Methods of increasing secretion of polypeptides having biological activity

DOEpatents

Merino, Sandra

2014-10-28

The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

Methods of increasing secretion of polypeptides having biological activity

DOEpatents

Merino, Sandra

2015-04-14

The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

Methods of increasing secretion of polypeptides having biological activity

DOEpatents

Merino, Sandra

2013-10-01

The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

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

PubMed

Friedman, Mendel; Rasooly, Reuven

2013-04-23

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

Review of the Inhibition of Biological Activities of Food-Related Selected Toxins by Natural Compounds

PubMed Central

Friedman, Mendel; Rasooly, Reuven

2013-01-01

There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term ‘chemical genetics’ has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet. PMID:23612750

Biosynthesis and biological action of pineal allopregnanolone

PubMed Central

Tsutsui, Kazuyoshi; Haraguchi, Shogo

2014-01-01

The pineal gland transduces photoperiodic changes to the neuroendocrine system by rhythmic secretion of melatonin. We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ and actively produces a variety of neurosteroids de novo from cholesterol in birds. Notably, allopregnanolone is a major pineal neurosteroid that is far more actively produced in the pineal gland than the brain and secreted by the pineal gland in juvenile birds. Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds. Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death. Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3. It thus appears that pineal allopregnanolone prevents cell death of Purkinje cells by suppressing the activity of caspase-3 during development. This paper highlights new aspects of the biosynthesis and biological action of pineal allopregnanolone. PMID:24834027

Biologic Potential of Calcium Phosphate Biopowders Produced via Decomposition Combustion Synthesis

PubMed Central

Vollmer, N.; King, K.B.; Ayers, R.

2015-01-01

The aim of this research was to evaluate the biologic potential of calcium phosphate (CaP) biopowders produced with a novel reaction synthesis system. Decomposition combustion synthesis (DCS) is a modified combustion synthesis method capable of producing CaP powders for use in bone tissue engineering applications. During DCS, the stoichiometric ratio of reactant salt to fuel was adjusted to alter product chemistry and morphology. In vitro testing methods were utilized to determine the effects of controlling product composition on cytotoxicity, proliferation, biocompatibility and biomineralization. In vitro, human fetal osteoblasts (ATCC, CRL-11372) cultured with CaP powder displayed a flattened morphology, and uniformly encompassed the CaP particulates. Matrix vesicles containing calcium and phosphorous budded from the osteoblast cells. CaP powders produced via DCS are a source of biologically active, synthetic, bone graft substitute materials PMID:26034341

Cysteine Cathepsins in the Secretory Vesicle Produce Active Peptides: Cathepsin L Generates Peptide Neurotransmitters and Cathepsin B Produces Beta-Amyloid of Alzheimer’s Disease

PubMed Central

Hook, Vivian; Funkelstein, Lydiane; Wegrzyn, Jill; Bark, Steven; Kindy, Mark; Hook, Gregory

2011-01-01

Recent new findings indicate significant biological roles of cysteine cathepsin proteases in secretory vesicles for production of biologically active peptides. Notably, cathepsin L in secretory vesicles has been demonstrated as a key protease for proteolytic processing of proneuropeptides (and prohormones) into active neuropeptides that are released to mediate cell-cell communication in the nervous system for neurotransmission. Moreover, cathepsin B in secretory vesicles has been recently identified as a β-secretase for production of neurotoxic β-amyloid (Aβ) peptides that accumulate in Alzheimer’s disease (AD), participating as a notable factor in the severe memory loss in AD. These secretory vesicle functions of cathepsins L and B for production of biologically active peptides contrasts with the well-known role of cathepsin proteases in lysosomes for the degradation of proteins to result in their inactivation. The unique secretory vesicle proteome indicates proteins of distinct functional categories that provide the intravesicular environment for support of cysteine cathepsin function. Features of the secretory vesicle protein systems insure optimized intravesicular conditions that support the proteolytic activity of cathepsins. These new findings of recently discovered biological roles of cathepsins L and B indicate their significance in human health and disease. PMID:21925292

Fungal Phytotoxins with Potential Herbicidal Activity to Control Chenopodium album.

PubMed

Cimmino, Alessio; Masi, Marco; Evidente, Marco; Evidente, Antonio

2015-06-01

This review deals with the isolation and chemical and biological characterization of phytotoxins produced by Ascochyta caulina and Phoma chenopodiicola proposed as mycoherbicides for the biological control of Chenopodium album, a worldwide spread weed which causes serious problems to some agrarian crops, including sugar beet and maize. Studies on the structure activity relationships and on the modes of actions of toxins isolated are also described, as well as the optimization of analytical methods focused on selection of the best fungal toxin producers. The attempts to scale up production of these phytotoxins aimed to obtain sufficient amounts for their application in greenhouse and field trials are also reported.

[Methodology of Screening New Antibiotics: Present Status and Prospects].

PubMed

Trenin, A S

2015-01-01

Due to extensive distribution of pathogen resistance to available pharmaceuticals and serious problems in the treatment of various infections and tumor diseases, the necessity of new antibiotics is urgent. The basic methodological approaches to chemical synthesis of antibiotics and screening of new antibiotics among natural products, mainly among microbial secondary metabolites, are considered in the review. Since the natural compounds are very much diverse, screening of such substances gives a good opportunity to discover antibiotics of various chemical structure and mechanism of action. Such an approach followed by chemical or biological transformation, is capable of providing the health care with new effective pharmaceuticals. The review is mainly concentrated on screening of natural products and methodological problems, such as: isolation of microbial producers from the habitats, cultivation of microorganisms producing appropriate substances, isolation and chemical characterization of microbial metabolites, identification of the biological activity of the metabolites. The main attention is paid to the problems of microbial secondary metabolism and design of new models for screening biologically active compounds. The last achievements in the field of antibiotics and most perspective approaches to future investigations are discussed. The main methodological approach to isolation and cultivation of the producers remains actual and needs constant improvement. The increase of the screening efficiency can be achieved by more rapid chemical identification of antibiotics and design of new screening models based on the biological activity detection.

Pharmaceutically active secondary metabolites of marine actinobacteria.

PubMed

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2014-04-01

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

Biological consilience of hydrogen sulfide and nitric oxide in plants: Gases of primordial earth linking plant, microbial and animal physiologies.

PubMed

Yamasaki, Hideo; Cohen, Michael F

2016-05-01

Hydrogen sulfide (H2S) is produced in the mammalian body through the enzymatic activities of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). A growing number of studies have revealed that biogenic H2S produced in tissues is involved in a variety of physiological responses in mammals including vasorelaxation and neurotransmission. It is now evident that mammals utilize H2S to regulate multiple signaling systems, echoing the research history of the gaseous signaling molecules nitric oxide (NO) and carbon monoxide (CO) that had previously only been recognized for their cytotoxicity. In the human diet, meats (mammals, birds and fishes) and vegetables (plants) containing cysteine and other sulfur compounds are the major dietary sources for endogenous production of H2S. Plants are primary producers in ecosystems on the earth and they synthesize organic sulfur compounds through the activity of sulfur assimilation. Although plant H2S-producing activities have been known for a long time, our knowledge of H2S biology in plant systems has not been updated to the extent of mammalian studies. Here we review recent progress on H2S studies, highlighting plants and bacteria. Scoping the future integration of H2S, NO and O2 biology, we discuss a possible linkage between physiology, ecology and evolutional biology of gas metabolisms that may reflect the historical changes of the Earth's atmospheric composition. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional inclusion bodies produced in the yeast Pichia pastoris.

PubMed

Rueda, Fabián; Gasser, Brigitte; Sánchez-Chardi, Alejandro; Roldán, Mònica; Villegas, Sandra; Puxbaum, Verena; Ferrer-Miralles, Neus; Unzueta, Ugutz; Vázquez, Esther; Garcia-Fruitós, Elena; Mattanovich, Diethard; Villaverde, Antonio

2016-10-01

Bacterial inclusion bodies (IBs) are non-toxic protein aggregates commonly produced in recombinant bacteria. They are formed by a mixture of highly stable amyloid-like fibrils and releasable protein species with a significant extent of secondary structure, and are often functional. As nano structured materials, they are gaining biomedical interest because of the combination of submicron size, mechanical stability and biological activity, together with their ability to interact with mammalian cell membranes for subsequent cell penetration in absence of toxicity. Since essentially any protein species can be obtained as IBs, these entities, as well as related protein clusters (e.g., aggresomes), are being explored in biocatalysis and in biomedicine as mechanically stable sources of functional protein. One of the major bottlenecks for uses of IBs in biological interfaces is their potential contamination with endotoxins from producing bacteria. To overcome this hurdle, we have explored here the controlled production of functional IBs in the yeast Pichia pastoris (Komagataella spp.), an endotoxin-free host system for recombinant protein production, and determined the main physicochemical and biological traits of these materials. Quantitative and qualitative approaches clearly indicate the formation of IBs inside yeast, similar in morphology, size and biological activity to those produced in E. coli, that once purified, interact with mammalian cell membranes and penetrate cultured mammalian cells in absence of toxicity. Structurally and functionally similar from those produced in E. coli, the controlled production of IBs in P. pastoris demonstrates that yeasts can be used as convenient platforms for the biological fabrication of self-organizing protein materials in absence of potential endotoxin contamination and with additional advantages regarding, among others, post-translational modifications often required for protein functionality.

Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal Macrophage Activation.

PubMed

Kozicky, Lisa; Sly, Laura M

2017-12-26

Macrophages are phagocytic innate immune cells, which initiate immune responses to pathogens and contribute to healing and tissue restitution. Macrophages are equally important in turning off inflammatory responses. We have shown that macrophages stimulated with intravenous immunoglobulin (IVIg) can produce high amounts of the anti-inflammatory cytokine, interleukin 10 (IL-10), and low levels of pro-inflammatory cytokines in response to bacterial lipopolysaccharides (LPS). IVIg is a polyvalent antibody, primarily immunoglobulin Gs (IgGs), pooled from the plasma of more than 1,000 blood donors. It is used to supplement antibodies in patients with immune deficiencies or to suppress immune responses in patients with autoimmune or inflammatory conditions. Infliximab, a therapeutic anti-tumor necrosis factor alpha (TNFα) antibody, has also been shown to activate macrophages to produce IL-10 in response to inflammatory stimuli. IVIg and other antibody-based biologics can be tested to determine their effects on macrophage activation. This paper describes methods for derivation, stimulation, and assessment of murine bone marrow macrophages activated by antibodies in vitro and murine peritoneal macrophages activated with antibodies in vivo. Finally, we demonstrate the use of western blotting to determine the contribution of specific cell signaling pathways to anti-inflammatory macrophage activity. These protocols can be used with genetically modified mice, to determine the effect of a specific protein(s) on anti-inflammatory macrophage activation. These techniques can also be used to assess whether specific biologics may act by changing macrophages to an IL-10-producing anti-inflammatory activation state that reduces inflammatory responses in vivo. This can provide information on the role of macrophage activation in the efficacy of biologics during disease models in mice, and provide insight into a potential new mechanism of action in people. Conversely, this may caution against the use of specific antibody-based biologics to treat infectious disease, particularly if macrophages play an important role in host defense against that infection.

Novel chlorinated dibenzofurans isolated from the cellular slime mold, Polysphondylium filamentosum, and their biological activities.

PubMed

Kikuchi, Haruhisa; Kubohara, Yuzuru; Nguyen, Van Hai; Katou, Yasuhiro; Oshima, Yoshiteru

2013-08-01

Cellular slime molds are expected to have the huge potential for producing secondary metabolites including polyketides, and we have studied the diversity of secondary metabolites of cellular slime molds for their potential utilization as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium filamentosum, we obtained new chlorinated benzofurans Pf-1 (4) and Pf-2 (5) which display multiple biological activities; these include stalk cell differentiation-inducing activity in the well-studied cellular slime mold, Dictyostelium discoideum, and inhibitory activities on cell proliferation in mammalian cells and gene expression in Drosophila melanogaster. Copyright © 2013 Elsevier Ltd. All rights reserved.

Streptomyces metabolites in divergent microbial interactions.

PubMed

Takano, Hideaki; Nishiyama, Tatsuya; Amano, Sho-ichi; Beppu, Teruhiko; Kobayashi, Michihiko; Ueda, Kenji

2016-03-01

Streptomyces and related bacteria produce a wide variety of secondary metabolites. Of these, many compounds have industrial applications, but the question of why this group of microorganism produces such various kinds of biologically active substances has not yet been clearly answered. Here, we overview the results from our studies on the novel function and role of Streptomyces metabolites. The diverged action of negative and positive influences onto the physiology of various microorganisms infers the occurrence of complex microbial interactions due to the effect of small molecules produced by Streptomyces. The interactions may serve as a basis for the constitution of biological community.

Biologically Active Metabolites Synthesized by Microalgae

PubMed Central

Costa, Jorge Alberto Vieira

2015-01-01

Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences. PMID:26339647

Effect of Producing Different Phenazines on Bacterial Fitness and Biological Control in Pseudomonas chlororaphis 30-84

PubMed Central

Yu, Jun Myoung; Wang, Dongping; Pierson, Leland S.; Pierson, Elizabeth A.

2018-01-01

Pseudomonas chlororaphis 30-84 is a biological control agent selected for its ability to suppress diseases caused by fungal pathogens. P. chlororaphis 30-84 produces three phenazines: phenazine-1-carboxylic acid (PCA), 2-hydroxy-phenazine-1-carboxylic acid (2OHPCA) and a small amount of 2-hydroxy-phenazine (2OHPHZ), and these are required for fungal pathogen inhibition and wheat rhizosphere competence. The two, 2-hydroxy derivatives are produced from PCA via the activity of a phenazine-modifying enzyme encoded by phzO. In addition to the seven biosynthetic genes responsible for the production of PCA, many other Pseudomonas strains possess one or more modifying genes, which encode enzymes that act independently or together to convert PCA into other phenazine derivatives. In order to understand the fitness effects of producing different phenazines, we constructed isogenic derivatives of P. chlororaphis 30-84 that differed only in the type of phenazines produced. Altering the type of phenazines produced by P. chlororaphis 30-84 enhanced the spectrum of fungal pathogens inhibited and altered the degree of take-all disease suppression. These strains also differed in their ability to promote extracellular DNA release, which may contribute to the observed differences in the amount of biofilm produced. All derivatives were equally important for survival over repeated plant/harvest cycles, indicating that the type of phenazines produced is less important for persistence in the wheat rhizosphere than whether or not cells produce phenazines. These findings provide a better understanding of the effects of different phenazines on functions important for biological control activity with implications for applications that rely on introduced or native phenazine producing populations. PMID:29422787

A zinc-dependent epitope on the molecule of thymulin, a thymic hormone.

PubMed Central

Dardenne, M; Savino, W; Berrih, S; Bach, J F

1985-01-01

Thymulin is a nonapeptide hormone produced by thymic epithelial cells. Its biological activity is strictly dependent on the presence of the metal zinc in the molecule. Antithymulin monoclonal antibodies have been produced against either the synthetic (AS1) or the natural intraepithelial (AE1) molecule. These monoclonal antibodies were screened for their abilities to inhibit the zinc-dependent biological activity of the hormone and were shown to bind to thymic epithelial cells. By using biological and immunofluorescence assays, the two antibodies were shown to recognize exclusively the zinc-coupled thymulin molecule. Other antithymulin antibodies screened by RIA or ELISA (using a zinc-deprived substrate) recognized a zinc-independent epitope on the thymulin molecule. These data indicate the existence of a zinc-specific conformation on the thymulin molecule. They are in agreement with NMR studies showing that the zinc-containing hormone has a unique structure. Images PMID:2413455

Application of Oxygen-Enriched Aeration in the Production of Bacitracin by Bacillus licheniformis

PubMed Central

Flickinger, M. C.; Perlman, D.

1979-01-01

The physiological effects of controlling the dissolved oxygen tension at 0.01, 0.02, and 0.05 atm by the use of oxygen-enriched aeration were investigated during growth and bacitracin production by Bacillus licheniformis ATCC 10716. Up to a 2.35-fold increase in the final antibiotic yield and a 4-fold increase in the rate of bacitracin synthesis were observed in response to O2-enriched aeration. The increase in antibiotic production was accompanied by increased respiratory activity and an increase in the specific productivity of the culture from 1.3 to 3.6 g of antibiotic per g of cell mass produced. Oxygen enrichment of the aeration decreased medium carbohydrate uptake and the maximum specific growth rate of B. licheniformis from 0.6 h−1 to as low as 0.15 h−1, depending upon the level of enrichment and the conditions of oxygen transfer rate (impeller speed). The response of this culture to O2 enrichment suggests that this method of controlling the dissolved oxygen tension for antibiotic-producing cultures may simulate conditions that would occur if the carbon source were fed slowly, as is often employed to optimize antibiotic production. Analysis of the biologically active bacitracins produced by B. licheniformis ATCC 10716 suggested that the ratio of biologically active peptides was not changed by O2 enrichment, nor were any new biologically active compounds formed. Images PMID:34361

Milk inhibits the biological activity of ricin

USDA-ARS?s Scientific Manuscript database

Ricin is a highly toxic protein produced by the castor plant Ricinus communis. The toxin is relatively easy to isolate and can be used as a biological weapon. There is great interest in identifying effective inhibitors for ricin. In this study, we demonstrated by three independent assays that compon...

Martinomycin, a new polyether antibiotic produced by Streptomyces salvialis. I. Taxonomy, fermentation and biological activity.

PubMed

Bernan, V S; Montenegro, D A; Goodman, J J; Alluri, M R; Carter, G T; Abbanat, D R; Pearce, C J; Maiese, W M; Greenstein, M

1994-12-01

Actinomycete culture LL-D37187 has been found to produce the new polyether antibiotic martinomycin. Taxonomic studies, including morphological, physiological, and cell wall chemistry analyses, revealed that culture LL-D37187 is a novel streptomycete species, and the proposed name is Streptomyces salvialis. Martinomycin exhibits activity against the Southern Army Worm (Spodoptera eridania) and Gram-positive bacteria.

Steroidogenesis in the skin: implications for local immune functions

PubMed Central

Slominski, Andrzej; Zbytek, Bazej; Nikolakis, Georgios; Manna, Pulak R.; Skobowiat, Cezary; Zmijewski, Michal; Li, Wei; Janjetovic, Zorica; Postlethwaite, Arnold; Zouboulis, Christos C.; Tuckey, Robert C.

2013-01-01

The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases. PMID:23435015

Phylogenetic Diversity and Biological Activity of Actinobacteria Isolated from the Chukchi Shelf Marine Sediments in the Arctic Ocean

PubMed Central

Yuan, Meng; Yu, Yong; Li, Hui-Rong; Dong, Ning; Zhang, Xiao-Hua

2014-01-01

Marine environments are a rich source of Actinobacteria and have the potential to produce a wide variety of biologically active secondary metabolites. In this study, we used four selective isolation media to culture Actinobacteria from the sediments collected from the Chukchi Shelf in the Arctic Ocean. A total of 73 actinobacterial strains were isolated. Based on repetitive DNA fingerprinting analysis, we selected 30 representatives for partial characterization according to their phylogenetic diversity, antimicrobial activities and secondary-metabolite biosynthesis genes. Results from the 16S rRNA gene sequence analysis indicated that the 30 strains could be sorted into 18 phylotypes belonging to 14 different genera: Agrococcus, Arsenicicoccus, Arthrobacter, Brevibacterium, Citricoccus, Janibacter, Kocuria, Microbacterium, Microlunatus, Nocardioides, Nocardiopsis, Saccharopolyspora, Salinibacterium and Streptomyces. To our knowledge, this paper is the first report on the isolation of Microlunatus genus members from marine habitats. Of the 30 isolates, 11 strains exhibited antibacterial and/or antifungal activity, seven of which have activities against Bacillus subtilis and Candida albicans. All 30 strains have at least two biosynthetic genes, one-third of which possess more than four biosynthetic genes. This study demonstrates the significant diversity of Actinobacteria in the Chukchi Shelf sediment and their potential for producing biologically active compounds and novel material for genetic manipulation or combinatorial biosynthesis. PMID:24663116

Antimicrobial activities of endophytic fungi obtained from the arid zone invasive plant Opuntia dillenii and the isolation of equisetin, from endophytic Fusarium sp.

PubMed

Ratnaweera, Pamoda B; de Silva, E Dilip; Williams, David E; Andersen, Raymond J

2015-07-10

Opuntia dillenii is an invasive plant well established in the harsh South-Eastern arid zone of Sri Lanka. Evidence suggests it is likely that the endophytic fungal populations of O. dillenii assist the host in overcoming biotic and abiotic stress by producing biologically active metabolites. With this in mind there is potential to discover novel natural products with useful biological activities from this hitherto poorly investigated source. Consequently, an investigation of the antimicrobial activities of the endophytes of O. dillenii, that occupies a unique ecological niche, may well provide useful leads in the discovery of new pharmaceuticals. Endophytic fungi were isolated from the surface sterilized cladodes and flowers of O. dillenii using several nutrient media and the antimicrobial activities were evaluated against three Gram-positive and two Gram-negative bacteria and Candida albicans. The two most bioactive fungi were identified by colony morphology and DNA sequencing. The secondary metabolite of the endophyte Fusarium sp. exhibiting the best activity was isolated via bioassay guided chromatography. The chemical structure was elucidated from the ESIMS and NMR spectroscopic data obtained for the active metabolite. The minimum inhibitory concentrations (MICs) of the active compound were determined. Eight endophytic fungi were isolated from O. dillenii and all except one showed antibacterial activities against at least one of the test bacteria. All extracts were inactive against C. albicans. The most bioactive fungus was identified as Fusarium sp. and the second most active as Aspergillus niger. The structure of the major antibacterial compound of the Fusarium sp. was shown to be the tetramic acid derivative, equisetin. The MIC's for equisetin were 8 μg mL(-1) against Bacillus subtilis, 16 μg mL(-1) against Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus (MRSA). O. dillenii, harbors several endophytic fungi capable of producing antimicrobial substances with selective antibacterial properties. By producing biologically active secondary metabolites, such as equisetin isolated from the endophytic Fusarium sp., the endophytic fungal population may be assisting the host to successfully withstand stressful environmental conditions. Further investigations on the secondary metabolites produced by these endophytes may provide additional drug leads.

A comparative pharmacological investigation of three samples of 'Guduchi ghrita' for adaptogenic activity against forced swimming induced gastric ulceration and hematological changes in albino rats

PubMed Central

Savrikar, Shriram S.; Dole, Vilas; Ravishankar, B.; Shukla, Vinay J.

2010-01-01

This study was undertaken to investigate the impact of formulation factors and adjuvants on the expression of biological activity of Tinospora cordifolia (Willd.) Miers. The adaptogenic effect of three samples of Guduchi ghrita, prepared using plain ghee (clarified butter) obtained from three different sources was studied in albino rats and compared with expressed juice of stem of Guduchi. The test preparations were evaluated against forced–swimming induced hypothermia, gastric ulceration and changes in the hematological parameters. The test drug given in the form of 'ghrita' produced better effect in comparison to the expressed juice. Among the three 'ghrita' preparations evaluated, only the 'Solapur Guduchi ghrita' (SGG) was found to produce significant inhibition of stress hypothermia and gastric ulceration. The other two preparations 'Nanded Guduchi ghrita' (NGG), and 'Wardha Guduchi ghrita' (WGG) could produce only a marginal effect. In hematological parameters 'Guduchi' juice produced better reversal of the stress-induced changes in comparison to the test 'ghrita' preparations. The present study provides evidence highlighting the importance of formulation factors for the expression of biological activity. PMID:20814518

Challenges and complexity of functionality evaluation of flavan-3-ol derivatives.

PubMed

Saito, Akiko

2017-06-01

Flavan-3-ol derivatives are common plant-derived bioactive compounds. In particular, (-)-epigallocatechin-3-O-gallate shows various moderate biological activities without severe toxicity, and its health-promoting effects have been widely studied because it is a main ingredient in green tea and is commercially available at low cost. Although various biologically active flavan-3-ol derivatives are present as minor constituents in plants as well as in green tea, their biological activities have yet to be revealed, mainly due to their relative unavailability. Here, I outline the major factors contributing to the complexity of functionality studies of flavan-3-ol derivatives, including proanthocyanidins and oligomeric flavan-3-ols. I emphasize the importance of conducting structure-activity relationship studies using synthesized flavan-3-ol derivatives that are difficult to obtain from plant extracts in pure form to overcome this challenge. Further discovery of these minor constituents showing strong biological activities is expected to produce useful information for the development of functional health foods.

Biological control products for aflatoxin prevention in Italy: Commercial field evaluation of atoxigenic A.flavus active ingredients

USDA-ARS?s Scientific Manuscript database

Since 2003, non-compliant aflatoxin concentrations have been detected in maize produced in Italy. The most successful worldwide experiments in aflatoxin prevention resulted from distribution of atoxigenic strains of Aspergillus flavus to displace aflatoxin-producers during crop development. The disp...

Erabulenols, inhibitors of cholesteryl ester transfer protein produced by Penicillium sp. FO-5637. I.Production, isolation and biological properties.

PubMed

Tomoda, H; Tabata, N; Masuma, R; Si, S Y; Omura, S

1998-07-01

Penicillium sp. FO-5637, a soil isolate, was found to produce a series of inhibitors of cholesteryl ester transfer protein (CETP). Novel active compounds, designated erabulenols A and B, were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and HPLC. Erabulenols A and B inhibit human CETP activity with IC50 values of 47.7 and 58.2 microM in an in vitro assay system containing 200 microM BSA, respectively.

Use of the short-term inflammatory response in the mouse peritoneal cavity to assess the biological activity of leached vitreous fibers.

PubMed Central

Donaldson, K; Addison, J; Miller, B G; Cullen, R T; Davis, J M

1994-01-01

We used a special-purpose glass microfiber sample, Johns-Manville Code 100/475, to study the effects of various acid and alkali treatments on biological activity as assessed by inflammation in the mouse peritoneal cavity, the leaching of Si, and the phase contrast optical microscopy (PCOM) fiber number. We used mild and medium treatments with oxalic acid and Tris buffer and harsh treatment with concentrated HCl and NaOH. Mild oxalic acid and Tris treatment for 2 weeks had no effect on any of the end-points, but prolonging the mild oxalic acid treatment time to 2 months reduced the biological activity and the fiber number. Medium oxalic acid treatment reduced the biological activity and the fiber number and caused a loss of Si. Medium Tris alkali treatment reduced the PCOM-countable fibers and the biological activity but did not cause a substantial loss of Si. Harsh treatment with strong HCl did not affect the fiber number or cause leaching but the biological activity was reduced; strong NaOH reduced the fiber number and biological activity, and caused marked leaching of Si. The medium oxalic acid conditions (pH 1.4) were more acid than those found in lung cells but produced the same effects (reduction in fiber number and biological activity) as the more physiological mild treatment (pH 4.0), when prolonged. This study suggests that medium oxalic acid treatment can be used as a short-term assay to compare loss of Si, reduction in fiber number, and change in biological activity of vitreous fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882922

Endophytic actinobacteria: Diversity, secondary metabolism and mechanisms to unsilence biosynthetic gene clusters.

PubMed

Dinesh, Raghavan; Srinivasan, Veeraraghavan; T E, Sheeja; Anandaraj, Muthuswamy; Srambikkal, Hamza

2017-09-01

Endophytic actinobacteria, which reside in the inner tissues of host plants, are gaining serious attention due to their capacity to produce a plethora of secondary metabolites (e.g. antibiotics) possessing a wide variety of biological activity with diverse functions. This review encompasses the recent reports on endophytic actinobacterial species diversity, in planta habitats and mechanisms underlying their mode of entry into plants. Besides, their metabolic potential, novel bioactive compounds they produce and mechanisms to unravel their hidden metabolic repertoire by activation of cryptic or silent biosynthetic gene clusters (BGCs) for eliciting novel secondary metabolite production are discussed. The study also reviews the classical conservative techniques (chemical/biological/physical elicitation, co-culturing) as well as modern microbiology tools (e.g. next generation sequencing) that are being gainfully employed to uncover the vast hidden scaffolds for novel secondary metabolites produced by these endophytes, which would subsequently herald a revolution in drug engineering. The potential role of these endophytes in the agro-environment as promising biological candidates for inhibition of phytopathogens and the way forward to thoroughly exploit this unique microbial community by inducing expression of cryptic BGCs for encoding unseen products with novel therapeutic properties are also discussed.

Effects of enterally- and parenterally-administered bombesin on intestinal luminal tryptic activity and protein in the suckling rat.

PubMed

Pollack, P F; Adamson, C; Koldovsky, O

1989-04-15

Because of the presence of bombesin-like immunoreactivity in milk, we investigated if enteral administration of bombesin affects the intestinal luminal content of trypsin and protein in 12-14-day-old rats. Bombesin (40 micrograms/kg), given either orogastrically or subcutaneously, produced a significant elevation in the intestinal content of trypsin activity. Thus, enterally-administered bombesin can produce acute biologic effects in suckling rats.

Natural Product Potential of the Genus Nocardiopsis

PubMed Central

Ibrahim, Alyaa Hatem; Desoukey, Samar Yehia; Fouad, Mostafa A.; Kamel, Mohamed Salah; Gulder, Tobias A. M.; Abdelmohsen, Usama Ramadan

2018-01-01

Actinomycetes are a relevant source of novel bioactive compounds. One of the pharmaceutically and biotechnologically important genera that attract natural products research is the genus Nocardiopsis, mainly for its ability to produce a wide variety of secondary metabolites accounting for its wide range of biological activities. This review covers the literature from January 2015 until February 2018 making a complete survey of all the compounds that were isolated from the genus Nocardiopsis, their biological activities, and natural sources, whenever applicable. PMID:29710816

Cell-Specific Production and Antimicrobial Activity of Naphthoquinones in Roots of Lithospermum erythrorhizon1

PubMed Central

Brigham, Lindy A.; Michaels, Paula J.; Flores, Hector E.

1999-01-01

Pigmented naphthoquinone derivatives of shikonin are produced at specific times and in specific cells of Lithospermum erythrorhizon roots. Normal pigment development is limited to root hairs and root border cells in hairy roots grown on “noninducing” medium, whereas induction of additional pigment production by abiotic (CuSO4) or biotic (fungal elicitor) factors increases the amount of total pigment, changes the ratios of derivatives produced, and initiates production of pigment de novo in epidermal cells. When the biological activity of these compounds was tested against soil-borne bacteria and fungi, a wide range of sensitivity was recorded. Acetyl-shikonin and β-hydroxyisovaleryl-shikonin, the two most abundant derivatives in both Agrobacterium rhizogenes-transformed “hairy-root” cultures and greenhouse-grown plant roots, were the most biologically active of the seven compounds tested. Hyphae of the pathogenic fungi Rhizoctonia solani, Pythium aphanidermatum, and Nectria hematococca induced localized pigment production upon contact with the roots. Challenge by R. solani crude elicitor increased shikonin derivative production 30-fold. We have studied the regulation of this suite of related, differentially produced, differentially active compounds to understand their role(s) in plant defense at the cellular level in the rhizosphere. PMID:9952436

Anticlastogenic activity exhibited by botryosphaeran, a new exopolysaccharide produced by Botryosphaeria rhodina MAMB-05.

PubMed

Miranda, Carolina C B O; Dekker, Robert F H; Serpeloni, Juliana M; Fonseca, Eveline A I; Cólus, Ilce M S; Barbosa, Aneli M

2008-03-01

Biopolymers such as exopolysaccharides (EPS) are produced by microbial species and possess unusual properties known to modify biological responses, among them are antimutagenicity and immunomodulation. Botryosphaeran, a newly described fungal (1-->3; 1-->6)-beta-d-glucan produced by Botryosphaeria rhodina MAMB-05, was administered by gavage to mice at three doses (7.5, 15 and 30mg/kgb.w.per day) over 15 days, and found to be non-genotoxic by the micronucleus test in peripheral blood and bone marrow. Botryosphaeran administered at doses of 15 and 30mg EPS/kgb.w. decreased significantly (p<0.001) the clastogenic effect of cyclophosphamide-induced micronucleus formation resulting in a reduction of the frequency of micronucleated cells of 78 and 82% in polychromatic erythrocytes of bone marrow, and reticulocytes in peripheral blood, respectively. The protective effect was dose-dependent, and strong anticlastogenic activity was exerted at low EPS doses. Variance analysis (ANOVA) showed no significant differences (p<0.05) among the median body weights of the groups of mice treated with botryosphaeran during experiments evaluating genotoxic and protective activities of botryosphaeran. This is the first report on the biological activity attributed to botryosphaeran.

Purification and molecular and biological characterisation of the 1-hydroxyphenazine, produced by an environmental strain of Pseudomonas aeruginosa.

PubMed

Prabhu, Meghanath S; Walawalkar, Yogesh D; Furtado, Irene

2014-12-01

Pseudomonas aeruginosa--an opportunistic pathogen, perhaps best known for chronic lung infections, produces wide range of pigments that possess specific activities which either assist the organism's survival or bring about changes within host. A similar blue-green diffusible pigment producing P. aeruginosa was isolated from dug-well water, so as to extract 1-hydroxyphenazine from its crude pigment. The compound was purified from the crude pigment using column chromatography followed by a preparative thin layer chromatography that showed a single yellow spot. Further molecular characterisation of the purified component was carried out using UV-Vis spectrophotometer, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy which showed respective peaks corresponding to 1-hydroxyphenazine. Biological characterisation using in vitro assays revealed that 1-hydroxyphenazine showed anti-bacterial activity only against Bacillus sp. and a concentration of 30 µg/ml induced noticeable morphological alteration in A549 human lung adenocarcinoma cells followed by cell death after 48 h. Thus, such active components within bacterial pigments can be characterized and used as possible anti-bacterial or anti-cancer agents.

Extracellular production of an intact and biologically active human growth hormone by the Bacillus brevis system.

PubMed

Kajino, T; Saito, Y; Asami, O; Yamada, Y; Hirai, M; Udata, S

1997-10-01

The characteristic features of the Bacillus brevis system are very high productivity of heterologous proteins and very low extracellular protease activity. However, degradation of some heterologous proteins, especially mammalian proteins, can be observed and resulted in a lowering of protein productivity. By using a mutant expressing low levels of proteases and the addition of EDTA to the medium, intact human growth hormone (hGH) was successfully produced with the B. brevis system. Signal peptide modification with higher basicity in the amino terminal region and higher hydrophobicity in the middle region brought about a twelve-fold increase in hGH production. The hGH yield was further elevated to 240 mg L-1 by optimization of culture conditions. Thus, biologically active and mature hGH can be efficiently produced directly in the medium with the B. brevis system.

Biosynthesis, Chemical Structure, and Structure-Activity Relationship of Orfamide Lipopeptides Produced by Pseudomonas protegens and Related Species

PubMed Central

Ma, Zongwang; Geudens, Niels; Kieu, Nam P.; Sinnaeve, Davy; Ongena, Marc; Martins, José C.; Höfte, Monica

2016-01-01

Orfamide-type cyclic lipopeptides (CLPs) are biosurfactants produced by Pseudomonas and involved in lysis of oomycete zoospores, biocontrol of Rhizoctonia and insecticidal activity against aphids. In this study, we compared the biosynthesis, structural diversity, in vitro and in planta activities of orfamides produced by rhizosphere-derived Pseudomonas protegens and related Pseudomonas species. Genetic characterization together with chemical identification revealed that the main orfamide compound produced by the P. protegens group is orfamide A, while the related strains Pseudomonas sp. CMR5c and CMR12a produce orfamide B. Comparison of orfamide fingerprints led to the discovery of two new orfamide homologs (orfamide F and orfamide G) in Pseudomonas sp. CMR5c. The structures of these two CLPs were determined by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. Mutagenesis and complementation showed that orfamides determine the swarming motility of parental Pseudomonas sp. strain CMR5c and their production was regulated by luxR type regulators. Orfamide A and orfamide B differ only in the identity of a single amino acid, while orfamide B and orfamide G share the same amino acid sequence but differ in length of the fatty acid part. The biological activities of orfamide A, orfamide B, and orfamide G were compared in further bioassays. The three compounds were equally active against Magnaporthe oryzae on rice, against Rhizoctonia solani AG 4-HGI in in vitro assays, and caused zoospore lysis of Phytophthora and Pythium. Furthermore, we could show that orfamides decrease blast severity in rice plants by blocking appressorium formation in M. oryzae. Taken all together, our study shows that orfamides produced by P. protegens and related species have potential in biological control of a broad spectrum of fungal plant pathogens. PMID:27065956

Pollution Impact and Alternative Treatment for Produced Water

NASA Astrophysics Data System (ADS)

Hedar, Yusran; Budiyono

2018-02-01

Oil and gas exploration and production are two of the activities that potentially cause pollution and environmental damage. The largest waste generated from this activity is produced water. Produced water contains hazardous pollutants of both organic and inorganic materials, so that the produced water of oil and gas production cannot be discharged directly to the environment. Uncontrolled discharge can lead to the environmental damage, killing the life of water and plants. The produced water needs to be handled and fulfill the quality standards before being discharged to the environment. Several studies to reduce the contaminants in the produced water were conducted by researchers. Among them were gravity based separation - flotation, separation technique based on filtration, and biological process treatment. Therefore, some of these methods can be used as an alternative waste handling of produced water.

Biological activities of ophiobolin K and 6-epi-ophiobolin K produced by the endophytic fungus Aspergillus calidoustus

USDA-ARS?s Scientific Manuscript database

The endophytic fungus, Aspergillus calidoustus, was isolated from the plant species Acanthospermum australe (Asteraceae). A dichloromethane extract of the fungus displayed antifungal, antiprotozoal, and cytotoxic activities. Aspergillus calidoustus was identified using molecular, physiological and m...

76 FR 66274 - Small Takes of Marine Mammals Incidental to Specified Activities; Pier 36/Brannan Street Wharf...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

... biological functions including, but not limited to, (1) Social interactions; (2) foraging; (3) orientation...). Pinnipeds produce a wide range of social signals, most occurring at relatively low frequencies (Southall et... piers or opportunistically foraging. Pinnipeds produce a wide range of social signals, most occurring at...

Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation.

PubMed

Li, Yangmei; Cazares, Margret; Wu, Jinhua; Houghten, Richard A; Toll, Laurence; Dooley, Colette

2016-02-11

To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing a Phe(3) was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys(2)-Xxx(3) is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

Biologically Active and Antimicrobial Peptides from Plants

PubMed Central

Salas, Carlos E.; Badillo-Corona, Jesus A.; Ramírez-Sotelo, Guadalupe; Oliver-Salvador, Carmen

2015-01-01

Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application. PMID:25815307

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. I. Taxonomy of producing strain, fermentation, isolation and biological activities.

PubMed

Nose, H; Seki, A; Yaguchi, T; Hosoya, A; Sasaki, T; Hoshiko, S; Shomura, T

2000-01-01

Two novel antifungal antibiotics, PF1163A and B, were isolated from the fermentation broth of Penicillium sp. They were purified from the solid cultures of rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies. PF1163A and B showed potent growth inhibitory activity against pathogenic fungal strain Candida albicans but did not show cytotoxic activity against mammalian cells. These compounds inhibited the ergosterol biosynthesis in Candida albicans.

Exploiting biological activities of brown seaweed Ecklonia cava for potential industrial applications: a review.

PubMed

Wijesinghe, W A J P; Jeon, You-Jin

2012-03-01

Seaweeds are rich in vitamins, minerals, dietary fibres, proteins, polysaccharides and various functional polyphenols. Many researchers have focused on brown algae as a potential source of bioactive materials in the past few decades. Ecklonia cava is a brown seaweed that is abundant in the subtidal regions of Jeju Island in the Republic of Korea. This seaweed attracted extensive interest due to its multiple biological activities. E. cava has been identified as a potential producer of wide spectrum of natural substances such as carotenoids, fucoidans and phlorotannins showing different biological activities in vital industrial applications including pharmaceutical, nutraceutical, cosmeceutical and functional food. This review focuses on biological activities of the brown seaweed E. cava based on latest research results, including antioxidant, anticoagulative, antimicrobial, antihuman immunodeficiency virus, anti-inflammatory, immunomodulatory, antimutagenic, antitumour and anticancer effects. The facts summarized here may provide novel insights into the functions of E. cava and its derivatives and potentially enable their use as functional ingredients in potential industrial applications.

Applications of Carboxylic Acid Reductases in Oleaginous Microbes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Resch, Michael G.; Linger, Jeffrey; McGeehan, John

2016-05-26

Carboxylic acid reductases (CARs) are recently emerging reductive enzymes for the direct production of aldehydes from biologically-produced carboxylic acids. Recent work has demonstrated that these powerful enzymes are able to reduce a very broad range of volatile- to long-chain fatty acids as well as aromatic acids. Here, we express four CAR enzymes from different fungal origins to test their activity against fatty acids commonly produced in oleaginous microbes. These in vitro results will inform metabolic engineering strategies to conduct mild biological reduction of carboxylic acids in situ, which is conventionally done via hydrotreating catalysis at high temperatures and hydrogen pressures.

Synthesis, structural studies and biological properties of new TBA analogues containing an acyclic nucleotide.

PubMed

Coppola, Teresa; Varra, Michela; Oliviero, Giorgia; Galeone, Aldo; D'Isa, Giuliana; Mayol, Luciano; Morelli, Elena; Bucci, Maria-Rosaria; Vellecco, Valentina; Cirino, Giuseppe; Borbone, Nicola

2008-09-01

A new modified acyclic nucleoside, namely N(1)-(3-hydroxy-2-hydroxymethyl-2-methylpropyl)-thymidine, was synthesized and transformed into a building block useful for oligonucleotide (ON) automated synthesis. A series of modified thrombin binding aptamers (TBAs) in which the new acyclic nucleoside replaces, one at the time, the thymidine residues were then synthesized and characterized by UV, CD, MS, and (1)H NMR. The biological activity of the resulting TBAs was tested by Prothrombin Time assay (PT assay) and by purified fibrinogen clotting assay. From a structural point of view, nearly all the new TBA analogues show a similar behavior as the unmodified counterpart, being able to fold into a bimolecular or monomolecular quadruplex structure depending on the nature of monovalent cations (sodium or potassium) coordinated in the quadruplex core. From the comparison of structural and biological data, some important structure-activity relationships emerged, particularly when the modification involved the TT loops. In agreement with previous studies we found that the folding ability of TBA analogues is more affected by modifications involving positions 4 and 13, rather than positions 3 and 12. On the other hand, the highest anti-thrombin activities were detected for aptamers containing the modification at T13 or T12 positions, thus indicating that the effects produced by the introduction of the acyclic nucleoside on the biological activity are not tightly connected with structure stabilities. It is noteworthy that the modification at T7 produces an ON being more stable and active than the natural TBA.

Particle complexation of mitochondrial iron produces superoxide generation and activates MAP kinases, NF-kappa B, nrf-2 in human respiratory epithelial cell

EPA Science Inventory

The biological effect of particles is associated with a disruption in cell iron homeostasis. We tested the postulate that complexation of cell iron by silica (Si02) results in both an oxidative stress and biological effect. BEAS-2B cells were exposed to either media or 100 ug/ml....

Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans

PubMed Central

Zhang, Xinxing; Bhar, Subhradeep; Jones Lipinski, Rachel A; Han, Jungsoo; Feng, Likui

2018-01-01

Caenorhabditis elegans produces ascaroside pheromones to control its development and behavior. Even minor structural differences in the ascarosides have dramatic consequences for their biological activities. Here, we identify a mechanism that enables C. elegans to dynamically tailor the fatty-acid side chains of the indole-3-carbonyl (IC)-modified ascarosides it has produced. In response to starvation, C. elegans uses the peroxisomal acyl-CoA synthetase ACS-7 to activate the side chains of medium-chain IC-ascarosides for β-oxidation involving the acyl-CoA oxidases ACOX-1.1 and ACOX-3. This pathway rapidly converts a favorable ascaroside pheromone that induces aggregation to an unfavorable one that induces the stress-resistant dauer larval stage. Thus, the pathway allows the worm to respond to changing environmental conditions and alter its chemical message without having to synthesize new ascarosides de novo. We establish a new model for biosynthesis of the IC-ascarosides in which side-chain β-oxidation is critical for controlling the type of IC-ascarosides produced. PMID:29863473

[Advance in flavonoids biosynthetic pathway and synthetic biology].

PubMed

Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

2016-11-01

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

Meprin A and meprin {alpha} generate biologically functional IL-1{beta} from pro-IL-1{beta}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herzog, Christian; University of Arkansas for Medical Sciences, Department of Medicine, Little Rock, AR 72205; Haun, Randy S.

The present study demonstrates that both oligomeric metalloendopeptidase meprin A purified from kidney cortex and recombinant meprin {alpha} are capable of generating biologically active IL-1{beta} from its precursor pro-IL-1{beta}. Amino-acid sequencing analysis reveals that meprin A and meprin {alpha} cleave pro-IL-1{beta} at the His{sup 115}-Asp{sup 116} bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin {beta} site. The biological activity of the pro-IL-1{beta} cleaved product produced by meprin A, determined by proliferative response of helper T-cells, was 3-fold higher to that of the IL-1{beta} product produced by meprin {beta}more » or caspase-1. In a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum IL-1{beta}, meprin inhibitor actinonin significantly reduces levels of serum IL-1{beta}. Meprin A and meprin {alpha} may therefore play a critical role in the production of active IL-1{beta} during inflammation and tissue injury.« less

Corrosion resistance and biological activity of TiO2 implant coatings produced in oxygen-rich environments.

PubMed

Zhang, Rui; Wan, Yi; Ai, Xing; Liu, Zhanqiang; Zhang, Dong

2017-01-01

The physical and chemical properties of bio-titanium alloy implant surfaces play an important role in their corrosion resistance and biological activity. New turning and turning-rolling processes are presented, employing an oxygen-rich environment in order to obtain titanium dioxide layers that can both protect implants from corrosion and also promote cell adhesion. The surface topographies, surface roughnesses and chemical compositions of the sample surfaces were obtained using scanning electron microscopy, a white light interferometer, and the Auger electron spectroscopy, respectively. The corrosion resistance of the samples in a simulated body fluid was determined using electrochemical testing. Biological activity on the samples was also analyzed, using a vitro cell culture system. The results show that compared with titanium oxide layers formed using a turning process in air, the thickness of the titanium oxide layers formed using turning and turning-rolling processes in an oxygen-rich environment increased by 4.6 and 7.3 times, respectively. Using an oxygen-rich atmosphere in the rolling process greatly improves the corrosion resistance of the resulting samples in a simulated body fluid. On samples produced using the turning-rolling process, cells spread quickly and exhibited the best adhesion characteristics.

Profiling of red pigment produced by Streptomyces sp. JAR6 and its bioactivity.

PubMed

Abraham, Jayanthi; Chauhan, Ritika

2018-01-01

Actinomycetes strain was isolated from leaf litter soil sample and was identified as Streptomyces sp. by conventional and molecular approaches. The biologically active compound responsible for antimicrobial and anticancer activity of the strain JAR6 was elucidated by solid state fermentation followed by subsequent chromatographic and spectroscopic analysis. Extraction, purification and structural confirmation of red pigment metabolite viz undecylprodigiosin were established on the basis of spectroscopic studies and comparing the data from the literature. The biologically active compound was tested against Gram-positive and Gram-negative clinical isolates and its minimum inhibitory concentration was recorded. The antimicrobial activity of undecylprodigiosin is more prominent against Salmonella sp., Proteus mirabilis , Shigella sp. and Enterococcus sp. whereas, it was less effective against Staphylococcus aureus , Klebsiella pneumonia and Escherichia coli . The anticancer activity of undecylprodigiosin was tested against HeLa cell lines and it exhibited commendable cytotoxicity effect with IC 50 value of 145 µg/ml. The present investigation reveals that undecylprodigiosin produced by Streptomyces strain JAR6 is a potent bioactive metabolite with effective pharmaceutical properties.

Mass Spectrometric Detection of Bacterial Protein Toxins and Their Enzymatic Activity.

PubMed

Kalb, Suzanne R; Boyer, Anne E; Barr, John R

2015-08-31

Mass spectrometry has recently become a powerful technique for bacterial identification. Mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. With some bacteria, such as Bacillus anthracis and Clostridium botulinum, the health threat posed by these organisms is not the organism itself, but rather the protein toxins produced by the organisms. One such example is botulinum neurotoxin (BoNT), a potent neurotoxin produced by C. botulinum. There are seven known serotypes of BoNT, A-G, and many of the serotypes can be further differentiated into toxin variants, which are up to 99.9% identical in some cases. Mass spectrometric proteomic techniques have been established to differentiate the serotype or toxin variant of BoNT produced by varied strains of C. botulinum. Detection of potent biological toxins requires high analytical sensitivity and mass spectrometry based methods have been developed to determine the enzymatic activity of BoNT and the anthrax lethal toxins produced by B. anthracis. This enzymatic activity, unique for each toxin, is assessed with detection of the toxin-induced cleavage of strategically designed peptide substrates by MALDI-TOF mass spectrometry offering unparalleled specificity. Furthermore, activity assays allow for the assessment of the biological activity of a toxin and its potential health risk. Such methods have become important diagnostics for botulism and anthrax. Here, we review mass spectrometry based methods for the enzymatic activity of BoNT and the anthrax lethal factor toxin.

Mass Spectrometric Detection of Bacterial Protein Toxins and Their Enzymatic Activity

PubMed Central

Kalb, Suzanne R.; Boyer, Anne E.; Barr, John R.

2015-01-01

Mass spectrometry has recently become a powerful technique for bacterial identification. Mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. With some bacteria, such as Bacillus anthracis and Clostridium botulinum, the health threat posed by these organisms is not the organism itself, but rather the protein toxins produced by the organisms. One such example is botulinum neurotoxin (BoNT), a potent neurotoxin produced by C. botulinum. There are seven known serotypes of BoNT, A–G, and many of the serotypes can be further differentiated into toxin variants, which are up to 99.9% identical in some cases. Mass spectrometric proteomic techniques have been established to differentiate the serotype or toxin variant of BoNT produced by varied strains of C. botulinum. Detection of potent biological toxins requires high analytical sensitivity and mass spectrometry based methods have been developed to determine the enzymatic activity of BoNT and the anthrax lethal toxins produced by B. anthracis. This enzymatic activity, unique for each toxin, is assessed with detection of the toxin-induced cleavage of strategically designed peptide substrates by MALDI-TOF mass spectrometry offering unparalleled specificity. Furthermore, activity assays allow for the assessment of the biological activity of a toxin and its potential health risk. Such methods have become important diagnostics for botulism and anthrax. Here, we review mass spectrometry based methods for the enzymatic activity of BoNT and the anthrax lethal factor toxin. PMID:26404376

The role of proteolysis in the biological activity of Bt insecticidal crystal proteins

USDA-ARS?s Scientific Manuscript database

The crystal toxins (Cry) produced by the bacterium Bacillus thuringiensis have been successfully used in both spray formulations and transgenic crops to control some of the most problematic insect pests. The delta-endotoxins of B. thuringiensis are functionally-active in the insect gut and interact ...

Marine Polysaccharides in Pharmaceutical Applications: An Overview

PubMed Central

Laurienzo, Paola

2010-01-01

The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest. PMID:20948899

Activity-based protein profiling: from enzyme chemistry to proteomic chemistry.

PubMed

Cravatt, Benjamin F; Wright, Aaron T; Kozarich, John W

2008-01-01

Genome sequencing projects have provided researchers with a complete inventory of the predicted proteins produced by eukaryotic and prokaryotic organisms. Assignment of functions to these proteins represents one of the principal challenges for the field of proteomics. Activity-based protein profiling (ABPP) has emerged as a powerful chemical proteomic strategy to characterize enzyme function directly in native biological systems on a global scale. Here, we review the basic technology of ABPP, the enzyme classes addressable by this method, and the biological discoveries attributable to its application.

Biological Relevance of Free Radicals and Nitroxides.

PubMed

Prescott, Christopher; Bottle, Steven E

2017-06-01

Nitroxides are stable, kinetically-persistent free radicals which have been successfully used in the study and intervention of oxidative stress, a critical issue pertaining to cellular health which results from an imbalance in the levels of damaging free radicals and redox-active species in the cellular environment. This review gives an overview of some of the biological processes that produce radicals and other reactive oxygen species with relevance to oxidative stress, and then discusses interactions of nitroxides with these species in terms of the use of nitroxides as redox-sensitive probes and redox-active therapeutic agents.

Investigation of the effect of biologically active threo-Ds-isocitric acid on oxidative stress in Paramecium caudatum.

PubMed

Morgunov, Igor G; Karpukhina, Olga V; Kamzolova, Svetlana V; Samoilenko, Vladimir A; Inozemtsev, Anatoly N

2018-01-02

The effect of biologically active form (threo-Ds-) of isocitric acid (ICA) on oxidative stress was studied using the infusorian Paramecium caudatum stressed by hydrogen peroxide and salts of some heavy metals (Cu, Pb, Zn, and Cd). ICA at concentrations between 0.5 and 10 mM favorably influenced the infusorian cells with oxidative stress induced by the toxicants studied. The maximal antioxidant effect of ICA was observed at its concentration 10 mM irrespective of the toxicant used (either H 2 O 2 or heavy metal ions). ICA was found to be a more active antioxidant than ascorbic acid. Biologically active pharmaceutically pure threo-Ds-ICA was produced through cultivation of the yeast Yarrowia lipolytica and isolated from the culture liquid in the form of crystalline monopotassium salt with a purity of 99.9%.

Evaluation of the effects of a plasma activated medium on cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohades, S.; Laroussi, M., E-mail: mlarouss@odu.edu; Sears, J.

2015-12-15

The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma tomore » a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.« less

Natural plant chemicals: source of industrial and medicinal materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balandrin, M.F.; Klocke, J.A.; Wurtele, E.S.

1985-01-01

Many higher plants produce economically important organic compounds such as oils, resins, tannins, natural rubber, gums, waxes, dyes, flavors and fragrances, pharmaceuticals, and pesticides. However, most species of higher plants have never been described, much less surveyed for chemical or biologically active constituents, and new sources of commercially valuable materials remain to be discovered. Advances in biotechnology, particularly methods for culturing plants cells and tissues, should provide new means for the commercial processing of even rare plants and the chemicals they produce. These new technologies will extend and enhance the usefulness of plants as renewable resources of valuable chemicals. Inmore » the future, biologically active plant-derived chemicals can be expected to play an increasingly significant role in the commercial development of new products for regulating plant growth and for insect and weed control. 65 references.« less

Functional properties of honey, propolis, and royal jelly.

PubMed

Viuda-Martos, M; Ruiz-Navajas, Y; Fernández-López, J; Pérez-Alvarez, J A

2008-11-01

Honey, propolis, and royal jelly, products originating in the beehive, are attractive ingredients for healthy foods. Honey has been used since ancient times as part of traditional medicine. Several aspects of this use indicate that it also has functions such as antibacterial, antioxidant, antitumor, anti-inflamatory, antibrowning, and antiviral. Propolis is a resinous substance produced by honeybees. This substance has been used in folk medicine since ancient times, due to its many biological properties to possess, such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects, among others. Royal jelly has been demonstrated to possess numerous functional properties such as antibacterial activity, anti-inflammatory activity, vasodilative and hypotensive activities, disinfectant action, antioxidant activity, antihypercholesterolemic activity, and antitumor activity. Biological activities of honey, propolis, and royal jelly are mainly attributed to the phenolic compounds such as flavonoids. Flavonoids have been reported to exhibit a wide range of biological activities, including antibacterial, antiviral, anti-inflammatory, antiallergic, and vasodilatory actions. In addition, flavonoids inhibit lipid peroxidation, platelet aggregation, capillary permeability and fragility, and the activity of enzyme systems including cyclo-oxygenase and lipoxygenase.

An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER-/PR-/Her2- Human Breast Cancer Cells.

PubMed

Novikov, Olga; Wang, Zhongyan; Stanford, Elizabeth A; Parks, Ashley J; Ramirez-Cardenas, Alejandra; Landesman, Esther; Laklouk, Israa; Sarita-Reyes, Carmen; Gusenleitner, Daniel; Li, Amy; Monti, Stefano; Manteiga, Sara; Lee, Kyongbum; Sherr, David H

2016-11-01

The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER - /PR - /Her2 - breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER - /PR - /Her2 - cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness. Copyright © 2016 by The Author(s).

An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER−/PR−/Her2− Human Breast Cancer Cells

PubMed Central

Novikov, Olga; Wang, Zhongyan; Stanford, Elizabeth A.; Parks, Ashley J.; Ramirez-Cardenas, Alejandra; Landesman, Esther; Laklouk, Israa; Sarita-Reyes, Carmen; Gusenleitner, Daniel; Li, Amy; Monti, Stefano; Manteiga, Sara; Lee, Kyongbum

2016-01-01

The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER−/PR−/Her2− breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER−/PR−/Her2− cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness. PMID:27573671

Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

PubMed

Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

2013-01-01

Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

Heterologous Acidothermus cellulolyticus 1,4-β-Endoglucanase E1 Produced Within the Corn Biomass Converts Corn Stover Into Glucose

NASA Astrophysics Data System (ADS)

Ransom, Callista; Balan, Venkatesh; Biswas, Gadab; Dale, Bruce; Crockett, Elaine; Sticklen, Mariam

Commercial conversion of lignocellulosic biomass to fermentable sugars requires inexpensive bulk production of biologically active cellulase enzymes, which might be achieved through direct production of these enzymes within the biomass crops. Transgenic corn plants containing the catalytic domain of Acidothermus cellulolyticus E1 endo-1,4-β glucanase and the bar bialaphos resistance coding sequences were generated after Biolistic® (BioRad Hercules, CA) bombardment of immature embryo-derived cells. E1 sequences were regulated under the control of the cauliflower mosaic virus 35S promoter and tobacco mosaic virus translational enhancer, and E1 protein was targeted to the apoplast using the signal peptide of tobacco pathogenesis-related protein to achieve accumulation of this enzyme. The integration, expression, and segregation of E1 and bar transgenes were demonstrated, respectively, through Southern and Western blotting, and progeny analyses. Accumulation of up to 1.13% of transgenic plant total soluble proteins was detected as biologically active E1 by enzymatic activity assay. The corn-produced, heterologous E1 could successfully convert ammonia fiber explosion-pretreated corn stover polysaccharides into glucose as a fermentable sugar for ethanol production, confirming that the E1 enzyme is produced in its active from.

Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons

PubMed Central

2002-01-01

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host’s ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats. PMID:12141970

Biological effects of contaminated silicon carbide particles from a workstation in a plant producing abrasives.

PubMed

Governa, M; Valentino, M; Amati, M; Visonà, I; Botta, G C; Marcer, G; Gemignani, C

1997-06-01

A sample of silicon carbide dust taken in the field from a plant producing abrasives was studied in vitro. The SiC particles (part unmilled and part milled) were able to disturb the structure of erythrocyte membranes and to lead to blood red-cell lysis; they also either interfered with complement and activated the alternate pathway, or interacted with biological media and polymorphonuclear leucocyte membranes, thus eliciting reactive oxygen species production. These in vitro properties were detected both in original large particles and unmilled particles, over 40% of which were of respirable size. The ability of these SiC particles to produce complement activation in vitro lends support to the previous hypothesis, that the radiographic opacities found in two workers employed in the same area of the plant from which the dust tested was taken are due to a reaction by pulmonary interstitial structures to SiC particle inhalation. It is speculated that SiC particles could act like asbestos, the ability of which to activate complement through the alternate pathway is considered to be one of the mechanisms by which the initial asbestotic lesions and subsequent fibrotic inflammatory infiltrates are generated in the lung.

Speciation and formation of iodinated trihalomethane from microbially derived organic matter during the biological treatment of micro-polluted source water.

PubMed

Wei, Yuanyuan; Liu, Yan; Ma, Luming; Wang, Hongwu; Fan, Jinhong; Liu, Xiang; Dai, Rui-Hua

2013-09-01

Water sources are micro-polluted by the increasing range of anthropogenic activities around them. Disinfection byproduct (DBP) precursors in water have gradually expanded from humic acid (HA) and fulvic acid to other important sources of potential organic matter. This study aimed to provide further insights into the effects of microbially derived organic matter as precursors on iodinated trihalomethane (I-THM) speciation and formation during the biological treatment of micro-polluted source water. The occurrence of I-THMs in drinking water treated by biological processes was investigated. The results showed for the first time that CHCl2I and CHBrClI are emerging DBPs in China. Biological pre-treatment and biological activated carbon can increase levels of microbes, which could serve as DBP precursors. Chlorination experiments with bovine serum albumin (BSA), starch, HA, deoxyribonucleic acid (DNA), and fish oil, confirmed the close correlation between the I-THM species identified during the treatment processes and those predicted from the model compounds. The effects of iodide and bromide on the I-THM speciation and formation were related to the biochemical composition of microbially derived organic precursors. Lipids produced up to 16.98μgL(-1) of CHCl2I at an initial iodide concentration of 2mgL(-1). HA and starch produced less CHCl2I at 3.88 and 3.54μgL(-1), respectively, followed by BSA (1.50μgL(-1)) and DNA (1.35μgL(-1)). Only fish oil produced I-THMs when iodide and bromide were both present in solution; the four other model compounds formed brominated species. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioactive Metabolites from Pathogenic and Endophytic Fungi of Forest Trees.

