natural product discovery: Topics by WorldWideScience.org

Sample records for natural product discovery

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.

Science.gov (United States)

Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R

2018-06-13

The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.
Culture-independent discovery of natural products from soil metagenomes.

Science.gov (United States)

Katz, Micah; Hover, Bradley M; Brady, Sean F

2016-03-01

Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately, traditional culture-based methods for natural product discovery have been deemphasized by pharmaceutical companies due in large part to high rediscovery rates. Culture-independent, or "metagenomic," methods, which rely on the heterologous expression of DNA extracted directly from environmental samples (eDNA), have the potential to provide access to metabolites encoded by a large fraction of the earth's microbial biosynthetic diversity. As soil is both ubiquitous and rich in bacterial diversity, it is an appealing starting point for culture-independent natural product discovery efforts. This review provides an overview of the history of soil metagenome-driven natural product discovery studies and elaborates on the recent development of new tools for sequence-based, high-throughput profiling of environmental samples used in discovering novel natural product biosynthetic gene clusters. We conclude with several examples of these new tools being employed to facilitate the recovery of novel secondary metabolite encoding gene clusters from soil metagenomes and the subsequent heterologous expression of these clusters to produce bioactive small molecules.
Emerging trends in the discovery of natural product antibacterials

DEFF Research Database (Denmark)

Bologa, Cristian G; Ursu, Oleg; Oprea, Tudor

2013-01-01

This article highlights current trends and advances in exploiting natural sources for the deployment of novel and potent anti-infective countermeasures. The key challenge is to therapeutically target bacterial pathogens that exhibit a variety of puzzling and evolutionarily complex resistance...... mechanisms. Special emphasis is given to the strengths, weaknesses, and opportunities in the natural product antibacterial drug discovery arena, and to emerging applications driven by advances in bioinformatics, chemical biology, and synthetic biology in concert with exploiting bacterial phenotypes....... These efforts have identified a critical mass of natural product antibacterial lead compounds and discovery technologies with high probability of successful implementation against emerging bacterial pathogens....
Importance of microbial natural products and the need to revitalize their discovery.

Science.gov (United States)

Demain, Arnold L

2014-02-01

Microbes are the leading producers of useful natural products. Natural products from microbes and plants make excellent drugs. Significant portions of the microbial genomes are devoted to production of these useful secondary metabolites. A single microbe can make a number of secondary metabolites, as high as 50 compounds. The most useful products include antibiotics, anticancer agents, immunosuppressants, but products for many other applications, e.g., antivirals, anthelmintics, enzyme inhibitors, nutraceuticals, polymers, surfactants, bioherbicides, and vaccines have been commercialized. Unfortunately, due to the decrease in natural product discovery efforts, drug discovery has decreased in the past 20 years. The reasons include excessive costs for clinical trials, too short a window before the products become generics, difficulty in discovery of antibiotics against resistant organisms, and short treatment times by patients for products such as antibiotics. Despite these difficulties, technology to discover new drugs has advanced, e.g., combinatorial chemistry of natural product scaffolds, discoveries in biodiversity, genome mining, and systems biology. Of great help would be government extension of the time before products become generic.
Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

Directory of Open Access Journals (Sweden)

Nicholas Ekow Thomford

2018-05-01

Full Text Available The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug
Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

Science.gov (United States)

Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

2018-05-25

The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review
Natural Products in the Discovery of Agrochemicals.

Science.gov (United States)

Loiseleur, Olivier

2017-12-01

Natural products have a long history of being used as, or serving as inspiration for, novel crop protection agents. Many of the discoveries in agrochemical research in the last decades have their origin in a wide range of natural products from a variety of sources. In light of the continuing need for new tools to address an ever-changing array of fungal, weed and insect pests, new agricultural practices and evolving regulatory requirements, the needs for new agrochemical tools remains as critical as ever. In that respect, nature continues to be an important source for novel chemical structures and biological mechanisms to be applied for the development of pest control agents. Here we review several of the natural products and their derivatives which contributed to shape crop protection research in past and present.
Discovery of the leinamycin family of natural products by mining actinobacterial genomes.

Science.gov (United States)

Pan, Guohui; Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Yang, Dong; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen; Shen, Ben

2017-12-26

Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm -type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.
Plant natural products research in tuberculosis drug discovery and ...

African Journals Online (AJOL)

Plant natural products research in tuberculosis drug discovery and development: A situation report ... African Journal of Biotechnology ... tuberculosis (XDR-TB), call for the development of new anti-tuberculosis drugs to combat this disease.
Insects: an underrepresented resource for the discovery of biologically active natural products

Directory of Open Access Journals (Sweden)

Lauren Seabrooks

2017-07-01

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

Science.gov (United States)

Choi, Si-Sun; Katsuyama, Yohei; Bai, Linquan; Deng, Zixin; Ohnishi, Yasuo; Kim, Eung-Soo

2018-03-03

The discovery and development of microbial natural products (MNPs) have played pivotal roles in the fields of human medicine and its related biotechnology sectors over the past several decades. The post-genomic era has witnessed the development of microbial genome mining approaches to isolate previously unsuspected MNP biosynthetic gene clusters (BGCs) hidden in the genome, followed by various BGC awakening techniques to visualize compound production. Additional microbial genome engineering techniques have allowed higher MNP production titers, which could complement a traditional culture-based MNP chasing approach. Here, we describe recent developments in the MNP research paradigm, including microbial genome mining, NP BGC activation, and NP overproducing cell factory design. Copyright © 2018 Elsevier Ltd. All rights reserved.
Leveraging ecological theory to guide natural product discovery.

Science.gov (United States)

Smanski, Michael J; Schlatter, Daniel C; Kinkel, Linda L

2016-03-01

Technological improvements have accelerated natural product (NP) discovery and engineering to the point that systematic genome mining for new molecules is on the horizon. NP biosynthetic potential is not equally distributed across organisms, environments, or microbial life histories, but instead is enriched in a number of prolific clades. Also, NPs are not equally abundant in nature; some are quite common and others markedly rare. Armed with this knowledge, random 'fishing expeditions' for new NPs are increasingly harder to justify. Understanding the ecological and evolutionary pressures that drive the non-uniform distribution of NP biosynthesis provides a rational framework for the targeted isolation of strains enriched in new NP potential. Additionally, ecological theory leads to testable hypotheses regarding the roles of NPs in shaping ecosystems. Here we review several recent strain prioritization practices and discuss the ecological and evolutionary underpinnings for each. Finally, we offer perspectives on leveraging microbial ecology and evolutionary biology for future NP discovery.
Natural Products as Leads in Schistosome Drug Discovery

Directory of Open Access Journals (Sweden)

Bruno J. Neves

2015-01-01

Full Text Available Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ, the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.
Natural product derived insecticides: discovery and development of spinetoram.

Science.gov (United States)

Galm, Ute; Sparks, Thomas C

2016-03-01

This review highlights the importance of natural product research and industrial microbiology for product development in the agricultural industry, based on examples from Dow AgroSciences. It provides an overview of the discovery and development of spinetoram, a semisynthetic insecticide derived by a combination of a genetic block in a specific O-methylation of the rhamnose moiety of spinosad coupled with neural network-based QSAR and synthetic chemistry. It also emphasizes the key role that new technologies and multidisciplinary approaches play in the development of current spinetoram production strains.
Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

Science.gov (United States)

Altmann, Karl-Heinz

2017-10-25

The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.
Application of Combination High-Throughput Phenotypic Screening and Target Identification Methods for the Discovery of Natural Product-Based Combination Drugs.

Science.gov (United States)

Isgut, Monica; Rao, Mukkavilli; Yang, Chunhua; Subrahmanyam, Vangala; Rida, Padmashree C G; Aneja, Ritu

2018-03-01

Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple targets and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural products in drug discovery. Natural products consist of a multitude of constituents that can act on a variety of targets in the body to induce pharmacodynamic responses that may together culminate in an additive or synergistic therapeutic effect. Although natural products cannot be patented, they can be used as starting points in the discovery of potent combination therapeutics. The optimal mix of bioactive ingredients in natural products can be determined via phenotypic screening. The targets and molecular mechanisms of action of these active ingredients can then be determined using chemical proteomics, and by implementing a reverse pharmacokinetics approach. This review article provides evidence supporting the potential benefits of natural product-based combination drugs, and summarizes drug discovery methods that can be applied to this class of drugs. © 2017 Wiley Periodicals, Inc.
ASM Inaugural Lecture 2010: Single crystal X-ray structural determination: A powerful technique for natural products research and drug discovery

International Nuclear Information System (INIS)

Fun Hoong Kun; Chantrapromma, S.; Boonnak, N.; Lee, V.S.

2010-01-01

Drug discovery from natural products resources have been extensively studied worldwide because natural products with their great structural diversity have traditionally provided most of the drugs in use. They offer major opportunities for finding novel low molecular weight leading-structures that are active against a wide range of assay targets. The most important step in the discovery process is the identification of compounds with interesting biological activity. Single crystal X-ray structure determination is a powerful technique for natural products research and drug discovery. The detailed three-dimensional structures that emerge can be co-related to the activities to these structures. In this article the following is presented: (i) co-crystal and disorder structures; (ii) determination of absolute configuration and (iii) the ability to distinguish between whether a natural product compound is a natural product or a natural product artifact. All these three properties are unique to the technique of single crystal X-ray structure determination. Case (iii) was demonstrated with a compound containing a chromene ring, namely macluraxanthone (which was isolated from Cratoxylum formosum subsp. pruniflorum, a Thai medicinal plant). (author)
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents.

Science.gov (United States)

Choi, Chang-Ik

2016-08-27

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.
Rationale for a natural products approach to herbicide discovery.

Science.gov (United States)

Dayan, Franck E; Owens, Daniel K; Duke, Stephen O

2012-04-01

Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry. Published 2012 by John Wiley & Sons, Ltd.
Sodium-Glucose Cotransporter 2 (SGLT2 Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents

Directory of Open Access Journals (Sweden)

Chang-Ik Choi

2016-08-01

Full Text Available Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2 for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.

Genome-Based Studies of Marine Microorganisms to Maximize the Diversity of Natural Products Discovery for Medical Treatments

Directory of Open Access Journals (Sweden)

Xin-Qing Zhao

2011-01-01

Full Text Available Marine microorganisms are rich source for natural products which play important roles in pharmaceutical industry. Over the past decade, genome-based studies of marine microorganisms have unveiled the tremendous diversity of the producers of natural products and also contributed to the efficiency of harness the strain diversity and chemical diversity, as well as the genetic diversity of marine microorganisms for the rapid discovery and generation of new natural products. In the meantime, genomic information retrieved from marine symbiotic microorganisms can also be employed for the discovery of new medical molecules from yet-unculturable microorganisms. In this paper, the recent progress in the genomic research of marine microorganisms is reviewed; new tools of genome mining as well as the advance in the activation of orphan pathways and metagenomic studies are summarized. Genome-based research of marine microorganisms will maximize the biodiscovery process and solve the problems of supply and sustainability of drug molecules for medical treatments.
Multiplexed Thiol Reactivity Profiling for Target Discovery of Electrophilic Natural Products.

Science.gov (United States)

Tian, Caiping; Sun, Rui; Liu, Keke; Fu, Ling; Liu, Xiaoyu; Zhou, Wanqi; Yang, Yong; Yang, Jing

2017-11-16

Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified α,β-unsaturated γ-lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.
Harnessing the potential of natural products in drug discovery from a cheminformatics vantage point.

Science.gov (United States)

Rodrigues, Tiago

2017-11-15

Natural products (NPs) present a privileged source of inspiration for chemical probe and drug design. Despite the biological pre-validation of the underlying molecular architectures and their relevance in drug discovery, the poor accessibility to NPs, complexity of the synthetic routes and scarce knowledge of their macromolecular counterparts in phenotypic screens still hinder their broader exploration. Cheminformatics algorithms now provide a powerful means of circumventing the abovementioned challenges and unlocking the full potential of NPs in a drug discovery context. Herein, I discuss recent advances in the computer-assisted design of NP mimics and how artificial intelligence may accelerate future NP-inspired molecular medicine.
Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products.

Science.gov (United States)

Baptista, Rafael; Bhowmick, Sumana; Nash, Robert J; Baillie, Les; Mur, Luis Aj

2018-04-01

Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target predefined pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to define the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products.
An assessment of natural product discovery from marine (sensu strictu) and marine-derived fungi

Science.gov (United States)

Overy, David P.; Bayman, Paul; Kerr, Russell G.; Bills, Gerald F.

2014-01-01

The natural products community has been investigating secondary metabolites from marine fungi for several decades, but when one attempts to search for validated reports of new natural products from marine fungi, one encounters a literature saturated with reports from ‘marine-derived’ fungi. Of the 1000+ metabolites that have been characterized to date, only approximately 80 of these have been isolated from species from exclusively marine lineages. These metabolites are summarized here along with the lifestyle and habitats of their producing organisms. Furthermore, we address some of the reasons for the apparent disconnect between the stated objectives of discovering new chemistry from marine organisms and the apparent neglect of the truly exceptional obligate marine fungi. We also offer suggestions on how to reinvigorate enthusiasm for marine natural products discovery from fungi from exclusive marine lineages and highlight the need for critically assessing the role of apparently terrestrial fungi in the marine environment. PMID:25379338
Next Generation Sequencing of Actinobacteria for the Discovery of Novel Natural Products

Science.gov (United States)

Gomez-Escribano, Juan Pablo; Alt, Silke; Bibb, Mervyn J.

2016-01-01

Like many fields of the biosciences, actinomycete natural products research has been revolutionised by next-generation DNA sequencing (NGS). Hundreds of new genome sequences from actinobacteria are made public every year, many of them as a result of projects aimed at identifying new natural products and their biosynthetic pathways through genome mining. Advances in these technologies in the last five years have meant not only a reduction in the cost of whole genome sequencing, but also a substantial increase in the quality of the data, having moved from obtaining a draft genome sequence comprised of several hundred short contigs, sometimes of doubtful reliability, to the possibility of obtaining an almost complete and accurate chromosome sequence in a single contig, allowing a detailed study of gene clusters and the design of strategies for refactoring and full gene cluster synthesis. The impact that these technologies are having in the discovery and study of natural products from actinobacteria, including those from the marine environment, is only starting to be realised. In this review we provide a historical perspective of the field, analyse the strengths and limitations of the most relevant technologies, and share the insights acquired during our genome mining projects. PMID:27089350
Recent Advances in the Discovery and Development of Marine Natural Products with Cardiovascular Pharmacological Effects.

Science.gov (United States)

Zhou, Jie-Bin; Luo, Rong; Zheng, Ying-Lin; Pang, Ji-Yan

2018-01-01

Numerous studies have indicated that marine natural products are one of the most important sources of the lead compounds in drug discovery for their unique structures, various bioactivities and less side effects. In this review, the marine natural products with cardiovascular pharmacological effects reported after 2000 will be presented. Their structural types, relevant biological activities, origin of isolation and information of strain species will be discussed in detail. Finally, by describing our studies as an example, we also discuss the chances and challenges for translating marine-derived compounds into preclinical or clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
The 4th Euro-Mediterranean Conference of Natural Products and Drug Discovery: Back to Mother Nature (BioNat-IV, Cairo/Sharm El-Sheikh, Egypt, March 3–7, 2015

Directory of Open Access Journals (Sweden)

Ashraf A. Khalil

2016-04-01

Full Text Available The 4th Euro-Mediterranean Conference of Natural Products and Drug Discovery: Back to Mother Nature (BioNat-IV was recently (from March 3rd through 7th, 2015 convened in Cairo and Sharm El-Sheikh along the Red Sea coast of Egypt. Overall, the meeting provided a platform for scientists from different nations to discuss emerging ideas that focused on cell signaling in cancer; the pathogenesis of autoimmune diseases; the identification and use of natural products as well as novel drug delivery approaches for the treatment of cancer, arthritis, diabetes, tuberculosis, fungal infection, etc.; and untapped or unconventional sources for natural products. This fourth in a row conference tried to bridge the gap not only between basic research and clinical applications, but also between developed nations and developing countries. With the continuing success of these past meetings, the fifth Euro-Mediterranean Conference of Natural Products and Drug Discovery (BioNat-V is slated to be in February 2017.
High content live cell imaging for the discovery of new antimalarial marine natural products

Directory of Open Access Journals (Sweden)

Cervantes Serena

2012-01-01

Full Text Available Abstract Background The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, Plasmodium falciparum. Methods A high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown in vitro in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope. Results Image analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts. Conclusion Collectively, our results show that high-content live cell-imaging (HCLCI can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials.
High content live cell imaging for the discovery of new antimalarial marine natural products.

Science.gov (United States)

Cervantes, Serena; Stout, Paige E; Prudhomme, Jacques; Engel, Sebastian; Bruton, Matthew; Cervantes, Michael; Carter, David; Tae-Chang, Young; Hay, Mark E; Aalbersberg, William; Kubanek, Julia; Le Roch, Karine G

2012-01-03

The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, Plasmodium falciparum. A high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown in vitro in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope. Image analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts. Collectively, our results show that high-content live cell-imaging (HCLCI) can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials. © 2011 Cervantes et al; licensee BioMed Central Ltd.
Natural product mode of action (MOA) studies: a link between natural and synthetic worlds.

Science.gov (United States)

La Clair, James J

2010-07-01

In our understanding of matter, natural products deliver plots that would stun even the best productions of the legendary filmmaker, Sergio Leone. While every decade heralds a new genre of film (as well as avenues of small-molecule discovery), natural products and their "untamed prehistoric" plots continue to dazzle the fields of biotechnology, drug discovery, fragrances, food additives and agrochemistry. This review provides an abridged synopsis of the modes of natural product action discovered within the last decade and the tools and methods used in their discovery. Their stories are united in a common theme that unveils one of the more vital aspects of chemical biological research:understanding the global activity of Nature's arsenal of secondary metabolites.
Building a discovery partnership with Sarawak Biodiversity Centre: a gateway to access natural products from the rainforests.

Science.gov (United States)

Yeo, Tiong Chia; Naming, Margarita; Manurung, Rita

2014-03-01

The Sarawak Biodiversity Centre (SBC) is a state government agency which regulates research and promotes the sustainable use of biodiversity. It has a program on documentation of traditional knowledge (TK) and is well-equipped with facilities for natural product research. SBC maintains a Natural Product Library (NPL) consisting of local plant and microbial extracts for bioprospecting. The NPL is a core discovery platform for screening of bioactive compounds by researchers through a formal agreement with clear benefit sharing obligations. SBC aims to develop partnerships with leading institutions and the industries to explore the benefits of biodiversity.
Microbial genome mining for accelerated natural products discovery: is a renaissance in the making?

Science.gov (United States)

Bachmann, Brian O; Van Lanen, Steven G; Baltz, Richard H

2014-02-01

Microbial genome mining is a rapidly developing approach to discover new and novel secondary metabolites for drug discovery. Many advances have been made in the past decade to facilitate genome mining, and these are reviewed in this Special Issue of the Journal of Industrial Microbiology and Biotechnology. In this Introductory Review, we discuss the concept of genome mining and why it is important for the revitalization of natural product discovery; what microbes show the most promise for focused genome mining; how microbial genomes can be mined; how genome mining can be leveraged with other technologies; how progress on genome mining can be accelerated; and who should fund future progress in this promising field. We direct interested readers to more focused reviews on the individual topics in this Special Issue for more detailed summaries on the current state-of-the-art.
Natural Products from Mangrove Actinomycetes

Science.gov (United States)

Xu, Dong-Bo; Ye, Wan-Wan; Han, Ying; Deng, Zi-Xin; Hong, Kui

2014-01-01

Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery. PMID:24798926
Natural Products and HIV/AIDS.

Science.gov (United States)

Cary, Daniele C; Peterlin, B Matija

2018-01-01

The study of natural products in biomedical research is not a modern concept. Many of the most successful medical therapeutics are derived from natural products, including those studied in the field of HIV/AIDS. Biomedical research has a rich history of discovery based on screens of medicinal herbs and traditional medicine practices. Compounds derived from natural products, which repress HIV and those that activate latent HIV, have been reported. It is important to remember the tradition in medical research to derive therapies based on these natural products and to overcome the negative perception of natural products as an "alternative medicine."
Price discovery in European natural gas markets

International Nuclear Information System (INIS)

Schultz, Emma; Swieringa, John

2013-01-01

We provide the first high-frequency investigation of price discovery within the physical and financial layers of Europe's natural gas markets. Testing not only looks at short-term return dynamics, but also considers each security's contribution to price equilibrium in the longer-term. Results show that UK natural gas futures traded on the Intercontinental Exchange display greater price discovery than physical trading at various hubs throughout Europe. - Highlights: • We use intraday data to gauge price discovery in European natural gas markets. • We explore short and long-term dynamics in physical and financial market layers. • Results show ICE's UK natural gas futures are the main venue for price discovery
Cracking the regulatory code of biosynthetic gene clusters as a strategy for natural product discovery.

Science.gov (United States)

Rigali, Sébastien; Anderssen, Sinaeda; Naômé, Aymeric; van Wezel, Gilles P

2018-01-05

The World Health Organization (WHO) describes antibiotic resistance as "one of the biggest threats to global health, food security, and development today", as the number of multi- and pan-resistant bacteria is rising dangerously. Acquired resistance phenomena also impair antifungals, antivirals, anti-cancer drug therapy, while herbicide resistance in weeds threatens the crop industry. On the positive side, it is likely that the chemical space of natural products goes far beyond what has currently been discovered. This idea is fueled by genome sequencing of microorganisms which unveiled numerous so-called cryptic biosynthetic gene clusters (BGCs), many of which are transcriptionally silent under laboratory culture conditions, and by the fact that most bacteria cannot yet be cultivated in the laboratory. However, brute force antibiotic discovery does not yield the same results as it did in the past, and researchers have had to develop creative strategies in order to unravel the hidden potential of microorganisms such as Streptomyces and other antibiotic-producing microorganisms. Identifying the cis elements and their corresponding transcription factors(s) involved in the control of BGCs through bioinformatic approaches is a promising strategy. Theoretically, we are a few 'clicks' away from unveiling the culturing conditions or genetic changes needed to activate the production of cryptic metabolites or increase the production yield of known compounds to make them economically viable. In this opinion article, we describe and illustrate the idea beyond 'cracking' the regulatory code for natural product discovery, by presenting a series of proofs of concept, and discuss what still should be achieved to increase the rate of success of this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.
Natural Products from Mangrove Actinomycetes

Directory of Open Access Journals (Sweden)

Dong-Bo Xu

2014-05-01

Full Text Available Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery.
Combinatorial synthesis of natural products

DEFF Research Database (Denmark)

Nielsen, John

2002-01-01

Combinatorial syntheses allow production of compound libraries in an expeditious and organized manner immediately applicable for high-throughput screening. Natural products possess a pedigree to justify quality and appreciation in drug discovery and development. Currently, we are seeing a rapid...... increase in application of natural products in combinatorial chemistry and vice versa. The therapeutic areas of infectious disease and oncology still dominate but many new areas are emerging. Several complex natural products have now been synthesised by solid-phase methods and have created the foundation...... for preparation of combinatorial libraries. In other examples, natural products or intermediates have served as building blocks or scaffolds in the synthesis of complex natural products, bioactive analogues or designed hybrid molecules. Finally, structural motifs from the biologically active parent molecule have...
Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

Directory of Open Access Journals (Sweden)

Yuri Pevzner

2014-05-01

Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

Directory of Open Access Journals (Sweden)

Yuri Pevzner

2015-08-01

Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.
Biosynthesis of therapeutic natural products using synthetic biology.

Science.gov (United States)

Awan, Ali R; Shaw, William M; Ellis, Tom

2016-10-01

Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.
Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products.

Science.gov (United States)

Prescher, Horst; Koch, Guido; Schuhmann, Tim; Ertl, Peter; Bussenault, Alex; Glick, Meir; Dix, Ina; Petersen, Frank; Lizos, Dimitrios E

2017-02-01

A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD). Copyright © 2016 Elsevier Ltd. All rights reserved.
From Discovery to Production: Biotechnology of Marine Fungi for the Production of New Antibiotics

Science.gov (United States)

Silber, Johanna; Kramer, Annemarie; Labes, Antje; Tasdemir, Deniz

2016-01-01

Filamentous fungi are well known for their capability of producing antibiotic natural products. Recent studies have demonstrated the potential of antimicrobials with vast chemodiversity from marine fungi. Development of such natural products into lead compounds requires sustainable supply. Marine biotechnology can significantly contribute to the production of new antibiotics at various levels of the process chain including discovery, production, downstream processing, and lead development. However, the number of biotechnological processes described for large-scale production from marine fungi is far from the sum of the newly-discovered natural antibiotics. Methods and technologies applied in marine fungal biotechnology largely derive from analogous terrestrial processes and rarely reflect the specific demands of the marine fungi. The current developments in metabolic engineering and marine microbiology are not yet transferred into processes, but offer numerous options for improvement of production processes and establishment of new process chains. This review summarises the current state in biotechnological production of marine fungal antibiotics and points out the enormous potential of biotechnology in all stages of the discovery-to-development pipeline. At the same time, the literature survey reveals that more biotechnology transfer and method developments are needed for a sustainable and innovative production of marine fungal antibiotics. PMID:27455283
Multi-channel counter-current chromatography for high-throughput fractionation of natural products for drug discovery.

Science.gov (United States)

Wu, Shihua; Yang, Lu; Gao, Yuan; Liu, Xiaoyue; Liu, Feiyan

2008-02-08

A multi-channel counter-current chromatography (CCC) method has been designed and fabricated for the high-throughput fractionation of natural products without complications sometimes encountered with other conventional chromatographic systems, such as irreversible adsorptive constituent losses and deactivation, tailing of solute peaks and contamination. It has multiple independent CCC channels and each channel connects independent separation column(s) by parallel flow tubes, and thus the multi-channel CCC apparatus can achieve simultaneously two or more independent chromatographic processes. Furthermore, a high-throughput CCC fractionation method for natural products has been developed by a combination of a new three-channel CCC apparatus and conventional parallel chromatographic devices including pumps, sample injectors, effluent detectors and collectors, and its performance has been displayed on the fractionation of ethyl acetate extracts of three natural materials Solidago canadensis, Suillus placidus, and Trichosanthes kirilowii, which are found to be potent cytotoxic to tumor cell lines in the course of screening the antitumor candidates. By combination of biological screening programs and preparative high-performance liquid chromatography (HPLC) purification, 22.8 mg 6 beta-angeloyloxykolavenic acid and 29.4 mg 6 beta-tigloyloxykolavenic acid for S. canadensis, 25.3mg suillin for S. placidus, and 6.8 mg 23,24-dihydrocucurbitacin B for T. Kirilowii as their major cytotoxic principles were isolated from each 1000 mg crude ethyl acetate extract. Their chemical structures were characterized by electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance. The overall results indicate the multi-channel CCC is very useful for high-throughput fractionation of natural products for drug discovery in spite of the solvent balancing requirement and the lower resolution of the shorter CCC columns.
Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

Directory of Open Access Journals (Sweden)

Michael Poulsen

2011-02-01

Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.
Synthesis of Polycyclic Natural Products

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Tuan Hoang [Iowa State Univ., Ames, IA (United States)

2003-01-01

With the continuous advancements in molecular biology and modern medicine, organic synthesis has become vital to the support and extension of those discoveries. The isolations of new natural products allow for the understanding of their biological activities and therapeutic value. Organic synthesis is employed to aid in the determination of the relationship between structure and function of these natural products. The development of synthetic methodologies in the course of total syntheses is imperative for the expansion of this highly interdisciplinary field of science. In addition to the practical applications of total syntheses, the structural complexity of natural products represents a worthwhile challenge in itself. The pursuit of concise and efficient syntheses of complex molecules is both gratifying and enjoyable.
Recent advances in discovery and development of natural products as source for anti-Parkinson's disease lead compounds.

Science.gov (United States)

Zhang, Hongjia; Bai, Lan; He, Jun; Zhong, Lei; Duan, Xingmei; Ouyang, Liang; Zhu, Yuxuan; Wang, Ting; Zhang, Yiwen; Shi, Jianyou

2017-12-01

Parkinson's disease (PD) is a common chronic degenerative disease of the central nervous system. Although the cause remains unknown, several pathological processes and central factors such as oxidative stress, mitochondrial injury, inflammatory reactions, abnormal deposition of α-synuclein, and cell apoptosis have been reported. Currently, anti-PD drugs are classified into two major groups: drugs that affect dopaminergic neurons and anti-cholinergic drugs. Unfortunately, the existing conventional strategies against PD are with numerous side effects, and cannot fundamentally improve the degenerative process of dopaminergic neurons. Therefore, novel therapeutic approaches which have a novel structure, high efficiency, and fewer side effects are needed. For many years, natural products have provided an efficient resource for the discovery of potential therapeutic agents. Among them, many natural products possess anti-PD properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding protein misfolding and the regulatory effects of PD related pathways. Indeed, with the steady improvement in the technologies for the isolation and purification of natural products and the in-depth studies on the pathogenic mechanisms of PD, many monomer components of natural products that have anti-PD effects have been gradually discovered. In this article, we reviewed the research status of 37 natural products that have been discovered to have significant anti-PD effects as well as their mode of action. Overall, this review may guide the design of novel therapeutic drugs in PD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Super Natural II--a database of natural products.

Science.gov (United States)

Banerjee, Priyanka; Erehman, Jevgeni; Gohlke, Björn-Oliver; Wilhelm, Thomas; Preissner, Robert; Dunkel, Mathias

2015-01-01

Natural products play a significant role in drug discovery and development. Many topological pharmacophore patterns are common between natural products and commercial drugs. A better understanding of the specific physicochemical and structural features of natural products is important for corresponding drug development. Several encyclopedias of natural compounds have been composed, but the information remains scattered or not freely available. The first version of the Supernatural database containing ∼ 50,000 compounds was published in 2006 to face these challenges. Here we present a new, updated and expanded version of natural product database, Super Natural II (http://bioinformatics.charite.de/supernatural), comprising ∼ 326,000 molecules. It provides all corresponding 2D structures, the most important structural and physicochemical properties, the predicted toxicity class for ∼ 170,000 compounds and the vendor information for the vast majority of compounds. The new version allows a template-based search for similar compounds as well as a search for compound names, vendors, specific physical properties or any substructures. Super Natural II also provides information about the pathways associated with synthesis and degradation of the natural products, as well as their mechanism of action with respect to structurally similar drugs and their target proteins. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Using Genomics for Natural Product Structure Elucidation.

Science.gov (United States)

Tietz, Jonathan I; Mitchell, Douglas A

2016-01-01

Natural products (NPs) are the most historically bountiful source of chemical matter for drug development-especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.
Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity

Science.gov (United States)

Azman, Adzzie-Shazleen; Othman, Iekhsan; Velu, Saraswati S.; Chan, Kok-Gan; Lee, Learn-Han

2015-01-01

Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer, and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings. PMID:26347734
Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity.

Science.gov (United States)

Azman, Adzzie-Shazleen; Othman, Iekhsan; Velu, Saraswati S; Chan, Kok-Gan; Lee, Learn-Han

2015-01-01

Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer, and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings.
Mangrove rare actinobacteria: Taxonomy, natural compound and discovery of bioactivity

Directory of Open Access Journals (Sweden)

Adzzie-Shazleen eAzman

2015-08-01

Full Text Available Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings.
Natural product synthesis at the interface of chemistry and biology

Science.gov (United States)

2014-01-01

Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880
Natural products from microbes associated with insects

DEFF Research Database (Denmark)

Beemelmanns, Christine; Guo, Huijuan; Rischer, Maja

2016-01-01

Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We...
Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

Science.gov (United States)

Rayan, Anwar; Raiyn, Jamal; Falah, Mizied

2017-01-01

Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.
Automated genome mining of ribosomal peptide natural products

Energy Technology Data Exchange (ETDEWEB)

Mohimani, Hosein; Kersten, Roland; Liu, Wei; Wang, Mingxun; Purvine, Samuel O.; Wu, Si; Brewer, Heather M.; Pasa-Tolic, Ljiljana; Bandeira, Nuno; Moore, Bradley S.; Pevzner, Pavel A.; Dorrestein, Pieter C.

2014-07-31

Ribosomally synthesized and posttranslationally modified peptides (RiPPs), especially from microbial sources, are a large group of bioactive natural products that are a promising source of new (bio)chemistry and bioactivity (1). In light of exponentially increasing microbial genome databases and improved mass spectrometry (MS)-based metabolomic platforms, there is a need for computational tools that connect natural product genotypes predicted from microbial genome sequences with their corresponding chemotypes from metabolomic datasets. Here, we introduce RiPPquest, a tandem mass spectrometry database search tool for identification of microbial RiPPs and apply it for lanthipeptide discovery. RiPPquest uses genomics to limit search space to the vicinity of RiPP biosynthetic genes and proteomics to analyze extensive peptide modifications and compute p-values of peptide-spectrum matches (PSMs). We highlight RiPPquest by connection of multiple RiPPs from extracts of Streptomyces to their gene clusters and by the discovery of a new class III lanthipeptide, informatipeptin, from Streptomyces viridochromogenes DSM 40736 as the first natural product to be identified in an automated fashion by genome mining. The presented tool is available at cy-clo.ucsd.edu.
Discovery and characterization of natural products that act as pheromones in fish.

Science.gov (United States)

Li, Ke; Buchinger, Tyler J; Li, Weiming

2018-06-20

Covering: up to 2018 Fish use a diverse collection of molecules to communicate with conspecifics. Since Karlson and Lüscher termed these molecules 'pheromones', chemists and biologists have joined efforts to characterize their structures and functions. In particular, the understanding of insect pheromones developed at a rapid pace, set, in part, by the use of bioassay-guided fractionation and natural product chemistry. Research on vertebrate pheromones, however, has progressed more slowly. Initially, biologists characterized fish pheromones by screening commercially available compounds suspected to act as pheromones based upon their physiological function. Such biology-driven screening has proven a productive approach to studying pheromones in fish. However, the many functions of fish pheromones and diverse metabolites that fish release make predicting pheromone identity difficult and necessitate approaches led by chemistry. Indeed, the few cases in which pheromone identification was led by natural product chemistry indicated novel or otherwise unpredicted compounds act as pheromones. Here, we provide a brief review of the approaches to identifying pheromones, placing particular emphasis on the promise of using natural product chemistry together with assays of biological activity. Several case studies illustrate bioassay-guided fractionation as an approach to pheromone identification in fish and the unexpected diversity of pheromone structures discovered by natural product chemistry. With recent advances in natural product chemistry, bioassay-guided fractionation is likely to unveil an even broader collection of pheromone structures and enable research that spans across disciplines.
Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

Directory of Open Access Journals (Sweden)

Anwar Rayan

Full Text Available Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.
Natural Products Research in South Africa: End of an Era on Land or ...

African Journals Online (AJOL)

NICO

single era of natural product chemistry research in South Africa but rather three ... The Specialization Era (ca. 1960–1990) ... South African Natural Products in the International Drug. Discovery .... subsequently proposed that 24 was formed through an initial ... complete elimination of M. grisea infestation by the commercial.

Natural Product Biosynthetic Diversity and Comparative Genomics of the Cyanobacteria.

Science.gov (United States)

Dittmann, Elke; Gugger, Muriel; Sivonen, Kaarina; Fewer, David P

2015-10-01

Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with intricate chemical structures and potent biological activities. The bulk of these natural products are known from just a handful of genera. Recent efforts have elucidated the mechanisms underpinning the biosynthesis of a diverse array of natural products from cyanobacteria. Many of the biosynthetic mechanisms are unique to cyanobacteria or rarely described from other organisms. Advances in genome sequence technology have precipitated a deluge of genome sequences for cyanobacteria. This makes it possible to link known natural products to biosynthetic gene clusters but also accelerates the discovery of new natural products through genome mining. These studies demonstrate that cyanobacteria encode a huge variety of cryptic gene clusters for the production of natural products, and the known chemical diversity is likely to be just a fraction of the true biosynthetic capabilities of this fascinating and ancient group of organisms. Copyright © 2015. Published by Elsevier Ltd.
High-throughput screening platform for natural product-based drug discovery against 3 neglected tropical diseases: human African trypanosomiasis, leishmaniasis, and Chagas disease.

Science.gov (United States)

Annang, F; Pérez-Moreno, G; García-Hernández, R; Cordon-Obras, C; Martín, J; Tormo, J R; Rodríguez, L; de Pedro, N; Gómez-Pérez, V; Valente, M; Reyes, F; Genilloud, O; Vicente, F; Castanys, S; Ruiz-Pérez, L M; Navarro, M; Gamarro, F; González-Pacanowska, D

2015-01-01

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography-mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites. © 2014 Society for Laboratory Automation and Screening.
Trends in the Discovery of New Marine Natural Products from Invertebrates over the Last Two Decades – Where and What Are We Bioprospecting?

Science.gov (United States)

Leal, Miguel Costa; Puga, João; Serôdio, João; Gomes, Newton C. M.; Calado, Ricardo

2012-01-01

It is acknowledged that marine invertebrates produce bioactive natural products that may be useful for developing new drugs. By exploring untapped geographical sources and/or novel groups of organisms one can maximize the search for new marine drugs to treat human diseases. The goal of this paper is to analyse the trends associated with the discovery of new marine natural products from invertebrates (NMNPI) over the last two decades. The analysis considers different taxonomical levels and geographical approaches of bioprospected species. Additionally, this research is also directed to provide new insights into less bioprospected taxa and world regions. In order to gather the information available on NMNPI, the yearly-published reviews of Marine Natural Products covering 1990–2009 were surveyed. Information on source organisms, specifically taxonomical information and collection sites, was assembled together with additional geographical information collected from the articles originally describing the new natural product. Almost 10000 NMNPI were discovered since 1990, with a pronounced increase between decades. Porifera and Cnidaria were the two dominant sources of NMNPI worldwide. The exception was polar regions where Echinodermata dominated. The majority of species that yielded the new natural products belong to only one class of each Porifera and Cnidaria phyla (Demospongiae and Anthozoa, respectively). Increased bioprospecting efforts were observed in the Pacific Ocean, particularly in Asian countries that are associated with the Japan Biodiversity Hotspot and the Kuroshio Current. Although results show comparably less NMNPI from polar regions, the number of new natural products per species is similar to that recorded for other regions. The present study provides information to future bioprospecting efforts addressing previously unexplored taxonomic groups and/or regions. We also highlight how marine invertebrates, which in some cases have no commercial value
Applied metabolomics in drug discovery.

Science.gov (United States)

Cuperlovic-Culf, M; Culf, A S

2016-08-01

The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.
Marine Natural Products as Prototype Agrochemical Agents

Science.gov (United States)

Peng, Jiangnan; Shen, Xiaoyu; El Sayed, Khalid A.; Dunbar, D. C Harles; Perry, Tony L.; Wilkins, Scott P.; Hamann, Mark T.; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A.

