dieckmann, Christoph; Flot, David; McSweeney, Sean; Cipriani, Florent; Theveneau, Pascal; Leonard, Gordon A.

    2016-01-01

    Automation of the mounting of cryocooled samples is now a feature of the majority of beamlines dedicated to macromolecular crystallography (MX). Robotic sample changers have been developed over many years, with the latest designs increasing capacity, reliability and speed. Here, the development of a new sample changer deployed at the ESRF beamline MASSIF-1 (ID30A-1), based on an industrial six-axis robot, is described. The device, named RoboDiff, includes a high-capacity dewar, acts as both a sample changer and a high-accuracy goniometer, and has been designed for completely unattended sample mounting and diffraction data collection. This aim has been achieved using a high level of diagnostics at all steps of the process from mounting and characterization to data collection. The RoboDiff has been in service on the fully automated endstation MASSIF-1 at the ESRF since September 2014 and, at the time of writing, has processed more than 20 000 samples completely automatically. PMID:27487827

  16. Distinct Contribution of Electrostatics, Initial Conformational Ensemble, and Macromolecular Stability in RNA Folding

    Energy Technology Data Exchange (ETDEWEB)

    Laederach,A.; Shcherbakova, I.; Jonikas, M.; Altman, R.; Brenowitz, M.

    2007-01-01

    We distinguish the contribution of the electrostatic environment, initial conformational ensemble, and macromolecular stability on the folding mechanism of a large RNA using a combination of time-resolved 'Fast Fenton' hydroxyl radical footprinting and exhaustive kinetic modeling. This integrated approach allows us to define the folding landscape of the L-21 Tetrahymena thermophila group I intron structurally and kinetically from its earliest steps with unprecedented accuracy. Distinct parallel pathways leading the RNA to its native form upon its Mg2+-induced folding are observed. The structures of the intermediates populating the pathways are not affected by variation of the concentration and type of background monovalent ions (electrostatic environment) but are altered by a mutation that destabilizes one domain of the ribozyme. Experiments starting from different conformational ensembles but folding under identical conditions show that whereas the electrostatic environment modulates molecular flux through different pathways, the initial conformational ensemble determines the partitioning of the flux. This study showcases a robust approach for the development of kinetic models from collections of local structural probes.

  17. MetalPDB: a database of metal sites in biological macromolecular structures.

    Science.gov (United States)

    Andreini, Claudia; Cavallaro, Gabriele; Lorenzini, Serena; Rosato, Antonio

    2013-01-01

    We present here MetalPDB (freely accessible at http://metalweb.cerm.unifi.it), a novel resource aimed at conveying the information available on the three-dimensional (3D) structures of metal-binding biological macromolecules in a consistent and effective manner. This is achieved through the systematic and automated representation of metal-binding sites in proteins and nucleic acids by way of Minimal Functional Sites (MFSs). MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure embedding the site(s), and are the central objects of MetalPDB design. MFSs are grouped into equistructural (broadly defined as sites found in corresponding positions in similar structures) and equivalent sites (equistructural sites that contain the same metals), allowing users to easily analyse similarities and variations in metal-macromolecule interactions, and to link them to functional information. The web interface of MetalPDB allows access to a comprehensive overview of metal-containing biological structures, providing a basis to investigate the basic principles governing the properties of these systems. MetalPDB is updated monthly in an automated manner.

  18. Effects of sound exposure on the growth and intracellular macromolecular synthesis of E. coli k-12

    Directory of Open Access Journals (Sweden)

    Shaobin Gu

    2016-04-01

    Full Text Available Microbes, as one of the primary producers of the biosphere, play an important role in ecosystems. Exploring the mechanism of adaptation and resistance of microbial population to various environmental factors has come into focus in the fields of modern microbial ecology and molecular ecology. However, facing the increasingly serious problem of acoustic pollution, very few efforts have been put forth into studying the relation of single cell organisms and sound field exposure. Herein, we studied the biological effects of sound exposure on the growth of E. coli K-12 with different acoustic parameters. The effects of sound exposure on the intracellular macromolecular synthesis and cellular morphology of E. coli K-12 were also analyzed and discussed. Experimental results indicated that E. coli K-12 exposed to sound waves owned a higher biomass and a faster specific growth rate compared to the control group. Also, the average length of E. coli K-12 cells increased more than 27.26%. The maximum biomass and maximum specific growth rate of the stimulation group by 8000 Hz, 80dB sound wave was about 1.7 times and 2.5 times that of the control group, respectively. Moreover, it was observed that E. coli K-12 can respond rapidly to sound stress at both the transcriptional and posttranscriptional levels by promoting the synthesis of intracellular RNA and total protein. Some potential mechanisms may be involved in the responses of bacterial cells to sound stress.

  19. Optimizing the spatial distribution of dose in X-ray macromolecular crystallography.

    Science.gov (United States)

    Zeldin, Oliver B; Gerstel, Markus; Garman, Elspeth F

    2013-01-01

    X-ray data collection for macromolecular crystallography can lead to highly inhomogeneous distributions of dose within the crystal volume for cases when the crystal is larger than the beam or when the beam is non-uniform (gaussian-like), particularly when crystal rotation is fully taken into account. Here the spatial distribution of dose is quantitatively modelled in order to compare the effectiveness of two dose-spreading data-collection protocols: helical scanning and translational collection. Their effectiveness in reducing the peak dose per unit diffraction is investigated via simulations for four common crystal shapes (cube, plate, long and short needles) and beams with a wide range of full width half maximum values. By inspection of the chosen metric, it is concluded that the optimum strategy is always to use as flat (top-hat) a beam as possible and to either match the beam size in both dimensions to the crystal, or to perform a helical scan with a beam which is narrow along the rotation axis and matched to the crystal size along the perpendicular axis. For crystal shapes where this is not possible, the reduction in peak dose per unit diffraction achieved through dose spreading is quantified and tabulated as a reference for experimenters.

  20. Competitive interactions of ligands and macromolecular crowders with maltose binding protein.

    Directory of Open Access Journals (Sweden)

    Andrew C Miklos

    Full Text Available Cellular signaling involves a cascade of recognition events occurring in a complex environment with high concentrations of proteins, polysaccharides, and other macromolecules. The influence of macromolecular crowders on protein binding affinity through hard-core repulsion is well studied, and possible contributions of protein-crowder soft attraction have been implicated recently. Here we present direct evidence for weak association of maltose binding protein (MBP with a polysaccharide crowder Ficoll, and that this association effectively competes with the binding of the natural ligand, maltose. Titration data over wide ranges of maltose and Ficoll concentrations fit well with a three-state competitive binding model. Broadening of MBP (1H-(15N TROSY spectra by the addition of Ficoll indicates weak protein-crowder association, and subsequent recovery of sharp NMR peaks upon addition of maltose indicates that the interactions of the crowder and the ligand with MBP are competitive. We hypothesize that, in the Escherichia coli periplasm, the competitive interactions of polysaccharides and maltose with MBP could allow MBP to shuttle between the peptidoglycan attached to the outer membrane and the ATP-binding cassette transporter in the inner membrane.