PubMed

Masi, Marco; Maddau, Lucia; Linaldeddu, Benedetto Teodoro; Scanu, Bruno; Evidente, Antonio; Cimmino, Alessio

2018-01-01

Fungi play an important role in terrestrial ecosystems interacting positively or negatively with plants. These interactions are complex and the outcomes are different depending on the fungal lifestyles, saprotrophic, mutualistic or pathogenic. Furthermore, fungi are well known for producing secondary metabolites, originating from different biosynthetic pathways, which possess biological properties of considerable biotechnological interest. Among the terrestrial ecosystems, temperate forests represent an enormous reservoir of fungal diversity. This review will highlight the goldmine of secondary metabolites produced by pathogenic and endophytic fungi of forest trees with focus on their biological activities. A structured search of bibliographic databases for peer-reviewed research literature was undertaken using a research discovery application providing access to a large and authoritative source of references. The papers selected were examined and the main results were reported and discussed. Two hundred forthy-one papers were included in the review, outlined a large number of secondary metabolites produced by pathogenic and endophiltic fungi and their biological activities, including phytotoxic, antifungal, antioomycetes, antibacterial, brine shrimp lethality, mosquito biting deterrence and larvicidal, cytotoxic, antiproliferative and many other bioactivities. The findings of this review confirm the importance of secondary metabolites produced by pathogenic and endophytic fungi from forest plants growing in temperate regions as an excellent prospects to discover compounds with new bioactivities and mode of actions. In addition, the potential of some metabolites as a source of new drugs and biopesticides is underlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed Central

Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom “yun zhi”, Trametes versicolor, traditionally used for (cit.) “replenish essence and qi (vital energy)”. Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied. PMID:28829786

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

PubMed

Scarpari, Marzia; Reverberi, Massimo; Parroni, Alessia; Scala, Valeria; Fanelli, Corrado; Pietricola, Chiara; Zjalic, Slaven; Maresca, Vittoria; Tafuri, Agostino; Ricciardi, Maria R; Licchetta, Roberto; Mirabilii, Simone; Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

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

Synthetic fermentation of bioactive non-ribosomal peptides without organisms, enzymes or reagents

NASA Astrophysics Data System (ADS)

Huang, Yi-Lin; Bode, Jeffrey W.

2014-10-01

Microbial fermentation can rapidly provide potent compounds that can be easily screened for biological activity, and the active components can be isolated. Its success in drug discovery has inspired extensive efforts to modulate and control the products. In this Article, we document a ‘synthetic fermentation’ of bioactive, unnatural peptides ‘grown’ from small building blocks in water using amide-forming ligations. No organisms, enzymes or reagents are needed. The sequences, structures and compositions of the products can be modulated by adjusting the building blocks and conditions. No specialized knowledge of organic chemistry or handling of toxic material is required to produce complex organic molecules. The ‘fermentations’ can be conducted in arrays and screened for biological activity without isolation or workup. As a proof-of-concept, about 6,000 unnatural peptides were produced from just 23 building blocks, from which a hepatitis C virus NS3/4A protease inhibitor with a half-maximum inhibitory concentration of 1.0 μM was identified and characterized.

Biological effects of diethylene glycol (DEG) and produced waters (PWs) released from offshore activities: a multi-biomarker approach with the sea bass Dicentrarchus labrax.

PubMed

Stefania, Gorbi; Maura, Benedetti; Claudia, Virno Lamberti; Barbara, Pisanelli; Ginevra, Moltedo; Francesco, Regoli

2009-11-01

Diethylene glycol (DEG) is largely used during oil and gas exploitation by offshore platforms. The aim of this work was to investigate if this compound induces direct molecular/cellular effects in marine organisms, or indirectly modulate those of produced waters (PWs). Sea bass (Dicentrarchus labrax) were exposed to DEG dosed alone or in combination with PWs from an Adriatic platform. A wide array of analysed biomarkers included cytochrome P450-dependent enzymatic activity, bile metabolites, glutathione S-transferases, acetylcholinesterase, peroxisomal proliferation, antioxidant defences (catalase, glutathione reductase, glutathione peroxidases, glutathione), total oxyradical scavenging capacity, malondialdehyde and DNA integrity (single strand breaks and frequency of micronuclei). Results did not reveal marked effects of DEG, while PWs influenced the biotransformation system, the oxidative status and the onset of genotoxic damages. Co-exposures caused only limited differences of biomarker responses at some experimental conditions, overall suggesting a limited biological impact of DEG at levels normally deriving from offshore activities.

The isolation and characterization of actinobacteria from dominant benthic macroinvertebrates endemic to Lake Baikal.

PubMed

Axenov-Gribanov, Denis; Rebets, Yuriy; Tokovenko, Bogdan; Voytsekhovskaya, Irina; Timofeyev, Maxim; Luzhetskyy, Andriy

2016-03-01

The high demand for new antibacterials fosters the isolation of new biologically active compounds producing actinobacteria. Here, we report the isolation and initial characterization of cultured actinobacteria from dominant benthic organisms' communities of Lake Baikal. Twenty-five distinct strains were obtained from 5 species of Baikal endemic macroinvertebrates of amphipods, freshwater sponges, turbellaria worms, and insects (caddisfly larvae). The 16S ribosomal RNA (rRNA)-based phylogenic analysis of obtained strains showed their affiliation to Streptomyces, Nocardia, Pseudonocardia, Micromonospora, Aeromicrobium, and Agromyces genera, revealing the diversity of actinobacteria associated with the benthic organisms of Lake Baikal. The biological activity assays showed that 24 out of 25 strains are producing compounds active against at least one of the test cultures used, including Gram-negative bacteria and Candida albicans. Complete dereplication of secondary metabolite profiles of two isolated strains led to identification of only few known compounds, while the majority of detected metabolites are not listed in existing antibiotic databases.

Bacterial symbionts and natural products.

PubMed

Crawford, Jason M; Clardy, Jon

2011-07-21

The study of bacterial symbionts of eukaryotic hosts has become a powerful discovery engine for chemistry. This highlight looks at four case studies that exemplify the range of chemistry and biology involved in these symbioses: a bacterial symbiont of a fungus and a marine invertebrate that produce compounds with significant anticancer activity, and bacterial symbionts of insects and nematodes that produce compounds that regulate multilateral symbioses.

Staphylococcus simulans Recombinant Lysostaphin: Production, Purification, and Determination of Antistaphylococcal Activity.

PubMed

Boksha, I S; Lavrova, N V; Grishin, A V; Demidenko, A V; Lyashchuk, A M; Galushkina, Z M; Ovchinnikov, R S; Umyarov, A M; Avetisian, L R; Chernukha, M Iu; Shaginian, I A; Lunin, V G; Karyagina, A S

2016-05-01

Staphylococcus simulans lysostaphin is an endopeptidase lysing staphylococcus cell walls by cleaving pentaglycine cross-bridges in their peptidoglycan. A synthetic gene encoding S. simulans lysostaphin was cloned in Escherichia coli cells, and producer strains were designed. The level of produced biologically active lysostaphin comprised 6-30% of total E. coli cell protein (depending on E. coli M15 or BL21 producer) under batch cultivation conditions. New methods were developed for purification of lysostaphin without affinity domains and for testing its enzymatic activity. As judged by PAGE, the purified recombinant lysostaphin is of >97% purity. The produced lysostaphin lysed cells of Staphylococcus aureus and Staphylococcus haemolyticus clinical isolates. In vitro activity and general biochemical properties of purified recombinant lysostaphin produced by M15 or BL21 E. coli strains were identical to those of recombinant lysostaphin supplied by Sigma-Aldrich (USA) and used as reference in other known studies. The prepared recombinant lysostaphin represents a potential product for development of enzymatic preparation for medicine and veterinary due to the simple purification scheme enabling production of the enzyme of high purity and antistaphylococcal activity.

Tribology of alternative bearings.

PubMed

Fisher, John; Jin, Zhongmin; Tipper, Joanne; Stone, Martin; Ingham, Eileen

2006-12-01

The tribological performance and biological activity of the wear debris produced has been compared for highly cross-linked polyethylene, ceramic-on-ceramic, metal-on-metal, and modified metal bearings in a series of in vitro studies from a single laboratory. The functional lifetime demand of young and active patients is 10-fold greater than the estimated functional lifetime of traditional polyethylene. There is considerable interest in using larger diameter heads in these high demand patients. Highly cross-linked polyethylene show a four-fold reduction in functional biological activity. Ceramic-on-ceramic bearings have the lowest wear rates and least reactive wear debris. The functional biological activity is 20-fold lower than with highly cross-linked polyethylene. Hence, ceramic-on-ceramic bearings address the tribological lifetime demand of highly active patients. Metal-on-metal bearings have substantially lower wear rates than highly cross-linked polyethylene and wear decreases with head diameter. Bedding in wear is also lower with reduced radial clearance. Differential hardness ceramic-on-metal bearings and the application of ceramic-like coatings reduce metal wear and ion levels.

Enzymes in Human Milk.

PubMed

Dallas, David C; German, J Bruce

2017-01-01

Milk proteins are a complex and diverse source of biological activities. Beyond their function, intact milk proteins also act as carriers of encrypted functional sequences that, when released as peptides, exert biological functions, including antimicrobial and immunomodulatory activity, which could contribute to the infant's competitive success. Research has now revealed that the release of these functional peptides begins within the mammary gland itself. A complex array of proteases produced in mother's milk has been shown to be active in the milk, releasing these peptides. Moreover, our recent research demonstrates that these milk proteases continue to digest milk proteins within the infant's stomach, possibly even to a larger extent than the infant's own proteases. As the neonate has relatively low digestive capacity, the activity of milk proteases in the infant may provide important assistance to digesting milk proteins. The coordinated release of these encrypted sequences is accomplished by selective proteolytic action provided by an array of native milk proteases and infant-produced enzymes. The task for scientists is now to discover the selective advantages of this protein-protease-based peptide release system. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Engineering soya bean seeds as a scalable platform to produce cyanovirin-N, a non-ARV microbicide against HIV.

PubMed

O'Keefe, Barry R; Murad, André M; Vianna, Giovanni R; Ramessar, Koreen; Saucedo, Carrie J; Wilson, Jennifer; Buckheit, Karen W; da Cunha, Nicolau B; Araújo, Ana Claudia G; Lacorte, Cristiano C; Madeira, Luisa; McMahon, James B; Rech, Elibio L

2015-09-01

There is an urgent need to provide effective anti-HIV microbicides to resource-poor areas worldwide. Some of the most promising microbicide candidates are biotherapeutics targeting viral entry. To provide biotherapeutics to poorer areas, it is vital to reduce the cost. Here, we report the production of biologically active recombinant cyanovirin-N (rCV-N), an antiviral protein, in genetically engineered soya bean seeds. Pure, biologically active rCV-N was isolated with a yield of 350 μg/g of dry seed weight. The observed amino acid sequence of rCV-N matched the expected sequence of native CV-N, as did the mass of rCV-N (11 009 Da). Purified rCV-N from soya is active in anti-HIV assays with an EC50 of 0.82-2.7 nM (compared to 0.45-1.8 nM for E. coli-produced CV-N). Standard industrial processing of soya bean seeds to harvest soya bean oil does not diminish the antiviral activity of recovered rCV-N, allowing the use of industrial soya bean processing to generate both soya bean oil and a recombinant protein for anti-HIV microbicide development. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Effects of Lactobacillus formosensis S215T and Lactobacillus buchneri on quality and in vitro ruminal biological activity of condensed tannins in sweet potato vines silage.

PubMed

Mangwe, M C; Rangubhet, K T; Mlambo, V; Yu, B; Chiang, H I

2016-11-01

This study investigated the influence of two microbial inoculants; Lactobacillus formosensis and Lactobacillus buchneri on fermentation quality, chemical composition, aerobic stability and in vitro ruminal biological activity of condensed tannins in sweet potato vines silage. Sweet potato vines were ensiled for 28 and 60 days; without inoculant (CON), with Lact. buchneri (LB) or with Lact. formosensis (LF), both inoculants applied to achieve 1 × 10 6  CFU g -1 fresh forage. Lactobacillus formosensis silage had lower pH and higher lactic acid than all treatments. Yeasts and moulds were not detected in LB silage after ensiling. Lactobacillus buchneri silage was more aerobically stable than all treatments, whereas LF was more stable than CON silage. In vitro ruminal biological activity of condensed tannins was lower in microbial-inoculated silages than CON after ensiling. Lactobacillus formosensis improved fermentability by reducing silage pH and improved aerobic stability by producing more propionate, which inhibited yeast activity. Lactobacillus buchneri improved aerobic stability of the silage by producing more acetate. Both strains effectively reduced the antinutritional effect of condensed tannins after ensiling. Lactobacillus formosensis has the potential to be used as a silage inoculant because of its ability to improve fermentability and aerobic stability in sweet potato vines silage. © 2016 The Society for Applied Microbiology.

Further Characterization of an Interleukin-2-1Ike Cytokine Produced by Xenopus Laevis T Lymphocytes

PubMed Central

Haynes, Laura

1993-01-01

A T-cell growth factor (TCGF) is produced by antigen- or mitogen-stimulated T lymphocytes from the South African clawed frog Xenopus laevis. This study further defines the physical and biological properties of this cytokine and demonstrates that TCGF is biochemically similar to mammalian interleukin-2 (IL-2). Biologically active TCGF eluted from SDS-PAGE displays a Mr of 16 kD and lectin-affinity chromatography indicates that the three-dimensionmal configuration of carbohydrates on TCGF and human IL-2 is similar. Secretion of TCGF is detectable 1 day after stimulation of splenocytes with the T-cell mitogen phytohemagglutinin (PHA) and peaks following 2 to 3 days of stimulation. Finally, despite the biological and physical similarities between Xenopus TCGF and mammalian IL-2, anti-human IL-2 monoclonal antibodies do not recognize Xenopus TCGF. PMID:8281036

76 FR 56735 - Small Takes of Marine Mammals Incidental to Specified Activities; Cape Wind's High Resolution...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... contexts and use sound for various biological functions including, but not limited to, (1) Social interactions; (2) foraging; (3) orientation; and (4) predator detection. Interference with producing or...

Biological Activity of Peanut (Arachis hypogaea) Phytoalexins and Selected Natural and Synthetic Stilbenoids

PubMed Central

SOBOLEV, VICTOR S.; KHAN, SHABANA I.; TABANCA, NURHAYAT; WEDGE, DAVID E.; MANLY, SUSAN P.; CUTLER, STEPHEN J.; COY, MONIQUE R.; BECNEL, JAMES J.; NEFF, SCOTT A.; GLOER, JAMES B.

2011-01-01

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene, have been acknowledged by several investigators. Despite considerable progress in peanut research, relatively little is known about the biological activity of the stilbenoid phytoalexins. This study investigated the activities of some of these compounds in a broad spectrum of biological assays. Since peanut stilbenoids appear to play roles in plant defense mechanisms, they were evaluated for their effects on economically important plant pathogenic fungi of the genera Colletotrichum, Botrytis, Fusarium, and Phomopsis. We further investigated these peanut phytoalexins, together with some related natural and synthetic stilbenoids (a total of 24 compounds) in a panel of bioassays to determine their anti-inflammatory, cytotoxic, and antioxidant activities in mammalian cells. Several of these compounds were also evaluated as mammalian opioid receptor competitive antagonists. Assays for adult mosquito and larvae toxicity were also performed. The results of these studies reveal that peanut stilbenoids, as well as related natural and synthetic stilbene derivatives, display a diverse range of biological activities. PMID:21314127

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

PubMed

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Fungal phytotoxins with potential herbicidal activity: chemical and biological characterization.

PubMed

Cimmino, Alessio; Masi, Marco; Evidente, Marco; Superchi, Stefano; Evidente, Antonio

2015-12-19

Covering: 2007 to 2015 Fungal phytotoxins are secondary metabolites playing an important role in the induction of disease symptoms interfering with host plant physiological processes. Although fungal pathogens represent a heavy constraint for agrarian production and for forest and environmental heritage, they can also represent an ecofriendly alternative to manage weeds. Indeed, the phytotoxins produced by weed pathogenic fungi are an efficient tool to design natural, safe bioherbicides. Their use could avoid that of synthetic pesticides causing resistance in the host plants and the long term impact of residues in agricultural products with a risk to human and animal health. The isolation and structural and biological characterization of phytotoxins produced by pathogenic fungi for weeds, including parasitic plants, are described. Structure activity relationships and mode of action studies for some phytotoxins are also reported to elucidate the herbicide potential of these promising fungal metabolites.

[The biological and clinical relevance of estrogen metabolome].

PubMed

Kovács, Krisztián; Vásárhelyi, Barna; Mészáros, Katalin; Patócs, Attila; Karvaly, Gellért

2017-06-01

Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929-937.

Contribution to the Chemistry of Plasma-Activated Water

NASA Astrophysics Data System (ADS)

Julák, J.; Hujacová, A.; Scholtz, V.; Khun, J.; Holada, K.

2018-01-01

Plasma-activated water (PAW) was prepared by exposure to nonthermal plasma produced by a positive dc corona discharge in a transient spark regime. The activation of water was performed in atmosphere of various surrounding gases (air, nitrogen, carbon dioxide, and argon). This PAW retains its biological activity, measured on the mouse neuroblastoma cells culture, even after storage for more than one year. The highest hydrogen peroxide content was found for PAWs prepared in the atmospheres of argon or carbon dioxide, whereas the PAWs prepared in air and nitrogen exhibited lower hydrogen peroxide content. The acidity of PAWs mediated by nitric and nitrous acid formation displayed an opposite trend. It is concluded that the long-lasting biological effect of PAW is mediated by hydrogen peroxide in acid milieu only, whereas other possible active components decompose rapidly.

Multiple, novel biologically active endophytic actinomycetes isolated from upper Amazonian rainforests.

PubMed

Bascom-Slack, Carol A; Ma, Cong; Moore, Emily; Babbs, Beatrice; Fenn, Kathleen; Greene, Joshua S; Hann, Bradley D; Keehner, Jocelyn; Kelley-Swift, Elizabeth G; Kembaiyan, Vivek; Lee, Sun Jin; Li, Puyao; Light, David Y; Lin, Emily H; Schorn, Michelle A; Vekhter, Daniel; Boulanger, Lori-Ann; Hess, W M; Vargas, Percy Núñez; Strobel, Gary A; Strobel, Scott A

2009-08-01

Microbial biodiversity provides an increasingly important source of medically and industrially useful compounds. We have isolated 14 actinomycete species from a collection of approximately 300 plant stem samples from the upper Amazonian rainforest in Peru. All of the cultured isolates produce substances with inhibitory activity directed at a range of potential fungal and bacterial pathogens. For some organisms, this activity is very broad in spectrum while other organisms show specific activity against a limited number of organisms. Two of these organisms preferentially inhibit bacterial test organisms over eukaryotic organisms. rDNA sequence analysis indicates that these organisms are not equivalent to any other cultured deposits in GenBank. Our results provide evidence of the untapped biodiversity in the form of biologically active microbes present within the tissues of higher plants.

Bio-speckle assessment of bruising in fruits

NASA Astrophysics Data System (ADS)

Pajuelo, M.; Baldwin, G.; Rabal, H.; Cap, N.; Arizaga, R.; Trivi, M.

2003-07-01

The dynamic speckle patterns or bio-speckle is a phenomenon produced by laser illumination of active materials, such as a biological tissue. Fruits, even hard peel ones, show a speckle activity that can be related to maturity, turgor, damage, aging, and mechanical properties. In this case, we suggest a bio-speckle technique as a potential methodology for the study of impact on apples and the analysis of bruises produced by them. The aim is to correlate physical properties of apples with quality factors using a non-contact and non-invasive technique.

Yaequinolones, new insecticidal antibiotics produced by Penicillium sp. FKI-2140. I. Taxonomy, fermentation, isolation and biological activity.

PubMed

Uchida, Ryuji; Imasato, Rie; Yamaguchi, Yuichi; Masuma, Rokuro; Shiomi, Kazuro; Tomoda, Hiroshi; Omura, Satoshi

2006-10-01

New nine insecticidal antibiotics designated yaequinolones were isolated from the culture broth of the fungal strain Penicillium sp. FKI-2140 by solvent extraction, centrifugal partition chromatography and HPLC. Yaequinolones showed growth inhibitory activity against brine shrimp (Artemia salina). Among them, yaequinolone F has the most potent activity with MIC value of 0.19 microg/ml.

Marennine, Promising Blue Pigments from a Widespread Haslea Diatom Species Complex

PubMed Central

Gastineau, Romain; Turcotte, François; Pouvreau, Jean-Bernard; Morançais, Michèle; Fleurence, Joël; Windarto, Eko; Semba Prasetiya, Fiddy; Arsad, Sulastri; Jaouen, Pascal; Babin, Mathieu; Coiffard, Laurence; Couteau, Céline; Bardeau, Jean-François; Jacquette, Boris; Leignel, Vincent; Hardivillier, Yann; Marcotte, Isabelle; Bourgougnon, Nathalie; Tremblay, Réjean; Deschênes, Jean-Sébastien; Badawy, Hope; Pasetto, Pamela; Davidovich, Nikolai; Hansen, Gert; Dittmer, Jens; Mouget, Jean-Luc

2014-01-01

In diatoms, the main photosynthetic pigments are chlorophylls a and c, fucoxanthin, diadinoxanthin and diatoxanthin. The marine pennate diatom Haslea ostrearia has long been known for producing, in addition to these generic pigments, a water-soluble blue pigment, marennine. This pigment, responsible for the greening of oysters in western France, presents different biological activities: allelopathic, antioxidant, antibacterial, antiviral, and growth-inhibiting. A method to extract and purify marennine has been developed, but its chemical structure could hitherto not be resolved. For decades, H. ostrearia was the only organism known to produce marennine, and can be found worldwide. Our knowledge about H. ostrearia-like diatom biodiversity has recently been extended with the discovery of several new species of blue diatoms, the recently described H. karadagensis, H. silbo sp. inedit. and H. provincialis sp. inedit. These blue diatoms produce different marennine-like pigments, which belong to the same chemical family and present similar biological activities. Aside from being a potential source of natural blue pigments, H. ostrearia-like diatoms thus present a commercial potential for aquaculture, cosmetics, food and health industries. PMID:24879542

Active cycling of organic carbon in the central Arctic Ocean

NASA Astrophysics Data System (ADS)

Wheeler, Patricia A.; Gosselin, Michel; Sherr, Evelyn; Thibaultc, Delphine; Kirchman, David L.; Benner, Ronald; Whitledge, Terry E.

1996-04-01

THE notion of a barren central Arctic Ocean has been accepted since English's pioneering work1 on drifting ice-islands. The year-round presence of ice, a short photosynthetic season and low temperatures were thought to severely limit biological production1,2, although the paucity of data was often noted. Because primary production appeared to be low1,2, subsequent studies assumed that most organic carbon was either derived from river inputs or imported from adjacent continental-shelf regions3,4. Here we present shipboard measurements of biological produc-tion, biomass and organic carbon standing-stocks made during a cruise through the ice covering the central Arctic Ocean. Our results indicate that the central Arctic region is not a biological desert. Although it is less productive than oligotrophic ocean regions not covered by ice, it supports an active biological community which contributes to the cycling of organic carbon through dissolved and particulate pools.

Biologically active protein fragments containing specific binding regions of serum albumin or related proteins

NASA Technical Reports Server (NTRS)

Carter, Daniel C. (Inventor)

1998-01-01

In accordance with the present invention, biologically active protein fragments can be constructed which contain only those specific portions of the serum albumin family of proteins such as regions known as subdomains IIA and IIIA which are primarily responsible for the binding properties of the serum albumins. The artificial serums that can be prepared from these biologically active protein fragments are advantageous in that they can be produced much more easily than serums containing the whole albumin, yet still retain all or most of the original binding potential of the full albumin proteins. In addition, since the protein fragment serums of the present invention can be made from non-natural sources using conventional recombinant DNA techniques, they are far safer than serums containing natural albumin because they do not carry the potentially harmful viruses and other contaminants that will be found in the natural substances.

Human milk proteins: key components for the biological activity of human milk.

PubMed

Lönnerdal, Bo

2004-01-01

Human milk contains a wide array of proteins that provide biologic activities ranging from antimicrobial effects to immunostimulatory functions. Proteins like lactoferrin, secretory IgA, kappa-casein, lactoperoxidase, haptocorrin, lactadherin and peptides formed from human milk proteins during digestion can inhibit the growth of pathogenic bacteria and viruses and therefore protect against infection. At the same time, proteins like lactoferrin, bile-salt stimulated lipase, haptocorrin, kappa-casein, and folate-binding protein can facilitate the absorption of nutrients in the neonatal gut. However, the proteins in human milk themselves also provide adequate amounts of essential amino acids to the growing infant. This suggests a highly adapted digestive system, which allows the survival of some proteins and peptides in the upper gastrointestinal tract, while still allowing amino acid utilization from these proteins further down in the gut. It is now possible to produce recombinant human milk proteins in transgenic plants and animals, which makes it possible to further study the bioactivity of these proteins. Provided these proteins can be produced in large scale at low cost, that they show biologic activity and pose no safety concerns, it may be possible to add some human milk proteins to infant diets, such as formula and complementary foods. Human milk proteins produced in rice or potatoes, for example, could be added without much purification, because these staples commonly are used in weaning foods. Thus, some qualities provided by human milk may be included into other diets, although it is highly unlikely that all unique components of human milk can be copied this way.

Mycotoxins from mould infested building materials.

PubMed

Nielsen, K F

2000-03-01

Only limited documentation of non-allergenic, especially toxic reactions after inhalation of microfungal spores in water damaged buildings exists. Recently attention has been drawn to the mycotoxins as causal compounds, as some the dominating genera found in buildings are well known mycotoxin producers.Penicillium chrysogenum and A. ustus do not seem to produce any known mycotoxins when growing on building materials, whereasP. brevicompactum produces mycophenolic acid, someP. polonicum produces verrucosidin and verrucofortine,A. versicolor produces sterigmatocystins,A. niger produces nigragillin, orlandin, naphtho-γ-pyrones and tetracyclic compounds, someA. ochraceus produces ochratoxin A,Alternaria spp. produce alternariol and alternariol monomethyl ether,Chaetomium globosum produce chaetoglobosins, and finally 30-40% ofStachybotrys chartarum isolates from buildings produce macrocyclic trichothecenes and a number of other biologically active compounds.

Active matter at the interface between materials science and cell biology

NASA Astrophysics Data System (ADS)

Needleman, Daniel; Dogic, Zvonimir

2017-09-01

The remarkable processes that characterize living organisms, such as motility, self-healing and reproduction, are fuelled by a continuous injection of energy at the microscale. The field of active matter focuses on understanding how the collective behaviours of internally driven components can give rise to these biological phenomena, while also striving to produce synthetic materials composed of active energy-consuming components. The synergistic approach of studying active matter in both living cells and reconstituted systems assembled from biochemical building blocks has the potential to transform our understanding of both cell biology and materials science. This methodology can provide insight into the fundamental principles that govern the dynamical behaviours of self-organizing subcellular structures, and can lead to the design of artificial materials and machines that operate away from equilibrium and can thus attain life-like properties. In this Review, we focus on active materials made of cytoskeletal components, highlighting the role of active stresses and how they drive self-organization of both cellular structures and macroscale materials, which are machines powered by nanomachines.

Repellence and toxicity of Schinus molle extracts on Blattella germanica.

PubMed

Ferrero, A A; Chopa, C Sánchez; González, J O Werdin; Alzogaray, R A

2007-06-01

The biological activities of ethanol and petroleum ether extracts from leaves and fruits of Schinus molle against adults of Blattella germanica were examined by repellence test and topical application. All extracts produced significant repellent effect and mortality.

Serum Albumin Beads: An Injectable, Biodegradable System for the Sustained Release of Drugs

NASA Astrophysics Data System (ADS)

Lee, Timothy K.; Sokoloski, Theodore D.; Royer, Garfield P.

1981-07-01

Biologically active compounds were entrapped in cross-linked serum albumin microbeads. Injection of these drug-impregnated beads into rabbits produced no adverse immunological reactions. Sustained release (20 days) of progesterone was demonstrated in vivo.

Inhibition of Pseudogymnoascus destructans growth from conidia and mycelial extension by bacterially produced volatile organic compounds.

PubMed

Cornelison, Christopher T; Gabriel, Kyle T; Barlament, Courtney; Crow, Sidney A

2014-02-01

The recently identified causative agent of white-nose syndrome (WNS), Pseudogymnoascus destructans, has been implicated in the mortality of an estimated 5.5 million North American bats since its initial documentation in 2006 (Frick et al. in Science 329:679-682, 2010). In an effort to identify potential biological and chemical control options for WNS, 6 previously described bacterially produced volatile organic compounds (VOCs) were screened for anti-P. destructans activity. The compounds include decanal; 2-ethyl-1-hexanol; nonanal; benzothiazole; benzaldehyde; andN,N-dimethyloctylamine. P. destructans conidia and mycelial plugs were exposed to the VOCs in a closed air space at 15 and 4 °C and then evaluated for growth inhibition. All VOCs inhibited growth from conidia as well as inhibiting radial mycelial extension, with the greatest effect at 4 °C. Studies of the ecology of fungistatic soils and the natural abundance of the fungistatic VOCs present in these environments suggest a synergistic activity of select VOCs may occur. The evaluation of formulations of two or three VOCs at equivalent concentrations was supportive of synergistic activity in several cases. The identification of bacterially produced VOCs with anti-P. destructans activity indicates disease-suppressive and fungistatic soils as a potentially significant reservoir of biological and chemical control options for WNS and provides wildlife management personnel with tools to combat this devastating disease.

Recombinant Collagenlike Proteins

NASA Technical Reports Server (NTRS)

Fertala, Andzej

2007-01-01

A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, "Synthesis of human procollagens and collagens in recombinant DNA systems." Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications. Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.

Development of a Novel Segmental Bone Defect Construct

DTIC Science & Technology

2017-10-01

differentiation, and biological activity of both primary synoviocytes and bone marrow derived connective tissue progenitor cells. During the majority of...halted activity on the project from the dates of 31 May 2016 to 13 July 2017. However, the project is on schedule with the current, revised project...supervised all project activities and participated in the preparation of the manuscript that was produced during this reporting period. Name: Dr

Processing and characterization of silk sericin from Bombyx mori and its application in biomaterials and biomedicines.

PubMed

Cao, Ting-Ting; Zhang, Yu-Qing

2016-04-01

Bombyx mori silk is composed of 60-80% fibroin, 15-35% sericin and 1-5% non-sericin component including wax, pigments, sugars and other impurities. For two decades, the protein-based silk fibroin was extensively used in the research and development of medical biomaterials and biomedicines. Sericin is frequently ignored and abandoned as a byproduct or waste in the processing of traditional silk fabrics, silk floss or modern silk biomaterials. However, similar to fibroin, sericin is not only a highly useful biological material, but also a lot of biological activity. Moreover, the non-sericin component present with sericin in the cocoon shell also has a strong biological activity. In this review, the extraction and recovery methods of sericin and the non-sericin component from the cocoon layer are reported, and their composition, properties and biological activity are described to produce a comprehensive report on biomedical materials and biological drugs. In addition, related problems or concerns present in the research and development of sericin are discussed, and a potential application of sericin in sustainable development is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

A rapid Q-PCR titration protocol for adenovirus and helper-dependent adenovirus vectors that produces biologically relevant results

PubMed Central

Gallaher, Sean D.; Berk, Arnold J.

2013-01-01

Adenoviruses are employed in the study of cellular processes and as expression vectors used in gene therapy. The success and reproducibility of these studies is dependent in part on having accurate and meaningful titers of replication competent and helper-dependent adenovirus stocks, which is problematic due to the use of varied and divergent titration protocols. Physical titration methods, which quantify the total number of viral particles, are used by many, but are poor at estimating activity. Biological titration methods, such as plaque assays, are more biologically relevant, but are time consuming and not applicable to helper-dependent gene therapy vectors. To address this, a protocol was developed called “infectious genome titration” in which viral DNA is isolated from the nuclei of cells ~3 h post-infection, and then quantified by Q-PCR. This approach ensures that only biologically active virions are counted as part of the titer determination. This approach is rapid, robust, sensitive, reproducible, and applicable to all forms of adenovirus. Unlike other Q-PCR-based methods, titers determined by this protocol are well correlated with biological activity. PMID:23624118

ATP monitoring technology for microbial growth control in potable water systems

NASA Astrophysics Data System (ADS)

Whalen, Patrick A.; Whalen, Philip J.; Cairns, James E.

2006-05-01

ATP (Adenosine Triphosphate) is the primary energy transfer molecule present in all living biological cells on Earth. ATP cannot be produced or maintained by anything but a living organism, and as such, its measurement is a direct indication of biological activity. The main advantage of ATP as a biological indicator is the speed of the analysis - from collecting the sample to obtaining the result, only minutes are required. The technology to measure ATP is already widely utilized to verify disinfection efficacy in the food industry and is also commonly applied in industrial water processes such as cooling water systems to monitor microbial growth and biocide applications. Research has indicated that ATP measurement technology can also play a key role in such important industries as potable water distribution and biological wastewater treatment. As will be detailed in this paper, LuminUltra Technologies has developed and applied ATP measurement technologies designed for any water type, and as such can provide a method to rapidly and accurately determine the level of biological activity in drinking water supplies. Because of its speed and specificity to biological activity, ATP measurement can play a key role in defending against failing drinking water quality, including those encountered during routine operation and also bioterrorism.

Characteristics of activated carbon produced from biosludge and its use in wastewater post-treatment.

PubMed

Pikkov, L; Kallas, J; Rüütmann, T; Rikmann, E

2001-02-01

Experimental research into the bench-scale production of activated carbon from waste-activated sludge from water purification, sawdust, peat, and their mixtures, by carbonisation and activation was undertaken. The research work was carried out to determine possible methods of production of cheap activated carbon from local raw materials and to use it in water purification technology. Along with the samples produced, several commercial activated carbons (namely RB-1, F 100, CA (adsorbent from military gas masks), BAY (product of the USSR)) were tested to compare adsorption properties in the adsorption of phenols, xylidines, amines, methylene blue and molasses. It has been found that the activated carbon produced from waste biosludge was of higher quality than that produced from either sawdust or peat, and performed similarly to RB-1 and F100 in adsorption tests. It was also determined that the activated carbon produced from biosludge could possibly be used in the post-treatment of wastewater. Residual sludge from the biological treatment of the wastewater from the purification of oil-shale in the chemical processing industry could cover up to 80% of the need for activated carbon. Some of this activated carbon could be used in the post-treatment of the same water, adsorbing polyalcaline phenols from the initial content of 4 mg l-1 to the demanded level of 1 mg l-1.

Saponins from sea cucumber and their biological activities.

PubMed

Zhao, Yingcai; Xue, Changhu; Zhang, Tiantian; Wang, YuMing

2018-06-22

Sea cucumbers, belonging to the phylum Echinodermata, have been valued for centuries as a nutritious and functional food with various bioactivities. Sea cucumbers can produce highly active substances, notably saponins, the main secondary metabolites, which are the basis of their chemical defense. The saponins are mostly triterpene glycosides with triterpenes or steroid in aglycone, which possess multiple biological properties including anti-tumor, hypolipidemic activity, improvement of nonalcoholic fatty liver, inhibition of fat accumulation, anti-hyperuricemia, promotion of bone marrow hematopoiesis, anti-hypertension, etc. Sea cucumber saponins have received attention due to their rich sources, low toxicity, high efficiency, and few side effects. This review summarizes current research on the structure and activities of sea cucumber saponins based on the physiological and pharmacological activities from source, experimental models, efficacy and mechanisms, which may provide a valuable reference for the development of sea cucumber saponins.

Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. I. Producing strain, fermentation, isolation, and biological activities.

PubMed

Omura, S; Inokoshi, J; Uchida, R; Shiomi, K; Masuma, R; Kawakubo, T; Tanaka, H; Iwai, Y; Kosemura, S; Yamamura, S

1996-05-01

New protein farnesyltransferase inhibitors, andrastins A-C, have been discovered in the cultured broth of Penicillium sp. FO-3929. Andrastins extracted from broth supernatant were purified by silica gel chromatography, ODS chromatography and HPLC. The IC50 of andrastins A, B, and C against protein farnesyltransferase were 24.9, 47.1, and 13.3 microM, respectively.

Identification of an antifungal metabolite produced by a potential biocontrol Actinomyces strain A01

PubMed Central

Lu, Cai Ge; Liu, Wei Cheng; Qiu, Ji Yan; Wang, Hui Min; Liu, Ting; De Liu, Wen

2008-01-01

Actinomyces strain A01 was isolated from soil of a vegetable field in the suburb of Beijing, China. According to the morphological, cultural, physiological and biochemical characteristics, and 16S rDNA sequence analysis, strain A01 was identified as Streptomyces lydicus. In the antimicrobial spectrum test strain A01 presented a stable and strong inhibitory activity against several plant pathogenic fungi such as Fusarium oxysporum, Botrytis cinerea, Monilinia laxa, etc. However, no antibacterial activity was found. In pot experiments in greenhouse, the development of tomato gray mold was markedly suppressed by treatment with the fermentation broth of the strain A01, and the control efficacy was higher than those of Pyrimethanil and Polyoxin. A main antifungal compound (purity 99.503%) was obtained from the fermentation broth of strain A01 using column chromatography and HPLC. The chemical structural analysis with U V, IR, MS, and NMR confirmed that the compound produced by the strain A01 is natamycin, a polyene antibiotic produced by S. chattanovgensis, S. natalensis, and S. gilvosporeus, widely used as a natural biological preservative for food according to previous reports. The present study revealed a new producing strain of natamycin and its potential application as a biological control agent for fungal plant diseases. PMID:24031293

Chemical and biological monitoring of MIOR on the pilot area of Vyngapour oil field, West Sibera, Russia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arinbasarov, M.U.; Murygina, V.P.; Mats, A.A.

1995-12-31

The pilot area of the Vyngapour oil field allotted for MIOR tests contains three injection and three producing wells. These wells were treated in summer 1993 and 1994. Before, during, and after MIOR treatments on the pilot area the chemical compounds of injected and formation waters were studied, as well as the amount and species of microorganisms entering the stratum with the injected water and indigenous bacteria presented in bottomhole zones of the wells. The results of monitoring showed that the bottomhole zone of the injection well already had biocenosis of heterotrophic, hydrocarbon-oxidizing, methanogenic, and sulfate-reducing bacteria, which were besidesmore » permanently introduced into the reservoir during the usual waterflooding. The nutritious composition activated vital functions of all bacterial species presented in the bottomhole zone of the injection well. The formation waters from producing wells showed the increase of the content of nitrate, sulfate, phosphate, and bicarbonate ions by the end of MIOR. The amount of hydrocarbon-oxidizing bacteria in formation waters of producing wells increased by one order. The chemical and biological monitoring revealed the activation of the formation microorganisms, but no transport of food industry waste bacteria through the formation from injection to producing wells was found.« less

Saccharomyces cerevisiae: A novel and efficient biological control agent for Colletotrichum acutatum during pre-harvest.

PubMed

Lopes, Marcos Roberto; Klein, Mariana Nadjara; Ferraz, Luriany Pompeo; da Silva, Aline Caroline; Kupper, Katia Cristina

2015-06-01

In this study, we evaluated the efficiency of six isolates of Saccharomyces cerevisiae in controlling Colletotrichum acutatum, the causal agent of postbloom fruit drop that occur in pre-harvest citrus. We analyzed the mechanisms of action involved in biological control such as: production of antifungal compounds, nutrient competition, detection of killer activity, and production of hydrolytic enzymes of the isolates of S. cerevisiae on C. acutatum and their efficiency in controlling postbloom fruit drop on detached citrus flowers. Our results showed that all six S. cerevisiae isolates produced antifungal compounds, competed for nutrients, inhibited pathogen germination, and produced killer activity and hydrolytic enzymes when in contact with the fungus wall. The isolates were able to control the disease when detached flowers were artificially inoculated, both preventively and curatively. In this work we identified a novel potential biological control agent for C. acutatum during pre-harvest. This is the first report of yeast efficiency for the biocontrol of postbloom fruit drop, which represents an important contribution to the field of biocontrol of diseases affecting citrus populations worldwide. Copyright © 2015 Elsevier GmbH. All rights reserved.

Detection of endogenous lithium in neuropsychiatric disorders--a model for biological transmutation.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2002-01-01

The human hypothalamus produces an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na(+)-K(+) ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na(+)-K(+) ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg(++). The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na(+)-K(+) ATPase inhibition. The role of membrane Na(+)-K(+) ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na(+)-K(+) ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. Copyright 2002 John Wiley & Sons, Ltd.

DIRECT AND INDIRECT BIOLOGICAL EFFECTS OF RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hobitz, H.

1961-01-01

The primary physical processes, ionization and excitation, induced by radiation in biological materials are discussed. Their effects in causing reduction, decarboxylation, and depolymerization in proteins and deoxyribonucleic acid of the cell nucleus are examined. The action of radiation doses of 100,000- 600,000 r on pollen of Digitalis purpurea maintained at room temperature and at approximates 190 deg C showed that biological activity was destroyed by doses >200,000 r at room temperature, but at approximates 190 deg the pollen retained some activity even after the highest dose. A similar effect was seen with Bacterium cadaveris cells, about 0.5% of which survivedmore » 50000 r given at l8O deg whereas no cells survived 20000 r given at 4 deg . The presence of 1% cysteamine at the higher temperature increased survival 20-fold. Cytochrome c showed markedly different responses to radiation in dry form as compared with aqueous solution. The anhydrous enzyme showed a linear decline in log activity with radiation dose but in aqueous solution the activity declined more slowly at higher doses. The radiation dose to-produce 50% inactivation was 4 x 10/sup 7/ r in dry form and 6 x 10/sup 5/ r in solution, a 67-fold difference. The results suggest that diffusion of the free radicals (H: or OH:) produced in the primary process is considerably hindered at low temperature and by the absence of water. (H.H.D.)« less

The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-kappa B in human T-cell lines.

PubMed

Paul, N L; Millet, I; Ruddle, N H

1993-07-01

The HTLV-I transcriptional activator tax was used to gain insight into the mechanism of lymphotoxin (LT; TNF-beta) gene induction. Tax-expressing cell lines produce LT biologic activity. An LT promoter (LT-293) CAT construct that contained an NF-kappa B site was active in the LT-producing C81-66-45 cell line, which contains defective HTLV-I but expresses tax. The observation that a mutated LT-kappa B construct (M1-CAT) was inactive in C81-66-45, confirmed the importance of NF-kappa B in LT gene expression. Tax was transfected into HTLV-I-negative human T-cell lines. Jurkat T cells stably expressing tax contained elevated levels of NF-kappa B that directly bound to the LT-kappa B site. Tax co-transfected with reporter constructs into Jurkat cells maximally activated HTLV-I-LTR-CAT and kappa B-fos-CAT and also activated LT-293 to a lesser extent. In JM T cells, tax induced LT-293 activity by two- to four-fold, though there was no induction of M1-CAT. The increase in LT-293 CAT activity mirrored the increase in LT biologic activity seen under these conditions. These studies, the first to demonstrate induction of LT promoter activity over basal levels, indicate that HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter, at least in part through activation of NF-kappa B.

Enzymes in human milk

PubMed Central

Dallas, David C.; German, J. Bruce

2017-01-01

Milk proteins are a complex and diverse source of biological activities. Beyond their function intact, milk proteins also act as carriers of encrypted functional sequences that when released as peptides exert biological functions, including antimicrobial and immunomodulatory, which could contribute to the infant’s competitive success. Research has now revealed that the release of these functional peptides begins within the mammary gland itself. A complex array of proteases produced in mother’s milk have been shown to be active in the milk, releasing these peptides. Moreover, our recent research demonstrates that these milk proteases continue to digest milk proteins within the infant’s stomach, possibly even to a larger extent than the infant’s own proteases. As the neonate has relatively low digestive capacity, the activity of milk proteases in the infant may provide important assistance to digesting milk proteins. The coordinated release of these encrypted sequences is accomplished by selective proteolytic action provided by an array of native milk proteases and infant-produced enzymes. The task for scientists is now to discover the selective advantages of this protein-protease based peptide release system. PMID:28346930

Structure and Chemical Synthesis of a Biologically Active Form of Renilla (Sea Pansy) Luciferin*

PubMed Central

Hori, Kazuo; Cormier, Milton J.

1973-01-01

The structure of a biologically active form of Renilla (sea pansy) luciferin has been elucidated; this structure, confirmed by total chemical synthesis, is 3,7-dihydro-2-methyl-6-(p-hydroxyphenyl)-8-benzylimidazo [1,2-a] pyrazin-3-one. In the natural compound the methyl group at the 2 position is replaced by an unknown, more complex group. For this reason the synthetic compound is 10% as active as the natural compound in producing light with Renilla luciferase. However, the spectral properties of the two compounds are identical. In addition the rates of the luminescent reaction with both compounds are similar, and the color of the light produced is identical in each case. A compound isolated from the calcium-triggered photoprotein aequorin has been identified by Shimomura and Johnson [(1972) Biochemistry 11, 1602] to be 2-amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine. This compound forms an integral part of the structure of Renilla luciferin. This, and other evidence, suggests that the structure elucidated for Renilla luciferin is a more general one associated with the luciferins of most, if not all, bioluminescent coelenterates. PMID:16592045

Inhibition of cathelicidin activity by bacterial exopolysaccharides.

PubMed

Foschiatti, Michela; Cescutti, Paola; Tossi, Alessandro; Rizzo, Roberto

2009-06-01

The interaction of bacterial exopolysaccharides, produced by opportunistic lung pathogens, with antimicrobial peptides of the innate primate immune system was investigated. The exopolysaccharides were produced by Pseudomonas aeruginosa, Inquilinus limosus and clinical isolates of the Burkholderia cepacia complex, bacteria that are all involved in lung infections of cystic fibrosis patients. The effects of the biological activities of three orthologous cathelicidins from Homo sapiens sapiens, Pongo pygmaeus (orangutan) and Presbitys obscurus (dusky leaf monkey) were examined. Inhibition of the antimicrobial activity of peptides was assessed using minimum inhibitory concentration assays on a reference Escherichia coli strain in the presence and absence of exopolysaccharides, whereas complex formation between peptides and exopolysaccharides was investigated by means of circular dichroism, fluorescence spectroscopy and atomic force microscopy. Biological assays revealed that the higher the negative charge of exopolysaccharides the stronger was their inhibiting effect. Spectroscopic studies indicated the formation of molecular complexes of varying stability between peptides and exopolysaccharides, explaining the inhibition. Atomic force microscopy provided a direct visualization of the molecular complexes. A model is proposed where peptides with an alpha-helical conformation interact with exopolysaccharides through electrostatic and other non-covalent interactions.

[Dietary supplements from ground fish meat with DNA for treatment and prophylaxis].

PubMed

Boiarkina, L G; Kas'ianenko, Iu I; Epshteĭn, L M; Iakush, E V

1998-01-01

It has been developed a receipt of a new treatment-and-prophylactic products based on fish farce with treatment-and-prophylactic additive--DNA. It is recommended to be produced. As biological active additive keeps its initial pharmacological characteristics under technological processing this product is recommended for rendering general effect and increasing of physical and mental activity of organism.

Upregulation and Identification of Antibiotic Activity of a Marine-Derived Streptomyces sp. via Co-Cultures with Human Pathogens.

PubMed

Sung, Anne A; Gromek, Samantha M; Balunas, Marcy J

2017-08-11

Marine natural product drug discovery has begun to play an important role in the treatment of disease, with several recently approved drugs. In addition, numerous microbial natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces , due to their metabolic diversity for production of biologically active secondary metabolites. However, many secondary metabolites cannot be produced under laboratory conditions because growth conditions in flask culture differ from conditions in the natural environment. Various experimental conditions (e.g., mixed fermentation) have been attempted to increase yields of previously described metabolites, cause production of previously undetected metabolites, and increase antibiotic activity. Adult ascidians-also known as tunicates-are sessile marine invertebrates, making them vulnerable to predation and therefore are hypothesized to use host-associated bacteria that produce biologically active secondary metabolites for chemical defense. A marine-derived Streptomyces sp. strain PTY087I2 was isolated from a Panamanian tunicate and subsequently co-cultured with human pathogens including Bacillus subtilis , methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa , followed by extraction. Co-culture of Streptomyces sp. PTY087I2 with each of these human pathogens resulted in increased production of three antibiotics: granaticin, granatomycin D, and dihydrogranaticin B, as well as several analogues seen via molecular networking. In addition, co-cultures resulted in strongly enhanced biological activity against the Gram positive human pathogens used in these experiments. Expanded utilization of co-culture experiments to allow for competitive interactions may enhance metabolite production and further our understanding of these microbial interactions.

Review lipopeptides biosurfactants: Mean classes and new insights for industrial, biomedical, and environmental applications.

PubMed

Mnif, Inès; Ghribi, Dhouha

2015-05-01

Lipopeptides are microbial surface active compounds produced by a wide variety of bacteria, fungi, and yeast. They are characterized by high structural diversity and have the ability to decrease the surface and interfacial tension at the surface and interface, respectively. Surfactin, iturin, and fengycin of Bacillus subtilis are among the most popular lipopeptides. Lipopepetides can be applied in diverse domains as food and cosmetic industries for their emulsification/de-emulsification capacity, dispersing, foaming, moisturizing, and dispersing properties. Also, they are qualified as viscosity reducers, hydrocarbon solubilizing and mobilizing agents, and metal sequestering candidates for application in environment and bioremediation. Moreover, their ability to form pores and destabilize biological membrane permits their use as antimicrobial, hemolytic, antiviral, antitumor, and insecticide agents. Furthermore, lipopeptides can act at the surface and can modulate enzymes activity permitting the enhancement of the activity of certain enzymes ameliorating microbial process or the inhibition of certain other enzymes permitting their use as antifungal agents. This article will present a detailed classification of lipopeptides biosurfactant along with their producing strain and biological activities and will discuss their functional properties and related applications. © 2015 Wiley Periodicals, Inc.

[Antiradical activity and resistance of flaxseed oil enriched with the antioxidants to oxidative changes].

PubMed

Guseva, D A; Prozorovskaia, N N; Rusina, I F; Ipatova, O M

2008-01-01

Using the chemiluminescence technique, the effective concentration of antioxidants (AO) and its reactivity towards peroxyl radicals (constant k7) have been measured for the oil "Ubicato-flax" (biological active supplement) and flaxseed oil, enriched with Aronia melanocarpa extract. Ubicato-flax exhibited the highest antiradical activity but it was less resistant to oxidative changes as compared with flaxseed oil + extract. Ubicato oil produced on basis of natural AO exhibited higher antiradical activity in comparison with Ubicato oil produced on basis of the chemical synthetic AO. Aronia extract added to flaxseed oil caused marked inhibition of the increase in the peroxide value. Ubicato-flax may serve as a source of AO for not more than 6 months.

Environmental Fate and Biological Consequences of Chemicals Related to Air Force Activities

DTIC Science & Technology

1982-09-01

milliliters of a 10% solution over a 78.5-square centimeter surface. Sample treated cores were tested under laboratory conditions and in field studies and using...natural weather conditions for comparative tests. No Sig- nificant differences were noted between field and laboratory conditions . Biological...JP-4- and JP-5-dosed cores initially show a stressed condition as indicated by an increased rate in CO2 produc- tion followed by a rate of CO2

Biological Bases for Radiation Adaptive Responses in the Lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, Bobby R.; Lin, Yong; Wilder, Julie

2015-03-01

Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung, and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis, which now is known to be unsupported by a large volume of data.

Isolation, characterization, and diversity of novel radiotolerant carotenoid-producing bacteria.

PubMed

Asker, Dalal; Awad, Tarek S; Beppu, Teruhiko; Ueda, Kenji

2012-01-01

Carotenoids are natural pigments that exhibit many biological functions, such as antioxidants (i.e., promote oxidative stress resistance), membrane stabilizers, and precursors for vitamin A. The link between these biological activities and many health benefits (e.g., anticarcinogenic activity, prevention of chronic diseases, etc.) has raised the interest of several industrial sectors, especially in the cosmetics and pharmaceutical industries. The use of microorganisms in biotechnology to produce carotenoids is favorable by consumer and can help meet the growing demand for these bioactive compounds in the food, feed, and pharmaceutical industries. This methodological chapter details the development of a rapid and selective screening method for isolation and identification of carotenoid-producing microorganisms based on UV treatment, sequencing analysis of 16S rRNA genes, and carotenoids' analysis using rapid and effective High-Performance Liquid Chromatography-Diodearray-MS methods. The results of a comprehensive 16S rRNA gene-based phylogenetic analysis revealed a diversity of carotenoid-producing microorganisms (104 isolates) that were isolated at a high frequency from water samples collected at Misasa (Tottori, Japan), a region known for its high natural radioactivity content. These carotenoid-producing isolates were classified into 38 different species belonging to 7 bacterial classes (Flavobacteria, Sphingobacteria, α-Proteobacteria, γ-Proteobacteria, Deinococci, Actinobacteria, and Bacilli). The carotenoids produced by the isolates were zeaxanthin (6 strains), dihydroxyastaxanthin (24 strains), astaxanthin (27 strains), canthaxanthin (10 strains), and unidentified molecular species that were produced by the isolates related to Deinococcus, Exiguobacterium, and Flectobacillus. Here, we describe the methods used to isolate and classify these microorganisms.

Oligodeoxyribonucleotides derived from salmon sperm DNA: an alternative to defibrotide.

PubMed

Hui, Chang-Ye; Guo, Yan; Zhang, Xi; Shao, Jian-Hua; Yang, Xue-Qin; Zhang, Wen

2013-05-01

Defibrotide is a single-stranded nucleic acid polymer originally derived from porcine mucosa. Cheap salmon sperm DNA is commercially available and widely used in drug production. In this study, oligodeoxyribonucleotides were successfully obtained from the controlled depolymerization of salmon sperm DNA. The obtained product shared similar chemical and biological properties with defibrotide produced by Gentium SpA, Italy. It was also found that oligodeoxyribonucleotides derived from non-mammalian origins could also directly stimulate tissue plasminogen activator (t-PA) release from cultured human endothelial cells, and enhance fibrinolytic activity in the rabbit. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Synthesis, biological activity and dyeing performance of some novel azo disperse dyes incorporating pyrazolo[1,5-a]pyrimidines for dyeing of polyester fabrics

NASA Astrophysics Data System (ADS)

Sayed, Ahmed Z.; Aboul-Fetouh, Mahmoud S.; Nassar, Hesham S.

2012-02-01

Several novel pyrazolopyrimidine azo compounds were achieved from diazotization of 4-aminoacetanilide and coupling with malononitrile and then refluxed with hydrazine hydrate to furnish 3,5-diamino-4-(4-acetamidophenylazo)-1H-pyrazole. The later compound was diazotized and coupled with substituted α-cyanocinnamate, α-cyanocinnamonitrile, 2-cyano-3-ethoxyacrylic acid ethyl ester, chalcones and ethylacetoacetate to produce novel dyestuffs. Structures of the dyes were fully characterized by using FT-IR, 1H NMR, mass spectroscopy and elemental analysis. The dyes were applied to polyester fiber, affording satisfactory results and showed biological activity towards various microorganisms.

Aloe vera: Potential candidate in health management via modulation of biological activities

PubMed Central

Rahmani, Arshad H.; Aldebasi, Yousef H.; Srikar, Sauda; Khan, Amjad A.; Aly, Salah M.

2015-01-01

Treatment based on natural products is rapidly increasing worldwide due to the affordability and fewer side effects of such treatment. Various plants and the products derived from them are commonly used in primary health treatment, and they play a pivotal role in the treatment of diseases via modulation of biochemical and molecular pathways. Aloe vera, a succulent species, produces gel and latex, plays a therapeutic role in health management through antioxidant, antitumor, and anti-inflammatory activities, and also offers a suitable alternative approach for the treatment of various types of diseases. In this review, we summarize the possible mechanism of action and the therapeutic implications of Aloe vera in health maintenance based on its modulation of various biological activities. PMID:26392709

Biological activity and photostability of biflorin micellar nanostructures.

PubMed

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

2015-05-13

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

[Biologics - nomenclature and classification].

PubMed

Eichbaum, Christine; Haefeli, Walter E

2011-11-01

Biological medicines are a heterogeneous group of drugs that are produced by living organisms using genetic or biological technology. Unlike chemically derived small molecules biologics are structurally complex making characterization and manufacturing difficult. Moreover, biological medicines show a great variety concerning their clinical use. To appropriately consider these particularities, there are other standards and guidelines for approval of similar derivatives of biologics, the so-called biosimilars or follow-on biologics. In contrast to a generic medicinal product containing a chemically identical active ingredient, a biosimilar is only expected to be similar to the innovator drug. Nowadays, monoclonal antibodies, fragments of antibodies, and fusion proteins manufactured by recombinant procedures play an important role. They have been used in many specialties for diagnostic and therapeutic purposes and are subject to continuous further development and improvement. Their nomenclature is based on a classification by the WHO which allows drawing conclusions for class of substance, origin, and pharmacological target.

Pharmacokinetic and pharmacodynamic comparisons between human granulocyte colony-stimulating factor purified from human bladder carcinoma cell line 5637 culture medium and recombinant human granulocyte colony-stimulating factor produced in Escherichia coli.

PubMed

Tanaka, H; Kaneko, T

1992-07-01

The pharmacokinetics and biological activities of recombinant human granulocyte colony-stimulating factor (hG-CSF) produced in Escherichia coli were compared with those of hG-CSF purified from human bladder carcinoma cell line 5637 culture medium (5637-hG-CSF). Recombinant hG-CSF was biologically active in a bone marrow cell proliferation assay in vitro, with a dose-response curve similar to that of 5637-hG-CSF. The effects of 5637- and recombinant hG-CSF administered via i.v. injection to rats showed similar response patterns of neutrophil counts in peripheral blood. From these results, it is concluded that the O-linked sugar chain of hG-CSF does not contribute to the in vitro and in vivo biological activities. The pharmacokinetics of both forms of hG-CSF in rats were investigated using a sandwich enzyme-linked immunosorbent assay. After i.v. administration, the serum concentration-time curves of 5637- and recombinant hG-CSF declined biexponentially. Total body clearance and steady-state volume of distribution of 5637-hG-CSF were smaller than those for the recombinant form. After s.c. administration, a lower peak serum level, smaller AUC, and lower bioavailability of 5637-hG-CSF were observed compared to recombinant hG-CSF.

Recombinant production of enzymatically active male contraceptive drug target hTSSK2 - Localization of the TSKS domain phosphorylated by TSSK2.

PubMed

Shetty, Jagathpala; Sinville, Rondedrick; Shumilin, Igor A; Minor, Wladek; Zhang, Jianhai; Hawkinson, Jon E; Georg, Gunda I; Flickinger, Charles J; Herr, John C

2016-05-01

The testis-specific serine/threonine kinase 2 (TSSK2) has been proposed as a candidate male contraceptive target. Development of a selective inhibitor for this kinase first necessitates the production of highly purified, soluble human TSSK2 and its substrate, TSKS, with high yields and retention of biological activity for crystallography and compound screening. Strategies to produce full-length, soluble, biologically active hTSSK2 in baculovirus expression systems were tested and refined. Soluble preparations of TSSK2 were purified by immobilized-metal affinity chromatography (IMAC) followed by gel filtration chromatography. The biological activities of rec.hTSSK2 were verified by in vitro kinase and mobility shift assays using bacterially produced hTSKS (isoform 2), casein, glycogen synthase peptide (GS peptide) and various TSKS peptides as target substrates. Purified recombinant hTSSK2 showed robust kinase activity in the in vitro kinase assay by phosphorylating hTSKS isoform 2 and casein. The ATP Km values were similar for highly and partially purified fractions of hTSSK2 (2.2 and 2.7 μM, respectively). The broad spectrum kinase inhibitor staurosporine was a potent inhibitor of rec.hTSSK2 (IC50 = 20 nM). In vitro phosphorylation experiments carried out with TSKS (isoform 1) fragments revealed particularly strong phosphorylation of a recombinant N-terminal region representing aa 1-150 of TSKS, indicating that the N-terminus of human TSKS is phosphorylated by human TSSK2. Production of full-length enzymatically active recombinant TSSK2 kinase represents the achievement of a key benchmark for future discovery of TSSK inhibitors as male contraceptive agents. Copyright © 2016 Elsevier Inc. All rights reserved.