2016-01-01

In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents. PMID:12670165
Chemical Biology of Microbial Anticancer Natural Products

DEFF Research Database (Denmark)

Bladt, Tanja Thorskov; Gotfredsen, Charlotte Held

than 100 years. New natural products (NPs) are continually discovered and with the increase in selective biological assays, previously described compounds often also display novel bioactivities, justifying their presence in novel screening efforts. Screening and discovery of compounds with activity...... towards chronic lymphocytic leukemia (CLL) cells is crucial since CLL is considered as an incurable disease. To discover novel agents that targets CLL cells is complicated. CLL cells rapidly undergo apoptosis in vitro when they are removed from their natural microenvironment, even though they are long...
Symbiotic Microbes from Marine Invertebrates: Driving a New Era of Natural Product Drug Discovery

Directory of Open Access Journals (Sweden)

Alix Blockley

2017-10-01

Full Text Available Invertebrates account for more than 89% of all extant organisms in the marine environment, represented by over 174,600 species (recorded to date. Such diversity is mirrored in (or more likely increased by the microbial symbionts associated with this group and in the marine natural products (or MNPs that they produce. Since the early 1950s over 20,000 MNPs have been discovered, including compounds produced by symbiotic bacteria, and the chemical diversity of compounds produced from marine sources has led to them being referred to as "blue gold" in the search for new drugs. For example, 80% of novel antibiotics stemming from the marine environment have come from Actinomycetes, many of which can be found associated with marine sponges, and compounds with anti-tumorigenic and anti-diabetic potential have also been isolated from marine symbionts. In fact, it has been estimated that marine sources formed the basis of over 50% of FDA-approved drugs between 1981 and 2002. In this review, we explore the diversity of marine microbial symbionts by examining their use as the producers of novel pharmaceutical actives, together with a discussion of the opportunities and constraints offered by “blue gold” drug discovery.
The Budding Yeast “Saccharomyces cerevisiae” as a Drug Discovery Tool to Identify Plant-Derived Natural Products with Anti-Proliferative Properties

Directory of Open Access Journals (Sweden)

Bouchra Qaddouri

2011-01-01

Full Text Available The budding yeast Saccharomyces cerevisiae is a valuable system to study cell-cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell-cycle machinery between yeast and humans, yeast studies are directly relevant to anticancer-drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second-generation molecules. Here we describe our methodology for screening a library of plant-derived natural products in yeast in order to identify and characterize new compounds with anti-proliferative properties.
Impact of Recent Discoveries on Petroleum and Natural Gas Exploration: Emphasis on India

OpenAIRE

Herndon, J. Marvin

2010-01-01

Two discoveries have greatly impacted understanding relevant to the origination and emplacement of petroleum and natural gas deposits. One discovery, pertaining to hydrocarbon formation from methane broadens significantly potential regions where abiotic petroleum and natural gas deposits might be found. The other, discovery of the physical impossibility of Earth-mantle convection, restricts the range and domain of geodynamic behavior, and leads to new insights on the formation of petroleum an...
LC-NMR: profiling and dereplication of natural product extracts

International Nuclear Information System (INIS)

Urban, Sylvia

2006-01-01

Natural products have served as a major source of drugs for centuries, with over half of the pharmaceuticals in use today derived from natural origins. Natural products continue to play a dominant role in the discovery of leads for the development of drugs for the treatment of human diseases. Much remains to be explored, particularly the marine and microbial environments, from which a host of novel bioactive chemical entities await discovery. The search for new drugs from natural origins (either terrestrial or marine) involves screening of extracts for the presence of novel compounds and an investigation of their biological activities. Suspected novel or bioactive compounds are usually isolated to elucidate the structure and for further biological and toxicological testing. The path that leads from the intact terrestrial or marine organism to the pure constituents is long, involving work that might last from weeks to years. Recognition of natural products at the earliest possible stage of separation is known as dereplication and is essential to avoid the time-consuming isolation of common constituents and nuisance compounds. In the search for new natural products, crude extracts are typically subjected to multi-step work-up and isolation procedures, which include various separation methods, in order to obtain pure compounds whose structure is then elucidated using off-line spectroscopic methods such as nuclear magnetic resonance (NMR) and mass spectroscopy (MS). The characterisation of a natural product can be summarised by the information obtained from each of the individual spectroscopic techniques. With the application of one or more of these individual techniques a dereplication by partial characterisation is possible. As natural product extracts often contain a large number of closely related, and thus difficult to separate, compounds, this classical approach may become very tedious and time-consuming. The characterisation of natural products in complex
Informatic search strategies to discover analogues and variants of natural product archetypes.

Science.gov (United States)

Johnston, Chad W; Connaty, Alex D; Skinnider, Michael A; Li, Yong; Grunwald, Alyssa; Wyatt, Morgan A; Kerr, Russell G; Magarvey, Nathan A

2016-03-01

Natural products are a crucial source of antimicrobial agents, but reliance on low-resolution bioactivity-guided approaches has led to diminishing interest in discovery programmes. Here, we demonstrate that two in-house automated informatic platforms can be used to target classes of biologically active natural products, specifically, peptaibols. We demonstrate that mass spectrometry-based informatic approaches can be used to detect natural products with high sensitivity, identifying desired agents present in complex microbial extracts. Using our specialised software packages, we could elaborate specific branches of chemical space, uncovering new variants of trichopolyn and demonstrating a way forward in mining natural products as a valuable source of potential pharmaceutical agents.
[Elaboration of Pseudo-natural Products Using Artificial In Vitro Biosynthesis Systems].

Science.gov (United States)

Goto, Yuki

2018-01-01

Peptidic natural products often consist of not only proteinogenic building blocks but also unique non-proteinogenic structures such as macrocyclic scaffolds and N-methylated backbones. Since such non-proteinogenic structures are important structural motifs that contribute to diverse bioactivity, we have proposed that peptides with non-proteinogenic structures should be attractive candidates as artificial bioactive peptides mimicking natural products, or so-called pseudo-natural products. We previously devised an engineered translation system for pseudo-natural peptides, referred to as the flexible in vitro translation (FIT) system. This system enabled "one-pot" synthesis of highly diverse pseudo-natural peptide libraries, which can be rapidly screened by mRNA display technology for the discovery of pseudo-natural peptides with diverse bioactivities.
The Traditional Medicine and Modern Medicine from Natural Products

Directory of Open Access Journals (Sweden)

Haidan Yuan

2016-04-01

Full Text Available Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.
The Traditional Medicine and Modern Medicine from Natural Products.

Science.gov (United States)

Yuan, Haidan; Ma, Qianqian; Ye, Li; Piao, Guangchun

2016-04-29

Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.
Chemistry of natural products: A veritable approach to the ...

African Journals Online (AJOL)

Even with the advent of newer technologies such as combinatorial chemistry, robotics, high throughput screening (HTS), bioinformatics, and in silico molecular modelling, natural products still play a crucial role in drug discovery. This is because they provide an unparalleled range of chemical diversity on which the newer ...
Gas reserves, discoveries and production

International Nuclear Information System (INIS)

Saniere, A.

2006-01-01

Between 2000 and 2004, new discoveries, located mostly in the Asia/Pacific region, permitted a 71% produced reserve replacement rate. The Middle East and the offshore sector represent a growing proportion of world gas production Non-conventional gas resources are substantial but are not exploited to any significant extent, except in the United States, where they account for 30% of U.S. gas production. (author)
Anti-cancer natural products isolated from chinese medicinal herbs

Directory of Open Access Journals (Sweden)

Wu Guosheng

2011-07-01

Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.
Mass spectrometry-driven drug discovery for development of herbal medicine.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.
The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

Directory of Open Access Journals (Sweden)

Peter Mubanga Cheuka

2016-12-01

Full Text Available Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness, leishmaniasis, schistosomiasis and lymphatic filariasis.
Integrated analytical approaches towards toxic algal natural products discovery

DEFF Research Database (Denmark)

Larsen, Thomas Ostenfeld; Rasmussen, Silas Anselm; Gedsted Andersen, Mikael

Microalgae are known to produce toxins which affect the marine ecosystems. This include compounds active against competitors, grazers and in many cases also fish (1,2). Many strategies can be followed for discovery of novel bioactive secondary metabolites from marine sources. We have previously...... is dereplication, where we use explorative solid-phase extraction (E-SPE), and UHPLC-state-of-the-art high resolution mass spectrometry (waste time isolating and elucidating...

Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.

Science.gov (United States)

Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio

2014-07-01

Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.
Flavin-catalyzed redox tailoring reactions in natural product biosynthesis.

Science.gov (United States)

Teufel, Robin

2017-10-15

Natural products are distinct and often highly complex organic molecules that constitute not only an important drug source, but have also pushed the field of organic chemistry by providing intricate targets for total synthesis. How the astonishing structural diversity of natural products is enzymatically generated in biosynthetic pathways remains a challenging research area, which requires detailed and sophisticated approaches to elucidate the underlying catalytic mechanisms. Commonly, the diversification of precursor molecules into distinct natural products relies on the action of pathway-specific tailoring enzymes that catalyze, e.g., acylations, glycosylations, or redox reactions. This review highlights a selection of tailoring enzymes that employ riboflavin (vitamin B2)-derived cofactors (FAD and FMN) to facilitate unusual redox catalysis and steer the formation of complex natural product pharmacophores. Remarkably, several such recently reported flavin-dependent tailoring enzymes expand the classical paradigms of flavin biochemistry leading, e.g., to the discovery of the flavin-N5-oxide - a novel flavin redox state and oxygenating species. Copyright © 2017 Elsevier Inc. All rights reserved.
A High-Throughput Screening Platform of Microbial Natural Products for the Discovery of Molecules with Antibiofilm Properties against Salmonella

Science.gov (United States)

Paytubi, Sonia; de La Cruz, Mercedes; Tormo, Jose R.; Martín, Jesús; González, Ignacio; González-Menendez, Victor; Genilloud, Olga; Reyes, Fernando; Vicente, Francisca; Madrid, Cristina; Balsalobre, Carlos

2017-01-01

In this report, we describe a High-Throughput Screening (HTS) to identify compounds that inhibit biofilm formation or cause the disintegration of an already formed biofilm using the Salmonella Enteritidis 3934 strain. Initially, we developed a new methodology for growing Salmonella biofilms suitable for HTS platforms. The biomass associated with biofilm at the solid-liquid interface was quantified by staining both with resazurin and crystal violet, to detect living cells and total biofilm mass, respectively. For a pilot project, a subset of 1120 extracts from the Fundación MEDINA's collection was examined to identify molecules with antibiofilm activity. This is the first validated HTS assay of microbial natural product extracts which allows for the detection of four types of activities which are not mutually exclusive: inhibition of biofilm formation, detachment of the preformed biofilm and antimicrobial activity against planktonic cells or biofilm embedded cells. Currently, several extracts have been selected for further fractionation and purification of the active compounds. In one of the natural extracts patulin has been identified as a potent molecule with antimicrobial activity against both, planktonic cells and cells within the biofilm. These findings provide a proof of concept that the developed HTS can lead to the discovery of new natural compounds with antibiofilm activity against Salmonella and its possible use as an alternative to antimicrobial therapies and traditional disinfectants. PMID:28303128
Exploring Natural Products from the Biodiversity of Pakistan for Computational Drug Discovery Studies: Collection, Optimization, Design and Development of A Chemical Database (ChemDP).

Science.gov (United States)

Mirza, Shaher Bano; Bokhari, Habib; Fatmi, Muhammad Qaiser

2015-01-01

Pakistan possesses a rich and vast source of natural products (NPs). Some of these secondary metabolites have been identified as potent therapeutic agents. However, the medicinal usage of most of these compounds has not yet been fully explored. The discoveries for new scaffolds of NPs as inhibitors of certain enzymes or receptors using advanced computational drug discovery approaches are also limited due to the unavailability of accurate 3D structures of NPs. An organized database incorporating all relevant information, therefore, can facilitate to explore the medicinal importance of the metabolites from Pakistani Biodiversity. The Chemical Database of Pakistan (ChemDP; release 01) is a fully-referenced, evolving, web-based, virtual database which has been designed and developed to introduce natural products (NPs) and their derivatives from the biodiversity of Pakistan to Global scientific communities. The prime aim is to provide quality structures of compounds with relevant information for computer-aided drug discovery studies. For this purpose, over 1000 NPs have been identified from more than 400 published articles, for which 2D and 3D molecular structures have been generated with a special focus on their stereochemistry, where applicable. The PM7 semiempirical quantum chemistry method has been used to energy optimize the 3D structure of NPs. The 2D and 3D structures can be downloaded as .sdf, .mol, .sybyl, .mol2, and .pdb files - readable formats by many chemoinformatics/bioinformatics software packages. Each entry in ChemDP contains over 100 data fields representing various molecular, biological, physico-chemical and pharmacological properties, which have been properly documented in the database for end users. These pieces of information have been either manually extracted from the literatures or computationally calculated using various computational tools. Cross referencing to a major data repository i.e. ChemSpider has been made available for overlapping
Dereplication of Microbial Natural Products by LC-DAD-TOFMS

DEFF Research Database (Denmark)

Nielsen, Kristian Fog; Månsson, Maria; Rank, Christian

2011-01-01

Dereplication, the rapid identification of known compounds present in a mixture, is crucial to the fast discovery of novel natural products. Determining the elemental composition of compounds in mixtures and tentatively identifying natural products using MS/MS and UV/vis spectra is becoming easier...... with advances in analytical equipment and better compound databases. Here we demonstrate the use of LC-UV/vis-MS-based dereplication using data from UV/vis diode array detection and ESI+/ESI– time-of-flight MS for assignment of 719 microbial natural product and mycotoxin reference standards. ESI+ was the most...... unambiguously using multiple adduct ions, while a further 41% of the compounds were detected only as [M – H]−. The most reliable interpretations of conflicting ESI+ and ESI– data on a chromatographic peak were from the ionization polarity with the most intense ionization. Poor ionization was most common...
Synthesis and Biological Investigation of Antioxidant Pyrrolomorpholine Spiroketal Natural Products

Science.gov (United States)

Verano, Alyssa Leigh

The pyrrolomorpholine spiroketal natural product family is comprised of epimeric furanose and pyranose isomers. These compounds were isolated from diverse plant species, all of which are used as traditional Chinese medicines for the treatment of a variety of diseases. Notably, the spiroketal natural products acortatarins A and B exhibit antioxidant activity in a diabetic renal cell model, significantly attenuating hyperglycemia-induced production of reactive oxygen species (ROS), a hallmark of diabetic nephropathy. The xylapyrrosides, additional members of the family, also inhibit t-butyl hydroperoxide-induced cytotoxicity in rat vascular smooth muscle cells. Accordingly, these natural products have therapeutic potential for the treatment of oxidative stress-related pathologies, and synthetic access would provide an exciting opportunity to investigate bioactivity and mechanism of action. Herein, we report the stereoselective synthesis of acortatarins A and B, furanose members of the pyrrolomorpholine spiroketal family. Our synthetic route was expanded to synthesize the pyranose congeners, thus completing entire D-enantiomeric family of natural products. Efficient access towards these scaffolds enabled systematic analogue synthesis, investigation of mechanism-of-action, and the discovery of novel antioxidants.
Structure-based synthesis from natural products to drug prototypes

International Nuclear Information System (INIS)

Hanessian, S.

2009-01-01

X-Ray crystallographic data available from complexes of natural and synthetic molecules with the enzyme thrombin has aided to the design and synthesis of truncated and hybrid molecules exhibiting excellent inhibition in vitro. The vital importance of natural products for the well-being of man has been known lor millennia. Their therapeutic benefits to alleviate pain or cure diseases continue to rank natural products among the primary sources of potential drugs. Great advances have been made in the methods of isolation, identification, and structure elucidation of some of the most complex natural products in recent years. The advent of molecular biology and genetic mapping has also aided in our understanding of the intriguing biosynthetic pathways leading to various classes of therapeutically relevant antibiotic, anticancer, and related natural products. Elegant and practical methodology has been developed leading to the total synthesis of virtually every class of medicinally important natural product. In some cases, natural products or their chemically modified congeners have been manufactured by total synthesis on an industrial level which is a testament to the ingenuity of process chemists. In spite of their potent activities HI enzymatic ox receptor-mediated assays, not all natural products are amenable to being developed as marketable drags. In many instances unfavorable pharmacological effects cannot be overcome without drastic structural and functional modifications, which may also result in altered efficacy. Structure modification through truncation, functional group variations, isosteric replacements, and skeletal rigidifications aided by molecular modeling, X ray crystallography of protein targets, or NMR data are valid objectives in the context of small molecule drug discovery starting with bioactive natural products. A large proportion of these pertain to chemotherapeutic agents against cancer
Natural Products Combating Neurodegeneration: Parkinson's Disease.

Science.gov (United States)

Solayman, Md; Islam, Md Asiful; Alam, Fahmida; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua

2017-01-01

Parkinson's disease (PD) is characterized by neurodegeneration and a progressive functional impairment of the midbrain nigral dopaminergic neurons. The cause remains unknown; however, several pathological processes and central factors, such as protein aggregation, mitochondrial dysfunction, iron accumulation, neuroinflammation and oxidative stress, have been reported. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors and anticholinergics to replace DA. When drug therapy is not satisfactory, surgical treatments are recommended. Unfortunately, the existing conventional strategies that target PD are associated with numerous side effects and possess an economic burden. Therefore, novel therapeutic approaches that regulate the pathways leading to neuronal death and dysfunction are necessary. For many years, nature has provided the primary resource for the discovery of potential therapeutic agents. Remarkably, many natural products from medicinal plants, fruits and vegetables have been demonstrated to be efficacious anti-Parkinson agents. These products possess neuroprotective properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding iron accumulation, protein misfolding and the maintenance of proteasomal degradation, as well as mitochondrial homeostasis. The aim of this review is to report the available anti-Parkinson agents based on natural products and delineate their therapeutic actions, which act on various pathways. Overall, this review emphasizes the types of natural products that are potential future resources in the treatment of PD as novel regimens or supplementary agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Biomimicry as a basis for drug discovery.

Science.gov (United States)

Kolb, V M

1998-01-01

Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term "natural product" is often used synonymously with "secondary metabolite." Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed "inventive evolution." It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products ("unnatural natural products"), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.
Screening of a virtual mirror-image library of natural products.

Science.gov (United States)

Noguchi, Taro; Oishi, Shinya; Honda, Kaori; Kondoh, Yasumitsu; Saito, Tamio; Ohno, Hiroaki; Osada, Hiroyuki; Fujii, Nobutaka

2016-06-08

We established a facile access to an unexplored mirror-image library of chiral natural product derivatives using d-protein technology. In this process, two chemical syntheses of mirror-image substances including a target protein and hit compound(s) allow the lead discovery from a virtual mirror-image library without the synthesis of numerous mirror-image compounds.
Recent advances in the elucidation of enzymatic function in natural product biosynthesis [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Gao-Yi Tan

2016-02-01

Full Text Available With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.
Recent advances in the elucidation of enzymatic function in natural product biosynthesis [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Tan Gao-Yi

2015-12-01

Full Text Available With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.
Pre-fractionated Microbial Samples Ã¢Â€Â“ The Second Generation Natural Products Library at Wyeth

Directory of Open Access Journals (Sweden)

Melissa M. Wagenaar

2008-06-01

Full Text Available From the beginning of the antibiotic era in the 1940s to the present, Wyeth has sustained an active research program in the area of natural products discovery. This program has continually evolved through the years in order to best align with the Ã¢Â€ÂœcurrentÃ¢Â€Â drug discovery paradigm in the pharmaceutical industry. The introduction of highthroughput screening and the miniaturization of assays have created a need to optimize natural product samples to better suit these new technologies. Furthermore, natural product programs are faced with an ever shortening time period from hit detection to lead characterization. To address these issues, Wyeth has created a pre-fractionated natural products library using reversed-phase HPLC to complement their existing library of crude extracts. The details of the pre-fractionated library and a cost-benefit analysis will be presented in this review.
UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small molecule natural product libraries

Science.gov (United States)

Generation of natural product libraries containing column fractions, each with only a few small molecules, by a high throughput, automated fractionation system has made it possible to implement an improved dereplication strategy for selection and prioritization of hits in a natural product discovery...
Natural product-based nanomedicine: recent advances and issues

Directory of Open Access Journals (Sweden)

Watkins R

2015-09-01

Full Text Available Rebekah Watkins,1,2,* Ling Wu,1,* Chenming Zhang,3–5 Richey M Davis,3,5,6 Bin Xu1,3 1Department of Biochemistry, 2Program in Nanoscience, 3Center for Drug Discovery, 4Department of Biological Systems Engineering, 5Institute for Critical Technology and Applied Science, 6Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA *These authors contributed equally to this work Abstract: Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. Keywords: natural products, nanomedicine, drug delivery, bioavailability, targeting, controlled release
Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

Science.gov (United States)

Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

2015-01-01

Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.
Direct capture and heterologous expression of Salinispora natural product genes for the biosynthesis of enterocin.

Science.gov (United States)

Bonet, Bailey; Teufel, Robin; Crüsemann, Max; Ziemert, Nadine; Moore, Bradley S

2015-03-27

Heterologous expression of secondary metabolic pathways is a promising approach for the discovery and characterization of bioactive natural products. Herein we report the first heterologous expression of a natural product from the model marine actinomycete genus Salinispora. Using the recently developed method of yeast-mediated transformation-associated recombination for natural product gene clusters, we captured a type II polyketide synthase pathway from Salinispora pacifica with high homology to the enterocin pathway from Streptomyces maritimus and successfully produced enterocin in two different Streptomyces host strains. This result paves the way for the systematic interrogation of Salinispora's promising secondary metabolome.
An Overview on Marine Sponge-Symbiotic Bacteria as Unexhausted Sources for Natural Product Discovery

Directory of Open Access Journals (Sweden)

Candice M. Brinkmann

2017-09-01

Full Text Available Microbial symbiotic communities of marine macro-organisms carry functional metabolic profiles different to the ones found terrestrially and within surrounding marine environments. These symbiotic bacteria have increasingly been a focus of microbiologists working in marine environments due to a wide array of reported bioactive compounds of therapeutic importance resulting in various patent registrations. Revelations of symbiont-directed host specific functions and the true nature of host-symbiont interactions, combined with metagenomic advances detecting functional gene clusters, will inevitably open new avenues for identification and discovery of novel bioactive compounds of biotechnological value from marine resources. This review article provides an overview on bioactive marine symbiotic organisms with specific emphasis placed on the sponge-associated ones and invites the international scientific community to contribute towards establishment of in-depth information of the environmental parameters defining selection and acquisition of true symbionts by the host organisms.
A roadmap for natural product discovery based on large-scale genomics and metabolomics

Science.gov (United States)

Actinobacteria encode a wealth of natural product biosynthetic gene clusters, whose systematic study is complicated by numerous repetitive motifs. By combining several metrics we developed a method for global classification of these gene clusters into families (GCFs) and analyzed the biosynthetic ca...
Phylogeny-guided (meta)genome mining approach for the targeted discovery of new microbial natural products.

Science.gov (United States)

Kang, Hahk-Soo

2017-02-01

Genomics-based methods are now commonplace in natural products research. A phylogeny-guided mining approach provides a means to quickly screen a large number of microbial genomes or metagenomes in search of new biosynthetic gene clusters of interest. In this approach, biosynthetic genes serve as molecular markers, and phylogenetic trees built with known and unknown marker gene sequences are used to quickly prioritize biosynthetic gene clusters for their metabolites characterization. An increase in the use of this approach has been observed for the last couple of years along with the emergence of low cost sequencing technologies. The aim of this review is to discuss the basic concept of a phylogeny-guided mining approach, and also to provide examples in which this approach was successfully applied to discover new natural products from microbial genomes and metagenomes. I believe that the phylogeny-guided mining approach will continue to play an important role in genomics-based natural products research.

Natural Gas Reserves, Development and Production in Qatar

International Nuclear Information System (INIS)

Naji, Abi-Aad.

1998-01-01

Qatar entered the club of natural gas exporters in early 1997 when the first shipment of liquefied natural gas left the state for Japan. Qatar was helped by the discovery in 1971 of supergiant North Field gas field, the country's suitable location between the established gas consuming markets in Europe and Southeast Asia, and its proximity to developing markets in the Indian subcontinent and in neighbouring countries. All that have combined to make gas export projects from Qatar economically viable and commercially attractive. In addition to export-oriented development, increased gas production from the North Field is planned for meeting a growing domestic demand for gas as fuel and feedstock for power generation and desalination plants, as well as value-added petrochemical and fertilizer industries
Price interactions and discovery among natural gas spot markets in North America

International Nuclear Information System (INIS)

Park, Haesun; Mjelde, James W.; Bessler, David A.

2008-01-01

Recent advances in modeling causal flows with time series analysis are used to study relationships among eight North American natural gas spot market prices. Results indicate that the Canadian and US natural gas market is a single highly integrated market. Further results indicate that price discovery tends to reflect both regions of excess demand and supply. Across North America, Malin Hub in Oregon, Chicago Hub, Illinois, Waha, Texas, and Henry Hub, Louisiana region, are the most important markets for price discovery. Opal Hub in Wyoming is an information sink in contemporaneous time, receiving price information but passing on no price information. AECO Hub in Alberta, Canada, receives price signals from several markets and passes on information to Opal and the Oklahoma region. (author)
Design of compound libraries based on natural product scaffolds and protein structure similarity clustering (PSSC)

NARCIS (Netherlands)

Balamurugan, Rengarajan; Dekker, Frank J; Waldmann, Herbert; Dekker, Frans

Recent advances in structural biology, bioinformatics and combinatorial chemistry have significantly impacted the discovery of small molecules that modulate protein functions. Natural products which have evolved to bind to proteins may serve as biologically validated starting points for the design
Exploitation of Aspergillus terreus for the Production of Natural Statins

Directory of Open Access Journals (Sweden)

Mishal Subhan

2016-04-01

Full Text Available The fungus Aspergillus (A. terreus has dominated the biological production of the “blockbuster” drugs known as statins. The statins are a class of drugs that inhibit HMG-CoA reductase and lead to lower cholesterol production. The statins were initially discovered in fungi and for many years fungi were the sole source for the statins. At present, novel chemically synthesised statins are produced as inspired by the naturally occurring statin molecules. The isolation of the natural statins, compactin, mevastatin and lovastatin from A. terreus represents one of the great achievements of industrial microbiology. Here we review the discovery of statins, along with strategies that have been applied to scale up their production by A. terreus strains. The strategies encompass many of the techniques available in industrial microbiology and include the optimization of media and fermentation conditions, the improvement of strains through classical mutagenesis, induced genetic manipulation and the use of statistical design.
Scientific workflows as productivity tools for drug discovery.

Science.gov (United States)

Shon, John; Ohkawa, Hitomi; Hammer, Juergen

2008-05-01

Large pharmaceutical companies annually invest tens to hundreds of millions of US dollars in research informatics to support their early drug discovery processes. Traditionally, most of these investments are designed to increase the efficiency of drug discovery. The introduction of do-it-yourself scientific workflow platforms has enabled research informatics organizations to shift their efforts toward scientific innovation, ultimately resulting in a possible increase in return on their investments. Unlike the handling of most scientific data and application integration approaches, researchers apply scientific workflows to in silico experimentation and exploration, leading to scientific discoveries that lie beyond automation and integration. This review highlights some key requirements for scientific workflow environments in the pharmaceutical industry that are necessary for increasing research productivity. Examples of the application of scientific workflows in research and a summary of recent platform advances are also provided.
Marine Sponge Derived Natural Products between 2001 and 2010: Trends and Opportunities for Discovery of Bioactives

Science.gov (United States)

Mehbub, Mohammad Ferdous; Lei, Jie; Franco, Christopher; Zhang, Wei

2014-01-01

Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity of sponge-derived new natural products discovered between 2001 and 2010. The data has been analyzed with a view to gaining an outlook on the future trends and opportunities in the search for new compounds and their sources from marine sponges. PMID:25196730
Discovery of a natural product-like iNOS inhibitor by molecular docking with potential neuroprotective effects in vivo.

Directory of Open Access Journals (Sweden)

Hai-Jing Zhong

Full Text Available In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications.
Nephrotoxicity of Natural Products.

Science.gov (United States)

Nauffal, Mary; Gabardi, Steven

2016-01-01

The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education. © 2016 S. Karger AG, Basel.
Investigating Nature's Mysteries for Drug Development

Science.gov (United States)

More than half of the drugs approved to treat cancer come from a natural product or a natural product prototype. Scientists in NCI-Frederick's Natural Products Branch are exploring ways to harness chemicals produced by marine invertebrates, other animals, plants, and microbes for cancer drug discovery.
Comparative analysis of chemical similarity methods for modular natural products with a hypothetical structure enumeration algorithm.

Science.gov (United States)

Skinnider, Michael A; Dejong, Chris A; Franczak, Brian C; McNicholas, Paul D; Magarvey, Nathan A

2017-08-16

Natural products represent a prominent source of pharmaceutically and industrially important agents. Calculating the chemical similarity of two molecules is a central task in cheminformatics, with applications at multiple stages of the drug discovery pipeline. Quantifying the similarity of natural products is a particularly important problem, as the biological activities of these molecules have been extensively optimized by natural selection. The large and structurally complex scaffolds of natural products distinguish their physical and chemical properties from those of synthetic compounds. However, no analysis of the performance of existing methods for molecular similarity calculation specific to natural products has been reported to date. Here, we present LEMONS, an algorithm for the enumeration of hypothetical modular natural product structures. We leverage this algorithm to conduct a comparative analysis of molecular similarity methods within the unique chemical space occupied by modular natural products using controlled synthetic data, and comprehensively investigate the impact of diverse biosynthetic parameters on similarity search. We additionally investigate a recently described algorithm for natural product retrobiosynthesis and alignment, and find that when rule-based retrobiosynthesis can be applied, this approach outperforms conventional two-dimensional fingerprints, suggesting it may represent a valuable approach for the targeted exploration of natural product chemical space and microbial genome mining. Our open-source algorithm is an extensible method of enumerating hypothetical natural product structures with diverse potential applications in bioinformatics.
Discovery of Natural Products as Novel and Potent FXR Antagonists by Virtual Screening

Science.gov (United States)

Diao, Yanyan; Jiang, Jing; Zhang, Shoude; Li, Shiliang; Shan, Lei; Huang, Jin; Zhang, Weidong; Li, Honglin

2018-04-01

Farnesoid X receptor (FXR) is a member of nuclear receptor family involved in multiple physiological processes through regulating specific target genes. The critical role of FXR as a transcriptional regulator makes it a promising target for diverse diseases, especially those related to metabolic disorders such as diabetes and cholestasis. However, the underlying activation mechanism of FXR is still a blur owing to the absence of proper FXR modulators. To identify potential FXR modulators, an in-house natural product database (NPD) containing over 4000 compounds was screened by structure-based virtual screening strategy and subsequent hit-based similarity searching method. After the yeast two-hybrid (Y2H) assay, six natural products were identified as FXR antagonists which blocked the CDCA-induced SRC-1 association. The IC50 values of compounds 2a, a diterpene bearing polycyclic skeleton, and 3a, named daphneone with chain scaffold, are as low as 1.29 μM and 1.79 μM, respectively. Compared to the control compound guggulsterone (IC50 = 6.47 μM), compounds 2a and 3a displayed 5-fold and 3-fold higher antagonistic activities against FXR, respectively. Remarkably, the two representative compounds shared low topological similarities with other reported FXR antagonists. According to the putative binding poses, the molecular basis of these antagonists against FXR was also elucidated in this report.
Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials.

Science.gov (United States)

Choudhary, Alka; Naughton, Lynn M; Montánchez, Itxaso; Dobson, Alan D W; Rai, Dilip K

2017-08-28

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis and chemical structure elucidation, have accelerated the numbers of antimicrobial molecules originating from the ocean moving into clinical trials. The chemical diversity associated with these marine-derived molecules is immense, varying from simple linear peptides and fatty acids to complex alkaloids, terpenes and polyketides, etc. Such an array of structurally distinct molecules performs functionally diverse biological activities against many pathogenic bacteria and fungi, making marine-derived natural products valuable commodities, particularly in the current age of antimicrobial resistance. In this review, we have highlighted several marine-derived natural products (and their synthetic derivatives), which have gained recognition as effective antimicrobial agents over the past five years (2012-2017). These natural products have been categorized based on their chemical structures and the structure-activity mediated relationships of some of these bioactive molecules have been discussed. Finally, we have provided an insight into how genome mining efforts are likely to expedite the discovery of novel antimicrobial compounds.
Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca2+ Current Inhibitors for Hypotensive Agent Discovery

Directory of Open Access Journals (Sweden)

Hélène Carreyre

2017-05-01

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

Directory of Open Access Journals (Sweden)

Moon Nyeo Park

2017-01-01

Full Text Available Common care for glioblastoma multiforme (GBM is a surgical resection followed by radiotherapy and temozolomide- (TMZ- based chemotherapy. Unfortunately, these therapies remain inadequate involving severe mortality and recurrence. Recently, new approaches discovering combinations of multiple inhibitors have been proposed along with the identification of key driver mutations that are specific to each patient. To date, this approach is still limited by the lack of effective therapy. Hopefully, novel compounds derived from natural products are suggested as potential solutions. Inhibitory effects of natural products on angiogenesis and metastasis and cancer suppressive effect of altering miRNA expression are provident discoveries. Angelica sinensis accelerates apoptosis by their key substances influencing factors of apoptosis pathways. Brazilin displays antitumor features by making influence on reactive oxygen species (ROS intensity. Sargassum serratifolium, flavonoids, and so on have antimetastasis effect. Ficus carica controls miRNA that inhibits translation of certain secretory pathway proteins during the UPR. Serratia marcescens and patupilone (EPO 906 are physically assessed materials through clinical trials related to GBM progression. Consequently, our review puts emphasis on the potential of natural products in GBM treatment by regulating multiple malignant cancer-related pathway solving pending problem such as reducing toxicity and side effect.
Discovery of a novel amino acid racemase through exploration of natural variation in Arabidopsis thaliana

Science.gov (United States)

Strauch, Renee C.; Svedin, Elisabeth; Dilkes, Brian; Chapple, Clint; Li, Xu

2015-01-01

Plants produce diverse low-molecular-weight compounds via specialized metabolism. Discovery of the pathways underlying production of these metabolites is an important challenge for harnessing the huge chemical diversity and catalytic potential in the plant kingdom for human uses, but this effort is often encumbered by the necessity to initially identify compounds of interest or purify a catalyst involved in their synthesis. As an alternative approach, we have performed untargeted metabolite profiling and genome-wide association analysis on 440 natural accessions of Arabidopsis thaliana. This approach allowed us to establish genetic linkages between metabolites and genes. Investigation of one of the metabolite–gene associations led to the identification of N-malonyl-d-allo-isoleucine, and the discovery of a novel amino acid racemase involved in its biosynthesis. This finding provides, to our knowledge, the first functional characterization of a eukaryotic member of a large and widely conserved phenazine biosynthesis protein PhzF-like protein family. Unlike most of known eukaryotic amino acid racemases, the newly discovered enzyme does not require pyridoxal 5′-phosphate for its activity. This study thus identifies a new d-amino acid racemase gene family and advances our knowledge of plant d-amino acid metabolism that is currently largely unexplored. It also demonstrates that exploitation of natural metabolic variation by integrating metabolomics with genome-wide association is a powerful approach for functional genomics study of specialized metabolism. PMID:26324904
Influenza neuraminidase: a druggable target for natural products.

Science.gov (United States)

Grienke, Ulrike; Schmidtke, Michaela; von Grafenstein, Susanne; Kirchmair, Johannes; Liedl, Klaus R; Rollinger, Judith M

2012-01-01

The imminent threat of influenza pandemics and repeatedly reported emergence of new drug-resistant influenza virus strains demonstrate the urgent need for developing innovative and effective antiviral agents for prevention and treatment. At present, influenza neuraminidase (NA), a key enzyme in viral replication, spread, and pathogenesis, is considered to be one of the most promising targets for combating influenza. Despite the substantial medical potential of NA inhibitors (NAIs), only three of these drugs are currently on the market (zanamivir, oseltamivir, and peramivir). Moreover, sudden changes in NAI susceptibility revealed the urgent need in the discovery/identification of novel inhibitors. Nature offers an abundance of biosynthesized compounds comprising chemical scaffolds of high diversity, which present an infinite pool of chemical entities for target-oriented drug discovery in the battle against this highly contagious pathogen. This review illuminates the increasing research efforts of the past decade (2000-2011), focusing on the structure, function and druggability of influenza NA, as well as its inhibition by natural products. Following a critical discussion of publications describing some 150 secondary plant metabolites tested for their inhibitory potential against influenza NA, the impact of three different strategies to identify and develop novel NAIs is presented: (i) bioactivity screening of herbal extracts, (ii) exploitation of empirical knowledge, and (iii) computational approaches. This work addresses the latest developments in theoretical and experimental research on properties of NA that are and will be driving anti-influenza drug development now and in the near future.
Economic impacts of natural resources on a regional economy: the case of the pre-salt oil discoveries in Espirito Santo, Brazil

Directory of Open Access Journals (Sweden)

Eduardo Amaral Haddad

2014-03-01

Full Text Available The Brazilian government has recently confirmed the discovery of a huge oil and natural gas field in the pre-salt layer of the country’s southeastern coast. It has been said that the oil fields can boost Brazil’s oil production and turn the country into one of the largest oil producers in the world. The fields are spatially concentrated in the coastal areas of a few Brazilian states that may directly benefit from oil production. This paper uses an interregional computable general equilibrium model to assess the impacts of pre-salt on the economy of the State of Espírito Santo, a region already characterized by an economic base that is heavily reliant on natural resources. We focus our analysis on the structural economic impacts on the local economy
Recent advances in combinatorial biosynthesis for drug discovery

Directory of Open Access Journals (Sweden)

Sun H

2015-02-01

Full Text Available Huihua Sun,1,* Zihe Liu,1,* Huimin Zhao,1,2 Ee Lui Ang1 1Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, Singapore; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA *These authors contributed equally to this work Abstract: Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1 precursor-directed biosynthesis; 2 enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3 pathway-level recombination. Recent examples of combinatorial biosynthesis employing these
Higgs Discovery

DEFF Research Database (Denmark)

Sannino, Francesco

2013-01-01

has been challenged by the discovery of a not-so-heavy Higgs-like state. I will therefore review the recent discovery \\cite{Foadi:2012bb} that the standard model top-induced radiative corrections naturally reduce the intrinsic non-perturbative mass of the composite Higgs state towards the desired...... via first principle lattice simulations with encouraging results. The new findings show that the recent naive claims made about new strong dynamics at the electroweak scale being disfavoured by the discovery of a not-so-heavy composite Higgs are unwarranted. I will then introduce the more speculative......I discuss the impact of the discovery of a Higgs-like state on composite dynamics starting by critically examining the reasons in favour of either an elementary or composite nature of this state. Accepting the standard model interpretation I re-address the standard model vacuum stability within...
Inhibitors of Microglial Neurotoxicity: Focus on Natural Products

Directory of Open Access Journals (Sweden)

Kyoungho Suk

2011-01-01

Full Text Available Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels.

Antiplasmodial Natural Products

Directory of Open Access Journals (Sweden)

Cláudio R. Nogueira

2011-03-01

Full Text Available Malaria is a human infectious disease that is caused by four species of Plasmodium. It is responsible for more than 1 million deaths per year. Natural products contain a great variety of chemical structures and have been screened for antiplasmodial activity as potential sources of new antimalarial drugs. This review highlights studies on natural products with antimalarial and antiplasmodial activity reported in the literature from January 2009 to November 2010. A total of 360 antiplasmodial natural products comprised of terpenes, including iridoids, sesquiterpenes, diterpenes, terpenoid benzoquinones, steroids, quassinoids, limonoids, curcubitacins, and lanostanes; flavonoids; alkaloids; peptides; phenylalkanoids; xanthones; naphthopyrones; polyketides, including halenaquinones, peroxides, polyacetylenes, and resorcylic acids; depsidones; benzophenones; macrolides; and miscellaneous compounds, including halogenated compounds and chromenes are listed in this review.
An Overview of Some Natural Products with Two A-Level Science Club Natural Products Experiments

Science.gov (United States)

Sosabowski, Michael Hal; Olivier, George W. J.; Jawad, Hala; Maatta, Sieja

2017-01-01

Natural products are ubiquitous in nature but do not form a large proportion of the A-level syllabuses in the UK. In this article we briefly discuss a small selection of natural products, focusing on alcohols, aldehydes and ketones, and alkaloids. We then outline two natural product experiments that are suitable for A-level chemistry clubs or…
Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study.