Milk Inhibits the Biological Activity of Ricin

PubMed Central

Rasooly, Reuven; He, Xiaohua; Friedman, Mendel

2012-01-01

Ricin is a highly toxic protein produced by the castor plant Ricinus communis. The toxin is relatively easy to isolate and can be used as a biological weapon. There is great interest in identifying effective inhibitors for ricin. In this study, we demonstrated by three independent assays that a component of reconstituted powdered milk has a high binding affinity to ricin. We discovered that milk can competitively bind to and reduce the amount of toxin available to asialofetuin type II, which is used as a model to study the binding of ricin to galactose cell-surface receptors. Milk also removes ricin bound to the microtiter plate. In parallel experiments, we demonstrated by activity assay and by immuno-PCR that milk can bind competitively to 1 ng/ml ricin, reducing the amount of toxin uptake by the cells, and thus inhibit the biological activity of ricin. The inhibitory effect of milk on ricin activity in Vero cells was at the same level as by anti-ricin antibodies. We also found that (a) milk did not inhibit ricin at concentrations of 10 or 100 ng/ml; (b) autoclaving 10 and 100 ng/ml ricin in DMEM at 121 °C for 30 min completely abolished activity; and (c) milk did not affect the activity of another ribosome inactivating protein, Shiga toxin type 2 (Stx2), produced by pathogenic Escherichia coli O157:H7. Unlike ricin, which is internalized into the cells via a galactose-binding site, Stx2 is internalized through the cell surface receptor glycolipid globotriasylceramides Gb3 and Gb4. These observations suggest that ricin toxicity may possibly be reduced at room temperature by a widely consumed natural liquid food. PMID:22733821

Composition and biological activities of the aqueous extracts of three scleractinian corals from the Mexican Caribbean: Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea.

PubMed

García-Arredondo, Alejandro; Rojas-Molina, Alejandra; Ibarra-Alvarado, César; Lazcano-Pérez, Fernando; Arreguín-Espinosa, Roberto; Sánchez-Rodríguez, Judith

2016-01-01

Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa , Porites astreoides and Siderastrea siderea , three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A 2 (PLA 2 ), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A 2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.

Validation of a motor activity system by a robotically controlled vehicle and using standard reference compounds.

PubMed

Patterson, John P; Markgraf, Carrie G; Cirino, Maria; Bass, Alan S

2005-01-01

A series of experiments were undertaken to evaluate the accuracy, precision, specificity, and sensitivity of an automated, infrared photo beam-based open field motor activity system, the MotorMonitor v. 4.01, Hamilton-Kinder, LLC, for use in a good laboratory practices (GLP) Safety Pharmacology laboratory. This evaluation consisted of two phases: (1) system validation, employing known inputs using the EM-100 Controller Photo Beam Validation System, a robotically controlled vehicle representing a rodent and (2) biologic validation, employing groups of rats treated with the standard pharmacologic agents diazepam or D-amphetamine. The MotorMonitor's parameters that described the open-field activity of a subject were: basic movements, total distance, fine movements, x/y horizontal ambulations, rearing, and total rest time. These measurements were evaluated over a number of zones within each enclosure. System validation with the EM-100 Controller Photo Beam Validation System showed that all the parameters accurately and precisely measured what they were intended to measure, with the exception of fine movements and x/y ambulations. Biologic validation using the central nervous system depressant diazepam at 1, 2, or 5 mg/kg, i.p. produced the expected dose-dependent reduction in rat motor activity. In contrast, the central nervous system stimulant D-amphetamine produced the expected increases in rat motor activity at 0.1 and 1 mg/kg, i.p, demonstrating the specificity and sensitivity of the system. Taken together, these studies of the accuracy, precision, specificity, and sensitivity show the importance of both system and biologic validation in the evaluation of an automated open field motor activity system for use in a GLP compliant laboratory.

Toolbox for Antibiotics Discovery from Microorganisms.

PubMed

Fisch, Katja M; Schäberle, Till F

2016-09-01

Microorganisms produce a vast array of biologically active metabolites. Such compounds are applied by humans to positively influence their health and, therefore, natural products serve as drug leads for pharmaceutical and medicinal chemistry. In this minireview, tools for the discovery and the production of potential drug leads are explained. A snapshot is provided, starting from the isolation of new producer strains, across genomic mining of (meta)genomes to identify biosynthetic gene clusters corresponding to natural products, toward heterologous expression to produce potential drug leads. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biochemical And Genetic Modification Of Polysaccharides

NASA Technical Reports Server (NTRS)

Kern, Roger G.; Petersen, Gene R.; Richards, Gil F.

1993-01-01

Bacteriophages producing endopolysaccharase-type enzymes used to produce, isolate, and purify high yields of modified polysaccharides from polysaccharides produced by, and incorporated into capsules of, certain bacteria. Bacteriophages used in conversion of native polysaccharide materials into polymers of nearly uniform high molecular weight or, alternatively, into highly pure oligosaccharides. Also used in genetic selection of families of polysaccharides structurally related to native polysaccharide materials, but having altered properties. Resulting new polysaccharides and oligosaccharides prove useful in variety of products, including pharmaceutical chemicals, coating materials, biologically active carbohydrates, and drag-reducing additives for fluids.

IFNα enhances the production of IL-6 by human neutrophils activated via TLR8.

PubMed

Zimmermann, Maili; Arruda-Silva, Fabio; Bianchetto-Aguilera, Francisco; Finotti, Giulia; Calzetti, Federica; Scapini, Patrizia; Lunardi, Claudio; Cassatella, Marco A; Tamassia, Nicola

2016-01-21

Recently, we reported that human neutrophils produce biologically active amounts of IL-6 when incubated with agonists activating TLR8, a receptor recognizing viral single strand RNA. In this study, we demonstrate that IFNα, a cytokine that modulates the early innate immune responses toward viral and bacterial infections, potently enhances the production of IL-6 in neutrophils stimulated with R848, a TLR8 agonist. We also show that such an effect is not caused by an IFNα-dependent induction of TLR7 and its consequent co-activation with TLR8 in response to R848, but, rather, it is substantially mediated by an increased production and release of endogenous TNFα. The latter cytokine, in an autocrine manner, leads to an augmented synthesis of the IkBζ co-activator and an enhanced recruitment of the C/EBPβ transcription factor to the IL-6 promoter. Moreover, we show that neutrophils from SLE patients with active disease state, hence displaying an IFN-induced gene expression signature, produce increased amounts of both IL-6 and TNFα in response to R848 as compared to healthy donors. Altogether, data uncover novel effects that type I IFN exerts in TLR8-activated neutrophils, which therefore enlarge our knowledge on the various biological actions which type I IFN orchestrates during infectious and autoimmune diseases.

BioCO2 - a multidisciplinary, biological approach using solar energy to capture CO2 while producing H2 and high value products.

PubMed

Skjånes, Kari; Lindblad, Peter; Muller, Jiri

2007-10-01

Many areas of algae technology have developed over the last decades, and there is an established market for products derived from algae, dominated by health food and aquaculture. In addition, the interest for active biomolecules from algae is increasing rapidly. The need for CO(2) management, in particular capture and storage is currently an important technological, economical and global political issue and will continue to be so until alternative energy sources and energy carriers diminish the need for fossil fuels. This review summarizes in an integrated manner different technologies for use of algae, demonstrating the possibility of combining different areas of algae technology to capture CO(2) and using the obtained algal biomass for various industrial applications thus bringing added value to the capturing and storage processes. Furthermore, we emphasize the use of algae in a novel biological process which produces H(2) directly from solar energy in contrast to the conventional CO(2) neutral biological methods. This biological process is a part of the proposed integrated CO(2) management scheme.

Directed Fluid Transport and Mixing with Biomimetic Cilia Arrays

NASA Astrophysics Data System (ADS)

Shields, A. R.; Evans, B. A.; Carstens, B. L.; Falvo, M. R.; Washburn, S.; Superfine, R.

2009-03-01

We present results on the long-range, directed fluid transport and fluidic mixing produced by the collective beating of arrays of biomimetic cilia. These artificial cilia are arrays of free-standing nanorods roughly the size of biological cilia, which we fabricate from a polymer-magnetic nanoparticle composite material and actuate with permanent magnets to mimic biological cilia. Biological cilia have evolved to produce microscale fluid transport and are increasingly being recognized as critical components in a wide range of biological systems. However, despite much effort cilia generated fluid flows remain an area of active study. In the last decade, cilia-driven fluid flow in the embryonic node of vertebrates has been implicated as the initial left-right symmetry breaking event in these embryos. With silia we generate directional fluid transport by mimicking the tilted conical beating of these nodal cilia. By seeding fluorescent microparticles into the fluid we have noted the existence of two distinct flow regimes. The fluid flow is directional and coherent above the cilia tips, while between the cilia tips and the floor particle motion is complicated and suggestive of chaotic advection.

Violacein-producing Collimonas sp. from the sea surface microlayer of costal waters in Trøndelag, Norway.

PubMed

Hakvåg, Sigrid; Fjaervik, Espen; Klinkenberg, Geir; Borgos, Sven Even F; Josefsen, Kjell D; Ellingsen, Trond E; Zotchev, Sergey B

2009-11-12

A new strain belonging to the genus Collimonas was isolated from the sea surface microlayer off the coast of Trøndelag, Norway. The bacterium, designated Collimonas CT, produced an antibacterial compound active against Micrococcus luteus. Subsequent studies using LC-MS identified this antibacterial compound as violacein, known to be produced by several marine-derived bacteria. Fragments of the violacein biosynthesis genes vioA and vioB were amplified by PCR from the Collimonas CT genome and sequenced. Phylogenetic analysis of these sequences demonstrated close relatedness of the Collimonas CT violacein biosynthetic gene cluster to those in Janthinobacterium lividum and Duganella sp., suggesting relatively recent horizontal gene transfer. Considering diverse biological activities of violacein, Collimonas CT shall be further studied as a potential producer of this compound.

Violacein-Producing Collimonas sp. from the Sea Surface Microlayer of Costal Waters in Trøndelag, Norway

PubMed Central

Hakvåg, Sigrid; Fjærvik, Espen; Klinkenberg, Geir; Borgos, Sven Even F.; Josefsen, Kjell D.; Ellingsen, Trond E.; Zotchev, Sergey B.

2009-01-01

A new strain belonging to the genus Collimonas was isolated from the sea surface microlayer off the coast of Trøndelag, Norway. The bacterium, designated Collimonas CT, produced an antibacterial compound active against Micrococcus luteus. Subsequent studies using LC-MS identified this antibacterial compound as violacein, known to be produced by several marine-derived bacteria. Fragments of the violacein biosynthesis genes vioA and vioB were amplified by PCR from the Collimonas CT genome and sequenced. Phylogenetic analysis of these sequences demonstrated close relatedness of the Collimonas CT violacein biosynthetic gene cluster to those in Janthinobacterium lividum and Duganella sp., suggesting relatively recent horizontal gene transfer. Considering diverse biological activities of violacein, Collimonas CT shall be further studied as a potential producer of this compound. PMID:20098599

Algae as promising organisms for environment and health

PubMed Central

2011-01-01

Algae, like other plants, produce a variety of remarkable compounds collectively referred to as secondary metabolites. They are synthesized by these organisms at the end of the growth phase and/or due to metabolic alterations induced by environmental stress conditions. Carotenoids, phenolic compounds, phycobiliprotein pigments, polysaccharides and unsaturated fatty acids are same of the algal natural products, which were reported to have variable biological activities, including antioxidant activity, anticancer activity, antimicroabial activity against bacteria-virus-algae-fungi, organic fertilizer and bioremediation potentials. PMID:21862867

Bill E. Kunkle Interdisciplinary Beef Symposium: Overlapping physiological responses and endocrine biomarkers that are indicative of stress responsiveness and immune function in beef cattle.

PubMed

Carroll, J A; Burdick Sanchez, N C

2014-12-01

Acknowledgment that modern livestock production systems impose stress on animals has been accepted by the scientific community and producers. As the economic burden has increased for livestock producers, expectations for animal performance have increased, thus placing more strain on the entire production system. Whether or not periodic exposure to stress within the production system jeopardizes the well-being of animals continues to be an area of debate largely because of the inability to accurately quantify the magnitude and severity of the stress response on other biological systems. Adding to the confusion is the fact that activation of the stress axis can be both beneficial and detrimental to the body depending on the duration of the stress response and the frequency at which an animal is exposed to stressful stimuli. Few would argue that continuous long-term stress inhibits livestock productivity and overall well-being. Less clear is whether or not occasional exposure to acute stress jeopardizes the productivity and well-being of livestock. To fully appreciate the complexity associated with activation of the stress axis and the overall biological impact on the body, one must delve deep into the scientific literature and examine the science in an unbiased manner. It is imperative to appreciate and understand that activation of the stress axis is an essential survival mechanism necessary to maintain homeostasis during biologically challenging times. Acute activation of the stress axis leads to repartitioning of energy to organs and tissues essential for coping with stress, redirection of blood flow from the peripheral to large muscle groups, decreased digestive function, and priming of the immune system to prepare for subsequent infections. Conversely, chronic activation of the stress axis disrupts digestive function, causes catabolism of muscle and adipose tissue, and suppresses overall immune function, thus making an animal more susceptible to disease. But what parameters are needed to distinguish periods of acute stress from those of chronic stress, and what biological markers are the best indicators of "stress" in an animal? Although there are a plethora of physiological responses and endocrine biomarkers that can be quantified, an integrative tool that has been readily embraced by scientists and producers as an effective and efficient indicator of the duration and magnitude of stress that an animal is experiencing has yet to be identified.

Plant defense activators as elicitors of oat avenanthramide biosynthesis

USDA-ARS?s Scientific Manuscript database

Oats produce a group of phenolic secondary metabolites termed “avenanthramides”. Among food crops these metabolites are unique to oat. In addition to their biological role as phytoalexins, the avenanthramides are potent antioxidants in vitro and have potential as nutraceuticals. In cellular assays ...

The coronafacoyl phytotoxins: structure, biosynthesis, regulation and biological activities.

PubMed

Bignell, Dawn R D; Cheng, Zhenlong; Bown, Luke

2018-05-01

Phytotoxins are secondary metabolites that contribute to the development and/or severity of diseases caused by various plant pathogenic microorganisms. The coronafacoyl phytotoxins are an important family of plant toxins that are known or suspected to be produced by several phylogenetically distinct plant pathogenic bacteria, including the gammaproteobacterium Pseudomonas syringae and the actinobacterium Streptomyces scabies. At least seven different family members have been identified, of which coronatine was the first to be described and is the best-characterized. Though nonessential for disease development, coronafacoyl phytotoxins appear to enhance the severity of disease symptoms induced by pathogenic microbes during host infection. In addition, the identification of coronafacoyl phytotoxin biosynthetic genes in organisms not known to be plant pathogens suggests that these metabolites may have additional roles other than as virulence factors. This review focuses on our current understanding of the structures, biosynthesis, regulation, biological activities and evolution of coronafacoyl phytotoxins as well as the different methods that are used to detect these metabolites and the organisms that produce them.

Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents

NASA Astrophysics Data System (ADS)

El-Helby, Abdel Ghany A.; Ayyad, Rezk R.; Sakr, Helmy M.; Abdelrahim, Adel S.; El-Adl, K.; Sherbiny, Farag S.; Eissa, Ibrahim H.; Khalifa, Mohamed M.

2017-02-01

In view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4-22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues.

Structures and biological activities of azaphilones produced by Penicillium sp. KCB11A109 from a ginseng field.

PubMed

Son, Sangkeun; Ko, Sung-Kyun; Kim, Jong Won; Lee, Jae Kyoung; Jang, Mina; Ryoo, In-Ja; Hwang, Gwi Ja; Kwon, Min Cheol; Shin, Kee-Sun; Futamura, Yushi; Hong, Young-Soo; Oh, Hyuncheol; Kim, Bo Yeon; Ueki, Masashi; Takahashi, Shunji; Osada, Hiroyuki; Jang, Jae-Hyuk; Ahn, Jong Seog

2016-02-01

Twelve metabolites, including five highly oxygenated azaphilones, geumsanols A-E, along with seven known analogues were isolated from Penicillium sp. KCB11A109, a fungus derived from a ginseng field. Their structures were assigned by spectroscopic means (NMR and MS), and stereochemistries were determined by extensive spectroscopic analyses ((1)H-(1)H coupling constants, NOESY, and HETLOC) and chemical derivatizations (modified Mosher's method and acetonide formation). The isolates were evaluated for their anticancer, antimicrobial, antimalarial activities, and phenotypic effects in zebrafish development. Of these compounds possessing no pyranoquinone core, only geumsanol E exhibited cytotoxic activities and toxic effects on zebrafish embryos, suggesting that a double bond at C-11 and C-12 is important for biological activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

[The advance in synthetic biology: towards a microbe-derived paclitaxel intermediates].

PubMed

Wang, Wei; Yang, Yan; Zheng, Xiao-Dong; Huang, Shu-Qiong; Guo, Lei; Kong, Jian-Qiang; Cheng, Ke-Di

2013-02-01

The synthetic biology matures to promote the heterologous biosynthesis of the well-known drug paclitaxel that is one of the most important and active chemotherapeutic agents for the first-line clinical treatment of cancer. This review focuses on the construction and regulation of the biosynthetic pathway of paclitaxel intermediates in both Escherichia coli and Saccharomyces cerevisiae. In particular, the review also features the early efforts to design and overproduce taxadiene and the bottleneck of scale fermentation for producing the intermediates.

An Update on the Biological Activities of Euterpe edulis (Juçara).

PubMed

Cardoso, Alyne Lizane; de Liz, Sheyla; Rieger, Débora Kurrle; Farah, Ana Carolina Aguiar; Kunradi Vieira, Francilene Gracieli; Altenburg de Assis, Maria Alice; Di Pietro, Patricia Faria

2018-05-01

The palm tree Euterpe edulis , known as juçara, produces spherical and purple fruits, similar to those of the Euterpe oleracea and Euterpe precatoria palm trees, from which the common name açaí originates. Juçara fruit has been gaining prominence in the scientific world for its interesting nutritional composition, which is rich in antioxidants, and for its sustainable production model. Recently, relevant biological activities have been associated with the juçara fruit, and its use in alimentation has become an important nutritional, environmental, and economic alternative. The aim of this review is to compile recent scientific data about the phytochemical characterization and biological activities of E. edulis. A review of the literature was conducted in two electronic databases, Medline and Science Direct. The eligibility criteria were as follows: phytochemicals characterize of the E. edulis fruits and evaluate biological effects in vitro or in vivo with pulp, extract, juice, or product of juçara fruits. Investigations were excluded if they used other parts of the plant (seeds), did not assess biological activities, or have tested methodologies for compound extraction. From the identified reports, 25 articles were eligible for this study. The promotion of health benefits related to juçara fruits seems to have improved antioxidant activity in vivo, benefits to lipid and glycemic profiles, and modulation of inflammatory status in experimental studies in animals. Georg Thieme Verlag KG Stuttgart · New York.

Marine actinobacteria: an important source of bioactive natural products.

PubMed

Manivasagan, Panchanathan; Kang, Kyong-Hwa; Sivakumar, Kannan; Li-Chan, Eunice C Y; Oh, Hyun-Myung; Kim, Se-Kwon

2014-07-01

Marine environment is largely an untapped source for deriving actinobacteria, having potential to produce novel, bioactive natural products. Actinobacteria are the prolific producers of pharmaceutically active secondary metabolites, accounting for about 70% of the naturally derived compounds that are currently in clinical use. Among the various actinobacterial genera, Actinomadura, Actinoplanes, Amycolatopsis, Marinispora, Micromonospora, Nocardiopsis, Saccharopolyspora, Salinispora, Streptomyces and Verrucosispora are the major potential producers of commercially important bioactive natural products. In this respect, Streptomyces ranks first with a large number of bioactive natural products. Marine actinobacteria are unique enhancing quite different biological properties including antimicrobial, anticancer, antiviral, insecticidal and enzyme inhibitory activities. They have attracted global in the last ten years for their ability to produce pharmaceutically active compounds. In this review, we have focused attention on the bioactive natural products isolated from marine actinobacteria, possessing unique chemical structures that may form the basis for synthesis of novel drugs that could be used to combat resistant pathogenic microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Purified high molecular weight synthetic Aβ(1-42) and biological Aβ oligomers are equipotent in rapidly inducing MTT formazan exocytosis.

PubMed

Weidner, Adam M; Housley, Molly; Murphy, M Paul; Levine, Harry

2011-06-15

Synthetic soluble Aβ oligomers are often used as a surrogate for biologic material in a number of model systems. We compared the activity of Aβ oligomers (synthetic and cell culture media derived) on the human SH-SY5Y neuroblastoma and C2C12 mouse myoblast cell lines in a novel, modified MTT assay. Separating oligomers from monomeric peptide by size exclusion chromatography produced effects at peptide concentrations approaching physiologic levels (10-100 nM). Purified oligomers, but not monomers or fibrils, elicited an increase of a detergent-insoluble form of MTT formazan within 2h as opposed to a control toxin (H(2)O(2)). This effect was comparable for biological and synthetic peptide in both cell types. Monomeric Aβ attenuated the effect of soluble oligomers. This study suggests that the activities of biological and synthetic oligomers are indistinguishable during early stages of Aβ oligomer-cell interaction. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology.

PubMed

Wang, Baojun; Kitney, Richard I; Joly, Nicolas; Buck, Martin

2011-10-18

Modular and orthogonal genetic logic gates are essential for building robust biologically based digital devices to customize cell signalling in synthetic biology. Here we constructed an orthogonal AND gate in Escherichia coli using a novel hetero-regulation module from Pseudomonas syringae. The device comprises two co-activating genes hrpR and hrpS controlled by separate promoter inputs, and a σ(54)-dependent hrpL promoter driving the output. The hrpL promoter is activated only when both genes are expressed, generating digital-like AND integration behaviour. The AND gate is demonstrated to be modular by applying new regulated promoters to the inputs, and connecting the output to a NOT gate module to produce a combinatorial NAND gate. The circuits were assembled using a parts-based engineering approach of quantitative characterization, modelling, followed by construction and testing. The results show that new genetic logic devices can be engineered predictably from novel native orthogonal biological control elements using quantitatively in-context characterized parts. © 2011 Macmillan Publishers Limited. All rights reserved.

Investigation of Marine-Derived Fungal Diversity and Their Exploitable Biological Activities

PubMed Central

Hong, Joo-Hyun; Jang, Seokyoon; Heo, Young Mok; Min, Mihee; Lee, Hwanhwi; Lee, Young Min; Lee, Hanbyul; Kim, Jae-Jin

2015-01-01

Marine fungi are potential producers of bioactive compounds that may have pharmacological and medicinal applications. Fungi were cultured from marine brown algae and identified using multiple target genes to confirm phylogenetic placement. These target genes included the internal transcribed spacer (ITS), the nuclear large subunit (LSU), and the β-tubulin region. Various biological activities of marine-derived fungi were evaluated, including their antifungal, antioxidant and cellulolytic enzyme activities. As a result, a total of 50 fungi was isolated from the brown algae Sargassum sp. Among the 50 isolated fungi, Corollospora angusta was the dominant species in this study. The genus Arthrinium showed a relatively strong antifungal activity to all of the target plant pathogenic fungi. In particular, Arthrinium saccharicola KUC21221 showed high radical scavenging activity and the highest activities in terms of filter paper units (0.39 U/mL), endoglucanase activity (0.38 U/mL), and β-glucosidase activity (1.04 U/mL). PMID:26133554

Characterization of the corrosion resistance of several alloys to dilute biologically active solutions

NASA Technical Reports Server (NTRS)

Walsh, Daniel W.

1990-01-01

Sulfate reducing bacteria and acid producing bacteria/fungi detected in hygiene waters increased the corrosion rate in aluminum alloy. Biologically active media enhanced the formation of pits on metal coupons. Direct observation of gas evolved at the corrosion sample, coupled with scanning electron microscopy (SEM) and energy dispersive x-ray analysis of the corrosion products indicates that the corrosion rate is increased because the presence of bacteria favor the reduction of hydrogen as the cathodic reaction through the reaction of oxygen and water. SEM verifies the presence of microbes in a biofilm on the surface of corroding samples. The bacterial consortia are associated with anodic sites on the metal surface, aggressive pitting occurs adjacent to biofilms. Many pits are associated with triple points and inclusions in the aluminum alloy microstructure. Similar bacterial colonization was found on the stainless steel samples. Fourier transform Infrared Spectroscopy confirmed the presence of carbonyl groups in pitted areas of samples exposed to biologically active waters.

Development and Mining of a Volatile Organic Compound Database

PubMed Central

Abdullah, Azian Azamimi; Ono, Naoaki; Sugiura, Tadao; Morita, Aki Hirai; Katsuragi, Tetsuo; Muto, Ai; Nishioka, Takaaki; Kanaya, Shigehiko

2015-01-01

Volatile organic compounds (VOCs) are small molecules that exhibit high vapor pressure under ambient conditions and have low boiling points. Although VOCs contribute only a small proportion of the total metabolites produced by living organisms, they play an important role in chemical ecology specifically in the biological interactions between organisms and ecosystems. VOCs are also important in the health care field as they are presently used as a biomarker to detect various human diseases. Information on VOCs is scattered in the literature until now; however, there is still no available database describing VOCs and their biological activities. To attain this purpose, we have developed KNApSAcK Metabolite Ecology Database, which contains the information on the relationships between VOCs and their emitting organisms. The KNApSAcK Metabolite Ecology is also linked with the KNApSAcK Core and KNApSAcK Metabolite Activity Database to provide further information on the metabolites and their biological activities. The VOC database can be accessed online. PMID:26495281

Cooperativity to increase Turing pattern space for synthetic biology.

PubMed

Diambra, Luis; Senthivel, Vivek Raj; Menendez, Diego Barcena; Isalan, Mark

2015-02-20

It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspired by components that we recently described in a synthetic biology study in mammalian cells.1 The model employs a single promoter to express both the activator and inhibitor genes and produces Turing patterns over large regions of parameter space, using biologically interpretable Hill function reactions. We applied a stability analysis and identified rules for choosing biologically tunable parameter relationships to increase the likelihood of successful patterning. We show how to control Turing pattern sizes and time evolution by manipulating the values for production and degradation relationships. More importantly, our analysis predicts that steep dose-response functions arising from cooperativity are mandatory for Turing patterns. Greater steepness increases parameter space and even reduces the requirement for differential diffusion between activator and inhibitor. These results demonstrate some of the limitations of linear scenarios for reaction-diffusion systems and will help to guide projects to engineer synthetic Turing patterns.

The use of mineral crystals as bio-markers in the search for life on Mars

NASA Technical Reports Server (NTRS)

Schwartz, D. E.; Mancinelli, R. L.; Kaneshiro, E. S.

1992-01-01

It is proposed that minerals resulting from biologically controlled mineralization processes be utilized as biomarkers because of their favorable qualities. Universal signatures of life (biomarkers) are discussed in terms of their terrestrial forms and hypothetical Martian counterparts including organics, suites of specific inorganic and organic compounds, and isotopic ratios. It is emphasized that minerals produced under biologic control have morphological and isotopic compositions that are not found in their abiotic counterparts. Other biomarkers are not necessarily indicative of biological origin and are therefore unreliable resources for scientific study. Mineral crystals are also stable over long geological periods, and the minerals from Martian fluvial features can therefore be employed to search for fossils and biomarkers of early biological activity.

Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation.

PubMed

Ní Ógáin, Orla; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

2012-09-01

The aim of this study was to determine if spray-drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation. Trypsin was spray-dried with raffinose from a methanol : n-butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co-spray-dried with raffinose, trehalose or hydroxpropyl-β-cyclodextrin. The spray-dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in-vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed. The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray-drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl-β-cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high-humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs. NPMPs of trypsin : excipient systems can be produced by spray-drying by adjustment of the solvent system to allow for adequate solubility of trypsin. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Biological Role of Paenilarvins, Iturin-Like Lipopeptide Secondary Metabolites Produced by the Honey Bee Pathogen Paenibacillus larvae

PubMed Central

Gensel, Sebastian; Garcia-Gonzalez, Eva; Ebeling, Julia; Skobalj, Ranko; Kuthning, Anja; Süssmuth, Roderich D.

2016-01-01

The Gram-positive bacterium Paenibacillus larvae (P. larvae) is the causative agent of a deadly honey bee brood disease called American Foulbrood (AFB). AFB is a notifiable epizootic in most countries and, hence, P. larvae is of considerable relevance for veterinarians and apiculturists alike. Over the last decade, much progress has been made in the understanding of the (patho)biology of P. larvae. Recently, several non-ribosomally produced peptides (NRP) and peptide/polyketide (NRP/PK) hybrids produced by P. larvae were identified. Among these NRPs were iturin-like lipopeptides, the paenilarvins A-C. Iturins are known to exhibit strong anti-fungal activity; for some iturins, cytotoxic activity towards mammalian erythrocytes and human cancer cell lines are described. We here present our results on the analysis of the natural function of the paenilarvins during pathogenesis of P. larvae infections. We demonstrated production of paenilarvins in infected larvae. However, we could neither demonstrate cytotoxicity of paenilarvins towards cultured insect cells nor towards larvae in feeding assays. Accordingly, exposure bioassays performed with larvae infected by wild-type P. larvae and a knockout mutant of P. larvae lacking production of paenilarvins did not substantiate a role for the paenilarvins as virulence factor. Further experiments are necessary to analyze the relevance of the paenilarvins’ anti-fungal activity for P. larvae infections in the presence of fungal competitors in the larval midgut or cadaver. PMID:27760211

Biological Role of Paenilarvins, Iturin-Like Lipopeptide Secondary Metabolites Produced by the Honey Bee Pathogen Paenibacillus larvae.

PubMed

Hertlein, Gillian; Seiffert, Marlene; Gensel, Sebastian; Garcia-Gonzalez, Eva; Ebeling, Julia; Skobalj, Ranko; Kuthning, Anja; Süssmuth, Roderich D; Genersch, Elke

2016-01-01

The Gram-positive bacterium Paenibacillus larvae (P. larvae) is the causative agent of a deadly honey bee brood disease called American Foulbrood (AFB). AFB is a notifiable epizootic in most countries and, hence, P. larvae is of considerable relevance for veterinarians and apiculturists alike. Over the last decade, much progress has been made in the understanding of the (patho)biology of P. larvae. Recently, several non-ribosomally produced peptides (NRP) and peptide/polyketide (NRP/PK) hybrids produced by P. larvae were identified. Among these NRPs were iturin-like lipopeptides, the paenilarvins A-C. Iturins are known to exhibit strong anti-fungal activity; for some iturins, cytotoxic activity towards mammalian erythrocytes and human cancer cell lines are described. We here present our results on the analysis of the natural function of the paenilarvins during pathogenesis of P. larvae infections. We demonstrated production of paenilarvins in infected larvae. However, we could neither demonstrate cytotoxicity of paenilarvins towards cultured insect cells nor towards larvae in feeding assays. Accordingly, exposure bioassays performed with larvae infected by wild-type P. larvae and a knockout mutant of P. larvae lacking production of paenilarvins did not substantiate a role for the paenilarvins as virulence factor. Further experiments are necessary to analyze the relevance of the paenilarvins' anti-fungal activity for P. larvae infections in the presence of fungal competitors in the larval midgut or cadaver.

Watermelon profilin: characterization of a major allergen as a model for plant-derived food profilins.

PubMed

Cases, Bárbara; Pastor-Vargas, Carlos; Dones, Félix Gil; Perez-Gordo, Marina; Maroto, Aroa S; de las Heras, Manuel; Vivanco, Fernando; Cuesta-Herranz, Javier

2010-01-01

Plant profilins have been reported as minor allergens. They are a well-known pan-allergen family responsible for cross-reactivity between plant-derived foods and pollens. Watermelon profilin has been reported to be a major allergen in watermelon (Citrullus lanatus).The aim of this study was to characterize recombinant watermelon profilin, confirming its reactivity for diagnostic purposes and the development of immunotherapy. Native profilin was purified from watermelon extract by affinity chromatography using poly-L-proline. Recombinant His-tagged profilin was produced in Pichia pastoris yeast using pPICZαA vector and purified by metal chelate affinity chromatography. ELISA and immunoblot were carried out with sera from 17 watermelon-allergic patients. Biological activity was tested by the basophil activation test. Native profilin and recombinant profilin were purified and identified by mass spectrometry. Both show similar IgE reactivity in vitro and are biologically active. Similarities were found in the IgE-binding patterns and biological activity of recombinant profilin and native profilin. Recombinant profilin may be a powerful tool for specific diagnosis. Copyright © 2010 S. Karger AG, Basel.

Polarization: A Key Difference between Man-made and Natural Electromagnetic Fields, in regard to Biological Activity.

PubMed

Panagopoulos, Dimitris J; Johansson, Olle; Carlo, George L

2015-10-12

In the present study we analyze the role of polarization in the biological activity of Electromagnetic Fields (EMFs)/Electromagnetic Radiation (EMR). All types of man-made EMFs/EMR - in contrast to natural EMFs/EMR - are polarized. Polarized EMFs/EMR can have increased biological activity, due to: 1) Ability to produce constructive interference effects and amplify their intensities at many locations. 2) Ability to force all charged/polar molecules and especially free ions within and around all living cells to oscillate on parallel planes and in phase with the applied polarized field. Such ionic forced-oscillations exert additive electrostatic forces on the sensors of cell membrane electro-sensitive ion channels, resulting in their irregular gating and consequent disruption of the cell's electrochemical balance. These features render man-made EMFs/EMR more bioactive than natural non-ionizing EMFs/EMR. This explains the increasing number of biological effects discovered during the past few decades to be induced by man-made EMFs, in contrast to natural EMFs in the terrestrial environment which have always been present throughout evolution, although human exposure to the latter ones is normally of significantly higher intensities/energy and longer durations. Thus, polarization seems to be a trigger that significantly increases the probability for the initiation of biological/health effects.

Polarization: A Key Difference between Man-made and Natural Electromagnetic Fields, in regard to Biological Activity

PubMed Central

Panagopoulos, Dimitris J.; Johansson, Olle; Carlo, George L.

2015-01-01

In the present study we analyze the role of polarization in the biological activity of Electromagnetic Fields (EMFs)/Electromagnetic Radiation (EMR). All types of man-made EMFs/EMR - in contrast to natural EMFs/EMR - are polarized. Polarized EMFs/EMR can have increased biological activity, due to: 1) Ability to produce constructive interference effects and amplify their intensities at many locations. 2) Ability to force all charged/polar molecules and especially free ions within and around all living cells to oscillate on parallel planes and in phase with the applied polarized field. Such ionic forced-oscillations exert additive electrostatic forces on the sensors of cell membrane electro-sensitive ion channels, resulting in their irregular gating and consequent disruption of the cell’s electrochemical balance. These features render man-made EMFs/EMR more bioactive than natural non-ionizing EMFs/EMR. This explains the increasing number of biological effects discovered during the past few decades to be induced by man-made EMFs, in contrast to natural EMFs in the terrestrial environment which have always been present throughout evolution, although human exposure to the latter ones is normally of significantly higher intensities/energy and longer durations. Thus, polarization seems to be a trigger that significantly increases the probability for the initiation of biological/health effects. PMID:26456585

Polarization: A Key Difference between Man-made and Natural Electromagnetic Fields, in regard to Biological Activity

NASA Astrophysics Data System (ADS)

Panagopoulos, Dimitris J.; Johansson, Olle; Carlo, George L.

2015-10-01

In the present study we analyze the role of polarization in the biological activity of Electromagnetic Fields (EMFs)/Electromagnetic Radiation (EMR). All types of man-made EMFs/EMR - in contrast to natural EMFs/EMR - are polarized. Polarized EMFs/EMR can have increased biological activity, due to: 1) Ability to produce constructive interference effects and amplify their intensities at many locations. 2) Ability to force all charged/polar molecules and especially free ions within and around all living cells to oscillate on parallel planes and in phase with the applied polarized field. Such ionic forced-oscillations exert additive electrostatic forces on the sensors of cell membrane electro-sensitive ion channels, resulting in their irregular gating and consequent disruption of the cell’s electrochemical balance. These features render man-made EMFs/EMR more bioactive than natural non-ionizing EMFs/EMR. This explains the increasing number of biological effects discovered during the past few decades to be induced by man-made EMFs, in contrast to natural EMFs in the terrestrial environment which have always been present throughout evolution, although human exposure to the latter ones is normally of significantly higher intensities/energy and longer durations. Thus, polarization seems to be a trigger that significantly increases the probability for the initiation of biological/health effects.

Data integration in biological research: an overview.

PubMed

Lapatas, Vasileios; Stefanidakis, Michalis; Jimenez, Rafael C; Via, Allegra; Schneider, Maria Victoria

2015-12-01

Data sharing, integration and annotation are essential to ensure the reproducibility of the analysis and interpretation of the experimental findings. Often these activities are perceived as a role that bioinformaticians and computer scientists have to take with no or little input from the experimental biologist. On the contrary, biological researchers, being the producers and often the end users of such data, have a big role in enabling biological data integration. The quality and usefulness of data integration depend on the existence and adoption of standards, shared formats, and mechanisms that are suitable for biological researchers to submit and annotate the data, so it can be easily searchable, conveniently linked and consequently used for further biological analysis and discovery. Here, we provide background on what is data integration from a computational science point of view, how it has been applied to biological research, which key aspects contributed to its success and future directions.

Common Commercial and Consumer Products Contain Activators of the Aryl Hydrocarbon (Dioxin) Receptor

PubMed Central

Zhao, Bin; Bohonowych, Jessica E. S.; Timme-Laragy, Alicia; Jung, Dawoon; Affatato, Alessandra A.; Rice, Robert H.; Di Giulio, Richard T.; Denison, Michael S.

2013-01-01

Activation of the Ah receptor (AhR) by halogenated aromatic hydrocarbons (HAHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), can produce a wide variety of toxic and biological effects. While recent studies have shown that the AhR can bind and be activated by structurally diverse chemicals, how widespread of these AhR agonists are in environmental, biological and synthetic materials remains to be determined. Using AhR-based assays, we demonstrate the presence of potent AhR agonists in a variety of common commercial and consumer items. Solvent extracts of paper, rubber and plastic products contain chemicals that can bind to and stimulate AhR DNA binding and/or AhR-dependent gene expression in hepatic cytosol, cultured cell lines, human epidermis and zebrafish embryos. In contrast to TCDD and other persistent dioxin-like HAHs, activation of AhR-dependent gene expression by these extracts was transient, suggesting that the agonists are metabolically labile. Solvent extracts of rubber products produce AhR-dependent developmental toxicity in zebrafish in vivo, and inhibition of expression of the metabolic enzyme CYP1A, significantly increased their toxic potency. Although the identity of the responsible AhR-active chemicals and their toxicological impact remain to be determined, our data demonstrate that AhR active chemicals are widely distributed in everyday products. PMID:23441220

Drazepinone, a trisubstituted tetrahydronaphthofuroazepinone with herbicidal activity produced by Drechslera siccans.

PubMed

Evidente, Antonio; Andolfi, Anna; Vurro, Maurizio; Fracchiolla, Mariano; Zonno, Maria Chiara; Motta, Andrea

2005-03-01

When grown in a minimal-defined medium, a strain of Drechslera siccans, a pathogenic fungus isolated from seeds of Lolium perenne, produced phytotoxic metabolites. This strain is one of the best toxin producers among several grass pathogenic fungal strains collected and tested to find phytotoxins to be used as natural herbicides of monocot weeds. From the culture filtrates of D. siccans, we isolated a new phytotoxic trisubstituted naphthofuroazepinone, named drazepinone, and characterised it as a 3,5,12a-trimethyl-2,5,5a,12a-tetrahydro-1H-naphtho[2',3':4,5]furo[2,3-b]azepin-2-one. Assayed at 2 microg microl(-1) solution the novel metabolite proved to have broad-spectrum herbicidal properties, without antibacterial and antifungal activities, and low zootoxic activity. Its original chemical structure and the interesting biological properties make drazepinone a potential natural herbicide.

Evaluation of glycosyl hydrolases from thermophilic fungi for their potential in bioconversion of alkali and biologically treated Parthenium hysterophorus weed and rice straw into ethanol.

PubMed

Mahajan, Chhavi; Chadha, B S; Nain, Lata; Kaur, Amarjeet

2014-07-01

The aim of this work was to evaluate glycosyl hydrolases produced by diverse thermophilic fungal strains for saccharification of alkali and biologically (Trametes hirusita/Myrothecium roridum) treated Parthenium hysterophorus and rice straw. The compositional analysis of hydrolysates by HPLC showed distinct profiles of hexose, pentose and oligomeric sugars. Malbranchea cinnamomea was most efficient source of glycosyl hydrolases producing 283.8, 35.9, 129.6, 27,193, 4.66, 7.26(units/gds) of endoglucanase, cellobiohydrolase, β-glucosidase, xylanase, α-αrabinofuranosidase and β xylosidase, respectively. The saccharification of alkali and biologically treated carrot grass by culture extract of M. cinnamomea was further enhanced by supplementation of β-glucosidase produced by Aspergillus sp. mutant "O". The resultant hydrolysates containing glucose/xylose were fermented efficiently to ethanol by Saccharomyces cerevisiae owing to presence of xylose isomerase (0.8 units/gds) activity in culture extract of M. cinnamomea resulting in production of 16.5 and 15.0 g/l of ethanol from alkali treated rice straw and carrot grass, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Mono and Di-rhamnolipids on Biofilms Pre-formed by Bacillus subtilis BBK006.

PubMed

De Rienzo, Mayri A Díaz; Martin, Peter J

2016-08-01

Different microbial inhibition strategies based on the planktonic bacterial physiology have been known to have limited efficacy on the growth of biofilms communities. This problem can be exacerbated by the emergence of increasingly resistant clinical strains. Biosurfactants have merited renewed interest in both clinical and hygienic sectors due to their potential to disperse microbial biofilms. In this work, we explore the aspects of Bacillus subtilis BBK006 biofilms and examine the contribution of biologically derived surface-active agents (rhamnolipids) to the disruption or inhibition of microbial biofilms produced by Bacillus subtilis BBK006. The ability of mono-rhamnolipids (Rha-C10-C10) produced by Pseudomonas aeruginosa ATCC 9027 and the di-rhamnolipids (Rha-Rha-C14-C14) produced by Burkholderia thailandensis E264, and phosphate-buffered saline to disrupt biofilm of Bacillus subtilis BBK006 was evaluated. The biofilm produced by Bacillus subtilis BBK006 was more sensitive to the di-rhamnolipids (0.4 g/L) produced by Burkholderia thailandensis than the mono-rhamnolipids (0.4 g/L) produced by Pseudomonas aeruginosa ATCC 9027. Rhamnolipids are biologically produced compounds safe for human use. This makes them ideal candidates for use in new generations of bacterial dispersal agents and useful for use as adjuvants for existing microbial suppression or eradication strategies.

The beet Y locus encodes an anthocyanin-MYB-like protein that activates the betalain red pigment pathway

USDA-ARS?s Scientific Manuscript database

Almost all flowering plants produce red/violet, phenylalanine-based, anthocyanin pigments. A single order, the Caryophyllales, contains families that replace anthocyanins with tyrosine-based red and yellow betalain pigments. Close biological correlation of pigmentation patterns suggested that betala...

Gossypolone and Gossypolhemiquinone: Biological activity of terpenoids found in cotton (Gossypium)

USDA-ARS?s Scientific Manuscript database

The wild cotton plant, Gossypium thurberi grows in the Sonoran Desert in northern Mexico and southern Arizona, and is attacked by few herbivorous insects (Korban, 1999). In general, members of Gossypium produce a rich assortment of sesquiterpenoid and sesterterpenoids in the subepidermal pigment gl...

Characterizing a novel strain of Bacillus amyloliquefaciens BAC03 for potential biological control application

USDA-ARS?s Scientific Manuscript database

Aims: Identify and characterize a bacterial strain from suppressive soil, BAC03, evaluate its antimicrobial activity against Streptomyces scabies and other microorganisms, and characterize an antimicrobial substance produced by this strain. Methods and Results: Bacterial strain BAC03 (isolated from ...

Biological activity of peanut (Arachis hypogaea) phytoalexins and selected natural and synthetic stilbenoids

USDA-ARS?s Scientific Manuscript database

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene have be...

Organocatalytic atroposelective synthesis of axially chiral styrenes

NASA Astrophysics Data System (ADS)

Zheng, Sheng-Cai; Wu, San; Zhou, Qinghai; Chung, Lung Wa; Ye, Liu; Tan, Bin

2017-05-01

Axially chiral compounds are widespread in biologically active compounds and are useful chiral ligands or organocatalysts in asymmetric catalysis. It is well-known that styrenes are one of the most abundant and principal feedstocks and thus represent excellent prospective building blocks for chemical synthesis. Driven by the development of atroposelective synthesis of axially chiral styrene derivatives, we discovered herein the asymmetric organocatalytic approach via direct Michael addition reaction of substituted diones/ketone esters/malononitrile to alkynals. The axially chiral styrene compounds were produced with good chemical yields, enantioselectivities and almost complete E/Z-selectivities through a secondary amine-catalysed iminium activation strategy under mild conditions. Such structural motifs are important precursors for further transformations into biologically active compounds and synthetic useful intermediates and may have potential applications in asymmetric synthesis as olefin ligands or organocatalysts.

Sweat Gland Progenitors in Development, Homeostasis, and Wound Repair

PubMed Central

Lu, Catherine; Fuchs, Elaine

2014-01-01

The human body is covered with several million sweat glands. These tiny coiled tubular skin appendages produce the sweat that is our primary source of cooling and hydration of the skin. Numerous studies have been published on their morphology and physiology. Until recently, however, little was known about how glandular skin maintains homeostasis and repairs itself after tissue injury. Here, we provide a brief overview of sweat gland biology, including newly identified reservoirs of stem cells in glandular skin and their activation in response to different types of injuries. Finally, we discuss how the genetics and biology of glandular skin has advanced our knowledge of human disorders associated with altered sweat gland activity. PMID:24492848

Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide.

PubMed

Rothan, Hussin A; Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M; Rahman, Noorsaadah Abd; Yusof, Rohana

2013-11-01

Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

Antiviral Cationic Peptides as a Strategy for Innovation in Global Health Therapeutics for Dengue Virus: High Yield Production of the Biologically Active Recombinant Plectasin Peptide

PubMed Central

Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M.; Rahman, Noorsaadah Abd; Yusof, Rohana

2013-01-01

Abstract Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03±0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection. PMID:24044366

Diffuse light-sheet microscopy for stripe-free calcium imaging of neural populations.

PubMed

Taylor, Michael A; Vanwalleghem, Gilles C; Favre-Bulle, Itia A; Scott, Ethan K

2018-06-19

Light-sheet microscopy is used extensively in developmental biology and neuroscience. One limitation of this approach is that absorption and scattering produces shadows in the illuminating light sheet, resulting in stripe artifacts. Here, we introduce diffuse light-sheet microscopes that use a line diffuser to randomize the light propagation within the image plane, allowing the light sheets to reform after obstacles. We incorporate diffuse light sheets in two existing configurations: selective plane illumination microscopy (SPIM) in which the sample is illuminated with a static sheet of light, and digitally scanned light sheet (DSLS) in which a thin Gaussian beam is scanned across the image plane during each acquisition. We compare diffuse light-sheet microscopes to their conventional counterparts for calcium imaging of neural activity in larval zebrafish. We show that stripe artifacts can cast deep shadows that conceal some neurons, and that the stripes can flicker, producing spurious signals that could be interpreted as biological activity. Diffuse light sheets mitigate these problems, illuminating the blind spots produced by stripes and removing artifacts produced by the stripes' movements. The upgrade to diffuse light sheets is simple and inexpensive, especially in the case of DSLS, where it requires the addition of one optical element. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Biologically Active Secondary Metabolites from the Fungi.

PubMed

Bills, Gerald F; Gloer, James B

2016-11-01

Many Fungi have a well-developed secondary metabolism. The diversity of fungal species and the diversification of biosynthetic gene clusters underscores a nearly limitless potential for metabolic variation and an untapped resource for drug discovery and synthetic biology. Much of the ecological success of the filamentous fungi in colonizing the planet is owed to their ability to deploy their secondary metabolites in concert with their penetrative and absorptive mode of life. Fungal secondary metabolites exhibit biological activities that have been developed into life-saving medicines and agrochemicals. Toxic metabolites, known as mycotoxins, contaminate human and livestock food and indoor environments. Secondary metabolites are determinants of fungal diseases of humans, animals, and plants. Secondary metabolites exhibit a staggering variation in chemical structures and biological activities, yet their biosynthetic pathways share a number of key characteristics. The genes encoding cooperative steps of a biosynthetic pathway tend to be located contiguously on the chromosome in coregulated gene clusters. Advances in genome sequencing, computational tools, and analytical chemistry are enabling the rapid connection of gene clusters with their metabolic products. At least three fungal drug precursors, penicillin K and V, mycophenolic acid, and pleuromutilin, have been produced by synthetic reconstruction and expression of respective gene clusters in heterologous hosts. This review summarizes general aspects of fungal secondary metabolism and recent developments in our understanding of how and why fungi make secondary metabolites, how these molecules are produced, and how their biosynthetic genes are distributed across the Fungi. The breadth of fungal secondary metabolite diversity is highlighted by recent information on the biosynthesis of important fungus-derived metabolites that have contributed to human health and agriculture and that have negatively impacted crops, food distribution, and human environments.

Skeleton growth under uniformly distributed force conditions: producing spherical sea urchins

NASA Astrophysics Data System (ADS)

Cheng, Polly; Kambli, Ankita; Stone, Johnny

2017-10-01

Sea urchin skeletons, or tests, comprise rigid calcareous plates, interlocked and sutured together with collagen fibres. The tests are malleable due to mutability in the collagen fibres that loosen during active feeding, yielding interplate gaps. We designed an extraterrestrial simulation experiment wherein we subjected actively growing sea urchins to one factor associated with zero-gravity environments, by growing them under conditions in which reactionary gravitational forces were balanced, and observed how their tests responded. Preventing tests from adhering to surfaces during active growth produced more-spherical bodies, realized as increased height-to-diameter ratios. Sea urchin tests constitute ideal systems for obtaining data that could be useful in extraterrestrial biology research, particularly in how skeletons grow under altered-gravity conditions.

Characterization and biological activities of extracellular melanin produced by Schizophyllum commune (Fries).

PubMed

Arun, G; Eyini, M; Gunasekaran, P

2015-06-01

Melanins are enigmatic pigments produced by a wide variety of microorganisms including bacteria and fungi. Here, we have isolated and characterized extracellular melanin from mushroom fungus, Schizophyllum commune. The extracellular dark pigment produced by the broth culture of S. commune, after 21 days of incubation was recovered by hot acid-alkali treatment. The melanin nature of the pigment was characterized by biochemical tests and further, confirmed by UV, IR, EPR, NMR and MALDI-TOF Mass Spectra. Extracellular melanin, at 100 μg/ml, showed significant antibacterial activity against Escherichia coli, Bacillus subtilis, Klebsiella pneumoniae and Pseudomonas fluorescens and antifungal activity against Trichophyton simii and T. rubrum. At a concentration of 50 μg/ml, melanin showed high free radical scavenging activity of DPPH (2,2-diphenyl-1-picrylhydrazyl) indicating its antioxidant potential. It showed concentration dependent inhibition of cell proliferation of Human Epidermoid Larynx Carcinoma Cell Line (HEP-2). This study has demonstrated characterization of melanin from basidiomycetes mushroom fungus, Schizophyllum commune and its applications.

Effects of humic acids from landfill leachate on plants: An integrated approach using chemical, biochemical and cytogenetic analysis.

PubMed

Morozesk, Mariana; Bonomo, Marina Marques; Souza, Iara da Costa; Rocha, Lívia Dorsch; Duarte, Ian Drumond; Martins, Ian Oliveira; Dobbss, Leonardo Barros; Carneiro, Maria Tereza Weitzel Dias; Fernandes, Marisa Narciso; Matsumoto, Silvia Tamie

2017-10-01

Biological process treatment of landfill leachate produces a significant amount of sludge, characterized by high levels of organic matter from which humic acids are known to activate several enzymes of energy metabolism, stimulating plant growth. This study aimed to characterize humic acids extracted from landfill sludge and assess the effects on plants exposed to different concentrations (0.5, 1, 2 and 4 mM C L -1 ) by chemical and biological analysis, to elucidate the influence of such organic material and minimize potential risks of using sludge in natura. Landfill humic acids showed high carbon and nitrogen levels, which may represent an important source of nutrients for plants. Biochemical analysis demonstrated an increase of enzyme activity, especially H + -ATPase in 2 mM C L -1 landfill humic acid. Additionally, cytogenetic alterations were observed in meristematic and F 1 cells, through nuclear abnormalities and micronuclei. Multivariate statistical analysis provided integration of physical, chemical and biological data. Despite all the nutritional benefits of humic acids and their activation of plant antioxidant systems, the observed biological effects showed concerning levels of mutagenicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of chemical and biological surfactants on activated sludge of MBR system: microscopic analysis and foam test.

PubMed

Capodici, Marco; Di Bella, Gaetano; Nicosia, Salvatore; Torregrossa, Michele

2015-02-01

A bench-scale MBR unit was operated, under stressing condition, with the aim of stimulating the onset of foaming in the activated sludge. Possible synergies between synthetic surfactants in the wastewater and biological surfactants (Extra-Cellular Polymeric Substances, EPSs) were investigated by changing C/N ratio. The growth of filamentous bacteria was also discussed. The MBR unit provided satisfactory overall carbon removal overall efficiencies: in particular, synthetic surfactants were removed with efficiency higher than 90% and 95% for non-ionic and ionic surfactants, respectively. Lab investigation suggested also the importance to reduce synthetic surfactants presence entering into mixed liquor: otherwise, their presence can significantly worsen the natural foaming caused by biological surfactants (EPSs) produced by bacteria. Finally, a new analytic method based on "ink test" has been proposed as a useful tool to achieve a valuation of EPSs bound fraction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictors of weight gain: the biological-behavioural debate.

PubMed

Filozof, C; Gonzalez, C

2000-05-01

The rapidly increasing prevalence of obesity, in spite of an unchanged gene pool, makes it interesting to search for biological factors which increase the susceptibility at the individual level as well as searching for the responsible environmental factors. Among the identified metabolic factors is a low resting metabolic rate for given body size and composition, a high respiratory quotient (RQ) indicating a low fat oxidation and a low spontaneous physical activity, all factors which are regarded as being under substantial genetic influence. Among the environmental factors, it is low levels of physical activity, increasing inactivity and a high fat diet that are probably the most important ones. In this review we have focused on controversies in this area. Understanding the interaction between the constitutional biological factors and the environmentally determined lifestyle factors it is important to produce better options for both the prevention and treatment of obesity.

Synthesis of Novel Aza-aromatic Curcuminoids with Improved Biological Activities towards Various Cancer Cell Lines.

PubMed

Theppawong, Atiruj; Van de Walle, Tim; Grootaert, Charlotte; Bultinck, Margot; Desmet, Tom; Van Camp, John; D'hooghe, Matthias

2018-05-01

Curcumin, a natural compound extracted from the rhizomes of Curcuma longa , displays pronounced anticancer properties but lacks good bioavailability and stability. In a previous study, we initiated structure modification of the curcumin scaffold by imination of the labile β-diketone moiety to produce novel β-enaminone derivatives. These compounds showed promising properties for elaborate follow-up studies. In this work, we focused on another class of nitrogen-containing curcuminoids with a similar objective: to address the bioavailability and stability issues and to improve the biological activity of curcumin. This paper thus reports on the synthesis of new pyridine-, indole-, and pyrrole-based curcumin analogues (aza-aromatic curcuminoids) and discusses their water solubility, antioxidant activity, and antiproliferative properties. In addition, multivariate statistics, including hierarchical clustering analysis and principal component analysis, were performed on a broad set of nitrogen-containing curcuminoids. Compared to their respective mother structures, that is, curcumin and bisdemethoxycurcumin, all compounds, and especially the pyridin-3-yl β-enaminone analogues, showed better water solubility profiles. Interestingly, the pyridine-, indole-, and pyrrole-based curcumin derivatives demonstrated improved biological effects in terms of mitochondrial activity impairment and protein content, in addition to comparable or decreased antioxidant properties. Overall, the biologically active N -alkyl β-enaminone aza-aromatic curcuminoids were shown to offer a desirable balance between good solubility and significant bioactivity.

Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells.

PubMed Central

Takeuchi, M; Inoue, N; Strickland, T W; Kubota, M; Wada, M; Shimizu, R; Hoshi, S; Kozutsumi, H; Takasaki, S; Kobata, A

1989-01-01

Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. PMID:2813359

Atmospheric composition - Influence of biology

NASA Technical Reports Server (NTRS)

Mcelroy, M. B.

1983-01-01

The variability of atmospheric constituents influenced by biological organisms over various time scales is examined, together with the human contribution to atmospheric sulfur. The biogeochemistry of nitrogen is discussed, with an emphasis on N2O, NO, and microbially mediated reactions in soil and water. Carbon species are bound up mainly in sediments and the deep ocean, but human activities involving combustion may cause a doubling of the atmospheric levels of CO2 in the near future, which could produce a general low-level atmospheric warming. Longer term measurements are required to assess the effects of CH4 augmentation in the atmosphere through fuel combustion. Coal burning effectively doubles the amount of SO2 produced by natural sources, and reduces the pH of rainwater, thus posing hazards to fish, plankton, and mollusc life.

Dinitrosyl iron complexes with thiol-containing ligands as a "working form" of endogenous nitric oxide.

PubMed

Vanin, Anatoly F

2016-04-01

The material presented herein is an overview of the results obtained by our research team during the many years' study of biological activities and occurrence of dinitrosyl iron complexes (DNIC) with thiol-containing ligands in human and animal organisms. With regard to their dose dependence and vast diversity of biological activities, DNIC are similar to the system of endogenous NO, one of the most universal regulators of biological processes. The role of biologically active components in DNIC is played by their iron-dinitrosyl fragments, [Fe(NO)2], endowed with the ability to generate neutral NO molecules and nitrosonium ions (NO(+)). Their release is effected by heme-and thiol-containing proteins, which fulfill the function of biological targets and acceptors of NO and NO(+). Beneficial regulatory effects of DNIC on physiological and metabolic processes are numerous and diverse and include, among other things, lowering of arterial pressure and accelerated healing of skin wounds. In the course of fast decomposition of their Fe(NO)2 fragments (e.g., in the presence of iron chelators), DNIC produce adverse (cytotoxic) effects, which can best be exemplified by their ability to suppress the development of experimental endometriosis in animals. In animal tissues, DNIC with thiol-containing ligands are predominantly represented by the binuclear form, which, contrary to mononuclear DNIC detectable by the 2.03 signal, is EPR-silent. The ample body of evidence on biological activities and occurrence of DNIC gained so far clearly demonstrates that in human and animal organisms DNIC with thiol-containing ligands represent a "working form" of the system of endogenous NO responsible for its accumulation and stabilization in animal tissues as well as its further transfer to its biological targets. Copyright © 2016 Elsevier Inc. All rights reserved.

NRPS4 is responsible for the biosynthesis of destruxins in Metarhizium robertsii ARSEF 2575

USDA-ARS?s Scientific Manuscript database

Destruxins (DTXs) are a family of cyclic depsipeptides that include > 35 members produced by Ascomycetous fungi belonging to several different taxa. These metabolites display a plethora of biological activities including toxicity against insects, depolarization of Ca2+ gradient across the plasma mem...

PARTICLE NUMBER AND SURFACE CHARGE PREDICT THE BIOLOGICAL ACTIVATION OF HUMAN BRONCHIAL EPITHELIAL CELLS EXPOSED TO PARTICULATE MATTER.

EPA Science Inventory

Exposure to particulate matter (PM) produces a uniform degree of mortality in exposed populations, in spite of its diverse sources. This suggests a common mechanism of action to explain its initial toxicity. The present study relates certain physicochemical characteristics (i.e.,...

Development of a quail embryo model for the detection of botulinum neurotoxin activity

USDA-ARS?s Scientific Manuscript database

Clostridium botulinum is a ubiquitous microorganism that under anaerobic conditions produces botulinum neurotoxins. In regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or environmental sample e...

Lantibiotic engineering: molecular characterization and exploitation of lantibiotic-synthesizing enzymes for peptide engineering.

PubMed

Nagao, Jun-ichi; Aso, Yuji; Shioya, Kouki; Nakayama, Jiro; Sonomoto, Kenji

2007-01-01

Lanthionine-containing peptide antibiotics called lantibiotics are produced by a large number of Gram-positive bacteria. Nukacin ISK-1 produced by Staphylococcus warneri ISK-1 is type-A(II) lantibiotic. Ribosomally synthesized nukacin ISK-1 prepeptide (NukA) consists of an N-terminal leader peptide followed by a C-terminal propeptide moiety that undergoes several post-translational modification events including unusual amino acid formation by the modification enzyme NukM, cleavage of leader peptide and export by the dual functional ABC transporter NukT, finally yielding a biologically active peptide. Unusual amino acids in lantibiotics contribute to biological activity and also structural stability against proteases. Thus, lantibiotic-synthesizing enzymes have a high potentiality for peptide engineering by introduction of unusual amino acids into desired peptides with altering biological and physicochemical properties, e.g., activity and stability, termed lantibiotic engineering. We report the establishment of a heterologous expression of nukacin ISK-1 biosynthetic gene cluster by the nisin-controlled expression system and discuss our recent progress in understanding of the biosynthetic enzymes for nukacin ISK-1 such as localization, molecular interaction in biophysical and biochemical aspects. Substrate specificity of the lantibiotic-synthesizing enzymes was evaluated by complementation of the biosynthetic enzymes (LctM and LctT) of closely related lantibiotic lacticin 481 for nukacin ISK-1 biosynthesis. We further explored a rapid and powerful tool for introduction of unusual amino acids by co-expression of hexa-histidine-tagged NukA and NukM in Escherichia coli.

Evidence for biological shaping of hair ice

NASA Astrophysics Data System (ADS)

Hofmann, D.; Preuss, G.; Mätzler, C.

2015-07-01

An unusual ice type, called hair ice, grows on the surface of dead wood of broad-leaf trees at temperatures slightly below 0 °C. We describe this phenomenon and present physical, chemical, and biological investigations to gain insight in the properties and processes related to hair ice. Tests revealed that the biological activity of a winter-active fungus is required in the wood for enabling the growth of hair ice. We confirmed the fungus hypothesis originally suggested by Wegener (1918) by reproducing hair ice on wood samples. Treatment by heat and fungicide suppresses the formation of hair ice. Fruiting bodies of Asco- and Basidiomycota are identified on hair-ice-carrying wood. One species, Exidiopsis effusa (Ee), was present on all investigated samples. Both hair-ice-producing wood samples and those with killed fungus show essentially the same temperature variation, indicating that the heat produced by fungal metabolism is very small, that the freezing rate is not influenced by the fungus activity, and that ice segregation is the common mechanism of ice growth on the wood surface. The fungus plays the role of shaping the ice hairs and preventing them from recrystallisation. Melted hair ice indicates the presence of organic matter. Chemical analyses show a complex mixture of several thousand CHO(N,S) compounds similar to fulvic acids in dissolved organic matter (DOM). The evaluation reveals decomposed lignin as being the main constituent. Further work is needed to clarify its role in hair-ice growth and to identify the recrystallisation inhibitor.

Evidence for biological shaping of hair ice

NASA Astrophysics Data System (ADS)

Hofmann, D.; Preuss, G.; Mätzler, C.

2015-04-01

An unusual ice type, called hair ice, grows on the surface of dead wood of broad-leaf trees at temperatures slightly below 0 °C. We describe this phenomenon and present physical, chemical, and biological investigations to gain insight in the properties and processes related to hair ice. Tests revealed that the biological activity of a winter-active fungus is required in the wood for enabling the growth of hair ice. We confirmed the fungus hypothesis originally suggested by Wegener (1918) by reproducing hair ice on wood samples. Treatment by heat and fungicide, respectively, suppresses the formation of hair ice. Fruiting bodies of Asco- and Basidiomycota are identified on hair-ice carrying wood. One species, Exidiopsis effusa (Ee), has been present on all investigated samples. Both hair-ice producing wood samples and those with killed fungus show essentially the same temperature variation, indicating that the heat produced by fungal metabolism is very small, that the freezing rate is not influenced by the fungus activity and that ice segregation is the common mechanism of ice growth at the wood surface. The fungus plays the role of shaping the ice hairs and to prevent them from recrystallisation. Melted hair ice indicates the presence of organic matter. Chemical analyses show a complex mixture of several thousand CHO(N,S)-compounds similar to fulvic acids in dissolved organic matter (DOM). The evaluation reveals decomposed lignin as the main constituent. Further work is needed to clarify its role in hair-ice growth and to identify the recrystallisation inhibitor.

Ligand Based-Pharmacophore Modeling and Extended Bi oactivity Prediction for Salinosporamide A, B and C from Marine Actino mycetes Salinispora tropica.

PubMed

Dineshkumar, Kesavan; Vasudevan, Aparna; Hopper, Waheeta

2017-01-01

Actinomycetes produce structurally unique secondary metabolites with pharmaceutically essential bioactivities. Salinispora, an obligate marine actinomycete, produces structurally varied and unique secondary metabolites. There is plenty of scope for development of drugs from the novel compounds isolated from Salinispora. Anticancer, antibacterial and anti-protozoa activities have been shown for Salinosporamides A, B and C, the secondary metabolites identified from Salinispora, which make them interesting subjects for further extended biological activity prediction. An in silico ligand based-pharmacophore approach was used for the prediction of extended biological targets for salinosporamide A, B and C. Pharmacophore models of salinosporamide A, B and C were generated individually and screened against known drug databases. The drugs with best fitness score were shortlisted, and their respective targets pertaining to their bioactivity were retrieved. The predicted biological drug targets were docked with salinosporamide A, B and C for validation. The glucocorticoid receptor and methionine aminopeptidase 2 showed good docking score and binding energy with salinosporamide A, B and C. Molecular dynamics studies of the protein-ligand complexes showed stable interactions suggesting that the predicted new targets for salinosporamides might be promising. The glucocorticoid receptor and methionine aminopeptidase 2 could be possible new drug targets of bioactivity of salinosporamides. These proteins could be the druggable targets for antiinflammatory and anticancer activity of salinosporamides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Producing recombinant human milk proteins in the milk of livestock species.

PubMed

Bösze, Zsuzsanna; Baranyi, Mária; Whitelaw, C Bruce A

2008-01-01

Recombinant human proteins produced by the mammary glands of genetically modified transgenic livestock mammals represent a special aspect of milk bioactive components. For therapeutic applications, the often complex posttranslational modifications of human proteins should be recapitulated in the recombinant products. Compared to alternative production methods, mammary gland production is a viable option, underlined by a number of transgenic livestock animal models producing abundant biologically active foreign proteins in their milk. Recombinant proteins isolated from milk have reached different phases of clinical trials, with the first marketing approval for human therapeutic applications from the EMEA achieved in 2006.

Bacterial symbionts and natural products

PubMed Central

Crawford, Jason M.; Clardy, Jon

2011-01-01

The study of bacterial symbionts of eukaryotic hosts has become a powerful discovery engine for chemistry. This highlight looks at four case studies that exemplify the range of chemistry and biology involved in these symbioses: a bacterial symbiont of a fungus and a marine invertebrate that produce compounds with significant anticancer activity, and bacterial symbionts of insects and nematodes that produce compounds that regulate multilateral symbioses. In the last ten years, a series of shocking revelations – the molecular equivalents of a reality TV show’s uncovering the true parents of a well known individual or a deeply hidden family secret – altered the study of genetically encoded small molecules, natural products for short. These revelations all involved natural products produced by bacterial symbionts, and while details differed, two main plot lines emerged: parentage, in which the real producers of well known natural products with medical potential were not the organisms from which they were originally discovered, and hidden relationships, in which bacterially produced small molecules turned out to be the unsuspected regulators of complex interactions. For chemists, these studies led to new molecules, new biosynthetic pathways, and an understanding of the biological functions these molecules fulfill. PMID:21594283

Anti-HIV and immunomodulation activities of cacao mass lignin-carbohydrate complex.

PubMed

Sakagami, Hiroshi; Kawano, Michiyo; Thet, May Maw; Hashimoto, Ken; Satoh, Kazue; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Haishima, Yuji; Maeda, Yuuichi; Sakurai, Koji

2011-01-01

Recently, a prominent antiviral and macrophage stimulatory activity of cacao lignin-carbohydrate complex (LCC) has been reported. However, the solubility and sterility of LCC have not been considered yet. In the present study, complete solubilisation and sterilisation was achieved by autoclaving under mild alkaline conditions and the previously reported biological activities were re-examined. LCCs were obtained by 1% NaOH extraction and acid precipitation, and a repeated extraction-precipitation cycle. Nitric oxide (NO) and cytokine productions were assayed by the Griess method and ELISA, respectively. Inducible NO synthase (iNOS) expression was determined by Western blot analysis. Superoxide anion, hydroxyl radical and nitric oxide radical-scavenging activity was determined by ESR spectroscopy. Cacao mass LCC showed reproducibly higher anti-HIV activity than cacao husk LCC. Cacao mass LCC, up to 62.5 μg/ml, did not stimulate mouse macrophage-like cells (RAW264.7 and J774.1) to produce NO, nor did it induce iNOS protein, in contrast to lipopolysaccharide (LPS). Cacao mass LCC and LPS synergistically stimulated iNOS protein expression, suggesting a different point of action. Cacao mass LCC induced tumour necrosis factor-α production markedly less than LPS, and did not induce interleukin-1β, interferon-α or interferon-γ. ESR spectroscopy showed that cacao mass LCC, but not LPS, scavenged NO produced from NOC-7. This study demonstrated several new biological activities of LCCs distinct from LPS and further confirmed the promising antiviral and immunomodulating activities of LCCs.

Using Invention to Change How Students Tackle Problems

PubMed Central

Smith, Karen M.; van Stolk, Adrian P.; Spiegelman, George B.

2010-01-01

Invention activities challenge students to tackle problems that superficially appear unrelated to the course material but illustrate underlying fundamental concepts that are fundamental to material that will be presented. During our invention activities in a first-year biology class, students were presented with problems that are parallel to those that living cells must solve, in weekly sessions over a 13-wk term. We compared students who participated in the invention activities sessions with students who participated in sessions of structured problem solving and with students who did not participate in either activity. When faced with developing a solution to a challenging and unfamiliar biology problem, invention activity students were much quicker to engage with the problem and routinely provided multiple reasonable hypotheses. In contrast the other students were significantly slower in beginning to work on the problem and routinely produced relatively few ideas. We suggest that the invention activities develop a highly valuable skill that operates at the initial stages of problem solving. PMID:21123697

Full activation of RNaseL in animal cells requires binding of 2-5A within ankyrin repeats 6 to 9 of this interferon-inducible enzyme.

PubMed

Díaz-Guerra, M; Rivas, C; Esteban, M

1999-02-01

To define protein domains important for activation of the interferon (IFN)-induced enzyme 2-5A-dependent RNaseL, we have generated vaccinia virus (VV) recombinants able to express in cultured cells truncated forms of this protein and compared their biologic activities with those producing the wild-type enzyme, with and without coexpression of 2-5A synthetase. Our results show that full activation of RNaseL requires binding of 2-5A oligonucleotides within amino acid positions 212-339, corresponding to ankyrin repeats 6 to 9. The protein kinase and ribonuclease domains of RNaseL, amino acids 340-741, are sufficient for a constitutively active enzyme that is unresponsive to excess 2-5A. These results demonstrate in vivo the importance of the ankyrin domains in the biologic function of RNaseL. We suggest that ankyrin repeats act as key modulators of RNaseL activity.

Is equol the key to the efficacy of soy foods?

PubMed

Lampe, Johanna W

2009-05-01

Gut bacterial modification of soy isoflavones produces metabolites that differ in biological activity from the parent compounds. Hydrolysis of glycosides results in more active compounds. In contrast, further degradation and transformation of aglycones produce more or less active compounds, depending on the substrate metabolized and the product formed. Bacterial metabolism of soy isoflavones varies among individuals. The predominant daidzein metabolites produced by human intestinal bacteria are equol and O-desmethylangolensin. Among humans, 30-50% have the bacteria capable of producing equol and 80-90% harbor O-desmethylangolensin-producing bacteria. Factors that influence the capacity to produce equol and O-desmethylangolensin are not clearly established; however, gut physiology, host genetics, and diet are reported to contribute to interindividual differences in conversion of daidzein to equol. Effects of these phenotypes on human health are poorly characterized. Some studies in high soy-consuming populations reported an inverse association between urinary and serum equol concentrations and breast and prostate cancer risk. Furthermore, several studies of soy supplementation and bone density suggest that soy products may be more effective in maintaining bone density in equol-producing individuals. Factors that contribute to the phenotypes and the relation of these specific phenotypes to human health need to be further elucidated. The extent to which isoflavone metabolism is key to the efficacy of soy foods remains to be established.

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. I. Taxonomy, fermentation, isolation, physico-chemical and biological characterization.

PubMed

O'Sullivan, J; McCullough, J; Johnson, J H; Bonner, D P; Clark, J C; Dean, L; Trejo, W H

1990-08-01

Janthinocins A, B and C are novel antibacterial agents produced by Janthinobacterium lividum. They were isolated from fermentation broths and characterized by UV, IR, NMR and mass spectroscopy. They are cyclic decapeptide lactones with marked activity against aerobic and anaerobic Gram-positive bacteria and are 2 to 4 times more potent in vitro than vancomycin. Janthinocins A and B were also found to be effective in a Staphylococcus aureus systemic infection in mice.

Intracellular screen to identify metagenomic clones that induce or inhibit a quorum-sensing biosensor.

PubMed

Williamson, Lynn L; Borlee, Bradley R; Schloss, Patrick D; Guan, Changhui; Allen, Heather K; Handelsman, Jo

2005-10-01

The goal of this study was to design and evaluate a rapid screen to identify metagenomic clones that produce biologically active small molecules. We built metagenomic libraries with DNA from soil on the floodplain of the Tanana River in Alaska. We extracted DNA directly from the soil and cloned it into fosmid and bacterial artificial chromosome vectors, constructing eight metagenomic libraries that contain 53,000 clones with inserts ranging from 1 to 190 kb. To identify clones of interest, we designed a high throughput "intracellular" screen, designated METREX, in which metagenomic DNA is in a host cell containing a biosensor for compounds that induce bacterial quorum sensing. If the metagenomic clone produces a quorum-sensing inducer, the cell produces green fluorescent protein (GFP) and can be identified by fluorescence microscopy or captured by fluorescence-activated cell sorting. Our initial screen identified 11 clones that induce and two that inhibit expression of GFP. The intracellular screen detected quorum-sensing inducers among metagenomic clones that a traditional overlay screen would not. One inducing clone carries a LuxI homologue that directs the synthesis of an N-acyl homoserine lactone quorum-sensing signal molecule. The LuxI homologue has 62% amino acid sequence identity to its closest match in GenBank, AmfI from Pseudomonas fluorescens, and is on a 78-kb insert that contains 67 open reading frames. Another inducing clone carries a gene with homology to homocitrate synthase. Our results demonstrate the power of an intracellular screen to identify functionally active clones and biologically active small molecules in metagenomic libraries.

Effects of amendment of different biochars on soil physical and biological properties related to carbon mineralization

NASA Astrophysics Data System (ADS)

Zhang, Renduo; Zhu, Shuzhi; Ouyang, Lei

2014-05-01

Biochar addition to soils potentially affects various soil properties, and these effects are dependent on biochars derived from different feedstock materials and pyrolysis processes. The objective of this study was to investigate the effects of amendment of different biochars on soil physical and biological properties. Biochars were produced with dairy manure and woodchip at temperatures of 300, 500, and 700°C, respectively. Each biochar was mixed at 5% (w/w) with a forest soil and the mixture was incubated for 180 days, during which soil physical and biological properties, and soil respiration rates were measured. Results showed that the biochar addition significantly enhanced the formation of soil macroaggregates at the early incubation time. The biochar application significantly reduced soil bulk density, increased the amount of soil organic matter, and stimulated microbial activity and soil respiration rates at the early incubation stage. Biochar applications improved water retention capacity, with stronger effects by biochars produced at higher pyrolysis temperatures. At the same suction, the soil with woodchip biochars possessed higher water content than with the dairy manure biochars. Biochar addition significantly affected the soil physical and biological properties, which resulted in different soil carbon mineralization rates.

Directed Fluid Transport with Biomimetic ``Silia'' Arrays

NASA Astrophysics Data System (ADS)

Shields, A. R.; Evans, B. A.; Carstens, B. L.; Falvo, M. R.; Washburn, S.; Superfine, R.

2008-10-01

We present results on the long-range, directed fluid transport produced by the collective beating of arrays of biomimetic ``silia.'' Silia are arrays of free-standing nanorods roughly the size of biological cilia, which we fabricate from a polymer-magnetic nanoparticle composite material. With external permanent magnets we actuate our silia such that their motion mimics the beating of biological cilia. Biological cilia have evolved to produce microscale fluid transport and are increasingly being recognized as critical components in a wide range of biological systems. However, despite much effort cilia generated fluid flows remain an area of active study. In the last decade, cilia-driven fluid flow in the embryonic node of vertebrates has been implicated as the initial left-right symmetry breaking event in these embryos. With silia we generate directional fluid transport by mimicking the tilted conical beating of these nodal cilia and seek to answer open questions about the nature of particle advection in such a system. By seeding fluorescent microparticles into the fluid we have noted the existence of two distinct flow regimes. The fluid flow is directional and coherent above the tips of the silia, while between the silia tips and floor particle motion is complicated and suggestive of chaotic advection.

Physiological role of short peptides in nutrition.

PubMed

Tutel'yan, V A; Khavinson, V Kh; Malinin, V V

2003-01-01

Here we review new data about the physiological role of short peptides and their use as biologically active food additives (parapharmaceutics). Some approaches to the development of peptide preparations for peroral administration are considered and the mechanisms of nonspecific and tissue-specific effects produced by peroral peptide parapharmaceutics are discussed. Particular attention is given to biological properties of short peptides synthesized at the St. Petersburg Institute of Bioregulation and Gerontology. These peptides hold much promise for the synthesis of parapharmaceutics increasing organism's resistance to extreme factors and preventing accelerated aging and age-related diseases.

Impact of Space Exploration on Biology and Medicine

NASA Technical Reports Server (NTRS)

Randt, Clark T.

1960-01-01

Basic human drives for pioneering and conquest can find acceptable expression in extraterrestrial exploration. It is unmistakably clear that our civilization cannot survive a thermonuclear conflict. The expression of aggressive drives in war has repeatedly supplied an impetus for unusual increments in the growth of the arts and sciences.. A historical review of intellectual progress and concomitant technological advance gives reason to expect that expanded knowledge of the universe will produce an unprecedented burst of creative activity in biology and medicine as well as in the physical sciences and engineering.

The structural biology of phenazine biosynthesis

PubMed Central

Blankenfeldt, Wulf; Parsons, James F.

2014-01-01

The phenazines are a class of over 150 nitrogen-containing aromatic compounds of bacterial and archeal origin. Their redox properties not only explain their activity as broad-specificity antibiotics and virulence factors but also enable them to function as respiratory pigments, thus extending their importance to the primary metabolism of phenazine-producing species. Despite their discovery in the mid-19th century, the molecular mechanisms behind their biosynthesis have only been unraveled in the last decade. Here, we review the contribution of structural biology that has led to our current understanding of phenazine biosynthesis. PMID:25215885

Purification and biological characterization of soluble, recombinant mouse IFNβ expressed in insect cells.

PubMed

Stifter, Sebastian A; Gould, Jodee A; Mangan, Niamh E; Reid, Hugh H; Rossjohn, Jamie; Hertzog, Paul J; de Weerd, Nicole A

2014-02-01

Interferon β (IFNβ) is a member of the type I interferon family of cytokines widely recognised for their anti-viral, anti-proliferative and immunomodulatory properties. Recombinant, biologically active forms of this cytokine are used clinically for the treatment of multiple sclerosis and in laboratories to study the role of this cytokine in health and disease. Established methods for expression of IFNβ utilise either bacterial systems from which the insoluble recombinant proteins must be refolded, or mammalian expression systems in which large volumes of cell culture are required for recovery of acceptable yields. Utilising the baculovirus expression system and Trichoplusia ni (Cabbage Looper) BTI-TN-5B1-4 cell line, we report a reproducible method for production and purification of milligram/litre quantities of biologically active murine IFNβ. Due to the design of our construct and the eukaryotic nature of insect cells, the resulting soluble protein is secreted allowing purification of the Histidine-tagged natively-folded protein from the culture supernatant. The IFNβ purification method described is a two-step process employing immobilised metal-ion affinity chromatography (IMAC) and reverse-phase high performance liquid chromatography (RP-HPLC) that results in production of significantly more purified IFNβ than any other reported eukaryotic-based expression system. Recombinant murine IFNβ produced by this method was natively folded and demonstrated hallmark type I interferon biological effects including antiviral and anti-proliferative activities, and induced genes characteristic of IFNβ activity in vivo. Recombinant IFNβ also had specific activity levels exceeding that of the commercially available equivalent. Together, our findings provide a method for production of highly pure, biologically active murine IFNβ. Copyright © 2013 Elsevier Inc. All rights reserved.

Enzymatic production of defined chitosan oligomers with a specific pattern of acetylation using a combination of chitin oligosaccharide deacetylases

NASA Astrophysics Data System (ADS)

Hamer, Stefanie Nicole; Cord-Landwehr, Stefan; Biarnés, Xevi; Planas, Antoni; Waegeman, Hendrik; Moerschbacher, Bruno Maria; Kolkenbrock, Stephan

2015-03-01

Chitin and chitosan oligomers have diverse biological activities with potentially valuable applications in fields like medicine, cosmetics, or agriculture. These properties may depend not only on the degrees of polymerization and acetylation, but also on a specific pattern of acetylation (PA) that cannot be controlled when the oligomers are produced by chemical hydrolysis. To determine the influence of the PA on the biological activities, defined chitosan oligomers in sufficient amounts are needed. Chitosan oligomers with specific PA can be produced by enzymatic deacetylation of chitin oligomers, but the diversity is limited by the low number of chitin deacetylases available. We have produced specific chitosan oligomers which are deacetylated at the first two units starting from the non-reducing end by the combined use of two different chitin deacetylases, namely NodB from Rhizobium sp. GRH2 that deacetylates the first unit and COD from Vibrio cholerae that deacetylates the second unit starting from the non-reducing end. Both chitin deacetylases accept the product of each other resulting in production of chitosan oligomers with a novel and defined PA. When extended to further chitin deacetylases, this approach has the potential to yield a large range of novel chitosan oligomers with a fully defined architecture.

Impact of co-incorporating laminin peptide dopants and neurotrophic growth factors on conducting polymer properties.

PubMed

Green, Rylie A; Lovell, Nigel H; Poole-Warren, Laura A

2010-01-01

Conductive neural interfaces tailored for cell interaction by incorporation of bioactive factors are hypothesized to produce superior neuroprostheses with improved charge transfer capabilities. This study examined the effect of entrapping nerve growth factor (NGF) within the conducting polymer poly(ethylene dioxythiophene) (PEDOT) during electrodeposition to create a polymer capable of stimulating neurite outgrowth from proximal neural tissue. NGF entrapment was performed on polymers doped with laminin peptides DEDEDYFQRYLI and DCDPGYIGSR and, additionally, a conventional dopant, paratoluene sulphonate (pTS). All polymer coatings were analysed for a range of physical, electrical and mechanical properties, with the biological activity of ligands examined using a PC12 neurite outgrowth assay. NGF was successfully entrapped in PEDOT during electrodeposition and was shown to produce a softer interface than conventional conducting polymers and films without the NGF modification. However, it was found that the use of a peptide dopant combined with NGF entrapment resulted in polymers with diminished electrical and mechanical stability. Entrapped NGF was determined to be biologically active, with PEDOT/pTS/NGF producing neurite outgrowth comparable with control films where NGF was supplied via the medium. Future studies will determine the effect of typical neural prosthetic stimulation regimes on the release of neurotrophins and subsequent cell response.

Disulfide Bond Formation and Activation of Escherichia coli β-Galactosidase under Oxidizing Conditions

PubMed Central

Seras-Franzoso, Joaquin; Affentranger, Roman; Ferrer-Navarro, Mario; Daura, Xavier; Villaverde, Antonio

2012-01-01

Escherichia coli β-galactosidase is probably the most widely used reporter enzyme in molecular biology, cell biology, and biotechnology because of the easy detection of its activity. Its large size and tetrameric structure make this bacterial protein an interesting model for crystallographic studies and atomic mapping. In the present study, we investigate a version of Escherichia coli β-galactosidase produced under oxidizing conditions, in the cytoplasm of an Origami strain. Our data prove the activation of this microbial enzyme under oxidizing conditions and clearly show the occurrence of a disulfide bond in the β-galactosidase structure. Additionally, the formation of this disulfide bond is supported by the analysis of a homology model of the protein that indicates that two cysteines located in the vicinity of the catalytic center are sufficiently close for disulfide bond formation. PMID:22286993

Accessing Nature’s diversity through metabolic engineering and synthetic biology

PubMed Central

King, Jason R.; Edgar, Steven; Qiao, Kangjian; Stephanopoulos, Gregory

2016-01-01

In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents. PMID:27081481

Professional equity as reported by biology teachers

NASA Astrophysics Data System (ADS)

Douglas, Claudia B.; Lakes Matyas, Marsha; Butler Kahle, Jane

In 1982, the National Association of Biology Teachers surveyed its membership in order to assess the role and status of women in biology education. Items describing roles, salaries, assignments, professional activities, and sexual bias were included in the survey. This paper compares the responses of male and female biology educators, draws conclusions from the data, and suggests implications for the science education profession. Inequality in several professional areas was revealed. More women than men were single and reported no dependent children. Women exceeded men in both the lower and upper ends of the distribution of years of experience. However, the percentage of men exceeded that of women in most salary brackets beyond $20,000 and more men reported paid consulting opportunities. Men tended to teach at larger institutions and, at all academic levels, more men taught advanced classes. More men than women were involved with research activities. However, neither sex felt that the other one received preferential treatment in regard to salary and promotion. The majority of education administrators as well as science and biology faculties were male. However, the recent influx of women into science education positions may produce important changes. It is recommended that a comparative study be conducted in five years.

Radiation interactions with biological systems.

PubMed

Islam, Muhammad Torequl

2017-05-01

The use of radiation, especially ionizing radiation (IR), is currently attracting great attention in the field of medical sciences. However, it should be mentioned that IR has both beneficial and harmful effects in biological systems. This review aims to focus on IR-mediated physiological events in a mechanistic way. Evidence from the databases, mainly from PUBMED and SCIENCE DIRECT were considered. IR directly and/or with their lyses products (indirect) causes oxidative stresses to biological systems. These activities may be localized and systematic. Otherwise, IR-induced non-/multi-targeted effects are also evident. IR in diagnosis and cancer radiotherapy is well-known. Reactive species produced by IR are not only beneficial, but also can exert harmful effects in a biological system such as aging, genetic instability and mutagenicity, membrane lysis and cell death, alteration of enzymatic activity and metabolic events, mitochondrial dysfunction, and even cancer. Additionally, DNA adducts formation, after IR-induced DNA breakage, is a cause of blockage of DNA repair capability with an increase in cellular radiosensitivity. These may allow cellular ruin even at low IR levels. Dependent on the dose, duration of action and quality, IR plays diverse roles in biological systems.

[Quod medicina aliis, aliis est acre venenum**--venoms as a source of anticancer agents].

PubMed

Kucińska, Małgorzata; Ruciński, Piotr; Murias, Marek

2013-01-01

Natural product derived from plants and animals were used in folk medicine for centuries. The venoms produced by animals for hunting of self-defence are rich in bioactive compounds with broad spectrum of biological activity. The papers presents the most promising compounds isolated from venoms of snakes, scorpions and toads. For these compounds both: mechanism of anticancer activity as well as possibilities of clinical use are presented.

FR258900, a novel glycogen phosphorylase inhibitor isolated from Fungus No. 138354. I. Taxonomy, fermentation, isolation and biological activities.

PubMed

Furukawa, Shigetada; Tsurumi, Yasuhisa; Murakami, Kana; Nakanishi, Tomoko; Ohsumi, Keisuke; Hashimoto, Michizane; Nishikawa, Motoaki; Takase, Shigehiro; Nakayama, Osamu; Hino, Motohiro

2005-08-01

FR258900 is a novel glycogen synthesis activator produced by Fungus No. 138354. This compound was isolated from the culture broth by solvent extraction and reverse-phase column chromatography. FR258900 stimulated glycogen synthesis and glycogen synthase activity in primary rat hepatocytes. FR258900 exhibited a potent inhibitory effect on the activity of liver glycogen phosphorylase, suggesting that this compound may activate hepatic glycogen synthesis via glycogen phosphorylase inhibition. Thus, this glycogen phosphorylase inhibitor may be useful in the treatment of postprandial hyperglycemia in type 2 diabetes.

Natural Products from the Lithistida: A Review of the Literature since 2000

PubMed Central

Winder, Priscilla L.; Pomponi, Shirley A.; Wright, Amy E.

2011-01-01

Lithistid sponges are known to produce a diverse array of compounds ranging from polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and sterols. A majority of these structurally complex compounds have very potent and interesting biological activities. It has been a decade since a thorough review has been published that summarizes the literature on the natural products reported from this amazing sponge order. This review provides an update on the current taxonomic classification of the Lithistida, describes structures and biological activities of 131 new natural products, and discusses highlights from the total syntheses of 16 compounds from marine sponges of the Order Lithistida providing a compilation of the literature since the last review published in 2002. PMID:22363244

Structures and properties of naturally occurring polyether antibiotics.

PubMed

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

Structures and Properties of Naturally Occurring Polyether Antibiotics

PubMed Central

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties. PMID:23586016

Gas expulsions and biological activity recorded offshore Molene Island, Brittany (France): video supervised recording of OBS data and analogue modelling

NASA Astrophysics Data System (ADS)

Klingelhoefer, F.; Géli, L.; Dellong, D.; Evangelia, B.; Tary, J. B.; Bayrakci, G.; Lantéri, N.; Lin, J. Y.; Chen, Y. F.; Chang, E. T. Y.

2016-12-01

Ocean bottom seismometers (OBS) commonly record signals from Short Duration Events (SDEs), having characteristics that are very different from those produced by tectonic earthquakes, e.g.: durations < 1 s, frequencies between 10 and 30 Hz, and one single-wave trains, with no identified P- nor S-wave arrivals. SDES were first reported by Burkisk et al (1981) who proposed biological activity as a possible cause. Since then, SDEs have been disregarded or discarded as noise by scientists interested in earthquake studies. Interest in SDEs came back recently, when it was realized that SDEs are commonly found and could be due to gas expulsions from the seafloor. To discriminate between the 2 hypotheses (biological activity vs gas emissions), different tests have been made, including seismic recordings combined with video surveillance and analogue experiments. In May 2016, two OBS (4.5 Hz) were deployed offshore Molene Island, Brittany within the field of view of the EMSO-Molene underwater observatory, at a water depth of 12 m. The camera images and the recordings reveal the presence of crabs, octopus and several species of fish. Other acoustic signals can be related to the presence of moving algae or the influence from bad weather. Tides produce characteristic curves in the noise recorded on the geophones. SDEs have been recorded on both instruments, that may well have been caused by gas expulsions from the seabed into the water. In order to verify this hypothesis, an aquarium was filled with water overlying an even grain-sized quartz sand layer. A constant air supply through a narrow tube produced gas bubbles in a regular manner and an immersed ocean bottom geophone recorded the resulting acoustic signals. The bubbles tend to have a uniform size and to produce a waveform very close to those found on the OBSs. By comparing the number of SDEs and the volume of escaped air, estimates can be made regarding the volume of gas escaping the seafloor in different environments.

Crisamicin A, a new antibiotic from Micromonospora. I. Taxonomy of the producing strain, fermentation, isolation, physico-chemical characterization and antimicrobial properties.

PubMed

Nelson, R A; Pope, J A; Luedemann, G M; McDaniel, L E; Schaffner, C P

1986-03-01

A microorganism, designated as RV-79-9-101 and now identified as Micromonospora purpureochromogenes subsp. halotolerans, isolated from a mud sample in the Philippines, has been shown to produce a complex of antibiotics called crisamicins. Thin-layer chromatography and bioautography, employing solvent extracts of whole fermentation broths, revealed a minimum of five antimicrobial components. The major biologically-active component of the antibiotic complex, crisamicin A, was obtained in pure form after preparative silica gel column chromatography followed by crystallization. Based on physico-chemical data crisamicin A has been identified as a novel member of the isochromanequinone group of antibiotics. It exhibits excellent in vitro activity against Gram-positive bacteria but little or no activity towards Gram-negative bacteria or fungi.

Generation of knockout rabbits using transcription activator-like effector nucleases.

PubMed

Wang, Yu; Fan, Nana; Song, Jun; Zhong, Juan; Guo, Xiaogang; Tian, Weihua; Zhang, Quanjun; Cui, Fenggong; Li, Li; Newsome, Philip N; Frampton, Jon; Esteban, Miguel A; Lai, Liangxue

2014-01-01

Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platforms contributing to redefine the boundaries of modern biological research. They are composed of a non-specific cleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications by inducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases have been employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively. This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies, biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbits using transcription activator-like effector nucleases, and a perspective of the field.

Marine Rare Actinobacteria: Isolation, Characterization, and Strategies for Harnessing Bioactive Compounds

PubMed Central

Dhakal, Dipesh; Pokhrel, Anaya Raj; Shrestha, Biplav; Sohng, Jae Kyung

2017-01-01

Actinobacteria are prolific producers of thousands of biologically active natural compounds with diverse activities. More than half of these bioactive compounds have been isolated from members belonging to actinobacteria. Recently, rare actinobacteria existing at different environmental settings such as high altitudes, volcanic areas, and marine environment have attracted attention. It has been speculated that physiological or biochemical pressures under such harsh environmental conditions can lead to the production of diversified natural compounds. Hence, marine environment has been focused for the discovery of novel natural products with biological potency. Many novel and promising bioactive compounds with versatile medicinal, industrial, or agricultural uses have been isolated and characterized. The natural compounds cannot be directly used as drug or other purposes, so they are structurally modified and diversified to ameliorate their biological or chemical properties. Versatile synthetic biological tools, metabolic engineering techniques, and chemical synthesis platform can be used to assist such structural modification. This review summarizes the latest studies on marine rare actinobacteria and their natural products with focus on recent approaches for structural and functional diversification of such microbial chemicals for attaining better applications. PMID:28663748

Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

DOEpatents

Jessen, Holly Jean [Chanhassen, MN; Liao, Hans H [Eden Prairie, MN; Gort, Steven John [Apple Valley, MN; Selifonova, Olga V [Plymouth, MN

2011-10-04

The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

Cognitive Functions of the Cerebellum Explain How Ericsson's Deliberate Practice Produces Giftedness

ERIC Educational Resources Information Center

Vandervert, Larry R.

2007-01-01

A critical issue for Ericsson et al.'s proposal is the development of a fully adequate description of neurophysiological substrates for deliberate practice. Ericsson et al. do provide two substantial subsections on biological substrates--namely, their subsections, "Acquisition of superior power, control, and speed of motor activities" and…

Kazakhstan In situ BioTransformation of Mercury-Contaminated Groundwater utilizing Native Aerobic and Anaerobic Bacteria

EPA Science Inventory

Our final international work on the biological decontamination of the mercury contamination of soils in the Northern outskirts of Pavlodar as a result of activity at the former PO “Khimprom” chemical plant is reported here. The plant produced chlorine and alkali from the 1970s i...

78 FR 7402 - Small Takes of Marine Mammals Incidental to Specified Activities; Cape Wind's High Resolution...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-01

... contexts and use sound for various biological functions including, but not limited to, (1) social interactions; (2) foraging; (3) orientation; and (4) predator detection. Interference with producing or... successful mother/calf interactions could have more serious impacts if it were in the same frequency band as...

Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

DOEpatents

Jessen, Holly Jean; Liao, Hans H; Gort, Steven John; Selifonova, Olga V

2014-11-18

The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

Kunitz trypsin inhibitor in addition to Bowman-Birk inhibitor influence stability of lunasin against pepsin-pancreatin hydrolysis

USDA-ARS?s Scientific Manuscript database

Soybean contains several biologically active components and one of this belongs to the bioactive peptide group. The objectives of this study were to produce different lunasin-enriched preparations (LEP) and determine the effect of Bowman-Birk inhibitor and Kunitz trypsin concentrations on the stabil...

Inhibition of Biological Activity of Staphylococcal Enterotoxin A (SEA) by Apple Juice and Apple Polyphenols

USDA-ARS?s Scientific Manuscript database

The foodborne pathogen Staphylococcus aureus produces the virulent staphylococcal entertoxin A (SEA), a single-chain protein that consists of 233 amino acid residues with a molecular weight of 27 078 Da. SEA is a superantigen that is reported to contribute to animal (mastitis) and human (emesis, dia...

Development of a quail embryo model for the detection of botulinum toxin type A activity

USDA-ARS?s Scientific Manuscript database

Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...

Effect of Cooperative Learning Strategy on Students' Acquisition and Practice of Scientific Skills in Biology

ERIC Educational Resources Information Center

Chatila, Hanadi; Al Husseiny, Fatima

2017-01-01

Recent research findings have shown that cooperative learning improves students' thinking skills as it allows them to communicate actively with each other (Johnson, Johnson and Smith, 2014). Therefore, cooperative learning has been proposed by many educators to be implemented in classrooms to produce lifelong learners and critical thinkers…

IDENTIFYING THE SIGNATURE OF THE NATURAL ATTENUATION IN THE MICROBIAL ECOLOGY OF HYDROCARBON CONTAMINATED GROUNDWATER USING MOLECULAR METHODS AND &LDQUO;BUG TRAPS&RDQUO;

EPA Science Inventory

These related projects have combined biological molecular methods and a novel passive sampling system (bio-trap) to produce a technology that will allow the active component of any contaminated groundwater microbial community to be investigated. Conventional sampling methods c...

Dynamic Bubble Surface Tension Measurements in Northwest Atlantic Seawater

NASA Astrophysics Data System (ADS)

Kieber, D. J.; Long, M. S.; Keene, W. C.; Kinsey, J. D.; Frossard, A. A.; Beaupre, S. R.; Duplessis, P.; Maben, J. R.; Lu, X.; Chang, R.; Zhu, Y.; Bisgrove, J.

2017-12-01

Numerous reports suggest that most organic matter (OM) associated with newly formed primary marine aerosol (PMA) originates from the sea-surface microlayer. However, surface-active OM rapidly adsorbs onto bubble surfaces in the water column and is ejected into the atmosphere when bubbles burst at the air-water interface. Here we present dynamic surface tension measurements of bubbles produced in near surface seawater from biologically productive and oligotrophic sites and in deep seawater collected from 2500 m in the northwest Atlantic. In all cases, the surface tension of bubble surfaces decreased within seconds after the bubbles were exposed to seawater. These observations demonstrate that bubble surfaces are rapidly saturated by surfactant material scavenged from seawater. Spatial and diel variability in bubble surface evolution indicate corresponding variability in surfactant concentrations and/or composition. Our results reveal that surface-active OM is found throughout the water column, and that at least some surfactants are not of recent biological origin. Our results also support the hypothesis that the surface microlayer is a minor to negligible source of OM associated with freshly produced PMA.

Evaluation of DNA extraction methods for the analysis of microbial community in biological activated carbon.

PubMed

Zheng, Lu; Gao, Naiyun; Deng, Yang

2012-01-01

It is difficult to isolate DNA from biological activated carbon (BAC) samples used in water treatment plants, owing to the scarcity of microorganisms in BAC samples. The aim of this study was to identify DNA extraction methods suitable for a long-term, comprehensive ecological analysis of BAC microbial communities. To identify a procedure that can produce high molecular weight DNA, maximizes detectable diversity and is relatively free from contaminants, the microwave extraction method, the cetyltrimethylammonium bromide (CTAB) extraction method, a commercial DNA extraction kit, and the ultrasonic extraction method were used for the extraction of DNA from BAC samples. Spectrophotometry, agarose gel electrophoresis and polymerase chain reaction (PCR)-restriction fragment length polymorphisms (RFLP) analysis were conducted to compare the yield and quality of DNA obtained using these methods. The results showed that the CTAB method produce the highest yield and genetic diversity of DNA from BAC samples, but DNA purity was slightly less than that obtained with the DNA extraction-kit method. This study provides a theoretical basis for establishing and selecting DNA extraction methods for BAC samples.

Development of water quality thresholds during dredging for the protection of benthic primary producer habitats.

PubMed

Sofonia, Jeremy J; Unsworth, Richard K F

2010-01-01

Given the potential for adverse effects of ocean dredging on marine organisms, particularly benthic primary producer communities, the management and monitoring of those activities which cause elevated turbidity and sediment loading is critical. In practice, however, this has proven challenging as the development of water quality threshold values, upon which management responses are based, are subject to a large number of physical and biological parameters that are spatially and temporally specific. As a consequence, monitoring programs to date have taken a wide range of different approaches, most focusing on measures of turbidity reported as nephelometric turbidity units (NTU). This paper presents a potential approach in the determination of water quality thresholds which utilises data gathered through the long-term deployment of in situ water instruments, but suggests a focus on photosynthetic active radiation (PAR) rather than NTU as it is more relevant biologically and inclusive of other site conditions. A simple mathematical approach to data interpretation is also presented which facilitates threshold value development, not individual values of concentrations over specific intervals, but as an equation which may be utilized in numerical modelling.

Phenolics from Winemaking By-Products Better Decrease VLDL-Cholesterol and Triacylglycerol Levels than Those of Red Wine in Wistar Rats.

PubMed

de Oliveira, Walkia Polliana; Biasoto, Aline Camarão Telles; Marques, Valquíria Fernanda; Dos Santos, Ieda Maria; Magalhães, Kedma; Correa, Luiz Claudio; Negro-Dellacqua, Melissa; Miranda, Maria Spínola; de Camargo, Adriano Costa; Shahidi, Fereidoon

2017-10-01

Winemaking by-products account for more than 30% of the grape production, but this inexpensive feedstock has not yet been fully exploited. Accordingly, we evaluated the potential biological activity of winemaking by-products produced with Syrah grapes in comparison with those of the wine produced using the same grape cultivar. Winemaking by-products showed higher contents of total anthocyanins, flavonols, stilbenes, and flavanols than red wine as evaluated by HPLC-DAD-FD (on a dry weight basis). In contrast, red wine was a better source of phenolic acids. However, the contribution of phenolic acids was minor for both samples. Furthermore, equivalent concentration of winemaking by-products (100 mg/kg/d) showed greater biological activity by than that of red wine by decreasing the levels of VLDL-cholesterol and triacylglycerols in Wistar rats. Therefore, this study supports the use of winemaking by-products as an economical source of bioactive phenolics with potential use in the food and nutraceutical industries. © 2017 Institute of Food Technologists®.

Extraction, Identification and Biological Activities of Saponins in Sea Cucumber Pearsonothuria graeffei.

PubMed

Khattab, Rafat Afifi; Elbandy, Mohamed; Lawrence, Andrew; Paget, Tim; Rae-Rho, Jung; Binnaser, Yaser S; Ali, Imran

2018-01-01

Secondary metabolism in marine organisms produces a diversity of biologically important natural compounds that are not present in terrestrial species. Sea cucumbers belong to the invertebrate Echinodermata and are famous for their nutraceutical, medical and food values. They are known for possession triterpenoid glycosides (saponins) with various ecological roles. The current work aimed to separate, identify and test various biological activities (antibacterial, antifungal, antileishmanial and anticancer properties) of saponins produced by the holothurian Pearsonothuria graeffei from the Red Sea, Egypt. The structures were identified by 1D and 2D NMR (1H, 13C, TOCSY, COSY, HSQC, HMBC, and ROESY) experiments and acid hydrolysis. The crude and purified fractions was analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)/MS to identify saponins and characterize their molecular structures. Partially purified fraction, mainly containing compounds 1 and 2, was screened for its antifungal activity against three clinical isolates of Candida albicans (Candida 580 (1), Candida 581(2) and Candida MEO47228. Antileishmanial activity against Leishmania major and toxicity on colon cell-line were also evaluated. Two lanostane type sulfated triterpene monoglycosides were isolated from the Holothurian Pearsonothuria graeffei from the Red Sea, Egypt. Holothurin A (1) and echinoside A (2) triterpene saponins were separated by reversed phase semi-preparative HPLC. LC50 values (µg/mL); calculated for the fraction containing saponins 1 and 2 as major constituents; against Candida albicans, Leishmania major and colon cell-line were 10, 20 and 0.50, respectively. Consequently, this study demonstrated the potential use of sea cucumber Pearsonothuria graeffei not only as appreciated functional food or nutraceuticals but also as the source of functional ingredients for pharmaceutical products with antifungal, antileishmanial and anticancer properties. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparing sixteen scoring functions for predicting biological activities of ligands for protein targets.

PubMed

Xu, Weijun; Lucke, Andrew J; Fairlie, David P

2015-04-01

Accurately predicting relative binding affinities and biological potencies for ligands that interact with proteins remains a significant challenge for computational chemists. Most evaluations of docking and scoring algorithms have focused on enhancing ligand affinity for a protein by optimizing docking poses and enrichment factors during virtual screening. However, there is still relatively limited information on the accuracy of commercially available docking and scoring software programs for correctly predicting binding affinities and biological activities of structurally related inhibitors of different enzyme classes. Presented here is a comparative evaluation of eight molecular docking programs (Autodock Vina, Fitted, FlexX, Fred, Glide, GOLD, LibDock, MolDock) using sixteen docking and scoring functions to predict the rank-order activity of different ligand series for six pharmacologically important protein and enzyme targets (Factor Xa, Cdk2 kinase, Aurora A kinase, COX-2, pla2g2a, β Estrogen receptor). Use of Fitted gave an excellent correlation (Pearson 0.86, Spearman 0.91) between predicted and experimental binding only for Cdk2 kinase inhibitors. FlexX and GOLDScore produced good correlations (Pearson>0.6) for hydrophilic targets such as Factor Xa, Cdk2 kinase and Aurora A kinase. By contrast, pla2g2a and COX-2 emerged as difficult targets for scoring functions to predict ligand activities. Although possessing a high hydrophobicity in its binding site, β Estrogen receptor produced reasonable correlations using LibDock (Pearson 0.75, Spearman 0.68). These findings can assist medicinal chemists to better match scoring functions with ligand-target systems for hit-to-lead optimization using computer-aided drug design approaches. Copyright © 2015 Elsevier Inc. All rights reserved.

Insights into biogenic and chemical production of inorganic nanomaterials and nanostructures.

PubMed

Faramarzi, Mohammad Ali; Sadighi, Armin

2013-03-01

The synthesis of inorganic nanomaterials and nanostructures by the means of diverse physical, chemical, and biological principles has been developed in recent decades. The nanoscale materials and structures creation continue to be an active area of researches due to the exciting properties of the resulting nanomaterials and their innovative applications. Despite physical and chemical approaches which have been used for a long time to produce nanomaterials, biological resources as green candidates that can replace old production methods have been focused in recent years to generate various inorganic nanoparticles (NPs) or other nanoscale structures. Cost-effective, eco-friendly, energy efficient, and nontoxic produced nanomaterials using diverse biological entities have been received increasing attention in the last two decades in contrast to physical and chemical methods owe using toxic solvents, generate unwanted by-products, and high energy consumption which restrict the popularity of these ways employed in nanometric science and engineering. In this review, the biosynthesis of gold, silver, gold-silver alloy, magnetic, semiconductor nanocrystals, silica, zirconia, titania, palladium, bismuth, selenium, antimony sulfide, and platinum NPs, using bacteria, actinomycetes, fungi, yeasts, plant extracts and also informational bio-macromolecules including proteins, polypeptides, DNA, and RNA have been reported extensively to mention the current status of the biological inorganic nanomaterial production. In other hand, two well-known wet chemical techniques, namely chemical reduction and sol-gel methods, used to produce various types of nanocrystalline powders, metal oxides, and hybrid organic-inorganic nanomaterials have presented. Copyright © 2012 Elsevier B.V. All rights reserved.

Physical and biological mechanisms of nanosecond- and microsecond-pulsed FE-DBD plasma interaction with biological objects

NASA Astrophysics Data System (ADS)

Dobrynin, Danil

2013-09-01

Mechanisms of plasma interaction with living tissues and cells can be quite complex, owing to the complexity of both the plasma and the tissue. Thus, unification of all the mechanisms under one umbrella might not be possible. Here, analysis of interaction of floating electrode dielectric barrier discharge (FE-DBD) with living tissues and cells is presented and biological and physical mechanisms are discussed. In physical mechanisms, charged species are identified as the major contributors to the desired effect and a mechanism of this interaction is proposed. Biological mechanisms are also addressed and a hypothesis of plasma selectivity and its effects is offered. Spatially uniform nanosecond and sub-nanosecond short-pulsed dielectric barrier discharge plasmas are gaining popularity in biological and medical applications due to their increased uniformity, lower plasma temperature, lower surface power density, and higher concentration of the active species produced. In this presentation we will compare microsecond pulsed plasmas with nanosecond driven systems and their applications in biology and medicine with specific focus on wound healing and tissue regeneration. Transition from negative to positive streamer will be discussed with proposed hypothesis of uniformity mechanisms of positive streamer and the reduced dependence on morphology and surface chemistry of the second electrode (human body) being treated. Uniform plasma offers a more uniform delivery of active species to the tissue/surface being treated thus leading to better control over the biological results.

Integrated aerobic biological-chemical treatment of winery wastewater diluted with urban wastewater. LED-based photocatalysis in the presence of monoperoxysulfate.

PubMed

Solís, Rafael R; Rivas, Francisco Javier; Ferreira, Leonor C; Pirra, Antonio; Peres, José A

2018-01-28

The oxidation of Winery Wastewater (WW) by conventional aerobic biological treatment usually leads to inefficient results due to the presence of organic substances, which are recalcitrant or toxic in conventional procedures. This study explores the combination of biological and chemical processes in order to complete the oxidation of biodegradable and non-biodegradable compounds in two sequential steps. Thus, a biological oxidation of a diluted WW is carried out by using the activated sludge process. Activated sludge was gradually acclimated to the Diluted Winery Wastewater (DWW). Some aspects concerning the biological process were evaluated (kinetics of the oxidation and sedimentation of the sludge produced). The biological treatment of the DWW led to a 40-50% of Chemical Oxygen Demand (COD) removal in 8 h, being necessary the application of an additional process. Different chemical processes combining UVA-LEDs radiation, monoperoxysulfate (MPS) and photocatalysts were applied in order to complete the COD depletion and efficient removal of polyphenols content, poorly oxidized in the previous biological step. From the options tested, the combination of UVA, MPS and a novel LaCoO 3 -TiO 2 composite, with double route of MPS decomposition through heterogeneous catalysis and photocatalysis, led to the best results (95% of polyphenol degradation, and additional 60% of COD removal). Initial MPS concentration and pH effect in this process were assessed.

Discovery of chitin in skeletons of non-verongiid Red Sea demosponges.

PubMed

Ehrlich, Hermann; Shaala, Lamiaa A; Youssef, Diaa T A; Żółtowska-Aksamitowska, Sonia; Tsurkan, Mikhail; Galli, Roberta; Meissner, Heike; Wysokowski, Marcin; Petrenko, Iaroslav; Tabachnick, Konstantin R; Ivanenko, Viatcheslav N; Bechmann, Nicole; Joseph, Yvonne; Jesionowski, Teofil

2018-01-01

Marine demosponges (Porifera: Demospongiae) are recognized as first metazoans which have developed over millions of years of evolution effective survival strategies based on unique metabolic pathways to produce both biologically active secondary metabolites and biopolymer-based stiff skeletons with 3D architecture. Up to date, among marine demosponges, only representatives of the Verongiida order have been known to synthetize biologically active substances as well as skeletons made of structural polysaccharide chitin. This work, to our knowledge, demonstrates for the first time that chitin is an important structural component within skeletons of non-verongiid demosponges Acarnus wolffgangi and Echinoclathria gibbosa collected in the Red Sea. Calcofluor white staining, FTIR and Raman analysis, ESI-MS, SEM, and fluorescence microscopy as well as a chitinase digestion assay were applied in order to confirm, with strong evidence, the finding of α-chitin in the skeleton of both species. We suggest that, the finding of chitin within these representatives of Poecilosclerida order is a promising step in the evaluation of these sponges as novel renewable sources for both biologically active metabolites and chitin, which are of prospective application for pharmacology and biomedicine.

Protein Hydrolysates and Biopeptides: Production, Biological Activities, and Applications in Foods and Health Benefits. A Review.

PubMed

Nasri, M

In recent years, a great deal of interest has been expressed regarding the production, characterization, and applications of protein hydrolysates and food-derived biopeptides due to their numerous beneficial health effects. In this regard, research is mainly focused on investigating the therapeutic potential of these natural compounds. Based on their amino acids composition, sequences, hydrophobicity, and length, peptides released from food proteins, beyond their nutritional properties, can exhibit various biological activities including antihypertensive, antioxidative, antithrombotic, hypoglycemic, hypocholesterolemic, and antibacterial activities among others. Protein hydrolysates are essentially produced by enzymatic hydrolysis of whole protein sources by appropriate proteolytic enzymes under controlled conditions, followed by posthydrolysis processing to isolate desired and potent bioactive peptides from a complex mixture of active and inactive peptides. Therefore, because of their human health potential and safety profiles, protein hydrolysates and biopeptides may be used as ingredients in functional foods and pharmaceuticals to improve human health and prevent diseases. In this review, we have focused on the major variables influencing the enzymatic process of protein hydrolysates production. The biological properties of protein hydrolysates will be described as well as their applications in foods and health benefits. © 2017 Elsevier Inc. All rights reserved.

[Evaluation of the total biological activity and allergenic composition of allergenic extracts].

PubMed

Lombardero, M; González, R; Duffort, O; Juan, F; Ayuso, R; Ventas, P; Cortés, C; Carreira, J

1986-01-01

In the present study, a complete procedure is presented in order to standardize allergenic extracts, the meaning of which is the measurement of the total allergenic activity and the determination of the allergenic composition. The measurement of the biological activity comprises 2 steps: Preparation of Reference Extracts and determination of their "in vivo" activity. Evaluation of the total allergenic activity of extracts for clinical use. Reference extracts were prepared from the main allergens and their "in vivo" biological activity was determined by a quantitative skin prick test in a sample of at least 30 allergic patients. By definition, the protein concentration of Reference Extract that produces, in the allergic population, a geometric mean wheal of 75 mm.2 has an activity of 100 biological units (BUs). The determination of the biological activity of a problem extract is made by RAST inhibition. The sample is compared with the corresponding Reference Extract by this technique and, from this comparison, it is possible to quantify the activity of the problem extract in biologic units (BUs) with clinical significance. Likewise, different techniques have been used to determine the allergenic composition of extracts. These techniques comprise 2 steps: Separation of the components of the extract. Identification of the components that bind specific human IgE. The separation of the components of the extract has been carried out by isoelectric focusing (IEF) and electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE). In order to identify the allergenic components, an immunoblotting technique has been employed. The separated components in the IEF gel or SDS-PAGE gel are transferred to a nitrocellulose sheet and later on, this membrane is overlaid with a serum pool from allergic patients and a mouse monoclonal anti-human IgE, labelled with 125I. Finally, the autoradiography of the nitrocellulose membrane is obtained. In this way it is possible to compare the allergenic composition of an extract with the corresponding Reference Extract and so to employ for clinical use only those extracts with the right allergenic composition.

An autonomous molecular computer for logical control of gene expression.

PubMed

Benenson, Yaakov; Gil, Binyamin; Ben-Dor, Uri; Adar, Rivka; Shapiro, Ehud

2004-05-27

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems. Recently, simple molecular-scale autonomous programmable computers were demonstrated allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for 'logical' control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug.

Carbon footprint of aerobic biological treatment of winery wastewater.

PubMed

Rosso, D; Bolzonella, D

2009-01-01

The carbon associated with wastewater and its treatment accounts for approximately 6% of the global carbon balance. Within the wastewater treatment industry, winery wastewater has a minor contribution, although it can have a major impact on wine-producing regions. Typically, winery wastewater is treated by biological processes, such as the activated sludge process. Biomass produced during treatment is usually disposed of directly, i.e. without digestion or other anaerobic processes. We applied our previously published model for carbon-footprint calculation to the areas worldwide producing yearly more than 10(6) m(3) of wine (i.e., France, Italy, Spain, California, Argentina, Australia, China, and South Africa). Datasets on wine production from the Food and Agriculture Organisation were processed and wastewater flow rates calculated with assumptions based on our previous experience. Results show that the wine production, hence the calculated wastewater flow, is reported as fairly constant in the period 2005-2007. Nevertheless, treatment process efficiency and energy-conservation may play a significant role on the overall carbon-footprint. We performed a sensitivity analysis on the efficiency of the aeration process (alphaSOTE per unit depth, or alphaSOTE/Z) in the biological treatment operations and showed significant margin for improvement. Our results show that the carbon-footprint reduction via aeration efficiency improvement is in the range of 8.1 to 12.3%.

Ratchet Effects in Active Matter Systems

NASA Astrophysics Data System (ADS)

Reichhardt, C. J. Olson; Reichhardt, C.

2017-03-01

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth of possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. We describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle-particle interactions, and nondissipative effects.

Biological activity of green-synthesized silver nanoparticles depends on the applied natural extracts: a comprehensive study.

PubMed

Rónavári, Andrea; Kovács, Dávid; Igaz, Nóra; Vágvölgyi, Csaba; Boros, Imre Miklós; Kónya, Zoltán; Pfeiffer, Ilona; Kiricsi, Mónika

2017-01-01

Due to obvious disadvantages of the classical chemical methods, green synthesis of metallic nanoparticles has attracted tremendous attention in recent years. Numerous environmentally benign synthesis methods have been developed yielding nanoparticles via low-cost, eco-friendly, and simple approaches. In this study, our aim was to determine the suitability of coffee and green tea extracts in green synthesis of silver nanoparticles as well as to compare the performance of the obtained materials in different biological systems. We successfully produced silver nanoparticles (C-AgNP and GT-AgNP) using coffee and green tea extracts; moreover, based on our comprehensive screening, we delineated major differences in the biological activity of C-AgNPs and GT-AgNPs. Our results indicate that although GT-AgNPs exhibited excellent antimicrobial activity against all the examined microbial pathogens, these particles were also highly toxic to mammalian cells, which limits their potential applications. On the contrary, C-AgNPs manifested substantial inhibitory action on the tested microbes but were nontoxic to human and mouse cells, indicating an outstanding capacity to discriminate between potential pathogens and mammalian cells. These results clearly show that the various green materials used for stabilization and for reduction of metal ions have a defining role in determining and fine-tuning the biological activity of the obtained nanoparticles.

Biological activity of green-synthesized silver nanoparticles depends on the applied natural extracts: a comprehensive study

PubMed Central

Rónavári, Andrea; Kovács, Dávid; Igaz, Nóra; Vágvölgyi, Csaba; Boros, Imre Miklós; Kónya, Zoltán; Pfeiffer, Ilona; Kiricsi, Mónika

2017-01-01

Due to obvious disadvantages of the classical chemical methods, green synthesis of metallic nanoparticles has attracted tremendous attention in recent years. Numerous environmentally benign synthesis methods have been developed yielding nanoparticles via low-cost, eco-friendly, and simple approaches. In this study, our aim was to determine the suitability of coffee and green tea extracts in green synthesis of silver nanoparticles as well as to compare the performance of the obtained materials in different biological systems. We successfully produced silver nanoparticles (C-AgNP and GT-AgNP) using coffee and green tea extracts; moreover, based on our comprehensive screening, we delineated major differences in the biological activity of C-AgNPs and GT-AgNPs. Our results indicate that although GT-AgNPs exhibited excellent antimicrobial activity against all the examined microbial pathogens, these particles were also highly toxic to mammalian cells, which limits their potential applications. On the contrary, C-AgNPs manifested substantial inhibitory action on the tested microbes but were nontoxic to human and mouse cells, indicating an outstanding capacity to discriminate between potential pathogens and mammalian cells. These results clearly show that the various green materials used for stabilization and for reduction of metal ions have a defining role in determining and fine-tuning the biological activity of the obtained nanoparticles. PMID:28184158

Predicting lymph node output efficiency using systems biology

PubMed Central

Gong, Chang; Mattila, Joshua T.; Miller, Mark; Flynn, JoAnne L.; Linderman, Jennifer J.; Kirschner, D.