Directory of Open Access Journals (Sweden)

Simina M Boca

Full Text Available Serum metabolite profiling in Duchenne muscular dystrophy (DMD may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.
Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

Science.gov (United States)

Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.
A Natural Love of Natural Products

OpenAIRE

Kingston, David G. I.

2008-01-01

Recent research on the chemistry of natural products from the author?s group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies wit...
An analysis of the sponge Acanthostrongylophora igens’ microbiome yields an actinomycete that produces the natural product manzamine A

Directory of Open Access Journals (Sweden)

Amanda Leigh Waters

2014-10-01

Full Text Available Sponges have generated significant interest as a source of bioactive and elaborate secondary metabolites that hold promise for the development of novel therapeutics for the control of an array of human diseases. However, research and development of marine natural products can often be hampered by the difficulty associated with obtaining a stable and sustainable production source. Herein we report the first successful characterization and utilization of the microbiome of a marine invertebrate to identify a sustainable production source for an important natural product scaffold. Through molecular-microbial community analysis, optimization of fermentation conditions and MALDI-MS imaging, we provide the first report of a sponge-associated bacterium (Micromonospora sp. that produces the manzamine class of antimalarials from the Indo-Pacific sponge Acanthostrongylophora ingens (Thiele, 1899 (Class Demospongiae, Order Haplosclerida, Family Petrosiidae. These findings suggest that a general strategy of analysis of the macroorganism’s microbiome could significantly transform the field of natural products drug discovery by gaining access to not only novel drug leads, but the potential for sustainable production sources and biosynthetic genes at the same time.
Management and Treatment of Dengue and Chikungunya - Natural Products to the Rescue.

Science.gov (United States)

Suroowan, Shanoo; Mahomoodally, Fawzi; Ragoo, Luxcha

2016-01-01

Neglected tropical diseases (NTDs) flourish mostly in impoverished developing nations of the world. It is estimated that NTDs plague up to 1 billion people every year thereby inducing a massive economic and health burden worldwide. Following explosive outbreaks mostly in Asia, Latin America, Europe and the Indian Ocean, two common NTDs namely, Chikungunya and Dengue both transmitted by an infected mosquito vector principally Aedes aegypti have emerged as a major public health threat. Given the limitations of conventional medicine in specifically targeting the Chikungunya and Dengue virus (CHIKV and DENV), natural products present an interesting avenue to explore in the quest of developing novel anti; mosquito, CHIKV and DENV agents. In this endeavor, a number of plant extracts, isolated phytochemicals, essential oils and seaweeds have shown promising larvicidal and insecticidal activity against some mosquito vectors as well as anti CHIKV and DENV activity invitro. Other natural products that have depicted good potential against these diseases include; the symbiotic bacterial genus Wolbachia which can largely reduce the life span and infectivity of mosquito vectors and the marine Cyanobacterium Trichodesmium erythraeum which has shown anti- CHIKV activity at minimal cytotoxic level. The impetus of modern drug discovery approaches such as high throughput screening, drug repositioning, synthesis and computer-aided drug design will undeniably enhance the process of developing more stable lead molecules from natural products which have shown promising antiviral activity in-vitro.
Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via O–H Insertion

Science.gov (United States)

Chamni, Supakarn; He, Qing-Li; Dang, Yongjun; Bhat, Shridhar; Liu, Jun O.; Romo, Daniel

2011-01-01

Natural products are essential tools for basic cellular studies leading to the identification of medically relevant protein targets and the discovery of potential therapeutic leads. The development of methods that enable mild and selective derivatization of natural products continues to be of significant interest for mining their information-rich content. Herein, we describe novel diazo reagents for simultaneous arming and structure-activity relationship (SAR) studies of alcohol-containing natural products with a small steric footprint, namely an α-trifluoroethyl (HTFB) substituted reagent. The Rh(II)-catalyzed O–H insertion reaction of several natural products, including the potent translation inhibitor lactimidomycin, was investigated and useful reactivity and both chemo- and site (chemosite) selectivities were observed. Differential binding to the known protein targets of both FK506 and fumagillol was demonstrated, validating the advantage of the smaller steric footprint of trifluoroethyl derivatives. A p-azidophenyl diazo reagent is also described that will prove useful for photoaffinity labeling of low affinity small molecule protein receptors. PMID:21894934
Synthesis of ent-BE-43547A1 reveals a potent hypoxia-selective anticancer agent and uncovers the biosynthetic origin of the APD-CLD natural products

Science.gov (United States)

Villadsen, Nikolaj L.; Jacobsen, Kristian M.; Keiding, Ulrik B.; Weibel, Esben T.; Christiansen, Bjørn; Vosegaard, Thomas; Bjerring, Morten; Jensen, Frank; Johannsen, Mogens; Tørring, Thomas; Poulsen, Thomas B.

2017-03-01

Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration. Discrepancies between the spectroscopic signatures of the synthetic compounds with that originally reported for the BE-43547 members stimulated us to re-isolate the natural product from a BE-43547-producing microorganism during which we elucidated the biosynthetic gene clusters for the BE-43547 family as well as for all other known APD-CLDs. Our studies underline the exciting possibilities for the further development of the anticancer activities of these natural products.
Advances in Chance Discovery : Extended Selection from International Workshops

CERN Document Server

Abe, Akinori

2013-01-01

Since year 2000, scientists on artificial and natural intelligences started to study chance discovery - methods for discovering events/situations that significantly affect decision making. Partially because the editors Ohsawa and Abe are teaching at schools of Engineering and of Literature with sharing the interest in chance discovery, this book reflects interdisciplinary aspects of progress: First, as an interdisciplinary melting pot of cognitive science, computational intelligence, data mining/visualization, collective intelligence, … etc, chance discovery came to reach new application domains e.g. health care, aircraft control, energy plant, management of technologies, product designs, innovations, marketing, finance etc. Second, basic technologies and sciences including sensor technologies, medical sciences, communication technologies etc. joined this field and interacted with cognitive/computational scientists in workshops on chance discovery, to obtain breakthroughs by stimulating each other. Third, �...
Synthetic biology for pharmaceutical drug discovery

Directory of Open Access Journals (Sweden)

Trosset JY

2015-12-01

Full Text Available Jean-Yves Trosset,1 Pablo Carbonell2,3 1Bioinformation Research Laboratory, Sup’Biotech, Villejuif, France; 2Faculty of Life Sciences, SYNBIOCHEM Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK; 3Department of Experimental and Health Sciences (DCEXS, Research Programme on Biomedical Informatics (GRIB, Hospital del Mar Medical Research Institute (IMIM, Universitat Pompeu Fabra (UPF, Barcelona, Spain Abstract: Synthetic biology (SB is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. Keywords: metabolic engineering, plant synthetic biology, natural products, synthetic quorum sensing, drug resistance
Growing with dinosaurs: natural products from the Cretaceous relict Metasequoia glyptostroboides Hu & Cheng?a molecular reservoir from the ancient world with potential in modern medicine

OpenAIRE

Juvik, Ole Johan; Nguyen, Xuan Hong Thy; Andersen, Heidi Lie; Fossen, Torgils

2015-01-01

After the sensational rediscovery of living exemplars of the Cretaceous relict Metasequoia glyptostroboides—a tree previously known exclusively from fossils from various locations in the northern hemisphere, there has been an increasing interest in discovery of novel natural products from this unique plant source. This article includes the first complete compilation of natural products reported from M. glyptostroboides during the entire period in which the tree has been investigated (1954–201...
Explorative Solid-Phase Extraction (E-SPE) for Accelerated Microbial Natural Product Discovery, Dereplication, and Purification

DEFF Research Database (Denmark)

Månsson, Maria; Phipps, Richard Kerry; Gram, Lone

2010-01-01

Microbial natural products (NP) cover a high chemical diversity, and in consequence extracts from microorganisms are often complex to analyze and purify. A distribution analysis of calculated pK(a) values from the 34390 records in Antibase2008 revealed that within pH 2-11, 44% of all included......-phase extraction" (E-SPE) protocol using SAX, Oasis MAX, SCX, and LH-20 columns for targeted exploitation of chemical functionalities. E-SPE provides a minimum of fractions (15) for chemical and biological analyses and implicates development into a preparative scale methodology. Overall, this allows fast extract...
Expanding the chemical space for natural products by Aspergillus-Streptomyces co-cultivation and biotransformation

Science.gov (United States)

Wu, Changsheng; Zacchetti, Boris; Ram, Arthur F.J.; van Wezel, Gilles P.; Claessen, Dennis; Hae Choi, Young

2015-01-01

Actinomycetes and filamentous fungi produce a wide range of bioactive compounds, with applications as antimicrobials, anticancer agents or agrochemicals. Their genomes contain a far larger number of gene clusters for natural products than originally anticipated, and novel approaches are required to exploit this potential reservoir of new drugs. Here, we show that co-cultivation of the filamentous model microbes Streptomyces coelicolor and Aspergillus niger has a major impact on their secondary metabolism. NMR-based metabolomics combined with multivariate data analysis revealed several compounds that correlated specifically to co-cultures, including the cyclic dipeptide cyclo(Phe-Phe) and 2-hydroxyphenylacetic acid, both of which were produced by A. niger in response to S. coelicolor. Furthermore, biotransformation studies with o-coumaric acid and caffeic acid resulted in the production of the novel compounds (E)-2-(3-hydroxyprop-1-en-1-yl)-phenol and (2E,4E)-3-(2-carboxy-1-hydroxyethyl)-2,4-hexadienedioxic acid, respectively. This highlights the utility of microbial co-cultivation combined with NMR-based metabolomics as an efficient pipeline for the discovery of novel natural products. PMID:26040782
Natural products as promising drug candidates for the treatment of Alzheimer's disease: molecular mechanism aspect.

Science.gov (United States)

Ansari, Niloufar; Khodagholi, Fariba

2013-07-01

Alzheimer's disease (AD) is the most common neurodegenerative disorder to date, with no curative or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles. Extent studies on pathology of the disease have made important discoveries regarding mechanism of disease and potential therapeutic targets. Many cellular changes including oxidative stress, disruption of Ca2+ homeostasis, inflammation, metabolic disturbances, and accumulation of unfolded/misfolded proteins can lead to programmed cell death in AD. Despite intensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look at alternative therapies. Use of natural products and culinary herbs in medicine has gained popularity in recent years. Several natural substances with neuroprotective effects have been widely studied. Most of these compounds have remarkable antioxidant properties and act mainly by scavenging free radical species. Some of them increase cell survival and improve cognition by directly affecting amyloidogenesis and programmed cell death pathways. Further studies on these natural products and their mechanism of action, parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine. This review discussed some natural products with potential neuroprotective properties against Aβ with respect to their mechanism of action.
Natural products for pest control: an analysis of their role, value and future.

Science.gov (United States)

Gerwick, B Clifford; Sparks, Thomas C

2014-08-01

Natural products (NPs) have long been used as pesticides and have broadly served as a source of inspiration for a great many commercial synthetic organic fungicides, herbicides and insecticides that are in the market today. In light of the continuing need for new tools to address an ever-changing array of fungal, weed and insect pests, NPs continue to be a source of models and templates for the development of new pest control agents. Interestingly, an examination of the literature suggests that NP models exist for many of the pest control agents that were discovered by other means, suggesting that, had circumstances been different, these NPs could have served as inspiration for the discovery of a great many more of today's pest control agents. Here, an attempt is made to answer questions regarding the existence of an NP model for existing classes of pesticides and what is needed for the discovery of new NPs and NP models for pest control agents. © 2014 Society of Chemical Industry.
Discovery of DNA Topoisomerase I Inhibitors with Low-Cytotoxicity Based on Virtual Screening from Natural Products

Directory of Open Access Journals (Sweden)

Lan-Ting Xin

2017-07-01

Full Text Available Currently, DNA topoisomerase I (Topo I inhibitors constitute a family of antitumor agents with demonstrated clinical effects on human malignancies. However, the clinical uses of these agents have been greatly limited due to their severe toxic effects. Therefore, it is urgent to find and develop novel low toxic Topo I inhibitors. In recent years, during our ongoing research on natural antitumor products, a collection of low cytotoxic or non-cytotoxic compounds with various structures were identified from marine invertebrates, plants, and their symbiotic microorganisms. In the present study, new Topo I inhibitors were discovered from low cytotoxic and non-cytotoxic natural products by virtual screening with docking simulations in combination with bioassay test. In total, eight potent Topo I inhibitors were found from 138 low cytotoxic or non-cytotoxic compounds from coral-derived fungi and plants. All of these Topo I inhibitors demonstrated activities against Topo I-mediated relaxation of supercoiled DNA at the concentrations of 5–100 µM. Notably, the flavonoids showed higher Topo I inhibitory activities than other compounds. These newly discovered Topo I inhibitors exhibited structurally diverse and could be considered as a good starting point for the development of new antitumor lead compounds.
Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling.

Science.gov (United States)

Sheremet, Michael; Kapoor, Shobhna; Schröder, Peter; Kumar, Kamal; Ziegler, Slava; Waldmann, Herbert

2017-09-19

Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small-molecule modulators of Wnt-related processes are in high demand. Here we describe the synthesis of small molecules inspired by withanolide natural products by using a pregnenolone-derived β-lactone as the key intermediate that was transformed into a δ-lactone appended to the D-ring of the steroidal scaffold. This natural-product-inspired compound library contained potent inhibitors of Wnt signaling that act upstream of the destruction complex to stabilize Axin in a tankyrase-independent manner. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Natural products used for diabetes.

Science.gov (United States)

Shapiro, Karen; Gong, William C

2002-01-01

To review the efficacy and safety of natural products commonly used for diabetes. English and Spanish-language journals retrieved through a MEDLINE search of articles published between 1960 and December 2001 using these index terms: Opuntia, karela, gymnema, tecoma, alpha lipoic acid, thioctic acid, ginseng, panaxans, and diabetes. Natural products have long been used in traditional systems of medicine for diabetes. Products in common use include nopal (prickly pear cactus), fenu-greek, karela (bitter melon), gymnema, ginseng, tronadora, chromium, and alpha-lipoic acid. The popularity of these products varies among people of different ethnicities. Nopal is the most commonly used herbal hypoglycemic among persons of Mexican descent. Karela is more commonly used by persons from Asian countries. Some of these agents have gained universal appeal. For a select number of products, studies have revealed single or multiple mechanisms of action. For several of these, high soluble fiber content is a contributing factor. Based on the available evidence, several natural products in common use can lower blood glucose in patients with diabetes. Commonly used natural products often have a long history of traditional use, and pharmacists who have a stronger understanding of these products are better positioned to counsel patients on their appropriate use.
Elaborating the Role of Natural Products-Induced Autophagy in Cancer Treatment: Achievements and Artifacts in the State of the Art

Directory of Open Access Journals (Sweden)

Ning Wang

2015-01-01

Full Text Available Autophagy is a homeostatic process that is highly conserved across different types of mammalian cells. Autophagy is able to relieve tumor cell from nutrient and oxidative stress during the rapid expansion of cancer. Excessive and sustained autophagy may lead to cell death and tumor shrinkage. It was shown in literature that many anticancer natural compounds and extracts could initiate autophagy in tumor cells. As summarized in this review, the tumor suppressive action of natural products-induced autophagy may lead to cell senescence, provoke apoptosis-independent cell death, and complement apoptotic cell death by robust or target-specific mechanisms. In some cases, natural products-induced autophagy could protect tumor cells from apoptotic death. Technical variations in detecting autophagy affect data quality, and study focus should be made on elaborating the role of autophagy in deciding cell fate. In vivo study monitoring of autophagy in cancer treatment is expected to be the future direction. The clinical-relevant action of autophagy-inducing natural products should be highlighted in future study. As natural products are an important resource in discovery of lead compound of anticancer drug, study on the role of autophagy in tumor suppressive effect of natural products continues to be necessary and emerging.

Quantifying the Ease of Scientific Discovery.

Science.gov (United States)

Arbesman, Samuel

2011-02-01

It has long been known that scientific output proceeds on an exponential increase, or more properly, a logistic growth curve. The interplay between effort and discovery is clear, and the nature of the functional form has been thought to be due to many changes in the scientific process over time. Here I show a quantitative method for examining the ease of scientific progress, another necessary component in understanding scientific discovery. Using examples from three different scientific disciplines - mammalian species, chemical elements, and minor planets - I find the ease of discovery to conform to an exponential decay. In addition, I show how the pace of scientific discovery can be best understood as the outcome of both scientific output and ease of discovery. A quantitative study of the ease of scientific discovery in the aggregate, such as done here, has the potential to provide a great deal of insight into both the nature of future discoveries and the technical processes behind discoveries in science.
A plug-and-play pathway refactoring workflow for natural product research in Escherichia coli and Saccharomyces cerevisiae.

Science.gov (United States)

Ren, Hengqian; Hu, Pingfan; Zhao, Huimin

2017-08-01

Pathway refactoring serves as an invaluable synthetic biology tool for natural product discovery, characterization, and engineering. However, the complicated and laborious molecular biology techniques largely hinder its application in natural product research, especially in a high-throughput manner. Here we report a plug-and-play pathway refactoring workflow for high-throughput, flexible pathway construction, and expression in both Escherichia coli and Saccharomyces cerevisiae. Biosynthetic genes were firstly cloned into pre-assembled helper plasmids with promoters and terminators, resulting in a series of expression cassettes. These expression cassettes were further assembled using Golden Gate reaction to generate fully refactored pathways. The inclusion of spacer plasmids in this system would not only increase the flexibility for refactoring pathways with different number of genes, but also facilitate gene deletion and replacement. As proof of concept, a total of 96 pathways for combinatorial carotenoid biosynthesis were built successfully. This workflow should be generally applicable to different classes of natural products produced by various organisms. Biotechnol. Bioeng. 2017;114: 1847-1854. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Does Osmotic Stress Affect Natural Product Expression in Fungi?

Science.gov (United States)

Overy, David; Correa, Hebelin; Roullier, Catherine; Chi, Wei-Chiung; Pang, Ka-Lai; Rateb, Mostafa; Ebel, Rainer; Shang, Zhuo; Capon, Rob; Bills, Gerald; Kerr, Russell

2017-08-13

The discovery of new natural products from fungi isolated from the marine environment has increased dramatically over the last few decades, leading to the identification of over 1000 new metabolites. However, most of the reported marine-derived species appear to be terrestrial in origin yet at the same time, facultatively halo- or osmotolerant. An unanswered question regarding the apparent chemical productivity of marine-derived fungi is whether the common practice of fermenting strains in seawater contributes to enhanced secondary metabolism? To answer this question, a terrestrial isolate of Aspergillus aculeatus was fermented in osmotic and saline stress conditions in parallel across multiple sites. The ex-type strain of A. aculeatus was obtained from three different culture collections. Site-to-site variations in metabolite expression were observed, suggesting that subculturing of the same strain and subtle variations in experimental protocols can have pronounced effects upon metabolite expression. Replicated experiments at individual sites indicated that secondary metabolite production was divergent between osmotic and saline treatments. Titers of some metabolites increased or decreased in response to increasing osmolite (salt or glycerol) concentrations. Furthermore, in some cases, the expression of some secondary metabolites in relation to osmotic and saline stress was attributed to specific sources of the ex-type strains.
A petroleum discovery-rate forecast revisited-The problem of field growth

Science.gov (United States)

Drew, L.J.; Schuenemeyer, J.H.

1992-01-01

A forecast of the future rates of discovery of crude oil and natural gas for the 123,027-km2 Miocene/Pliocene trend in the Gulf of Mexico was made in 1980. This forecast was evaluated in 1988 by comparing two sets of data: (1) the actual versus the forecasted number of fields discovered, and (2) the actual versus the forecasted volumes of crude oil and natural gas discovered with the drilling of 1,820 wildcat wells along the trend between January 1, 1977, and December 31, 1985. The forecast specified that this level of drilling would result in the discovery of 217 fields containing 1.78 billion barrels of oil equivalent; however, 238 fields containing 3.57 billion barrels of oil equivalent were actually discovered. This underestimation is attributed to biases introduced by field growth and, to a lesser degree, the artificially low, pre-1970's price of natural gas that prevented many smaller gas fields from being brought into production at the time of their discovery; most of these fields contained less than 50 billion cubic feet of producible natural gas. ?? 1992 Oxford University Press.
Covalent attachment of the plant natural product naringenin to small glass and ceramic beads

Directory of Open Access Journals (Sweden)

Grotewold Erich

2005-10-01

Full Text Available Abstract Background Natural products have numerous medicinal applications and play important roles in the biology of the organisms that accumulate them. Few methods are currently available for identifying proteins that bind to small molecules, therefore the discovery of cellular targets for natural products with pharmacological activity continues to pose a significant challenge in drug validation. Similarly, the identification of enzymes that participate in the biosynthesis or modification of natural products remains a formidable bottleneck for metabolic engineering. Flavonoids are one large group of natural products with a diverse number of functions in plants and in human health. The coupling of flavonoids to small ceramic and glass beads provides a first step in the development of high-throughput, solid-support base approaches to screen complex libraries to identify proteins that bind natural products. Results The utilization of small glass and ceramic beads as solid supports for the coupling of small molecules was explored. Initial characterization of the beads indicated uniform and high capacity loading of amino groups. Once the beads were deemed adequate for the linking of small molecules by the coupling of NHS-fluorescein followed by microscopy, chemical hydrolysis and fluorometry, the flavonoid naringenin was modified with 1,4-dibromobutane, followed by the attachment of aminopropyltriethoxysilane. After NMR structural confirmation, the resulting 7-(4-(3-(triethoxysilylpropylaminobutoxy naringenin was attached to the ceramic beads. Conclusion Our results demonstrate that ceramic and glass beads provide convenient solid supports for the efficient and facile coupling of small molecules. We succeeded in generating naringenin-coupled ceramic and glass beads. We also developed a convenient series of steps that can be applied for the solid-support coupling of other related flavonoids. The availability of solid-support coupled naringenin opens
Rational synthetic pathway refactoring of natural products biosynthesis in actinobacteria.

Science.gov (United States)

Tan, Gao-Yi; Liu, Tiangang

2017-01-01

Natural products (NPs) and their derivatives are widely used as frontline treatments for many diseases. Actinobacteria spp. are used to produce most of NP antibiotics and have also been intensively investigated for NP production, derivatization, and discovery. However, due to the complicated transcriptional and metabolic regulation of NP biosynthesis in Actinobacteria, especially in the cases of genome mining and heterologous expression, it is often difficult to rationally and systematically engineer synthetic pathways to maximize biosynthetic efficiency. With the emergence of new tools and methods in metabolic engineering, the synthetic pathways of many chemicals, such as fatty acids and biofuels, in model organisms (e.g. Escherichia coli ), have been refactored to realize precise and flexible control of production. These studies also offer a promising approach for synthetic pathway refactoring in Actinobacteria. In this review, the great potential of Actinobacteria as a microbial cell factory for biosynthesis of NPs is discussed. To this end, recent progress in metabolic engineering of NP synthetic pathways in Actinobacteria are summarized and strategies and perspectives to rationally and systematically refactor synthetic pathways in Actinobacteria are highlighted. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

DEFF Research Database (Denmark)

Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon

2011-01-01

and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...... phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest....
22 CFR 224.21 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...
A simple and rapid method for calixarene-based selective extraction of bioactive molecules from natural products.

Science.gov (United States)

Segneanu, Adina-Elena; Damian, Daniel; Hulka, Iosif; Grozescu, Ioan; Salifoglou, Athanasios

2016-03-01

Natural products derived from medicinal plants have gained an important role in drug discovery due to their complex and abundant composition of secondary metabolites, with their structurally unique molecular components bearing a significant number of stereo-centers exhibiting high specificity linked to biological activity. Usually, the extraction process of natural products involves various techniques targeting separation of a specific class of compounds from a highly complex matrix. Aiding the process entails the use of well-defined and selective molecular extractants with distinctly configured structural attributes. Calixarenes conceivably belong to that class of molecules. They have been studied intensely over the years in an effort to develop new and highly selective receptors for biomolecules. These macrocycles, which display remarkable structural architectures and properties, could help usher a new approach in the efficient separation of specific classes of compounds from complex matrices in natural products. A simple and rapid such extraction method is presented herein, based on host-guest interaction(s) between a calixarene synthetic receptor, 4-tert-butyl-calix[6]arene, and natural biomolecular targets (amino acids and peptides) from Helleborus purpurascens and Viscum album. Advanced physicochemical methods (including GC-MS and chip-based nanoESI-MS analysis) suggest that the molecular structure and specifically the calixarene cavity size are closely linked to the nature of compounds separated. Incorporation of biomolecules and modification of the macrocyclic architecture during separation were probed and confirmed by scanning electronic microscopy and atomic force microscopy. The collective results project calixarene as a promising molecular extractant candidate, facilitating the selective separation of amino acids and peptides from natural products.
Natural Gas Energy Educational Kit.

Science.gov (United States)

American Gas Association, Arlington, VA. Educational Services.

Prepared by energy experts and educators to introduce middle school and high school students to natural gas and its role in our society, this kit is designed to be incorporated into existing science and social studies curricula. The materials and activities focus on the origin, discovery, production, delivery, and use of natural gas. The role of…
15 CFR 25.21 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...
RNA Editing and Drug Discovery for Cancer Therapy

Directory of Open Access Journals (Sweden)

Wei-Hsuan Huang

2013-01-01

Full Text Available RNA editing is vital to provide the RNA and protein complexity to regulate the gene expression. Correct RNA editing maintains the cell function and organism development. Imbalance of the RNA editing machinery may lead to diseases and cancers. Recently, RNA editing has been recognized as a target for drug discovery although few studies targeting RNA editing for disease and cancer therapy were reported in the field of natural products. Therefore, RNA editing may be a potential target for therapeutic natural products. In this review, we provide a literature overview of the biological functions of RNA editing on gene expression, diseases, cancers, and drugs. The bioinformatics resources of RNA editing were also summarized.
Alternative Fuels Data Center: Conventional Natural Gas Production

Science.gov (United States)

Conventional Natural Gas Production to someone by E-mail Share Alternative Fuels Data Center : Conventional Natural Gas Production on Facebook Tweet about Alternative Fuels Data Center: Conventional Natural Gas Production on Twitter Bookmark Alternative Fuels Data Center: Conventional Natural Gas Production
Natural gas reserve/production ratio in Russia, Iran, Qatar and Turkmenistan: A political and economic perspective

International Nuclear Information System (INIS)

Esen, Vedat; Oral, Bulent

2016-01-01

In this study, changes in natural gas reserve/production ratio (R/P) of the four countries having the highest natural gas reserves (Russia, Iran, Qatar, Turkmenistan), the importance of which increases in the world market each day due to developing technology and the demand for clean energy, has been analyzed depending on the economic and political developments in national and international fields. Change of R/P ratio depending on years has been displayed on graphics from different sources and these alterations have been tried to be associated with such issues as natural gas agreements in history, handover of political authority, economic crises etc. Therefore; it has been put forward whether or not political and economic changes of the countries are factors on the amount of natural gas production and the discovery of new reserve fields with the addition aim of providing a general overview on natural gas market. - Highlights: •Russia, Iran, Qatar and Turkmenistan are the top four countries with the highest natural gas reserves. •R/P ratios of Russia, Iran, Qatar and Turkmenistan are presented in this study. •Change of R/P ratio has been associated with the political and economic events of the countries are being analyzed. •The effect of political and economic changes on the ratio of natural gas R/P has been proposed.
40 CFR 27.21 - Discovery.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Discovery. 27.21 Section 27.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...
On the threshold of discovery

International Nuclear Information System (INIS)

Cherenkov, P.A.

1986-01-01

The author, the discoverer of the Cherenkov radiation, recalls some interesting circumstances of his discoery 50 years ago and puts it into the context of the knowledge of the period. The discovery of Cherenkov radiation which today is in practice used especially for the detection of charged particles, was correctly understood and appreciated somewhat belatedly. At first the discovery was met with distrust and the original article announcing it was rejected by the magazine Nature. In effect, the discovery was not the result of any planned experiment but was the by-product of another research. It was, of course, allowed by previous achievements in various fields of physics, namely progress reached in the study of luminescence by S.I. Vavilov and his pupils. The discovery was made during an experimental study of luminescence induced in liquids by the β and γ radiations of uranyl salts. During his attempts to suppress the background radiation from vessel walls the autor found a ''background'' from pure solvent which differed from luminescence by being independent of the concentration, temperature and viscosity of the liquid. A closer examination of the phenomenon more or less by accident revealed its marked spatial asymmetry which had major importance for the development of the theory of the new phenomenon by I.V. Tamm and I.M. Frank. (A.K.)
22 CFR 521.21 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Discovery. 521.21 Section 521.21 Foreign... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...
In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin.

Science.gov (United States)

Ntie-Kang, Fidele; Lifongo, Lydia L; Mbah, James A; Owono Owono, Luc C; Megnassan, Eugene; Mbaze, Luc Meva'a; Judson, Philip N; Sippl, Wolfgang; Efange, Simon M N

2013-01-01

Drug metabolism and pharmacokinetics (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. The use of computer modelling to predict the DMPK and toxicity properties of a natural product library derived from medicinal plants from Central Africa (named ConMedNP). Material from some of the plant sources are currently employed in African Traditional Medicine. Computer-based methods are slowly gaining ground in this area and are often used as preliminary criteria for the elimination of compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of discovery of a drug. In the present study, we present an in silico assessment of the DMPK and toxicity profile of a natural product library containing ~3,200 compounds, derived from 379 species of medicinal plants from 10 countries in the Congo Basin forests and savannas, which have been published in the literature. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination and toxicity (ADMET) of the compounds. This survey demonstrated that about 45% of the compounds within the ConMedNP compound library are compliant, having properties which fall within the range of ADME properties of 95% of currently known drugs, while about 69% of the compounds have ≤ 2 violations. Moreover, about 73% of the compounds within the corresponding "drug-like" subset showed compliance. In addition to the verified levels of "drug-likeness", diversity and the wide range of measured biological activities, the compounds from medicinal plants in Central Africa show interesting DMPK profiles and hence could represent an important starting point for hit/lead discovery.
Pep2Path: automated mass spectrometry-guided genome mining of peptidic natural products.

Directory of Open Access Journals (Sweden)

Marnix H Medema

2014-09-01

Full Text Available Nonribosomally and ribosomally synthesized bioactive peptides constitute a source of molecules of great biomedical importance, including antibiotics such as penicillin, immunosuppressants such as cyclosporine, and cytostatics such as bleomycin. Recently, an innovative mass-spectrometry-based strategy, peptidogenomics, has been pioneered to effectively mine microbial strains for novel peptidic metabolites. Even though mass-spectrometric peptide detection can be performed quite fast, true high-throughput natural product discovery approaches have still been limited by the inability to rapidly match the identified tandem mass spectra to the gene clusters responsible for the biosynthesis of the corresponding compounds. With Pep2Path, we introduce a software package to fully automate the peptidogenomics approach through the rapid Bayesian probabilistic matching of mass spectra to their corresponding biosynthetic gene clusters. Detailed benchmarking of the method shows that the approach is powerful enough to correctly identify gene clusters even in data sets that consist of hundreds of genomes, which also makes it possible to match compounds from unsequenced organisms to closely related biosynthetic gene clusters in other genomes. Applying Pep2Path to a data set of compounds without known biosynthesis routes, we were able to identify candidate gene clusters for the biosynthesis of five important compounds. Notably, one of these clusters was detected in a genome from a different subphylum of Proteobacteria than that in which the molecule had first been identified. All in all, our approach paves the way towards high-throughput discovery of novel peptidic natural products. Pep2Path is freely available from http://pep2path.sourceforge.net/, implemented in Python, licensed under the GNU General Public License v3 and supported on MS Windows, Linux and Mac OS X.
Discovery and development of new antibacterial drugs: learning from experience?

Science.gov (United States)

Jackson, Nicole; Czaplewski, Lloyd; Piddock, Laura J V

2018-06-01

Antibiotic (antibacterial) resistance is a serious global problem and the need for new treatments is urgent. The current antibiotic discovery model is not delivering new agents at a rate that is sufficient to combat present levels of antibiotic resistance. This has led to fears of the arrival of a 'post-antibiotic era'. Scientific difficulties, an unfavourable regulatory climate, multiple company mergers and the low financial returns associated with antibiotic drug development have led to the withdrawal of many pharmaceutical companies from the field. The regulatory climate has now begun to improve, but major scientific hurdles still impede the discovery and development of novel antibacterial agents. To facilitate discovery activities there must be increased understanding of the scientific problems experienced by pharmaceutical companies. This must be coupled with addressing the current antibiotic resistance crisis so that compounds and ultimately drugs are delivered to treat the most urgent clinical challenges. By understanding the causes of the failures and successes of the pharmaceutical industry's research history, duplication of discovery programmes will be reduced, increasing the productivity of the antibiotic drug discovery pipeline by academia and small companies. The most important scientific issues to address are getting molecules into the Gram-negative bacterial cell and avoiding their efflux. Hence screening programmes should focus their efforts on whole bacterial cells rather than cell-free systems. Despite falling out of favour with pharmaceutical companies, natural product research still holds promise for providing new molecules as a basis for discovery.

Natural products as starting points for future anti-malarial therapies: going back to our roots?

Directory of Open Access Journals (Sweden)

Wells Timothy NC

2011-03-01

Full Text Available Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal
Bioactive natural products from novel microbial sources.

Science.gov (United States)

Challinor, Victoria L; Bode, Helge B

2015-09-01

Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics. © 2015 New York Academy of Sciences.
Natural compounds as next-generation herbicides.

Science.gov (United States)

Dayan, Franck E; Duke, Stephen O

2014-11-01

Herbicides with new modes of action (MOAs) are badly needed due to the rapidly evolving resistance to commercial herbicides, but a new MOA has not been introduced in over 20 years. The greatest pest management challenge for organic agriculture is the lack of effective natural product herbicides. The structural diversity and evolved biological activity of natural phytotoxins offer opportunities for the development of both directly used natural compounds and synthetic herbicides with new target sites based on the structures of natural phytotoxins. Natural phytotoxins are also a source for the discovery of new herbicide target sites that can serve as the focus of traditional herbicide discovery efforts. There are many examples of strong natural phytotoxins with MOAs other than those used by commercial herbicides, which indicates that there are molecular targets of herbicides that can be added to the current repertoire of commercial herbicide MOAs. © 2014 American Society of Plant Biologists. All Rights Reserved.
Opportunities and Challenges for the Extraction of Natural Gas in ...

African Journals Online (AJOL)

The discovery and production of natural gas on a commercial scale in ... that revenues from resource extraction are intrinsically time limited; natural gas reserves will be .... Secondly, natural resource wealth has specific features which distinguish it ..... demands strengthening with a view to enable them to effectively audit the ...
Antifouling Activity of Marine Natural Products

KAUST Repository

Qian, Pei-Yuan

2012-01-01

With the global ban of application of organotin-based marine coatings by International Maritime Organization in 2008, there is a practical and urgent need of identifying environmentally friendly low-toxic and nontoxic antifouling compounds for marine industries. Marine natural products have been considered as one of the most promising sources of antifouling compounds in recent years. In antifouling compound screening processes, bioassay systems often play most critical/vital roles in screening efforts. To meet various needs, a variety of bioassay systems have been developed and/or adopted in both research and commercial laboratories. In this chapter, we provide a brief outline of common bioassay procedures for both antimicrofouling and antimacrofouling assays, which can serve as a general guideline for setting up bioassay systems in laboratories engaged in antifouling compound screening. Some bioassay procedures currently practiced in various laboratories are not included in this book chapter for various reasons. Individual laboratories should modify bioassay protocols based on their research interests or needs. Nevertheless, we highly recommend the research laboratories to adapt high-throughput assays as much as possible for preliminary screening assays, followed by more complex bioassay processes using multiple target species. We argue strongly for studies in mode-of-action of antifouling compounds against settling propagules, which shall lead to discovery of molecular biomarkers (genes, proteins, receptors, or receptor system) and will allow us to design more targeted bioassay systems.
Targeted capture and heterologous expression of the Pseudoalteromonas alterochromide gene cluster in Escherichia coli represents a promising natural product exploratory platform.

Science.gov (United States)

Ross, Avena C; Gulland, Lauren E S; Dorrestein, Pieter C; Moore, Bradley S

2015-04-17

Marine pseudoalteromonads represent a very promising source of biologically important natural product molecules. To access and exploit the full chemical capacity of these cosmopolitan Gram-(-) bacteria, we sought to apply universal synthetic biology tools to capture, refactor, and express biosynthetic gene clusters for the production of complex organic compounds in reliable host organisms. Here, we report a platform for the capture of proteobacterial gene clusters using a transformation-associated recombination (TAR) strategy coupled with direct pathway manipulation and expression in Escherichia coli. The ~34 kb pathway for production of alterochromide lipopeptides by Pseudoalteromonas piscicida JCM 20779 was captured and heterologously expressed in E. coli utilizing native and E. coli-based T7 promoter sequences. Our approach enabled both facile production of the alterochromides and in vivo interrogation of gene function associated with alterochromide's unusual brominated lipid side chain. This platform represents a simple but effective strategy for the discovery and biosynthetic characterization of natural products from marine proteobacteria.
Atmospheric Precipitations, Hailstone and Rainwater, as a Novel Source of Streptomyces Producing Bioactive Natural Products

Science.gov (United States)

Sarmiento-Vizcaíno, Aida; Espadas, Julia; Martín, Jesús; Braña, Alfredo F.; Reyes, Fernando; García, Luis A.; Blanco, Gloria

2018-01-01

produce an extraordinary repertoire of bioactive molecules, thus providing a very promising source for the discovery of novel pharmaceutical natural products. PMID:29740412
Natural products as photoprotection.

Science.gov (United States)

Saewan, Nisakorn; Jimtaisong, Ampa

2015-03-01

The rise in solar ultraviolet radiation on the earth's surface has led to a depletion of stratospheric ozone over recent decades, thus accelerating the need to protect human skin against the harmful effects of UV radiation such as erythema, edema, hyperpigmentation, photoaging, and skin cancer. There are many different ways to protect skin against UV radiation's harmful effects. The most popular way to reduce the amount of UV radiation penetrating the skin is topical application of sunscreen products that contain UV absorbing or reflecting active molecules. Based on their protection mechanism, the active molecules in sunscreens are broadly divided into inorganic and organic agents. Inorganic sunscreens reflect and scatter UV and visible radiation, while organic sunscreens absorb UV radiation and then re-emit energy as heat or light. These synthetic molecules have limited concentration according to regulation concern. Several natural compounds with UV absorption property have been used to substitute for or to reduce the quantity of synthetic sunscreen agents. In addition to UV absorption property, most natural compounds were found to act as antioxidants, anti-inflammatory, and immunomodulatory agents, which provide further protection against the damaging effects of UV radiation exposure. Compounds derived from natural sources have gained considerable attention for use in sunscreen products and have bolstered the market trend toward natural cosmetics. This adds to the importance of there being a wide selection of active molecules in sunscreen formulations. This paper summarizes a number of natural products derived from propolis, plants, algae, and lichens that have shown potential photoprotection properties against UV radiation exposure-induced skin damage. © 2015 Wiley Periodicals, Inc.
Learning Organic Chemistry Through Natural Products

Indian Academy of Sciences (India)

SERIES I ARTICLE. Learning Organic Chemistry. Through Natural Products. 2. Determination of Absolute Stereochemistry. N R Krishnaswamy was initiated into the world of natural products by T R. Seshadri at University of. Delhi and has carried on the glorious traditions of his mentor. He has taught at Bangalore University,.
A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service

Science.gov (United States)

Foster, Anita K.; MacDonald, Jean B.