2013-01-01

Dendritic cells (DCs) capture pathogens and foreign antigen (Ag) in peripheral tissues and migrate to secondary lymphoid tissues, such as lymph nodes (LNs), where they present processed Ag as MHC-bound peptide (pMHC) to naïve T cells. Interactions between DCs and T cells result, over periods of hours, in activation, clonal expansion and differentiation of antigen-specific T cells, leading to primed cells that can now participate in immune responses. Two-photon microscopy (2PM) has been widely adopted to analyze lymphocyte dynamics and can serve as a powerful in vivo assay for cell trafficking and activation over short length and time scales. Linking biological phenomena between vastly different spatiotemporal scales can be achieved using a systems biology approach. We developed a 3D agent-based cellular model of a LN that allows for the simultaneous in silico simulation of T cell trafficking, activation and production of effector cells under different antigen (Ag) conditions. The model anatomy is based on in situ analysis of LN sections (from primates and mice) and cell dynamics based on quantitative measurements from 2PM imaging of mice. Our simulations make three important predictions. First, T cell encounters by DCs and T cell receptor (TCR) repertoire scanning are more efficient in a 3D model compared with 2D, suggesting that a 3D model is needed to analyze LN function. Second, LNs are able to produce primed CD4+T cells at the same efficiency over broad ranges of cognate frequencies (from 10−5 to 10−2). Third, reducing the time that naïve T cells are required to bind DCs before becoming activated will increase the rate at which effector cells are produced. This 3D model provides a robust platform to study how T cell trafficking and activation dynamics relate to the efficiency of T cell priming and clonal expansion. We envision that this systems biology approach will provide novel insights for guiding vaccine development and understanding immune responses to infection. PMID:23816876

Bioremediation of trace organic compounds found in precious metals refineries' wastewaters: a review of potential options.

PubMed

Barbosa, V L; Tandlich, R; Burgess, J E

2007-07-01

Platinum group metal (PGM) refining processes produce large quantities of wastewater, which is contaminated with the compounds that make up the solvents/extractants mixtures used in the process. These compounds often include solvesso, beta-hydroxyxime, amines, amides and methyl isobutyl ketone. A process to clean up PGM refinery wastewaters so that they could be re-used in the refining process would greatly contribute to continual water storage problems and to cost reduction for the industry. Based on the concept that organic compounds that are produced biologically can be destroyed biologically, the use of biological processes for the treatment of organic compounds in other types of waste stream has been favoured in recent years, owing to their low cost and environmental acceptability. This review examines the available biotechnologies and their effectiveness for treating compounds likely to be contained in precious metal extraction process wastewaters. The processes examined include: biofilters, fluidized bed reactors, trickle-bed bioreactors, bioscrubbers, two-phase partitioning bioreactors, membrane bioreactors and activated sludge. Although all processes examined showed adequate to excellent removal of organic compounds from various gaseous and fewer liquid waste streams, there was a variation in their effectiveness. Variations in performance of laboratory-scale biological processes are probably due to the inherent change in the microbial population composition due to selection pressure, environmental conditions and the time allowed for adaptation to the organic compounds. However, if these factors are disregarded, it can be established that activated sludge and membrane bioreactors are the most promising processes for use in the treatment of PGM refinery wastewaters.

[Effect of medicinal plant extracts on the growth of microorganisms].

PubMed

Baronets, N G; Adlova, G P; Mel'nikova, V A

2001-01-01

Extracts obtained from sweatweed and licorice roots, flax seeds, milfoil, bur-marigold, plantain, coltsfoot, nettle, Indian corn stigmas, laminaria produced a stimulating effect on the growth of Candida albicans test strain and Streptococcus pyogenes test strain Dick 1. Sweatweed, licorice, Aerva lanata and violet extracts influenced the growth of Corynebacterium xerosis 1911, while sweatweed, violet, horse-tail, bur-marigold, camomile, plantain, and nettle extracts influenced the growth of shigellae. The stimulating effect could be supposedly produced by biologically active substances contained in medicinal plants (organic acids, alkaloids, carotinoids, vitamins, microelements). Further studies aimed at the identification of substances producing the stimulating effect are planned.

In Vitro Dermo-Cosmetic Evaluation of Bark Extracts from Common Temperate Trees.

PubMed

Hubert, Jane; Angelis, Apostolis; Aligiannis, Nektarios; Rosalia, Michalea; Abedini, Amin; Bakiri, Ali; Reynaud, Romain; Nuzillard, Jean-Marc; Gangloff, Sophie C; Skaltsounis, Alexios-Leandros; Renault, Jean-Hugues

2016-10-01

Wood residues produced from forestry activities represent an interesting source of biologically active, high value-added secondary metabolites. In this study, 30 extracts from 10 barks of deciduous and coniferous tree species were investigated for their potential dermo-cosmetic use. The extracts were obtained from Fagus sylvatica, Quercus robur, Alnus glutinosa, Prunus avium, Acer pseudoplatanus, Fraxinus excelsior, Populus robusta, Larix decidua, Picea abies , and Populus tremula after three successive solid/liquid extractions of the barks with n- heptane, methanol, and methanol/water. All extracts were evaluated for their radical scavenging capacity, for their elastase, collagenase, and tyrosinase inhibitory activities, as well as for their antibacterial activity against gram-positive Staphylococcus aureus . In parallel, the global metabolite profiles of all extracts were established by 1D and 2D NMR and related to their biological activity. The results showed that the methanol extracts of Q. robur, A. glutinosa, L. decidua , and P. abies barks exhibit particularly high activities on most bioassays, suggesting their promising use as active ingredients in the dermo-cosmetic industry. Georg Thieme Verlag KG Stuttgart · New York.

Effects of high-voltage transmission lines on honeybees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenberg, B.; Bindokas, V.P.; Gauger, J.R.

When shielded and exposed colonies were placed at incremental distances at a right angle from a 760-kV transmission line different thresholds for biologic effects were obtained. Hive exposures were controlled (E-field: 7, 5.5, 4.1, 1.8, and 0.65 to 0.85 kV/m) by variable height current collectors; shielded hives under the line behave normally. Exposure to 7 kV/m can produce the following sequence of events: (1) increased motor activity and transient hive temperature increase; (2) abnormal propolization; (3) retarded hive weight gain; (4) excess queen cell production with queen loss; (5) reduction of sealed brood area; and (6) poor winter survival. Nomore » biological effects were detected below 4.1 kV/m, thus the ''biological effects corridor'' is limited to approximately 23 m beyond a ground projection of each outer phase wire. Hive architecture enhances E-fields and creates shock hazards for bees. Intra-hive E-fields (15 to 100+ kV/m) were measured with a displacement current sensor and fiber optic telemetry link. Step-potential-induced currents up to 0.5 uA were measured with a bee model in hives at 7 kV/m. To investigate further the role of shock versus electric field exposure the study was continued to develop hive entrance extensions (porches), which produce controlled bee exposure to E-field or shock, and to test the feasibility of using these porches in such a study. Biological effects (e.g., abnormal propolization, retarded hive weight, queen loss) found in colonies with total-hive exposure were produced by entrance-only exposure of adult bees. We now have an exposure system in which E-field and shock can be separately controlled to reproduce the biological effects. 10 refs.« less

Atmospheric energy for subsurface life on Mars?

NASA Technical Reports Server (NTRS)

Weiss, B. P.; Yung, Y. L.; Nealson, K. H.

2000-01-01

The location and density of biologically useful energy sources on Mars will limit the biomass, spatial distribution, and organism size of any biota. Subsurface Martian organisms could be supplied with a large energy flux from the oxidation of photochemically produced atmospheric H(2) and CO diffusing into the regolith. However, surface abundance measurements of these gases demonstrate that no more than a few percent of this available flux is actually being consumed, suggesting that biological activity driven by atmospheric H(2) and CO is limited in the top few hundred meters of the subsurface. This is significant because the available but unused energy is extremely large: for organisms at 30-m depth, it is 2,000 times previous estimates of hydrothermal and chemical weathering energy and far exceeds the energy derivable from other atmospheric gases. This also implies that the apparent scarcity of life on Mars is not attributable to lack of energy. Instead, the availability of liquid water may be a more important factor limiting biological activity because the photochemical energy flux can only penetrate to 100- to 1,000-m depth, where most H(2)O is probably frozen. Because both atmospheric and Viking lander soil data provide little evidence for biological activity, the detection of short-lived trace gases will probably be a better indicator of any extant Martian life.

Atmospheric energy for subsurface life on Mars?

PubMed

Weiss, B P; Yung, Y L; Nealson, K H

2000-02-15

The location and density of biologically useful energy sources on Mars will limit the biomass, spatial distribution, and organism size of any biota. Subsurface Martian organisms could be supplied with a large energy flux from the oxidation of photochemically produced atmospheric H(2) and CO diffusing into the regolith. However, surface abundance measurements of these gases demonstrate that no more than a few percent of this available flux is actually being consumed, suggesting that biological activity driven by atmospheric H(2) and CO is limited in the top few hundred meters of the subsurface. This is significant because the available but unused energy is extremely large: for organisms at 30-m depth, it is 2,000 times previous estimates of hydrothermal and chemical weathering energy and far exceeds the energy derivable from other atmospheric gases. This also implies that the apparent scarcity of life on Mars is not attributable to lack of energy. Instead, the availability of liquid water may be a more important factor limiting biological activity because the photochemical energy flux can only penetrate to 100- to 1,000-m depth, where most H(2)O is probably frozen. Because both atmospheric and Viking lander soil data provide little evidence for biological activity, the detection of short-lived trace gases will probably be a better indicator of any extant Martian life.

Structural and functional characterization of recombinant napin-like protein of Momordica charantia expressed in methylotrophic yeast Pichia pastoris.

PubMed

Yadav, Shailesh Kumar R; Sahu, Tejram; Dixit, Aparna

2016-08-01

Napin and napin-like proteins belong to the 2S albumin seed storage family of proteins and have been shown to display a variety of biological activities. However, due to a high degree of polymorphism, purification of a single napin or napin-like protein exhibiting biological activity is extremely difficult. In the present study, we have produced the napin-like protein of Momordica charantia using the methylotrophic Pichia pastoris expression system. The recombinant napin-like protein (rMcnapin) secreted in the extracellular culture supernatant was enriched by ammonium sulfate precipitation, and purified using size exclusion chromatography at a yield of ∼290 mg/L of culture. Secondary structure analysis of the purified rMcnapin revealed it to be predominantly α-helical with minimal β strand content. CD spectroscopic and fluorescence spectroscopic analyses revealed the rMcnapin to be stable at a wide range of temperatures and pH. The rMcnapin exhibited antifungal activity against Trichoderma viride with an IC50 of ∼3.7 μg/ml and trypsin inhibitor activity with an IC50 of 4.2 μM. Thus, large amounts of homogenous preparations of the biologically active rMcnapin could be obtained at shake flask level, which is otherwise difficult from its natural source.

Carbon wastewater treatment process

NASA Technical Reports Server (NTRS)

Humphrey, M. F.; Simmons, G. M.; Dowler, W. L.

1974-01-01

A new powdered-carbon treatment process is being developed for the elimination of the present problems, associated with the disposal of biologically active sewage waste solids, and with water reuse. This counter-current flow process produces an activated carbon, which is obtained from the pyrolysis of the sewage solids, and utilizes this material to remove the adulterating materials from the water. Additional advantages of the process are the elimination of odors, the removal of heavy metals, and the potential for energy conservation.

A Metabolic Probe-Enabled Strategy Reveals Uptake and Protein Targets of Polyunsaturated Aldehydes in the Diatom Phaeodactylum tricornutum

PubMed Central

Wolfram, Stefanie; Wielsch, Natalie; Hupfer, Yvonne; Mönch, Bettina; Lu-Walther, Hui-Wen; Heintzmann, Rainer; Werz, Oliver; Svatoš, Aleš; Pohnert, Georg

2015-01-01

Diatoms are unicellular algae of crucial importance as they belong to the main primary producers in aquatic ecosystems. Several diatom species produce polyunsaturated aldehydes (PUAs) that have been made responsible for chemically mediated interactions in the plankton. PUA-effects include chemical defense by reducing the reproductive success of grazing copepods, allelochemical activity by interfering with the growth of competing phytoplankton and cell to cell signaling. We applied a PUA-derived molecular probe, based on the biologically highly active 2,4-decadienal, with the aim to reveal protein targets of PUAs and affected metabolic pathways. By using fluorescence microscopy, we observed a substantial uptake of the PUA probe into cells of the diatom Phaeodactylum tricornutum in comparison to the uptake of a structurally closely related control probe based on a saturated aldehyde. The specific uptake motivated a chemoproteomic approach to generate a qualitative inventory of proteins covalently targeted by the α,β,γ,δ-unsaturated aldehyde structure element. Activity-based protein profiling revealed selective covalent modification of target proteins by the PUA probe. Analysis of the labeled proteins gave insights into putative affected molecular functions and biological processes such as photosynthesis including ATP generation and catalytic activity in the Calvin cycle or the pentose phosphate pathway. The mechanism of action of PUAs involves covalent reactions with proteins that may result in protein dysfunction and interference of involved pathways. PMID:26496085

Single and multiple streamer DBD micro-discharges for testing inactivation of biologically contaminated surfaces

NASA Astrophysics Data System (ADS)

Prukner, Vaclav; Dolezalova, Eva; Simek, Milan

2014-10-01

Highly reactive environment produced by atmospheric-pressure, non-equilibrium plasmas generated by surface dielectric barrier discharges (SDBDs) may be used for inactivation of biologically contaminated surfaces. We investigated decontamination efficiency of reactive environment produced by single/multiple surface streamer micro-discharge driven by amplitude-modulated AC power in coplanar electrode geometry on biologically contaminated surface by Escherichia coli. The discharges were fed by synthetic air with water vapor admixtures at atmospheric pressure, time of treatment was set from 10 second to 10 minutes, diameters of used SDBD electrodes (single and multiple streamer) and homogeneously contaminated disc samples were equal (25 mm), the distance between the electrode and contaminated surface was 2 mm. Both a conventional cultivation and fluorescent method LIVE/DEAD Bacterial Viability kit were applied to estimate counts of bacteria after the plasma treatment. Inactivation was effective and bacteria partly lost ability to grow and became injured and viable/active but non-cultivable (VBNC/ABNC). Work was supported by the MEYS under Project LD13010, VES13 COST CZ (COST Action MP 1101).

Recent advances on biological production of difructose dianhydride III.

PubMed

Zhu, Yingying; Yu, Shuhuai; Zhang, Wenli; Zhang, Tao; Guang, Cuie; Mu, Wanmeng

2018-04-01

Difructose dianhydride III (DFA III) is a cyclic difructose containing two reciprocal glycosidic linkages. It is easily generated with a small amount by sucrose caramelization and thus occurs in a wide range of food-stuffs during food processing. DFA III has half sweetness but only 1/15 energy of sucrose, showing potential industrial application as low-calorie sucrose substitute. In addition, it displays many benefits including prebiotic effect, low cariogenicity property, and hypocholesterolemic effect, and improves absorption of minerals, flavonoids, and immunoglobulin G. DFA III is biologically produced from inulin by inulin fructotransferase (IFTase, EC 4.2.2.18). Plenty of DFA III-producing enzymes have been identified. The crystal structure of inulin fructotransferase has been determined, and its molecular modification has been performed to improve the catalytic activity and structural stability. Large-scale production of DFA III has been studied by various IFTases, especially using an ultrafiltration membrane bioreactor. In this article, the recent findings on physiological effects of DFA III are briefly summarized; the research progresses on identification, expression, and molecular modification of IFTase and large-scale biological production of DFA III by IFTase are reviewed in detail.

Exploring environment-dependent effects of Pd nanostructures on reactive oxygen species (ROS) using electron spin resonance (ESR) technique: implications for biomedical applications.

PubMed

Wen, Tao; He, Weiwei; Chong, Yu; Liu, Yi; Yin, Jun-Jie; Wu, Xiaochun

2015-10-14

Recently, because of the great advances in tailoring their shape and structure, palladium nanoparticles (Pd NPs) have been receiving increasing attention in biomedical fields apart from their traditional application as industrial catalysts. When considering the potential uses of Pd NPs in biomedicine, their catalytic properties need to be evaluated under physiologically relevant conditions. In this article, we demonstrate that Pd nanostructures (NSs, both commercial Pd NPs and in-house-prepared Au@Pd nanorods) can induce O2 or ˙OH production depending on pH values in the presence of H2O2. We observed that O2 is produced under neutral and alkaline conditions but ˙OH under acidic conditions. We also found that Pd NSs can scavenge superoxide and singlet oxygen, which may provide protection in biological systems. On the other hand, their oxidase-like activity may accelerate the oxidation of ascorbic acid and thus may produce negative biological effects. The presented study will provide useful guidance for designing noble metal nanostructures with desired catalytic and biological properties in biomedical applications.

Context-dependent role of IL-18 in cancer biology and counter-regulation by IL-18BP.

PubMed

Fabbi, Marina; Carbotti, Grazia; Ferrini, Silvano

2015-04-01

IL-18 is a proinflammatory and immune regulatory cytokine, member of the IL-1 family. IL-18 was initially identified as an IFN-γ-inducing factor in T and NK cells, involved in Th1 responses. IL-18 is produced as an inactive precursor (pro-IL-18) that is enzymatically processed into a mature form by Casp1. Different cells, such as macrophages, DCs, microglial cells, synovial fibroblasts, and epithelial cells, express pro-IL-18, and the production of bioactive IL-18 is mainly regulated at the processing level. PAMP or DAMP molecules activate inflammasomes, which trigger Casp1 activation and IL-18 conversion. The natural inhibitor IL-18BP , whose production is enhanced by IFN-γ and IL-27, further regulates IL-18 activity in the extracellular environment. Inflammasomes and IL-18 represent double-edged swords in cancer, as their activation may promote tumor development and progression or oppositely, enhance anti-tumor immunity and limit tumor growth. IL-18 has shown anti-tumor activity in different preclinical models of cancer immunotherapy through the activation of NK and/or T cell responses and has been tested in clinical studies in cancer patients. However, the dual role of IL-18 in different experimental tumor models and human cancers raises critical issues on its therapeutic use in cancer. This review will summarize the biology of the IL-18/IL-18R/IL-18BP system and will address the role of IL-18 and its inhibitor, IL-18BP, in cancer biology and immunotherapy. © Society for Leukocyte Biology.

David and Goliath: chemical perturbation of eukaryotes by bacteria.

PubMed

Ho, Louis K; Nodwell, Justin R

2016-03-01

Environmental microbes produce biologically active small molecules that have been mined extensively as antibiotics and a smaller number of drugs that act on eukaryotic cells. It is known that there are additional bioactives to be discovered from this source. While the discovery of new antibiotics is challenged by the frequent discovery of known compounds, we contend that the eukaryote-active compounds may be less saturated. Indeed, despite there being far fewer eukaryotic-active natural products these molecules interact with a far richer diversity of molecular and cellular targets.

Self-assembling biomolecular catalysts for hydrogen production

NASA Astrophysics Data System (ADS)

Jordan, Paul C.; Patterson, Dustin P.; Saboda, Kendall N.; Edwards, Ethan J.; Miettinen, Heini M.; Basu, Gautam; Thielges, Megan C.; Douglas, Trevor

2016-02-01

The chemistry of highly evolved protein-based compartments has inspired the design of new catalytically active materials that self-assemble from biological components. A frontier of this biodesign is the potential to contribute new catalytic systems for the production of sustainable fuels, such as hydrogen. Here, we show the encapsulation and protection of an active hydrogen-producing and oxygen-tolerant [NiFe]-hydrogenase, sequestered within the capsid of the bacteriophage P22 through directed self-assembly. We co-opted Escherichia coli for biomolecular synthesis and assembly of this nanomaterial by expressing and maturing the EcHyd-1 hydrogenase prior to expression of the P22 coat protein, which subsequently self assembles. By probing the infrared spectroscopic signatures and catalytic activity of the engineered material, we demonstrate that the capsid provides stability and protection to the hydrogenase cargo. These results illustrate how combining biological function with directed supramolecular self-assembly can be used to create new materials for sustainable catalysis.

Bioactivity and Applications of Sulphated Polysaccharides from Marine Microalgae

PubMed Central

de Jesus Raposo, Maria Filomena; de Morais, Rui Manuel Santos Costa; de Morais, Alcina Maria Miranda Bernardo

2013-01-01

Marine microalgae have been used for a long time as food for humans, such as Arthrospira (formerly, Spirulina), and for animals in aquaculture. The biomass of these microalgae and the compounds they produce have been shown to possess several biological applications with numerous health benefits. The present review puts up-to-date the research on the biological activities and applications of polysaccharides, active biocompounds synthesized by marine unicellular algae, which are, most of the times, released into the surrounding medium (exo- or extracellular polysaccharides, EPS). It goes through the most studied activities of sulphated polysaccharides (sPS) or their derivatives, but also highlights lesser known applications as hypolipidaemic or hypoglycaemic, or as biolubricant agents and drag-reducers. Therefore, the great potentials of sPS from marine microalgae to be used as nutraceuticals, therapeutic agents, cosmetics, or in other areas, such as engineering, are approached in this review. PMID:23344113

Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?

PubMed Central

2015-01-01

High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as pan-assay interference compounds (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as invalid metabolic panaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence–bioactivity–effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base. PMID:26505758

RNA Cap Methyltransferase Activity Assay

PubMed Central

Trotman, Jackson B.; Schoenberg, Daniel R.

2018-01-01

Methyltransferases that methylate the guanine-N7 position of the mRNA 5′ cap structure are ubiquitous among eukaryotes and commonly encoded by viruses. Here we provide a detailed protocol for the biochemical analysis of RNA cap methyltransferase activity of biological samples. This assay involves incubation of cap-methyltransferase-containing samples with a [32P]G-capped RNA substrate and S-adenosylmethionine (SAM) to produce RNAs with N7-methylated caps. The extent of cap methylation is then determined by P1 nuclease digestion, thin-layer chromatography (TLC), and phosphorimaging. The protocol described here includes additional steps for generating the [32P]G-capped RNA substrate and for preparing nuclear and cytoplasmic extracts from mammalian cells. This assay is also applicable to analyzing the cap methyltransferase activity of other biological samples, including recombinant protein preparations and fractions from analytical separations and immunoprecipitation/pulldown experiments. PMID:29644259

Jasmonic and salicylic acids enhanced phytochemical production and biological activities in cell suspension cultures of spine gourd (Momordica dioica Roxb).

PubMed

Chung, Ill-Min; Rekha, Kaliyaperumal; Rajakumar, Govindasamy; Thiruvengadam, Muthu

2017-03-01

In vitro cell suspension culture was established for the production of commercially valuable phytochemicals in Momordica dioica. The influence of elicitors in jasmonic acid (JA) and salicylic acid (SA) increased their effect on phytochemical production and biomass accumulation in M. dioica. The results indicate that compared with non-elicited cultures, JA- and SA-elicited cell suspension cultures had significantly enhanced phenolic, flavonoid, and carotenoid production, as well as antioxidant, antimicrobial, and antiproliferative activities. Furthermore, elicited cultures produced 22 phenolic compounds, such as flavonols, hydroxycinnamic acids, and hydroxybenzoic acids. Greater biomass production, phytochemical accumulation, and biological activity occurred in JA- than in SA-elicited cell cultures. This study is the first to successfully establish M. dioica cell suspension cultures for the production of phenolic compounds and carotenoids, as well as for biomass accumulation.

Biological activities of the polysaccharides produced in submerged culture of two edible Pleurotus ostreatus mushrooms.

PubMed

Vamanu, Emanuel

2012-01-01

Exopolysaccharides (EPS) and internal (intracellular) polysaccharides (IPS) obtained from the Pleurotus ostreatus M2191 and PBS281009 cultivated using the batch system revealed an average of between 0.1-2 (EPS) and 0.07-1.5 g/L/day (IPS). The carbohydrate analysis revealed that the polysaccharides comprised 87-89% EPS and 68-74% IPS. The investigation of antioxidant activity in vitro revealed a good antioxidant potential, particularly for the IPS and EPS isolated from PBS281009, as proved by the EC(50) value for DPPH, ABTS scavenging activity, reducing power, and iron chelating activity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reichhardt, Cynthia Jane; Reichhardt, Charles

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth ofmore » possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. Here, we describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle–particle interactions, and nondissipative effects.« less

Reorienting the Fab Domains of Trastuzumab Results in Potent HER2 Activators

PubMed Central

Scheer, Justin M.; Sandoval, Wendy; Elliott, J. Michael; Shao, Lily; Luis, Elizabeth; Lewin-Koh, Sock-Cheng; Schaefer, Gabriele; Vandlen, Richard

2012-01-01

The structure of the Fab region of antibodies is critical to their function. By introducing single cysteine substitutions into various positions of the heavy and light chains of the Fab region of trastuzumab, a potent antagonist of HER2, and using thiol chemistry to link the different Fabs together, we produced a variety of monospecific F(ab′)2-like molecules with activities spanning from activation to inhibition of breast tumor cell growth. These isomers (or bis-Fabs) of trastuzumab, with varying relative spatial arrangements between the Fv-regions, were able to either promote or inhibit cell-signaling activities through the PI3K/AKT and MAPK pathways. A quantitative phosphorylation mapping of HER2 indicated that the agonistic isomers produced a distinct phosphorylation pattern associated with activation. This study suggests that antibody geometric isomers, found both in nature and during synthetic antibody development, can have profoundly different biological activities independent of their affinities for their target molecules. PMID:23284778

The Madeira Archipelago As a Significant Source of Marine-Derived Actinomycete Diversity with Anticancer and Antimicrobial Potential

PubMed Central

Prieto-Davó, Alejandra; Dias, Tiago; Gomes, Sofia E.; Rodrigues, Sara; Parera-Valadez, Yessica; Borralho, Pedro M.; Pereira, Florbela; Rodrigues, Cecilia M. P.; Santos-Sanches, Ilda; Gaudêncio, Susana P.

2016-01-01

Marine-derived actinomycetes have demonstrated an ability to produce novel compounds with medically relevant biological activity. Studying the diversity and biogeographical patterns of marine actinomycetes offers an opportunity to identify genera that are under environmental pressures, which may drive adaptations that yield specific biosynthetic capabilities. The present study describes research efforts to explore regions of the Atlantic Ocean, specifically around the Madeira Archipelago, where knowledge of the indigenous actinomycete diversity is scarce. A total of 400 actinomycetes were isolated, sequenced, and screened for antimicrobial and anticancer activities. The three most abundant genera identified were Streptomyces, Actinomadura, and Micromonospora. Phylogenetic analyses of the marine OTUs isolated indicated that the Madeira Archipelago is a new source of actinomycetes adapted to life in the ocean. Phylogenetic differences between offshore (>100 m from shore) and nearshore (< 100 m from shore) populations illustrates the importance of sampling offshore in order to isolate new and diverse bacterial strains. Novel phylotypes from chemically rich marine actinomycete groups like MAR4 and the genus Salinispora were isolated. Anticancer and antimicrobial assays identified Streptomyces, Micromonospora, and Salinispora as the most biologically active genera. This study illustrates the importance of bioprospecting efforts at unexplored regions of the ocean to recover bacterial strains with the potential to produce novel and interesting chemistry. PMID:27774089

Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans.

PubMed

Deline, Marshall; Keller, Julia; Rothe, Michael; Schunck, Wolf-Hagen; Menzel, Ralph; Watts, Jennifer L

2015-10-21

Dietary fats are not created equally, slight differences in structure lead to crucial differences in function. Muticellular organisms use polyunsaturated fatty acid as substrates to produce potent signaling molecules crucial for many physiological processes, including reproduction. Here we explored the mechanism responsible for germ cell loss induced by dietary supplementation of dihomo-gamma-linolenic acid (DGLA, 20:3n-6) in the roundworm Caenorhabditis elegans. In this study we found that C. elegans CYP-33E2 activity produces a range of epoxy and hydroxy metabolites from dietary DGLA. Knockdown of cyp-33E2 suppressed the DGLA-induced sterility phenotype. Additionally, direct exposure of two specific DGLA-derived epoxy products, 8,9- and 14,15-epoxyeicosadienoic acids, produced germ cell abnormalities in the C. elegans gonad. We propose that sterility is mediated by the production of toxic DGLA-derived epoxides that trigger germ cell destruction. These studies are the first to establish a biological activity for a CYP-produced metabolite of DGLA.

Biological effects of paenilamicin, a secondary metabolite antibiotic produced by the honey bee pathogenic bacterium Paenibacillus larvae.

PubMed

Garcia-Gonzalez, Eva; Müller, Sebastian; Hertlein, Gillian; Heid, Nina; Süssmuth, Roderich D; Genersch, Elke

2014-10-01

Paenibacillus larvae is the etiological agent of American Foulbrood (AFB) a world-wide distributed devastating disease of the honey bee brood. Previous comparative genome analysis and more recently, the elucidation of the bacterial genome, provided evidence that this bacterium harbors putative functional nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) and therefore, might produce nonribosomal peptides (NRPs) and polyketides (PKs). Such biosynthesis products have been shown to display a wide-range of biological activities such as antibacterial, antifungal or cytotoxic activity. Herein we present an in silico analysis of the first NRPS/PKS hybrid of P. larvae and we show the involvement of this cluster in the production of a compound named paenilamicin (Pam). For the characterization of its in vitro and in vivo bioactivity, a knock-out mutant strain lacking the production of Pam was constructed and subsequently compared to wild-type species. This led to the identification of Pam by mass spectrometry. Purified Pam-fractions showed not only antibacterial but also antifungal and cytotoxic activities. The latter suggested a direct effect of Pam on honey bee larval death which could, however, not be corroborated in laboratory infection assays. Bee larvae infected with the non-producing Pam strain showed no decrease in larval mortality, but a delay in the onset of larval death. We propose that Pam, although not essential for larval mortality, is a virulence factor of P. larvae influencing the time course of disease. These findings are not only of significance in elucidating and understanding host-pathogen interactions but also within the context of the quest for new compounds with antibiotic activity for drug development. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

CFP-10 from Mycobacterium tuberculosis Selectively Activates Human Neutrophils through a Pertussis Toxin-Sensitive Chemotactic Receptor

PubMed Central

Björnsdottir, Halla; Winther, Malene; Christenson, Karin; Oprea, Tudor; Karlsson, Anna; Forsman, Huamei; Dahlgren, Claes; Bylund, Johan

2014-01-01

Upon infection with Mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. Through a type VII secretion system, M. tuberculosis releases a heterodimeric protein complex, containing a 6-kDa early secreted antigenic target (ESAT-6) and a 10-kDa culture filtrate protein (CFP-10), that is essential for virulence. Whereas the ESAT-6 component possesses multiple virulence-related activities, no direct biological activity of CFP-10 has been shown, and CFP-10 has been described as a chaperone protein for ESAT-6. We here show that the ESAT-6:CFP-10 complex induces a transient release of Ca2+ from intracellular stores in human neutrophils. Surprisingly, CFP-10 rather than ESAT-6 was responsible for triggering the Ca2+ response, in a pertussis toxin-sensitive manner, suggesting the involvement of a G-protein-coupled receptor. In line with this, the response was accompanied by neutrophil chemotaxis and activation of the superoxide-producing NADPH-oxidase. Neutrophils were unique among leukocytes in responding to CFP-10, as monocytes and lymphocytes failed to produce a Ca2+ signal upon stimulation with the M. tuberculosis protein. Hence, CFP-10 may contribute specifically to neutrophil recruitment and activation during M. tuberculosis infection, representing a novel biological role for CFP-10 in the ESAT-6:CFP-10 complex, beyond the previously described chaperone function. PMID:25332123

Redox Control of Inflammation in Macrophages

PubMed Central

Dehne, Nathalie; Grossmann, Nina; Jung, Michaela; Namgaladze, Dmitry; Schmid, Tobias; von Knethen, Andreas; Weigert, Andreas

2013-01-01

Abstract Macrophages are present throughout the human body, constitute important immune effector cells, and have variable roles in a great number of pathological, but also physiological, settings. It is apparent that macrophages need to adjust their activation profile toward a steadily changing environment that requires altering their phenotype, a process known as macrophage polarization. Formation of reactive oxygen species (ROS), derived from NADPH-oxidases, mitochondria, or NO-producing enzymes, are not necessarily toxic, but rather compose a network signaling system, known as redox regulation. Formation of redox signals in classically versus alternatively activated macrophages, their action and interaction at the level of key targets, and the resulting physiology still are insufficiently understood. We review the identity, source, and biological activities of ROS produced during macrophage activation, and discuss how they shape the key transcriptional responses evoked by hypoxia-inducible transcription factors, nuclear-erythroid 2-p45-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor-γ. We summarize the mechanisms how redox signals add to the process of macrophage polarization and reprogramming, how this is controlled by the interaction of macrophages with their environment, and addresses the outcome of the polarization process in health and disease. Future studies need to tackle the option whether we can use the knowledge of redox biology in macrophages to shape their mediator profile in pathophysiology, to accelerate healing in injured tissue, to fight the invading pathogens, or to eliminate settings of altered self in tumors. Antioxid. Redox Signal. 19, 595–637. PMID:23311665

Synthetic Biology and Personalized Medicine

PubMed Central

Jain, K.K.

2013-01-01

Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

Biological Activities of Stilbenoids.

PubMed

Akinwumi, Bolanle C; Bordun, Kimberly-Ann M; Anderson, Hope D

2018-03-09

Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene, but differ in the nature and position of substituents. Stilbenoids are classified as phytoalexins, which are antimicrobial compounds produced de novo in plants to protect against fungal infection and toxins. In this review, the biological effects of stilbenoids such as resveratrol, pterostilbene, gnetol and piceatannol are discussed. Stilbenoids exert various biological activities ranging from cardioprotection, neuroprotection, anti-diabetic properties, depigmentation, anti-inflammation, cancer prevention and treatment. The results presented cover a myriad of models, from cell culture to animal studies as well as clinical human trials. Although positive results were obtained in most cell culture and animal studies, further human studies are needed to substantiate beneficial effects of stilbenoids. Resveratrol remains the most widely studied stilbenoid. However, there is limited information regarding the potential of less common stilbenoids. Therefore, further research is warranted to evaluate the salutary effects of various stilbenoids.

Biological Activities of Stilbenoids

PubMed Central

Bordun, Kimberly-Ann M.

2018-01-01

Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene, but differ in the nature and position of substituents. Stilbenoids are classified as phytoalexins, which are antimicrobial compounds produced de novo in plants to protect against fungal infection and toxins. In this review, the biological effects of stilbenoids such as resveratrol, pterostilbene, gnetol and piceatannol are discussed. Stilbenoids exert various biological activities ranging from cardioprotection, neuroprotection, anti-diabetic properties, depigmentation, anti-inflammation, cancer prevention and treatment. The results presented cover a myriad of models, from cell culture to animal studies as well as clinical human trials. Although positive results were obtained in most cell culture and animal studies, further human studies are needed to substantiate beneficial effects of stilbenoids. Resveratrol remains the most widely studied stilbenoid. However, there is limited information regarding the potential of less common stilbenoids. Therefore, further research is warranted to evaluate the salutary effects of various stilbenoids. PMID:29522491

Developing Guided Inquiry-Based Student Lab Worksheet for Laboratory Knowledge Course

NASA Astrophysics Data System (ADS)

Rahmi, Y. L.; Novriyanti, E.; Ardi, A.; Rifandi, R.

2018-04-01

The course of laboratory knowledge is an introductory course for biology students to follow various lectures practicing in the biology laboratory. Learning activities of laboratory knowledge course at this time in the Biology Department, Universitas Negeri Padang has not been completed by supporting learning media such as student lab worksheet. Guided inquiry learning model is one of the learning models that can be integrated into laboratory activity. The study aimed to produce student lab worksheet based on guided inquiry for laboratory knowledge course and to determine the validity of lab worksheet. The research was conducted using research and developmet (R&D) model. The instruments used in data collection in this research were questionnaire for student needed analysis and questionnaire to measure the student lab worksheet validity. The data obtained was quantitative from several validators. The validators consist of three lecturers. The percentage of a student lab worksheet validity was 94.18 which can be categorized was very good.

Extraction, Characterization, Stability and Biological Activity of Flavonoids Isolated from Chamomile Flowers

PubMed Central

Srivastava, Janmejai K; Gupta, Sanjay

2009-01-01

Dried flowers of Chamomile (Matricaria chamomilla) are largely used for their medicinal properties. In the present study, we examined the pharmacological properties of aqueous and methanolic fraction isolated from two varieties of German chamomile. HPLC-MS analysis of chamomile extract confirmed apigenin-7-O-glucoside as the major constituent of chamomile; some minor glycoside components were observed along with essential oils. These glucosides are highly stable in solution at different temperature range and their degradation occurs after long-term storage and extraction conditions at different pH and solvent. Methanolic fraction isolated from chamomile flowers demonstrated higher biologic response in inhibiting cell growth and causing induction of apoptosis in various human cancer cell lines compared to aqueous chamomile fraction. Apigenin glucosides inhibited cancer cell growth through deconjugation of glycosides that occurs in the cellular compartment to produce aglycone, apigenin. Taken together, the pharmacological profile of chamomile extract was dependent upon extraction process, storage conditions which affected the biological activity. PMID:20098626

Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology.

PubMed

Gogineni, Vedanjali; Hamann, Mark T

2018-01-01

The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of mussel shell addition on the chemical and biological properties of a Cambisol.

PubMed

Paz-Ferreiro, J; Baez-Bernal, D; Castro Insúa, J; García Pomar, M I

2012-03-01

The use of a by-product of the fisheries industry (mussel shell) combined with cattle slurry was evaluated as soil amendment, with special attention to the biological component of soil. A wide number of properties related to soil quality were measured: microbial biomass, soil respiration, net N mineralization, dissolved organic carbon, dissolved organic nitrogen, dissolved inorganic nitrogen, dehydrogenase, β-glucosidase, urease and phosphomonoesterase activities. The amendments showed an enhancement of soil biological activity and a decrease of aluminium held in the cation exchange complex. No adverse effects were observed on soil properties. Given that mussel shells are produced in coastal areas as a by-product and have to be managed as a waste and the fertility constraints in the local soils due to their low pH, our research suggest that there is an opportunity for disposing a residue into the soil and improving soil fertility. Copyright © 2011 Elsevier Ltd. All rights reserved.

Engineering modular polyketide synthases for production of biofuels and industrial chemicals.

PubMed

Cai, Wenlong; Zhang, Wenjun

2018-04-01

Polyketide synthases (PKSs) are one of the most profound biosynthetic factories for producing polyketides with diverse structures and biological activities. These enzymes have been historically studied and engineered to make un-natural polyketides for drug discovery, and have also recently been explored for synthesizing biofuels and industrial chemicals due to their versatility and customizability. Here, we review recent advances in the mechanistic understanding and engineering of modular PKSs for producing polyketide-derived chemicals, and provide perspectives on this relatively new application of PKSs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Re-inventing Willis

NASA Astrophysics Data System (ADS)

Simkin, M. V.; Roychowdhury, V. P.

2011-05-01

Scientists often re-invent things that were long known. Here we review these activities as related to the mechanism of producing power law distributions, originally proposed in 1922 by Yule to explain experimental data on the sizes of biological genera, collected by Willis. We also review the history of re-invention of closely related branching processes, random graphs and coagulation models.

Synthesis of a novel biologically active amide ester of 7,10-dihydroxy-8(E)-octadecanoic acid (DOD) using lipase

USDA-ARS?s Scientific Manuscript database

Hydroxy fatty acids (HFA) are known to have industrial potential because of their special properties such as high viscosity and reactivity. Among the hydroxy fatty acids, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) was successfully produced from oleic acid and lipid containing oleic acid by a bacter...

Medicinal chemistry and anti-inflammatory activity of nitric oxide-releasing NSAI drugs.

PubMed

Koç And, Esra; Küçükgüzel, S Güniz

2009-05-01

Nitric Oxide, which acts as a non-specific cytotoxic mediator and a biological messenger on immunological competence, has been gaining significantly increasing importance. As an alternative to conventional NSAIDs having significant side effects, pharmacologically improved and therapeutically enhanced NO releasing non-steroidal anti-inflammatory drugs with less side effects are being planned to produce.

Reactive decontamination formulation

DOEpatents

Giletto, Anthony [College Station, TX; White, William [College Station, TX; Cisar, Alan J [Cypress, TX; Hitchens, G Duncan [Bryan, TX; Fyffe, James [Bryan, TX

2003-05-27

The present invention provides a universal decontamination formulation and method for detoxifying chemical warfare agents (CWA's) and biological warfare agents (BWA's) without producing any toxic by-products, as well as, decontaminating surfaces that have come into contact with these agents. The formulation includes a sorbent material or gel, a peroxide source, a peroxide activator, and a compound containing a mixture of KHSO.sub.5, KHSO.sub.4 and K.sub.2 SO.sub.4. The formulation is self-decontaminating and once dried can easily be wiped from the surface being decontaminated. A method for decontaminating a surface exposed to chemical or biological agents is also disclosed.

Crystallization and diffraction analysis of [beta]-N-acetylhexosaminidase from Aspergillus oryzae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vanek, Ondrej; Brynd, Jirí; Hofbauerová, Katerina

2012-05-08

Fungal {beta}-N-acetylhexosaminidases are enzymes that are used in the chemoenzymatic synthesis of biologically interesting oligosaccharides. The enzyme from Aspergillus oryzae was produced and purified from its natural source and crystallized using the hanging-drop vapor-diffusion method. Diffraction data from two crystal forms (primitive monoclinic and primitive tetragonal) were collected to resolutions of 3.2 and 2.4 {angstrom}, respectively. Electrophoretic and quantitative N-terminal protein-sequencing analyses confirmed that the crystals are formed by a complete biologically active enzyme consisting of a glycosylated catalytic unit and a noncovalently attached propeptide.

Characterisation of Streptomyces spp. isolated from water-damaged buildings.

PubMed

Suutari, Merja; Rönkä, Elina; Lignell, Ulla; Rintala, Helena; Nevalainen, Aino

2002-01-01

Abstract Saprophytic Streptomyces spp. common in soil and producing biologically active compounds have been related to abnormal microbial growth in buildings where occupants may have health problems. We characterised 11 randomly selected water-damaged building isolates. The 16S rDNA sequence similarity was over 95.4% between strains so that seven, three, and one sequences had greater than 99.8, 99.7 and 99.7% similarity with those of Streptomyces griseus ATCC 10137 (Y15501), Streptomyces albidoflavus DSM 40455(T) (Z76676), and Streptomyces coelicolor A3(2) (Y00411), respectively. Although differences in morphology, pigmentation, fatty acids, biological activity and pH tolerance indicated that strains did not necessarily match with three single phenotypes, they all appeared to belong to two or three branches of Streptomyces spp. most common environmental isolates.

Determinants Affecting Physical Activity Levels In Animal Models

NASA Technical Reports Server (NTRS)

Tou, Janet C. L.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play all underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multi-factorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked making it difficult to determine whether a single, combination or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to tile ventral medial hypothalamus and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

Determinants affecting physical activity levels in animal models

NASA Technical Reports Server (NTRS)

Tou, Janet C L.; Wade, Charles E.

2002-01-01

Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

The recombinant expression and activity detection of MAF-1 fusion protein.

PubMed

Fu, Ping; Wu, Jianwei; Gao, Song; Guo, Guo; Zhang, Yong; Liu, Jian

2015-10-01

This study establishes the recombinant expression system of MAF-1 (Musca domestica antifungal peptide-1) and demonstrates the antifungal activity of the expression product and shows the relationship between biological activity and structure. The gene segments on mature peptide part of MAF-1 were cloned, based on the primers designed according to the cDNA sequence of MAF-1. We constructed the recombinant prokaryotic expression plasmid using prokaryotic expression vector (pET-28a(+)) and converted it to the competent cell of BL21(DE3) to gain recombinant MAF-1 fusion protein with His tag sequence through purifying affinity chromatographic column of Ni-NTA. To conduct the Western Blotting test, recombinant MAF-1 fusion protein was used to produce the polyclonal antibody of rat. The antifungal activity of the expression product was detected using Candida albicans (ATCC10231) as the indicator. The MAF-1 recombinant fusion protein was purified to exhibit obvious antifungal activity, which lays the foundation for the further study of MAF-1 biological activity, the relationship between structure and function, as well as control of gene expression.

Cysteine cathepsin S processes leptin, inactivating its biological activity.

PubMed

Oliveira, Marcela; Assis, Diego M; Paschoalin, Thaysa; Miranda, Antonio; Ribeiro, Eliane B; Juliano, Maria A; Brömme, Dieter; Christoffolete, Marcelo Augusto; Barros, Nilana M T; Carmona, Adriana K

2012-08-01

Leptin is a 16  kDa hormone mainly produced by adipocytes that plays an important role in many biological events including the regulation of appetite and energy balance, atherosclerosis, osteogenesis, angiogenesis, the immune response, and inflammation. The search for proteolytic enzymes capable of processing leptin prompted us to investigate the action of cysteine cathepsins on human leptin degradation. In this study, we observed high cysteine peptidase expression and hydrolytic activity in white adipose tissue (WAT), which was capable of degrading leptin. Considering these results, we investigated whether recombinant human cysteine cathepsins B, K, L, and S were able to degrade human leptin. Mass spectrometry analysis revealed that among the tested enzymes, cathepsin S exhibited the highest catalytic activity on leptin. Furthermore, using a Matrigel assay, we observed that the leptin fragments generated by cathepsin S digestion did not exhibit angiogenic action on endothelial cells and were unable to inhibit food intake in Wistar rats after intracerebroventricular administration. Taken together, these results suggest that cysteine cathepsins may be putative leptin activity regulators in WAT.

Phytochemical contents and biological evaluation of Ruta chalepennsis L. growing in Saudi Arabia.

PubMed

Alotaibi, Shorok M; Saleem, Monerah S; Al-Humaidi, Jehan G

2018-05-01

Phytochemical screening of Ruta chalepensis L. exhibited the presence of different chemical groups. The dried aerial parts of the plant was total extracted by ethanol and successively using chloroform, ethyl acetate and Butanol, out of the successive extracts four compounds namely, scopletin, kaempferol, quercetin, quercetin 3- O -α-L-rhamno glucopyranosyl (Rutin) were isolated and biological evaluations. Total ethanol and successive extracts; chloroform, ethyl acetate and Butanol were produced excellent antimicrobial activities against gram negative bacteria, gram positive bacteria and fungi. Ethyl acetate extract was the best for inhibition of the microorganism's growth. All extracts (total ethanol, and successive extracts) showed DPPH radical scavenging activity in a concentration-dependent manner. The best antioxidant activity was obtained by ethyl acetate & n -butanol extract (94.28%, IC 50  = 56.6 µg/ml). Also All extracts (total ethanol, and successive extracts) showed anticoagulant activity at higher concentration with prolonged clotting time 6:30 and 4:30 s at 10 mg/ml concentrations, respectively.

Characterization of 2,3-diarylxanthones by electrospray mass spectrometry: gas-phase chemistry versus known antioxidant activity properties.

PubMed

Silva, Eduarda M P; Barros, Cristina M R F; Santos, Clementina M M; Barros, António S; Domingues, M Rosário M; Silva, Artur M S

2016-10-30

Xanthones (XH) are a class of heterocyclic compounds widely distributed in nature that hold numerous noteworthy biological and antioxidant activities. Therefore, it is of utmost importance to achieve relevant detailed structural information to understand and assist prediction of their biological properties. The potential relationship between radical-mediated xanthone chemistry in the gas phase and their promising antioxidant activities has not been previously explored. Protonated xanthones XH1-9 were generated in the gas phase by electrospray ionization (ESI) and the main fragmentation pathways of the protonated XH1-9 formed due to collision-induced dissociation (CID) were investigated. In the CID-MS/MS spectra of [M+H](+) ions of XH1, XH2 and XH4 the product ions formed due to H2 O elimination corresponding to the base peak of the spectra. For the remaining six xanthones (XH3, XH5-9), showing the most promising biological profile, the product ion produced with the highest relative abundance (RA) corresponded to the one formed through concomitant loss of H2 O plus CO. Indicative of an inexistent or lower biological activity is the combined loss of CO plus O unique to the CID-MS/MS spectra of XH1, XH2, XH4, and XH5. The product ion formed by loss of 64 Da (concomitant loss of two molecules of H2 O plus CO) is only observed for xanthones containing a catechol unit (XH3 and XH6-9). This product ion has the highest RA for the most potent scavenger of reactive oxygen and nitrogen species XH9 that contains two of these catechol moieties. A strong relationship between some of the biological activities of the studied 2,3-diarylxanthones and their ESI-MS/MS fragmentation spectra was found. The multivariate statistical analysis results suggest that the selected MS features are related to the important biological features. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Guiding Development Based Approach Practicum Vertebrates Taxonomy Scientific Study Program for Students of Biology Education

NASA Astrophysics Data System (ADS)

Arieska, M.; Syamsurizal, S.; Sumarmin, R.

2018-04-01

Students having difficulty in identifying and describing the vertebrate animals as well as less skilled in science process as practical. Increased expertise in scientific skills, one of which is through practical activities using practical guidance based on scientific approach. This study aims to produce practical guidance vertebrate taxonomy for biology education students PGRI STKIP West Sumatra valid. This study uses a model of Plomp development consisting of three phases: the initial investigation, floating or prototype stage, and the stage of assessment. Data collection instruments used in this study is a validation sheet guiding practicum. Data were analyzed descriptively based on data obtained from the field. The result of the development of practical guidance vertebrate taxonomic validity value of 3.22 is obtained with very valid category. Research and development has produced a practical guide based vertebrate taxonomic scientific approach very valid.

Creating biological nanomaterials using synthetic biology.

PubMed

Rice, MaryJoe K; Ruder, Warren C

2014-02-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

A process for polyhydroxyalkanoate (PHA) production from municipal wastewater treatment with biological carbon and nitrogen removal demonstrated at pilot-scale.

PubMed

Bengtsson, Simon; Karlsson, Anton; Alexandersson, Tomas; Quadri, Luca; Hjort, Markus; Johansson, Peter; Morgan-Sagastume, Fernando; Anterrieu, Simon; Arcos-Hernandez, Monica; Karabegovic, Lamija; Magnusson, Per; Werker, Alan

2017-03-25

A process was developed for biological treatment of municipal wastewater for carbon and nitrogen removal while producing added-value polyhydroxyalkanoates (PHAs). The process comprised steps for pre-denitrification, nitrification and post-denitrification and included integrated fixed-film activated sludge (IFAS) with biofilm carrier media to support nitrification. In a pilot-scale demonstration (500-800L), wastewater treatment performance, in line with European standards, were achieved for total chemical oxygen demand (83% removal) and total nitrogen (80% removal) while producing a biomass that was able to accumulate up to 49% PHA of volatile suspended solids with acetic acid or fermented organic residues as substrates. Robust performance in wastewater treatment and enrichment of PHA-producing biomass was demonstrated under realistic conditions including influent variability during 225days of operation. The IFAS system was found to be advantageous since maintaining nitrification on the biofilm allowed for a relatively low (2days) solids retention time (SRT) for the suspended biomass in the bulk phase. Lower SRT has advantages in higher biomass yield and higher active fraction in the biomass which leads to higher PHA productivity and content. The outcomes show that production of added-value biopolymers may be readily integrated with carbon and nitrogen removal from municipal wastewater. Copyright © 2016 Elsevier B.V. All rights reserved.

Production of polyunsaturated fatty acids in yeast Saccharomyces cerevisiae and its relation to alkaline pH tolerance.

PubMed

Yazawa, Hisashi; Iwahashi, Hitoshi; Kamisaka, Yasushi; Kimura, Kazuyoshi; Uemura, Hiroshi

2009-03-01

Saccharomyces cerevisiae produces saturated and monounsaturated fatty acids of 16- and 18-carbon atoms and no polyunsaturated fatty acids (PUFAs) with more than two double bonds. To study the biological significance of PUFAs in yeast, we introduced Kluyveromyces lactis Delta12 fatty acid desaturase (KlFAD2) and omega3 fatty acid desaturase (KlFAD3) genes into S. cerevisiae to produce linoleic and alpha-linolenic acids in S. cerevisiae. The strain producing linoleic and alpha-linolenic acids showed an alkaline pH-tolerant phenotype. DNA microarray analyses showed that the transcription of a set of genes whose expressions are under the repression of Rim101p were downregulated in this strain, suggesting that Rim101p, a transcriptional repressor which governs the ion tolerance, was activated. In line with this activation, the strain also showed elevated resistance to Li(+) and Na(+) ions and to zymolyase, a yeast lytic enzyme preparation containing mainly beta-1,3-glucanase, indicating that the cell wall integrity was also strengthened in this strain. Our findings demonstrate a novel influence of PUFA production on transcriptional control that is likely to play an important role in the early stage of alkaline stress response. The Accession No. for microarray data in the Center for Information Biology Gene Expression database is CBX68.

Immunomodulatory Properties of Plants and Mushrooms.

PubMed

Martel, Jan; Ko, Yun-Fei; Ojcius, David M; Lu, Chia-Chen; Chang, Chih-Jung; Lin, Chuan-Sheng; Lai, Hsin-Chih; Young, John D

2017-11-01

Plants and mushrooms are used for medicinal purposes and the screening of molecules possessing biological activities. A single plant or mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on experimental conditions, but the reason behind this dichotomy remains obscure. We present here a large body of experimental data showing that water extracts of plants and mushrooms usually activate immune cells, whereas ethanol extracts inhibit immune cells. The mode of extraction of plants and mushrooms may thus determine the effects produced on immune cells, possibly due to differential solubility and potency of stimulatory and inhibitory compounds. We also examine the possibility of using such plant and mushroom extracts to treat immune system disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rational Diversification of a Promoter Providing Fine-Tuned Expression and Orthogonal Regulation for Synthetic Biology

PubMed Central

Blount, Benjamin A.; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex “multi-wire” logic functions. PMID:22442681

Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology.

PubMed

Blount, Benjamin A; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex "multi-wire" logic functions.

Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. I. Taxonomy, fermentation, isolation and biological properties.

PubMed

Fukuda, Takashi; Yamaguchi, Yuichi; Masuma, Rokuro; Tomoda, Hiroshi; Omura, Satoshi

2005-05-01

New phenylfuropyridinones and related compounds, designated citridones A, B, B' and C, were isolated along with known CJ-16,173, from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. Citridones (75 microM) potentiate the miconazole activity against Candida albicans, decreasing the IC50 value of miconazole from 14.5 nM to 3.5 to approximately 6.3 nM.

Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

PubMed Central

Potts, Malia B.; Kim, Hyun Seok; Fisher, Kurt W.; Hu, Youcai; Carrasco, Yazmin P.; Bulut, Gamze Betul; Ou, Yi-Hung; Herrera-Herrera, Mireya L.; Cubillos, Federico; Mendiratta, Saurabh; Xiao, Guanghua; Hofree, Matan; Ideker, Trey; Xie, Yang; Huang, Lily Jun-shen; Lewis, Robert E.; MacMillan, John B.; White, Michael A.

2014-01-01

A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, we developed a new marine-derived, renewable natural products resource and a method for linking bioactive derivatives of this library to the proteins and biological processes that they target in cells. We used cell-based screening and computational analysis to match gene expression signatures produced by natural products to those produced by siRNA and synthetic microRNA libraries. With this strategy, we matched proteins and microRNAs with diverse biological processes and also identified putative protein targets and mechanisms of action for several previously undescribed marine-derived natural products. We confirmed mechanistic relationships for selected short-interfering RNAs, microRNAs, and compounds with functional roles in autophagy, chemotaxis mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus, this approach may be an effective method for screening new drugs while simultaneously identifying their targets. PMID:24129700

Pyrroloquinoline quinone (PQQ) is reduced to pyrroloquinoline quinol (PQQH2) by vitamin C, and PQQH2 produced is recycled to PQQ by air oxidation in buffer solution at pH 7.4.

PubMed

Mukai, Kazuo; Ouchi, Aya; Nagaoka, Shin-ichi; Nakano, Masahiko; Ikemoto, Kazuto

2016-01-01

Measurements of the reaction of sodium salt of pyrroloquinoline quinone (PQQNa2) with vitamin C (Vit C) were performed in phosphate-buffered solution (pH 7.4) at 25 °C under nitrogen atmosphere, using UV-vis spectrophotometry. The absorption spectrum of PQQNa2 decreased in intensity due to the reaction with Vit C and was changed to that of pyrroloquinoline quinol (PQQH2, a reduced form of PQQ). One molecule of PQQ was reduced by two molecules of Vit C producing a molecule of PQQH2 in the buffer solution. PQQH2, thus produced, was recycled to PQQ due to air oxidation. PQQ and Vit C coexist in many biological systems, such as vegetables, fruits, as well as in human tissues. The results obtained suggest that PQQ is reduced by Vit C and functions as an antioxidant in biological systems, because it has been reported that PQQH2 shows very high free-radical scavenging and singlet-oxygen quenching activities in buffer solutions.

Producing a Mouse Model to Explore the Linkages Between Tocopherol Biology and Prostate Cancer

DTIC Science & Technology

2005-07-01

Edwards, Prostate cancer and supplementation with alpha-tocopherol and beta -carotene: incidence and mortality in a controlled trial. J Natl Cancer ...1-0153 TITLE: Producing a Mouse Model to Explore the Linkages Between Tocopherol Biology and Prostate Cancer ...TITLE AND SUBTITLE Producing a Mouse Model to Explore the Linkages Between Tocopherol 5a. CONTRACT NUMBER Biology and Prostate Cancer 5b. GRANT

Novel analgesic triglycerides from cultures of Agaricus macrosporus and other basidiomycetes as selective inhibitors of neurolysin.

PubMed

Stadler, Marc; Hellwig, Veronika; Mayer-Bartschmid, Anke; Denzer, Dirk; Wiese, Burkhard; Burkhardt, Nils

2005-12-01

The agaricoglycerides are a new class of fungal secondary metabolites that constitute esters of chlorinated 4-hydroxy benzoic acid and glycerol. They are produced in cultures of the edible mushroom, Agaricus macrosporus, and several other basidiomycetes of the genera Agaricus, Hypholoma, Psathyrella and Stropharia. The main active principle, agaricoglyceride A, showed strong activities against neurolysin, a protease involved in the regulation of dynorphin and neurotensin metabolism (IC50 = 200 nM), and even exhibited moderate analgesic in vivo activities in an in vivo model. Agaricoglyceride monoacetates (IC50 = 50 nM) showed even stronger in vitro activities. Several further co-metabolites with weaker or lacking bioactivities were also obtained and characterized. Among those were further agaricoglyceride derivatives, as well as further chlorinated phenol derivatives such as the new compound, agaricic ester. The characteristics of the producer organisms, the isolation of bioactive metabolites from cultures of A. macrosporus, their biological activities, and preliminary results on their occurrence in basidiomycetes, are described.

Mutational analysis of vaccinia virus E3 protein: the biological functions do not correlate with its biochemical capacity to bind double-stranded RNA.