2013-01-01

Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…
Anthelmintics: From discovery to resistance II (San Diego, 2016

Directory of Open Access Journals (Sweden)

Richard J. Martin

2016-12-01

Full Text Available The second scientific meeting in the series: “Anthelmintics: From Discovery to Resistance” was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand. The papers were a great representation of the field, and included the use of C. elegans for lead discovery, mechanisms of anthelmintic resistance, nematode neuropeptides, proteases, B. thuringiensis crystal protein, nicotinic receptors, emodepside, benzimidazoles, P-glycoproteins, natural products, microfluidic techniques and bioinformatics approaches. The NIH also presented NIAID-specific parasite genomic priorities and initiatives. From these papers we introduce below selected papers with a focus on anthelmintic drug screening and development.
10 CFR 1013.21 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Discovery. 1013.21 Section 1013.21 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) PROGRAM FRAUD CIVIL REMEDIES AND PROCEDURES § 1013.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...
22 CFR 35.21 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 35.21 Section 35.21 Foreign Relations DEPARTMENT OF STATE CLAIMS AND STOLEN PROPERTY PROGRAM FRAUD CIVIL REMEDIES § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...
49 CFR 31.21 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Discovery. 31.21 Section 31.21 Transportation Office of the Secretary of Transportation PROGRAM FRAUD CIVIL REMEDIES § 31.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...
Natural gas product and strategic analysis

Energy Technology Data Exchange (ETDEWEB)

Layne, A.W.; Duda, J.R.; Zammerilli, A.M.

1993-12-31

Product and strategic analysis at the Department of Energy (DOE)/Morgantown Energy Technology Center (METC) crosscuts all sectors of the natural gas industry. This includes the supply, transportation, and end-use sectors of the natural-gas market. Projects in the Natural Gas Resource and Extraction supply program have been integrated into a new product focus. Product development facilitates commercialization and technology transfer through DOE/industry cost-shared research, development, and demonstration (RD&D). Four products under the Resource and Extraction program include Resource and Reserves; Low Permeability Formations; Drilling, Completion, and Stimulation: and Natural Gas Upgrading. Engineering process analyses have been performed for the Slant Hole Completion Test project. These analyses focused on evaluation of horizontal-well recovery potential and applications of slant-hole technology. Figures 2 and 3 depict slant-well in situ stress conditions and hydraulic fracture configurations. Figure 4 presents Paludal Formation coal-gas production curves used to optimize the hydraulic fracture design for the slant well. Economic analyses have utilized data generated from vertical test wells to evaluate the profitability of horizontal technology for low-permeability formations in Yuma County, Colorado, and Maverick County, Texas.
6 CFR 13.21 - Discovery.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) In general. (1) The following types of discovery are authorized: (i) Requests for production of...
20 CFR 355.21 - Discovery.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Discovery. 355.21 Section 355.21 Employees... UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...
28 CFR 71.21 - Discovery.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 71.21 Section 71.21 Judicial... REMEDIES ACT OF 1986 Implementation for Actions Initiated by the Department of Justice § 71.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...
34 CFR 33.21 - Discovery.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 33.21 Section 33.21 Education Office of the Secretary, Department of Education PROGRAM FRAUD CIVIL REMEDIES ACT § 33.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying...
7 CFR 1.322 - Discovery.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Discovery. 1.322 Section 1.322 Agriculture Office of... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types of discovery are authorized: (1) Requests for production, inspection and photocopying of documents; (2...

45 CFR 79.21 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...
12 CFR 308.520 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Discovery. 308.520 Section 308.520 Banks and... PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...
Teaching 'natural product chemistry' in Tanzania | Buchanan ...

African Journals Online (AJOL)

Natural products 'historically' and 'today' have vast importance. This article describes the course 'Natural Product Chemistry', a new course in the 2011/2012 academic year in the Faculty of Natural and Applied Sciences at St. John's University of Tanzania. It reveals how the course has been applied to the African and ...
42 CFR 93.512 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 93.512 Section 93.512 Public Health... Process § 93.512 Discovery. (a) Request to provide documents. A party may only request another party to...) Responses to a discovery request. Within 30 days of receiving a request for the production of documents, a...
42 CFR 3.516 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 3.516 Section 3.516 Public Health PUBLIC... AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.516 Discovery. (a) A party may make a request... and any forms of discovery, other than those permitted under paragraph (a) of this section, are not...
29 CFR 22.21 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Discovery. 22.21 Section 22.21 Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...
New perspectives on innovative drug discovery: an overview.

Science.gov (United States)

Pan, Si Yuan; Pan, Shan; Yu, Zhi-Ling; Ma, Dik-Lung; Chen, Si-Bao; Fong, Wang-Fun; Han, Yi-Fan; Ko, Kam-Ming

2010-01-01

Despite advances in technology, drug discovery is still a lengthy, expensive, difficult, and inefficient process, with a low rate of success. Today, advances in biomedical science have brought about great strides in therapeutic interventions for a wide spectrum of diseases. The advent of biochemical techniques and cutting-edge bio/chemical technologies has made available a plethora of practical approaches to drug screening and design. In 2010, the total sales of the global pharmaceutical market will reach 600 billion US dollars and expand to over 975 billion dollars by 2013. The aim of this review is to summarize available information on contemporary approaches and strategies in the discovery of novel therapeutic agents, especially from the complementary and alternative medicines, including natural products and traditional remedies such as Chinese herbal medicine.
Natural Connections on Riemannian Product Manifolds

OpenAIRE

Gribacheva, Dobrinka

2011-01-01

A Riemannian almost product manifold with integrable almost product structure is called a Riemannian product manifold. In the present paper the natural connections on such manifolds are studied, i.e. the linear connections preserving the almost product structure and the Riemannian metric.
University of Texas Southwestern Medical Center: Lung Cancer Oncogenotype-Selective Drug Target Discovery (Natural Products Focus) | Office of Cancer Genomics

Science.gov (United States)

The goal of this project is to use small molecules and RNAi to functionally define subtypes of non-small cell lung cancer (NSCLC) using a panel of cell lines prepared and molecularly annotated by Drs. John Minna and Adi Gazdar. Experimental Approaches Lung Cancer Natural Products Screening/Chemical Library Screening
Nature tourism: a sustainable tourism product

Directory of Open Access Journals (Sweden)

Violante Martínez Quintana

2017-11-01

Full Text Available Nature tourism has emerged in the tourism field as a result of a logical evolution in line with public policies and academic research. After negative outcomes from traditional models first raised the alarm, the entire sector has tried to foster local development based on models of responsibility and sustainability. This article revises key concepts of nature – based tourism and shows new tendencies and the perception of cultural landscapes that are seen as tourism products. Finally, it concludes by analysing new tendencies to foster alternative nature – based tourism. It also presents a planning proposal based on a responsible and sustainable tourism model to guarantee a sustainable tourism product within the natural and cultural heritage context.
New Synthetic Methods for Hypericum Natural Products

Energy Technology Data Exchange (ETDEWEB)

Jeon, Insik [Iowa State Univ., Ames, IA (United States)

2006-01-01

Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.
Sceneries and projections of demands of natural gas in Brazil; Cenario e projecoes das demandas de gas natural no pais

Energy Technology Data Exchange (ETDEWEB)

Chianca, Marcos Duilio de Oliveira; Marques, Ziney Dias [SENAI - Servico Nacional de Aprendizagem Industrial, Rio de Janeiro, RJ (Brazil). Sistema FIRJAN

2004-07-01

Interest in Natural Gas in Brazil emerged in the second half of the twentieth century, against a background in which the global giants of the petroleum and gas industries stated that reserves within the country were not commercially viable. This scenario changed with the discovery of numerous oil and gas fields and resulted in the participation of numerous foreign companies bidding for exploration and production rights in the new fields established by ANP. Natural Gas has come to assume a new dimension with further recent discoveries in Santos, Espirito Santo, Sergipe and Urucu, with proven reserves in the order of 490 billion m3. This new dimension is reinforced by PETROBRAS's current strategic plan which considers investments in the order of 3.5 Billion U$ dollars for the production, processing and transport of Natural Gas and half a billion dollars for thermoelectric power stations. The use of Natural Gas in industries, in general, and in the generation of electricity will provide a strong push for the country's economy, substituting other sources of energy with the recognized advantages for production and reduced environmental impact. In this new era 24 gas distribution companies, widely distributed throughout Brazil, are also programming new investments to make best the use of Natural Gas for industry, commerce, for the residential sector and throughout all the national territory. (author)
Sceneries and projections of demands of natural gas in Brazil; Cenario e projecoes das demandas de gas natural no pais

Energy Technology Data Exchange (ETDEWEB)

Chianca, Marcos Duilio de Oliveira; Marques, Ziney Dias [SENAI - Servico Nacional de Aprendizagem Industrial, Rio de Janeiro, RJ (Brazil). Sistema FIRJAN

2004-07-01

Interest in Natural Gas in Brazil emerged in the second half of the twentieth century, against a background in which the global giants of the petroleum and gas industries stated that reserves within the country were not commercially viable. This scenario changed with the discovery of numerous oil and gas fields and resulted in the participation of numerous foreign companies bidding for exploration and production rights in the new fields established by ANP. Natural Gas has come to assume a new dimension with further recent discoveries in Santos, Espirito Santo, Sergipe and Urucu, with proven reserves in the order of 490 billion m3. This new dimension is reinforced by PETROBRAS's current strategic plan which considers investments in the order of 3.5 Billion U$ dollars for the production, processing and transport of Natural Gas and half a billion dollars for thermoelectric power stations. The use of Natural Gas in industries, in general, and in the generation of electricity will provide a strong push for the country's economy, substituting other sources of energy with the recognized advantages for production and reduced environmental impact. In this new era 24 gas distribution companies, widely distributed throughout Brazil, are also programming new investments to make best the use of Natural Gas for industry, commerce, for the residential sector and throughout all the national territory. (author)
Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational Approaches.

Science.gov (United States)

Luo, Yao; Wang, Ling

2017-11-16

The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. This protein is an attractive target for new anticancer drug development. Significant progress has been made in hit discovery, lead optimization, drug candidate development and determination of the three-dimensional (3D) structure of mTOR. Computational methods have been applied to accelerate the discovery and development of mTOR inhibitors helping to model the structure of mTOR, screen compound databases, uncover structure-activity relationship (SAR) and optimize the hits, mine the privileged fragments and design focused libraries. Besides, computational approaches were also applied to study protein-ligand interactions mechanisms and in natural product-driven drug discovery. Herein, we survey the most recent progress on the application of computational approaches to advance the discovery and development of compounds targeting mTOR. Future directions in the discovery of new mTOR inhibitors using computational methods are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
An innovative model for regulating supplement products: Natural health products in Canada

International Nuclear Information System (INIS)

Nestmann, Earle R.; Harwood, Melody; Martyres, Stephanie

2006-01-01

On 1 January 2004, Health Canada officially added a new term to the global list of synonyms for dietary supplements: natural health products (NHP). Developed with the intent of providing Canadian consumers with ready access to NHP that are safe, effective, and of high quality, the Natural Health Products Regulations (the NHP regulations) are applicable to the sale, manufacture, packaging, labelling, importation, distribution, and storage of NHP, and are administered by the recently formed Natural Health Products Directorate (NHPD) within Health Canada. This paper provides an overview of the process for regulating supplement products in Canada
Ultra-High-Throughput Screening of Natural Product Extracts to Identify Proapoptotic Inhibitors of Bcl-2 Family Proteins.

Science.gov (United States)

Hassig, Christian A; Zeng, Fu-Yue; Kung, Paul; Kiankarimi, Mehrak; Kim, Sylvia; Diaz, Paul W; Zhai, Dayong; Welsh, Kate; Morshedian, Shana; Su, Ying; O'Keefe, Barry; Newman, David J; Rusman, Yudi; Kaur, Harneet; Salomon, Christine E; Brown, Susan G; Baire, Beeraiah; Michel, Andrew R; Hoye, Thomas R; Francis, Subhashree; Georg, Gunda I; Walters, Michael A; Divlianska, Daniela B; Roth, Gregory P; Wright, Amy E; Reed, John C

2014-09-01

Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach. © 2014 Society for Laboratory Automation and Screening.
Bioengineering natural product biosynthetic pathways for therapeutic applications.

Science.gov (United States)

Wu, Ming-Cheng; Law, Brian; Wilkinson, Barrie; Micklefield, Jason

2012-12-01

With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.
NMR structural studies of oligosaccharides and other natural products

DEFF Research Database (Denmark)

Kjærulff, Louise

produce secondary metabolites for signaling and competing against other organisms, and these molecules are important in drug discovery due to their inherent biological activities. From a marine Photobacterium (P. halotolerans) we isolated the solonamides and the ngercheumicins, two families of cyclic...... through the nJCH correlation, this experiment has exciting applications for configurational assignment of e.g. carbohydrates and for residual dipolar couplings. Identification of known molecules and discovery of novel molecules are other important applications of NMR spectroscopy. Bacteria and fungi....... fijiensis, was also investigated for production of novel secondary metabolites, and a new pyranonigrin (E) was isolated and structure elucidated by NMR spectroscopy along with JBIR-74 and decumbenone A, two known metabolites previously isolated from Aspergillus and Penicillium species. Oligosaccharides...
Defining Creativity with Discovery

OpenAIRE

Wilson, Nicholas Charles; Martin, Lee

2017-01-01

The standard definition of creativity has enabled significant empirical and theoretical advances, yet contains philosophical conundrums concerning the nature of novelty and the role of recognition and values. In this work we offer an act of conceptual valeting that addresses these issues and in doing so, argue that creativity definitions can be extended through the use of discovery. Drawing on dispositional realist philosophy we outline why adding the discovery and bringing into being of new ...
Nigerian Journal of Natural Products and Medicine

African Journals Online (AJOL)

Nigerian Journal of Natural Products and Medicine is published by the Nigerian Society of Pharmacognosy, a non profit organisation established in 1982 dedicated to the promotion of Pharmacognosy, Natural Products and Traditional Medicine. It has a current circulation of about 500 to scientists in Nigeria and abroad.

Synthetic biology of antimicrobial discovery.

Science.gov (United States)

Zakeri, Bijan; Lu, Timothy K

2013-07-19

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.
Learning Organic Chemistry Through Natural Products

Indian Academy of Sciences (India)

Higher Learning. ... The Series on "learning Organic Chemistry Through Natural Products". Nature is a remarkable ... skeletal structure to the interior electronic configu- ration ... Among the advantages of this approach are the fact that unlike the.
Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.

Science.gov (United States)

Lee, M L; Schneider, G

2001-01-01

Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.
Natural product-based nanomedicine: recent advances and issues

Science.gov (United States)

Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

2015-01-01

Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. PMID:26451111
Natural Products as New Treatment Options for Trichomoniasis: A Molecular Docking Investigation

Directory of Open Access Journals (Sweden)

Mary Snow Setzer

2017-01-01

Full Text Available Trichomoniasis, caused by the parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually-transmitted disease, and there can be severe complications from trichomoniasis. Antibiotic resistance in T. vaginalis is increasing, but there are currently no alternatives treatment options. There is a need to discover and develop new chemotherapeutic alternatives. Plant-derived natural products have long served as sources for new medicinal agents, as well as new leads for drug discovery and development. In this work, we have carried out an in silico screening of 952 antiprotozoal phytochemicals with specific protein drug targets of T. vaginalis. A total of 42 compounds showed remarkable docking properties to T. vaginalis methionine gamma-lyase (TvMGL and to T. vaginalis purine nucleoside phosphorylase (TvPNP. The most promising ligands were polyphenolic compounds, and several of these showed docking properties superior to either co-crystallized ligands or synthetic enzyme inhibitors.
Marine Microorganism-Invertebrate Assemblages: Perspectives to Solve the “Supply Problem” in the Initial Steps of Drug Discovery

Science.gov (United States)

Leal, Miguel Costa; Sheridan, Christopher; Osinga, Ronald; Dionísio, Gisela; Rocha, Rui Jorge Miranda; Silva, Bruna; Rosa, Rui; Calado, Ricardo

2014-01-01

The chemical diversity associated with marine natural products (MNP) is unanimously acknowledged as the “blue gold” in the urgent quest for new drugs. Consequently, a significant increase in the discovery of MNP published in the literature has been observed in the past decades, particularly from marine invertebrates. However, it remains unclear whether target metabolites originate from the marine invertebrates themselves or from their microbial symbionts. This issue underlines critical challenges associated with the lack of biomass required to supply the early stages of the drug discovery pipeline. The present review discusses potential solutions for such challenges, with particular emphasis on innovative approaches to culture invertebrate holobionts (microorganism-invertebrate assemblages) through in toto aquaculture, together with methods for the discovery and initial production of bioactive compounds from these microbial symbionts. PMID:24983638
Marine Microorganism-Invertebrate Assemblages: Perspectives to Solve the “Supply Problem” in the Initial Steps of Drug Discovery

Directory of Open Access Journals (Sweden)

Miguel Costa Leal

2014-06-01

Full Text Available The chemical diversity associated with marine natural products (MNP is unanimously acknowledged as the “blue gold” in the urgent quest for new drugs. Consequently, a significant increase in the discovery of MNP published in the literature has been observed in the past decades, particularly from marine invertebrates. However, it remains unclear whether target metabolites originate from the marine invertebrates themselves or from their microbial symbionts. This issue underlines critical challenges associated with the lack of biomass required to supply the early stages of the drug discovery pipeline. The present review discusses potential solutions for such challenges, with particular emphasis on innovative approaches to culture invertebrate holobionts (microorganism-invertebrate assemblages through in toto aquaculture, together with methods for the discovery and initial production of bioactive compounds from these microbial symbionts.
Optical Pulsars and Black Arrows: Discoveries as Occasioned Productions

Science.gov (United States)

Koschmann, Timothy; Zemel, Alan

2009-01-01

The current article represents a methodological proposal. It seeks to address the question of how one might recognize a discovery as a discovery without knowing in advance what is available to be discovered. We propose a solution and demonstrate it using data from a study previously reported by J. Roschelle (1992). Roschelle investigated 2…
Natural bioactive compounds: antibiotics | Dezfully | Journal of ...

African Journals Online (AJOL)

Antibiotics are powerful therapeutic agents that are produced by diverse living organisms. Over the last several decades, natural bioactive products particularly antibiotics have continued to play a significant role in drug discovery and has expanded the process for developing drugs with high degree of therapeutic index and ...
Separation process design for isolation and purification of natural products

DEFF Research Database (Denmark)

Malwade, Chandrakant R.

Natural products are defined as secondary metabolites produced by plants and form a vast pool of compounds with unlimited chemical and functional diversity. Many of these secondary metabolites are high value added chemicals that are frequently used as ingredients in food, cosmetics, pharmaceuticals...... and other consumer products. Therefore, process technology towards industrial scale production of such high value chemicals from plants has significant value. Natural products can be obtained in pure form via synthetic or semi-synthetic route, but due to their complicated nature these methods have not been...... developed to the extent of industrial production for majority of natural products. Thus, isolation and purification of such natural products from plants is the most viable way to obtain natural products in pure form. This PhD project is mainly concerned with the design of separation process to isolate...
Synthetic biology of antimicrobial discovery

Science.gov (United States)

Zakeri, Bijan; Lu, Timothy K.

2012-01-01

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251
Affinity Crystallography: A New Approach to Extracting High-Affinity Enzyme Inhibitors from Natural Extracts.

Science.gov (United States)

Aguda, Adeleke H; Lavallee, Vincent; Cheng, Ping; Bott, Tina M; Meimetis, Labros G; Law, Simon; Nguyen, Nham T; Williams, David E; Kaleta, Jadwiga; Villanueva, Ivan; Davies, Julian; Andersen, Raymond J; Brayer, Gary D; Brömme, Dieter

2016-08-26

Natural products are an important source of novel drug scaffolds. The highly variable and unpredictable timelines associated with isolating novel compounds and elucidating their structures have led to the demise of exploring natural product extract libraries in drug discovery programs. Here we introduce affinity crystallography as a new methodology that significantly shortens the time of the hit to active structure cycle in bioactive natural product discovery research. This affinity crystallography approach is illustrated by using semipure fractions of an actinomycetes culture extract to isolate and identify a cathepsin K inhibitor and to compare the outcome with the traditional assay-guided purification/structural analysis approach. The traditional approach resulted in the identification of the known inhibitor antipain (1) and its new but lower potency dehydration product 2, while the affinity crystallography approach led to the identification of a new high-affinity inhibitor named lichostatinal (3). The structure and potency of lichostatinal (3) was verified by total synthesis and kinetic characterization. To the best of our knowledge, this is the first example of isolating and characterizing a potent enzyme inhibitor from a partially purified crude natural product extract using a protein crystallographic approach.
Natural gas and production of electricity

International Nuclear Information System (INIS)

Defago, E.

2005-01-01

The forthcoming power supply shortage in Switzerland due to increasing consumption is discussed, as are the possibilities for securing the future supply. Today, the main sources are hydroelectric (roughly 55 %) and nuclear (40 %) power. The share of electricity from natural gas amounts to only 1.4 %. The possibilities of further economic production of hydropower are practically exhausted. Therefore, further electric power has to be either imported or generated from other energy sources (renewable, nuclear, fossil) in the country itself. Due to the low acceptance of nuclear energy and the limited potential of renewable energy sources, natural gas is the most favoured candidate. The advantages of distributed production in cogeneration plants are compared with the centralized production in larger plants using combined cycles. Finally, a project currently under development is presented: an existing thermal power plant fueled with heavy fuel oil shall be refurbished and converted to natural gas as the new fuel
Pharmaceuticals from natural products: current trends

Directory of Open Access Journals (Sweden)

PETER R. SEIDL

2002-03-01

Full Text Available The use of products extracted from plants for medicinal purposes can be traced to the beginnings of civilization and up until the end of the nineteenth century natural products were the principal source of medicines. Since then their relative importance has oscillated according to the strategies of large pharmaceutical companies. Now that these strategies are changing, there are new opportunities for countries like Brazil, in which a large proportion of the world's biodiversity is located. There are, however, new circumstances that must be taken into consideration: material must be collected by groups which are formally authorized to do so and under the conditions of the Convention of Biological Diversity, the discovery process is being successively outsourced to smaller specialized firms and there is a growing integration with producers of cosmetics and phytomedicines.O uso de produtos extraídos de plantas para fins medicinais pode ser tracejado aos inícios da civilização e até o fim do século XIX, os produtos naturais constituíram a principal fonte de medicamentos. Desde então, a importância relativa dos produtos naturais tem oscilado de acordo com as estratégias de grandes companhias farmacêuticas. Agora que estas estratégias vêm mudando, há novas oportunidades para países como o Brasil, no qual está localizada uma vasta proporção da biodiversidade mundial. Há, entretanto, novas circunstâncias que devem ser levadas em consideração: o material deve ser coletado por grupos que estão formalmente autorizados para tal, com a coleta sendo feita sob as condições da Convenção de Diversidade Biológica, o processo de descoberta está sendo sucessivamente terceirizado no sentido de firmas especializadas menores e há uma integração crescente como produtores de cosméticos e fitomedicamentos.
Bioprospecting Deep-Sea Actinobacteria for Novel Anti-infective Natural Products

Directory of Open Access Journals (Sweden)

Dongbo Xu

2018-04-01

Full Text Available The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA, and Pseudomonas aeruginosa. More than half of the tested strains (27 were identified as active in at least one assay. The rare earth salt lanthanum chloride (LaCl3 was shown to be as an effective elicitor. Among the 27 strains, the anti-microbial activity of 15 were induced or enhanced by the addition of LaCl3. This part of study focused on one strain R818, in which potent antifungal activity was induced by the addition of LaCl3. We found that the LaCl3-activated metabolites in R818 are likely antimycin-type compounds. One of them, compound 1, has been purified. Spectroscopic analyses including HR-MS and 1D NMR indicated that this compound is urauchimycin D. The antifungal activity of compound 1 was confirmed with a minimal inhibitory concentration (MIC of 25 μg/mL; the purified compound also showed a moderate activity against C. difficile. Additional notable strains are: strain N217 which showed both antifungal and antibacterial (including P. aeruginosa activities and strain M864 which showed potent activity against C. difficile with an MIC value (0.125 μg/mL lower than those of vancomycin and metronidazole. Our preliminary studies show that deep-sea actinobacteria is a promising source of anti-infective natural products.
Bioactive activities of natural products against herpesvirus infection.

Science.gov (United States)

Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

2013-10-01

More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.
Hybrid combinations containing natural products and antimicrobial drugs that interfere with bacterial and fungal biofilms.

Science.gov (United States)

Zacchino, Susana A; Butassi, Estefanía; Cordisco, Estefanía; Svetaz, Laura A

2017-12-15

Biofilms contribute to the pathogenesis of many chronic and difficult-to eradicate infections whose treatment is complicated due to the intrinsic resistance to conventional antibiotics. As a consequence, there is an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. The combination therapy comprising an antimicrobial drug with a low molecular weight (MW) natural product and an antimicrobial drug (antifungal or antibacterial) appeared as a good alternative to eradicate biofilms. The aims of this review were to perform a literature search on the different natural products that have showed the ability of potentiating the antibiofilm capacity of antimicrobial drugs, to analyze which are the antimicrobial drugs most used in combination, and to have a look on the microbial species most used to prepare biofilms. Seventeen papers, nine on combinations against antifungal biofilms and eight against antibacterial biofilms were collected. Within the text, the following topics have been developed: breaf history of the discovery of biofilms; stages in the development of a biofilm; the most used methodologies to assess antibiofilm-activity; the natural products with capacity of eradicating biofilms when acting alone; the combinations of low MW natural products with antibiotics or antifungal drugs as a strategy for eradicating microbial biofilms and a list of the low MW natural products that potentiate the inhibition capacity of antifungal and antibacterial drugs against biofilms. Regarding combinations against antifungal biofilms, eight over the nine collected works were carried out with in vitro studies while only one was performed with in vivo assays by using Caenorhabditis elegans nematode. All studies use biofilms of the Candida genus. A 67% of the potentiators were monoterpenes and sesquiterpenes and six over the nine works used FCZ as the antifungal drug. The activity of AmpB and Caspo was enhanced in one and two
Plants as natural antioxidants for meat products

Science.gov (United States)

Tomović, V.; Jokanović, M.; Šojić, B.; Škaljac, S.; Ivić, M.

2017-09-01

The meat industry is demanding antioxidants from natural sources to replace synthetic antioxidants because of the negative health consequences or beliefs regarding some synthetic ones. Plants materials provide good alternatives. Spices and herbs, generally used for their flavouring characteristics, can be added to meat products in various forms: whole, ground, or as isolates from their extracts. These natural antioxidants contain some active compounds, which exert antioxidative potential in meat products. This antioxidant activity is most often due to phenolic acids, phenolic diterpenes, flavonoids and volatile oils. Each of these compounds often has strong H-donating activity, thus making them extremely effective antioxidants; some compounds can chelate metals and donate H to oxygen radicals, thus slowing oxidation via two mechanisms. Numerous studies have demonstrated the efficacy of natural antioxidants when used in meat products. Based on this literature review, it can be concluded that natural antioxidants are added to fresh and processed meat and meat products to delay, retard, or prevent lipid oxidation, retard development of off-flavours (rancidity), improve colour stability, improve microbiological quality and extend shelf-life, without any damage to the sensory or nutritional properties.
Purity-activity relationships of natural products: the case of anti-TB active ursolic acid.

Science.gov (United States)

Jaki, Birgit U; Franzblau, Scott G; Chadwick, Lucas R; Lankin, David C; Zhang, Fangqiu; Wang, Yuehong; Pauli, Guido F

2008-10-01

The present study explores the variability of biological responses from the perspective of sample purity and introduces the concept of purity-activity relationships (PARs) in natural product research. The abundant plant triterpene ursolic acid (1) was selected as an exemplary natural product due to the overwhelming number yet inconsistent nature of its approximate 120 reported biological activities, which include anti-TB potential. Nine different samples of ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative 1H NMR (qHNMR). Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive 1H NMR spin system analysis, determination of nearly all J couplings and the complete NOE pattern, and led to the revision of earlier reports. As a net result, a sigmoid PAR profile of 1 was obtained, demonstrating the inverse correlation of purity and anti-TB bioactivity. The results imply that synergistic effects of 1 and its varying impurities are the likely cause of previously reported antimycobacterial potential. Generating PARs is a powerful extension of the routinely performed quantitative correlation of structure and activity ([Q]SAR). Advanced by the use of primary analytical methods such as qHNMR, PARs enable the elucidation of cases like 1 when increasing purity voids biological activity. This underlines the potential of PARs as a tool in drug discovery and synergy research and accentuates the need to routinely combine biological testing with purity assessment.
Alternative solvents for natural products extraction

CERN Document Server

Chemat, Farid

2014-01-01

This book presents a complete picture of the current state-of-the-art in alternative and green solvents used for laboratory and industrial natural product extraction in terms of the latest innovations, original methods and safe products. It provides the necessary theoretical background and details on extraction, techniques, mechanisms, protocols, industrial applications, safety precautions and environmental impacts. This book is aimed at professionals from industry, academicians engaged in extraction engineering or natural product chemistry research, and graduate level students. The individual chapters complement one another, were written by respected international researchers and recognized professionals from the industry, and address the latest efforts in the field. It is also the first sourcebook to focus on the rapid developments in this field.

Protein Complex Production from the Drug Discovery Standpoint.

Science.gov (United States)

Moarefi, Ismail

2016-01-01

Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.
Linking neuroethology to the chemical biology of natural products

DEFF Research Database (Denmark)

Olivera, Baldomero M.; Raghuraman, Shrinivasan; Schmidt, Eric W.

2017-01-01

From a biological perspective, a natural product can be defined as a compound evolved by an organism for chemical interactions with another organism including prey, predator, competitor, pathogen, symbiont or host. Natural products hold tremendous potential as drug leads and have been extensively...... a better understanding of the evolution, biology and biochemistry of natural products will facilitate both neuroscience and the potential for drug leads. The larger goal is to establish a new sub-discipline in the broader field of neuroethology that we refer to as “Chemical Neuroethology”, linking...... the substantial work carried out by chemists on natural products with accelerating advances in neuroethology....
Discovery of a diazo-forming enzyme in cremeomycin biosynthesis.

Science.gov (United States)

Waldman, Abraham J; Balskus, Emily P

2018-05-17

The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N-N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology and enable genome-based discovery of new diazo-containing metabolites.
Discovery of potent broad spectrum antivirals derived from marine actinobacteria.

Directory of Open Access Journals (Sweden)

Avi Raveh

Full Text Available Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable
Harnessing natural product assembly lines: structure, promiscuity, and engineering.

Science.gov (United States)

Ladner, Christopher C; Williams, Gavin J

2016-03-01

Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies has been developed that enables the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and non-ribosomal peptide analogues.
The discovery of radioactivity: the centenary

International Nuclear Information System (INIS)

Patil, S.K.

1995-01-01

In the last decade of the nineteenth century, a number of fundamental discoveries of outstanding importance were made unexpectedly which marked the beginning of a new era in physics. A cascade of spectacular discoveries began with the announcement of the discovery of x-rays by Roentgen followed by the discoveries, in quick succession, of radioactivity by Becquerel, of Zeeman effect, of electron by J.J. Thomson, and of polonium and radium by the Curies. Both x-rays and radioactivity have wide applications in scientific, medical and industrial fields and have made outstanding contribution to the advancement of human knowledge and welfare. Radioactivity is well known and no other discovery in the field of physics or chemistry has had a more profound effect on our fundamental knowledge of nature. Present article, on the occasion of the centenary of the discovery of radioactivity, makes an attempt to describe some glimpses of the history of radioactivity. (author). 59 refs
Radioactivity. Centenary of radioactivity discovery

International Nuclear Information System (INIS)

Charpak, G.; Tubiana, M.; Bimbot, R.

1997-01-01

This small booklet was edited for the occasion of the exhibitions of the celebration of the centenary of radioactivity discovery which took place in various locations in France from 1996 to 1998. It recalls some basic knowledge concerning radioactivity and its applications: history of discovery, atoms and isotopes, radiations, measurement of ionizing radiations, natural and artificial radioactivity, isotope dating and labelling, radiotherapy, nuclear power and reactors, fission and fusion, nuclear wastes, dosimetry, effects and radioprotection. (J.S.)
3D in vitro technology for drug discovery.

Science.gov (United States)

Hosseinkhani, Hossein

2012-02-01

Three-dimensional (3D) in vitro systems that can mimic organ and tissue structure and function in vivo, will be of great benefit for a variety of biological applications from basic biology to toxicity testing and drug discovery. There have been several attempts to generate 3D tissue models but most of these models require costly equipment, and the most serious disadvantage in them is that they are too far from the mature human organs in vivo. Because of these problems, research and development in drug discovery, toxicity testing and biotech industries are highly expensive, and involve sacrifice of countless animals and it takes several years to bring a single drug/product to the market or to find the toxicity or otherwise of chemical entities. Our group has been actively working on several alternative models by merging biomaterials science, nanotechnology and biological principles to generate 3D in vitro living organs, to be called "Human Organs-on-Chip", to mimic natural organ/tissues, in order to reduce animal testing and clinical trials. We have fabricated a novel type of mechanically and biologically bio-mimicking collagen-based hydrogel that would provide for interconnected mini-wells in which 3D cell/organ culture of human samples in a manner similar to human organs with extracellular matrix (ECM) molecules would be possible. These products mimic the physical, chemical, and biological properties of natural organs and tissues at different scales. This paper will review the outcome of our several experiments so far in this direction and the future perspectives.
Plant-Derived Antimalarial Agents: New Leads and Efficient Phytomedicines. Part II. Non-Alkaloidal Natural Products

Directory of Open Access Journals (Sweden)

Alaíde Braga de Oliveira

2009-08-01

Full Text Available Malaria is still the most destructive and dangerous parasitic infection in many tropical and subtropical countries. The burden of this disease is getting worse, mainly due to the increasing resistance of Plasmodium falciparum against the widely available antimalarial drugs. There is an urgent need for new, more affordable and accessible antimalarial agents possessing original modes of action. Natural products have played a dominant role in the discovery of leads for the development of drugs to treat human diseases, and this fact anticipates that new antimalarial leads may certainly emerge from tropical plant sources. This present review covers most of the recently-published non-alkaloidal natural compounds from plants with antiplasmodial and antimalarial properties, belonging to the classes of terpenes, limonoids, flavonoids, chromones, xanthones, anthraquinones, miscellaneous and related compounds, besides the majority of papers describing antiplasmodial crude extracts published in the last five years not reviewed before. In addition, some perspectives and remarks on the development of new drugs and phytomedicines for malaria are succinctly discussed.
The Dynamic Radio Sky: An Opportunity for Discovery

Science.gov (United States)

2010-01-01

giant pulses from the Crab pulsar , a small number of dedicated radio transient surveys, and the serendipitous discovery of transient radio sources...used in the discovery of over 1800 radio pulsars . In 2003, the Parkes Multibeam Survey had covered the entire Galactic plane visible from Parkes... pulsars , and confirmed the neutron star nature of these sources, dubbed Rotating Radio Transients (RRATs). Since the discovery of the original 11 RRATs
An analysis of FDA-approved drugs: natural products and their derivatives.

Science.gov (United States)

Patridge, Eric; Gareiss, Peter; Kinch, Michael S; Hoyer, Denton

2016-02-01

Natural products contribute greatly to the history and landscape of new molecular entities (NMEs). An assessment of all FDA-approved NMEs reveals that natural products and their derivatives represent over one-third of all NMEs. Nearly one-half of these are derived from mammals, one-quarter from microbes and one-quarter from plants. Since the 1930s, the total fraction of natural products has diminished, whereas semisynthetic and synthetic natural product derivatives have increased. Over time, this fraction has also become enriched with microbial natural products, which represent a significant portion of approved antibiotics, including more than two-thirds of all antibacterial NMEs. In recent years, the declining focus on natural products has impacted the pipeline of NMEs from specific classes, and this trend is likely to continue without specific investment in the pursuit of natural products. Copyright © 2015 Elsevier Ltd. All rights reserved.
Mining manufacturing data for discovery of high productivity process characteristics.

Science.gov (United States)

Charaniya, Salim; Le, Huong; Rangwala, Huzefa; Mills, Keri; Johnson, Kevin; Karypis, George; Hu, Wei-Shou

2010-06-01

Modern manufacturing facilities for bioproducts are highly automated with advanced process monitoring and data archiving systems. The time dynamics of hundreds of process parameters and outcome variables over a large number of production runs are archived in the data warehouse. This vast amount of data is a vital resource to comprehend the complex characteristics of bioprocesses and enhance production robustness. Cell culture process data from 108 'trains' comprising production as well as inoculum bioreactors from Genentech's manufacturing facility were investigated. Each run constitutes over one-hundred on-line and off-line temporal parameters. A kernel-based approach combined with a maximum margin-based support vector regression algorithm was used to integrate all the process parameters and develop predictive models for a key cell culture performance parameter. The model was also used to identify and rank process parameters according to their relevance in predicting process outcome. Evaluation of cell culture stage-specific models indicates that production performance can be reliably predicted days prior to harvest. Strong associations between several temporal parameters at various manufacturing stages and final process outcome were uncovered. This model-based data mining represents an important step forward in establishing a process data-driven knowledge discovery in bioprocesses. Implementation of this methodology on the manufacturing floor can facilitate a real-time decision making process and thereby improve the robustness of large scale bioprocesses. 2010 Elsevier B.V. All rights reserved.
Marine Microorganism-Invertebrate Assemblages: Perspectives to Solve the “Supply Problem” in the Initial Steps of Drug Discovery

NARCIS (Netherlands)

Leal, M.C.; Sheridan, C.; Osinga, R.; Dionisio, G.; Rocha, R.J.M.; Silva, B.; Rosa, R.; Calado, R.

2014-01-01

The chemical diversity associated with marine natural products (MNP) is unanimously acknowledged as the “blue gold” in the urgent quest for new drugs. Consequently, a significant increase in the discovery of MNP published in the literature has been observed in the past decades, particularly from
Discoveries of isotopes by fission

Indian Academy of Sciences (India)

country of discovery as well as the production mechanism used to produce the isotopes. ... the disintegration products of bombarded uranium, as a consequence of a ..... advanced accelerator and newly developed separation and detection ...
Bioprospecting of Marine Invertebrates for New Natural Products — A Chemical and Zoogeographical Perspective

Directory of Open Access Journals (Sweden)

Ricardo Calado

2012-08-01

Full Text Available Bioprospecting for new marine natural products (NPs has increased significantly over the last decades, leading to an unprecedented discovery of new molecules. Marine invertebrates have been the most important source of these NPs, with researchers commonly targeting particular taxonomic groups, marine regions and/or molecules from specific chemical groups. The present review focuses on new NPs identified from marine invertebrates between 2000 and 2009, and performs a detailed analysis on: (1 the chemical groups of these NPs; (2 the association of particular chemical groups to specific marine invertebrate taxa; and (3 the yielding of molecules from the same chemical group from organisms occurring in a particular geographic region. Our survey revealed an increasing number of new terpenoids being discovered between 2000 and 2009, contrasting with the decreasing trend in the discovery of new alkaloids and aliphatic molecules. Overall, no particular association was identified between marine invertebrate taxa and chemical groups of new NPs. Nonetheless, it is worth noting that most NPs recorded from cnidarians and mollusks were terpenoids, while most NPs identified in echinoderms were aliphatic compounds or carbohydrates. The geographical trends observed in our study do not support the idea of particular chemical groups of new NPs being associated with marine invertebrates from any specific geographical region, as NPs from different chemical groups were commonly distributed worldwide.
Israel-New natural gas producer in the Mediterranean

International Nuclear Information System (INIS)

Shaffer, Brenda

2011-01-01

In 2009 and 2010, major offshore natural gas reserves were discovered near the State of Israel. This article examines Israel's newly discovered natural gas reserves and the implications of this discovery for Israel, the Middle East, and the Mediterranean region. The article will discuss Israel's energy security approach; the role of natural gas in Israel's energy consumption patterns; the organization of Israel's natural gas sector; regional political and security implications of the natural gas discoveries; the prospects for export, and the outlook for various natural gas markets. These new discoveries significantly improve Israel's energy security. They may also spur Israel to develop technologies related to utilization of natural gas in a variety of sectors, such as transportation. The discoveries may contribute to the emergence of a number of maritime border delimitation conflicts in the Eastern Mediterranean. At current volumes, the Israeli discoveries will not be a game-changer for gas markets in southern Europe or liquefied natural gas (LNG) markets. However, they will lead to expanded natural gas consumption in the region. In addition, offshore exploration efforts in Israel and in neighboring countries are intensifying. Additional discoveries may turn the Eastern Mediterranean region into a new source of natural gas and oil. - Highlights: → In 2009 and 2010, major natural gas deposits were discovered offshore of Israel's port city of Haifa. → They will satisfy a large portion of Israel's domestic energy consumption needs for a number of decades. → The gas discoveries have created an opportunity to fundamentally change the country's energy policies. → Additional discoveries may turn the Eastern Mediterranean region into a new source of natural gas and oil. → Israel could become a supplier of natural gas to neighbors in the Middle East region, such as Jordan.
Natural products against cancer: A comprehensive bibliometric study of the research projects, publications, patents and drugs

Directory of Open Access Journals (Sweden)

Jian Du

2014-01-01

Full Text Available Objectives: To analyze multi-source data including awards, publications, patents and drugs, and try to draw the whole landscape of the research and development community in the area of natural products (NPs against cancer. Materials and Methods: Awards, publications, patents and drugs data from National Institute of Health/Natural Science Foundation of China (NIH/NSFC, PubMed, Derwent Innovation Index and Cortellis were collected. Bibliometric methodologies and technology are used to investigate publications/patents/drugs, their contents and relationships. Results: NIH and NSFC respectively demonstrated a stable and sustained expenditure growth in this area. The number of publications is continuously increasing. Yet the annual patent applications worldwide and FDA drug approvals were little changed or not obviously fluctuated in 2003-2013. USA and several Asia-pacific countries/territories are important contributing powers. We described the evolution of major research topics by those MeSH Major Topics indexed in PubMed with the largest growth range in three intervals, and analyzed hot research topics in the recent 10 years which include NPs or NPs derivatives, cell line/animal model, laboratory technologies and activation mechanisms. Conclusions: China published the most publications and received the most patent applications, but drug discovery performance is no better than USA and Japan. Research on anti-neoplastic structures and compounds originated from Chinese traditional medicine (TCM, medicinal plants, herbal medicine and marine NPs are major research topics in the recent 10 years. There still exits translational gap between basic research and drug discovery. Translational research should be undertaken to strengthen the applicability of NPs.
Marine actinobacteria: an important source of bioactive natural products.

Science.gov (United States)

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.
Applications of natural products in the control of mosquito ...

African Journals Online (AJOL)

Applications of natural products in the control of mosquito-transmitted ... African Journal of Biotechnology ... Ultimately, a paradigm shift in research that evaluates natural products in a comparative manner will help to produce new materials for ...
Review: Natural products from Genus Selaginella (Selaginellaceae

Directory of Open Access Journals (Sweden)

AHMAD DWI SETYAWAN

2011-01-01

Full Text Available Setyawan AD. 2011. Natural products from Genus Selaginella (Selaginellaceae. Nusantara Bioscience 3: 44-58. Selaginella is a potent medicinal-stuff, which contains diverse of natural products such as alkaloid, phenolic (flavonoid, and terpenoid. This species is traditionally used to cure several diseases especially for wound, after childbirth, and menstrual disorder. Biflavonoid, a dimeric form of flavonoids, is the most valuable natural products of Selaginella, which constituted at least 13 compounds, namely amentoflavone, 2',8''-biapigenin, delicaflavone, ginkgetin, heveaflavone, hinokiflavone, isocryptomerin, kayaflavone, ochnaflavone, podocarpusflavone A, robustaflavone, sumaflavone, and taiwaniaflavone. Ecologically, plants use biflavonoid to response environmental condition such as defense against pests, diseases, herbivory, and competitions; while human medically use biflavonoid especially for antioxidant, anti-inflammatory, and anti carcinogenic. Selaginella also contains valuable disaccharide, namely trehalose that has long been known for protecting from desiccation and allows surviving severe environmental stress. The compound has very prospects as molecular stabilizer in the industries based bioresources.

A Framework for Automatic Web Service Discovery Based on Semantics and NLP Techniques

Directory of Open Access Journals (Sweden)

Asma Adala

2011-01-01

Full Text Available As a greater number of Web Services are made available today, automatic discovery is recognized as an important task. To promote the automation of service discovery, different semantic languages have been created that allow describing the functionality of services in a machine interpretable form using Semantic Web technologies. The problem is that users do not have intimate knowledge about semantic Web service languages and related toolkits. In this paper, we propose a discovery framework that enables semantic Web service discovery based on keywords written in natural language. We describe a novel approach for automatic discovery of semantic Web services which employs Natural Language Processing techniques to match a user request, expressed in natural language, with a semantic Web service description. Additionally, we present an efficient semantic matching technique to compute the semantic distance between ontological concepts.
Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database.

Science.gov (United States)

Zhong, Zhangfeng; Liu, Li-Juan; Dong, Zhi-Qiang; Lu, Lihua; Wang, Modi; Leung, Chung-Hang; Ma, Dik-Lung; Wang, Yitao

2015-06-30

We report herein the identification of an immunomodulatory natural product-like compound as a direct inhibitor of TLR1-TLR2 heterodimerization. Compound suppressed TNF-α and IL-6 secretion in Pam3CSK4-induced macrophages. Moreover, compound inhibited the phagocytic activity of macrophages, presumably through modulation of TLR1-TLR2 signaling and inactivation of NF-κB. Molecular docking revealed that compound bound to the interface region of TLR1-TLR2 by forming two hydrogen bonds with residues lining the binding site. To our knowledge, compound has been only the second inhibitor overall of TLR1-TLR2 heterodimerization reported to date.
World statistics on natural gas reserves, production and utilization

International Nuclear Information System (INIS)

Raikaslehto, S.

2001-01-01

By reviewing the statistics of BP Amoco on natural gas reserves, production and usage, it is easy to see that Russia and USA, both being large natural gas producers, differ significantly from each other. The natural gas reserves of USA are 6th largest in the world, simultaneously the natural gas consumption and import are largest in the world. About one third of the known natural gas reserves of the world are in Russia. The known natural gas reserves of both USA and Canada have decreases, but they have potential gas reserves left. Known natural gas reserves of the USA have been calculated to be sufficient for 9 years consumption at present usage and those of Canada for 11 years. The reserves of Algeria correspond to the usage of 55 years, and the Russian reserves for are about 83 years. Annual production figures of both Russia and the USA are nearly the same. Russia is the largest exporter (125.5 billion m 3 ) of natural gas and the USA the largest importer (96 billion m 3 ). The natural gas reserves of the largest European producers, the Netherlands and Norway have been estimated to be sufficient for use of about 20 years, but those of Great Britain only for about 10 years. The annual production of Russia has varied in the 1990s between nearly 600 billion m 3 and present 550 billion m 3 , the minimum being in 1997 only about 532 billion m 3 . Ten largest natural gas consumers use 67% of the natural gas consumed annually in the world. USA consumes about 27% of the total natural gas produced in the world, the amount of Russia being 364 billion m 3 (16%). Other large natural gas consumers are Great Britain, Germany, Japan, Ukraine, Canada, Italy, Iran and Uzbekistan. The share of these countries of the total consumption varied in between 2-4%. Only Japan has no natural gas production of its own. The foreign trade between Japan and Indonesia is trade on LNG. On the other hand the natural gas consumption of the world's 10th largest producer Norway is nearly zero, so
Ribosomally Synthesized and Post-translationally Modified Peptide Natural Products: New Insights Into the Role of Leader and Core Peptides During Biosynthesis

Science.gov (United States)

Yang, Xiao; van der Donk, Wilfred A.

2013-01-01

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with a high degree of structural diversity and a wide variety of bioactivities. Understanding the biosynthetic machinery of these RiPPs will benefit the discovery and development of new molecules with potential pharmaceutical applications. In this review, we discuss the features of the biosynthetic pathways to different RiPP classes, and propose mechanisms regarding recognition of the precursor peptide by the posttranslational modification enzymes. We propose that the leader peptides function as allosteric regulators that bind the active form of the biosynthetic enzymes in a conformational selection process. We also speculate how enzymes that generate polycyclic products of defined topologies may have been selected for during evolution. PMID:23666908
Natural personal care products-analysis of ingredient lists and legal situation.

Science.gov (United States)

Klaschka, Ursula

2016-01-01

Many natural substances are classified as dangerous substances according to the European regulation on classification and labelling. Are they used in natural personal care products today? One hundred ingredient lists were analyzed to find this out. All products with natural substances contained dangerous natural substances or they contained natural substances, for which the information about their classification as dangerous substances is not available. 54 natural substances quoted in the ingredient lists were found to be classified, with 37 substances being classified due to hazardous effects for skin and eyes. However, the most frequently used natural substances are not classified as dangerous. Natural substances are multi-constituent compounds, leading to two main problems in personal care products: the potential interactions of a multitude of substances and the fact that dangerous constituents are not disclosed in the ingredient lists. For example, the fragrance allergens citral, farnesol, limonene, and linalool are frequent components of the natural substances employed. In addition, 82 products listed allergenic fragrance ingredients as single substances in their ingredient lists. Recommendations for sensitive skin in a product's name do not imply that the '26 fragrance allergens' are omitted. Furthermore, 80 products listed 'parfum'/'aroma', and 50 products listed ethanol. The data show that the loopholes for natural substances and for personal care products in the present European chemical legislation (e.g. the exception for classification and labelling of cosmetic products and the exception for information transfer in the supply chain) are not in line with an adequate consumer and environmental protection.
Discovery and Innovation

African Journals Online (AJOL)

Discovery and Innovation is a journal of the African Academy of Sciences (AAS) ... World (TWAS) meant to focus attention on science and technology in Africa and the ... of Non-wood Forest Products: Potential Impacts and Challenges in Africa ...
Psychoactive natural products: overview of recent developments

Directory of Open Access Journals (Sweden)

István Ujváry

2014-03-01

Full Text Available Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural products are also mentioned.
In silico Design of "Un-Natural" Natural Products

Directory of Open Access Journals (Sweden)

Zucko; J. ...(et al.

2008-05-01

Full Text Available Polyketides and non-ribosomal peptides represent a large class of structurally diverse natural products much studied over recent years because the enzymes that synthesise them, the modular polyketide synthases (PKSs and the non-ribosomal peptide synthetases (NRPSs, share striking architectural similarities that can be exploited to generate "un-natural" natural products. PKS and NRPS proteins are multifunctional, composed of a co-linear arrangement of discrete protein domains representing each enzymic activity needed for chain elongation using either carboxylic acid or amino acid building blocks. Each domain is housed within larger modules which form the complex. Polyketide and peptide antibiotics, antifungals, antivirals, cytostatics, immunosuppressants, antihypertensives, antidiabetics, antimalarials and anticholesterolemics are in clinical use. Of commercial importance are also polyketide and peptide antiparasitics, coccidiostatics,animal growth promoters and natural insecticides.Polyketides are assembled through serial condensations of activated coenzyme-A thioester monomers derived from simple organic acids such as acetate, propionate and butyrate. The choice of organic acid allows the introduction of different chiral centres into the polyketide backbone. The active sites required for condensation include an acyltransferase (AT, an acyl carrier protein (ACP and a ß-ketoacylsynthase (KS. Each condensation results in a ß-keto group that undergoes all, some or none of a series of processing steps. Active sites that perform these reactions are contained within the following domains; ketoreductase (KR, dehydratase (DH and an enoylreductase (ER. The absence of any ß-keto processing results in the incorporation of a ketone group into the growing polyketide chain, a KR alone gives rise to a hydroxyl moiety, a KR and DH produce an alkene, while the combination of KR, DH and ER domains lead to complete reduction to an alkane. Most often, the last
Planning of optimum production from a natural gas field

Energy Technology Data Exchange (ETDEWEB)

Van Dam, J

1968-03-01

The design of an optimum development plan for a natural gas field always depends on the typical characteristics of the producing field, as well as those of the market to be served by this field. Therefore, a good knowledge of the field parameters, such as the total natural gas reserves, the well productivity, and the dependence of production rates on pipeline pressure and depletion of natural gas reserves, is required prior to designing the development scheme of the field, which in fact depends on the gas-sales contract to be concluded in order to commit the natural gas reserves to the market. In this paper these various technical parameters are discussed in some detail, and on this basis a theoretical/economical analysis of natural gas production is given. For this purpose a simplified economical/mathematical model for the field is proposed, from which optimum production rates at various future dates can be calculated. The results of these calculations are represented in a dimensionless diagram which may serve as an aid in designing optimum development plans for a natural gas field. The use of these graphs is illustrated in a few examples.
Marine Natural Products as Models to Circumvent Multidrug Resistance

Directory of Open Access Journals (Sweden)

Solida Long

2016-07-01

Full Text Available Multidrug resistance (MDR to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC transporter P-glycoprotein (P-gp, which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.
Natural product-like virtual libraries: recursive atom-based enumeration.

Science.gov (United States)

Yu, Melvin J

2011-03-28

A new molecular enumerator is described that allows chemically and architecturally diverse sets of natural product-like and drug-like structures to be generated from a core structure as simple as a single carbon atom or as complex as a polycyclic ring system. Integrated with a rudimentary machine-learning algorithm, the enumerator has the ability to assemble biased virtual libraries enriched in compounds predicted to meet target criteria. The ability to dynamically generate relatively small focused libraries in a recursive manner could reduce the computational time and infrastructure necessary to construct and manage extremely large static libraries. Depending on enumeration conditions, natural product-like structures can be produced with a wide range of heterocyclic and alicyclic ring assemblies. Because natural products represent a proven source of validated structures for identifying and designing new drug candidates, mimicking the structural and topological diversity found in nature with a dynamic set of virtual natural product-like compounds may facilitate the creation of new ideas for novel, biologically relevant lead structures in areas of uncharted chemical space.
Virtual drug discovery: beyond computational chemistry?

Science.gov (United States)

Gilardoni, Francois; Arvanites, Anthony C

2010-02-01

This editorial looks at how a fully integrated structure that performs all aspects in the drug discovery process, under one company, is slowly disappearing. The steps in the drug discovery paradigm have been slowly increasing toward virtuality or outsourcing at various phases of product development in a company's candidate pipeline. Each step in the process, such as target identification and validation and medicinal chemistry, can be managed by scientific teams within a 'virtual' company. Pharmaceutical companies to biotechnology start-ups have been quick in adopting this new research and development business strategy in order to gain flexibility, access the best technologies and technical expertise, and decrease product developmental costs. In today's financial climate, the term virtual drug discovery has an organizational meaning. It represents the next evolutionary step in outsourcing drug development.
Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure.

Science.gov (United States)

Chen, Rui; Wan, Jing; Song, Jing; Qian, Yan; Liu, Yong; Gu, Shuiming

2017-12-01

Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy. This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay. A large library of structurally diverse, drug-like natural products was compiled, from which those with unsatisfactory pharmacokinetic profile and/or structurally redundant compounds were excluded. The binding mode of remaining candidates to PPARγ ligand-binding domain (LBD) was computationally modelled using molecular docking and their relative binding potency was ranked by an empirical scoring scheme. Consequently, eight commercially available hits with top scores were selected and their biological activity was determined using a cell-based reporter-gene assay. Four natural product compounds, namely ZINC13408172, ZINC4292805, ZINC44179 and ZINC901461, were identified to have high or moderate agonistic potency against human PPARγ with EC 50 values of 0.084, 2.1, 0.35 and 5.6 μM, respectively, which are comparable to or even better than that of the approved PPARγ full agonists pioglitazone (EC 50 = 0.16 μM) and rosiglitazone (EC 50 = 0.034 μM). Hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PPARγ LBD domain with these agonist ligands, while few hydrogen bonds, salt bridges and/or π-π stacking at the complex interfaces confer selectivity and specificity for the domain-agonist recognition. The integrated in vitro-in silico screening strategy can be successfully applied to rational discovery of
Cyclic Investigation of Geophysical Studies in the Exploration and Discovery of Natural Resources in Our Country

International Nuclear Information System (INIS)

Gonulalan, A. U.

2007-01-01

Although the methods of exploration geophysics were first utilized after the discovery of an oil field in 1921, they have also applied in the old centuries. Likewise, the half of the total production in the United States of America is covered by new oil fields discovered by utilizing geophysical methods. The industry's energy necessity increases the interest to oil. The investments in the field of geophysics by the companies which makes large amount of money in order to discover new oil fields, widespread use of computers, the developments of space technology and world-wide nuclear competition even though its great danger for human beings have great share in the development of geophysics. Our country has 18 different types mines which has more than 10 billion $ potential. Geophysical engineers have great Kowledge and labor in the discovery of 1,795 trillion wealth from borax to building stone, and 60 billion $ oil and gas. On the other hand, as 1,5 billion investment in the field of geophysics is only 0.08 % of total investments, the increase of investments will add more contribution
Discovery of single top quark production

Energy Technology Data Exchange (ETDEWEB)

Gillberg, Dag [Simon Fraser Univ., Burnaby, BC (Canada)

2009-04-01

The top quark is by far the heaviest known fundamental particle with a mass nearing that of a gold atom. Because of this strikingly high mass, the top quark has several unique properties and might play an important role in electroweak symmetry breaking - the mechanism that gives all elementary particles mass. Creating top quarks requires access to very high energy collisions, and at present only the Tevatron collider at Fermilab is capable of reaching these energies. Until now, top quarks have only been observed produced in pairs via the strong interaction. At hadron colliders, it should also be possible to produce single top quarks via the electroweak interaction. Studies of single top quark production provide opportunities to measure the top quark spin, how top quarks mix with other quarks, and to look for new physics beyond the standard model. Because of these interesting properties, scientists have been looking for single top quarks for more than 15 years. This thesis presents the first discovery of single top quark production. An analysis is performed using 2.3 fb^-1 of data recorded by the D0 detector at the Fermilab Tevatron Collider at centre-of-mass energy √s = 1.96 TeV. Boosted decision trees are used to isolate the single top signal from background, and the single top cross section is measured to be σ(p$\\bar{p}$ → tb + X, tqb + X) = 3.74_-0.74^+0.95 pb. Using the same analysis, a measurement of the amplitude of the CKM matrix element V_tb, governing how top and b quarks mix, is also performed. The measurement yields: |V{sub tb}|f₁^L| = 1.05 -_0.12^+0.13, where f₁^L is the left-handed Wtb coupling. The separation of signal from background is improved by combining the boosted decision trees with two other multivariate techniques. A new cross section measurement is performed, and the significance for the excess over the predicted background exceeds 5
Perspectives on the agrochemical industry and agrochemical discovery.

Science.gov (United States)

Sparks, Thomas C; Lorsbach, Beth A

2017-04-01

Agrochemicals have been critical to the production of food and fiber, as well as the control of vectors of disease. The need for the discovery and development of new agrochemicals continues unabated due to the loss of existing products through the development of resistance, the desire for products with more favorable environmental and toxicological profiles, shifting pest spectra, and changing agricultural needs and practices. As presented in the associated analysis of the agrochemical industry, the rising costs and complexities of agrochemical discovery have, in part, led to increasing consolidation, especially in the USA and Europe. However, as demonstrated by the present analysis, the discovery of new agrochemicals continues in spite of the challenges. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
Discovery, biosynthesis, and rational engineering of novel enterocin and wailupemycin polyketide analogues.

Science.gov (United States)

Kalaitzis, John A

2013-01-01

The marine actinomycete Streptomyces maritimus produces a structurally diverse set of unusual polyketide natural products including the major metabolite enterocin. Investigations of enterocin biosynthesis revealed that the unique carbon skeleton is derived from an aromatic polyketide pathway which is genetically coded by the 21.3 kb enc gene cluster in S. maritimus. Characterization of the enc biosynthesis gene cluster and subsequent manipulation of it via heterologous expression and/or mutagenesis enabled the discovery of other enc-based metabolites that were produced in only very minor amounts in the wild type. Also described are techniques used to harness the enterocin biosynthetic machinery in order to generate unnatural enc-derived polyketide analogues. This review focuses upon the molecular methods used in combination with classical natural products detection and isolation techniques to access minor metabolites of the S. maritimus secondary metabolome.
Anti-Enterovirus 71 Agents of Natural Products.

Science.gov (United States)

Wang, Liyan; Wang, Junfeng; Wang, Lishu; Ma, Shurong; Liu, Yonghong

2015-09-09

This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.
Exposures from consumption of agricultural and semi-natural products

International Nuclear Information System (INIS)

Strand, P.; Skuterud, L.; Balonov, M.; Travnikova, I.; Hove, K.; Howard, B.; Prister, B.S.; Ratnikov, A.

1996-01-01

The importance of food from different production systems to the internal dose from radiocesium, was investigated in selected study sites in Ukraine and Russia. Food products from semi-natural ecosystems are major contributors to the individual internal dose to rural population in areas affected by the Chernobyl accident. At the selected study sites it is estimated in 1995 that foods from private farms and forests contribute on average 35% to 60%, to the individual internal dose, variation relating to soil types and implemented countermeasures. The importance of food products from private farms and particularly forest products increases with time since Cs concentration in some of the natural food products have longer ecological half life than food products from agricultural systems. A significant relationship was observed between consumption of mushrooms and whole body content of radiocesium in rural people. The contribution to the collective dose of food products produced in the semi-natural ecosystems is less than the contribution to the individual internal dose for the local rural population
CamMedNP: building the Cameroonian 3D structural natural products database for virtual screening.

Science.gov (United States)

Ntie-Kang, Fidele; Mbah, James A; Mbaze, Luc Meva'a; Lifongo, Lydia L; Scharfe, Michael; Hanna, Joelle Ngo; Cho-Ngwa, Fidelis; Onguéné, Pascal Amoa; Owono Owono, Luc C; Megnassan, Eugene; Sippl, Wolfgang; Efange, Simon M N

2013-04-16

Computer-aided drug design (CADD) often involves virtual screening (VS) of large compound datasets and the availability of such is vital for drug discovery protocols. We present CamMedNP - a new database beginning with more than 2,500 compounds of natural origin, along with some of their derivatives which were obtained through hemisynthesis. These are pure compounds which have been previously isolated and characterized using modern spectroscopic methods and published by several research teams spread across Cameroon. In the present study, 224 distinct medicinal plant species belonging to 55 plant families from the Cameroonian flora have been considered. About 80 % of these have been previously published and/or referenced in internationally recognized journals. For each compound, the optimized 3D structure, drug-like properties, plant source, collection site and currently known biological activities are given, as well as literature references. We have evaluated the "drug-likeness" of this database using Lipinski's "Rule of Five". A diversity analysis has been carried out in comparison with the ChemBridge diverse database. CamMedNP could be highly useful for database screening and natural product lead generation programs.

The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use.

Science.gov (United States)

Cassinelli, Giuseppe

2016-06-02

In May 1960, the Farmitalia CEO Dr. Bertini and the director of the Istituto Nazionale dei Tumori of Milan Prof. Bucalossi (talent scout and city's Mayor) signed a research agreement for the discovery and development up to clinical trials of new natural antitumor agents. This agreement can be considered as a pioneering and fruitful example of a translational discovery program with relevant transatlantic connections. Owing to an eclectic Streptomyces, found near Castel del Monte (Apulia), and to the skilled and motivated participants of both institutions, a new natural antitumor drug, daunomycin, was ready for clinical trials within 3 years. Patent interference by the Farmitalia French partner was overcome by the good quality of the Italian drug and by the cooperation between Prof. Di Marco, director of the Istituto Ricerche Farmitalia Research Laboratories for Microbiology and Chemotherapy, and Prof. Karnofsky, head of the Sloan-Kettering Cancer Institute of New York, leading to the first transatlantic clinical trials. The search for daunomycin's sister anthracyclines led to the discovery and development of adriamycin, one of the best drugs born in Milan. This was the second act prologue of the history of Italian antitumor discovery and clinical oncology, which started in July 1969 when Prof. Di Marco sent Prof. Bonadonna the first vials of adriamycin (doxorubicin) to be tested in clinical trials. This article reviews the Milan scene in the 1960s, a city admired and noted for the outstanding scientific achievements of its private and public institutions in drugs and industrial product discovery.
Regulation of natural health products in Canada.

Science.gov (United States)

Smith, Alysyn; Jogalekar, Sumedha; Gibson, Adam

2014-12-02

In Canada, all natural health products (NHPs) are regulated by Health Canada (HC) under the Food and Drugs Act and the Natural Health Product Regulations. All authorized products undergo pre-market assessment for safety, efficacy and quality and the degree of pre-market oversight varies depending on the risk of the product. In Canada, over 70,000 products have been authorized for sale and over 2000 sites have been licensed to produce NHPs. In the management of NHPs on the Canadian market, HC employs a number of active and collaborative methods to address the most common issues such as contamination, adulteration and deceptive or misleading advertising practices. HC is currently evolving its approaches to NHPs to recognize them as part of the larger group of health products available without a prescription. As such, the regulatory responsibility for all over-the-counter (OTC) drugs, including non-prescription drugs and NHPs, has been transferred to a single federal division. As a result of this transition a number of benefits are being realized with respect to government efficiency, clarity for industry, support for new innovations and consolidated government interactions with the Canadian market. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Natural products: the new engine for African trade growth

OpenAIRE

Bennett, Ben

2006-01-01

This report was to further develop the trade component of the Natural Resources Enterprise Programme (NATPRO). The field work was undertaken in Malawi, Zimbabwe, Namibia, the Republic of South Africa and the United Kingdom between 9th January and 25th February 2006. The work concentrated on ten countries in Southern Africa with potential to export significant quantities of natural products. These products are defined by the project as follows: being plant derived, occurring naturally, wild ha...
Discovery of natural resources

Science.gov (United States)

Guild, P.W.

1976-01-01

Mankind will continue to need ores of more or less the types and grades used today to supply its needs for new mineral raw materials, at least until fusion or some other relatively cheap, inexhaustible energy source is developed. Most deposits being mined today were exposed at the surface or found by relatively simple geophysical or other prospecting techniques, but many of these will be depleted in the foreseeable future. The discovery of deeper or less obvious deposits to replace them will require the conjunction of science and technology to deduce the laws that governed the concentration of elements into ores and to detect and evaluate the evidence of their whereabouts. Great theoretical advances are being made to explain the origins of ore deposits and understand the general reasons for their localization. These advances have unquestionable value for exploration. Even a large deposit is, however, very small, and, with few exceptions, it was formed under conditions that have long since ceased to exist. The explorationist must suppress a great deal of "noise" to read and interpret correctly the "signals" that can define targets and guide the drilling required to find it. Is enough being done to ensure the long-term availability of mineral raw materials? The answer is probably no, in view of the expanding consumption and the difficulty of finding new deposits, but ingenuity, persistence, and continued development of new methods and tools to add to those already at hand should put off the day of "doing without" for many years. The possibility of resource exhaustion, especially in view of the long and increasing lead time needed to carry out basic field and laboratory studies in geology, geophysics, and geochemistry and to synthesize and analyze the information gained from them counsels against any letting down of our guard, however (17). Research and exploration by government, academia, and industry must be supported and encouraged; we cannot wait until an eleventh
Learning Organic Chemistry Through Natural Products

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 12. Learning Organic Chemistry Through Natural Products - Architectural Designs in Molecular Constructions. N R Krishnaswamy. Volume 16 Issue 12 December 2011 pp 1287-1293 ...
Anti-Enterovirus 71 Agents of Natural Products

Directory of Open Access Journals (Sweden)

Liyan Wang

2015-09-01

Full Text Available This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.
Natural products in soil microbe interactions and evolution.

Science.gov (United States)

Traxler, Matthew F; Kolter, Roberto

2015-07-01

In recent years, bacterial interspecies interactions mediated by small molecule natural products have been found to give rise to a surprising array of phenotypes in soil-dwelling bacteria, especially among Streptomyces and Bacillus species. This review examines these interspecies interactions, and the natural products involved, as they have been presented in literature stemming from four disciplines: soil science, interspecies microbiology, ecology, and evolutionary biology. We also consider how these interactions fit into accepted paradigms of signaling, cueing, and coercion.
Antifouling Activity of Marine Natural Products

KAUST Repository

Qian, Pei-Yuan; Xu, Sharon Ying

2012-01-01

for marine industries. Marine natural products have been considered as one of the most promising sources of antifouling compounds in recent years. In antifouling compound screening processes, bioassay systems often play most critical/vital roles in screening
Learning Organic Chemistry Through Natural Products

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 2. Learning Organic Chemistry Through Natural Products Determination of Absolute Stereochemistry. N R Krishnaswamy. Series Article Volume 1 Issue 2 February 1996 pp 40-46 ...
PERSONAL AND CIRCUMSTANTIAL FACTORS INFLUENCING THE ACT OF DISCOVERY.

Science.gov (United States)

OSTRANDER, EDWARD R.

HOW STUDENTS SAY THEY LEARN WAS INVESTIGATED. INTERVIEWS WITH A RANDOM SAMPLE OF 74 WOMEN STUDENTS POSED QUESTIONS ABOUT THE NATURE, FREQUENCY, PATTERNS, AND CIRCUMSTANCES UNDER WHICH ACTS OF DISCOVERY TAKE PLACE IN THE ACADEMIC SETTING. STUDENTS WERE ASSIGNED DISCOVERY RATINGS BASED ON READINGS OF TYPESCRIPTS. EACH STUDENT WAS CLASSIFIED AND…
Effective Online Group Discovery in Trajectory Databases

DEFF Research Database (Denmark)

Li, Xiaohui; Ceikute, Vaida; Jensen, Christian S.

2013-01-01

GPS-enabled devices are pervasive nowadays. Finding movement patterns in trajectory data stream is gaining in importance. We propose a group discovery framework that aims to efficiently support the online discovery of moving objects that travel together. The framework adopts a sampling-independen......GPS-enabled devices are pervasive nowadays. Finding movement patterns in trajectory data stream is gaining in importance. We propose a group discovery framework that aims to efficiently support the online discovery of moving objects that travel together. The framework adopts a sampling......-independent approach that makes no assumptions about when positions are sampled, gives no special importance to sampling points, and naturally supports the use of approximate trajectories. The framework's algorithms exploit state-of-the-art, density-based clustering (DBScan) to identify groups. The groups are scored...
α-Haloaldehydes: versatile building blocks for natural product synthesis.

Science.gov (United States)

Britton, Robert; Kang, Baldip

2013-02-01

The diastereoselective addition of organometallic reagents to α-chloroaldehydes was first reported in 1959 and occupies a historically significant role as the prototypical reaction for Cornforth's model of stereoinduction. Despite clear synthetic potential for these reagents, difficulties associated with producing enantiomerically enriched α-haloaldehydes limited their use in natural product synthesis through the latter half of the 20th century. In recent years, however, a variety of robust, organocatalytic processes have been reported that now provide direct access to optically enriched α-haloaldehydes and have motivated renewed interest in their use as building blocks for natural product synthesis. This Highlight summarizes the methods available for the enantioselective preparation of α-haloaldehydes and their stereoselective conversion into natural products.
Discovery and History of Amino Acid Fermentation.

Science.gov (United States)

Hashimoto, Shin-Ichi

There has been a strong demand in Japan and East Asia for L-glutamic acid as a seasoning since monosodium glutamate was found to present umami taste in 1907. The discovery of glutamate fermentation by Corynebacterium glutamicum in 1956 enabled abundant and low-cost production of the amino acid, creating a large market. The discovery also prompted researchers to develop fermentative production processes for other L-amino acids, such as lysine. Currently, the amino acid fermentation industry is so huge that more than 5 million metric tons of amino acids are manufactured annually all over the world, and this number continues to grow. Research on amino acid fermentation fostered the notion and skills of metabolic engineering which has been applied for the production of other compounds from renewable resources. The discovery of glutamate fermentation has had revolutionary impacts on both the industry and science. In this chapter, the history and development of glutamate fermentation, including the very early stage of fermentation of other amino acids, are reviewed.
Benchmarking of Processes for the Biosynthesis of Natural Products

DEFF Research Database (Denmark)

Seita, Catarina Sanches

putida GS1. (R)-perillic acid is a monoterpenoic acid with antimicrobial properties. It has a strong inhibitory effect on bacteria and fungus, which makes it an attractive compound to be used as a preservative for instance in cosmetic industry, but on the other hand makes the biosynthesis a complicated....... These biological activities can be of interest for use in different sectors of chemical industry, in particular pharmaceutical industry where several drugs are derived or inspired by natural products structure. However, the large scale production of natural products is hindered by its relatively poor abundance...... of the process in comparison with other sweeteners. The main benefit of this early-stage evaluation is putting the biosynthesis of natural products into context in relation to demands of an industrially feasible chemical process. Moreover, it can give very meaningful insight into process development and provides...
Learning Organic Chemistry Through Natural Products

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 10. Learning Organic Chemistry Through Natural Products Architectural Designs in Molecular Constructions. N R Krishnaswamy. Series Article Volume 1 Issue 10 October 1996 pp 37-43 ...
Learning Organic Chemistry Through Natural Products

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 7. Learning Organic Chemistry Through Natural engine Products - Structure and Biological Functions. N R Krishnaswamy. Series Article Volume 1 Issue 7 July 1996 pp 23-30 ...
Deposits of naturally occurring radioactivity in production of oil and natural gas

International Nuclear Information System (INIS)

Strand, T.; Lysebo, I.; Kristensen, D.; Birovljev, A.

1997-01-01

Deposits of naturally occurring radioactive materials is an increasing problem in Norwegian oil and gas production. Activity concentration in solid-state samples and production water, and doses to workers involved in different operations off-shore, have been measured. The report also includes a discussion of different methods of monitoring and alternatives for final disposal of wastes. 154 refs
Learning Organic Chemistry Through Natural Products

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 5. Learning Organic Chemistry Through Natural Products From Molecular and Electronic Structures to Reactivity. N R Krishnaswamy. Series Article Volume 1 Issue 5 May 1996 pp 12-18 ...
Ecopharmacognosy: Exploring The Chemical And Biological Potential Of Nature For Human Health

Directory of Open Access Journals (Sweden)

Geoffrey A. Cordell

2014-04-01

Full Text Available “Why didn’t they develop natural product drugs in a sustainable manner at the beginning of this century?” In 2035, when about 10.0 billion will inhabit Earth, will this be our legacy as the world contemplates the costs and availability of synthetic and gene-based products for primary health care? Acknowledging the recent history of the relationship between humankind and the Earth, it is essential that the health care issues being left for our descendants be considered in terms of resources. For most people in the world, there are two vast health care “gaps”, access to quality drugs and the development of drugs for major global and local diseases. Consequently for all of these people, plants, in their various forms, remain a primary source of health care. In the developed countries, natural products derived from plants assume a relatively minor role in health care, as prescription and over-the-counter products, even with the widespread use of phytotherapeutical preparations. Significantly, pharmaceutical companies have retrenched substantially in their disease areas of focus. These research areas do not include the prevalent diseases of the middle- and lower-income countries, and important diseases of the developed world, such as drug resistance. What then is the vision for natural product research to maintain the choices of drug discovery and pharmaceutical development for future generations? In this discussion some facets of how natural products must be involved globally, in a sustainable manner, for improving health care will be examined within the framework of the new term “ecopharmacognosy”, which invokes sustainability as the basis for research on biologically active natural products. Access to the biome, the acquisition, analysis and dissemination of plant knowledge, natural product structure diversification, biotechnology development, strategies for natural product drug discovery, and aspects of multitarget
Remote methods of indicating oil products in natural waters

Energy Technology Data Exchange (ETDEWEB)

Shlyakhova, L A

1981-01-01

A survey is made of domestic and foreign publications covering remote methods of monitoring film petroleum products and oil in natural waters. The given methods are realized in practice with the use of different sections of the electromagnetic spectrum. Remote quality control of the natural waters at the modern level may be an indicator of water pollution with film petroleum products.

Bioactive natural products from Chinese marine flora and fauna.

Science.gov (United States)

Zhou, Zhen-Fang; Guo, Yue-Wei

2012-09-01

In recent decades, the pharmaceutical application potential of marine natural products has attracted much interest from both natural product chemists and pharmacologists. Our group has long been engaged in the search for bioactive natural products from Chinese marine flora (such as mangroves and algae) and fauna (including sponges, soft corals, and mollusks), resulting in the isolation and characterization of numerous novel secondary metabolites spanning a wide range of structural classes and various biosynthetic origins. Of particular interest is the fact that many of these compounds show promising biological activities, including cytotoxic, antibacterial, and enzyme inhibitory effects. By describing representative studies, this review presents a comprehensive summary regarding the achievements and progress made by our group in the past decade. Several interesting examples are discussed in detail.
The discovery of fission

International Nuclear Information System (INIS)

McKay, H.A.C.

1978-01-01

In this article by the retired head of the Separation Processes Group of the Chemistry Division, Atomic Energy Research Establishment, Harwell, U.K., the author recalls what he terms 'an exciting drama, the unravelling of the nature of the atomic nucleus' in the years before the Second World War, including the discovery of fission. 12 references. (author)
Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

Science.gov (United States)

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.
Anticancer drug discovery and pharmaceutical chemistry: a history.

Science.gov (United States)

Braña, Miguel F; Sánchez-Migallón, Ana

2006-10-01

There are several procedures for the chemical discovery and design of new drugs from the point of view of the pharmaceutical or medicinal chemistry. They range from classical methods to the very new ones, such as molecular modeling or high throughput screening. In this review, we will consider some historical approaches based on the screening of natural products, the chances for luck, the systematic screening of new chemical entities and serendipity. Another group comprises rational design, as in the case of metabolic pathways, conformation versus configuration and, finally, a brief description on available new targets to be carried out. In each approach, the structure of some examples of clinical interest will be shown.
NASA Reverb: Standards-Driven Earth Science Data and Service Discovery

Science.gov (United States)

Cechini, M. F.; Mitchell, A.; Pilone, D.