PubMed

Dueck, Kevin J; Hu, YuanShen Sandy; Chen, Peter; Deschambault, Yvon; Lee, Jocelyn; Varga, Jessie; Cao, Jingxin

2015-05-01

Vaccinia E3 protein has the biochemical capacity of binding to double-stranded RNA (dsRNA). The best characterized biological functions of the E3 protein include its host range function, suppression of cytokine expression, and inhibition of interferon (IFN)-induced antiviral activity. Currently, the role of the dsRNA binding capacity in the biological functions of the E3 protein is not clear. To further understand the mechanism of the E3 protein biological functions, we performed alanine scanning of the entire dsRNA binding domain of the E3 protein to examine the link between its biochemical capacity of dsRNA binding and biological functions. Of the 115 mutants examined, 20 were defective in dsRNA binding. Although the majority of the mutants defective in dsRNA binding also showed defective replication in HeLa cells, nine mutants (I105A, Y125A, E138A, F148A, F159A, K171A, L182A, L183A, and I187/188A) retained the host range function to various degrees. Further examination of a set of representative E3L mutants showed that residues essential for dsRNA binding are not essential for the biological functions of E3 protein, such as inhibition of protein kinase R (PKR) activation, suppression of cytokine expression, and apoptosis. Thus, data described in this communication strongly indicate the E3 protein performs its biological functions via a novel mechanism which does not correlate with its dsRNA binding activity. dsRNAs produced during virus replication are important pathogen-associated molecular patterns (PAMPs) for inducing antiviral immune responses. One of the strategies used by many viruses to counteract such antiviral immune responses is achieved by producing dsRNA binding proteins, such as poxvirus E3 family proteins, influenza virus NS1, and Ebola virus V35 proteins. The most widely accepted model for the biological functions of this class of viral dsRNA binding proteins is that they bind to and sequester viral dsRNA PAMPs; thus, they suppress the related antiviral immune responses. However, no direct experimental data confirm such a model. In this study of vaccinia E3 protein, we found that the biological functions of the E3 protein are not necessarily linked to its biochemical capacity of dsRNA binding. Thus, our data strongly point to a new concept of virus modulation of cellular antiviral responses triggered by dsRNA PAMPs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Nonthermal Biological Treatments Using Discharge Plasma Produced by Pulsed Power 4. Cleaning of Lakes and Marshes by Pulsed Power Produced Streamer Discharges in Water

NASA Astrophysics Data System (ADS)

Akiyama, Hidenori; Katsuki, Sunao; Namihira, Takao; Ishibashi, Kazuo; Kiyosaki, Noriaki

Pulsed power has been used to produce non-thermal plasmas in atmospheric pressure gases that generate a high electric field at the tips of streamer discharges, where high energy electrons, free radicals, ultraviolet rays, and ozone are produced. These manifestations of streamer discharges have been used in the treatment of exhaust gases, removal of volatile and toxic compounds such as dioxin, and the sterilization of microorganisms. Here, large volume streamer discharges in water are described. These streamer discharges in liquids are able to produce a high electric field, high energy electrons, ozone, chemically active species, ultraviolet rays, and shock waves, which readily sterilize microorganisms and decompose molecules and materials. An application of this phenomenon to the cleaning of lakes and marshes is also described.

Pretreatment of macroalgae for volatile fatty acid production.

PubMed

Pham, Thi Nhan; Um, Youngsoon; Yoon, Hyon Hee

2013-10-01

In this study, a novel method was proposed for the biological pretreatment of macroalgae (Laminaria japonica, Pachymeniopsis elliptica, and Enteromorpha crinita) for production of volatile fatty acid (VFA) by anaerobic fermentation. The amount of VFA produced from 40 g/L of L. japonica increased from 8.3 g/L (control) to 15.6 g/L when it was biologically pretreated with Vibrio harveyi. The biological treatment of L. japonica with Vibrio spp. was most effective likely due to the alginate lyase activity of Vibrio spp. However, a considerable effect was also observed after biological pretreatment of P. elliptica and E. crinita, which are red and green algae, respectively. Alkaline pretreatment of 40 g/L of L. japonica with 0.5 N NaOH resulted in an increase of VFA production to 12.2 g/L. These results indicate that VFA production from macroalgae can be significantly enhanced using the proposed biological pretreatments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improving large class performance and engagement through student-generated question banks.

PubMed

Hancock, Dale; Hare, Nicole; Denny, Paul; Denyer, Gareth

2018-03-12

Disciplines such as Biochemistry and Molecular Biology, which involve concepts not included in the high-school curriculum, are very challenging for many first year university students. These subjects are particularly difficult for students accustomed to surface learning strategies involving memorization and recall of facts, as a deeper understanding of the relationship between concepts is needed for successful transfer to related areas and subsequent study. In this article, we explore an activity in a very large first year Molecular Biology course, in which students create multiple-choice questions related to targeted learning outcomes, and then answer and evaluate one another's questions. This activity encompasses elements of both self- and peer-assessment and the generative tasks of creating questions and producing written feedback may contribute to a deeper understanding of the material. We make use of a free online platform to facilitate all aspects of the process and analyze the effect of student engagement with the task on overall course performance. When compared to previous semester's cohorts, we observe a pronounced improvement in class performance on exam questions targeting similar concepts to the student-generated questions. In addition, those students that engage to a greater extent with the activity perform significantly better on the targeted exam questions than those who are less active, yet all students perform similarly on a set of isolated control questions appearing on the same exam. © 2018 by The International Union of Biochemistry and Molecular Biology, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

Chemical analysis and biological testing of materials from the EDS coal liquefaction process: a status report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Later, D.W.; Pelroy, R.A.; Wilson, B.W.

1984-05-01

Representative process materials were obtained from the EDS pilot plant for chemical and biological analyses. These materials were characterized for biological activity and chemical composition using a microbial mutagenicity assay and chromatographic and mass spectrometric analytical techniques. The two highest boiling distillation cuts, as well as process solvent (PS) obtained from the bottoms recycle mode operation, were tested for initiation of mouse skin tumorigenicity. All three materials were active; the crude 800/sup 0 +/F cut was substantially more potent than the crude bottoms recycle PS or 750 to 800/sup 0/F distillate cut. Results from chemical analyses showed the EDS materials,more » in general, to be more highly alkylated and have higher hydroaromatic content than analogous SRC II process materials (no in-line process hydrogenation) used for comparison. In the microbial mutagenicity assays the N-PAC fractions showed greater activity than did the aliphatic hydrocarbon, hydroxy-PAH, or PAH fractions, although mutagenicity was detected in certain PAH fractions by a modified version of the standard microbial mutagenicity assay. Mutagenic activities for the EDS materials were lower, overall, than those for the corresponding materials from the SRC II process. The EDS materials produced under different operational modes had distinguishable differences in both their chemical constituency and biological activity. The primary differences between the EDS materials studied here and their SRC II counterparts used for comparison are most likely attributable to the incorporation of catalytic hydrogenation in the EDS process. 27 references, 28 figures, 27 tables.« less

The expression of antibiotic resistance genes in antibiotic-producing bacteria.

PubMed

Mak, Stefanie; Xu, Ye; Nodwell, Justin R

2014-08-01

Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance. © 2014 John Wiley & Sons Ltd.

An autonomous molecular computer for logical control of gene expression

PubMed Central

Benenson, Yaakov; Gil, Binyamin; Ben-Dor, Uri; Adar, Rivka; Shapiro, Ehud

2013-01-01

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems1–7. Recently, simple molecular-scale autonomous programmable computers were demonstrated8–15 allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for ‘logical’ control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton12–17; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes18–22 associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug. PMID:15116117

Nutritional, biochemical, and pharmaceutical potential of proteins and peptides from jatropha: review.

PubMed

Devappa, Rakshit K; Makkar, Harinder P S; Becker, Klaus

2010-06-09

Increased bioenergy consciousness and high demand for animal products have propelled the search for alternative resources that could meet the dual demands. Jatropha seeds have potential to fit these roles in view of their multipurpose uses, broad climatic adaptability features, and high oil and protein contents. During the past five years many large-scale cultivation projects have been undertaken to produce jatropha seed oil as a feedstock for the biodiesel industry. The present review aims at providing biological significance of jatropha proteins and peptides along with their nutritional and therapeutic applications. The nutritional qualities of the kernel meal and protein concentrates or isolates prepared from seed cake are presented, enabling their efficient use in animal nutrition. In addition, (a) biologically active proteins involved in plant protection, for example, aquaporin and betaine aldehyde dehydrogenase, which have roles in drought resistance, and beta-glucanase, which has antifungal activity, as well as those having pharmaceutical properties, and (b) cyclic peptides with various biological activities such as antiproliferative, immunomodulatory, antifungal, and antimalarial activity are discussed. It is expected that the information collated will open avenues for new applications of proteins present in jatropha plant, thereby contributing to enhance the financial viability and sustainability of a jatropha-based biodiesel industry.

Plantago maxima leaves extract inhibits adipogenic action of a high-fat diet in female Wistar rats.

PubMed

Tinkov, Alexey A; Nemereshina, Olga N; Popova, Elizaveta V; Polyakova, Valentina S; Gritsenko, Viktor A; Nikonorov, Alexandr A

2014-04-01

The primary objective of this study is to investigate the content of biologically active compounds producing an antioxidant effect in Plantago maxima and their influence on main mechanisms of dietary obesity development. Biologically active compounds in P. maxima were tested using paper chromatography. In in vivo experiment, high-fat-fed Wistar rats obtained P. maxima water extract for 3 months. Morphometric parameters, weight gain, serum adipokines, and cytokines, as well as oxidative stress biomarkers in rats’ tissues were evaluated. Gut microflora was also examined. Plantago maxima leaves used in the experiment contained significant amount of flavonoids, iridoids, phenol carboxylic acids, and tannins and ascorbic acid. Our in vivo experiment data demonstrate that P. maxima water extract prevents excessive adiposity in a diet-induced model. P. maxima consumption reduced serum leptin (twofold), macrophage chemoattractant protein-1 (sevenfold), tumornecrosis factor-α (25%), and interleukine-6 (26%) levels. P. maxima water extract decreased adipose tissue oxidative stress biomarkers in rats fed a high-fat diet. In addition, increased bacterial growth in the diet-induced obesity model was reversed by the P. maxima extract treatment. Plantago maxima water extract possessed antiadipogenic, antidiabetic, antiinflammatory, antioxidant activity, and normalized gut microflora in a rat model of diet-induced excessive adiposity due to a high content of biologically active compounds.

Bacillomycin D Produced by Bacillus amyloliquefaciens Is Involved in the Antagonistic Interaction with the Plant-Pathogenic Fungus Fusarium graminearum.

PubMed

Gu, Qin; Yang, Yang; Yuan, Qiming; Shi, Guangming; Wu, Liming; Lou, Zhiying; Huo, Rong; Wu, Huijun; Borriss, Rainer; Gao, Xuewen

2017-10-01

Fusarium graminearum (teleomorph: Ascomycota, Hypocreales, Gibberella , Gibberella zeae ) is a destructive fungal pathogen that threatens the production and quality of wheat and barley worldwide. Controlling this toxin-producing pathogen is a significant challenge. In the present study, the commercially available strain Bacillus amyloliquefaciens ( Bacteria , Firmicutes , Bacillales , Bacillus ) FZB42 showed strong activity against F. graminearum The lipopeptide bacillomycin D, produced by FZB42, was shown to contribute to the antifungal activity. Purified bacillomycin D showed strong activity against F. graminearum , and its 50% effective concentration was determined to be approximately 30 μg/ml. Analyses using scanning and transmission electron microscopy revealed that bacillomycin D caused morphological changes in the plasma membranes and cell walls of F. graminearum hyphae and conidia. Fluorescence microscopy combined with different dyes showed that bacillomycin D induced the accumulation of reactive oxygen species and caused cell death in F. graminearum hyphae and conidia. F. graminearum secondary metabolism also responded to bacillomycin D challenge, by increasing the production of deoxynivalenol. Biological control experiments demonstrated that bacillomycin D exerted good control of F. graminearum on corn silks, wheat seedlings, and wheat heads. In response to bacillomycin D, F. graminearum genes involved in scavenging reactive oxygen species were downregulated, whereas genes involved in the synthesis of deoxynivalenol were upregulated. Phosphorylation of MGV1 and HOG1, the mitogen-activated protein kinases of F. graminearum , was increased in response to bacillomycin D. Taken together, these findings reveal the mechanism of the antifungal action of bacillomycin D. IMPORTANCE Biological control of plant disease caused by Fusarium graminearum is desirable. Bacillus amyloliquefaciens FZB42 is a representative of the biocontrol bacterial strains. In this work, the lipopeptide bacillomycin D, produced by FZB42, showed strong fungicidal activity against F. graminearum Bacillomycin D caused morphological changes in the plasma membrane and cell wall of F. graminearum , induced accumulation of reactive oxygen species, and ultimately caused cell death in F. graminearum Interestingly, when F. graminearum was challenged with bacillomycin D, the deoxynivalenol production, gene expression, mitogen-activated protein kinase phosphorylation, and pathogenicity of F. graminearum were significantly altered. These findings clarified the mechanisms of the activity of bacillomycin D against F. graminearum and highlighted the potential of B. amyloliquefaciens FZB42 as a biocontrol agent against F. graminearum . Copyright © 2017 American Society for Microbiology.

A rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development.

PubMed

Betson, Martha; Settleman, Jeffrey

2007-08-01

The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing "rescue" studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of "combining" functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn.

Improving protein delivery of fibroblast growth factor-2 from bacterial inclusion bodies used as cell culture substrates.

PubMed

Seras-Franzoso, Joaquin; Peebo, Karl; García-Fruitós, Elena; Vázquez, Esther; Rinas, Ursula; Villaverde, Antonio

2014-03-01

Bacterial inclusion bodies (IBs) have recently been used to generate biocompatible cell culture interfaces, with diverse effects on cultured cells such as cell adhesion enhancement, stimulation of cell growth or induction of mesenchymal stem cell differentiation. Additionally, novel applications of IBs as sustained protein delivery systems with potential applications in regenerative medicine have been successfully explored. In this scenario, with IBs gaining significance in the biomedical field, the fine tuning of this functional biomaterial is crucial. In this work, the effect of temperature on fibroblast growth factor-2 (FGF-2) IB production and performance has been evaluated. FGF-2 was overexpressed in Escherichia coli at 25 and 37 °C, producing IBs with differences in size, particle structure and biological activity. Cell culture topographies made with FGF-2 IBs biofabricated at 25 °C showed higher levels of biological activity as well as a looser supramolecular structure, enabling a higher protein release from the particles. In addition, the controlled use of FGF-2 protein particles enabled the generation of functional topographies with multiple biological activities being effective on diverse cell types. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi′s productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances. PMID:27023571

Chemical Variability and Biological Activities of Eucalyptus spp. Essential Oils.

PubMed

Barbosa, Luiz Claudio Almeida; Filomeno, Claudinei Andrade; Teixeira, Robson Ricardo

2016-12-07

Many plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in Nature and have been utilized by mankind for different purposes, such as pharmaceuticals, agrochemicals, aromatherapy, and food flavorants. There are more than 3000 EOs reported in the literature, with approximately 300 in commercial use, including the EOs from Eucalyptus species. Most EOs from Eucalyptus species are rich in monoterpenes and many have found applications in pharmaceuticals, agrochemicals, food flavorants, and perfumes. Such applications are related to their diverse biological and organoleptic properties. In this study, we review the latest information concerning the chemical composition and biological activities of EOs from different species of Eucalyptus . Among the 900 species and subspecies of the Eucalyptus genus, we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricidal, insecticidal and herbicidal activities, hoping that such information will contribute to the development of research in this field. It is also intended that the information described in this study can be useful in the rationalization of the use of Eucalyptus EOs as components for pharmaceutical and agrochemical applications as well as food preservatives and flavorants.

The Pseudomonas aeruginosa oxyvinylglycine L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth of Erwinia amylovora and acts as a weak seed germination-arrest factor

USDA-ARS?s Scientific Manuscript database

The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) is demonstrated to share biological activities with 4-formylaminooxyvinylglycine, a related molecule produced by Pseudomonas fluorescens WH6. We found that culture filtrates of a P. aeruginosa strain overproduc...

A Photosynthesis Lab. Response of Algal Suspensions to a Gradient of Photosynthetically Active Radiation (PAR).

ERIC Educational Resources Information Center

Zee, Delmar Vander

1995-01-01

This photosynthesis exercise is intended for introductory college biology or botany courses. It is based on the principle that a closed suspension of algal cells may be expected to produce more dissolved oxygen with a greater photon fluence rate, but within limits of the photosynthetic capacity of the system. Describes materials and methods. (LZ)

Determination of Post-Culture Processing with Carbohydrates by MALDI-MS and TMS derivatization GC/MS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wunschel, David S.; Wahl, Karen L.; Melville, Angela M.

2011-09-30

Biological materials generally require stabilization to retain activity or viability in a dry form. A number of industrial products, such as vaccines, probiotics and biopesticides, have been produced as dry preparations. The same methods and materials used for stabilizing commercial microbial products may be applicable to preserving biothreat pathogens in a dry form.

Synthesis of a Biologically Active Oxazol-5-(4H)-One via an Erlenmeyer-Plo¨chl Reaction

ERIC Educational Resources Information Center

Rodrigues, Catarina A. B.; Martinho, Jose´ M. G.; Afonso, Carlos A. M.

2015-01-01

The synthesis of (Z)-4-(4-nitrobenzylidene)-2- phenyloxazol-5(4"H")-one, which is a potent immunomodulator and tyrosinase inhibitor, is described as an experiment for an upper-division undergraduate organic chemistry laboratory course. This compound is produced via an Erlenmeyer-Plo¨chl reaction in the absence of any additional solvents…

[Selected adjuvants as carriers of a dry extract of common ivy (Hedera helix L.)].

PubMed

Marczyński, Zbigniew; Zgoda, Marian Mikołaj; Bodek, Kazimiera Henryka

2011-01-01

The usefulness was tested of selected adjuvants: Vivapur 112, Carmellose calcium, Calcium carbonate CA 740, Calcium carbonate CA 800, Hypromellose as carriers of a dry extract of common ivy (Hedera helix L.) leaves in the process of direct tableting. The quality of the produced tablets was determined by examining their appearance, diameter, thickness, mass resistance to abrasion, crushing and disintegration time. Furthermore, the rate of release of biologically active components from the produced drug form to acceptor fluid was tested in accordance with the requirements of Polish Pharmacopoeia VII (PPVII). An attempt was made to estimate the effect of the used adjuvants on the course of this process. The applied adjuvants and acceptor fluid osmolarity decide significantly about the pharmaceutical availability of the therapeutic agents contained in the extract. The obtained model tablets are characterized by controlled release of biologically active substances, in majority of batches they fulfil the requirements as regards physicochemical properties. The formulation composition of the first batch (Extr. Hederae helices e fol.spir. sicc., Vivapur 112, Carmellose calcium, Sodium Stearyl Fumarate) appeared to be the most effective. The worked out method is optimal and provides technological reproducibility and high durability of the drug form.

Functional and structural characterization of soluble recombinant epsilon toxin of Clostridium perfringens D, causative agent of enterotoxaemia.

PubMed

Mathur, Deepika Dayal; Deshmukh, Sachin; Kaushik, Himani; Garg, Lalit C

2010-10-01

Clostridium perfringens types B and D are responsible for enterotoxaemia, one of the major causes of cattle mortality and is therefore of great economic concern. The epsilon toxin produced by the organism is the major antigenic determinant and has been directly implicated for the disease causation. In the present paper, we evaluated the biological activity of the recombinant epsilon toxin (rEtx) produced as soluble protein in Escherichia coli. The rEtx was purified to near homogeneity by a one-step anion-exchange chromatography. The immunological identity of purified rEtx was confirmed by Western blotting using a monoclonal antibody against the native toxin. The rEtx formed heptamer in the Madin-Darby canine kidney (MDCK) cells and synaptosomal membrane of mouse brain and was cytotoxic to the MDCK cells with a CT(50) of 30 ng/ml. The rEtx was highly stable and its thermostability profile related well with its biological activity. The rEtx was purified in large amounts and exhibited all the properties of native toxin and therefore can be used for the development of vaccine against the pathogen.

Specificity of Esthetic Experience for Artworks: An fMRI Study

PubMed Central

Di Dio, Cinzia; Canessa, Nicola; Cappa, Stefano F.; Rizzolatti, Giacomo

2011-01-01

In a previous functional magnetic resonance imaging (fMRI) study, where we investigated the neural correlates of esthetic experience, we found that observing canonical sculptures, relative to sculptures whose proportions had been modified, produced the activation of a network that included the lateral occipital gyrus, precuneus, prefrontal areas, and, most interestingly, the right anterior insula. We interpreted this latter activation as the neural signature underpinning hedonic response during esthetic experience. With the aim of exploring whether this specific hedonic response is also present during the observation of non-art biological stimuli, in the present fMRI study we compared the activations associated with viewing masterpieces of classical sculpture with those produced by the observation of pictures of young athletes. The two stimulus-categories were matched on various factors, including body postures, proportion, and expressed dynamism. The stimuli were presented in two conditions: observation and esthetic judgment. The two stimulus-categories produced a rather similar global activation pattern. Direct comparisons between sculpture and real-body images revealed, however, relevant differences, among which the activation of right antero-dorsal insula during sculptures viewing only. Along with our previous data, this finding suggests that the hedonic state associated with activation of right dorsal anterior insula underpins esthetic experience for artworks. PMID:22121344

Ratchet Effects in Active Matter Systems

DOE PAGES

Reichhardt, Cynthia Jane; Reichhardt, Charles

2016-12-21

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth ofmore » possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. Here, we describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle–particle interactions, and nondissipative effects.« less

The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

PubMed Central

Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

SER consensus statement on the use of biologic therapy for systemic lupus erythematosus.

PubMed

Calvo-Alén, Jaime; Silva-Fernández, Lucía; Úcar-Angulo, Eduardo; Pego-Reigosa, José María; Olivé, Alejandro; Martínez-Fernández, Carmen; Martínez-Taboada, Víctor; Luis Marenco, José; Loza, Estíbaliz; López-Longo, Javier; Gómez-Reino, Juan Jesús; Galindo-Izquierdo, María; Fernández-Nebro, Antonio; Cuadrado, María José; Aguirre-Zamorano, María Ángeles; Zea-Mendoza, Antonio; Rúa-Figueroa, Iñigo

2013-01-01

To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. We present the SER recommendations for the use of biological therapies in patients with SLE. Copyright © 2013 Elsevier España, S.L. All rights reserved.

A Microcosm of the Biomedical Research Experience for Upper-level Undergraduates

PubMed Central

2008-01-01

The skill set required of biomedical researchers continues to grow and evolve as biology matures as a natural science. Science necessitates creative yet critical thinking, persuasive communication skills, purposeful use of time, and adeptness at the laboratory bench. Teaching these skills can be effectively accomplished in an inquiry-based, active-learning environment at a primarily undergraduate institution. Cell Biology Techniques, an upper-level cell biology laboratory course at St. John Fisher College, features two independent projects that take advantage of the biology of the nematode Caenorhabditis elegans, a premier yet simple model organism. First, students perform a miniature epigenetic screen for novel phenotypes using RNA interference. The results of this screen combined with literature research direct students toward a singe gene that they attempt to subclone in the second project. The biology of the chosen gene/protein also becomes an individualized focal point with respect to the content of the laboratory. Progress toward course goals is evaluated using written, oral, and group-produced assignments, including a concept map. Pre- and postassessment indicates a significant increase in the understanding of broad concepts in cell biological research. PMID:18519612

Ligand-Enhanced Abiotic Iron Oxidation and the Effects of Chemical versus Biological Iron Cycling in Anoxic Environments

PubMed Central

2013-01-01

This study introduces a newly isolated, genetically tractable bacterium (Pseudogulbenkiania sp. strain MAI-1) and explores the extent to which its nitrate-dependent iron-oxidation activity is directly biologically catalyzed. Specifically, we focused on the role of iron chelating ligands in promoting chemical oxidation of Fe(II) by nitrite under anoxic conditions. Strong organic ligands such as nitrilotriacetate and citrate can substantially enhance chemical oxidation of Fe(II) by nitrite at circumneutral pH. We show that strain MAI-1 exhibits unambiguous biological Fe(II) oxidation despite a significant contribution (∼30–35%) from ligand-enhanced chemical oxidation. Our work with the model denitrifying strain Paracoccus denitrificans further shows that ligand-enhanced chemical oxidation of Fe(II) by microbially produced nitrite can be an important general side effect of biological denitrification. Our assessment of reaction rates derived from literature reports of anaerobic Fe(II) oxidation, both chemical and biological, highlights the potential competition and likely co-occurrence of chemical Fe(II) oxidation (mediated by microbial production of nitrite) and truly biological Fe(II) oxidation. PMID:23402562

Standardization of allergen products: 2. Detailed characterization of GMP-produced recombinant Phl p 5.0109 as European Pharmacopoeia reference standard.

PubMed

Himly, M; Nandy, A; Kahlert, H; Thilker, M; Steiner, M; Briza, P; Neubauer, A; Klysner, S; van Ree, R; Buchheit, K-H; Vieths, S; Ferreira, F

2016-04-01

The Biological Standardization Programme of the European Directorate for Quality of Medicines and Healthcare (EDQM) aims at the establishment of well-characterized reference standards based on recombinant allergens and validated assays for the quantification of major allergen content. The objective of this study was to examine the detailed physicochemical and immunological characterization of recombinant Phl p 5.0109, the second available allergen reference standard. Recombinant Phl p 5.0109 PP5ar06007 was produced under GMP conditions and analyzed by an array of physicochemical and immunological methods for identity, quantity, homogeneity, and folding stability in bulk solution, as well as thermal denaturation, aggregation state, and biological activity when formulated for long-time storage. PP5ar06007 revealed as a highly homogeneous, monomeric, well-folded preparation of rPhl p 5.0109, as documented by mass spectrometry, SDS-PAGE, isoelectric focusing, size-exclusion chromatography with light scattering, circular dichroism, and infrared spectroscopy. Upon storage at +4°C, PP5ar06007 retained the monomeric state for at least 2 months. A protein quantity of 1.56 ± 0.03 mg/ml was determined by amino acid analysis in PP5ar06007, and its biological activity was shown to be comparable to natural Phl p 5 in terms of basophil activation and T-cell reactivity. Recombinant Phl p 5.0109 PP5ar06007 was characterized extensively at the physicochemical and immunological level. It revealed to be a highly stable, monomeric, and immunologically equivalent of its natural counterpart. PP5ar06007 is now available as European Pharmacopoeia allergen reference standard for grass pollen products. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Atmospheric energy for subsurface life on Mars?

PubMed Central

Weiss, Benjamin P.; Yung, Yuk L.; Nealson, Kenneth H.

2000-01-01

The location and density of biologically useful energy sources on Mars will limit the biomass, spatial distribution, and organism size of any biota. Subsurface Martian organisms could be supplied with a large energy flux from the oxidation of photochemically produced atmospheric H2 and CO diffusing into the regolith. However, surface abundance measurements of these gases demonstrate that no more than a few percent of this available flux is actually being consumed, suggesting that biological activity driven by atmospheric H2 and CO is limited in the top few hundred meters of the subsurface. This is significant because the available but unused energy is extremely large: for organisms at 30-m depth, it is 2,000 times previous estimates of hydrothermal and chemical weathering energy and far exceeds the energy derivable from other atmospheric gases. This also implies that the apparent scarcity of life on Mars is not attributable to lack of energy. Instead, the availability of liquid water may be a more important factor limiting biological activity because the photochemical energy flux can only penetrate to 100- to 1,000-m depth, where most H2O is probably frozen. Because both atmospheric and Viking lander soil data provide little evidence for biological activity, the detection of short-lived trace gases will probably be a better indicator of any extant Martian life. PMID:10660689

[Current and prospective biologics and small molecules in the treatment of inflammatory bowel diseases].

PubMed

Buc, Milan

2018-01-01

Crohns disease (CD) and ulcerative colitis (UC) belong to chronic inflammatory bowel diseases, which are induced by autoimmune processes. While CD is characterized by over-activity of Th1, ILC1, and MAIT cells, UC is mediated by exaggerated activities of Th2 and ILC2 cells and cytokines they produce. Knowledge of the pathogenesis enabled a rational therapy based mostly on biologics and small molecules. TNF is the principal proinflammatory cytokine in both diseases. Anti-TNF monoclonal antibodies, mostly infliximab or adalimumab were therefore introduced to their treatment. Approximately 50-70 % of CD and more than 33 % of UC patients respond to primary treatment only, which resulted in the development of other biologics and small molecules. Out of them, monoclonal antibodies targeting adhesive molecules (vedolizumab, etrolizumab) and p40 chains shared by IL12 and IL23 (ustekinumab) have been already in clinical practice. There are also other small molecules in clinical trials: mongersen, tafacitinib, and ozanimod. Mongersen supports immunosuppressive activity of TGFβ; it has been tried for the treatment of CD. Tofacitinib inhibits activity of JAK kinases; it was shown to be effective in UC management. Ozanimod interferes with migrations of activated T cells to the site of inflammation and is a promising drug for the UC treatment.Key words: Crohns disease - mongersen - monoclonal antibodies - ozanimod - tofacitinib - ulcerative colitis.

Quality-assurance and data-management plan for water-quality activities in the Kansas Water Science Center, 2014

USGS Publications Warehouse

Rasmussen, Teresa J.; Bennett, Trudy J.; Foster, Guy M.; Graham, Jennifer L.; Putnam, James E.

2014-01-01

As the Nation’s largest water, earth, and biological science and civilian mapping information agency, the U.S. Geological Survey is relied on to collect high-quality data, and produce factual and impartial interpretive reports. This quality-assurance and data-management plan provides guidance for water-quality activities conducted by the Kansas Water Science Center. Policies and procedures are documented for activities related to planning, collecting, storing, documenting, tracking, verifying, approving, archiving, and disseminating water-quality data. The policies and procedures described in this plan complement quality-assurance plans for continuous water-quality monitoring, surface-water, and groundwater activities in Kansas.

Structure—activity relationships for insecticidal carbamates*

PubMed Central

Metcalf, Robert L.

1971-01-01

Carbamate insecticides are biologically active because of their structural complementarity to the active site of acetylcholinesterase (AChE) and their consequent action as substrates with very low turnover numbers. Carbamates behave as synthetic neurohormones that produce their toxic action by interrupting the normal action of AChE so that acetylcholine accumulates at synaptic junctions. The necessary properties for a suitable insecticidal carbamate are lipid solubility, suitable structural complementarity to AChE, and sufficient stability to multifunction-oxidase detoxification. The relationships between the structure and the activity of a large number of synthetic carbamates are analysed in detail, with particular attention to the second of these properties. PMID:5315358

Cyclotron production for the radiometal Zirconium-89 with an IBA cyclone 18/9 and COSTIS solid target system (STS)

NASA Astrophysics Data System (ADS)

Dabkowski, A. M.; Probst, K.; Marshall, C.

2012-12-01

The development of biological targeting agents such as proteins, peptides, antibodies and nanoparticles with a range of biological half-lives demands the production of new radionuclides with half-lives (physical) complementary to these biological properties. Zirconium-89 (89Zr) is a promising radionuclide for development of new immuno-PET agents due to its convenient half-life of 78.4 h, β+ emission rate of 23%, low maximum energy of 0.9 MeV resulting in good spatial resolution, stable daughter isotope of Yttrium-89 (89Y) and favorable imaging characteristics, with only one significant γ-line of 909 keV emitted during decay alongside the 511 keV positron photons. Our aim was to prove that isotopically pure 89Zr could be produced in an IBA Cyclone 18/9 cyclotron equipped with a COSTIS STS using the 89Y(p,n)89Zr reaction and optimise the yield by reducing the beam degrader thickness without producing either 88Zr or 88Y. The degradation of the beam energy with 400 and 500 μm thick Niobium foils were achieved without overheating problems with 2-3 hours long irradiation times. From repeated measurements of activity, it was clear that there is a bi-exponential decay of radioactivity due to the short lived 89mZr and 89Zr. The measured half-life of the longer lived radionulide was consistent with value for 89Zr. The energy spectrum from 89Zr had energy peaks at 511 keV and 909 keV and was consistent with 89Zr. Production of 89Zr with 500 μm thick Niobium beam degrader (Ep = 9.8MeV) was achieved, without producing either 88Zr or 88Y. It was necessary to wait at least 4 hours before measuring the activity and decay correct in order to calculate the 89gZr activity at the end of cyclotron production. Degrading the proton beam to 10 MeV produces radionuclidically pure 89Zr with yields from 8 to 9 MBq/μAh. Whilst this is enough for pre-clinical use, the yield is not enough for either clinical use or commercial supply. Using thinner beam degraders to increase the proton beam energy increases the radionuclidic yield but it is not yet possible to exclude the presence of radionuclidic impurities.

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

PubMed Central

Uzair, Bushra; Tabassum, Sobia; Rasheed, Madiha; Rehman, Saima Firdous

2012-01-01

The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria. PMID:22545008

Mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes, which induces biological effects.

PubMed

Jeyaseelan, S; Kannan, M S; Briggs, R E; Thumbikat, P; Maheswaran, S K

2001-10-01

The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces biological effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any effects. These findings suggest that the specificity of LktA effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to biological effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for biological effects. We used a biologically inactive mutant leukotoxin (DeltaLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The DeltaLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3'-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced biological effects.

Mannheimia haemolytica Leukotoxin Activates a Nonreceptor Tyrosine Kinase Signaling Cascade in Bovine Leukocytes, Which Induces Biological Effects

PubMed Central

Jeyaseelan, S.; Kannan, M. S.; Briggs, R. E.; Thumbikat, P.; Maheswaran, S. K.

2001-01-01

The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces biological effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any effects. These findings suggest that the specificity of LktA effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to biological effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for biological effects. We used a biologically inactive mutant leukotoxin (ΔLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The ΔLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3′-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced biological effects. PMID:11553552

Interplay of migratory and division forces as a generic mechanism for stem cell patterns

NASA Astrophysics Data System (ADS)

Hannezo, Edouard; Coucke, Alice; Joanny, Jean-François

2016-02-01

In many adult tissues, stem cells and differentiated cells are not homogeneously distributed: stem cells are arranged in periodic "niches," and differentiated cells are constantly produced and migrate out of these niches. In this article, we provide a general theoretical framework to study mixtures of dividing and actively migrating particles, which we apply to biological tissues. We show in particular that the interplay between the stresses arising from active cell migration and stem cell division give rise to robust stem cell patterns. The instability of the tissue leads to spatial patterns which are either steady or oscillating in time. The wavelength of the instability has an order of magnitude consistent with the biological observations. We also discuss the implications of these results for future in vitro and in vivo experiments.

[THERMAL STABILITY AS A PROGNOSTIC INDICATOR OF CONSERVATION OF LIVE EMBRYONIC SMALLPOX VACCINE (TEOVAC) DURING STORAGE].

PubMed

Zhukov, V A; Kokorev, S V; Rogozhkina, S V; Melnikov, D G; Terentiev, A I; Kovalchuk, E A; Vakhnov, E Yu; Borisevich, S V

2016-01-01

Determination of values of coefficients of thermal stability of TEOVac for prognosis of conservation of the vaccine (specific biological activity) during the process of warranty period storage. TEOVac (masticatory tablets) in primary packaging was kept at increased temperature (accelerated and stress-tests) and at the conditions established by PAP for the preparation (long-term tests). Biological activity of the vaccine was determined by titration on 12-day chicken embryos. A correlation between the value of coefficients of thermal stability and conservation of the prepared series of the condition preparation at the final date of storage was experimentally established. Coefficients of thermal stability could be used as a prognostic indicator of quality of the produced pelleted formulation of the preparation for evaluation of conservation of the vaccine during warranty period storage.

Quorum sensing is a key regulator for the antifungal and biocontrol activity of chitinase-producing Chromobacterium sp. C61.

PubMed

Kim, In Seon; Yang, Si Young; Park, Seur Kee; Kim, Young Cheol

2017-01-01

Chromobacterium sp. strain C61 has strong biocontrol activity; however, the genetic and biochemical determinants of its plant disease suppression activity are not well understood. Here, we report the identification and characterization of two new determinants of its biocontrol activity. Transposon mutagenesis was used to identify mutants that were deficient in fungal suppression. One of these mutants had an insertion in a homologue of depD, a structural gene in the dep operon, that encodes a protein involved in non-ribosomal peptide synthesis. In the second mutant, the insertion was in a homologue of the luxI gene, which encodes a homoserine lactone synthase. The luxI - and depD - mutants had no antifungal activity in vitro and a dramatically reduced capacity to suppress various plant diseases in planta. Antifungal production and biocontrol were restored by complementation of the luxI - mutant. Other phenotypes associated with effective biological control, including motility and lytic enzyme secretion, were also affected by the luxI mutation. Biochemical analysis of ethyl acetate extracts of culture filtrates of the mutant and wild-type strains showed that a key antifungal compound, chromobactomycin, was produced by wild-type C61 and the complemented luxI - mutant, but not by the luxI - or depD - mutant. These data suggest that multiple biocontrol-related phenotypes are regulated by homoserine lactones in C61. Thus, quorum sensing plays an essential role in the biological control potential of diverse bacterial lineages. © 2016 BSPP and John Wiley & Sons Ltd.

Modeling electrical power absorption and thermally-induced biological tissue damage.

PubMed

Zohdi, T I

2014-01-01

This work develops a model for thermally induced damage from high current flow through biological tissue. Using the first law of thermodynamics, the balance of energy produced by the current and the energy absorbed by the tissue are investigated. The tissue damage is correlated with an evolution law that is activated upon exceeding a temperature threshold. As an example, the Fung material model is used. For certain parameter choices, the Fung material law has the ability to absorb relatively significant amounts of energy, due to its inherent exponential response character, thus, to some extent, mitigating possible tissue damage. Numerical examples are provided to illustrate the model's behavior.

Preparation and biological evaluation of conformationally constrained BACE1 inhibitors.

PubMed

Winneroski, Leonard L; Schiffler, Matthew A; Erickson, Jon A; May, Patrick C; Monk, Scott A; Timm, David E; Audia, James E; Beck, James P; Boggs, Leonard N; Borders, Anthony R; Boyer, Robert D; Brier, Richard A; Hudziak, Kevin J; Klimkowski, Valentine J; Garcia Losada, Pablo; Mathes, Brian M; Stout, Stephanie L; Watson, Brian M; Mergott, Dustin J

2015-07-01

The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neutrons produced by known energies of ions abundant in space

NASA Technical Reports Server (NTRS)

Wadman, W. W., III

1972-01-01

Particle accelerator radiation measurements are applied to the problem of calculating biological dose from radiation produced in the walls of a spacecraft by various ions in space. Neutrons, one of the products of the interactions of energetic ions with matter, are usually quite penetrating and have large values of Q.F. or R.B.E. Ions of helium, boron, carbon, nitrogen, and oxygen were accelerated and directed onto target materials of copper or tantalum. The secondary neutron production was determined. Studies were made of the angular distribution and an inferred neutron spectrum was calculated from activities of threshold reaction detectors.

Cellulolytic systems in insects.

PubMed

Watanabe, Hirofumi; Tokuda, Gaku

2010-01-01

Despite the presence of many carbohydrolytic activities in insects, their cellulolytic mechanisms are poorly understood. Whereas cellulase genes are absent from the genomes of Drosophila melanogaster or Bombyx mori, other insects such as termites produce their own cellulases. Recent studies using molecular biological techniques have brought new insights into the mechanisms by which the insects and their microbial symbionts digest cellulose in the small intestine. DNA sequences of cellulase and associated genes, as well as physiological and morphological information about the digestive systems of cellulase-producing insects, may allow the efficient use of cellulosic biomass as a sustainable energy source.

The scientific production in health and biological sciences of the top 20 Brazilian universities.

PubMed

Zorzetto, R; Razzouk, D; Dubugras, M T B; Gerolin, J; Schor, N; Guimarães, J A; Mari, J J

2006-12-01

Brazilian scientific output exhibited a 4-fold increase in the last two decades because of the stability of the investment in research and development activities and of changes in the policies of the main funding agencies. Most of this production is concentrated in public universities and research institutes located in the richest part of the country. Among all areas of knowledge, the most productive are Health and Biological Sciences. During the 1998-2002 period these areas presented heterogeneous growth ranging from 4.5% (Pharmacology) to 191% (Psychiatry), with a median growth rate of 47.2%. In order to identify and rank the 20 most prolific institutions in these areas, searches were made in three databases (DataCAPES, ISI and MEDLINE) which permitted the identification of 109,507 original articles produced by the 592 Graduate Programs in Health and Biological Sciences offered by 118 public universities and research institutes. The 20 most productive centers, ranked according to the total number of ISI-indexed articles published during the 1998-2003 period, produced 78.7% of the papers in these areas and are strongly concentrated in the Southern part of the country, mainly in São Paulo State.

Biological treatment of chicken feather waste for improved biogas production.

PubMed

Forgács, Gergely; Alinezhad, Saeid; Mirabdollah, Amir; Feuk-Lagerstedt, Elisabeth; Horváth, Ilona Sárvári

2011-01-01

A two-stage system was developed which combines the biological degradation of keratin-rich waste with the production of biogas. Chicken feather waste was treated biologically with a recombinant Bacillus megaterium strain showing keratinase activity prior to biogas production. Chopped, autoclaved chicken feathers (4%, W/V) were completely degraded, resulting in a yellowish fermentation broth with a level of 0.51 mg/mL soluble proteins after 8 days of cultivation of the recombinant strain. During the subsequent anaerobic batch digestion experiments, methane production of 0.35 Nm3/kg dry feathers (i.e., 0.4 Nm3/kg volatile solids of feathers), corresponding to 80% of the theoretical value on proteins, was achieved from the feather hydrolyzates, independently of the pre-hydrolysis time period of 1, 2 or 8 days. Cultivation with a native keratinase producing strain, Bacillus licheniformis resulted in only 0.25 mg/mL soluble proteins in the feather hydrolyzate, which then was digested achieving a maximum accumulated methane production of 0.31 Nm3/kg dry feathers. Feather hydrolyzates treated with the wild type B. megaterium produced 0.21 Nm3 CH4/kg dry feathers as maximum yield.

Cyanobacterial Metabolite Calothrixins: Recent Advances in Synthesis and Biological Evaluation

PubMed Central

Xu, Su; Nijampatnam, Bhavitavya; Dutta, Shilpa; Velu, Sadanandan E.

2016-01-01

The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds and capacity to produce potent pharmaceutical and biotechnological traits. Calothrixins A and B are two cyanobacterial metabolites with a structural assembly of quinoline, quinone, and indole pharmacophores. This review surveys recent advances in the synthesis and evaluation of the biological activities of calothrixins. Due to the low isolation yields from the marine source and the promise this scaffold holds for anticancer and antimicrobial drugs, organic and medicinal chemists around the world have embarked on developing efficient synthetic routes to produce calothrixins. Since the first review appeared in 2009, 11 novel syntheses of calothrixins have been published in the efforts to develop methods that contain fewer steps and higher-yielding reactions. Calothrixins have shown their potential as topoisomerase I poisons for their cytotoxicity in cancer. They have also been observed to target various aspects of RNA synthesis in bacteria. Further investigation into the exact mechanism for their bioactivity is still required for many of its analogs. PMID:26771620

Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly

PubMed Central

2014-01-01

Background Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. It plays vital roles in honeybee biology and in the improvement of human health. However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. Results A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. Most of the glycosylated proteins were related to metabolic activities and health improvement. The 13 newly identified proteins were also mainly associated with metabolic processes and health improvement activities. Conclusion Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. The newly-identified proteins significantly extend the proteome coverage of RJ. These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. PMID:24529077

Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice.

PubMed

Bickert, Andreas; Ginkel, Christina; Kol, Matthijs; vom Dorp, Katharina; Jastrow, Holger; Degen, Joachim; Jacobs, René L; Vance, Dennis E; Winterhager, Elke; Jiang, Xian-Cheng; Dörmann, Peter; Somerharju, Pentti; Holthuis, Joost C M; Willecke, Klaus

2015-04-01

Besides bulk amounts of SM, mammalian cells produce small quantities of the SM analog ceramide phosphoethanolamine (CPE). Little is known about the biological role of CPE or enzymes responsible for CPE production. Heterologous expression studies revealed that SM synthase (SMS)2 is a bifunctional enzyme producing both SM and CPE, whereas SMS-related protein (SMSr) serves as monofunctional CPE synthase. Acute disruption of SMSr catalytic activity in cultured cells causes a rise in endoplasmic reticulum (ER) ceramides, fragmentation of ER exit sites, and induction of mitochondrial apoptosis. To address the relevance of CPE biosynthesis in vivo, we analyzed the tissue-specific distribution of CPE in mice and generated mouse lines lacking SMSr and SMS2 catalytic activity. We found that CPE levels were >300-fold lower than SM in all tissues examined. Unexpectedly, combined inactivation of SMSr and SMS2 significantly reduced, but did not eliminate, tissue-specific CPE pools and had no obvious impact on mouse development or fertility. While SMSr is widely expressed and serves as the principal CPE synthase in the brain, blocking its catalytic activity did not affect ceramide levels or secretory pathway integrity in the brain or any other tissue. Our data provide a first inventory of CPE species and CPE-biosynthetic enzymes in mammals. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Enhanced heterologous expression of biologically active human granulocyte colony stimulating factor in transgenic tobacco BY-2 cells by localization to endoplasmic reticulum.

PubMed

Nair, Nisha R; Chidambareswaren, M; Manjula, S

2014-09-01

Tobacco Bright Yellow-2 (BY-2) cells, one of the best characterized cell lines is an attractive expression system for heterologous protein expression. However, the expression of foreign proteins is currently hampered by their low yield, which is partially the result of proteolytic degradation. Human granulocyte colony stimulating factor (hG-CSF) is a hematopoietic cytokine. Recombinant hG-CSF is successfully being used for the treatment of chemotherapy-induced neutropenia in cancer patients. Here, we describe a simple strategy for producing biologically active hG-CSF in tobacco BY-2 cells, localized in the apoplast of BY-2 cells, as well as targeted to the endoplasmic reticulum (ER). ER targeting significantly enhanced recombinant production which scaled to 17.89 mg/l from 4.19 mg/l when expressed in the apoplasts. Southern blotting confirmed the stable integration of hG-CSF in the BY-2 nuclear genome, and the expression of hG-CSF was analysed by Western blotting. Total soluble protein containing hG-CSF isolated from positive calli showed proliferative potential when tested on HL-60 cell lines by MTT assay. We also report the potential of a Fluorescence-activated cell sorting approach for an efficient sorting of the hG-CSF-expressing cell lines, which will enable the generation of homogenous high-producing cell lines.

Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis.

PubMed

Mellows, Ben; Mitchell, Robert; Antonioli, Manuela; Kretz, Oliver; Chambers, David; Zeuner, Marie-Theres; Denecke, Bernd; Musante, Luca; Ramachandra, Durrgah L; Debacq-Chainiaux, Florence; Holthofer, Harry; Joch, Barbara; Ray, Steve; Widera, Darius; David, Anna L; Huber, Tobias B; Dengjel, Joern; De Coppi, Paolo; Patel, Ketan

2017-09-15

The secretome of human amniotic fluid stem cells (AFSCs) has great potential as a therapeutic agent in regenerative medicine. However, it must be produced in a clinically compliant manner before it can be used in humans. In this study, we developed a means of producing a biologically active secretome from AFSCs that is free of all exogenous molecules. We demonstrate that the full secretome is capable of promoting stem cell proliferation, migration, and protection of cells against senescence. Furthermore, it has significant anti-inflammatory properties. Most importantly, we show that it promotes tissue regeneration in a model of muscle damage. We then demonstrate that the secretome contains extracellular vesicles (EVs) that harbor much, but not all, of the biological activity of the whole secretome. Proteomic characterization of the EV and free secretome fraction shows the presence of numerous molecules specific to each fraction that could be key regulators of tissue regeneration. Intriguingly, we show that the EVs only contain miRNA and not mRNA. This suggests that tissue regeneration in the host is mediated by the action of EVs modifying existing, rather than imposing new, signaling pathways. The EVs harbor significant anti-inflammatory activity as well as promote angiogenesis, the latter may be the mechanistic explanation for their ability to promote muscle regeneration after cardiotoxin injury.

Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells.

PubMed

Shen, Lei; Zeng, Wen; Wu, Yang-Xiao; Hou, Chun-Li; Chen, Wen; Yang, Ming-Can; Li, Li; Zhang, Ya-Fang; Zhu, Chu-Hong

2013-01-01

Angiogenesis is a major obstacle for wound healing in patients with diabetic foot wounds. Mesenchymal stem cells (MSCs) have an important function in wound repair, and neurotrophin-3 (NT-3) can promote nerve regeneration and angiogenesis. We investigated the effect of NT-3 on accelerating wound healing in the diabetic foot by improving human bone marrow MSC (hMSC) activation. In vitro, NT-3 significantly promoted VEGF, NGF, and BDNF secretion in hMSCs. NT-3 improved activation of the hMSC conditioned medium, promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, and significantly improved the closure rate of HUVEC scratches. In addition, we produced nanofiber mesh biological tissue materials through the electrospinning technique using polylactic acid, mixed silk, and collagen. The hMSCs stimulated by NT-3 were implanted into the material. Compared with the control group, the NT-3-stimulated hMSCs in the biological tissue material significantly promoted angiogenesis in the feet of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. These results suggest that NT-3 significantly promotes hMSC secretion of VEGF, NGF, and other vasoactive factors and that it accelerates wound healing by inducing angiogenesis through improved activation of vascular endothelial cells. The hMSCs stimulated by NT-3 can produce materials that accelerate wound healing in the diabetic foot and other ischemic ulcers.

Immense essence of excellence: marine microbial bioactive compounds.

PubMed

Bhatnagar, Ira; Kim, Se-Kwon

2010-10-15

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery.

Electron shuttle-mediated biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine adsorbed to granular activated carbon.

PubMed

Millerick, Kayleigh; Drew, Scott R; Finneran, Kevin T

2013-08-06

Granular activated carbon (GAC) effectively removes hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) from groundwater but generates RDX-laden GAC that must be disposed of or regenerated. Batch reactors containing GAC to which RDX was preadsorbed were used in experiments to test the potential for adsorbed RDX reduction and daughter product formation using (i) chemically reduced anthrahydroquinone-2,6-disulfonate (AH2QDS), (ii) resting Geobacter metallireducens strain GS-15, and (iii) a combined system containing AQDS and GS-15. Approximately 97.0% of the adsorbed RDX was transformed in each of these experimental systems by 90 h. Chemically reduced AQDS (AH2QDS) transformed 99.2% of adsorbed RDX; formaldehyde was produced rapidly and was stoichiometric (3 mol HCHO per mol RDX). Geobacter metallireducens also reduced RDX with and without AQDS present. This is the first study to demonstrate biological transformation of RDX adsorbed to GAC. Formaldehyde increased and then decreased in biological systems, suggesting a previously unreported capacity for G. metallireducens to oxidize formaldehyde, which was confirmed with resting cell suspensions. These data suggest the masses of GAC waste currently produced by activated carbon at RDX remediation sites can be minimized, decreasing the carbon footprint of the treatment technology. Alternatively, this strategy may be used to develop a Bio-GAC system for ex situ RDX treatment.

Immense Essence of Excellence: Marine Microbial Bioactive Compounds

PubMed Central

Bhatnagar, Ira; Kim, Se-Kwon

2010-01-01

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery. PMID:21116414

Clostridial toxins active locally in the gastrointestinal tract.

PubMed

Wilkins, T; Krivan, H; Stiles, B; Carman, R; Lyerly, D

1985-01-01

Clostridium difficile and Clostridium spiroforme have only in recent years been recognized as intestinal pathogens. They both produce toxins that are also produced by other clostridia. C. difficile toxins A and B are produced by C. sordellii and a few strains of C. perfringens whereas C. spiroforme produces the same toxins as C. perfringens Type E (iota toxin). Iota toxin activity may be the product of two proteins. Toxigenic strains of C. spiroforme and Type E produce two antigens which possess much more biological activity when administered together than when given alone. C. difficile was thought for some time to produce only a single toxin, but then the enterotoxic activity was shown to be due to a separate toxin (toxin A). This toxin increases the oral toxicity of toxin B (the main cytotoxin) and may increase the permeability of the colon. Toxin A binds to a specific receptor in hamster brush border membranes and in the membranes of rabbit erythrocytes. This receptor appears to be a glycoprotein. The receptor can be extracted from the membrane with Triton and binds to immobilized toxin A. The receptor can be extracted and used to coat plastic plates as a first phase in an ELISA assay. Another assay has been developed in which the toxin A binds to the red cells and then the erythrocytes are agglutinated with antitoxin. An even more sensitive assay consists of using rabbit erythrocyte ghosts to bind the toxin and then precipitating the ghosts with antibody to toxin A attached to latex beads. Monoclonal antibodies to toxin A also have been developed and are used in these and other assays.

Production of bioactive chitosan oligosaccharides using the hypertransglycosylating chitinase-D from Serratia proteamaculans.

PubMed

Madhuprakash, Jogi; El Gueddari, Nour Eddine; Moerschbacher, Bruno M; Podile, Appa Rao

2015-12-01

The biological activities of chitosan and its oligosaccharides are greatly influenced by properties such as the degree of polymerization (DP), degree of acetylation (DA) and pattern of acetylation (PA). Here, structurally diverse chitosan oligosaccharides from chitosan polymers (DA=35% or 61%) were generated using Serratia proteamaculans wild-type chitinase D (SpChiD) and the W114A mutant which lacks transglycosylase activity. The crude oligosaccharide mixtures and purified fractions with specific DP and DA ranges were tested for their ability to induce an oxidative burst in rice cell suspension cultures. The crude mixtures were more active when produced by the W114A mutant whereas the purified fractions were more active when produced by wild-type SpChiD. Neither hydrolysis nor transglycosylation by SpChiD was inhibited in the presence of fully-deacetylated oligosaccharides, suggesting that SpChiD could be exploited to generate oligosaccharides with defined DA and PA values. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of electrospun nanofibers containing chitosan/PEO blend and phenolic compounds with antibacterial activity.

PubMed

Kuntzler, Suelen Goettems; Costa, Jorge Alberto Vieira; Morais, Michele Greque de

2018-05-31

Electrospun nanofibers can be formed with chitosan as the polymers found in biological sources have antibacterial ability. The objective of this work was to evaluate whether chitosan/polyethylene oxide (PEO) blend nanofibers containing microalgal phenolic compounds exhibit antibacterial activity. Nanofibers produced with a 3% chitosan/2% PEO blend containing 1% phenolic compounds had an average diameter of 214 ± 37 nm, which resulted in a high temperature of maximum degradation, an important parameter for food packaging. The potential antibacterial activity of this nanofibers was confirmed by their inhibition of Staphylococcus aureus ATCC 25923 (6.4 ± 1.1 mm) and Escherichia coli ATCC 25972 (5.5 ± 0.4 mm). The polymeric nanofibers produced from chitosan and containing phenolic compounds have properties that therefore allow their application as active packaging. In addition, chitosan is an excellent polymer for packaging as it presents biodegradability, biocompatibility and, non-toxicity. Copyright © 2018. Published by Elsevier B.V.

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

PubMed

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

2013-11-01

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

Pig Brain Mitochondria as a Biological Model for Study of Mitochondrial Respiration.

PubMed

Fišar, Z; Hroudová, J

2016-01-01

Oxidative phosphorylation is a key process of intracellular energy transfer by which mitochondria produce ATP. Isolated mitochondria serve as a biological model for understanding the mitochondrial respiration control, effects of various biologically active substances, and pathophysiology of mitochondrial diseases. The aim of our study was to evaluate pig brain mitochondria as a proper biological model for investigation of activity of the mitochondrial electron transport chain. Oxygen consumption rates of isolated pig brain mitochondria were measured using high-resolution respirometry. Mitochondrial respiration of crude mitochondrial fraction, mitochondria purified in sucrose gradient, and mitochondria purified in Percoll gradient were assayed as a function of storage time. Oxygen flux and various mitochondrial respiratory control ratios were not changed within two days of mitochondria storage on ice. Leak respiration was found higher and Complex I-linked respiration lower in purified mitochondria compared to the crude mitochondrial fraction. Damage to both outer and inner mitochondrial membrane caused by the isolation procedure was the greatest after purification in a sucrose gradient. We confirmed that pig brain mitochondria can serve as a biological model for investigation of mitochondrial respiration. The advantage of this biological model is the stability of respiratory parameters for more than 48 h and the possibility to isolate large amounts of mitochondria from specific brain areas without the need to kill laboratory animals. We suggest the use of high-resolution respirometry of pig brain mitochondria for research of the neuroprotective effects and/or mitochondrial toxicity of new medical drugs.

Enhanced Production of Anthraquinones and Phenolic Compounds and Biological Activities in the Cell Suspension Cultures of Polygonum multiflorum

PubMed Central

Thiruvengadam, Muthu; Rekha, Kaliyaperumal; Rajakumar, Govindasamy; Lee, Taek-Jun; Kim, Seung-Hyun; Chung, Ill-Min

2016-01-01

Anthraquinones (AQs) and phenolic compounds are important phytochemicals that are biosynthesized in cell suspension cultures of Polygonum multiflorum. We wanted to optimize the effects of plant growth regulators (PGRs), media, sucrose, l-glutamine, jasmonic acid (JA), and salicylic acid (SA) for the production of phytochemicals and biomass accumulation in a cell suspension culture of P. multiflorum. The medium containing Murashige and Skoog (MS) salts and 4% sucrose supplemented with 1 mg/L 2,4-dichlorophenoxyacetic acid, 0.5 mg/L thidiazuron, and 100 µM l-glutamine at 28 days of cell suspension culture was suitable for biomass accumulation and AQ production. Maximum biomass accumulation (12.5 and 12.35 g fresh mass (FM); 3 and 2.93 g dry mass (DM)) and AQ production (emodin 295.20 and 282 mg/g DM; physcion 421.55 and 410.25 mg/g DM) were observed using 100 µM JA and SA, respectively. JA- and SA-elicited cell cultures showed several-fold higher biomass accumulation and AQ production than the control cell cultures. Furthermore, the cell suspension cultures effectively produced 23 phenolic compounds, such as flavonols and hydroxycinnamic and hydroxybenzoic acid derivatives. PGR-, JA-, and SA-elicited cell cultures produced a higher amount of AQs and phenolic compounds. Because of these metabolic changes, the antioxidant, antimicrobial, and anticancer activities were high in the PGR-, JA-, and SA-elicited cell cultures. The results showed that the elicitors (JA and SA) induced the enhancement of biomass accumulation and phytochemical (AQs and phenolic compounds) production as well as biological activities in the cell suspension cultures of P. multiflorum. This optimized protocol can be developed for large-scale biomass accumulation and production of phytochemicals (AQs and phenolic compounds) from cell suspension cultures, and the phytochemicals can be used for various biological activities. PMID:27854330

Enhanced Anti-Inflammatory Activities by the Combination of Luteolin and Tangeretin.

PubMed

Funaro, Antonietta; Wu, Xian; Song, Mingyue; Zheng, Jinkai; Guo, Shanshan; Rakariyatham, Kanyasiri; Rodriguez-Estrada, Maria Teresa; Xiao, Hang

2016-05-01

Dietary components in combination may act synergistically and produce enhanced biological activities. Herein, we investigated the anti-inflammatory effects of 2 flavonoids, that is luteolin (LUT) and tangeretin (TAN) in combination. Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were treated with noncytotoxic concentrations of LUT, TAN, and their combinations. The results showed that LUT/TAN in combination produced synergistic inhibitory effects on LPS-stimulated production of nitric oxide (NO). ELISA results demonstrated that LUT/TAN in combination caused stronger suppression on the LPS-induced overexpression of proinflammatory mediators, such as prostaglandin E2 (PGE2 ), interleukin (IL)-1β, and IL-6 than LUT or TAN alone. Immunoblotting and Real-Time PCR analyses showed that LUT/TAN combination significantly decreased LPS-induced protein and mRNA expression of inducible nitric oxide synthase and cyclooxygenase-2. These inhibitory effects of the combination treatment were stronger than those produced by LUT or TAN alone. Overall, our results demonstrated for the first time that combination of LUT and TAN produced synergistic anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages. © 2016 Institute of Food Technologists®

[Melatonin, synthetic analogs, and the sleep/wake rhythm].

PubMed

Escames, G; Acuña-Castroviejo, D

Melatonin, a widespread hormone in the animal kingdom, is produced by several organs and tissues besides the pineal gland. Whilst extrapineal melatonin behaves as a cytoprotective molecule, the pineal produces the hormone in a rhythmic manner. The discovery of melatonin in 1958, and the characterization of its synthesis somewhat later, let to the description of its photoperiodic regulation and its relationship with the biological rhythms such as the sleep/wake rhythm. The suprachiasmatic nuclei are the anatomical seat of the biological clock, represented by the clock genes, which code for the period and frequency of the rhythms. The photoperiod synchronizes the activity of the auprachiasmatic biological clock, which in turn induces the melatonin's rhythm. The rhythm of melatonin, peaking at 2-3 am, acts as an endogenous synchronizer that translates the environmental photoperiodic signal in chemical information for the cells. The sleep/wake cycle is a typical biological rhythm synchronized by melatonin, and the sleep/wake cycle alterations of chronobiological origin, are very sensitive to melatonin treatment. Taking advantage of the chronobiotic and antidepressive properties of melatonin, a series of synthetic analogs of this hormone, with high interest in insomnia, are now available. Melatonin is a highly effective chronobiotic in the treatment of chronobiological alterations of the sleep/wake cycle. From a pharmacokinetic point of view, the synthetic drugs derived from melatonin are interesting tools in the therapy of these alterations.

Application of Nanoparticle Technology to Reduce the Anti-Microbial Resistance through β-Lactam Antibiotic-Polymer Inclusion Nano-Complex.