2011-12-01

NASA's Earth Observing System Data and Information System (EOSDIS) is a core capability in NASA's Earth Science Data Systems Program. NASA's EOS ClearingHOuse (ECHO) is a metadata catalog for the EOSDIS, providing a centralized catalog of data products and registry of related data services. Working closely with the EOSDIS community, the ECHO team identified a need to develop the next generation EOS data and service discovery tool. This development effort relied on the following principles: + Metadata Driven User Interface - Users should be presented with data and service discovery capabilities based on dynamic processing of metadata describing the targeted data. + Integrated Data & Service Discovery - Users should be able to discovery data and associated data services that facilitate their research objectives. + Leverage Common Standards - Users should be able to discover and invoke services that utilize common interface standards. Metadata plays a vital role facilitating data discovery and access. As data providers enhance their metadata, more advanced search capabilities become available enriching a user's search experience. Maturing metadata formats such as ISO 19115 provide the necessary depth of metadata that facilitates advanced data discovery capabilities. Data discovery and access is not limited to simply the retrieval of data granules, but is growing into the more complex discovery of data services. These services include, but are not limited to, services facilitating additional data discovery, subsetting, reformatting, and re-projecting. The discovery and invocation of these data services is made significantly simpler through the use of consistent and interoperable standards. By utilizing an adopted standard, developing standard-specific adapters can be utilized to communicate with multiple services implementing a specific protocol. The emergence of metadata standards such as ISO 19119 plays a similarly important role in discovery as the 19115 standard
Discovery of the Higgs boson and beyond

International Nuclear Information System (INIS)

Godbole, Rohini

2014-01-01

This talk is about the Higgs mechanism, the theoretical discovery of which, was awarded the 2013 Nobel Prize. It also discusses the discovery of the Higgs boson at the large hadron collider which provided the experimental proof that made the Nobel prize possible. It covers the implications of these for the quest of unravelling the fundamental laws of nature which seem to govern both, the behavior of the ultra small (subatomic particles) and the ultra large (the cosmos)
Flow chemistry syntheses of natural products.

Science.gov (United States)

Pastre, Julio C; Browne, Duncan L; Ley, Steven V

2013-12-07

The development and application of continuous flow chemistry methods for synthesis is a rapidly growing area of research. In particular, natural products provide demanding challenges to this developing technology. This review highlights successes in the area with an emphasis on new opportunities and technological advances.
Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

Science.gov (United States)

Zha, Weibin

2018-04-01

The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.
Panorama 2017 - New conventional oil and gas discoveries

International Nuclear Information System (INIS)

Hureau, Geoffroy; Vially, Roland

2017-01-01

In 2016, spending on exploration is expected to decline by approximately 35% for the second consecutive year (total exploration-production is down 24%). However, volumes discovered through conventional exploration should only fall by 25% due to several significant discoveries, particularly in Alaska and West Africa. The largest discovery in 2016 was an unconventional Permian shale basin in the United States, which could alone contain as many hydrocarbons as all of the year's conventional discoveries combined
Nature-Inspired Design : Strategies for Sustainable Product Development

NARCIS (Netherlands)

De Pauw, I.C.

2015-01-01

Product designers can apply different strategies, methods, and tools for sustainable product development. Nature-Inspired Design Strategies (NIDS) offer designers a distinct class of strategies that use ‘nature’ as a guiding source of knowledge and inspiration for addressing sustainability.
Discovery of the calcium, indium, tin, and platinum isotopes

International Nuclear Information System (INIS)

Amos, S.; Gross, J.L.; Thoennessen, M.

2011-01-01

Currently, twenty-four calcium, thirty-eight indium, thirty-eight tin, and thirty-nine platinum isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented. - Highlights: Documentation of the discovery of all calcium, indium, tin and platinum isotopes. → Summary of author, journal, year, place and country of discovery for each isotope. → Brief description of discovery history of each isotope.
T R Seshadri's Contributions to the Chemistry of Natural Products

Indian Academy of Sciences (India)

Sri Sathya Sai Institute of. Higher Learning. Generations of students would vouch for the fact that he has the uncanny ability to present the chemistry of natural products logically and with feeling. Keywords. Flavonoids, lichen metabolite, methylation, Elbs-Seshadri oxi- dation, structure elucidation, natural products synthesis.
39 CFR 3001.25 - Discovery-general policy.

Science.gov (United States)

2010-07-01

... only from the Postal Service. Discovery requests of this nature are permissible only for the purpose of... participant from introducing designated matters in evidence, or strike the evidence, complaint or pleadings or...
Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural Product YM-254890, Targeting the Gq Protein.

Science.gov (United States)

Zhang, Hang; Xiong, Xiao-Feng; Boesgaard, Michael W; Underwood, Christina R; Bräuner-Osborne, Hans; Strømgaard, Kristian

2017-06-07

Extracellular signals perceived by G protein-coupled receptors are transmitted via G proteins, and subsequent intracellular signaling cascades result in a plethora of physiological responses. The natural product cyclic depsipeptides YM-254890 and FR900359 are the only known compounds that specifically inhibit signaling mediated by the G q subfamily. In this study we exploit a newly developed synthetic strategy for this compound class in the design, synthesis, and pharmacological evaluation of eight new analogues of YM-254890. These structure-activity relationship studies led to the discovery of three new analogues, YM-13, YM-14, and YM-18, which displayed potent and selective G q inhibitory activity. This provides pertinent information for the understanding of the G q inhibitory mechanism by this class of compounds and importantly provides a pathway for the development of labeled YM-254890 analogues. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
The Discovery of Insulin: A Case Study of Scientific Methodology

Science.gov (United States)

Stansfield, William D.

2012-01-01

The nature of scientific research sometimes involves a trial-and-error procedure. Popular reviews of successful results from this approach often sanitize the story by omitting unsuccessful trials, thus painting the rosy impression that research simply follows a direct route from hypothesis to experiment to scientific discovery. The discovery of…
76 FR 65097 - National Forest Products Week, 2011

Science.gov (United States)

2011-10-20

... National Forest Products Week, 2011 By the President of the United States of America A Proclamation America... access clean water and air, drive discovery as natural laboratories, and make our communities more... and preservation of these national treasures. Through the America's Great Outdoors Initiative, my...
The discovery of the structure of DNA

Science.gov (United States)

Squires, G. L.

2003-04-01

On 25 April 1953, Nature published a letter by Francis Crick and James Watson, at the Cavendish Laboratory, Cambridge, proposing a structure for DNA. This letter marked the beginning of a revolution in biology. Besides Crick and Watson, two other scientists, Rosalind Franklin and Maurice Wilkins, played key roles in the discovery. After sketching the early careers of the four scientists, the present article gives an account of the physics and chemistry involved in the discovery, and the events leading up to it.
Naturally Efficient Emitters: Luminescent Organometallic Complexes Derived from Natural Products

Science.gov (United States)

Zhang, Wen-Hua; Young, David J.

2013-08-01

Naturally occurring molecules offer intricate structures and functionality that are the basis of modern medicinal chemistry, but are under-represented in materials science. Herein, we review recent literature describing the use of abundant and relatively inexpensive, natural products for the synthesis of ligands for luminescent organometallic complexes used for organic light emitting diodes (OLEDs) and related technologies. These ligands are prepared from the renewable starting materials caffeine, camphor, pinene and cinchonine and, with the exception of caffeine, impart performance improvements to the emissive metal complexes and resulting OLED devices, with emission wavelengths that span the visible spectrum from blue to red. The advantages of these biologically-derived molecules include improved solution processibility and phase homogeneity, brighter luminescence, higher quantum efficiencies and lower turn-on voltages. While nature has evolved these carbon-skeletons for specific purposes, they also offer some intriguing benefits in materials science and technology.
Viral pathogen discovery

Science.gov (United States)

Chiu, Charles Y

2015-01-01

Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease. PMID:23725672
Discovery of Intrinsic Primitives on Triangle Meshes

KAUST Repository

Solomon, Justin; Ben-Chen, Mirela; Butscher, Adrian; Guibas, Leonidas

2011-01-01

The discovery of meaningful parts of a shape is required for many geometry processing applications, such as parameterization, shape correspondence, and animation. It is natural to consider primitives such as spheres, cylinders and cones

Natural products to improve quality of life targeting for colon drug delivery.

Science.gov (United States)

Kim, Hyunjo

2012-03-01

The colon is largely being investigated as a site for administration of protein and peptides, which are degraded by digestive enzymes in the upper GIT. Also for local diseases of the colon such as inflammatory bowel disease, colorectal cancer and ameobiasis, drug administration to the site of action can not only reduce the dose to be administered, but also decrease the side effects. Inflammatory Bowel Disease (IBD) such as Ulcerative colitis and Crohn's disease are characterized by chronic intestinal inflammation. Intestinal bacteria initiate the activation of intestinal inflammatory processes, which are mediated by pro-inflammatory cytokines and chemokine. Increased chemokine expression has also been observed in epithelial cells, endothelial cells, and smooth muscle cells. Future trials of specific agents capable of inhibiting chemokine synthesis and secretion or blocking chemokine-chemokine receptor interaction will be important to study in patients with ulcerative colitis and Crohn's disease. Many important bioactive compounds have been discovered from natural sources using bioactivity directed fractionation and isolation (BDFl) Continuing discovery has also been facilitated by the recent development of new bioassay methods. These bioactive compounds are mostly plant secondary metabolites, and many naturally occurring pure compounds have become medicines, dietary supplements, and other useful commercial products. The present review includes various approaches investigated for colon drug delivery and their site specificity. To achieve successful colonic delivery, a drug needs to be protected from absorption and the environment of the upper gastrointestinal tract and then be abruptly released into the proximal colon, which is considered the optimum site for colon targeted delivery of drugs.
New oil and gas discoveries

International Nuclear Information System (INIS)

Alazard-Toux, N.

2004-01-01

During the period 1999-2003, new oil and gas fields generated additional reserves of nearly 11 000 bcm of natural gas and 62 Gbbl of oil and condensates, volumes very much superior to those discovered in the five previous years. Two-thirds of these discoveries were located offshore, half in deep water. (author)
Exploring the production of natural gas through the lenses of the ACEGES model

International Nuclear Information System (INIS)

Voudouris, Vlasios; Matsumoto, Ken'ichi; Sedgwick, John; Rigby, Robert; Stasinopoulos, Dimitrios; Jefferson, Michael

2014-01-01

Due to the increasing importance of natural gas for modern economic activity, and gas's non-renewable nature, it is extremely important to try to estimate possible trajectories of future natural gas production while considering uncertainties in resource estimates, demand growth, production growth and other factors that might limit production. In this study, we develop future scenarios for natural gas supply using the ACEGES computational laboratory. Conditionally on the currently estimated ultimate recoverable resources, the ‘Collective View’ and ‘Golden Age’ Scenarios suggest that the supply of natural gas is likely to meet the increasing demand for natural gas until at least 2035. The ‘Golden Age’ Scenario suggests significant ‘jumps’ of natural gas production – important for testing the resilience of long-term strategies. - Highlights: • We present the ‘Collective View’ and ‘Golden Age’ Scenarios for natural gas production. • We do not observe any significant supply demand pressure of natural gas until 2035. • We do observe ‘jumps’ in natural gas supply until 2035. • The ACEGES-based scenarios can assess the resilience of longterm strategies
NATpipe: an integrative pipeline for systematical discovery of natural antisense transcripts (NATs) and phase-distributed nat-siRNAs from de novo assembled transcriptomes

Science.gov (United States)

Yu, Dongliang; Meng, Yijun; Zuo, Ziwei; Xue, Jie; Wang, Huizhong

2016-01-01

Nat-siRNAs (small interfering RNAs originated from natural antisense transcripts) are a class of functional small RNA (sRNA) species discovered in both plants and animals. These siRNAs are highly enriched within the annealed regions of the NAT (natural antisense transcript) pairs. To date, great research efforts have been taken for systematical identification of the NATs in various organisms. However, developing a freely available and easy-to-use program for NAT prediction is strongly demanded by researchers. Here, we proposed an integrative pipeline named NATpipe for systematical discovery of NATs from de novo assembled transcriptomes. By utilizing sRNA sequencing data, the pipeline also allowed users to search for phase-distributed nat-siRNAs within the perfectly annealed regions of the NAT pairs. Additionally, more reliable nat-siRNA loci could be identified based on degradome sequencing data. A case study on the non-model plant Dendrobium officinale was performed to illustrate the utility of NATpipe. Finally, we hope that NATpipe would be a useful tool for NAT prediction, nat-siRNA discovery, and related functional studies. NATpipe is available at www.bioinfolab.cn/NATpipe/NATpipe.zip. PMID:26858106
Quantifying methane emissions from natural gas production in north-eastern Pennsylvania

Directory of Open Access Journals (Sweden)

Z. R. Barkley

2017-11-01

Full Text Available Natural gas infrastructure releases methane (CH4, a potent greenhouse gas, into the atmosphere. The estimated emission rate associated with the production and transportation of natural gas is uncertain, hindering our understanding of its greenhouse footprint. This study presents a new application of inverse methodology for estimating regional emission rates from natural gas production and gathering facilities in north-eastern Pennsylvania. An inventory of CH4 emissions was compiled for major sources in Pennsylvania. This inventory served as input emission data for the Weather Research and Forecasting model with chemistry enabled (WRF-Chem, and atmospheric CH4 mole fraction fields were generated at 3 km resolution. Simulated atmospheric CH4 enhancements from WRF-Chem were compared to observations obtained from a 3-week flight campaign in May 2015. Modelled enhancements from sources not associated with upstream natural gas processes were assumed constant and known and therefore removed from the optimization procedure, creating a set of observed enhancements from natural gas only. Simulated emission rates from unconventional production were then adjusted to minimize the mismatch between aircraft observations and model-simulated mole fractions for 10 flights. To evaluate the method, an aircraft mass balance calculation was performed for four flights where conditions permitted its use. Using the model optimization approach, the weighted mean emission rate from unconventional natural gas production and gathering facilities in north-eastern Pennsylvania approach is found to be 0.36 % of total gas production, with a 2σ confidence interval between 0.27 and 0.45 % of production. Similarly, the mean emission estimates using the aircraft mass balance approach are calculated to be 0.40 % of regional natural gas production, with a 2σ confidence interval between 0.08 and 0.72 % of production. These emission rates as a percent of production are
Quantifying methane emissions from natural gas production in north-eastern Pennsylvania

Science.gov (United States)

Barkley, Zachary R.; Lauvaux, Thomas; Davis, Kenneth J.; Deng, Aijun; Miles, Natasha L.; Richardson, Scott J.; Cao, Yanni; Sweeney, Colm; Karion, Anna; Smith, MacKenzie; Kort, Eric A.; Schwietzke, Stefan; Murphy, Thomas; Cervone, Guido; Martins, Douglas; Maasakkers, Joannes D.

2017-11-01

Natural gas infrastructure releases methane (CH4), a potent greenhouse gas, into the atmosphere. The estimated emission rate associated with the production and transportation of natural gas is uncertain, hindering our understanding of its greenhouse footprint. This study presents a new application of inverse methodology for estimating regional emission rates from natural gas production and gathering facilities in north-eastern Pennsylvania. An inventory of CH4 emissions was compiled for major sources in Pennsylvania. This inventory served as input emission data for the Weather Research and Forecasting model with chemistry enabled (WRF-Chem), and atmospheric CH4 mole fraction fields were generated at 3 km resolution. Simulated atmospheric CH4 enhancements from WRF-Chem were compared to observations obtained from a 3-week flight campaign in May 2015. Modelled enhancements from sources not associated with upstream natural gas processes were assumed constant and known and therefore removed from the optimization procedure, creating a set of observed enhancements from natural gas only. Simulated emission rates from unconventional production were then adjusted to minimize the mismatch between aircraft observations and model-simulated mole fractions for 10 flights. To evaluate the method, an aircraft mass balance calculation was performed for four flights where conditions permitted its use. Using the model optimization approach, the weighted mean emission rate from unconventional natural gas production and gathering facilities in north-eastern Pennsylvania approach is found to be 0.36 % of total gas production, with a 2σ confidence interval between 0.27 and 0.45 % of production. Similarly, the mean emission estimates using the aircraft mass balance approach are calculated to be 0.40 % of regional natural gas production, with a 2σ confidence interval between 0.08 and 0.72 % of production. These emission rates as a percent of production are lower than rates found in any
A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

Science.gov (United States)

Gormus, Bobby J; Martin, Louis N; Baskin, Gary B

2004-01-01

Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM). Our results together with observations of others led us to propose that both SIVmac and SIVDelta originated in SMM and that SIV emerged in humans as a result of early African nonhuman primate SIV trans-species infections in humans.
Big Data in Drug Discovery.

Science.gov (United States)

Brown, Nathan; Cambruzzi, Jean; Cox, Peter J; Davies, Mark; Dunbar, James; Plumbley, Dean; Sellwood, Matthew A; Sim, Aaron; Williams-Jones, Bryn I; Zwierzyna, Magdalena; Sheppard, David W

2018-01-01

Interpretation of Big Data in the drug discovery community should enhance project timelines and reduce clinical attrition through improved early decision making. The issues we encounter start with the sheer volume of data and how we first ingest it before building an infrastructure to house it to make use of the data in an efficient and productive way. There are many problems associated with the data itself including general reproducibility, but often, it is the context surrounding an experiment that is critical to success. Help, in the form of artificial intelligence (AI), is required to understand and translate the context. On the back of natural language processing pipelines, AI is also used to prospectively generate new hypotheses by linking data together. We explain Big Data from the context of biology, chemistry and clinical trials, showcasing some of the impressive public domain sources and initiatives now available for interrogation. © 2018 Elsevier B.V. All rights reserved.
Natural radionuclide distribution in phosphate fertilizer and superphosphate production technology

Energy Technology Data Exchange (ETDEWEB)

Lisachenko, Eh P; Ponikarova, T M; Lisitsyna, Yu Z

1987-01-01

The obtained data on the natural radionuclide distribution by phosphate fertilizer and superphosphate production process stages testify to phosphate fertilizer enrichment 2-4 times in relation to initial ore, depending in the raw material used. In this case uranium and thorium series element concentration value (in equilibrium with their decomposition products), proposed as a regulating one in phosphorus-containing fertilizers, is not achieved. However, the fact of lurichment as it is and the enrichment factor, stated in the course of the work, should be taken into account for evaluation of phosphorite new deposit raw material with higher concentrations of natural radionuclides. Natural radionuclide separation in the enrichment process and superphosphate production is not revealed.
Resource-estimation models and predicted discovery

International Nuclear Information System (INIS)

Hill, G.W.

1982-01-01

Resources have been estimated by predictive extrapolation from past discovery experience, by analogy with better explored regions, or by inference from evidence of depletion of targets for exploration. Changes in technology and new insights into geological mechanisms have occurred sufficiently often in the long run to form part of the pattern of mature discovery experience. The criterion, that a meaningful resource estimate needs an objective measure of its precision or degree of uncertainty, excludes 'estimates' based solely on expert opinion. This is illustrated by development of error measures for several persuasive models of discovery and production of oil and gas in USA, both annually and in terms of increasing exploration effort. Appropriate generalizations of the models resolve many points of controversy. This is illustrated using two USA data sets describing discovery of oil and of U 3 O 8 ; the latter set highlights an inadequacy of available official data. Review of the oil-discovery data set provides a warrant for adjusting the time-series prediction to a higher resource figure for USA petroleum. (author)
Vital signs: drilling rush accelerates, led by stellar B.C. natural gas discoveries

International Nuclear Information System (INIS)

Lunan, D.

2001-01-01

A recent survey of drilling activity in the Western Canadian Sedimentary Basin provide clear evidence of intensified efforts to match the aggressive forecast of 17,500 well completions in 2001, forecast by the Petroleum Services Association of Canada, or the 18,500 new wells forecast by the Canadian Association of Oilwell Drilling Contractors, and satisfy the expected strong natural gas demand. The rush for drilling properties boosted first-quarter land sale bonus payments by 78 per cent to more than $500 million, or about $356 per hectare from $282 million or $256 per hectare in the first three months of 2000. Land acquisition is most robust in northeastern British Columbia, where a series of 50-million-cubic feet-per-day discoveries in the Ladyfern region has ignited the hottest exploration play of this year, resulting in a 400 per cent increase in first quarter bonus payments to $212 million, or $613 per hectare. Overall Western Canada rig count peaked at 614 active units in late February, declining since to 264 rigs in April, due to the onset of spring breakup. Success rate in the first quarter of 2001 for exploratory drilling peaked at 72 per cent, up from 53 per cent a year ago. Industry-wide success rate jumped to 83 per cent from 75 per cent in 2000. Average depth in BC in the first quarter of 2001 reached 1,700 metres, the highest in Western Canada, compared to about 1,300 metres a year ago. Industry-wide, the average depth slipped from 1,143 metres to 1,134 metres, reflecting the continuing reliance on shallow gas drilling in an effort to attach known reserves as quickly as possible. Offshore drilling on East Coast provides a different picture: drilling depth averages climbed to 10,339 metres from 7,131 metres in 2000. Discovery of the Deep Panuke field by PanCanadian Petroleum is considered partly responsible for the sudden increase in well depth. tabs., 2 photos
Discovery of the cadmium isotopes

International Nuclear Information System (INIS)

Amos, S.; Thoennessen, M.

2010-01-01

Thirty-seven cadmium isotopes have been observed so far and the discovery of these isotopes is discussed here. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.
Discovery of the iron isotopes

International Nuclear Information System (INIS)

Schuh, A.; Fritsch, A.; Heim, M.; Shore, A.; Thoennessen, M.

2010-01-01

Twenty-eight iron isotopes have been observed so far and the discovery of these isotopes is discussed here. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.
Discovery of the silver isotopes

International Nuclear Information System (INIS)

Schuh, A.; Fritsch, A.; Ginepro, J.Q.; Heim, M.; Shore, A.; Thoennessen, M.

2010-01-01

Thirty-eight silver isotopes have been observed so far and the discovery of these isotopes is discussed here. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.
Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources.

Science.gov (United States)

Ni, Jun; Tao, Fei; Du, Huaiqing; Xu, Ping

2015-09-02

Plant secondary metabolites have been attracting people's attention for centuries, due to their potentials; however, their production is still difficult and costly. The rich diversity of microbes and microbial genome sequence data provide unprecedented gene resources that enable to develop efficient artificial pathways in microorganisms. Here, by mimicking a natural pathway of plants using microbial genes, a new metabolic route was developed in E. coli for the synthesis of vanillin, the most widely used flavoring agent. A series of factors were systematically investigated for raising production, including efficiency and suitability of genes, gene dosage, and culture media. The metabolically engineered strain produced 97.2 mg/L vanillin from l-tyrosine, 19.3 mg/L from glucose, 13.3 mg/L from xylose and 24.7 mg/L from glycerol. These results show that the metabolic route enables production of natural vanillin from low-cost substrates, suggesting that it is a good strategy to mimick natural pathways for artificial pathway design.
Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources

Science.gov (United States)

Ni, Jun; Tao, Fei; Du, Huaiqing; Xu, Ping

2015-01-01

Plant secondary metabolites have been attracting people’s attention for centuries, due to their potentials; however, their production is still difficult and costly. The rich diversity of microbes and microbial genome sequence data provide unprecedented gene resources that enable to develop efficient artificial pathways in microorganisms. Here, by mimicking a natural pathway of plants using microbial genes, a new metabolic route was developed in E. coli for the synthesis of vanillin, the most widely used flavoring agent. A series of factors were systematically investigated for raising production, including efficiency and suitability of genes, gene dosage, and culture media. The metabolically engineered strain produced 97.2 mg/L vanillin from l-tyrosine, 19.3 mg/L from glucose, 13.3 mg/L from xylose and 24.7 mg/L from glycerol. These results show that the metabolic route enables production of natural vanillin from low-cost substrates, suggesting that it is a good strategy to mimick natural pathways for artificial pathway design. PMID:26329726
Radon gas in oil and natural gas production facilities

International Nuclear Information System (INIS)

Chandler, W.P.

1994-01-01

Radon gas is a naturally occurring radionuclide that can be found in some oil and natural gas production facilities, either as a contaminant in a natural gas stream or derived from Radium dissolved in formation waters. The gas itself is not normally a health hazard, but it's decay products, which can be concentrated by plate-out or deposition as a scale in process equipment, can be a health hazard for maintenance personnel. To evaluate possible health hazards, it is necessary to monitor for naturally occurring radioactive materials (NORM) in the gas stream and in the formation water. If Radon and/or Radium is found, a monitoring programme should be initiated to comply with National or State requirements. In some instances, it has been found necessary to dispose of silt and scale materials as low level radioactive waste. 8 refs
The scientist as philosopher philosophical consequences of great scientific discoveries

CERN Document Server

Weinert, Friedel

2005-01-01

How do major scientific discoveries reshape their originators’, and our own, sense of reality and concept of the physical world? The Scientist as Philosopher explores the interaction between physics and philosophy. Clearly written and well illustrated, the book first places the scientist-philosophers in the limelight as we learn how their great scientific discoveries forced them to reconsider the time-honored notions with which science had described the natural world. Then, the book explains that what we understand by nature and science have undergone fundamental conceptual changes as a result of the discoveries of electromagnetism, thermodynamics and atomic structure. Even more dramatically, the quantum theory and special theory of relativity questioned traditional assumptions about causation and the passage of time. The author concludes that the dance between science and philosophy is an evolutionary process, which will keep them forever entwined.
Petroleum and natural gas economy in Arab Countries, in Iran, Namibia Niger and Nigeria

International Nuclear Information System (INIS)

Anon.

1993-01-01

This paper describes briefly main informations on petroleum prices and market trends, trade and contracts, production capacity, exports, demand, exploration and new discoveries. O.P.E.C. will have to invest $147-149 milliards to increase its petroleum production capacity to 37.49-38.69 Mb per day in year 2000. Gaz de France has announced the establishment of Iran Gas Europe, a joint venture entrusted to study the import of iranian liquefied natural gas in Europe. In Algeria, exploration contract has been signed by Petro-Canada and a new petroleum discovery has been announced by Repsol, in Illizi basin. In Namibia, Niger and Nigeria, new exploration permits have been conceded to Elf and Engen co
Natural products - plenty more where that came from

Energy Technology Data Exchange (ETDEWEB)

Arnold, M.

1980-12-22

In this article, natural products and their possible use as renewable resources are reviewed. The fermentation of corn for the production of alcohol for motor fuel is discussed and other crops for this purpose include sugar cane, cassava, sweet potato and Jerusalem artichoke. The hydrolysis of cellulose to sugars based on enzyme hydrolysis is currently being researched in the USA. Also in the USA, Melvin Calvin hopes to breed a rubber-bearing plant whose latex can be easily cracked to motor fuel. Guayule and jojoba rubber-bearing plants are also the focus of research at present. The importance of natural vegetation in the manufacturing of medicines and in the chemical and food industries is stressed. Finally products of the sea, particularly alginates and carragheenins are mentioned, but as yet, the full potential of the sea to yield renewable resources is unknown.

Synthesis of natural products of therapeutic significance

Indian Academy of Sciences (India)

system

2015-11-07

Nov 7, 2015 ... potential activity, while more natural products await the ... Treaty that prohibits commercial exploitation of Antarctic resources, the development of a synthetic strategy that allows the synthesis of palmerolide A and an array of its.
Catalyst-controlled oligomerization for the collective synthesis of polypyrroloindoline natural products.

Science.gov (United States)

Jamison, Christopher R; Badillo, Joseph J; Lipshultz, Jeffrey M; Comito, Robert J; MacMillan, David W C

2017-12-01

In nature, many organisms generate large families of natural product metabolites that have related molecular structures as a means to increase functional diversity and gain an evolutionary advantage against competing systems within the same environment. One pathway commonly employed by living systems to generate these large classes of structurally related families is oligomerization, wherein a series of enzymatically catalysed reactions is employed to generate secondary metabolites by iteratively appending monomers to a growing serial oligomer chain. The polypyrroloindolines are an interesting class of oligomeric natural products that consist of multiple cyclotryptamine subunits. Herein we describe an iterative application of asymmetric copper catalysis towards the synthesis of six distinct oligomeric polypyrroloindoline natural products: hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given the customizable nature of the small-molecule catalysts employed, we demonstrate that this strategy is further amenable to the construction of quadrigemine H-type alkaloids not isolated previously from natural sources.
Soil Properties and Plant Biomass Production in Natural Rangeland Management Systems

Directory of Open Access Journals (Sweden)

Romeu de Souza Werner

Full Text Available ABSTRACT Improper management of rangelands can cause land degradation and reduce the economic efficiency of livestock activity. The aim of this study was to evaluate soil properties and quantify plant biomass production in four natural rangeland management systems in the Santa Catarina Plateau (Planalto Catarinense of Brazil. The treatments, which included mowed natural rangeland (NR, burned natural rangeland (BR, natural rangeland improved through the introduction of plant species after harrowing (IH, and natural rangeland improved through the introduction of plant species after chisel plowing (IC, were evaluated in a Nitossolo Bruno (Nitisol. In the improved treatments, soil acidity was corrected, phosphate fertilizer was applied, and intercropped annual ryegrass (Lolium multiflorum, velvet grass (Holcus lanatus, and white clover (Trifolium repens were sown. Management systems with harrowed or chisel plowed soil showed improved soil physical properties; however, the effect decreased over time and values approached those of burned and mowed natural rangelands. Natural rangeland systems in the establishment phase had little influence on soil organic C. The mowed natural rangeland and improved natural rangeland exhibited greater production of grazing material, while burning the field decreased production and increased the proportion of weeds. Improvement of the natural rangelands increased leguminous biomass for pasture.
Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

Directory of Open Access Journals (Sweden)

Charu Sharma

2015-01-01

Full Text Available The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2 which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2 receptors. However, these synthetic based Cannabis derived compounds are known to exert adverse psychiatric effect and have also been exploited for drug abuse. This encourages us to find out an alternative and safe drug with the least psychiatric adverse effects. In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems. Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative. The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.
The discovery of X-rays diffraction: From crystals to DNA. A case study to promote understanding of the nature of science and of its interdisciplinary character

International Nuclear Information System (INIS)

Guerra, Francesco; Leone, Matteo; Robotti, Nadia

2015-01-01

The advantages of introducing history of science topics into the teaching of science has been advocated by a large number of scholars within the science education community. One of the main reasons given for using history of science in teaching is its power to promote understanding of the nature of science (NOS). In this respect, the historical case of X-rays diffraction, from the discovery of Max von Laue (1912) to the first X-rays diffraction photographs of DNA (1953), is a case in point for showing that a correct experimental strategy and a favourable theoretical context are not enough to make a scientific discovery.
Gas, gas, gas... discoveries and developments booming worldwide

International Nuclear Information System (INIS)

Maxwell, F.

2000-01-01

Deep water exploration is yielding more than billion barrel oil fields. Unocal's 3 May discovery of 2-3 Tcf of gas in its Kutei block of Indonesia marks the first major discovery of natural gas in the deep water frontier: Wildcats Gula and Gada were drilled in over 1800 m of water as part of an aggressive search for gas instigated by Unocal last year. The author makes a survey of gas exploration and development throughout the world. (author)
1996 petroleum exploration and production in France; 1996 recherche et production petrolieres en France

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

A detailed analysis and data compilations on petroleum exploration and production activities in France in 1996, are presented. Acreage evolution is decreasing despite a growth of new exploration licenses; a significant rise in the activity of seismic surveying has occurred, while exploration drilling activity (onshore only), equivalent to the previous year, led to two oil discoveries, and the investments in exploration showed a decrease of 28 percent compared to 1995. Production is declining for oil as well as natural gas (15 and 12 percent decrease resp.), while production investments dropped very sharply showing a reduction of 48 percent
1996 petroleum exploration and production in France; 1996 recherche et production petrolieres en France

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

A detailed analysis and data compilations on petroleum exploration and production activities in France in 1996, are presented. Acreage evolution is decreasing despite a growth of new exploration licenses; a significant rise in the activity of seismic surveying has occurred, while exploration drilling activity (onshore only), equivalent to the previous year, led to two oil discoveries, and the investments in exploration showed a decrease of 28 percent compared to 1995. Production is declining for oil as well as natural gas (15 and 12 percent decrease resp.), while production investments dropped very sharply showing a reduction of 48 percent
120 YEARS SINCE THE DISCOVERY OF X-RAYS.

Science.gov (United States)

Babic, Rade R; Stankovic Babic, Gordana; Babic, Strahinja R; Babic, Nevena R

2016-09-01

This paper is intended to celebrate the 120th anniversary of the discovery of X-rays. X-rays (Roentgen-rays) were discovered on the 8th ofNovember, 1895 by the German physicist Wilhelm Conrad Roentgen. Fifty days after the discovery of X-ray, on December 28, 1895. Wilhelm Conrad Roentgen published a paper about the discovery of X-rays - "On a new kind of rays" (Wilhelm Conrad Roentgen: Ober eine neue Art von Strahlen. In: Sitzungsberichte der Wurzburger Physik.-Medic.- Gesellschaft. 1895.). Therefore, the date of 28th ofDecember, 1895 was taken as the date of X-rays discovery. This paper describes the work of Wilhelm Conrad Roentgen, Nikola Tesla, Mihajlo Pupin and Maria Sklodowska-Curie about the nature of X-rays . The fantastic four - Wilhelm Conrad Roentgen, NikolaTesla, Mihajlo ldvorski Pupin and Maria Sklodowska-Curie set the foundation of radiology with their discovery and study of X-rays. Five years after the discovery of X-rays, in 1900, Dr Avram Vinaver had the first X-ray machine installed in abac, in Serbia at the time when many developed countries did not have an X-ray machine and thus set the foundation of radiology in Serbia.
Natural gas production from underground nuclear explosions

Energy Technology Data Exchange (ETDEWEB)

1965-01-01

A remote location in Rio Arriba County, NW. New Mexico, is being considered as the site for an experiment in the use of a nuclear explosive to increase production from a natural gas field. A feasibility study has been conducted by the El Paso Natural Gas Co., the U.S. Atomic Energy commission, and the U.S. Bureau of Mines. As presently conceived, a nuclear explosive would be set in an emplacement hole and detonated. The explosion would create a cylinder or ''chimney'' of collapsed rock, and a network of fractures extending beyond the chimney. The fractures are the key effect. These would consist of new fractures, enlargement of existing ones, and movement along planes where strata overlap. In addition, there are a number of intangible but important benefits that could accrue from the stimulating effect. Among these are the great increase in recoverable reserves and the deliverability of large volumes of gas during the periods of high demand. It is believed that this type of well stimulation may increase the total gas production of these low permeability natural gas fields by about 7 times the amounts now attainable.
Natural products as potential anticonvulsants: caffeoylquinic acids.

Science.gov (United States)

Kim, Hyo Geun; Oh, Myung Sook

2012-03-01

Current anticonvulsant therapies are generally directed at symptomatic treatment by suppressing excitability within the brain. Consequently, they have adverse effects such as cognitive impairment, dependence, and abuse. The need for more effective and less toxic anticonvulsants has generated renewed interest in natural products for the treatment of convulsions. Caffeoylquinic acids (CQs) are naturally occurring phenolic acids that are distributed widely in plants. There has been increasing interest in the biological activities of CQs in diseases of the central nervous system. In this issue, Nugroho et al. give evidence for the anticonvulsive effect of a CQ-rich extract from Aster glehni Franchet et Sckmidt. They optimized the extract solvent conditions, resulting in high levels of CQs and peroxynitrite-scavenging activity. Then, they investigated the sedative and anticonvulsive effects in pentobarbital- and pentylenetetrazole-induced models in mice. The CQ-rich extract significantly inhibited tonic convulsions as assessed by onset time, tonic extent, and mortality. They suggested that the CQ-rich extract from A. glehni has potential for treating convulsions. This report provides preclinical data which may be used for the development of anticonvulsants from natural products.
Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms.

Science.gov (United States)

Büschleb, Martin; Dorich, Stéphane; Hanessian, Stephen; Tao, Daniel; Schenthal, Kyle B; Overman, Larry E

2016-03-18

Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quaternary carbon atoms in their intricate structures are reviewed with 12 representative examples. Emphasis has been put on methods to create quaternary carbon stereocenters, including syntheses of the same natural product by different groups, thereby showcasing the diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quaternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The Rakicidin Family of Anticancer Natural Products

DEFF Research Database (Denmark)

Tsakos, Michail; Jacobsen, Kristian Mark; Yu, Wanwan

2016-01-01

Rakicidin A is a prominent member of a small class of macrocyclic lipodepsipeptide natural products that contain an electrophilic 4- amido-2,4-pentadienoate (APD) functionality. Rakicidin A displays selective growth inhibitory activity against hypoxic cancer cells as well as imatinib...
A role for physicians in ethnopharmacology and drug discovery.

Science.gov (United States)

Raza, Mohsin

2006-04-06

Ethnopharmacology investigations classically involved traditional healers, botanists, anthropologists, chemists and pharmacologists. The role of some groups of researchers but not of physician has been highlighted and well defined in ethnopharmacological investigations. Historical data shows that discovery of several important modern drugs of herbal origin owe to the medical knowledge and clinical expertise of physicians. Current trends indicate negligible role of physicians in ethnopharmacological studies. Rising cost of modern drug development is attributed to the lack of classical ethnopharmacological approach. Physicians can play multiple roles in the ethnopharmacological studies to facilitate drug discovery as well as to rescue authentic traditional knowledge of use of medicinal plants. These include: (1) Ethnopharmacological field work which involves interviewing healers, interpreting traditional terminologies into their modern counterparts, examining patients consuming herbal remedies and identifying the disease for which an herbal remedy is used. (2) Interpretation of signs and symptoms mentioned in ancient texts and suggesting proper use of old traditional remedies in the light of modern medicine. (3) Clinical studies on herbs and their interaction with modern medicines. (4) Advising pharmacologists to carryout laboratory studies on herbs observed during field studies. (5) Work in collaboration with local healers to strengthen traditional system of medicine in a community. In conclusion, physician's involvement in ethnopharmacological studies will lead to more reliable information on traditional use of medicinal plants both from field and ancient texts, more focused and cheaper natural product based drug discovery, as well as bridge the gap between traditional and modern medicine.
24 CFR 180.540 - Motion to compel discovery.

Science.gov (United States)

2010-04-01

... order compelling discovery in accordance with the request. The motion shall: (1) State the nature of the... secondary evidence concerning the information sought; (6) Striking any appropriate part of the pleadings or...
Zebrafish-Based Discovery of Antiseizure Compounds from the Red Sea: Pseurotin A2 and Azaspirofuran A.

Science.gov (United States)

Copmans, Daniëlle; Rateb, Mostafa; Tabudravu, Jioji N; Pérez-Bonilla, Mercedes; Dirkx, Nina; Vallorani, Riccardo; Diaz, Caridad; Pérez Del Palacio, José; Smith, Alan J; Ebel, Rainer; Reyes, Fernando; Jaspars, Marcel; de Witte, Peter A M

2018-04-19

In search for novel antiseizure drugs (ASDs), the European FP7-funded PharmaSea project used zebrafish embryos and larvae as a drug discovery platform to screen marine natural products to identify promising antiseizure hits in vivo for further development. Within the framework of this project, seven known heterospirocyclic γ-lactams, namely, pseurotin A, pseurotin A 2 , pseurotin F1, 11- O-methylpseurotin A, pseurotin D, azaspirofuran A, and azaspirofuran B, were isolated from the bioactive marine fungus Aspergillus fumigatus, and their antiseizure activity was evaluated in the larval zebrafish pentylenetetrazole (PTZ) seizure model. Pseurotin A 2 and azaspirofuran A were identified as antiseizure hits, while their close chemical analogues were inactive. Besides, electrophysiological analysis from the zebrafish midbrain demonstrated that pseurotin A 2 and azaspirofuran A also ameliorate PTZ-induced epileptiform discharges. Next, to determine whether these findings translate to mammalians, both compounds were analyzed in the mouse 6 Hz (44 mA) psychomotor seizure model. They lowered the seizure duration dose-dependently, thereby confirming their antiseizure properties and suggesting activity against drug-resistant seizures. Finally, in a thorough ADMET assessment, pseurotin A 2 and azaspirofuran A were found to be drug-like. Based on the prominent antiseizure activity in both species and the drug-likeness, we propose pseurotin A 2 and azaspirofuran A as lead compounds that are worth further investigation for the treatment of epileptic seizures. This study not only provides the first evidence of antiseizure activity of pseurotins and azaspirofurans, but also demonstrates the value of the zebrafish model in (marine) natural product drug discovery in general, and for ASD discovery in particular.
Pharmacophore-driven identification of PPARγ agonists from natural sources

DEFF Research Database (Denmark)

Petersen, R. K.; Christensen, Kathrine Bisgaard; Assimopoulou, A. N.

2011-01-01

mastic gum fractions, whereas some other sub-fractions exhibited also biological activity towards PPARγ. The results from the present work are two-fold: on the one hand we demonstrate that the pharmacophore model we developed is able to select novel ligand scaffolds that act as PPARγ agonists; while...... at the same time it manifests that natural products are highly relevant for use in virtual screening-based drug discovery....
Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute Configuration Assignment.

Science.gov (United States)

N L Batista, Andrea; M Dos Santos, Fernando; Batista, João M; Cass, Quezia B

2018-02-23

Chiral natural product molecules are generally assumed to be biosynthesized in an enantiomerically pure or enriched fashion. Nevertheless, a significant amount of racemates or enantiomerically enriched mixtures has been reported from natural sources. This number is estimated to be even larger since the enantiomeric purity of secondary metabolites is rarely checked in the natural product isolation pipeline. This latter fact may have drastic effects on the evaluation of the biological activity of chiral natural products. A second bottleneck is the determination of their absolute configurations. Despite the widespread use of optical rotation and electronic circular dichroism, most of the stereochemical assignments are based on empirical correlations with similar compounds reported in the literature. As an alternative, the combination of vibrational circular dichroism and quantum chemical calculations has emerged as a powerful and reliable tool for both conformational and configurational analysis of natural products, even for those lacking UV-Vis chromophores. In this review, we aim to provide the reader with a critical overview of the occurrence of enantiomeric mixtures of secondary metabolites in nature as well the best practices for their detection, enantioselective separation using liquid chromatography, and determination of absolute configuration by means of vibrational circular dichroism and density functional theory calculations.
Natural product terpenoids in Eocene and Miocene conifer fossils.

Science.gov (United States)

Otto, Angelika; White, James D; Simoneit, Bernd R T

2002-08-30

Numerous saturated and aromatic hydrocarbons, but not polar compounds, originating from plants and microorganisms (biomarkers) have been reported in sediments, coals, and petroleum. Here we describe natural product terpenoids found in two fossil conifers, Taxodium balticum (Eocene) and Glyptostrobus oregonensis (Miocene). A similar terpenoid pattern is also observed in extant Taxodium distichum. The preservation of characteristic terpenoids (unaltered natural products) in the fossil conifers supports their systematic assignment to the Cypress family (Cupressaceae sensu lato). The results also show that fossil conifers can contain polar terpenoids, which are valuable markers for (paleo)chemosystematics and phylogeny.
Natural products – learning chemistry from plants

NARCIS (Netherlands)

Staniek, A.; Bouwmeester, H.J.; Fraser, P.D.; Kayser, O.; Martens, S.; Tissier, A.; Krol, van der A.R.; Wessjohann, L.; Warzecha, H.

2014-01-01

Plant natural products (PNPs) are unique in that they represent a vast array of different structural features, ranging from relatively simple molecules to very complex ones. Given the fact that many plant secondary metabolites exhibit profound biological activity, they are frequently used as

Natural cold pressed oils as cosmetic products

Directory of Open Access Journals (Sweden)

Małgorzata Ligęza

2016-12-01

Full Text Available Background. It seems that patients may ask general practitioners about natural cosmetics applied on the skin regarding their safety and suitability. Objectives. The aim of the study was to analyze natural cold pressed oils as potential cosmetic products. Material and methods. Cold pressed oils obtained from selected seeds and fruit stones were analyzed, including: chokeberry seed oil, blackcurrant seed oil, elderberry seed oil, raspberry seed oil, apricot seed oil, tomato seed oil, strawberry seed oil, broccoli seed oil, Nigella sativa seed oil, hemp oil, safflower seed oil, Silybum marianum seed oil and coconut oil. 80 adult volunteers assessed the cosmetic properties of the analyzed oils. Each of the volunteers tested 2 to 4 different oils, by applying them on the skin. In addition, patch tests with all analyzed oils were performed on 23 individuals. Results. The majority of tested oils were positively evaluated by the participants: in the opinion of the participants, oil extracted from safflower had the best appearance (100% positive opinions, coconut oil had the best smell (70% positive opinions, while black currant seed oil showed the best absorbency (85% positive opinions. No irritation was observed within the analyzed product group, albeit one allergic reaction to apricot seed oil was observed with patch testing. Conclusions . Based on the achieved results, it could be suggested that natural cold pressed oils can be applied to the skin as cosmetics. Our observations may be helpful for general practitioners when choosing natural cosmetics.
A brief history of the ''Delayed'' discovery of nuclear fission

International Nuclear Information System (INIS)

Holden, N.E.

1989-08-01

This year marks the Fiftieth Anniversary of the discovery of Nuclear Fission. In the early 1930's, the neutron was discovered, followed by the discovery of artificial radioactivity and then the use of the neutron to produce artificial radioactivity. The first experiments resulting in the fission of uranium took place in 1934. A paper which speculated on fission as an explanation was almost immediately published, yet no one took it seriously not even the author herself. Why did it take an additional five years before anyone realized what had occurred? This is an abnormally long time in a period when discoveries, particularly in nuclear physics, seemed to be almost a daily occurrence. The events which led up to the discovery are recounted, with an attempt made to put them into their historical perspective. The role played by Mendeleev's Periodic Table, the role of the natural radioactive decay chain of uranium, the discovery of protactinium, the apparent discovery of masurium (technetium) and a speculation on the reason why Irene Curie may have missed the discovery of nuclear fission will all be discussed. 43 refs
Natural products as radiation response modifiers

International Nuclear Information System (INIS)

Colin Seymour; Carmel Mothersill

2007-01-01

Complete text of publication follows. Protection of cells and organisms against low doses of radiation is a complex issue which must be considered at the level of cells, tissues and organisms. 'Protection' at one level, for example, prevention of cell death, may be adverse at another level, if it allows a damaged cell to survive and form a malignant tumour. Conversely, death of a cell carrying damage can be protective for the organism if it eliminates a damaged cell. Thus, it is important to understand the mechanisms involved in protection against radiation damage at several hierarchical levels. The use of natural products as radiation response modifiers is very attractive. Many of these compounds are readily available and their function and pharmacology is well understood. Some derive from venoms or natural defenses and are currently used in medicine, others include vitamins, antioxidants or cofactors, which are tried and tested nutritional supplements. Radiation effects may be targeted or untargeted. Radiation may interact directly within a cell causing a direct DNA lesion or it may elicit a bystander response from the irradiated cell. A bystander effect is produced when the irradiated cell apparently exhibits no damage from the radiation, but passes on a biochemical signal which induces neighbouring cells to apoptose or undergo a number of other responses usually associated with irradiation such as mutation induction, transformation, induction of ROS responses etc.. Effects induced in progeny of non-targeted cells in receipt of bystander signals include genetic instability, mini and microsatellite mutations and carcinogenesis. A key characteristic of these non targeted effects is that they occur at very low acute doses (of the order of 5mGy) and saturate so that effective prevention requires an agent which can effectively shut off the mechanism. While the mechanism is not fully known, it is thought to involve signals from irradiated cells communicating via
Neutron Stars and the Discovery of Pulsars.

Science.gov (United States)

Greenstein, George

1985-01-01

Part one recounted the story of the discovery of pulsars and examined the Crab Nebula, supernovae, and neutron stars. This part (experts from the book "Frozen Star") shows how an understanding of the nature of pulsars allowed astronomers to tie these together. (JN)
Biotransformation and Production from Hansenula Anomala to Natural Ethyl Phenylacetate

Directory of Open Access Journals (Sweden)

Tian Xun

2015-01-01

Full Text Available Ethyl phenylacetate can be widely applied in many industries, such as food, medicines, cosmetics and medicinal herbs. At the moment, the production of natural ethyl phenylacetate is very limited. However, the biotransformation production of natural ethyl phenylacetate has an very extensive application prospect. This paper is written by taking the phenylacetic acid tolerance and the esterifying enzyme activity as the two indexes for screening the HA14 strain of hansenula anomala mutagenic which is regarded as the microorganism of ethyl phenylacetate production through biotransformation. By optimizing the production condition of phenylacetic acid and the esterification condition of ethyl phenylacetate, the production of ethyl phenylacetate accomplished through biotransformation within 72 hours can reach 864mg/L which is 171% of that of the initial bacterial strain.
Natural gas productive capacity for the lower 48 states, 1982--1993

International Nuclear Information System (INIS)

1993-01-01

The purpose of this report is to analyze monthly natural gas wellhead productive capacity and project this capacity for 1992 and 1993, based upon historical production data through 1991. Productive capacity is the volume of gas that can be produced from a well, reservoir, or field during a given period of time against a certain wellhead back-pressure under actual reservoir conditions excluding restrictions imposed by pipeline capacity, contracts, or regulatory bodies. For decades, natural gas supplies and productive capacity have been adequate, although in the 1970's the capacity surplus was small because of market structure (both interstate and intrastate), increasing demand, and insufficient drilling. In the early 1980's, lower demand together with increased drilling led to a large surplus of natural gas capacity. After 1986, this large surplus began to decline as demand for gas increased, gas prices dropped, and gas well completions dropped sharply. In late December 1989, this surplus decline, accompanied by exceptionally high demand and temporary weather-related production losses, led to concerns about the adequacy of monthly productive capacity for natural gas. This study indicates that monthly productive capacity will drop sharply during the 1992-1993 period. In the low gas price, low drilling case, gas productive capacity and estimated production demand will be roughly equal in December 1993. In base and high drilling cases, monthly productive capacity should be able to meet normal production demands through 1993 in the lower 48 States. Exceptionally high peak-day or peak-week production demand might not be met because of physical limitations. Beyond 1993, as the capacity of currently producing wells declines, a sufficient number of wells and/or imports must be added each year in order to ensure an adequate gas supply
North american natural gas supply forecast: the Hubbert method including the effects of institutions

International Nuclear Information System (INIS)

Reynolds, D. B.; Kolodziej, M.

2009-01-01

In this article, the U.S. and southern Canadian natural gas supply market is considered. An important model for oil and natural gas supply is the Hubbert curve. Not all regions of the world are producing oil or natural gas following a Hubbert curve, even when price and market conditions are accounted for. One reason is that institutions are affecting supply. We investigate the possible effects of oil and gas market institutions in North America on natural gas supply. A multi-cycle Hubbert curve with inflection points similar to the Soviet Union's oil production multi-cycle Hubbert curve is used to determine North American natural gas discovery rates and to analyze how market specific institutions caused the inflection points. In addition, we analyze the latest shale natural gas projections critically. While currently, unconventional resources of natural gas suggest that North American natural gas production will increase without bound, the model here suggests a peak in North American natural gas supplies could happen in 2013. (author)
The chemistry of isoindole natural products

OpenAIRE

Speck, Klaus; Magauer, Thomas

2013-01-01

Summary This review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples...
Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

Science.gov (United States)

Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

2016-10-01

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.
Chocolate: A Marvelous Natural Product of Chemistry

Science.gov (United States)

Tannenbaum, Ginger

2004-01-01

The study of chocolate, a natural product, can be beneficial for the chemistry students as they ask frequently about the relevancy of their chemistry classes. The history of chocolate, its chemical and physical changes during processing, its composition, different crystalline forms, tempering and its viscosity are discussed.
Inhibition of aflatoxin B production of Aspergillus flavus, isolated from soybean seeds by certain natural plant products.

Science.gov (United States)

Krishnamurthy, Y L; Shashikala, J

2006-11-01

The inhibitory effect of cowdung fumes, Captan, leaf powder of Withania somnifera, Hyptis suaveolens, Eucalyptus citriodora, peel powder of Citrus sinensis, Citrus medica and Punica granatum, neem cake and pongamia cake and spore suspension of Trichoderma harzianum and Aspergillus niger on aflatoxin B(1) production by toxigenic strain of Aspergillus flavus isolated from soybean seeds was investigated. Soybean seed was treated with different natural products and fungicide captan and was inoculated with toxigenic strain of A. flavus and incubated for different periods. The results showed that all the treatments were effective in controlling aflatoxin B(1) production. Captan, neem cake, spore suspension of T. harzianum, A. niger and combination of both reduced the level of aflatoxin B(1) to a great extent. Leaf powder of W. somnifera, H. suaveolens, peel powder of C. sinensis, C. medica and pongamia cake also controlled the aflatoxin B(1) production. All the natural product treatments applied were significantly effective in inhibiting aflatoxin B(1) production on soybean seeds by A. flavus. These natural plant products may successfully replace chemical fungicides and provide an alternative method to protect soybean and other agricultural commodities from aflatoxin B(1) production by A. flavus.
Fungal natural products targeting chronic lymphocytic leukemia

DEFF Research Database (Denmark)

Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen

2012-01-01

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds......,3 This includes analysis of the spectroscopic data generated from LC-DAD-MS to reveal whether the active principles are either structurally known compounds or are likely to be novel compounds. This paper will illustrate our integrated discovery approaches and recent findings of anti-leukemia compounds....
X-hitting: A new algorithm for novelty detection and dereplication by UV spectra of complex mixtures of natural products

DEFF Research Database (Denmark)

Hansen, Michael Edberg; Smedsgaard, Jørn; Larsen, Thomas Ostenfeld

2005-01-01

A major challenge in lead discovery is to detect well-known and trivial compounds rapidly, a process known as dereplication, so that isolation, structure elucidation, and pharmacological investigations can be focused on novel compounds. In this paper, we present a new algorithm, X-hitting, based...... on cross sample comparison of full UV spectra from HPLC analysis of highly complex natural product extracts/samples. X-Hitting allows automatic identification of known compounds but more important also allows finding of potentially new or similar compounds. We demonstrate this new algorithm by automatic...... identification of known structures, a task we call cross-hitting, and tentative identification of potentially new bioactive compounds, a task we call new-hitting, in HPLC data from analysis of fungal extracts. Both tasks are illustrated using 18 important reference compounds and complex fungal extracts obtained...
Application of natural and synthetic polymers in a production of paper

Directory of Open Access Journals (Sweden)

Jovanović Slobodan

2007-01-01

Full Text Available This work gives the review of most frequently used natural and synthetic polymers in production of paper, board and cardboard. Physical and chemical interaction of natural and synthetic polymers with cellulose fibers, and thus the way these polymers influence the improvement of both production process and the paper characteristics, have been presented.
Interdisciplinary researches for potential developments of drugs and natural products

Directory of Open Access Journals (Sweden)

Arunrat Chaveerach

2017-04-01

Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.
Interdisciplinary researches for potential developments of drugs and natural products

Institute of Scientific and Technical Information of China (English)

Arunrat Chaveerach; Runglawan Sudmoon; Tawatchai Tanee

2017-01-01

Developments of drugs or natural products from plants are possibly made,simple to use and lower cost than modern drugs.The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas,such as foods,traditional medicine,fragrances and seasonings.Then those data will be associated with scientific researches,namely plant collection and identification,phytochemical screening by gas chromatography-mass spectrometry,pharmacological study/review for their functions,and finally safety and efficiency tests in human.For safety testing,in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed.When active chemicals and functions containing plants were chosen with safety and efficacy for human uses,then,the potential medicinal natural products will be produced.Based on these procedures,the producing cost will be cheaper and the products can be evaluated for their clinical properties.Thus,the best and lowest-priced medicines and natural products can be distributed worldwide.
Biocombinatorial Engineering of Fungal PKS-NRPS Hybrids for Production of Novel Synthetic Natural Products

DEFF Research Database (Denmark)

Nielsen, Maria Lund

encoding a PKS-NRPS hybrid responsible for the production of a medically relevant compound in Talaromyces atroroseus. To the best of my knowledge, this study represents the first example of reverse engineering of a Talaromyces species. In the fourth study (chapter 5), I used the CRISPR-Cas9 system...... structure optimization. Within the last decade, an alternative approach for expanding natural product chemodiversity has been applied. This strategy, known as combinatorial biosynthesis, involves the re-engineering of biosynthetic pathways and ultimately the rational engineering of new natural product...... analogs. This field, however, has proved very challenging and many engineering efforts have resulted in enzymatic loss-of-function or reduced yields. Thus, the future success in combinatorial biosynthetic studies requires a thorough understanding of the structure and function of biosynthetic enzymes...
The use of natural products for consumption in Denmark

International Nuclear Information System (INIS)

Strandberg, M.

1996-05-01

Through a questionnaire it was indicated that Danes use products from 'natural' ecosystems in an amount of approximately 2 kg per year. The most used products are berries and meat from game animals, whereas freshwater fish and wild mushrooms are less common in Danish kitchens. (au)
Forecasting natural gas supply in China: Production peak and import trends

International Nuclear Information System (INIS)

Lin Boqiang; Wang Ting

2012-01-01

China's natural gas consumption has increased rapidly in recent years making China a net gas importer. As a nonrenewable energy, the gas resource is exhaustible. Based on the forecast of this article, China's gas production peak is likely to approach in 2022. However, China is currently in the industrialization and urbanization stage, and its natural gas consumption will persistently increase. With China's gas production peak, China will have to face a massive expansion in gas imports. As the largest developing country, China's massive imports of gas will have an effect on the international gas market. In addition, as China's natural gas price is still controlled by the government and has remained at a low level, the massive imports of higher priced gas will exert great pressure on China's gas price reform. - Highlights: ► We figured out the natural gas production peak of China. ► We predict the import trends of natural gas of China. ► We study the international and national impacts of China's increasing import of gas. ► It is important for China to accelerate price reformation of natural gas.
Chirality - The forthcoming 160th Anniversary of Pasteur's Discovery

OpenAIRE

Molčanov, K.; Kojić-Prodić., B.

2007-01-01

The presented review on chirality is dedicated to the centennial birth anniversary of Nobel laureate Vladimir Prelog and 160 years of Pasteur's discovery of chirality on tartrates. Chirality has been recognized in nature by artists and architects, who have used it for decorations and basic constructions, as shown in the Introduction. The progress of science through history has enabled the gathering of knowledge on chirality and its many ways of application. The key historical discoveries abou...

Symbiosis-inspired approaches to antibiotic discovery.

Science.gov (United States)

Adnani, Navid; Rajski, Scott R; Bugni, Tim S

2017-07-06

Covering: 2010 up to 2017Life on Earth is characterized by a remarkable abundance of symbiotic and highly refined relationships among life forms. Defined as any kind of close, long-term association between two organisms, symbioses can be mutualistic, commensalistic or parasitic. Historically speaking, selective pressures have shaped symbioses in which one organism (typically a bacterium or fungus) generates bioactive small molecules that impact the host (and possibly other symbionts); the symbiosis is driven fundamentally by the genetic machineries available to the small molecule producer. The human microbiome is now integral to the most recent chapter in animal-microbe symbiosis studies and plant-microbe symbioses have significantly advanced our understanding of natural products biosynthesis; this also is the case for studies of fungal-microbe symbioses. However, much less is known about microbe-microbe systems involving interspecies interactions. Microbe-derived small molecules (i.e. antibiotics and quorum sensing molecules, etc.) have been shown to regulate transcription in microbes within the same environmental niche, suggesting interspecies interactions whereas, intraspecies interactions, such as those that exploit autoinducing small molecules, also modulate gene expression based on environmental cues. We, and others, contend that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized. Particularly intriguing is the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Notably, many of the studies summarized here result from advances in "omics" technologies and highlight how symbioses have given rise to new anti-bacterial and antifungal natural products now being discovered.
The discovery of radioactivity and its aftermath : this article celebrates the 100th anniversary of the discovery of radioactivity by Becquerel

International Nuclear Information System (INIS)

Newbold, B.T.

1996-01-01

The year 1996 marks the 100th anniversary of the discovery of natural radioactivity by the French physicist Antoine Henri Becquerel while studying the behaviour of a fluorescent uranium salt on exposure to sunlight. The great importance of this development has been underlined by Bagnall who stated that 'The scientific scene at the dawn of the 20th century was dominated by the excitement generated from Becquerel's discovery ... ' [1]. However, the discovery of radioactivity did not attract much attention initially when compared with that accorded to the more penetrating X rays found by the German physicist Wilhelm Konrad Roentgen in 1895. Roentgen received the 1901 Nobel Prize for physics for his outstanding discovery. Fortunately, the significance of Becquerel's contribution was quickly realized and in 1903 he was also awarded the Nobel Prize for physics, which he shared with Pierre Curie and Marie Skoldowska Curie, who were honoured for their research on the radiation phenomenon reported by Becquerel. 9 refs., 1 tab
The discovery of radioactivity and its aftermath : this article celebrates the 100th anniversary of the discovery of radioactivity by Becquerel

Energy Technology Data Exchange (ETDEWEB)

Newbold, B T [Moncton Univ., NB (Canada). Dept. of Chemistry and Biochemistry

1996-09-01

The year 1996 marks the 100th anniversary of the discovery of natural radioactivity by the French physicist Antoine Henri Becquerel while studying the behaviour of a fluorescent uranium salt on exposure to sunlight. The great importance of this development has been underlined by Bagnall who stated that `The scientific scene at the dawn of the 20th century was dominated by the excitement generated from Becquerel`s discovery ... ` [1]. However, the discovery of radioactivity did not attract much attention initially when compared with that accorded to the more penetrating X rays found by the German physicist Wilhelm Konrad Roentgen in 1895. Roentgen received the 1901 Nobel Prize for physics for his outstanding discovery. Fortunately, the significance of Becquerel`s contribution was quickly realized and in 1903 he was also awarded the Nobel Prize for physics, which he shared with Pierre Curie and Marie Skoldowska Curie, who were honoured for their research on the radiation phenomenon reported by Becquerel. 9 refs., 1 tab.
Deposition of naturally occurring radioactivity in oil and gas production

International Nuclear Information System (INIS)

Lysebo, I.; Strand, T.

1997-01-01

This booklet contains general information about naturally occurring radioactive materials, NORM, in production of oil and natural gas, occupational doses, radiation protection procedures and measures, and classification methods of contaminated equipment. 6 refs., 1 fig., 1 tab
Natural gas potential in Canada

International Nuclear Information System (INIS)

1997-01-01

An independent assessment of the undiscovered gas potential in Canada was conducted by a group of volunteer geoscientists. This report is the first of a series of assessments that are planned to be issued every three to four years. Separate assessments were made of conventional gas resources, unconventional gas resources and frontier gas resources. The assessment for conventional gas resources was organized into three categories: (1) gas producing areas where new discoveries can be integrated into existing producing and transportation infrastructure, (2) frontier basins where gas discoveries have been made, but no production is currently underway, and (3) frontier areas where gas-containing sedimentary rocks are known to exist, but where no gas discoveries have been made to date. The committee used year-end 1993 reserves data from discovered pools in each exploration play to predict the undiscovered potential. Information about discovered pools, geological setting, geographic limits and pool sizes of undiscovered pools in each exploration play was provided. Results of the investigation led to the conclusion that the natural gas potential in Canada is in fact larger than hitherto expected. It was estimated that in the Western Canada Sedimentary Basin 47 per cent of the total volume of conventional gas is yet to be discovered. 152 figs
How does increased corn-ethanol production affect US natural gas prices?

International Nuclear Information System (INIS)

Whistance, Jarrett; Thompson, Wyatt

2010-01-01

In recent years, there has been a push to increase biofuel production in the United States. The biofuel of choice, so far, has been ethanol produced from corn. The effects of increased corn-ethanol production on the consumer prices of food and energy continue to be studied and debated. This study examines, in particular, the effects of increased corn-ethanol production on US natural gas prices. A structural model of the natural gas market is developed and estimated using two stage least squares. A baseline projection for the period 2007-2018 is determined, and two scenarios are simulated. In the first scenario, current biofuel policies including EISA mandates, tariffs, and tax credits are removed. In the second scenario, we hold ethanol production to the level required only for largely obligatory additive use. The results indicate that the increased level of corn-ethanol production occurring as a result of the current US biofuel policies may lead to natural gas prices that are as much as 0.25% higher, on average, than if no biofuel policies were in place. A similar comparison between the baseline and second scenario indicates natural gas prices could be as much as 0.5% higher, on average, for the same period.
Marine natural products: a new wave of drugs?

Science.gov (United States)

Montaser, Rana; Luesch, Hendrik

2011-01-01

The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future. PMID:21882941
Production of bio-synthetic natural gas in Canada.

Science.gov (United States)

Hacatoglu, Kevork; McLellan, P James; Layzell, David B

2010-03-15

Large-scale production of renewable synthetic natural gas from biomass (bioSNG) in Canada was assessed for its ability to mitigate energy security and climate change risks. The land area within 100 km of Canada's network of natural gas pipelines was estimated to be capable of producing 67-210 Mt of dry lignocellulosic biomass per year with minimal adverse impacts on food and fiber production. Biomass gasification and subsequent methanation and upgrading were estimated to yield 16,000-61,000 Mm(3) of pipeline-quality gas (equivalent to 16-63% of Canada's current gas use). Life-cycle greenhouse gas emissions of bioSNG-based electricity were calculated to be only 8.2-10% of the emissions from coal-fired power. Although predicted production costs ($17-21 GJ(-1)) were much higher than current energy prices, a value for low-carbon energy would narrow the price differential. A bioSNG sector could infuse Canada's rural economy with $41-130 billion of investments and create 410,000-1,300,000 jobs while developing a nation-wide low-carbon energy system.
Learning Organic Chemistry Through Natural Products -12 ...

Indian Academy of Sciences (India)

Higher Learning. Generations of students would vouch for the fact that he has the uncanny ability to present the chemistry of natural products logically and with feeling. The most interesting chemical aspect of a molecule is its. reactivHy pattern. NR Krishnaswamy. In this part of the series, dynamic organic chemistry and.
Management of natural health products in pediatrics: a provider-focused quality improvement project.

Science.gov (United States)

Gutierrez, Emily; Silbert-Flagg, JoAnne; Vohra, Sunita

2015-01-01

The use of natural health products by pediatric patients is common, yet health care providers often do not provide management guidance. The purpose of this project was to improve management of natural health products by pediatric nurse practitioners. Pediatric nurse practitioners from large metropolitan city were recruited (n = 32). A paired pretest-posttest design was used. Study participants were engaged to improve knowledge of natural health products, and a management toolkit was created and tested. Mean knowledge scores increased from 59.19 to 76.3 (p improved with regard to patient guidance (p product use (p = .51) and drug/herb interactions (p = .35) were not significant. This investigation is the first known study to improve knowledge and management of natural health products in pediatric clinical practice. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.
Chemical proteomics for target discovery of head-to-tail cyclized mini-proteins

Science.gov (United States)

Hellinger, Roland; Thell, Kathrin; Vasileva, Mina; Muhammad, Taj; Gunasekera, Sunithi; Kümmel, Daniel; Göransson, Ulf; Becker, Christian W.; Gruber, Christian W.

2017-10-01

Target deconvolution is one of the most challenging tasks in drug discovery, but a key step in drug development. In contrast to small molecules, there is a lack of validated and robust methodologies for target elucidation of peptides. In particular, it is difficult to apply these methods to cyclic and cysteine-stabilized peptides since they exhibit reduced amenability to chemical modification and affinity capture; however, such ribosomal synthesized and post-translationally modified peptide natural products are rich sources of promising drug candidates. For example, plant-derived circular peptides called cyclotides have recently attracted much attention due to their immunosuppressive effects and oral activity in the treatment of multiple sclerosis in mice, but their molecular target has hitherto not been reported. In this study a chemical proteomics approach using photo-affinity crosslinking was developed to determine a target of the circular peptide [T20K]kalata B1. Using this prototypic nature-derived peptide enabled the identification of a possible modulation of 14-3-3 proteins. This biochemical interaction was validated via competition pull down assays as well as a cellular reporter assay indicating an effect on 14-3-3-dependent transcriptional activity. As proof of concept, the presented approach may be applicable for target elucidation of various cyclic peptides and mini-proteins, in particular cyclotides, which represent a promising class of molecules in drug discovery and development.
The water-food nexus of natural rubber production

Science.gov (United States)

Chiarelli, D. D.; Rosa, L.; Rulli, M. C.; D'Odorico, P.

2017-12-01

The increasing global demand for natural rubber (100% increase in the last 15 years) is for most part met by Malaysia and Indonesia, and - to a lesser extent - other countries in south-east Asia and Africa. The consequent expansion of rubber plantation has often occurred at the expenses of agricultural land for staple food, particularly in southeast Asia, where most of the land suitable for agriculture is already harvested for food crops or other uses. Here we investigate the extent to which the ongoing increase in rubber production is competing with the food system and affecting the livelihoods of rural communities in the areas of production and their appropriation of natural resources, such as water. We also investigate to what extent the expansion of rubber plantations is taking place through large scale land acquisitions (LSLAs) and evaluate the impacts on rural communities. Our results show how rubber production has strong environmental, social and economic impacts. Despite their ability to bring employment and increase the average income of economically disadvantaged areas, rubber plantations may threaten the local water and food security and induce a loss of rural livelihoods, particularly when the new plantations result from LSLAs that displace semi-subsistence forms of production thereby forcing the local populations to depend on global markets.
Volatility Discovery

DEFF Research Database (Denmark)

Dias, Gustavo Fruet; Scherrer, Cristina; Papailias, Fotis

The price discovery literature investigates how homogenous securities traded on different markets incorporate information into prices. We take this literature one step further and investigate how these markets contribute to stochastic volatility (volatility discovery). We formally show...... that the realized measures from homogenous securities share a fractional stochastic trend, which is a combination of the price and volatility discovery measures. Furthermore, we show that volatility discovery is associated with the way that market participants process information arrival (market sensitivity......). Finally, we compute volatility discovery for 30 actively traded stocks in the U.S. and report that Nyse and Arca dominate Nasdaq....
Natural sweetening of food products by engineering Lactococcus lactis for glucose production

NARCIS (Netherlands)

Pool, Wietske A.; Neves, Ana Rute; Kok, Jan; Santos, Helena; Kuipers, Oscar P.

We show that sweetening of food products by natural fermentation can be achieved by a combined metabolic engineering and transcriptome analysis approach. A Lactococcus lactis ssp. cremoris strain was constructed in which glucose metabolism was completely disrupted by deletion of the genes coding for
Amorfrutins are potent antidiabetic dietary natural products

Science.gov (United States)

Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

2012-01-01

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006
Natural products for chronic cough: Text mining the East Asian historical literature for future therapeutics.

Science.gov (United States)

Shergis, Johannah Linda; Wu, Lei; May, Brian H; Zhang, Anthony Lin; Guo, Xinfeng; Lu, Chuanjian; Xue, Charlie Changli

2015-08-01

Chronic cough is a significant health burden. Patients experience variable benefits from over the counter and prescribed products, but there is an unmet need to provide more effective treatments. Natural products have been used to treat cough and some plant compounds such as pseudoephedrine from ephedra and codeine from opium poppy have been developed into drugs. Text mining historical literature may offer new insight for future therapeutic development. We identified natural products used in the East Asian historical literature to treat chronic cough. Evaluation of the historical literature revealed 331 natural products used to treat chronic cough. Products included plants, minerals and animal substances. These natural products were found in 75 different books published between AD 363 and 1911. Of the 331 products, the 10 most frequently and continually used products were examined, taking into consideration findings from contemporary experimental studies. The natural products identified are promising and offer new directions in therapeutic development for treating chronic cough. © The Author(s) 2015.
Natural Fostering in Fritillaria cirrhosa: Integrating herbal medicine production with biodiversity conservation

Directory of Open Access Journals (Sweden)

Xiwen Li

2012-02-01

Full Text Available Protected areas are generally regarded as a power tool to conserve biodiversity. Nonetheless, few protected areas could address three crucial problems simultaneously, namely funding, public participation and rural living. Here, we introduced a new protective approach, Natural Fostering, which integrated herbal medicine production with community conservation. The principles of Natural Fostering adopted species–species interaction at community level. Most effective chemical components of herbal medicine are derived from such interaction. Fritillaria cirrhosa was selected as an economic botany, one of herbal medicines, to carry out Natural Fostering. Community habitats, herbal medicine production, funding and income of local family were investigated to verify the feasibility of Natural Fostering for biodiversity. We found the density of plant populations and the annual average personal income of rural people increased. F. cirrhosa production could provide sufficient funds for sustainable conservation. Local people gradually changed their life style of wild collection and overgrazing, instead of herbal medicine production. The fostering area set up a good sustainable economic cycle. Natural Fostering can be presented as an effective and pragmatic way to conserve biological diversity and sustainable utilization of traditional medicinal resources.
43 CFR 423.29 - Natural and cultural resources.

Science.gov (United States)

2010-10-01

..., mountainsides, thermal features, or other natural formations. (d) You may bring firewood to or gather dead wood... discovery device, or use a metal detector or other geophysical discovery techniques to locate or recover... detector or other geophysical discovery device in a vehicle on a public road as allowed under applicable...
Sustainability, natural and organic cosmetics: consumer, products, efficacy, toxicological and regulatory considerations

Directory of Open Access Journals (Sweden)

Bruno Fonseca-Santos

2015-03-01

Full Text Available The interest in sustainable products has increased along the years, since the choice of products, packaging and production processes have a great impact on the environment. These products are classified by regulatory agencies in different categories, aggregating advantages to the product and increasing the demand by consumers. However, there is no harmonization in guidelines of these certifying agencies and each cosmetic industry formulates their product and packaging in a more rational way, which causes less damage to the environment. Many cosmetic products have in their formulation natural products that perform a specific biological function, but these products should be evaluated on efficacy and toxicological aspects. The aim of this article is to approach sustainability, natural and organic cosmetics, considering the consumer and the efficacy, toxicological and regulatory aspects.
In-use product stocks link manufactured capital to natural capital.

Science.gov (United States)

Chen, Wei-Qiang; Graedel, T E

2015-05-19

In-use stock of a product is the amount of the product in active use. In-use product stocks provide various functions or services on which we rely in our daily work and lives, and the concept of in-use product stock for industrial ecologists is similar to the concept of net manufactured capital stock for economists. This study estimates historical physical in-use stocks of 91 products and 9 product groups and uses monetary data on net capital stocks of 56 products to either approximate or compare with in-use stocks of the corresponding products in the United States. Findings include the following: (i) The development of new products and the buildup of their in-use stocks result in the increase in variety of in-use product stocks and of manufactured capital; (ii) substitution among products providing similar or identical functions reflects the improvement in quality of in-use product stocks and of manufactured capital; and (iii) the historical evolution of stocks of the 156 products or product groups in absolute, per capita, or per-household terms shows that stocks of most products have reached or are approaching an upper limit. Because the buildup, renewal, renovation, maintenance, and operation of in-use product stocks drive the anthropogenic cycles of materials that are used to produce products and that originate from natural capital, the determination of in-use product stocks together with modeling of anthropogenic material cycles provides an analytic perspective on the material linkage between manufactured capital and natural capital.

World natural gas supply and demand: Brief pause in production

International Nuclear Information System (INIS)

Coccia, G.

1993-01-01

With reference to the 1992 CEDIGAZ (Centre International sur le Gas Naturel et tous Hydrocarbures Gazeux) report on world natural gas supply and demand, this paper assesses current market and production trends in this industry. The slight drop in production in 1992, the first which has which has occurred after many consecutive years of steady increases, is ascribed to ownership disputes among the former-USSR republics and major changes in the organizational structure of the former-USSR's natural gas industry. Strong increases in demand are forecasted due to expected strong population growth and increased industrialization to take place in China and India. Price trends in natural gas should remain steady as a result of plentiful supplies of this fuel and coal, a major competitor. The use of relatively clean natural gas is suggested as a practical alternative to energy taxes now being proposed as a means for the reduction of greenhouse gas emissions
Growing with dinosaurs: natural products from the Cretaceous relict Metasequoia glyptostroboides Hu & Cheng-a molecular reservoir from the ancient world with potential in modern medicine.

Science.gov (United States)

Juvik, Ole Johan; Nguyen, Xuan Hong Thy; Andersen, Heidi Lie; Fossen, Torgils

2016-01-01

After the sensational rediscovery of living exemplars of the Cretaceous relict Metasequoia glyptostroboides -a tree previously known exclusively from fossils from various locations in the northern hemisphere, there has been an increasing interest in discovery of novel natural products from this unique plant source. This article includes the first complete compilation of natural products reported from M. glyptostroboides during the entire period in which the tree has been investigated (1954-2014) with main focus on the compounds specific to this plant source. Studies on the biological activity of pure compounds and extracts derived from M. glyptostroboides are reviewed for the first time. The unique potential of M. glyptostroboides as a source of bioactive constituents is founded on the fact that the tree seems to have survived unchanged since the Cretaceous era. Since then, its molecular defense system has resisted the attacks of millions of generations of pathogens. In line with this, some recent landmarks in Metasequoia paleobotany are covered. Initial spectral analysis of recently discovered intact 53 million year old wood and amber of Metasequoia strongly indicate that the tree has remained unchanged for millions of years at the molecular level.
Analysis of Specific Features of the Ukrainian Market of Natural Gas Production and Consumption

Directory of Open Access Journals (Sweden)

Lelyuk Oleksiy V.