PubMed

Salamanca, Constain H; Yarce, Cristhian J; Roman, Yony; Davalos, Andrés F; Rivera, Gustavo R

2018-02-10

Biocompatible polymeric materials with potential to form functional structures in association with different therapeutic molecules have a high potential for biological, medical and pharmaceutical applications. Therefore, the capability of the inclusion of nano-Complex formed between the sodium salt of poly(maleic acid- alt -octadecene) and a β-lactam drug (ampicillin trihydrate) to avoid the chemical and enzymatic degradation and enhance the biological activity were evaluated. PAM-18Na was produced and characterized, as reported previously. The formation of polymeric hydrophobic aggregates in aqueous solution was determined, using pyrene as a fluorescent probe. Furthermore, the formation of polymer-drug nano-complexes was characterized by Differential Scanning Calorimetry-DSC, viscometric, ultrafiltration/centrifugation assays, zeta potential and size measurements were determined by dynamic light scattering-DLS. The PAM-18Na capacity to avoid the chemical degradation was studied through stress stability tests. The enzymatic degradation was evaluated from a pure β-lactamase, while the biological degradation was determined by different β-lactamase producing Staphylococcus aureus strains. When ampicillin was associated with PAM-18Na, the half-life time in acidic conditions increased, whereas both the enzymatic degradation and the minimum inhibitory concentration decreased to a 90 and 75%, respectively. These results suggest a promissory capability of this polymer to protect the β-lactam drugs against chemical, enzymatic and biological degradation.

Application of Nanoparticle Technology to Reduce the Anti-Microbial Resistance through β-Lactam Antibiotic-Polymer Inclusion Nano-Complex

PubMed Central

Yarce, Cristhian J.; Roman, Yony; Davalos, Andrés F.; Rivera, Gustavo R.

2018-01-01

Biocompatible polymeric materials with potential to form functional structures in association with different therapeutic molecules have a high potential for biological, medical and pharmaceutical applications. Therefore, the capability of the inclusion of nano-Complex formed between the sodium salt of poly(maleic acid-alt-octadecene) and a β-lactam drug (ampicillin trihydrate) to avoid the chemical and enzymatic degradation and enhance the biological activity were evaluated. PAM-18Na was produced and characterized, as reported previously. The formation of polymeric hydrophobic aggregates in aqueous solution was determined, using pyrene as a fluorescent probe. Furthermore, the formation of polymer-drug nano-complexes was characterized by Differential Scanning Calorimetry-DSC, viscometric, ultrafiltration/centrifugation assays, zeta potential and size measurements were determined by dynamic light scattering-DLS. The PAM-18Na capacity to avoid the chemical degradation was studied through stress stability tests. The enzymatic degradation was evaluated from a pure β-lactamase, while the biological degradation was determined by different β-lactamase producing Staphylococcus aureus strains. When ampicillin was associated with PAM-18Na, the half-life time in acidic conditions increased, whereas both the enzymatic degradation and the minimum inhibitory concentration decreased to a 90 and 75%, respectively. These results suggest a promissory capability of this polymer to protect the β-lactam drugs against chemical, enzymatic and biological degradation. PMID:29439391

Antimycobacterial and antimalarial activities of endophytic fungi associated with the ancient and narrowly endemic neotropical plant Vellozia gigantea from Brazil.

PubMed

Ferreira, Mariana C; Cantrell, Charles L; Wedge, David E; Gonçalves, Vívian N; Jacob, Melissa R; Khan, Shabana; Rosa, Carlos A; Rosa, Luiz H

2017-10-01

Endophytic fungi, present mainly in the Ascomycota and Basidiomycota phyla, are associated with different plants and represent important producers of bioactive natural products. Brazil has a rich biodiversity of plant species, including those reported as being endemic. Among the endemic Brazilian plant species, Vellozia gigantea (Velloziaceae) is threatened by extinction and is a promising target to recover endophytic fungi. The present study focused on bioprospecting of bioactive compounds of the endophytic fungi associated with V. gigantea, an endemic, ancient, and endangered plant species that occurs only in the rupestrian grasslands of Brazil. The capability of 285 fungal isolates to produce antimicrobial and antimalarial activities was examined. Fungi were grown at solid-state fermentation to recover their crude extracts in dichloromethane. Bioactive extracts were analysed by chromatographic fractionation and NMR and displayed compounds with antimicrobial, antimycobacterial, and antimalarial activities. Five fungi produced antimicrobial and antimalarial compounds. Extracts of Diaporthe miriciae showed antifungal, antibacterial, and antimalarial activities; Trichoderma effusum displayed selective antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare; and three Penicillium species showed antibacterial activity. D. miriciae extract contained highly functionalised secondary metabolites, yielding the compound epoxycytochalasin H with high antimalarial activity against the chloroquine-resistant strain of Plasmodium falciparum, with an IC50 approximately 3.5-fold lower than that with chloroquine. Our results indicate that V. gigantea may represent a microhabitat repository hotspot of potential fungi producers of bioactive compounds and suggest that endophytic fungal communities might be an important biological component contributing to the fitness of the plants living in the rupestrian grassland.

Bacterial versus fungal laccase: potential for micropollutant degradation

PubMed Central

2013-01-01

Relatively high concentrations of micropollutants in municipal wastewater treatment plant (WWTP) effluents underscore the necessity to develop additional treatment steps prior to discharge of treated wastewater. Microorganisms that produce unspecific oxidative enzymes such as laccases are a potential means to improve biodegradation of these compounds. Four strains of the bacterial genus Streptomyces (S. cyaneus, S. ipomoea, S. griseus and S. psammoticus) and the white-rot fungus Trametes versicolor were studied for their ability to produce active extracellular laccase in biologically treated wastewater with different carbon sources. Among the Streptomyces strains evaluated, only S. cyaneus produced extracellular laccase with sufficient activity to envisage its potential use in WWTPs. Laccase activity produced by T. versicolor was more than 20 times greater, the highest activity being observed with ash branches as the sole carbon source. The laccase preparation of S. cyaneus (abbreviated LSc) and commercial laccase from T. versicolor (LTv) were further compared in terms of their activity at different pH and temperatures, their stability, their substrate range, and their micropollutant oxidation efficiency. LSc and LTv showed highest activities under acidic conditions (around pH 3 to 5), but LTv was active over wider pH and temperature ranges than LSc, especially at near-neutral pH and between 10 and 25°C (typical conditions found in WWTPs). LTv was also less affected by pH inactivation. Both laccase preparations oxidized the three micropollutants tested, bisphenol A, diclofenac and mefenamic acid, with faster degradation kinetics observed for LTv. Overall, T. versicolor appeared to be the better candidate to remove micropollutants from wastewater in a dedicated post-treatment step. PMID:24152339

Cortical network differences in the sighted versus early blind for recognition of human-produced action sounds

PubMed Central

Lewis, James W.; Frum, Chris; Brefczynski-Lewis, Julie A.; Talkington, William J.; Walker, Nathan A.; Rapuano, Kristina M.; Kovach, Amanda L.

2012-01-01

Both sighted and blind individuals can readily interpret meaning behind everyday real-world sounds. In sighted listeners, we previously reported that regions along the bilateral posterior superior temporal sulci (pSTS) and middle temporal gyri (pMTG) are preferentially activated when presented with recognizable action sounds. These regions have generally been hypothesized to represent primary loci for complex motion processing, including visual biological motion processing and audio-visual integration. However, it remained unclear whether, or to what degree, life-long visual experience might impact functions related to hearing perception or memory of sound-source actions. Using functional magnetic resonance imaging (fMRI), we compared brain regions activated in congenitally blind versus sighted listeners in response to hearing a wide range of recognizable human-produced action sounds (excluding vocalizations) versus unrecognized, backward-played versions of those sounds. Here we show that recognized human action sounds commonly evoked activity in both groups along most of the left pSTS/pMTG complex, though with relatively greater activity in the right pSTS/pMTG by the blind group. These results indicate that portions of the postero-lateral temporal cortices contain domain-specific hubs for biological and/or complex motion processing independent of sensory-modality experience. Contrasting the two groups, the sighted listeners preferentially activated bilateral parietal plus medial and lateral frontal networks, while the blind listeners preferentially activated left anterior insula plus bilateral anterior calcarine and medial occipital regions, including what would otherwise have been visual-related cortex. These global-level network differences suggest that blind and sighted listeners may preferentially use different memory retrieval strategies when attempting to recognize action sounds. PMID:21305666

Tunable Shape-Shifting Structures for Military Applications

DTIC Science & Technology

2014-01-01

autonomous (also self - healing and fault-tolerant) systems that can provide multifunctionality whilst minimising weight/size, particularly in extreme...The proof-of-concept approach was successfully demonstrated. It is possible to deform the surface of a multilayer soft structure with a high level...biological systems found in Nature (e.g. adaptive skin texture of cephalopods), active soft structures producing large deformations offer attractive ways to

Combined Administration of Recombinant Human Megakaryocyte Growth and Development Factor and Granulocyte Colony-Stimulating Factor Enhances Multilineage Hematopoietic Reconstitution in Nonhuman Primates after Radiation-Induced Marrow Aplasia

DTIC Science & Technology

1996-05-01

dose would yield an equivalent or better biological activity. Neupogen ® ( Filgrastim ), r-metHuG-CSF, was produced in E. coli as a...recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoi- etic recovery after otherwise lethal total body

Insertion of benzene rings into the amide bond: one-step synthesis of acridines and acridones from aryl amides.

PubMed

Pintori, Didier G; Greaney, Michael F

2010-01-01

Insertion of benzene rings into the amide bond using the reactive intermediate benzyne is described. Aromatic amides undergo smooth insertion when treated with O-triflatophenyl silane benzyne precursors, producing versatile aminobenzophenone products in good to excellent yield. The process is entirely metal-free and has been exemplified on the synthesis of biologically active acridones and acridines.

The unconventional antimicrobial peptides of the classical propionibacteria.

PubMed

Faye, Therese; Holo, Helge; Langsrud, Thor; Nes, Ingolf F; Brede, Dag A

2011-02-01

The classical propionibacteria produce genetically unique antimicrobial peptides, whose biological activities are without equivalents, and to which there are no homologous sequences in public databases. In this review, we summarize the genetics, biochemistry, biosynthesis, and biological activities of three extensively studied antimicrobial peptides from propionibacteria. The propionicin T1 peptide constitutes a bona fide example of an unmodified general secretory pathway (sec)-dependent bacteriocin, which is bactericidal towards all tested species of propionibacteria except Propionibacterium freudenreichii. The PAMP antimicrobial peptide represents a novel concept within bacterial antagonism, where an inactive precursor protein is secreted in large amounts, and which activation appears to rely on subsequent processing by proteases in its resident milieu. Propionicin F is a negatively charged bacteriocin that displays an intraspecies bactericidal inhibition spectrum. The biosynthesis of propionicin F appears to proceed through a series of unusual events requiring both N- and C-terminal processing of a precursor protein, which probably requires the radical SAM superfamily enzyme PcfB.

Non-plaque-forming virions of Modified Vaccinia virus Ankara express viral genes.

PubMed

Lülf, Anna-Theresa; Freudenstein, Astrid; Marr, Lisa; Sutter, Gerd; Volz, Asisa

2016-12-01

In cell culture infections with vaccinia virus the number of counted virus particles is substantially higher than the number of plaques obtained by titration. We found that standard vaccine preparations of recombinant Modified Vaccinia virus Ankara produce only about 20-30% plaque-forming virions in fully permissive cell cultures. To evaluate the biological activity of the non-plaque-forming particles, we generated recombinant viruses expressing fluorescent reporter proteins under transcriptional control of specific viral early and late promoters. Live cell imaging and automated counting by fluorescent microscopy indicated that virtually all virus particles can enter cells and switch on viral gene expression. Although most of the non-plaque-forming infections are arrested at the level of viral early gene expression, we detected activation of late viral transcription in 10-20% of single infected cells. Thus, non-plaque-forming particles are biologically active, and likely contribute to the immunogenicity of vaccinia virus vaccines. Copyright © 2016 Elsevier Inc. All rights reserved.

Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wehrens, Martijn; Rein ten Wolde, Pieter; Mugler, Andrew, E-mail: amugler@purdue.edu

2014-11-28

Clustering of molecules on biological membranes is a widely observed phenomenon. A key example is the clustering of the oncoprotein Ras, which is known to be important for signal transduction in mammalian cells. Yet, the mechanism by which Ras clusters form and are maintained remains unclear. Recently, it has been discovered that activated Ras promotes further Ras activation. Here we show using particle-based simulation that this positive feedback is sufficient to produce persistent clusters of active Ras molecules at the nanometer scale via a dynamic nucleation mechanism. Furthermore, we find that our cluster statistics are consistent with experimental observations ofmore » the Ras system. Interestingly, we show that our model does not support a Turing regime of macroscopic reaction-diffusion patterning, and therefore that the clustering we observe is a purely stochastic effect, arising from the coupling of positive feedback with the discrete nature of individual molecules. These results underscore the importance of stochastic and dynamic properties of reaction diffusion systems for biological behavior.« less

Computational properties of networks of synchronous groups of spiking neurons.

PubMed

Dayhoff, Judith E

2007-09-01

We demonstrate a model in which synchronously firing ensembles of neurons are networked to produce computational results. Each ensemble is a group of biological integrate-and-fire spiking neurons, with probabilistic interconnections between groups. An analogy is drawn in which each individual processing unit of an artificial neural network corresponds to a neuronal group in a biological model. The activation value of a unit in the artificial neural network corresponds to the fraction of active neurons, synchronously firing, in a biological neuronal group. Weights of the artificial neural network correspond to the product of the interconnection density between groups, the group size of the presynaptic group, and the postsynaptic potential heights in the synchronous group model. All three of these parameters can modulate connection strengths between neuronal groups in the synchronous group models. We give an example of nonlinear classification (XOR) and a function approximation example in which the capability of the artificial neural network can be captured by a neural network model with biological integrate-and-fire neurons configured as a network of synchronously firing ensembles of such neurons. We point out that the general function approximation capability proven for feedforward artificial neural networks appears to be approximated by networks of neuronal groups that fire in synchrony, where the groups comprise integrate-and-fire neurons. We discuss the advantages of this type of model for biological systems, its possible learning mechanisms, and the associated timing relationships.

AID Biology: A pathological and clinical perspective.

PubMed

Choudhary, Meenal; Tamrakar, Anubhav; Singh, Amit Kumar; Jain, Monika; Jaiswal, Ankit; Kodgire, Prashant

2018-01-02

Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs). The beneficial physiological role of AID in antibody diversification is outweighed by its detrimental role in the genesis of several chronic immune diseases, under non-physiological conditions. This review offers a comprehensive and better understanding of AID biology and its pathological aspects, as well as addresses the challenges involved in AID-related cancer therapeutics, based on various recent advances and evidence available in the literature till date. In this article, we discuss ways through which our interpretation of AID biology may reflect upon novel clinical insights, which could be successfully translated into designing clinical trials and improving patient prognosis and disease management.

Preconcentration and solid phase extraction method for the determination of Co, Cu, Ni, Zn and Cd in environmental and biological samples using activated carbon by FAAS.

PubMed

Kiran, K; Suresh Kumar, K; Suvardhan, K; Janardhanam, K; Chiranjeevi, P

2007-08-17

2-{[1-(2-Hydroxynaphthyl) methylidene] amino} benzoic acid (HNMABA) was synthesized for solid phase extraction (SPE) to the determination of Co, Cu, Ni, Zn and Cd in environmental and biological samples by flame atomic absorption spectrophotometry (FAAS). These metals were sorbed as HNMABA complexes on activated carbon (AC) at the pH range of 5.0+/-0.2 and eluted with 6 ml of 1M HNO3 in acetone. The effects of sample volume, eluent volume and recovery have been investigated to enhance the sensitivity and selectivity of proposed method. The effect of interferences on the sorption of metal ions was studied. The concentration of the metal ions detected after preconcentration was in agreement with the added amount. The detection limits for the metals studied were in the range of 0.75-3.82 microg ml(-1). The proposed system produced satisfactory results for the determination of Co, Cu, Ni, Zn and Cd metals in environmental and biological samples.

Smectite clays in Mars soil - Evidence for their presence and role in Viking biology experimental results

NASA Technical Reports Server (NTRS)

Banin, A.; Rishpon, J.

1979-01-01

Evidence for the presence of smectite clays in Martian soils is reviewed and results of experiments with certain active clays simulating the Viking biology experiments are reported. Analyses of Martian soil composition by means of X-ray fluorescence spectrometry and dust storm spectroscopy and Martian geological history strongly suggest the presence of a mixture of weathered ferro-silicate minerals, mainly nontronite and montmorillonite, accompanied by soluble sulphate salts, as major constituents. Samples of montmorillonite and nontronite incubated with (C-14)-formate or the radioactive nutrient medium solution used in the Viking Labeled Release experiment, were found to produce patterns of release of radioactive gas very similar to those observed in the Viking experiments, indicating the iron-catalyzed decomposition of formate as the reaction responsible for the Viking results. The experimental results of Hubbard (1979) simulating the results of the Viking Pyrolytic Release experiment using iron montmorillonites are pointed out, and it is concluded that many of the results of the Viking biology experiments can be explained in terms of the surface activity of smectite clays in catalysis and adsorption.

COMPENSATION FOR VARIABLE INTRINSIC NEURONAL EXCITABILITY BY CIRCUIT-SYNAPTIC INTERACTIONS

PubMed Central

Grashow, Rachel; Brookings, Ted; Marder, Eve

2010-01-01

Recent theoretical and experimental work indicates that neurons tune themselves to maintain target levels of excitation by modulating ion channel expression and synaptic strengths. As a result, functionally equivalent circuits can produce similar activity despite disparate underlying network and cellular properties. To experimentally test the extent to which synaptic and intrinsic conductances can produce target activity in the presence of variability in neuronal intrinsic properties, we used the dynamic clamp to create hybrid two-cell circuits built from four types of stomatogastric (STG) neurons coupled to the same model Morris-Lecar neuron by reciprocal inhibition. We measured six intrinsic properties (input resistance, minimum membrane potential, firing rate in response to +1nA of injected current, slope of the FI curve, spike height and spike voltage threshold) of Dorsal Gastric (DG), Gastric Mill (GM), Lateral Pyloric (LP) and Pyloric Dilator (PD) neurons from male crabs, Cancer borealis. The intrinsic properties varied two to seven-fold in each cell type. We coupled each biological neuron to the Morris-Lecar model with seven different values of inhibitory synaptic conductance, and also used the dynamic clamp to add seven different values of an artificial h-conductance, thus creating 49 different circuits for each biological neuron. Despite the variability in intrinsic excitability, networks formed from each neuron produced similar circuit performance at some values of synaptic and h-conductances. This work experimentally confirms results from previous modeling studies; tuning synaptic and intrinsic conductances can yield similar circuit output from neurons with variable intrinsic excitability. PMID:20610748

Metabolite profiles of Stachybotrys isolates from water-damaged buildings and their induction of inflammatory mediators and cytotoxicity in macrophages.

PubMed

Nielsen, Kristian Fog; Huttunen, Kati; Hyvärinen, Anne; Andersen, Birgitte; Jarvis, Bruce B; Hirvonen, Maija-Riitta

2002-01-01

The metabolite profiles of 20 Stachybotrys spp. isolates from Finnish water-damaged buildings were compared with their biological activities. Effects of purified compounds on cytotoxicity and production of inflammatory mediators such as nitric oxide, IL-6 and TNFalpha in murine RAW264.7 macrophage cells were studied. The 11 isolates belonging to the satratoxin-producing chemotype were highly cytotoxic to the macrophages. The isolates inducing inflammatory mediators all belonged to the atranone-producing chemotype, but pure atranones B, and D did not elicit a response in the bioassay. Altogether, cytotoxicity of Stachybotrys sp. isolates appear to be related to satratoxin production whereas the specific component inducing inflammatory responses in atranone-producing isolates remains obscure.

Robust expression of a bioactive mammalian protein in chlamydomonas chloroplast

DOEpatents

Mayfield, Stephen P.

2010-03-16

Methods and compositions are disclosed to engineer chloroplast comprising heterologous mammalian genes via a direct replacement of chloroplast Photosystem II (PSII) reaction center protein coding regions to achieve expression of recombinant protein above 5% of total protein. When algae is used, algal expressed protein is produced predominantly as a soluble protein where the functional activity of the peptide is intact. As the host algae is edible, production of biologics in this organism for oral delivery or proteins/peptides, especially gut active proteins, without purification is disclosed.

Robust expression of a bioactive mammalian protein in Chlamydomonas chloroplast

DOEpatents

Mayfield, Stephen P

2015-01-13

Methods and compositions are disclosed to engineer chloroplast comprising heterologous mammalian genes via a direct replacement of chloroplast Photosystem II (PSII) reaction center protein coding regions to achieve expression of recombinant protein above 5% of total protein. When algae is used, algal expressed protein is produced predominantly as a soluble protein where the functional activity of the peptide is intact. As the host algae is edible, production of biologics in this organism for oral delivery of proteins/peptides, especially gut active proteins, without purification is disclosed.

Cupping regulates local immunomodulation to activate neural-endocrine-immune worknet.

PubMed

Guo, Yang; Chen, Bo; Wang, Dong-Qiang; Li, Ming-Yue; Lim, Calista Hui-Min; Guo, Yi; Chen, Zelin

2017-08-01

Research on cupping therapy is lacking at home and abroad. However, cupping and acupuncture therapy are both surface stimulation therapies. This paper suggests the mechanism of cupping therapy and proposes that the same mechanism underlies both cupping and acupuncture therapy. The microenvironment is changed when stimulating the surface of the skin, and physical signals transform into biological signals, which also interact with each other in the body. These signalling cascades activate the neuroendocrine-immune system, which produces the therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Soil-free System for Assaying Nematicidal Activity of Chemicals

PubMed Central

Preiser, F. A.; Babu, J. R.; Haidri, A. A.

1981-01-01

A biological assay system for studying the nematicidal activity of chemicals has been devised using a model consisting of cucumber (Cucumis sativus L. cv. Long Marketer) seedlings growing in the diSPo® growth-pouch apparatus. Meloidogyne incognita was used as the test organism. The response was quantified in terms of the numbers of galls produced. Statistical procedures were applied to estimate the ED50 values of currently available nematicides. This system permits accurate quantification of galling and requires much less space and effort than the currently used methods. PMID:19300800

A Soil-free System for Assaying Nematicidal Activity of Chemicals.

PubMed

Preiser, F A; Babu, J R; Haidri, A A

1981-10-01

A biological assay system for studying the nematicidal activity of chemicals has been devised using a model consisting of cucumber (Cucumis sativus L. cv. Long Marketer) seedlings growing in the diSPo(R) growth-pouch apparatus. Meloidogyne incognita was used as the test organism. The response was quantified in terms of the numbers of galls produced. Statistical procedures were applied to estimate the ED(50) values of currently available nematicides. This system permits accurate quantification of galling and requires much less space and effort than the currently used methods.

Synthetic Biology for Specialty Chemicals.

PubMed

Markham, Kelly A; Alper, Hal S

2015-01-01

In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering-for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.

Use of Brevibacillus choshinensis for the production of biologically active brain-derived neurotrophic factor (BDNF).

PubMed

Angart, Phillip A; Carlson, Rebecca J; Thorwall, Sarah; Patrick Walton, S

2017-07-01

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family critical for neuronal cell survival and differentiation, with therapeutic potential for the treatment of neurological disorders and spinal cord injuries. The production of recombinant, bioactive BDNF is not practical in most traditional microbial expression systems because of the inability of the host to correctly form the characteristic cystine-knot fold of BDNF. Here, we investigated Brevibacillus choshinensis as a suitable expression host for bioactive BDNF expression, evaluating the effects of medium type (2SY and TM), temperature (25 and 30 °C), and culture time (48-120 h). Maximal BDNF bioactivity (per unit mass) was observed in cultures grown in 2SY medium at extended times (96 h at 30 °C or >72 h at 25 °C), with resulting bioactivity comparable to that of a commercially available BDNF. For cultures grown in 2SY medium at 25 °C for 72 h, the condition that led to the greatest quantity of biologically active protein in the shortest culture time, we recovered 264 μg/L of BDNF. As with other microbial expression systems, BDNF aggregates did form in all culture conditions, indicating that while we were able to recover biologically active BDNF, further optimization of the expression system could yield still greater quantities of bioactive protein. This study provides confirmation that B. choshinensis is capable of producing biologically active BDNF and that further optimization of culture conditions could prove valuable in increasing BDNF yields.

The effect of glutamate on ghrelin release in mice.

PubMed

Chacrabati, Rakhi; Gong, Zhi; Ikenoya, Chika; Kondo, Daisuke; Zigman, Jeffrey M; Sakai, Takafumi; Sakata, Ichiro

2017-03-01

Ghrelin is abundantly produced in the stomach. Here, we found that glutamate decreased ghrelin expression and release in ghrelin-producing cells, and decreased levels of food intake and plasma acyl-ghrelin in mice. Treatment with siRNA of G protein-coupled receptor, family C, group 5, member B (GPRC5B) in ghrelin-producing cell lines completely blocked the effect of glutamate-induced ghrelin suppression. In addition, glutamate inhibited ghrelin release via the extracellular signal-regulated kinase (ERK) activity pathway, and stimulated CREB2 mRNA expression in ghrelin-producing cell lines. These results suggest that glutamate inhibits ghrelin release via ERK-CREB2 pathway. These results suggest that the GPRC5B-ERK-CREB2 pathway is involved in the inhibition of ghrelin expression and secretion in ghrelin cells. © 2017 International Federation for Cell Biology.

Highly Enantioselective Production of Chiral Secondary Alcohols Using Lactobacillus paracasei BD101 as a New Whole Cell Biocatalyst and Evaluation of Their Antimicrobial Effects.

PubMed

Yılmaz, Durmuşhan; Şahin, Engin; Dertli, Enes

2017-11-01

Chiral secondary alcohols are valuable intermediates for many important enantiopure pharmaceuticals and biologically active molecules. In this work, we studied asymmetric reduction of aromatic ketones to produce the corresponding chiral secondary alcohols using lactic acid bacteria (LAB) as new biocatalysts. Seven LAB strains were screened for their ability to reduce acetophenones to their corresponding alcohols. Among these strains, Lactobacillus paracasei BD101 was found to be the most successful at reducing the ketones to the corresponding alcohols. The reaction conditions were further systematically optimized for this strain and high enantioselectivity (99%) and very good yields were obtained. These secondary alcohols were further tested for their antimicrobial activities against important pathogens and significant levels of antimicrobial activities were observed although these activities were altered depending on the secondary alcohols as well as their enantiomeric properties. The current methodology demonstrates a promising and alternative green approach for the synthesis of chiral secondary alcohols of biological importance in a cheap, mild, and environmentally useful process. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

A Role for History and Philosophy of Biology in Exploring New Questions in Biology

ERIC Educational Resources Information Center

Daggett, Melissa A. F.

2012-01-01

A number of current reports are challenging educators of undergraduate biology students to increase the role, interactions and approaches of other disciplines. The goal stated in these reports is to produce a college graduate with the skills and competencies to solve pressing global problems such as producing ample food, fuels, and making health…

Conformational changes accompany activation of reovirus RNA-dependent RNA transcription

PubMed Central

Mendez, Israel I.; Weiner, Scott G.; She, Yi-Min; Yeager, Mark; Coombs, Kevin M.

2009-01-01

Many critical biologic processes involve dynamic interactions between proteins and nucleic acids. Such dynamic processes are often difficult to delineate by conventional static methods. For example, while a variety of nucleic acid polymerase structures have been determined at atomic resolution, the details of how some multi-protein transcriptase complexes actively produce mRNA, as well as conformational changes associated with activation of such complexes, remain poorly understood. The mammalian reovirus innermost capsid (core) manifests all enzymatic activities necessary to produce mRNA from each of the 10 encased double-stranded RNA genes. We used rapid freezing and electron cryo-microscopy to trap and visualize transcriptionally active reovirus core particles and compared them to inactive core images. Rod-like density centered within actively transcribing core spike channels was attributed to exiting nascent mRNA. Comparative radial density plots of active and inactive core particles identified several structural changes in both internal and external regions of the icosahedral core capsid. Inactive and transcriptionally active cores were partially digested with trypsin and identities of initial tryptic peptides determined by mass spectrometry. Differentially-digested peptides, which also suggest transcription-associated conformational changes, were placed within the known 3-dimensional structures of major core proteins. PMID:18321727

ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense.

PubMed

Monath, Thomas P; Caldwell, Joseph R; Mundt, Wolfgang; Fusco, Joan; Johnson, Casey S; Buller, Mark; Liu, Jian; Gardner, Bridget; Downing, Greg; Blum, Paul S; Kemp, Tracy; Nichols, Richard; Weltzin, Richard

2004-10-01

The threat of smallpox as a biological weapon has spurred efforts to create stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in animal skin (the original method), we cloned vaccinia virus (New York City Board of Health strain, Dryvax by plaque purification and amplified the clone in cell culture. The overarching goal was to produce a modern vaccine that was equivalent to the currently licensed Dryvax in its preclinical and clinical properties, and could thus reliably protect humans against smallpox. A variety of clones were evaluated, and many were unacceptably virulent in animal models. One clonal virus (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid cells. ACAM1000 was comparable to Dryvax in immunogenicity and protective activity but was less neurovirulent for mice and nonhuman primates. To meet requirements for large quantities of vaccine after the events of September 11th 2001, the ACAM1000 master virus seed was used to prepare vaccine (designated ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three Phase 1 clinical trials. The vaccines produced major cutaneous reactions and evoked neutralizing antibody and cell-mediated immune responses in the vast majority of subjects and had a reactogenicity profile similar to that of Dryvax.

Purification and Characterization of Recombinant Darbepoetin Alfa from Leishmania tarentolae.

PubMed

Kianmehr, Anvarsadat; Mahrooz, Abdolkarim; Oladnabi, Morteza; Safdari, Yaghoub; Ansari, Javad; Veisi, Kamal; Evazalipour, Mehdi; Shahbazmohammadi, Hamid; Omidinia, Eskandar

2016-09-01

Darbepoetin alfa is a biopharmaceutical glycoprotein that stimulates erythropoiesis and is used to treat anemia, which associated with renal failure and cancer chemotherapy. We herein describe the structural characterization of recombinant darbepoetin alfa produced by Leishmania tarentolae T7-TR host. The DNA expression cassette was integrated into the L. tarentolae genome through homologous recombination. Transformed clones were selected by antibiotic resistance, diagnostic PCRs, and protein expression analysis. The structure of recombinant darbepoetin alfa was analyzed by isoelectric focusing, ultraviolet-visible spectrum, and circular dichroism (CD) spectroscopy. Expression analysis showed the presence of a protein band at 40 kDa, and its expression level was 51.2 mg/ml of culture medium. Darbepoetin alfa have 5 isoforms with varying degree of sialylation. The UV absorption and CD spectra were analogous to original drug (Aranesp), which confirmed that the produced protein was darbepoetin alfa. Potency test results revealed that the purified protein was biologically active. In brief, the structural and biological characteristics of expressed darbepoetin alfa were very similar to Aranesp which has been normally expressed in CHO. Our data also suggest that produced protein has potential to be developed for clinical use.

Extracellular Vesicles Produced by the Gram-positive Bacterium Bacillus subtilis are Disrupted by the Lipopeptide Surfactin

PubMed Central

Brown, Lisa; Kessler, Anne; Cabezas-Sanchez, Pablo; Luque-Garcia, Jose L.; Casadevall, Arturo

2014-01-01

Summary Previously, extracellular vesicle production in Gram-positive bacteria was dismissed due to the absence of an outer membrane, where Gram-negative vesicles originate, and the difficulty in envisioning how such a process could occur through the cell wall. However, recent work has shown that Gram-positive bacteria produce extracellular vesicles and that the vesicles are biologically active. In this study, we show that Bacillus subtilis produces extracellular vesicles similar in size and morphology to other bacteria, characterized vesicles using a variety of techniques, provide evidence that these vesicles are actively produced by cells, show differences in vesicle production between strains, and identified a mechanism for such differences based on vesicle disruption. We found that in wild strains of B. subtilis, surfactin disrupted vesicles while in laboratory strains harboring a mutation in the gene sfp, vesicles accumulated in the culture supernatant. Surfactin not only lysed B. subtilis vesicles, but also vesicles from Bacillus anthracis, indicating a mechanism that crossed species boundaries. To our knowledge, this is the first time a gene and a mechanism has been identified in the active disruption of extracellular vesicles and subsequent release of vesicular cargo in Gram-positive bacteria. We also identify a new mechanism of action for surfactin. PMID:24826903

Structural data and immunomodulatory properties of a water-soluble heteroglycan extracted from the mycelium of an Italian isolate of Ganoderma lucidum.

PubMed

Carrieri, Raffaele; Manco, Rosanna; Sapio, Daniela; Iannaccone, Marco; Fulgione, Andrea; Papaianni, Marina; de Falco, Bruna; Grauso, Laura; Tarantino, Paola; Ianniello, Flora; Lanzotti, Virginia; Lahoz, Ernesto; Capparelli, Rosanna

2017-09-01

Mushrooms produce a wide range of bioactive polysaccharides, different from each other in chemical structure and biological effects. In the last years, the idea to develop functional foods or drugs containing fungal polysaccharides is attracting great attention. Fruiting bodies of Basidiomycetes Ganoderma lucidum are commonly used in Oriental medicine to treat several disorders. G. lucidum polysaccharides - mainly β-glucans and heteroglycans - have numerous biological properties such as antitumour and immunomodulatory activities. This report shows, by gene expression analyses and bioenergetic assays, immunomodulatory properties and capacity to improve glucose metabolism of a water-soluble heteroglycan extracted from mycelium of an Italian isolate of G. lucidum. The findings suggest the use of the heteroglycan as probiotic or ingredient in functional foods, being easy to produce and disperse in a food matrix thanks to its water-solubility. Heteroglycan could exert protective effects in pro-inflammatory conditions and benefits for people characterised by suppressed immune response.

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides

PubMed Central

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-01-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. PMID:26747427

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

PubMed

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-05-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. © The Author 2016. Published by Oxford University Press.

Sensitive and quantitative detection of botulinum neurotoxin in neurons derived from mouse embryonic stem cells.

PubMed

Pellett, Sabine; Du, Zhong-wei; Pier, Christina L; Tepp, William H; Zhang, Su-chun; Johnson, Eric A

2011-01-07

Botulinum neurotoxins (BoNTs), the most poisonous protein toxins known, represent a serious bioterrorism threat but are also used as a unique and important bio-pharmaceutical to treat an increasing myriad of neurological disorders. The only currently accepted detection method by the United States Food and Drug Administration for biological activity of BoNTs and for potency determination of pharmaceutical preparations is the mouse bioassay (MBA). Recent advances have indicated that cell-based assays using primary neuronal cells can provide an equally sensitive and robust detection platform as the MBA to reliably and quantitatively detect biologically active BoNTs. This study reports for the first time a BoNT detection assay using mouse embryonic stem cells to produce a neuronal cell culture. The data presented indicate that this assay can reliably detect BoNT/A with a similar sensitivity as the MBA. Published by Elsevier Inc.

Preliminary environmental analysis of a geopressured-geothermal test well in Brazoria County, Texas

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, W.A.; McGraw, M.; Gustavson, T.C.

1977-11-16

Preliminary environmental data, including current land use, substrate lithology, soils, natural hazards, water resources, biological assemblages, meteorological data, and regulatory considerations have been collected and analyzed for approximately 150 km/sup 2/ of land near Chocolate Bayou, Brazoria County, Texas, in which a geopressured-geothermal test well is to be drilled in the fall of 1977. The study was designed to establish an environmental data base and to determine, within spatial constraints set by subsurface reservoir conditions, environmentally suitable sites for the proposed well. Preliminary analyses of data revealed the eed for focusing on the following areas: potential for subsidence and faultmore » activation, susceptibility of test well and support facilities to fresh- and salt-water flooding, possible effects of produced saline waters on biological assemblages and groundwaer resources, distribution of expansive soils, and effect of drilling and associated support activities on known archeological-cultural resources.« less

Physangulidine A, a withanolide from Physalis angulata, perturbs the cell cycle and induces cell death by apoptosis in prostate cancer cells.

PubMed

Reyes-Reyes, E Merit; Jin, Zhuang; Vaisberg, Abraham J; Hammond, Gerald B; Bates, Paula J

2013-01-25

Recently, our group reported the discovery of three new withanolides, physangulidines A-C, from Physalis angulata. In this study, the biological effects of physangulidine A (1), which was the most active and abundant of the three new constituents, are described. It was found that 1 significantly reduces survival in clonogenic assays for two hormone-independent prostate cancer cell lines. Flow cytometry and confocal microscopy studies in DU145 human prostate cancer cells indicated that 1 induces cell cycle arrest in the G(2)/M phase and causes defective mitosis. It was determined also that 1 produces programed cell death by apoptosis, as evidenced by biochemical markers and distinct changes in cell morphology. These results imply that the antimitotic and proapoptotic effects of 1 may contribute significantly to the biological activities and potential medicinal properties of its plant of origin.

Influence of culture medium growth variables on Ganoderma lucidum exopolysaccharides structural features.

PubMed

Fraga, Irene; Coutinho, João; Bezerra, Rui M; Dias, Albino A; Marques, Guilhermina; Nunes, Fernando M

2014-10-13

In this work the effect of carbon and nitrogen levels and initial pH of the wheat extract culture medium of submerged culture of Ganoderma lucidum on the amount, purity and structural features of exopolysaccharides (EPS) were studied. A low peptone level (1.65 g L(-1)) favored mycelium biomass, EPS purity, but a higher supply of peptone (4.80 g L(-1)) is needed for maximum EPS production. The carbohydrate composition of the EPS and structural features also changed significantly according to the different growing conditions, being observed significant differences in the (1 → 3)/(1 → 4)-Glcp ratio and also on the branching degree of EPS. As the biological activities of EPS are highly dependent on the polysaccharide structural features, this variability can have implications on the EPS biological activities, but can also be used advantageously to produce tailor made polysaccharides with specific applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Artificial transmembrane ion channels from self-assembling peptide nanotubes

NASA Astrophysics Data System (ADS)

Ghadiri, M. Reza; Granja, Juan R.; Buehler, Lukas K.

1994-05-01

NATURALLY occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and organic secon-dary metabolites whose vital biological functions include control of ion flow, signal transduction, molecular transport and produc-tion of cellular toxins. But despite the availability of a large amount of biochemical information about these molecules1, the design and synthesis of artificial systems that can mimic the bio-logical function of natural compounds remains a formidable task2-12. Here we present a simple strategy for the design of artifi-cial membrane ion channels based on a self-assembled cylindrical β-sheet peptide architecture13. Our systems-essentially stacks of peptide rings-display good channel-mediated ion-transport activ-ity with rates exceeding 107 ions s-1, rivalling the performance of many naturally occurring counterparts. Such molecular assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.

Induced Fit in Protein Multimerization: The HFBI Case

PubMed Central

Riccardi, Laura

2016-01-01

Hydrophobins, produced by filamentous fungi, are small amphipathic proteins whose biological functions rely on their unique surface-activity properties. Understanding the mechanistic details of the multimerization process is of primary importance to clarify the interfacial activity of hydrophobins. We used free energy calculations to study the role of a flexible β-hairpin in the multimerization process in hydrophobin II from Trichoderma reesei (HFBI). We characterized how the displacement of this β-hairpin controls the stability of the monomers/dimers/tetramers in solution. The regulation of the oligomerization equilibrium of HFBI will necessarily affect its interfacial properties, fundamental for its biological function and for technological applications. Moreover, we propose possible routes for the multimerization process of HFBI in solution. This is the first case where a mechanism by which a flexible loop flanking a rigid patch controls the protein-protein binding equilibrium, already known for proteins with charged binding hot-spots, is described within a hydrophobic patch. PMID:27832079

New Method for Producing Significant Amounts of RNA Labeled at Specific Sites | Center for Cancer Research

Cancer.gov

Among biomacromolecules, RNA is the most versatile, and it plays indispensable roles in almost all aspects of biology. For example, in addition to serving as mRNAs coding for proteins, RNAs regulate gene expression, such as controlling where, when, and how efficiently a gene gets expressed, participate in RNA processing, encode the genetic information of some viruses, serve as scaffolds, and even possess enzymatic activity. To study these RNAs and their biological functions and to make use of those RNA activities for biomedical applications, researchers first need to make various types of RNA. For structural biologists incorporating modified or labeled nucleotides at specific sites in RNA molecules of interest is critical to gain structural insight into RNA functions. However, placing labeled or modified residue(s) in desired positions in a large RNA has not been possible until now.

Dearomative dihydroxylation with arenophiles

NASA Astrophysics Data System (ADS)

Southgate, Emma H.; Pospech, Jola; Fu, Junkai; Holycross, Daniel R.; Sarlah, David

2016-10-01

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N-N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

Aromatic Medicinal Plants of the Lamiaceae Family from Uzbekistan: Ethnopharmacology, Essential Oils Composition, and Biological Activities

PubMed Central

Mamadalieva, Nilufar Z.; Akramov, Davlat Kh.; Ovidi, Elisa; Tiezzi, Antonio; Nahar, Lutfun; Azimova, Shahnoz S.; Sarker, Satyajit D.

2017-01-01

Plants of the Lamiaceae family are important ornamental, medicinal, and aromatic plants, many of which produce essential oils that are used in traditional and modern medicine, and in the food, cosmetics, and pharmaceutical industry. Various species of the genera Hyssopus, Leonurus, Mentha, Nepeta, Origanum, Perovskia, Phlomis, Salvia, Scutellaria, and Ziziphora are widespread throughout the world, are the most popular plants in Uzbek traditional remedies, and are often used for the treatment of wounds, gastritis, infections, dermatitis, bronchitis, and inflammation. Extensive studies of the chemical components of these plants have led to the identification of many compounds, as well as essentials oils, with medicinal and other commercial values. The purpose of this review is to provide a critical overview of the literature surrounding the traditional uses, ethnopharmacology, biological activities, and essential oils composition of aromatic plants of the family Lamiaceae, from the Uzbek flora. PMID:28930224

The role of exoproteases in governing intraneuronal metabolism of botulinum toxin.

PubMed

Simpson, Lance L; Maksymowych, Andrew B; Kouguchi, Hirokazu; Dubois, Garrett; Bora, Roop S; Joshi, Suresh

2005-04-01

Botulinum toxin type A has a long duration of action, and thus it can block transmitter release for several weeks to several months. However, little is known about the precise mechanism that accounts for termination of toxin action. Therefore, experiments were done to gauge the effects of aminopeptidases and carboxypeptidases on the structure and function of the toxin. Exoproteases were added to the holotoxin, the native light chain, and a recombinant light chain. Treated toxin and light chain were examined for their effects on neuromuscular transmission and on isolated substrate. The data showed that aminopeptidase attack did not alter the N-terminus of the toxin/light chain, nor did it produce losses in biological activity. Carboxypeptidase attack did alter the C-terminus of the light chain, but not sufficiently to alter biological activity. The data suggest that the tertiary structure of the light chain confers upon the molecule substantial resistance to exoproteases.

Introduction: the plurality of modeling.

PubMed

Huneman, Philippe; Lemoine, Maël

2014-08-01

Philosophers of science have recently focused on the scientific activity of modeling phenomena, and explicated several of its properties, as well as the activities embedded into it. A first approach to modeling has been elaborated in terms of representing a target system: yet other epistemic functions, such as producing data or detecting phenomena, are at least as relevant. Additional useful distinctions have emerged, such as the one between phenomenological and mechanistic models. In biological sciences, besides mathematical models, models now come in three forms: in vivo, in vitro and in silico. Each has been investigated separately, and many specific problems they raised have been laid out. Another relevant distinction is disciplinary: do models differ in significant ways according to the discipline involved-medicine or biology, evolutionary biology or earth science? Focusing on either this threefold distinction or the disciplinary boundaries reveals that they might not be sufficient from a philosophical perspective. On the contrary, focusing on the interaction between these various kinds of models, some interesting forms of explanation come to the fore, as is exemplified by the papers included in this issue. On the other hand, a focus on the use of models, rather than on their content, shows that the distinction between biological and medical models is theoretically sound.

Recent advances in food biopeptides: production, biological functionalities and therapeutic applications.

PubMed

Saadi, Sami; Saari, Nazamid; Anwar, Farooq; Abdul Hamid, Azizah; Ghazali, Hasanah Mohd

2015-01-01

The growing momentum of several common life-style diseases such as myocardial infarction, cardiovascular disorders, stroke, hypertension, diabetes, and atherosclerosis has become a serious global concern. Recent developments in the field of proteomics offering promising solutions to solving such health problems stimulates the uses of biopeptides as one of the therapeutic agents to alleviate disease-related risk factors. Functional peptides are typically produced from protein via enzymatic hydrolysis under in vitro or in vivo conditions using different kinds of proteolytic enzymes. An array of biological activities, including antioxidative, antihypertensive, antidiabetic and immunomodulating has been ascribed to different types of biopeptides derived from various food sources. In fact, biopeptides are nutritionally and functionally important for regulating some physiological functions in the body; however, these are yet to be extensively addressed with regard to their production through advance strategies, mechanisms of action and multiple biological functionalities. This review mainly focuses on recent biotechnological advances that are being made in the field of production in addition to covering the mode of action and biological activities, medicinal health functions and therapeutic applications of biopeptides. State-of-the-art strategies that can ameliorate the efficacy, bioavailability, and functionality of biopeptides along with their future prospects are likewise discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Biological Targets and Mechanisms of Action of Natural Products from Marine Cyanobacteria

PubMed Central

Salvador-Reyes, Lilibeth A.

2015-01-01

Marine cyanobacteria are an ancient group of organisms and prolific producers of bioactive secondary metabolites. These compounds are presumably optimized by evolution over billions of years to exert high affinity for their intended biological target in the ecologically relevant organism but likely also possess activity in different biological contexts such as human cells. Screening of marine cyanobacterial extracts for bioactive natural products has largely focused on cancer cell viability; however, diversification of the screening platform led to the characterization of many new bioactive compounds. Targets of compounds have oftentimes been elusive if the compounds were discovered through phenotypic assays. Over the past few years, technology has advanced to determine mechanism of action (MOA) and targets through reverse chemical genetic and proteomic approaches, which has been applied to certain cyanobacterial compounds and will be discussed in this review. Some cyanobacterial molecules are the most-potent-in-class inhibitors and therefore may become valuable tools for chemical biology to probe protein function but also be templates for novel drugs, assuming in vitro potency translates into cellular and in vivo activity. Our review will focus on compounds for which the direct targets have been deciphered or which were found to target a novel pathway, and link them to disease states where target modulation may be beneficial. PMID:25571978

Synergistic Synthetic Biology: Units in Concert

PubMed Central

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert.

PubMed

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Predicting Corticosteroid-Free Biologic Remission with Vedolizumab in Crohn's Disease.

PubMed

Waljee, Akbar K; Liu, Boang; Sauder, Kay; Zhu, Ji; Govani, Shail M; Stidham, Ryan W; Higgins, Peter D R

2018-05-18

Vedolizumab (VDZ) is effective for Crohn's disease (CD) but costly and is slow to produce remission. Early knowledge of whether vedolizumab is likely to succeed is valuable for physicians, patients, and insurers. Phase 3 clinical trial data on VZD for CD were used to predict outcomes. Random forest modeling on the training cohort was used to predict the outcome of corticosteroid-free biologic remission at week 52 on the testing cohort. Models were constructed using baseline data, or data through week 6 of VDZ therapy. The clinical trial included 594 subjects who received VDZ with baseline active inflammation [elevated C-reactive protein (>5 mg/L)]. Subjects with missing predictor variables (N = 120) or missing outcome data (N = 2) were excluded to produce a modeling dataset of 472 subjects. The Area Under the Receiver Operating Characteristic curve (AuROC) for corticosteroid-free biologic remission at week 52 using baseline data was only 0.65 (95% CI: 0.53 - 0.77), but was 0.75 (95% CI: 0.64 - 0.86) with data through week 6 of VDZ . Patients predicted to be in corticosteroid-free biologic remission at week 52 by the model achieved this endpoint 35.8% of the time, whereas patients predicted to fail only succeeded 6.7% of the time. An algorithm using laboratory data through week 6 of VDZ therapy was able to identify which CD patients with baseline inflammation would achieve corticosteroid-free biologic remission on VDZ at week 52. A majority of patients can be identified by week 6 as very unlikely to achieve remission.

42 CFR 7.2 - Establishment of a user charge.

Code of Federal Regulations, 2010 CFR

2010-10-01

... DISTRIBUTION OF REFERENCE BIOLOGICAL STANDARDS AND BIOLOGICAL PREPARATIONS § 7.2 Establishment of a user charge... producing and distributing reference biological standards and biological preparations. ...

Competitive helping increases with the size of biological markets and invades defection.

PubMed

Barclay, Pat

2011-07-21

Cooperation between unrelated individuals remains a puzzle in evolutionary biology. Recent work indicates that partner choice can select for high levels of helping. More generally, helping can be seen as but one strategy used to compete for partners within a broader biological market, yet giving within such markets has received little mathematical investigation. In the present model, individuals help others to attract attention from them and thus receive a larger share of any help actively or passively provided by those others. The evolutionarily stable level of helping increases with the size of the biological market and the degree of partner choice. Furthermore, if individuals passively produce some no-cost help to partners, competitive helping can then invade populations of non-helpers because helpers directly benefit from increasing their access to potential partners. This framework of competitive helping demonstrates how high helping can be achieved and why different populations may differ in helping levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

On the structural affinity of macromolecules with different biological properties: molecular dynamics simulations of a series of TEM-1 mutants.

PubMed

Giampaolo, Alessia Di; Mazza, Fernando; Daidone, Isabella; Amicosante, Gianfranco; Perilli, Mariagrazia; Aschi, Massimiliano

2013-07-12

Molecular Dynamics simulations have been carried out in order to provide a molecular rationalization of the biological and thermodynamic differences observed for a class of TEM β-lactamases. In particular we have considered the TEM-1(wt), the single point mutants TEM-40 and TEM-19 representative of IRT and ESBL classes respectively, and TEM-1 mutant M182T, TEM-32 and TEM-20 which differ from the first three for the additional of M182T mutation. Results indicate that most of the thermodynamic, and probably biological behaviour of these systems arise from subtle effects which, starting from the alterations of the local interactions, produce drastic modifications of the conformational space spanned by the enzymes. The present study suggests that systems showing essentially the same secondary and tertiary structure may differentiate their chemical-biological activity essentially (and probably exclusively) on the basis of the thermal fluctuations occurring in their physiological environment. Copyright © 2013 Elsevier Inc. All rights reserved.

Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases

PubMed Central

Gul, Waseem; Hamann, Mark T.

2016-01-01

The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities. PMID:16236327

[Regulation of the neuronal functional state by ultra low doses of different biologically active substances. Nonspecific effect ].

PubMed

Terekhova, S F; Grechenko, T N

2003-01-01

The role of biologically active substances in ultra-low doses (10(-15)-10(-27) mol/l) is discussed from the different points of view. The most detailed analysis of neurobiological effects produced by these doses can be studied on the preparate of completely isolated molluscan neurones. In this case the possibility arises to control the first modifications of action at the electrophysiological characteristics of neuronal activity. These changes of electrical activity can be regarded as a reaction to biologically active substance. The following characteristics were controlled: the level of membrane resting potential (MP), the electroexcitable membrane and pacemaker mechanism, chemical sensitivity of somatic membrane loci to neurotransmitter acetylcholine (Ach). Several substances were used in these experiments: two kinds of synthetic antioxidant, GABA, ethanol, serotonine, DSIP (delta-sleep inducing peptide), antibiotic ruboxil, nootrop GVS-111. The isolated neurones were placed into the special chamber. All these substances (0.35 ml) were added single dosing into this chamber with living physiological solution in concentration 10(-15)-10(-27) mol/l. The results demonstrated that all substances had initiated the development of prolonged neurophysiological responses. The intensities of neuronal reactions didn't depend in contact period on the concentration and on the type of substance. It is suggested that these data reveal the existence of unknown modes of regulation of neuronal functional states and presence of hidden channel for information transfer and receiving. This different way of regulation is extremely important influence living organisms.

Soluble microbial products (SMPs) release in activated sludge systems: a review

PubMed Central

2012-01-01

This review discusses the characterization, production and implications of soluble microbial products (SMPs) in biological wastewater treatment. The precise definition of SMPs is open to talk about, but is currently regarded as “the pool of organic compounds that are released into solution from substrate metabolism and biomass decay”'. Some of the SMPs have been identified as humic acids, polysaccharides, proteins, amino acids, antibiotics, extracellular enzymes and structural components of cells and products of energy metabolism. They adversely affect the kinetic activity, flocculating and settling properties of sludge. This review outlines some important findings with regard to biodegradability and treatability of SMPs and also the effect of process parameters on their production. As SMPs are produced during biological treatment process, their trace amounts normally remain in the effluent that defines the highest COD removal efficiency. Their presence in effluent represents a high potential risk of toxic by-product formation during chlorine disinfection. Studies have indicated that among all wastewater post-treatment processes, the adsorption by granular activated carbon combined with biologically induced degradation is the most effective method for removal of SMPs. However, it may be concludes that the knowledge regarding SMPs is still under progress and more work is required to fully understand their contribution to the treatment process. PMID:23369231

Inhibition of biological activity of staphylococcal enterotoxin A (SEA) by apple juice and apple polyphenols.

PubMed

Rasooly, Reuven; Do, Paula M; Friedman, Mendel

2010-05-12

The foodborne pathogen Staphylococcus aureus produces the virulent staphylococcal enterotoxin A (SEA), a single-chain protein that consists of 233 amino acid residues with a molecular weight of 27 078 Da. SEA is a superantigen that is reported to contribute to animal (mastitis) and human (emesis, diarrhea, atopic dermatitis, arthritis, and toxic shock) syndromes. Changes of the native structural integrity may inactivate the toxin by preventing molecular interaction with cell membrane receptor sites of their host cells. In the present study, we evaluated the ability of one commercial and two freshly prepared apple juices and a commercial apple polyphenol preparation (Apple Poly) to inhibit the biological activity of SEA. Dilutions of freshly prepared apple juices and Apple Poly inhibited the biological activity of SEA without any significant cytotoxic effect on the spleen cells. Additional studies with antibody-coated immunomagnetic beads bearing specific antibodies against the toxin revealed that SEA added to apple juice appears to be largely irreversibly bound to the juice constituents. The results suggest that food-compatible and safe anti-toxin phenolic compounds can be used to inactivate SEA in vitro and possibly also in vivo, even after induction of T-cell proliferation by long-term exposure to SEA. The significance of the results for microbial food safety and human health is discussed.

Soluble microbial products (SMPs) release in activated sludge systems: a review.

PubMed

Azami, Hamed; Sarrafzadeh, Mohammad Hossein; Mehrnia, Mohammad Reza

2012-12-18

This review discusses the characterization, production and implications of soluble microbial products (SMPs) in biological wastewater treatment. The precise definition of SMPs is open to talk about, but is currently regarded as "the pool of organic compounds that are released into solution from substrate metabolism and biomass decay"'. Some of the SMPs have been identified as humic acids, polysaccharides, proteins, amino acids, antibiotics, extracellular enzymes and structural components of cells and products of energy metabolism. They adversely affect the kinetic activity, flocculating and settling properties of sludge. This review outlines some important findings with regard to biodegradability and treatability of SMPs and also the effect of process parameters on their production. As SMPs are produced during biological treatment process, their trace amounts normally remain in the effluent that defines the highest COD removal efficiency. Their presence in effluent represents a high potential risk of toxic by-product formation during chlorine disinfection. Studies have indicated that among all wastewater post-treatment processes, the adsorption by granular activated carbon combined with biologically induced degradation is the most effective method for removal of SMPs. However, it may be concludes that the knowledge regarding SMPs is still under progress and more work is required to fully understand their contribution to the treatment process.

Stable heterologous expression of biologically active terpenoids in green plant cells

PubMed Central

Ikram, N. Kusaira B. K.; Zhan, Xin; Pan, Xi-Wu; King, Brian C.; Simonsen, Henrik T.

2015-01-01

Plants biosynthesize a great diversity of biologically active small molecules of interest for fragrances, flavors, and pharmaceuticals. Among specialized metabolites, terpenoids represent the greatest molecular diversity. Many terpenoids are very complex, and total chemical synthesis often requires many steps and difficult chemical reactions, resulting in a low final yield or incorrect stereochemistry. Several drug candidates with terpene skeletons are difficult to obtain by chemical synthesis due to their large number of chiral centers. Thus, biological production remains the preferred method for industrial production for many of these compounds. However, because these chemicals are often found in low abundance in the native plant, or are produced in plants which are difficult to cultivate, there is great interest in engineering increased production or expression of the biosynthetic pathways in heterologous hosts. Although there are many examples of successful engineering of microbes such as yeast or bacteria to produce these compounds, this often requires extensive changes to the host organism's metabolism. Optimization of plant gene expression, post-translational protein modifications, subcellular localization, and other factors often present challenges. To address the future demand for natural products used as drugs, new platforms are being established that are better suited for heterologous production of plant metabolites. Specifically, direct metabolic engineering of plants can provide effective heterologous expression for production of valuable plant-derived natural products. In this review, our primary focus is on small terpenoids and we discuss the benefits of plant expression platforms and provide several successful examples of stable production of small terpenoids in plants. PMID:25852702

[Medical and biologic aspects of regulation and evaluation of microclimate: results and prospects of further studies].

PubMed

Afanas'eva, R F

2008-01-01

The article deals with basic points concerning influence of microclimate on humans and tasks of its regulation in contemporary conditions. The authors described universality of microclimate from viewpoint of producing functional state and health state of human, so microclimate should be assessed consistently and systematically through all aspects of its influence, with complex approach to evaluation (clothing, physical activity, etc.).

Evaluation of acute ecotoxicity removal from industrial wastewater using a battery of rapid bioassays.

PubMed

Dries, Jan; Daens, Dominique; Geuens, Luc; Blust, Ronny

2014-01-01

The present study compares conventional wastewater treatment technologies (coagulation-flocculation and activated sludge) and powdered activated carbon (PAC) treatment for the removal of acute ecotoxicity from wastewater generated by tank truck cleaning (TTC) processes. Ecotoxicity was assessed with a battery of four commercially available rapid biological toxicity testing systems, verified by the US Environmental Protection Agency. Chemical coagulation-flocculation of raw TTC wastewater had no impact on the inhibition of the bioluminescence by Vibrio fischeri (BioTox assay). Subsequent biological treatment with activated sludge without PAC resulted in BioTox inhibition-free effluent (<10% inhibition). In contrast, activated sludge treatment without PAC produced an effluent that significantly inhibited (>50%) (i) the bioluminescence by Photobacterium leiognathi (ToxScreen³ test kit), (ii) the photosynthesis by the green algae Chlorella vulgaris (LuminoTox SAPS test kit), and (iii) the particle ingestion by the crustacean Thamnocephalus platyurus (Rapidtoxkit test kit). The lowest inhibition was measured after activated sludge treatment with the highest PAC dose (400 mg/L), demonstrating the effectiveness of PAC treatment for ecotoxicity removal from TTC wastewater. In conclusion, the combination of bioassays applied in the present study represents a promising test battery for rapid ecotoxicty assessment in wastewater treatment.

Electrically active bioceramics: a review of interfacial responses.

PubMed

Baxter, F R; Bowen, C R; Turner, I G; Dent, A C E

2010-06-01

Electrical potentials in mechanically loaded bone have been implicated as signals in the bone remodeling cycle. Recently, interest has grown in exploiting this phenomenon to develop electrically active ceramics for implantation in hard tissue which may induce improved biological responses. Both polarized hydroxyapatite (HA), whose surface charge is not dependent on loading, and piezoelectric ceramics, which produce electrical potentials under stress, have been studied in order to determine the possible benefits of using electrically active bioceramics as implant materials. The polarization of HA has a positive influence on interfacial responses to the ceramic. In vivo studies of polarized HA have shown polarized samples to induce improvements in bone ingrowth. The majority of piezoelectric ceramics proposed for implant use contain barium titanate (BaTiO(3)). In vivo and in vitro investigations have indicated that such ceramics are biocompatible and, under appropriate mechanical loading, induce improved bone formation around implants. The mechanism by which electrical activity influences biological responses is yet to be clearly defined, but is likely to result from preferential adsorption of proteins and ions onto the polarized surface. Further investigation is warranted into the use of electrically active ceramics as the indications are that they have benefits over existing implant materials.

Ionic Strength Is a Barrier to the Habitability of Mars.

PubMed

Fox-Powell, Mark G; Hallsworth, John E; Cousins, Claire R; Cockell, Charles S

2016-06-01

The thermodynamic availability of water (water activity) strictly limits microbial propagation on Earth, particularly in hypersaline environments. A considerable body of evidence indicates the existence of hypersaline surface waters throughout the history of Mars; therefore it is assumed that, as on Earth, water activity is a major limiting factor for martian habitability. However, the differing geological histories of Earth and Mars have driven variations in their respective aqueous geochemistry, with as-yet-unknown implications for habitability. Using a microbial community enrichment approach, we investigated microbial habitability for a suite of simulated martian brines. While the habitability of some martian brines was consistent with predictions made from water activity, others were uninhabitable even when the water activity was biologically permissive. We demonstrate experimentally that high ionic strength, driven to extremes on Mars by the ubiquitous occurrence of multivalent ions, renders these environments uninhabitable despite the presence of biologically available water. These findings show how the respective geological histories of Earth and Mars, which have produced differences in the planets' dominant water chemistries, have resulted in different physicochemical extremes which define the boundary space for microbial habitability. Habitability-Mars-Salts-Water activity-Life in extreme environments. Astrobiology 16, 427-442.

Some biological activities of pigments extracted from Micrococcus roseus (PTCC 1411) and Rhodotorula glutinis (PTCC 5257).

PubMed

Rostami, Hossein; Hamedi, Hassan; Yolmeh, Mahmoud

2016-12-01

The importance of replacing synthetic pigments with natural types is increasing day by day in the food industry due to the harmful effects of some synthetic pigments. Microorganisms are a major source of natural pigments, which nowadays have attracted the attention of researchers. In this study, carotenoid pigments were produced by Micrococcus roseus and Rhodotorula glutinis, and some of their biological properties such as antimicrobial, antioxidant, anticancer, and anti-inflammatory activities were evaluated. Given the results, bacteria, especially gram-positive bacteria, had higher sensitivity to the pigments extracted from M. roseus (PEM) and R. glutinis (PER) compared to molds so that Bacillus cereus and Alternaria citri had the highest and the lowest sensitivity, respectively. PER showed a higher antioxidant activity compared with PEM in the various methods of measuring antioxidant activity. In vitro and in vivo anti-tumor-promoting activities of PER were measured significantly more than PEM (P <0.05). Both pigment extracts remarkably inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, so that ID 50 (50% inhibitory dose) of PEM and PER were 0.22 and 0.09 mg/ear, respectively. © The Author(s) 2016.

Some biological activities of pigments extracted from Micrococcus roseus (PTCC 1411) and Rhodotorula glutinis (PTCC 5257)

PubMed Central

Rostami, Hossein; Hamedi, Hassan; Yolmeh, Mahmoud

2016-01-01

The importance of replacing synthetic pigments with natural types is increasing day by day in the food industry due to the harmful effects of some synthetic pigments. Microorganisms are a major source of natural pigments, which nowadays have attracted the attention of researchers. In this study, carotenoid pigments were produced by Micrococcus roseus and Rhodotorula glutinis, and some of their biological properties such as antimicrobial, antioxidant, anticancer, and anti-inflammatory activities were evaluated. Given the results, bacteria, especially gram-positive bacteria, had higher sensitivity to the pigments extracted from M. roseus (PEM) and R. glutinis (PER) compared to molds so that Bacillus cereus and Alternaria citri had the highest and the lowest sensitivity, respectively. PER showed a higher antioxidant activity compared with PEM in the various methods of measuring antioxidant activity. In vitro and in vivo anti-tumor-promoting activities of PER were measured significantly more than PEM (P <0.05). Both pigment extracts remarkably inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, so that ID50 (50% inhibitory dose) of PEM and PER were 0.22 and 0.09 mg/ear, respectively. PMID:27895288

Allergens/Antigens, toxins and polyketides of important Aspergillus species.

PubMed

Bhetariya, Preetida J; Madan, Taruna; Basir, Seemi Farhat; Varma, Anupam; Usha, Sarma P

2011-04-01

The medical, agricultural and biotechnological importance of the primitive eukaryotic microorganisms, the Fungi was recognized way back in 1920. Among various groups of fungi, the Aspergillus species are studied in great detail using advances in genomics and proteomics to unravel biological and molecular mechanisms in these fungi. Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Aspergillus nidulans and Aspergillus terreus are some of the important species relevant to human, agricultural and biotechnological applications. The potential of Aspergillus species to produce highly diversified complex biomolecules such as multifunctional proteins (allergens, antigens, enzymes) and polyketides is fascinating and demands greater insight into the understanding of these fungal species for application to human health. Recently a regulator gene for secondary metabolites, LaeA has been identified. Gene mining based on LaeA has facilitated new metabolites with antimicrobial activity such as emericellamides and antitumor activity such as terrequinone A from A. nidulans. Immunoproteomic approach was reported for identification of few novel allergens for A. fumigatus. In this context, the review is focused on recent developments in allergens, antigens, structural and functional diversity of the polyketide synthases that produce polyketides of pharmaceutical and biological importance. Possible antifungal drug targets for development of effective antifungal drugs and new strategies for development of molecular diagnostics are considered.

Multifunctional properties of phosphate-solubilizing microorganisms grown on agro-industrial wastes in fermentation and soil conditions.

PubMed

Vassileva, Maria; Serrano, Mercedes; Bravo, Vicente; Jurado, Encarnación; Nikolaeva, Iana; Martos, Vanessa; Vassilev, Nikolay

2010-02-01

One of the most studied approaches in solubilization of insoluble phosphates is the biological treatment of rock phosphates. In recent years, various techniques for rock phosphate solubilization have been proposed, with increasing emphasis on application of P-solubilizing microorganisms. The P-solubilizing activity is determined by the microbial biochemical ability to produce and release metabolites with metal-chelating functions. In a number of studies, we have shown that agro-industrial wastes can be efficiently used as substrates in solubilization of phosphate rocks. These processes were carried out employing various technologies including solid-state and submerged fermentations including immobilized cells. The review paper deals critically with several novel trends in exploring various properties of the above microbial/agro-wastes/rock phosphate systems. The major idea is to describe how a single P-solubilizing microorganism manifests wide range of metabolic abilities in different environments. In fermentation conditions, P-solubilizing microorganisms were found to produce various enzymes, siderophores, and plant hormones. Further introduction of the resulting biotechnological products into soil-plant systems resulted in significantly higher plant growth, enhanced soil properties, and biological (including biocontrol) activity. Application of these bio-products in bioremediation of disturbed (heavy metal contaminated and desertified) soils is based on another important part of their multifunctional properties.

Production of biomethane from palm oil mill effluent (POME) with fed batch system in beam-shaped digester

NASA Astrophysics Data System (ADS)

Aznury, Martha; Amin, Jaksen M.; Hasan, Abu; Himmatuliza, Astinesia

2017-05-01

Palm oil mill effluent (POME) is the biggest liquid waste which is produced from palm oil production. POME are containing organic matter, high levels of biological oxygen demand (BOD) and chemical oxygen demand (COD) were 28000 mg/L and 48000 mg/L. To reduce the levels of pollution caused by POME, is necessary to do stages of processing using a biological process that involves aerobic and anaerobic bacteria so that it can be utilized as a new product that has economic value, one is biogas. The processing into biogas in anaerobic performed by fed batch system. In the ratio between POME and activated microorganismes are 70:30%. The process of anaerobic fermentation in fed batch is done by time variation of the addition of the substrate. The mixture of POME and activated microorganismes were fermented for a month and then after one month substrates were added gradually as much as 1 liter into the digester with a variety of additional time are 1, 2, and 5 days. The interval of addition of the substrate give effect to the pH and the quantity of biogas produced. The highest increasing of the quantity of biomethane was 25.14 mol% at the time the addition of substrate every fifth day.

Antibiotic resistome promotion in drinking water during biological activated carbon treatment: Is it influenced by quorum sensing?

PubMed

Zheng, Ji; Chen, Tao; Chen, Hong

2018-01-15

The contamination of antibiotic resistance genes (ARGs) in drinking water may pose a direct threat to human health. This study applied high-throughput qPCR and sequencing to investigate the dynamics of ARGs and bacterial communities during the advanced treatment of drinking water using biological activated carbon. The promotion of ARGs was observed, and the normalized copy number of ARGs increased significantly after BAC treatment, raising the number of detected ARGs from 84 to 159. Twenty-nine ARGs were identified as biofilm-influencing sources in the BAC, and they persisted after chlorination. The shift of bacterial communities primarily had effects on the changes in resistome. Firmicutes, Cyanobacteria were related to persistent ARGs mostly in the BAC biofilm. Meanwhile, the Acyl-Homoserine Lactones (AHLs), quorum sensing molecules, and bacteria that produced AHLs were identified to understand the promotion of ARGs. The isolated AHL-producing bacteria belonged to the Proteobacteria, Firmicutes and Bacteroidetes phyla. Six detectable AHLs had an influence on plasmid-based horizontal gene transfer in the intragenus mating systems, indicating that the dynamics of ARGs were strongly affected by quorum sensing between specific bacteria in the biofilm. These results provide new insight into the mechanism of antibiotic resistome promotion in BAC biofilms. Copyright © 2017 Elsevier B.V. All rights reserved.

A Picrinine N-Methyltransferase Belongs to a New Family of γ-Tocopherol-Like Methyltransferases Found in Medicinal Plants That Make Biologically Active Monoterpenoid Indole Alkaloids1[OPEN

PubMed Central

Levac, Dylan; Cázares, Paulo; Yu, Fang

2016-01-01

Members of the Apocynaceae plant family produce a large number of monoterpenoid indole alkaloids (MIAs) with different substitution patterns that are responsible for their various biological activities. A novel N-methyltransferase involved in the vindoline pathway in Catharanthus roseus showing distinct similarity to γ-tocopherol C-methyltransferases was used in a bioinformatic screen of transcriptomes from Vinca minor, Rauvolfia serpentina, and C. roseus to identify 10 γ-tocopherol-like N-methyltransferases from a large annotated transcriptome database of different MIA-producing plant species (www.phytometasyn.ca). The biochemical function of two members of this group cloned from V. minor (VmPiNMT) and R. serpentina (RsPiNMT) have been characterized by screening their biochemical activities against potential MIA substrates harvested from the leaf surfaces of MIA-accumulating plants. The approach was validated by identifying the MIA picrinine from leaf surfaces of Amsonia hubrichtii as a substrate of VmPiNMT and RsPiNMT. Recombinant proteins were shown to have high substrate specificity and affinity for picrinine, converting it to N-methylpicrinine (ervincine). Developmental studies with V. minor and R. serpentina showed that RsPiNMT and VmPiNMT gene expression and biochemical activities were highest in younger leaf tissues. The assembly of at least 150 known N-methylated MIAs within members of the Apocynaceae family may have occurred as a result of the evolution of the γ-tocopherol-like N-methyltransferase family from γ-tocopherol methyltransferases. PMID:26848097

On the role of sparseness in the evolution of modularity in gene regulatory networks

PubMed Central

2018-01-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases. PMID:29775459

On the role of sparseness in the evolution of modularity in gene regulatory networks.

PubMed

Espinosa-Soto, Carlos

2018-05-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

Antigenic and functional characterization of p57 produced by Renibacterium salmoninarum

USGS Publications Warehouse

Weins, G.; Chien, M.S.; Winton, J.R.; Kaatari, S.L.

1999-01-01

Renibacterium salmoninarum, the causative agent of bacterial kidney disease, produces large quantities of a 57-58 kDa protein (p57) during growth in broth culture and during infection of salmonid fish. Biological activities of secreted p57 include agglutination of salrnonid leucocytes and rabbit erythrocytes. We define the location of epitopes on p57 recognized by agglutination-blocking monoclonal antibodies (MAbs) 4Cl1, 4H8 and 4D3, and demonstrate that the majority of secreted p57 is a nlonomer that retains salrnonid leucocyte agglutinat~ng activity. The 3 MAbs bound a recombinant, amino-terminal fragment of p57 (211 aa) but not a carboxy-terminal fragment (315 aa) demonstrating that the neutralizing epitopes are located within the amino-terminal portion of p57. When combinations of the MAbs were used in an antigen capture ELISA. the epitopes recognized by the 3 MAbs were shown to be sterically separate. However, when the same MAb was used as both the coating and detection MAb, binding of the biotinylated detection MAb was not observed. These data indicate that the epitopes recognized by the 3 agglutination-blocking antibodies are functionally available only once per molecule and that native p57 exists as a monomer Similar ELISA results were obtained when kidney tissues from 3 naturally infected chinook salmon were assayed. Finally, a p57 monomer was purified using anion exchange and size exclusion chromatography that retained in vitro agglutinating activity. A model in which p57 is released from R. salmoninarum as a biologically active monomer during infection of salmonid fish is proposed.

In vitro uses of biological cryoprotectants.

PubMed Central

Lillford, Peter J; Holt, Chris B

2002-01-01

Ice can be anything from a highly destructive agent in agriculture to a useful building material. Established industries are based on the known rules of physics and chemistry which allow some control of amounts of ice or ice crystal geometry. However, organisms have much more subtle requirements to maintain their delicate internal structure if they are to survive freezing. As a result they have selected specific molecules for freezing-point depression, osmotic regulation, ice nucleation and crystal growth inhibition. All these active species may have potential commercial use once they are identified, understood and produced at economic scales. We examine the progress made so far in extending biological subtlety into commercial processes, and look for prospects for further innovation. PMID:12171658

Ceramidastin, a novel bacterial ceramidase inhibitor, produced by Penicillium sp. Mer-f17067.

PubMed

Inoue, Hiroyuki; Someno, Tetsuya; Kato, Taira; Kumagai, Hiroyuki; Kawada, Manabu; Ikeda, Daishiro

2009-02-01

Decrease of ceramide in the skin is one of the aggravating factors of atopic dermatitis. The skin is often infected by ceramidase-producing bacteria, such as Pseudomonas aeruginosa. The bacterial ceramidase then degrades ceramide in the skin. To develop anti-atopic dermatitis drugs, we searched for ceramidase inhibitors, which led to the discovery of ceramidastin, a novel inhibitor of bacterial ceramidase, from the culture broth of Penicillium sp. Mer-f17067. Ceramidastin inhibited the bacterial ceramidase with an IC(50) value of 6.25 microg ml(-1). Here we describe the isolation, physicochemical properties, structure determination and biological activity of ceramidastin.

Microbial-Catalyzed Biotransformation of Multifunctional Triterpenoids Derived from Phytonutrients

PubMed Central

Shah, Syed Adnan Ali; Tan, Huey Ling; Sultan, Sadia; Mohd Faridz, Muhammad Afifi Bin; Mohd Shah, Mohamad Azlan Bin; Nurfazilah, Sharifah; Hussain, Munawar

2014-01-01

Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids. They offer efficient and economical ways to produce semi-synthetic analogues and novel lead molecules. Microorganisms such as bacteria and fungi could catalyze chemo-, regio- and stereospecific hydroxylations of diverse triterpenoid substrates that are extremely difficult to produce by chemical routes. During recent years, considerable research has been performed on the microbial transformation of bioactive triterpenoids, in order to obtain biologically active molecules with diverse structures features. This article reviews the microbial modifications of tetranortriterpenoids, tetracyclic triterpenoids and pentacyclic triterpenoids. PMID:25003642

Changing trends in biotechnology of secondary metabolism in medicinal and aromatic plants.

PubMed

Gandhi, Sumit G; Mahajan, Vidushi; Bedi, Yashbir S

2015-02-01

Medicinal and aromatic plants are known to produce secondary metabolites that find uses as flavoring agents, fragrances, insecticides, dyes and drugs. Biotechnology offers several choices through which secondary metabolism in medicinal plants can be altered in innovative ways, to overproduce phytochemicals of interest, to reduce the content of toxic compounds or even to produce novel chemicals. Detailed investigation of chromatin organization and microRNAs affecting biosynthesis of secondary metabolites as well as exploring cryptic biosynthetic clusters and synthetic biology options, may provide additional ways to harness this resource. Plant secondary metabolites are a fascinating class of phytochemicals exhibiting immense chemical diversity. Considerable enigma regarding their natural biological functions and the vast array of pharmacological activities, amongst other uses, make secondary metabolites interesting and important candidates for research. Here, we present an update on changing trends in the biotechnological approaches that are used to understand and exploit the secondary metabolism in medicinal and aromatic plants. Bioprocessing in the form of suspension culture, organ culture or transformed hairy roots has been successful in scaling up secondary metabolite production in many cases. Pathway elucidation and metabolic engineering have been useful to get enhanced yield of the metabolite of interest; or, for producing novel metabolites. Heterologous expression of putative plant secondary metabolite biosynthesis genes in a microbe is useful to validate their functions, and in some cases, also, to produce plant metabolites in microbes. Endophytes, the microbes that normally colonize plant tissues, may also produce the phytochemicals produced by the host plant. The review also provides perspectives on future research in the field.

Multiphoton microscopy and image guided light activated therapy using nanomaterials (Conference Presentation)

NASA Astrophysics Data System (ADS)

Prasad, Paras N.

2017-02-01

This talk will focus on design and applications of nanomaterials exhibiting strong multiphoton upconversion for multiphoton microscopy as well as for image-guided and light activated therapy .1-3 Such processes can occur by truly nonlinear optical interactions proceeding through virtual intermediate states or by stepwise coupled linear excitations through real intermediate states. Multiphoton processes in biocompatible multifunctional nanoparticles allow for 3D deep tissue imaging. In addition, they can produce in-situ photon conversion of deep tissue penetrating near IR light into a needed shorter wavelength light for photo-activated therapy at a targeted site, thus overcoming the limited penetration of UV or visible light into biological media. We are using near IR emitters such as silicon quantum dots which also exhibit strong multiphoton excitation for multiphoton microscopy. Another approach involves nonlinear nanocrystals such as ZnO which can produce four wave mixing, sum frequency generation as well as second harmonic generation to convert a deep tissue penetrating Near IR light at the targeted biological site to a desired shorter wavelength light suitable for bio imaging or activation of a therapy. We have utilized this approach to activate a photosensitizer for photodynamic therapy. Yet another type of upconversion materials is rare-earth ion doped optical nanotransformers which transform a Near IR (NIR) light from an external source by sequential single photon absorption, in situ and on demand, to a needed wavelength. Applications of these nanotransformers in multiphoton photoacoustic imaging will also be presented. An exciting direction pursued by us using these multiphoton nanoparticles, is functional imaging of brain. Simultaneously, they can effect optogenetics for regioselective stimulation of neurons for providing an effective intervention/augmentation strategy to enhance the cognitive state and lead to a foundation for futuristic vision of super human capabilities. Challenges and opportunities will be discussed.

Isolation and analysis of bacteria with antimicrobial activities from the marine sponge Haliclona simulans collected from Irish waters.

PubMed

Kennedy, Jonathan; Baker, Paul; Piper, Clare; Cotter, Paul D; Walsh, Marcella; Mooij, Marlies J; Bourke, Marie B; Rea, Mary C; O'Connor, Paula M; Ross, R Paul; Hill, Colin; O'Gara, Fergal; Marchesi, Julian R; Dobson, Alan D W

2009-01-01

Samples of the marine sponge Haliclona simulans were collected from Irish coastal waters, and bacteria were isolated from these samples. Phylogenetic analyses of the cultured isolates showed that four different bacterial phyla were represented; Bacteriodetes, Actinobacteria, Proteobacteria, and Firmicutes. The sponge bacterial isolates were assayed for the production of antimicrobial substances, and biological activities against Gram-positive and Gram-negative bacteria and fungi were demonstrated, with 50% of isolates showing antimicrobial activity against at least one of the test strains. Further testing showed that the antimicrobial activities extended to the important pathogens Pseudomonas aeruginosa, Clostridium difficile, multi-drug-resistant Staphylococcus aureus, and pathogenic yeast strains. The Actinomycetes were numerically the most abundant producers of antimicrobial activities, although activities were also noted from Bacilli and Pseudovibrio isolates. Surveys for the presence of potential antibiotic encoding polyketide synthase and nonribosomal peptide synthetase genes also revealed that genes for the biosynthesis of these secondary metabolites were present in most bacterial phyla but were particularly prevalent among the Actinobacteria and Proteobacteria. This study demonstrates that the culturable fraction of bacteria from the sponge H. simulans is diverse and appears to possess much potential as a source for the discovery of new medically relevant biological active agents.

Two insulin-like peptide family members from the mosquito Aedes aegypti exhibit differential biological and receptor binding activities

PubMed Central

Wen, Zhimou; Gulia, Monika; Clark, Kevin D.; Dhara, Animesh; Crim, Joe W.; Strand, Michael R.; Brown, Mark R.

2010-01-01

Insects encode multiple ILPs but only one homolog of the vertebrate IR that activates the insulin signaling pathway. However, it remains unclear whether all insect ILPs are high affinity ligands for the IR or have similar biological functions. The yellow fever mosquito, Aedes aegypti, encodes eight ILPs with prior studies strongly implicating ILPs from the brain in regulating metabolism and the maturation of eggs following blood feeding. Here we addressed whether two ILP family members expressed in the brain, ILP4 and ILP3, have overlapping functional and receptor binding activities. Our results indicated that ILP3 exhibits strong insulin-like activity by elevating carbohydrate and lipid storage in sugar-fed adult females, whereas ILP4 does not. In contrast, both ILPs exhibited dose-dependent gonadotropic activity in blood-fed females as measured by the stimulation of ovaries to produce ecdysteroids and the uptake of yolk by primary oocytes. Binding studies using ovary membranes indicated that ILP4 and ILP3 do not cross compete; a finding further corroborated by cross-linking and immunoblotting experiments showing that ILP3 binds the MIR while ILP4 binds an unknown 55 kDa membrane protein. In contrast, each ILP activated the insulin signaling pathway in ovaries as measured by enhanced phosphorylation of Akt. RNAi and inhibitor studies further indicated that the gonadotropic activity of ILP4 and ILP3 requires the MIR and a functional insulin signaling pathway. Taken together, our results indicate that two members of the Ae. aegypti ILP family exhibit partially overlapping biological activity and different binding interactions with the MIR. PMID:20643184

Apatite mineralization in elasmobranch skeletons via a polyphosphate intermediate

NASA Astrophysics Data System (ADS)

Omelon, Sidney; Lacroix, Nicolas; Lildhar, Levannia; Variola, Fabio; Dean, Mason

2014-05-01

All vertebrate skeletons are stiffened with apatite, a calcium phosphate mineral. Control of apatite mineralization is essential to the growth and repair of the biology of these skeletons, ensuring that apatite is deposited in the correct tissue location at the desired time. The mechanism of this biochemical control remains debated, but must involve increasing the localized apatite saturation state. It was theorized in 1923 that alkaline phosphatase (ALP) activity provides this control mechanism by increasing the inorganic phosphate (Pi) concentration via dephosphorylation of phosphorylated molecules. The ALP substrate for biological apatite is not known. We propose that polyphosphates (polyPs) produced by mitochondria may be the substrate for biological apatite formation by ALP activity. PolyPs (PO3-)n, also known as condensed phosphates, represent a concentrated, bioavailable Pi-storage strategy. Mitochondria import Pi and synthesize phosphate polymers through an unknown biochemical mechanism. When chelated with calcium and/or other cations, the effective P-concentration of these neutrally charged, amorphous, polyP species can be very high (~ 0.5 M), without inducing phosphate mineral crystallization. This P-concentration in the low Pi-concentration biological environment offers a method of concentrating P well above an apatite supersaturation required for nucleation. Bone is the most studied mineralized skeletal tissue. However, locating and analyzing active mineralizing areas is challenging. We studied calcified cartilage skeletons of elasmobranch fishes (sharks, stingrays and relatives) to analyse the phosphate chemistry in this continually mineralizing skeleton. Although the majority of the elasmobranch skeleton is unmineralized cartilage, it is wrapped in an outer layer of mineralized tissue comprised of small tiles called tesserae. These calcified tesserae continually grow through the formation of new mineral on their borders. Co-localization of ALP and polyPs were identified at the mineralizing tessera borders using Raman spectroscopy, fluorescence microscopy and histological methods. Application of exogenous ALP to skeletal tissue cross-sections resulted in polyP disappearance, and Pi production. It is proposed that elasmobranch skeletal cells produce polyP-containing granules as a concentrated P-source, while ALP activity controls when and where Pi is cleaved from polyP, increasing the apatite supersaturation to nucleate apatite minerals in the skeleton. These data support not only interaction of polyP and ALP as a cell-mediated apatite mineralization control mechanism, but also suggest that this mechanism arose millions of years ago and is common to both bony and cartilaginous skeletal systems.

Contaminants of emerging concern presence and adverse effects in fish: A case study in the Laurentian Great Lakes.

PubMed

Jorgenson, Zachary G; Thomas, Linnea M; Elliott, Sarah M; Cavallin, Jenna E; Randolph, Eric C; Choy, Steven J; Alvarez, David A; Banda, Jo A; Gefell, Daniel J; Lee, Kathy E; Furlong, Edward T; Schoenfuss, Heiko L

2018-05-01

The Laurentian Great Lakes are a valuable natural resource that is affected by contaminants of emerging concern (CECs), including sex steroid hormones, personal care products, pharmaceuticals, industrial chemicals, and new generation pesticides. However, little is known about the fate and biological effects of CECs in tributaries to the Great Lakes. In the current study, 16 sites on three rivers in the Great Lakes basin (Fox, Cuyahoga, and Raquette Rivers) were assessed for CEC presence using polar organic chemical integrative samplers (POCIS) and grab water samplers. Biological activity was assessed through a combination of in vitro bioassays (focused on estrogenic activity) and in vivo assays with larval fathead minnows. In addition, resident sunfish, largemouth bass, and white suckers were assessed for changes in biological endpoints associated with CEC exposure. CECs were present in all water samples and POCIS extracts. A total of 111 and 97 chemicals were detected in at least one water sample and POCIS extract, respectively. Known estrogenic chemicals were detected in water samples at all 16 sites and in POCIS extracts at 13 sites. Most sites elicited estrogenic activity in bioassays. Ranking sites and rivers based on water chemistry, POCIS chemistry, or total in vitro estrogenicity produced comparable patterns with the Cuyahoga River ranking as most and the Raquette River as least affected by CECs. Changes in biological responses grouped according to physiological processes, and differed between species but not sex. The Fox and Cuyahoga Rivers often had significantly different patterns in biological response Our study supports the need for multiple lines of evidence and provides a framework to assess CEC presence and effects in fish in the Laurentian Great Lakes basin. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inhibitory activity of Lactobacillus plantarum LMG P-26358 against Listeria innocua when used as an adjunct starter in the manufacture of cheese

PubMed Central

2011-01-01

Lactobacillus plantarum LMG P-26358 isolated from a soft French artisanal cheese produces a potent class IIa bacteriocin with 100% homology to plantaricin 423 and bacteriocidal activity against Listeria innocua and Listeria monocytogenes. The bacteriocin was found to be highly stable at temperatures as high as 100°C and pH ranges from 1-10. While this relatively narrow spectrum bacteriocin also exhibited antimicrobial activity against species of enterococci, it did not inhibit dairy starters including lactococci and lactobacilli when tested by well diffusion assay (WDA). In order to test the suitability of Lb. plantarum LMG P-26358 as an anti-listerial adjunct with nisin-producing lactococci, laboratory-scale cheeses were manufactured. Results indicated that combining Lb. plantarum LMG P-26358 (at 108 colony forming units (cfu)/ml) with a nisin producer is an effective strategy to eliminate the biological indicator strain, L. innocua. Moreover, industrial-scale cheeses also demonstrated that Lb. plantarum LMG P-26358 was much more effective than the nisin producer alone for protection against the indicator. MALDI-TOF mass spectrometry confirmed the presence of plantaricin 423 and nisin in the appropriate cheeses over an 18 week ripening period. A spray-dried fermentate of Lb. plantarum LMG P-26358 also demonstrated potent anti-listerial activity in vitro using L. innocua. Overall, the results suggest that Lb. plantarum LMG P-26358 is a suitable adjunct for use with nisin-producing cultures to improve the safety and quality of dairy products. PMID:21995443

Persistent organic pollutants and related biological responses measured in coastal fish using chemical and biological screening methods.

PubMed

Tairova, Zhanna; Strand, Jakob; Bossi, Rossana; Larsen, Martin M; Förlin, Lars; Bignert, Anders; Hedman, Jenny; Gercken, Jens; Lang, Thomas; Fricke, Nicolai F; Asmund, Gert; Long, Manhai; Bonefeld-Jørgensen, Eva C

2017-01-01

The aim of this study was to investigate the spatial distribution, levels of dioxin-like compounds (DLC), and biological responses in two fish species. The viviparous eelpout (Zoarces viviparus) was collected from various locations in the Baltic Sea and in fjords of Kattegat and Skagerrak, while shorthorn sculpin (Myoxocephalus scorpius) was obtained at the polychlorinated biphenyl (PCB) polluted site in North West Greenland. Significant differences were detected both in contaminant levels and relative contributions from either polychlorinated dibenzodioxins (PCDD) or polychlorinated dibenzofurans (PCDF or furans) and mono-ortho- and non-ortho (coplanar) polychlorinated biphenyls (dl-PCB). Fish from the eastern Baltic Sea generally displayed higher contributions from PCDD/F compared to dl-PCB, whereas dl-PCB were generally predominated in fish from Danish, Swedish, and German sites. Levels of dl-PCB in muscle tissues were above OSPAR environmental assessment criteria (EAC) for PCB118, indicating a potential risk of adverse biological effects in the ecosystem, whereas levels of the total WHO-TEQs were below threshold for sea food suggesting limited risks for humans. No significant relationships between levels of DLC (expressed as WHO-TEQ), and biological responses such as the induction of CYP1A enzymatic activity and fry reproductive disorders were observed in eelpout. No marked relationship between WHO-TEQ and combined biological aryl hydrocarbon receptor-mediated transactivity (expressed as AhR-TEQ) was noted. However, there was a positive correlation between polycyclic aromatic hydrocarbon (PAH) metabolites and induction of CYP1A activity, suggesting that PAH exhibited greater potential than DLC to produce biological effects in eelpout from the Baltic Sea.

Electrochemical Cathodic Polarization, a Simplified Method That Can Modified and Increase the Biological Activity of Titanium Surfaces: A Systematic Review

PubMed Central

2016-01-01

Background The cathodic polarization seems to be an electrochemical method capable of modifying and coat biomolecules on titanium surfaces, improving the surface activity and promoting better biological responses. Objective The aim of the systematic review is to assess the scientific literature to evaluate the cellular response produced by treatment of titanium surfaces by applying the cathodic polarization technique. Data, Sources, and Selection The literature search was performed in several databases including PubMed, Web of Science, Scopus, Science Direct, Scielo and EBSCO Host, until June 2016, with no limits used. Eligibility criteria were used and quality assessment was performed following slightly modified ARRIVE and SYRCLE guidelines for cellular studies and animal research. Results Thirteen studies accomplished the inclusion criteria and were considered in the review. The quality of reporting studies in animal models was low and for the in vitro studies it was high. The in vitro and in vivo results reported that the use of cathodic polarization promoted hydride surfaces, effective deposition, and adhesion of the coated biomolecules. In the experimental groups that used the electrochemical method, cellular viability, proliferation, adhesion, differentiation, or bone growth were better or comparable with the control groups. Conclusions The use of the cathodic polarization method to modify titanium surfaces seems to be an interesting method that could produce active layers and consequently enhance cellular response, in vitro and in vivo animal model studies. PMID:27441840

Health benefits of fermented foods.

PubMed

Şanlier, Nevin; Gökcen, Büşra Başar; Sezgin, Aybüke Ceyhun

2017-09-25

In the past, the beneficial effects of fermented foods on health were unknown, and so people primarily used fermentation to preserve foods, enhance shelf life, and improve flavour. Fermented foods became an important part of the diet in many cultures, and over time fermentation has been associated with many health benefits. Because of this, the fermentation process and the resulting fermented products have recently attracted scientific interest. In addition, microorganisms contributing to the fermentation process have recently been associated with many health benefits, and so these microorganisms have become another focus of attention. Lactic acid bacteria (LAB) have been some of the most studied microorganisms. During fermentation, these bacteria synthesize vitamins and minerals, produce biologically active peptides with enzymes such as proteinase and peptidase, and remove some non-nutrients. Compounds known as biologically active peptides, which are produced by the bacteria responsible for fermentation, are also well known for their health benefits. Among these peptides, conjugated linoleic acids (CLA) have a blood pressure lowering effect, exopolysaccharides exhibit prebiotic properties, bacteriocins show anti-microbial effects, sphingolipids have anti-carcinogenic and anti-microbial properties, and bioactive peptides exhibit anti-oxidant, anti-microbial, opioid antagonist, anti-allergenic, and blood pressure lowering effects. As a result, fermented foods provide many health benefits such as anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic and anti-atherosclerotic activity. However, some studies have shown no relationship between fermented foods and health benefits. Therefore, this paper aims to investigate the health effects of fermented foods.

Phaeophleospora vochysiae Savi & Glienke sp. nov. Isolated from Vochysia divergens Found in the Pantanal, Brazil, Produces Bioactive Secondary Metabolites.

PubMed

Savi, Daiani C; Shaaban, Khaled A; Gos, Francielly Maria Wilke Ramos; Ponomareva, Larissa V; Thorson, Jon S; Glienke, Chirlei; Rohr, Jürgen

2018-02-15

Microorganisms associated with plants are highly diverse and can produce a large number of secondary metabolites, with antimicrobial, anti-parasitic and cytotoxic activities. We are particularly interested in exploring endophytes from medicinal plants found in the Pantanal, a unique and widely unexplored wetland in Brazil. In a bio-prospecting study, strains LGMF1213 and LGMF1215 were isolated as endophytes from Vochysia divergens, and by morphological and molecular phylogenetic analyses were characterized as Phaeophleospora vochysiae sp. nov. The chemical assessment of this species reveals three major compounds with high biological activity, cercoscosporin (1), isocercosporin (2) and the new compound 3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone (3). Besides the isolation of P. vochysiae as endophyte, the production of cercosporin compounds suggest that under specific conditions this species causes leaf spots, and may turn into a pathogen, since leaf spots are commonly caused by species of Cercospora that produce related compounds. In addition, the new compound 3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone showed considerable antimicrobial activity and low cytotoxicity, which needs further exploration.

Engineering artificial cells by combining HeLa-based cell-free expression and ultra-thin double emulsion template

PubMed Central

Ho, Kwun Yin; Murray, Victoria L.; Liu, Allen P.

2015-01-01

Generation of artificial cells provides the bridge needed to cover the gap between studying the complexity of biological processes in whole cells and studying these same processes in an in vitro reconstituted system. Artificial cells are defined as the encapsulation of biologically active material in a biological or synthetic membrane. Here, we describe a robust and general method to produce artificial cells for the purpose of mimicking one or more behaviors of a cell. A microfluidic double emulsion system is used to encapsulate a mammalian cell free expression system that is able to express membrane proteins into the bilayer or soluble proteins inside the vesicles. The development of a robust platform that allows the assembly of artificial cells is valuable in understanding subcellular functions and emergent behaviors in a more cell-like environment as well as for creating novel signaling pathways to achieve specific cellular behaviors. PMID:25997354

SorghumFDB: sorghum functional genomics database with multidimensional network analysis.

PubMed

Tian, Tian; You, Qi; Zhang, Liwei; Yi, Xin; Yan, Hengyu; Xu, Wenying; Su, Zhen

2016-01-01

Sorghum (Sorghum bicolor [L.] Moench) has excellent agronomic traits and biological properties, such as heat and drought-tolerance. It is a C4 grass and potential bioenergy-producing plant, which makes it an important crop worldwide. With the sorghum genome sequence released, it is essential to establish a sorghum functional genomics data mining platform. We collected genomic data and some functional annotations to construct a sorghum functional genomics database (SorghumFDB). SorghumFDB integrated knowledge of sorghum gene family classifications (transcription regulators/factors, carbohydrate-active enzymes, protein kinases, ubiquitins, cytochrome P450, monolignol biosynthesis related enzymes, R-genes and organelle-genes), detailed gene annotations, miRNA and target gene information, orthologous pairs in the model plants Arabidopsis, rice and maize, gene loci conversions and a genome browser. We further constructed a dynamic network of multidimensional biological relationships, comprised of the co-expression data, protein-protein interactions and miRNA-target pairs. We took effective measures to combine the network, gene set enrichment and motif analyses to determine the key regulators that participate in related metabolic pathways, such as the lignin pathway, which is a major biological process in bioenergy-producing plants.Database URL: http://structuralbiology.cau.edu.cn/sorghum/index.html. © The Author(s) 2016. Published by Oxford University Press.

Manufacturing Economics of Plant-Made Biologics: Case Studies in Therapeutic and Industrial Enzymes

PubMed Central

Tusé, Daniel; McDonald, Karen A.

2014-01-01

Production of recombinant biologics in plants has received considerable attention as an alternative platform to traditional microbial and animal cell culture. Industrially relevant features of plant systems include proper eukaryotic protein processing, inherent safety due to lack of adventitious agents, more facile scalability, faster production (transient systems), and potentially lower costs. Lower manufacturing cost has been widely claimed as an intuitive feature of the platform by the plant-made biologics community, even though cost information resides within a few private companies and studies accurately documenting such an advantage have been lacking. We present two technoeconomic case studies representing plant-made enzymes for diverse applications: human butyrylcholinesterase produced indoors for use as a medical countermeasure and cellulases produced in the field for the conversion of cellulosic biomass into ethanol as a fuel extender. Production economics were modeled based on results reported with the latest-generation expression technologies on Nicotiana host plants. We evaluated process unit operations and calculated bulk active and per-dose or per-unit costs using SuperPro Designer modeling software. Our analyses indicate that substantial cost advantages over alternative platforms can be achieved with plant systems, but these advantages are molecule/product-specific and depend on the relative cost-efficiencies of alternative sources of the same product. PMID:24977145

Effects of Biochar Amendment on Soil Properties and Soil Carbon Sequestration

NASA Astrophysics Data System (ADS)

Zhang, R.; Zhu, S.

2015-12-01

Biochar addition to soils potentially affects various soil properties and soil carbon sequestration, and these effects are dependent on biochars derived from different feedstock materials and pyrolysis processes. The objective of this study was to investigate the effects of amendment of different biochars on soil physical and biological properties as well as soil carbon sequestration. Biochars were produced with dairy manure and woodchip at temperatures of 300, 500, and 700°C, respectively. Each biochar was mixed at 5% (w/w) with a forest soil and the mixture was incubated for 180 days, during which soil physical and biological properties, and soil respiration rates were measured. Results showed that the biochar addition significantly enhanced the formation of soil macroaggregates at the early incubation time. The biochar application significantly reduced soil bulk density, increased the amount of soil organic matter, and stimulated microbial activity and soil respiration rates at the early incubation stage. Biochar applications improved water retention capacity, with stronger effects by biochars produced at higher pyrolysis temperatures. At the same suction, the soil with woodchip biochars possessed higher water content than with the dairy manure biochars. Biochar addition significantly affected the soil physical and biological properties, which resulted in different soil carbon mineralization rates and the amount of soil carbon storage.

Manufacturing economics of plant-made biologics: case studies in therapeutic and industrial enzymes.

PubMed

Tusé, Daniel; Tu, Tiffany; McDonald, Karen A

2014-01-01

Production of recombinant biologics in plants has received considerable attention as an alternative platform to traditional microbial and animal cell culture. Industrially relevant features of plant systems include proper eukaryotic protein processing, inherent safety due to lack of adventitious agents, more facile scalability, faster production (transient systems), and potentially lower costs. Lower manufacturing cost has been widely claimed as an intuitive feature of the platform by the plant-made biologics community, even though cost information resides within a few private companies and studies accurately documenting such an advantage have been lacking. We present two technoeconomic case studies representing plant-made enzymes for diverse applications: human butyrylcholinesterase produced indoors for use as a medical countermeasure and cellulases produced in the field for the conversion of cellulosic biomass into ethanol as a fuel extender. Production economics were modeled based on results reported with the latest-generation expression technologies on Nicotiana host plants. We evaluated process unit operations and calculated bulk active and per-dose or per-unit costs using SuperPro Designer modeling software. Our analyses indicate that substantial cost advantages over alternative platforms can be achieved with plant systems, but these advantages are molecule/product-specific and depend on the relative cost-efficiencies of alternative sources of the same product.

Preparation of Biocomposite Microfibers Ready for Processing into Biologically Active Textile Fabrics for Bioremediation.

PubMed

Kaiser, Patrick; Reich, Steffen; Greiner, Andreas; Freitag, Ruth

2018-06-12

Biocomposites, i.e., materials consisting of metabolically active microorganisms embedded in a synthetic extracellular matrix, may find applications as highly specific catalysts in bioproduction and bioremediation. 3D constructs based on fibrous biocomposites, so-called "artificial biofilms," are of particular interest in this context. The inability to produce biocomposite fibers of sufficient mechanical strength for processing into bioactive fabrics has so far hindered progress in the area. Herein a method is proposed for the direct wet spinning of microfibers suitable for weaving and knitting. Metabolically active bacteria (either Shewanella oneidensis or Nitrobacter winogradskyi (N. winogradskyi)) are embedded in these fibers, using poly(vinyl alcohol) as matrix. The produced microfibers have a partially crystalline structure and are stable in water without further treatment, such as coating. In a first application, their potential for nitrite removal (N. winogradskyi) is demonstrated, a typical challenge in potable water treatment. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Natural bioactive compounds from winery by-products as health promoters: a review.

PubMed

Teixeira, Ana; Baenas, Nieves; Dominguez-Perles, Raul; Barros, Ana; Rosa, Eduardo; Moreno, Diego A; Garcia-Viguera, Cristina

2014-09-04

The relevance of food composition for human health has increased consumers' interest in the consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals. This fact has led to a growing attention of suppliers on reuse of agro-industrial wastes rich in healthy plant ingredients. On this matter, grape has been pointed out as a rich source of bioactive compounds. Currently, up to 210 million tons of grapes (Vitis vinifera L.) are produced annually, being the 15% of the produced grapes addressed to the wine-making industry. This socio-economic activity generates a large amount of solid waste (up to 30%, w/w of the material used). Winery wastes include biodegradable solids namely stems, skins, and seeds. Bioactive compounds from winery by-products have disclosed interesting health promoting activities both in vitro and in vivo. This is a comprehensive review on the phytochemicals present in winery by-products, extraction techniques, industrial uses, and biological activities demonstrated by their bioactive compounds concerning potential for human health.

From 'omics to otoliths: responses of an estuarine fish to endocrine disrupting compounds across biological scales.

PubMed

Brander, Susanne M; Connon, Richard E; He, Guochun; Hobbs, James A; Smalling, Kelly L; Teh, Swee J; White, J Wilson; Werner, Inge; Denison, Michael S; Cherr, Gary N

2013-01-01

Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i.e. sex ratio).

Redox-signals and macrophage biology (for the upcoming issue of molecular aspects of medicine on signaling by reactive oxygen species).

PubMed

Weigert, Andreas; von Knethen, Andreas; Fuhrmann, Dominik; Dehne, Nathalie; Brüne, Bernhard

2018-01-11

Macrophages are known for their versatile role in biology. They sense and clear structures that contain exogenous or endogenous pathogen-associated molecular patterns. This process is tightly linked to the production of a mixture of potentially harmful oxidants and cytokines. Their inherent destructive behavior is directed against foreign material or structures of 'altered self', which explains the role of macrophages during innate immune reactions and inflammation. However, there is also another side of macrophages when they turn into a tissue regenerative, pro-resolving, and healing phenotype. Phenotype changes of macrophages are termed macrophage polarization, representing a continuum between classical and alternative activation. Macrophages as the dominating producers of superoxide/hydrogen peroxide and nitric oxide are not only prone to oxidative modifications but also to more subtle signaling properties of redox-active molecules conveying redox regulation. We review basic concepts of the enzymatic nitric oxide and superoxide production within macrophages, refer to their unique chemical reactions and outline biological consequences not only for macrophage biology but also for their communication with cells in the microenvironment. These considerations link hypoxia to the NO system, addressing feedforward as well as feedback circuits. Moreover, we summarize the role of redox-signaling affecting epigenetics and reflect the central role of mitochondrial-derived oxygen species in inflammation. To better understand the diverse functions of macrophages during initiation as well as resolution of inflammation and to decode their versatile roles during innate and adaptive immunity with the entire spectrum of cell protective towards cell destructive activities we need to appreciate the signaling properties of redox-active species. Herein we discuss macrophage responses in terms of nitric oxide and superoxide formation with the modulating impact of hypoxia. Copyright © 2018. Published by Elsevier Ltd.

Observation and imitation of actions performed by humans, androids, and robots: an EMG study

PubMed Central

Hofree, Galit; Urgen, Burcu A.; Winkielman, Piotr; Saygin, Ayse P.

2015-01-01

Understanding others’ actions is essential for functioning in the physical and social world. In the past two decades research has shown that action perception involves the motor system, supporting theories that we understand others’ behavior via embodied motor simulation. Recently, empirical approach to action perception has been facilitated by using well-controlled artificial stimuli, such as robots. One broad question this approach can address is what aspects of similarity between the observer and the observed agent facilitate motor simulation. Since humans have evolved among other humans and animals, using artificial stimuli such as robots allows us to probe whether our social perceptual systems are specifically tuned to process other biological entities. In this study, we used humanoid robots with different degrees of human-likeness in appearance and motion along with electromyography (EMG) to measure muscle activity in participants’ arms while they either observed or imitated videos of three agents produce actions with their right arm. The agents were a Human (biological appearance and motion), a Robot (mechanical appearance and motion), and an Android (biological appearance and mechanical motion). Right arm muscle activity increased when participants imitated all agents. Increased muscle activation was found also in the stationary arm both during imitation and observation. Furthermore, muscle activity was sensitive to motion dynamics: activity was significantly stronger for imitation of the human than both mechanical agents. There was also a relationship between the dynamics of the muscle activity and motion dynamics in stimuli. Overall our data indicate that motor simulation is not limited to observation and imitation of agents with a biological appearance, but is also found for robots. However we also found sensitivity to human motion in the EMG responses. Combining data from multiple methods allows us to obtain a more complete picture of action understanding and the underlying neural computations. PMID:26150782

Bioengineered silkworms with butterfly cytotoxin-modified silk glands produce sericin cocoons with a utility for a new biomaterial.

PubMed

Otsuki, Ryosuke; Yamamoto, Masafumi; Matsumoto, Erika; Iwamoto, Shin-Ichi; Sezutsu, Hideki; Suzui, Masumi; Takaki, Keiko; Wakabayashi, Keiji; Mori, Hajime; Kotani, Eiji

2017-06-27

Genetically manipulated organisms with dysfunction of specific tissues are crucial for the study of various biological applications and mechanisms. However, the bioengineering of model organisms with tissue-specific dysfunction has not progressed because the challenges of expression of proteins, such as cytotoxins, in living cells of individual organisms need to be overcome first. Here, we report the establishment of a transgenic silkworm ( Bombyx mori ) with posterior silk glands (PSGs) that was designed to express the cabbage butterfly ( Pieris rapae ) cytotoxin pierisin-1A (P1A). P1A, a homolog of the apoptosis inducer pierisin-1, had relatively lower DNA ADP ribosyltransferase activity than pierisin-1; it also induced the repression of certain protein synthesis when expressed in B. mori -derived cultured cells. The transgene-derived P1A domain harboring enzymatic activity was successfully expressed in the transgenic silkworm PSGs. The glands showed no apoptosis-related morphological changes; however, an abnormal appearance was evident. The introduced truncated P1A resulted in the dysfunction of PSGs in that they failed to produce the silk protein fibroin. Cocoons generated by the silkworms solely consisted of the glue-like glycoprotein sericin, from which soluble sericin could be prepared to form hydrogels. Embryonic stem cells could be maintained on the hydrogels in an undifferentiated state and proliferated through stimulation by the cytokines introduced into the hydrogels. Thus, bioengineering with targeted P1A expression successfully produced silkworms with a biologically useful trait that has significant application potential.

Bioengineered silkworms with butterfly cytotoxin-modified silk glands produce sericin cocoons with a utility for a new biomaterial

PubMed Central

Otsuki, Ryosuke; Yamamoto, Masafumi; Matsumoto, Erika; Iwamoto, Shin-ichi; Sezutsu, Hideki; Suzui, Masumi; Takaki, Keiko; Wakabayashi, Keiji; Mori, Hajime; Kotani, Eiji

2017-01-01

Genetically manipulated organisms with dysfunction of specific tissues are crucial for the study of various biological applications and mechanisms. However, the bioengineering of model organisms with tissue-specific dysfunction has not progressed because the challenges of expression of proteins, such as cytotoxins, in living cells of individual organisms need to be overcome first. Here, we report the establishment of a transgenic silkworm (Bombyx mori) with posterior silk glands (PSGs) that was designed to express the cabbage butterfly (Pieris rapae) cytotoxin pierisin-1A (P1A). P1A, a homolog of the apoptosis inducer pierisin-1, had relatively lower DNA ADP ribosyltransferase activity than pierisin-1; it also induced the repression of certain protein synthesis when expressed in B. mori-derived cultured cells. The transgene-derived P1A domain harboring enzymatic activity was successfully expressed in the transgenic silkworm PSGs. The glands showed no apoptosis-related morphological changes; however, an abnormal appearance was evident. The introduced truncated P1A resulted in the dysfunction of PSGs in that they failed to produce the silk protein fibroin. Cocoons generated by the silkworms solely consisted of the glue-like glycoprotein sericin, from which soluble sericin could be prepared to form hydrogels. Embryonic stem cells could be maintained on the hydrogels in an undifferentiated state and proliferated through stimulation by the cytokines introduced into the hydrogels. Thus, bioengineering with targeted P1A expression successfully produced silkworms with a biologically useful trait that has significant application potential. PMID:28607081

Ex Vivo Application of Secreted Metabolites Produced by Soil-Inhabiting Bacillus spp. Efficiently Controls Foliar Diseases Caused by Alternaria spp.

PubMed Central

El-Sayed, Ashraf S. A.; Patel, Jaimin S.; Green, Kari B.; Ali, Mohammad; Brennan, Mary; Norman, David

2015-01-01

Bacterial biological control agents (BCAs) are largely used as live products to control plant pathogens. However, due to variable environmental and ecological factors, live BCAs usually fail to produce desirable results against foliar pathogens. In this study, we investigated the potential of cell-free culture filtrates of 12 different bacterial BCAs isolated from flower beds for controlling foliar diseases caused by Alternaria spp. In vitro studies showed that culture filtrates from two isolates belonging to Bacillus subtilis and Bacillus amyloliquefaciens displayed strong efficacy and potencies against Alternaria spp. The antimicrobial activity of the culture filtrate of these two biological control agents was effective over a wider range of pH (3.0 to 9.0) and was not affected by autoclaving or proteolysis. Comparative liquid chromatography-mass spectrometry (LC-MS) analyses showed that a complex mixture of cyclic lipopeptides, primarily of the fengycin A and fengycin B families, was significantly higher in these two BCAs than inactive Bacillus spp. Interaction studies with mixtures of culture filtrates of these two species revealed additive activity, suggesting that they produce similar products, which was confirmed by LC-tandem MS analyses. In in planta pre- and postinoculation trials, foliar application of culture filtrates of B. subtilis reduced lesion sizes and lesion frequencies caused by Alternaria alternata by 68 to 81%. Taken together, our studies suggest that instead of live bacteria, culture filtrates of B. subtilis and B. amyloliquefaciens can be applied either individually or in combination for controlling foliar diseases caused by Alternaria species. PMID:26519395

In response to: Unsolved enigma of atrial myxoma with biventricular dysfunction.

PubMed

Dixit, Aanchal; Tewari, Prabhat; Soori, Rashmi; Agarwal, Surendra Kumar

2018-01-01

Thanks to Raut et al.[1] for appreciating our efforts in managing the case of biatrial myxomas. A brief discussion is warranted here on the types, size of cardiac myxomas, interleukin 6 (IL-6) levels, left ventricle (LV) dysfunction, and their relation. IL-6 is a pleiotropic cytokine with a variety of biologic activities, including differentiation of B cell, thymocytes, and T cells; activation of macrophages; and stimulation of hepatocyte to produce acute-phase proteins such as C-reactive protein.[2],[3] It is also said to have paracrine, endocrine, and autocrine growth functions.[3].

Freezing-Out Technique Applied to the Concentration of Biologically Active Materials

PubMed Central

Wilson, T. E.; Evans, D. J.; Theriot, Mary L.

1964-01-01

When applied to a dilute solution of folic acid and glucose, a freezing-out (with agitation) technique was shown to be an effective method of achieving a 20-fold reduction in volume with a loss of 10% of the active material being concentrated. Concentration of a stimulatory factor for Lactobacillus casei produced by Candida albicans in a complex medium was limited by the total solute concentration. Salts in the medium were concentrated to levels inhibitory for L. casei. The process is not selective and all solutes are concentrated. Images FIG. 2 FIG. 3 PMID:14131370

Major secondary metabolites produced by two commercial Trichoderma strains active against different phytopathogens.

PubMed

Vinale, F; Marra, R; Scala, F; Ghisalberti, E L; Lorito, M; Sivasithamparam, K

2006-08-01

Trichoderma harzianum strains T22 and T39 are two micro-organisms used as active agents in a variety of commercial biopesticides and biofertilizers and widely applied amongst field and greenhouse crops. The production, isolation, biological and chemical characterization of the main secondary metabolites produced by these strains are investigated. Of the three major compounds produced by strain T22, one is a new azaphilone that shows marked in vitro inhibition of Rhizoctonia solani, Pythium ultimum and Gaeumannomyces graminis var. tritici. In turn, filtrates from strain T39 were demonstrated to contain two compounds previously isolated from other T. harzianum strains and a new butenolide. The production of the isolated metabolites was also monitored by liquid chromatography/mass spectrometry during in vitro interaction with R. solani. This paper reports the isolation and characterization of the main secondary metabolites obtained from culture filtrates of two T. harzianum strains and their production during antagonistic interaction with the pathogen R. solani. This is the first work on secondary metabolites produced by the commercially applied strains T22 and T39. Our results provide a better understanding of the metabolism of these fungi, which are both widely used as biopesticides and/or biofertilizers in biocontrol.

Comparison of vermicompost characteristics produced from sewage sludge of wood and paper industry and household solid wastes.

PubMed

Amouei, A I; Yousefi, Z; Khosravi, T

2017-01-01

The aim of this study was to determine the potential of produced compost from the sludge of wastewater treatment plant using earthworms and compare it with the vermicompost produced from household solid waste. In the current study, three treatments with the same conditions in terms of organic wastes type were prepared to produce vermicompost from household solid waste and sewage sludges using earthworms. The standard methods were used to determine the physical and chemical parameters in the different produced vermicomposts. The mean of C/N in the household solid waste, raw biological and chemical sludges was 32, 22.5, and 26.5, respectively. These levels were 16.5, 14.5, and 15 in the vermicomposts. The mean of nitrogen and phosphorus percentages in the vermicompost of solid waste, biological and chemical sludges was 2.2%, 2.6%, 2.3% and 0.72%, 0.54%, and 0.56%, respectively. The mean percentages of organic matters in the initial substrates and vermicomposts of solid waste, biological and chemical sludges were 97.2%, 90%, 80.5% and 65.8%, 67.8% and 63% respectively. The concentrations of heavy metals decreased in all vermicomposts. The EC levels in solid waste, biological and chemical sludges were 1459, 1041, and 1487 μs/cm, respectively. These levels were 544, 385 and 635 μs/cm in the produced compost. Eisenia fetida can convert household solid waste, and biological and chemical sludges produced from wastewater treatment plant into a high-quality and acceptable compost.

Biological and physicochemical properties of biosurfactants produced by Lactobacillus jensenii P6A and Lactobacillus gasseri P65.

PubMed

Morais, I M C; Cordeiro, A L; Teixeira, G S; Domingues, V S; Nardi, R M D; Monteiro, A S; Alves, R J; Siqueira, E P; Santos, V L

2017-09-19

Lactobacillus species produce biosurfactants that can contribute to the bacteria's ability to prevent microbial infections associated with urogenital and gastrointestinal tracts and the skin. Here, we described the biological and physicochemical properties of biosurfactants produced by Lactobacillus jensenii P 6A and Lactobacillus gasseri P 65 . The biosurfactants produced by L. jensenii P 6A and L. gasseri P 65 reduced the water surface tension from 72 to 43.2 mN m -1 and 42.5 mN m -1 as their concentration increased up to the critical micelle concentration (CMC) values of 7.1 and 8.58 mg mL -1 , respectively. Maximum emulsifying activity was obtained at concentrations of 1 and 5 mg mL -1 for the P 6A and P 65 strains, respectively. The Fourier transform infrared spectroscopy data revealed that the biomolecules consist of a mixture of carbohydrates, lipids and proteins. The gas chromatography-mass spectrum analysis of L. jensenii P 6A biosurfactant showed a major peak for 14-methypentadecanoic acid, which was the main fatty acid present in the biomolecule; conversely, eicosanoic acid dominated the biosurfactant produced by L. gasseri P 65 . Although both biosurfactants contain different percentages of the sugars galactose, glucose and ribose; rhamnose was only detected in the biomolecule produced by L. jensenii P 6A . Emulsifying activities were stable after a 60-min incubation at 100 °C, at pH 2-10, and after the addition of potassium chloride and sodium bicarbonate, but not in the presence of sodium chloride. The biomolecules showed antimicrobial activity against clinical isolates of Escherichia coli and Candida albicans, with MIC values of 16 µg mL -1 , and against Staphylococcus saprophyticus, Enterobacter aerogenes and Klebsiella pneumoniae at 128 µg mL -1 . The biosurfactants also disrupted preformed biofilms of microorganisms at varying concentrations, being more efficient against E. aerogenes (64%) (P 6A biosurfactant), and E. coli (46.4%) and S. saprophyticus (39%) (P 65 biosurfactant). Both strains of lactobacilli could also co-aggregate pathogens. This report presents the first characterization of biosurfactants produced by L. jensenii P 6A and L. gasseri P 65 . The antimicrobial properties and stability of these biomolecules indicate their potential use as alternative antimicrobial agents in the medical field for applications against pathogens that are responsible for infections in the gastrointestinal and urogenital tracts and the skin.

Biologically controlled minerals as potential indicators of life

NASA Technical Reports Server (NTRS)

Schwartz, D. E.; Mancinelli, R. L.; Kaneshiro, E.

1991-01-01

Minerals can be produced and deposited either by abiotic or biologic means. Regardless of their origin, mineral crystals reflect the environment conditions (e.g., temperature, pressure, chemical composition, and redox potential) present during crystal formation. Biologically-produced mineral crystals are grown or reworked under the control of their host organism and reflect an environment different from the abiotic environment. In addition, minerals of either biologic or abiotic origin have great longevities. For these reasons, biologically produced minerals have been proposed as biomarkers. Biomarkers are key morphological, chemical, and isotopic signatures of living systems that can be used to determine if life processes have occurred. Studies of biologically controlled minerals produced by the protist, Paramecium tetraurelia, were initiated since techniques have already been developed to culture them and isolate their crystalline material, and methods are already in place to analyze this material. Two direct crystalline phases were identified. One phase, whose chemical composition is high in Mg, was identified as struvite. The second phase, whose chemical composition is high in Ca, has not been previously found occurring naturally and may be considered a newly discovered material. Analyses are underway to determine the characteristics of these minerals in order to compare them with characteristics of these minerals in order to compare them with characteristics of minerals formed abiotically, but with the same chemical composition.

Active films based on cocoa extract with antioxidant, antimicrobial and biological applications.

PubMed

Calatayud, Marta; López-de-Dicastillo, Carolina; López-Carballo, Gracia; Vélez, Dinoraz; Hernández Muñoz, Pilar; Gavara, Rafael

2013-08-15

Novel films of ethylene-vinyl alcohol copolymer (EVOH) containing flavonoid-rich cocoa were developed. To understand their potential application as active packaging material, antioxidant and antimicrobial properties of the films were determined as well as the antioxidant activity of the release compounds in Caco-2 human epithelial colorectal adenocarcinoma cells. Exposure of the films to aqueous food simulant showed antioxidant capacity. The release of cocoa extract components was dependent on the antioxidant concentration incorporated in the film and on temperature. Cocoa extract and the fraction obtained after in vitro gastrointestinal digestion presented antioxidant activity against oxidative stress induced by hydrogen peroxide in Caco-2 cells. Films with 10%, 15%, and 20% cocoa extract produced bactericidal effect against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella enterica. The application of films to an infant milk formula, previously inoculated with L. monocytogenes, inhibited the growth of bacteria 1.5 log units the first day and showed sustained release, inhibiting 0.52 and 0.76 log units, respectively, by the sixth day, while cocoa powder added directly did not produce any effect. Published by Elsevier Ltd.