2013-11-01

Full Text Available The article provides results of the study of specific features of the Ukrainian market of natural gas production and consumption. It analyses dynamics of the specific weight of Ukraine in general volumes of natural gas consumption in the world, dynamics of natural gas consumption in Ukraine during 1990 – 2012 and dependence of natural gas consumption on GDP volumes by the purchasing power parity. It studies the structure of natural gas consumption by regions in 2012 and sectors of economy, resource base of natural gas in Ukraine and also dynamics of established resources of natural gas in Ukraine and dynamics of natural gas production. It analyses base rates of growth of natural gas resources and production in Ukraine. It considers dynamics of import of natural gas into Ukraine and its import prices and also the structure of natural gas import. It identifies the balance of the natural gas market in Ukraine. On the basis of the conducted analysis the article proves that Ukraine is a gas-deficit country of the world, which depends on natural gas import supplies.
Elementos para la evaluación eficaz de productos naturales con posibles efectos antihipertensivos Elements for the effective evaluation of natural products with possible antihypertensive effects

Directory of Open Access Journals (Sweden)

Mario Francisco Guerrero

2009-12-01

Full Text Available Desde el contexto de la farmacología experimental, en este ensayo se discuten algunos criterios que pueden ser útiles para estimar el potencial de productos naturales con posible actividad farmacológica para el tratamiento de la hipertensión, una de las enfermedades de mayor impacto epidemiológico en Colombia y en el mundo. Se acude para ello al análisis de algunas pruebas farmacológicas accesibles en nuestro medio: modelos de hipertensión arterial en la rata de laboratorio, pruebas in vitro e in vivo, y análisis microscópicos, que implementados con los protocolos adecuados y cotejadas en conjunto, pueden arrojar información valiosa a la hora de considerar las perspectivas de un producto natural en el campo de la hipertensión arterial.Within the context of experimental pharmacology, some criteria are discussed for estimating the potential of natural products with possible pharmacological activity for the treatment of hypertension. This disorder has great epidemiological impact in Colombia as well as elsewhere. Discovery of these products can be accomplished by use of accessible pharmacological tests such as the following: developing models of arterial hypertension in the laboratory rat, in vitro tests, in vivo tests and microscopic analysis. Suitable protocols associated with these techniques can capture valuable information about possible effects on hypertension during the evaluation phase of a natural product.
Discovery stories in the science classroom

Science.gov (United States)

Arya, Diana Jaleh

School science has been criticized for its lack of emphasis on the tentative, dynamic nature of science as a process of learning more about our world. This criticism is the guiding force for this present body of work, which focuses on the question: what are the educational benefits for middle school students of reading texts that highlight the process of science in the form of a discovery narrative? This dissertation traces my journey through a review of theoretical perspectives of narrative, an analysis of first-hand accounts of scientific discovery, the complex process of developing age-appropriate, cohesive and engaging science texts for middle school students, and a comparison study (N=209) that seeks to determine the unique benefits of the scientific discovery narrative for the interest in and retained understanding of conceptual information presented in middle school science texts. A total of 209 middle school participants in nine different classrooms from two different schools participated in the experimental study. Each subject read two science texts that differed in topic (the qualities of and uses for radioactive elements and the use of telescopic technology to see planets in space) and genre (the discovery narrative and the "conceptually known exposition" comparison text). The differences between the SDN and CKE versions for each topic were equivalent in all possible ways (initial introduction, overall conceptual accuracy, elements of human interest, coherence and readability level), save for the unique components of the discovery narrative (i.e., love for their work, acknowledgement of the known, identification of the unknown and the explorative or experimental process to discovery). Participants generally chose the discovery narrative version as the more interesting of the two texts. Additional findings from the experimental study suggest that science texts in the form of SDNs elicit greater long-term retention of key conceptual information, especially
Natural product synthesis: Making nematodes nervous

Science.gov (United States)

Snyder, Scott A.

2011-06-01

A highly inventive route for the synthesis of a key substance that stimulates potato cyst nematodes to hatch has been developed. This discovery has potential to impact food supplies, as treatment of crops with this compound could alleviate the devastating effect of these parasites.
Principal component analysis as a tool for library design: a case study investigating natural products, brand-name drugs, natural product-like libraries, and drug-like libraries.

Science.gov (United States)

Wenderski, Todd A; Stratton, Christopher F; Bauer, Renato A; Kopp, Felix; Tan, Derek S

2015-01-01

Principal component analysis (PCA) is a useful tool in the design and planning of chemical libraries. PCA can be used to reveal differences in structural and physicochemical parameters between various classes of compounds by displaying them in a convenient graphical format. Herein, we demonstrate the use of PCA to gain insight into structural features that differentiate natural products, synthetic drugs, natural product-like libraries, and drug-like libraries, and show how the results can be used to guide library design.
Causality discovery technology

Science.gov (United States)

Chen, M.; Ertl, T.; Jirotka, M.; Trefethen, A.; Schmidt, A.; Coecke, B.; Bañares-Alcántara, R.

2012-11-01

Causality is the fabric of our dynamic world. We all make frequent attempts to reason causation relationships of everyday events (e.g., what was the cause of my headache, or what has upset Alice?). We attempt to manage causality all the time through planning and scheduling. The greatest scientific discoveries are usually about causality (e.g., Newton found the cause for an apple to fall, and Darwin discovered natural selection). Meanwhile, we continue to seek a comprehensive understanding about the causes of numerous complex phenomena, such as social divisions, economic crisis, global warming, home-grown terrorism, etc. Humans analyse and reason causality based on observation, experimentation and acquired a priori knowledge. Today's technologies enable us to make observations and carry out experiments in an unprecedented scale that has created data mountains everywhere. Whereas there are exciting opportunities to discover new causation relationships, there are also unparalleled challenges to benefit from such data mountains. In this article, we present a case for developing a new piece of ICT, called Causality Discovery Technology. We reason about the necessity, feasibility and potential impact of such a technology.
Natural Products for the Treatment of Type 2 Diabetes Mellitus.

Science.gov (United States)

Ríos, José Luis; Francini, Flavio; Schinella, Guillermo R

2015-08-01

Type 2 diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia. High blood sugar can produce long-term complications such as cardiovascular and renal disorders, retinopathy, and poor blood flow. Its development can be prevented or delayed in people with impaired glucose tolerance by implementing lifestyle changes or the use of therapeutic agents. Some of these drugs have been obtained from plants or have a microbial origin, such as galegine isolated from Galega officinalis, which has a great similarity to the antidiabetic drug metformin. Picnogenol, acarbose, miglitol, and voglibose are other antidiabetic products of natural origin. This review compiles the principal articles on medicinal plants used for treating diabetes and its comorbidities, as well as mechanisms of natural products as antidiabetic agents. Inhibition of α-glucosidase and α-amylase, effects on glucose uptake and glucose transporters, modification of mechanisms mediated by the peroxisome proliferator-activated receptor, inhibition of protein tyrosine phosphatase 1B activity, modification of gene expression, and activities of hormones involved in glucose homeostasis such as adiponectin, resistin, and incretin, and reduction of oxidative stress are some of the mechanisms in which natural products are involved. We also review the most relevant clinical trials performed with medicinal plants and natural products such as aloe, banaba, bitter melon, caper, cinnamon, cocoa, coffee, fenugreek, garlic, guava, gymnema, nettle, sage, soybean, green and black tea, turmeric, walnut, and yerba mate. Compounds of high interest as potential antidiabetics are: fukugetin, palmatine, berberine, honokiol, amorfrutins, trigonelline, gymnemic acids, gurmarin, and phlorizin. Georg Thieme Verlag KG Stuttgart · New York.
Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function.

Science.gov (United States)

Rudolf, Jeffrey D; Chang, Chin-Yuan; Ma, Ming; Shen, Ben

2017-08-30

Covering: up to January 2017Cytochrome P450 enzymes (P450s) are some of the most exquisite and versatile biocatalysts found in nature. In addition to their well-known roles in steroid biosynthesis and drug metabolism in humans, P450s are key players in natural product biosynthetic pathways. Natural products, the most chemically and structurally diverse small molecules known, require an extensive collection of P450s to accept and functionalize their unique scaffolds. In this review, we survey the current catalytic landscape of P450s within the Streptomyces genus, one of the most prolific producers of natural products, and comprehensively summarize the functionally characterized P450s from Streptomyces. A sequence similarity network of >8500 P450s revealed insights into the sequence-function relationships of these oxygen-dependent metalloenzymes. Although only ∼2.4% and structurally characterized, respectively, the study of streptomycete P450s involved in the biosynthesis of natural products has revealed their diverse roles in nature, expanded their catalytic repertoire, created structural and mechanistic paradigms, and exposed their potential for biomedical and biotechnological applications. Continued study of these remarkable enzymes will undoubtedly expose their true complement of chemical and biological capabilities.
Learning Organic Chemistry Through Natural Products A Practical ...

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 9. Learning Organic Chemistry Through Natural Products A Practical Approach. N R Krishnaswamy. Series Article Volume 1 Issue 9 September 1996 pp 25-33. Fulltext. Click here to view fulltext PDF. Permanent link:
Utilization of Natural Products as Functional Feed

Directory of Open Access Journals (Sweden)

Stella Magdalena

2013-03-01

Full Text Available The use of antibiotics as feed additive improves performance in livestock. However, scientific data related to the use of antibiotics in feed merge spreading of bacterial resistance in animal and human bodies, therefore the usage of antibiotics in animal production is restricted. This condition raise the utilization of natural antibiotic as functional feed such as phytogenics (essential oil, flavonoid, saponin, and tannin, enzyme, probiotic, and prebiotic to improve the livestock’s performance, quality, and health. Functional feeds increase profitability in animal husbandry production and its use is feeds are expected to be functional foods that may have positive effects in human nutrition.
The discovery and history of knowledge of natural atmospheric radioactivity

International Nuclear Information System (INIS)

Renoux, A.

1996-01-01

Everybody knows that the radioactivity was discovered, 100 years ago, by the Frenchman Henri Becquerel at Paris, in Feb. 1896, stemmed from the discovery of X-rays by Roentgen in the preceding year. In 1899, Rutherford was able to show the existence of α and β rays, and in 1900 Villard showed the presence of a third class of rays, the γ rays. The discovery of the rare radioactive gas radon is attributed to P. and M. Curie in 1898 and F. Dorn in 1900. Thoron ( 220 Rn) was discovered by Rutherford and Owens in 1899-1900 and Actinon ( 219 Rn) by Debierne and Geisel about the same time. The radon's radiotoxicity was studied in France since 1904 by Bouchard and Balthazard and in 1924 it was formulated the hypothesis that the great mortality observed in the uranium miners of Schneeberg in Germany and Joachimsthal in Czechoslovakia was maybe due to the radon. But, in fact, Elster and Geitel were the first to see that the radioactivity is present in the atmosphere in about 1901. After this date, many investigations were made (M. Curie, for example), but it is during the fifties and, of course, until today that the most numerous works were developed. In this paper, we speak about the researches of the after second war pioneers: Evans, Wilkening, Kawano, Israel, Junge, Schuman, Bricard... Renoux, Madelaine, Blanc, Fontan, Siksna, Chamberlain, Dyson, Nolan, etc. and the works developed later. Finally, we reach to the nineties, period where the works are particularly directed in the aim of radon and radon progeny indoor, with in particular, many works effectuated in France. (author). 78 refs., 17 figs., 2 tabs
Natural radiation - a perspective to radiological risk factors of nuclear energy production

DEFF Research Database (Denmark)

Mustonen, R.; Christensen, T.; Stranden, E.

1992-01-01

Radiation doses from natural radiation and from man-made modifications on natural radiation, and different natural radiological environments in the Nordic countries are summarized and used as a perspective for the radiological consequences of nuclear energy production. The significance of different...... radiation sources can be judged against the total collective effective dose equivalent from natural radiation in the Nordic countries, 92 000 manSv per year. The collective dose from nuclear energy production during normal operation is estimated to 20 manSv per year and from non-nuclear energy production...... to 80 manSv per year. The increase in collective dose due to the conservation of heating energy in Nordic dwellings is estimated to 23 000 manSv per year, from 1973 to 1984. An indirect radiological danger index is defined in order to be able to compare the significance of estimated future releases...
Life Cycle Assessment Of Hydrogen Production From Natural Gas Reforming Process

International Nuclear Information System (INIS)

Ozturk, M.

2010-01-01

Society has become concerned about the issues of natural resource depletion and environmental degradation. The environmental performance of products or processes has become a key issue, which is why ways to minimize the effects on the environment are investigated. The most effective tool for this purpose is called life cycle assessment (LCA). This concept considers the entire life cycle of product or process. The life cycle of a product begins with the extraction of raw materials from the earth to create the product and ends at the point when all materials are returned to the earth. LCA makes it possible to estimate the cumulative environmental impacts resulting from all stages in the product life cycle, often including impacts not considered in more traditional analyses. Therefore, LCA provides a comprehensive view of the environmental aspects of the product or process and a more accurate picture of the true environmental trade-offs in product selection. In the case of this study, life cycle assessments of hydrogen production via natural gas reforming process are investigated for environmental affect.
A New Universe of Discoveries

Science.gov (United States)

Córdova, France A.

2016-01-01

The convergence of emerging advances in astronomical instruments, computational capabilities and talented practitioners (both professional and civilian) is creating an extraordinary new environment for making numerous fundamental discoveries in astronomy, ranging from the nature of exoplanets to understanding the evolution of solar systems and galaxies. The National Science Foundation is playing a critical role in supporting, stimulating, and shaping these advances. NSF is more than an agency of government or a funding mechanism for the infrastructure of science. The work of NSF is a sacred trust that every generation of Americans makes to those of the next generation, that we will build on the body of knowledge we inherit and continue to push forward the frontiers of science. We never lose sight of NSF's obligation to "explore the unexplored" and inspire all of humanity with the wonders of discovery. As the only Federal agency dedicated to the support of basic research and education in all fields of science and engineering, NSF has empowered discoveries across a broad spectrum of scientific inquiry for more than six decades. The result is fundamental scientific research that has had a profound impact on our nation's innovation ecosystem and kept our nation at the very forefront of the world's science-and-engineering enterprise.
Impacts of Marcellus Shale Natural Gas Production on Regional Air Quality

Science.gov (United States)

Swarthout, R.; Russo, R. S.; Zhou, Y.; Mitchell, B.; Miller, B.; Lipsky, E. M.; Sive, B. C.

2012-12-01

Natural gas is a clean burning alternative to other fossil fuels, producing lower carbon dioxide (CO2) emissions during combustion. Gas deposits located within shale rock or tight sand formations are difficult to access using conventional drilling techniques. However, horizontal drilling coupled with hydraulic fracturing is now widely used to enhance natural gas extraction. Potential environmental impacts of these practices are currently being assessed because of the rapid expansion of natural gas production in the U.S. Natural gas production has contributed to the deterioration of air quality in several regions, such as in Wyoming and Utah, that were near or downwind of natural gas basins. We conducted a field campaign in southwestern Pennsylvania on 16-18 June 2012 to investigate the impact of gas production operations in the Marcellus Shale on regional air quality. A total of 235 whole air samples were collected in 2-liter electropolished stainless- steel canisters throughout southwestern Pennsylvania in a regular grid pattern that covered an area of approximately 8500 square km. Day and night samples were collected at each grid point and additional samples were collected near active wells, flaring wells, fluid retention reservoirs, transmission pipelines, and a processing plant to assess the influence of different stages of the gas production operation on emissions. The samples were analyzed at Appalachian State University for methane (CH4), CO2, C2-C10 nonmethane hydrocarbons (NMHCs), C1-C2 halocarbons, C1-C5 alkyl nitrates and selected reduced sulfur compounds. In-situ measurements of ozone (O3), CH4, CO2, nitric oxide (NO), total reactive nitrogen (NOy), formaldehyde (HCHO), and a range of volatile organic compounds (VOCs) were carried out at an upwind site and a site near active gas wells using a mobile lab. Emissions associated with gas production were observed throughout the study region. Elevated mixing ratios of CH4 and CO2 were observed in the
Alkaloids as Cyclooxygenase Inhibitors in Anticancer Drug Discovery.

Science.gov (United States)

Hashmi, Muhammad Ali; Khan, Afsar; Farooq, Umar; Khan, Sehroon

2018-01-01

Cancer is the leading cause of death worldwide and anticancer drug discovery is a very hot area of research at present. There are various factors which control and affect cancer, out of which enzymes like cyclooxygenase-2 (COX-2) play a vital role in the growth of tumor cells. Inhibition of this enzyme is a very useful target for the prevention of various types of cancers. Alkaloids are a diverse group of naturally occurring compounds which have shown great COX-2 inhibitory activity both in vitro and in vivo. In this mini-review, we have discussed different alkaloids with COX-2 inhibitory activities and anticancer potential which may act as leads in modern anticancer drug discovery. Different classes of alkaloids including isoquinoline alkaloids, indole alkaloids, piperidine alkaloids, quinazoline alkaloids, and various miscellaneous alkaloids obtained from natural sources have been discussed in detail in this review. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
The sustainable management of a productive natural capital

DEFF Research Database (Denmark)

Daubanes, Julien Xavier

is relevant, among other examples, to the case of naturebased tourism. I study the sustainable management of a productive natural capital: the conditions under which its exploitation generates maximum long-run social benefits; the various ways in which a regulator can implement such an exploitation; the rent...
SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis

Science.gov (United States)

Ohashi, Masao; Liu, Fang; Hai, Yang; Chen, Mengbin; Tang, Man-Cheng; Yang, Zhongyue; Sato, Michio; Watanabe, Kenji; Houk, K. N.; Tang, Yi

2017-09-01

Pericyclic reactions—which proceed in a concerted fashion through a cyclic transition state—are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-L-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme ‘toolboxes’. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

Structure elucidation of secondary natural products

International Nuclear Information System (INIS)

Seger, C.

2001-06-01

The presented thesis deals with the structure elucidation of secondary natural products. Most of the compounds under investigation were terpenes, especially triterpenes, alkaloids and stilbenoids. Besides characterizing a multitude of already known and also new compounds, it was possible to detect and correct wrongly assigned literature data. The methodological aspect of this thesis lies - beside in the utilization of modern 2D NMR spectroscopy - in the evaluation of computer assisted structure elucidation (CASE) techniques in the course of spectroscopy supported structure elucidation processes. (author)
The potential of natural products for targeting PPARα

Directory of Open Access Journals (Sweden)

Daniela Rigano

2017-07-01

Full Text Available Peroxisome proliferator activated receptors (PPARs α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this “hot” target.
Antioxidants in bakery products: a review.

Science.gov (United States)

Nanditha, B; Prabhasankar, P

2009-01-01

Fats impart taste and texture to the product but it is susceptible to oxidation leading to the development of rancidity and off-flavor. Since ancient times it has been in practice to use antioxidants in foods. Discovery of synthetic antioxidants has revolutionized the use of antioxidants in food. The effect of these antioxidants in bakery products were reviewed and found to be effective in enhancing the shelf life. Animal experimental studies have shown that some of the synthetic antioxidants had toxigenic, mutagenic, and carcinogenic effects. Hence there is an increasing demand for the use of natural antioxidants in foods, especially in bakery products. Some of the natural antioxidants such as alpha-tocopherol, beta-carotene, and ascorbic acid were already used in bakery products. These natural antioxidants are found to be effective in enhancing the shelf life of bakery products but not to the extent of synthetic antioxidants. Baking processing steps may lower the antioxidative activity but techniques such as encapsulation of antioxidants can retain their activity. Antioxidative activity of the plant extracts such as garcinia, curcumin, vanillins, and mint were reviewed but studies on their role in bakery products were limited or very few. Hence there is a wide scope for study under this direction in depth.
A Discovery-Based Hydrochlorination of Carvone Utilizing a Guided-Inquiry Approach to Determine the Product Structure from [superscript 13]C NMR Spectra

Science.gov (United States)

Pelter, Michael W.; Walker, Natalie M.

2012-01-01

This experiment describes a discovery-based method for the regio- and stereoselective hydrochlorination of carvone, appropriate for a 3-h second-semester organic chemistry laboratory. The product is identified through interpretation of the [superscript 13]C NMR and DEPT spectra are obtained on an Anasazi EFT-60 at 15 MHz as neat samples. A…
Cordyceps fungi: natural products, pharmacological functions and developmental products.

Science.gov (United States)

Zhou, Xuanwei; Gong, Zhenghua; Su, Ying; Lin, Juan; Tang, Kexuan

2009-03-01

Parasitic Cordyceps fungi, such as Cordyceps sinensis, is a parasitic complex of fungus and caterpillar, which has been used for medicinal purposes for centuries particularly in China, Japan and other Asian countries. This article gives a general idea of the latest developments in C. sinensis research, with regard to the active chemical components, the pharmacological effects and the research and development of products in recent years. The common names for preparations include DongChongXiaCao in Chinese, winter worm summer grass in English. It has many bioactive components, such as 3'-deoxyadenosine, cordycepic acid and Cordyceps polysaccharides. It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. It also can be used to treat conditions such as night sweating, hyposexuality, hyperglycaemia, hyperlipidaemia, asthenia after severe illness, respiratory disease, renal dysfunction, renal failure, arrhythmias and other heart disease and liver disease. Because of its rarity and outstanding curative effects, several mycelia strains have been isolated from natural Cordyceps and manufactured by fermentation technology, and are commonly sold as health food products. In addition, some substitutes such as C. militaris and adulterants also have been used; therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy. Recent research advances in the study of Cordyceps, including Cordyceps mushrooms, chemical components, pharmacological functions and developmental products, has been reviewed and discussed. Developing trends in the field have also been appraised.
Defining "natural product" between public health and business, 17th to 21st centuries.

Science.gov (United States)

Stanziani, Alessandro

2008-07-01

The historical definition of a natural product stands at the crossroads of business, health, and the symbolic order of things. Until the end of the 19th century, "natural product" was a synonym of perishable. The emergency of organic chemistry made perishability be replaced with "toxicity". Nowadays, genetics is provoking a radical change in the notion and practises of "natural product". However, these concerns are never entirely opposed to "naturality" as a synonym for sacred and symbolic order. Traceability is largely based upon kosher practices and the association between organic and good for health is hardly based upon sound scientific arguments.
Knowledge based decision making: perspective on natural gas production

Energy Technology Data Exchange (ETDEWEB)

Ydstie, B. Erik; Stuland, Kjetil M.

2009-07-01

Conclusions (drawn by the author): Decarbonization of energy sources - From coal to renewable. Natural Gas Abundantly available - Norway is no. 3 exporter. Natural gas important as - Hydrogen source for chemicals; - Electricity; - End consumer usage (heating etc). Large potential for application of model based decision making; - Where and when to install platforms and drill wells - How to operate platforms and pipeline systems; - How to operate and optimize chemical production; - Optimization of electricity generation systems. (author)
Structure-Activity Relationships of New Natural Product-Based Diaryloxazoles with Selective Activity against Androgen Receptor-Positive Breast Cancer Cells.

Science.gov (United States)

Robles, Andrew J; McCowen, Shelby; Cai, Shengxin; Glassman, Michaels; Ruiz, Francisco; Cichewicz, Robert H; McHardy, Stanton F; Mooberry, Susan L

2017-11-22

Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved patient survival, but there are no therapies for triple negative breast cancers (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or amplification or overexpression of HER2. Gene expression profiling of TNBC has identified molecular subtypes and representative cell lines. An extract of the Texas native plant Amyris texana was found to have selective activity against MDA-MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC. Bioassay-guided fractionation identified two oxazole natural products with selective activity against this cell line. Conducted analog synthesis and structure-activity relationship studies provided analogs with more potent and selective activity against two LAR subtype cell line models, culminating in the discovery of compound 30 (CIDD-0067106). Lead compounds discovered have potent and selective antiproliferative activities, and mechanisms of action studies show they inhibit the activity of the mTORC1 pathway.
Natural radioactivity and estimated dose in Brazilian tobacco products

International Nuclear Information System (INIS)

Oliveira, Aline S.G.R. de; Damatto, Sandra R.

2017-01-01

Tobacco products contain significant concentrations of natural radionuclides from 238 U and 232 Th series. The consumption of these products increases the internal dose of radiation due to the inhalation of the natural radionuclides. Studies from literature emphasize that tobacco products have measurable concentrations of 210 Po and 210 Pb, and may contribute significantly to the increase of internal radiation dose and a large number of lung cancer in smokers. The objectives of this work were to determine the concentrations (Bq/kg) of the radionuclides 226 Ra, 228 Ra, 210 Pb and 210 Po and calculate the internal doses of radiation due to the consumption of these products. In the present work 71 samples were analyzed, consisting of cigars, unflavored and flavored cigarettes, straw cigarettes, cigars and roll smoke. The samples were purchased in Brazilian popular commercial establishments. The analytical techniques employed were the gross alpha and beta measurement after radiochemical separation for the radionuclides 226 Ra, 228 Ra, 210 Pb and alpha spectrometry for 210 Po. The internal radiation doses were calculated with the activity concentrations determined and using the ICRP Publication 119 dose coefficients. An annual consumption of 3,650 kg of tobacco products was considered. The inhalation rates of each radionuclide followed the rates of the current literature. The estimated mean annual dose varied from 76 to 263μSv/y for the tobacco product studied in this work. (author)
Natural radioactivity and estimated dose in Brazilian tobacco products

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Aline S.G.R. de; Damatto, Sandra R., E-mail: aline.oliveira@ipen.br, E-mail: damatto@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

2017-07-01

Tobacco products contain significant concentrations of natural radionuclides from {sup 238}U and {sup 232}Th series. The consumption of these products increases the internal dose of radiation due to the inhalation of the natural radionuclides. Studies from literature emphasize that tobacco products have measurable concentrations of {sup 210}Po and {sup 210}Pb, and may contribute significantly to the increase of internal radiation dose and a large number of lung cancer in smokers. The objectives of this work were to determine the concentrations (Bq/kg) of the radionuclides {sup 226}Ra, {sup 228}Ra, {sup 210}Pb and {sup 210}Po and calculate the internal doses of radiation due to the consumption of these products. In the present work 71 samples were analyzed, consisting of cigars, unflavored and flavored cigarettes, straw cigarettes, cigars and roll smoke. The samples were purchased in Brazilian popular commercial establishments. The analytical techniques employed were the gross alpha and beta measurement after radiochemical separation for the radionuclides {sup 226}Ra, {sup 228}Ra, {sup 210}Pb and alpha spectrometry for {sup 210}Po. The internal radiation doses were calculated with the activity concentrations determined and using the ICRP Publication 119 dose coefficients. An annual consumption of 3,650 kg of tobacco products was considered. The inhalation rates of each radionuclide followed the rates of the current literature. The estimated mean annual dose varied from 76 to 263μSv/y for the tobacco product studied in this work. (author)
T. rex, the Crater of Doom, and the Nature of Scientific Discovery

Science.gov (United States)

Lawson, Antone

Working from the 1970s to the early 1990s, Walter Alvarez and his research team sought the cause of the mass extinction that claimed the dinosaurs 65 million years ago. The present paper discusses that research in terms of eight puzzling observations, eight episodes of hypothetico-predictive reasoning, enumerative induction, and Jung's interrogative theory of scientific discovery. The Alvarez case history paints scientific discovery as a process in which causal questions are raised and answered through the creative use of analogical reasoning followed by an equally creative process of hypothesis testing in which predicted and observed results are compared. According to this account, puzzling observations, causal hypotheses, and imagined tests drive investigations and the search for evidence. Two implications follow. The first concerns the education of new scientists and science education researchers and the need to more clearly differentiate hypotheses from predictions in the research process. The second concerns standard science classroom instruction that should more frequently engage students in open inquiries that raise causal questions and encourage the generation of alternative causal hypotheses, which can then be explicitly tested in a hypothetico-predictive fashion.
Nuclear chemistry fifty years after the discovery of artificial radioactivity

International Nuclear Information System (INIS)

Lefort, M.

1984-01-01

In January 1934, the observation and the chemical identification of radiophosphorus as a reaction product in the bombardment of Aluminium by alpha particles have been the first step of a new scientific branch: Nuclear Chemistry. We describe here how this discovery in itself contains the frame of all the development which has followed. It consisted in four stages, each of them being a crucial starting point. The first one is the possibility for a total balance of the nuclear reaction in the exit channels, so that reaction mechanisms can be studied. The second, the most important perhaps, is the opening of nuclear synthesis. Nuclear chemists can now interfere into nuclear matter and instead of staying as observers of the radioactive decays of natural isotopes, they were able to build up a numerous chart of various nuclear species, going step by step further and further away from the nuclear stability conditions. The third aspect of the discovery was the appearance of a new mode of radioactive decay with the production of the first particle an antimater. 50 years later, the instability due to a much larger excess of protons is known to induce the proton emission radioactivity for new species like 109 I or 115 Cs, in the vicinity of proton unstability. Finally, the last point, so fertile for the future, was the observation of a neutron in the exit channel, so that neutron fluxes could result from alpha induced nuclear reactions and became such a strong tool for the production of transuranium elements and for nuclear fission. In the present survey, the wide interest of the second point, i.e. the nuclear synthesis, is emphasized, as well as the huge change in the technical methods
Constant rate natural gas production from a well in a hydrate reservoir

International Nuclear Information System (INIS)

Ji Chuang; Ahmadi, Goodarz; Smith, Duane H.

2003-01-01

Using a computational model, production of natural gas at a constant rate from a well that is drilled into a confined methane hydrate reservoir is studied. It is assumed that the pores in the reservoir are partially saturated with hydrate. A linearized model for an axisymmetric condition with a fixed well output is used in the analysis. For different reservoir temperatures and various well outputs, time evolutions of temperature and pressure profiles, as well as the gas flow rate in the hydrate zone and the gas region, are evaluated. The distance of the decomposition front from the well as a function of time is also computed. It is shown that to maintain a constant natural gas production rate, the well pressure must be decreased with time. A constant low production rate can be sustained for a long duration of time, but a high production rate demands unrealistically low pressure at the well after a relatively short production time. The simulation results show that the process of natural gas production in a hydrate reservoir is a sensitive function of reservoir temperature and hydrate zone permeability
Energy Security prospects in Cyprus and Israel: A focus on Natural Gas

Directory of Open Access Journals (Sweden)

Constantinos Taliotis

2014-06-01

Full Text Available The global production of natural gas has increased from 1226 bcm in 1973 to 3282 bcm in 2010 and is projected to continue rising by an annual growth rate of 1.6% between 2010 to 2035. Cyprus and Israel have recently made major offshore discoveries of natural gas, which can supply to a great extent the two countries’ current domestic energy needs for the next few decades and still export a substantial volume. MESSAGE, a global optimization model was used to explore the possible interactions between the two countries’ energy systems. Scenarios are presented that assess the export potential for electricity (generated by gas-fired power plants, liquefied natural gas (LNG or gas-to-liquid products (GTL. The results are compared to a scenario without any available reserves to illustrate the financial benefits that will arise from the exploitation of the gas resources in the two countries.
Novel fermentation processes for manufacturing plant natural products.

Science.gov (United States)

Zhou, Jingwen; Du, Guocheng; Chen, Jian

2014-02-01

Microbial production of plant natural products (PNPs), such as terpenoids, flavonoids from renewable carbohydrate feedstocks offers sustainable and economically attractive alternatives to their petroleum-based production. Rapid development of metabolic engineering and synthetic biology of microorganisms shows many advantages to replace the current extraction of these useful high price chemicals from plants. Although few of them were actually applied on a large scale for PNPs production, continuous research on these high-price chemicals and the rapid growing global market of them, show the promising future for the production of these PNPs by microorganisms with a more economic and environmental friendly way. Introduction of novel pathways and optimization of the native cellular processes by metabolic engineering of microorganisms for PNPs production are rapidly expanding its range of cell-factory applications. Here we review recent progress in metabolic engineering of microorganisms for the production of PNPs. Besides, factors restricting the yield improvement and application of lab-scale achievements to industrial applications have also been discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.
Natural gas productive capacity for the lower 48 States, 1980 through 1995

International Nuclear Information System (INIS)

1994-01-01

The purpose of this report is to analyze monthly natural gas wellhead productive capacity in the lower 48 States from 1980 through 1992 and project this capacity from 1993 through 1995. For decades, natural gas supplies and productive capacity have been adequate to meet demand. In the 1970's the capacity surplus was small because of market structure (split between interstate and intrastate), increasing demand, and insufficient drilling. In the early 1980's, lower demand, together with increased drilling, led to a large surplus capacity as new productive capacity came on line. After 1986, this large surplus began to decline as demand for gas increased, gas prices fell, and gas well completions dropped sharply. In late December 1989, the decline in this surplus, accompanied by exceptionally high demand and temporary weather-related production losses, led to concerns about the adequacy of monthly productive capacity for natural gas. These concerns should have been moderated by the gas system's performance during the unusually severe winter weather in March 1993 and January 1994. The declining trend in wellhead productive capacity is expected to be reversed in 1994 if natural gas prices and drilling meet or exceed the base case assumption. This study indicates that in the low, base, and high drilling cases, monthly productive capacity should be able to meet normal production demands through 1995 in the lower 48 States (Figure ES1). Exceptionally high peak-day or peak-week production demand might not be met because of physical limitations such as pipeline capacity. Beyond 1995, as the capacity of currently producing wells declines, a sufficient number of wells and/or imports must be added each year in order to ensure an adequate gas supply
Discovery and Innovation - Vol 11, No 3 (1999)

African Journals Online (AJOL)

Discovery and Innovation. ... Open Access DOWNLOAD FULL TEXT ... Product Yields and Kinetic Studies of Methylcyclopentane Reforming on Undried Pt – Re/ ... Rare Earth Metal Analysis Using Direct Excitation with 241 Americium Source.
Discovery and industrial applications of lytic polysaccharide mono-oxygenases.

Science.gov (United States)

Johansen, Katja S

2016-02-01

The recent discovery of copper-dependent lytic polysaccharide mono-oxygenases (LPMOs) has opened up a vast area of research covering several fields of application. The biotech company Novozymes A/S holds patents on the use of these enzymes for the conversion of steam-pre-treated plant residues such as straw to free sugars. These patents predate the correct classification of LPMOs and the striking synergistic effect of fungal LPMOs when combined with canonical cellulases was discovered when fractions of fungal secretomes were evaluated in industrially relevant enzyme performance assays. Today, LPMOs are a central component in the Cellic CTec enzyme products which are used in several large-scale plants for the industrial production of lignocellulosic ethanol. LPMOs are characterized by an N-terminal histidine residue which, together with an internal histidine and a tyrosine residue, co-ordinates a single copper atom in a so-called histidine brace. The mechanism by which oxygen binds to the reduced copper atom has been reported and the general mechanism of copper-oxygen-mediated activation of carbon is being investigated in the light of these discoveries. LPMOs are widespread in both the fungal and the bacterial kingdoms, although the range of action of these enzymes remains to be elucidated. However, based on the high abundance of LPMOs expressed by microbes involved in the decomposition of organic matter, the importance of LPMOs in the natural carbon-cycle is predicted to be significant. In addition, it has been suggested that LPMOs play a role in the pathology of infectious diseases such as cholera and to thus be relevant in the field of medicine. © 2016 Authors; published by Portland Press Limited.
Expanding Canadian natural gas production will strengthen growth of LP-gas industry

International Nuclear Information System (INIS)

Hawkins, D.J.

1994-01-01

In 1992, over 86% of Canadian propane and 70% of Canadian butane production originated in gas plants. Propane and butane production not recovered at gas plants is recovered in other processing facilities, primarily refineries and heavy oil upgraders. As a result, supplies of both products are largely tied to natural gas production, and the outlook for natural gas therefore provides the basis for any discussion on the outlook for gas processing and NGL industry infrastructure. The paper discusses gas processing, economies of scale, NGL supply, expected declines, industry structure and infrastructure, the two major centers of the Canadian NGL industry, new shippers, and required pipeline expansion
Natural Gas and Cellulosic Biomass: A Clean Fuel Combination? Determining the Natural Gas Blending Wall in Biofuel Production.

Science.gov (United States)

M Wright, Mark; Seifkar, Navid; Green, William H; Román-Leshkov, Yuriy

2015-07-07

Natural gas has the potential to increase the biofuel production output by combining gas- and biomass-to-liquids (GBTL) processes followed by naphtha and diesel fuel synthesis via Fischer-Tropsch (FT). This study reflects on the use of commercial-ready configurations of GBTL technologies and the environmental impact of enhancing biofuels with natural gas. The autothermal and steam-methane reforming processes for natural gas conversion and the gasification of biomass for FT fuel synthesis are modeled to estimate system well-to-wheel emissions and compare them to limits established by U.S. renewable fuel mandates. We show that natural gas can enhance FT biofuel production by reducing the need for water-gas shift (WGS) of biomass-derived syngas to achieve appropriate H2/CO ratios. Specifically, fuel yields are increased from less than 60 gallons per ton to over 100 gallons per ton with increasing natural gas input. However, GBTL facilities would need to limit natural gas use to less than 19.1% on a LHV energy basis (7.83 wt %) to avoid exceeding the emissions limits established by the Renewable Fuels Standard (RFS2) for clean, advanced biofuels. This effectively constitutes a blending limit that constrains the use of natural gas for enhancing the biomass-to-liquids (BTL) process.

What Is the Structure of the Antitubercular Natural Product Eucapsitrione?

Science.gov (United States)

Pullella, Glenn A; Wild, Duncan A; Nealon, Gareth L; Elyashberg, Mikhail; Piggott, Matthew J

2017-07-21

1,5,7-Trihydroxy-6H-indeno[1,2-b]anthracene-6,11,13-trione (1), proposed to be the antitubercular natural product eucapsitrione, has been synthesized in 43% overall yield and six steps, including a key Suzuki-Miyaura biaryl coupling and a directed remote metalation (DReM)-initiated cyclization. The physical and spectroscopic properties of 1 do not match the data reported for the natural product. At this time there is insufficient information available to enable a structure reassignment. During the optimization of the Suzuki-Miyaura coupling, an unprecedented biaryl coupling ortho to the borono group was observed. The scope of this unusual reaction has been investigated.
Strategies for enhancing the effectiveness of metagenomic-based enzyme discovery in lignocellulytic microbial communities

Energy Technology Data Exchange (ETDEWEB)

DeAngelis, K.M.; Gladden, J.G.; Allgaier, M.; D' haeseleer, P.; Fortney, J.L.; Reddy, A.; Hugenholtz, P.; Singer, S.W.; Vander Gheynst, J.; Silver, W.L.; Simmons, B.; Hazen, T.C.

2010-03-01

Producing cellulosic biofuels from plant material has recently emerged as a key U.S. Department of Energy goal. For this technology to be commercially viable on a large scale, it is critical to make production cost efficient by streamlining both the deconstruction of lignocellulosic biomass and fuel production. Many natural ecosystems efficiently degrade lignocellulosic biomass and harbor enzymes that, when identified, could be used to increase the efficiency of commercial biomass deconstruction. However, ecosystems most likely to yield relevant enzymes, such as tropical rain forest soil in Puerto Rico, are often too complex for enzyme discovery using current metagenomic sequencing technologies. One potential strategy to overcome this problem is to selectively cultivate the microbial communities from these complex ecosystems on biomass under defined conditions, generating less complex biomass-degrading microbial populations. To test this premise, we cultivated microbes from Puerto Rican soil or green waste compost under precisely defined conditions in the presence dried ground switchgrass (Panicum virgatum L.) or lignin, respectively, as the sole carbon source. Phylogenetic profiling of the two feedstock-adapted communities using SSU rRNA gene amplicon pyrosequencing or phylogenetic microarray analysis revealed that the adapted communities were significantly simplified compared to the natural communities from which they were derived. Several members of the lignin-adapted and switchgrass-adapted consortia are related to organisms previously characterized as biomass degraders, while others were from less well-characterized phyla. The decrease in complexity of these communities make them good candidates for metagenomic sequencing and will likely enable the reconstruction of a greater number of full length genes, leading to the discovery of novel lignocellulose-degrading enzymes adapted to feedstocks and conditions of interest.
Does species diversity limit productivity in natural grassland communities?

NARCIS (Netherlands)

Grace, James B.; Anderson, T. Michael; Smith, Melinda D.; Seabloom, Eric; Andelman, Sandy J.; Meche, Gayna; Weiher, Evan; Allain, Larry K.; Jutila, Heli; Sankaran, Mahesh; Knops, Johannes; Ritchie, Mark; Willig, Michael R.

Theoretical analyses and experimental studies of synthesized assemblages indicate that under particular circumstances species diversity can enhance community productivity through niche complementarity. It remains unclear whether this process has important effects in mature natural ecosystems where
Marine natural products in prevention and treatment of osteoporosis

Directory of Open Access Journals (Sweden)

Zahra Ghanbari

2015-05-01

Full Text Available Undoubtedly, pharmaceutical and nutritional factors play an important role in the prevention of age-related bone loss. According to the several studies so far, the effects of nutrients and bioactive components which are extracted from marine resources are very promising in osteoporosis. Most of these investigations have been done on various marine algae extracts. Since, algae are rich source of essential minerals, primary and secondary unique natural products, several amino acids and growth factors their extracts show favorable effects on bone metabolism. Moreover, it has been shown that marine nutrients such as marine fishes, shrimp and crabs increase the absorption of calcium and bone collagen synthesis or reduce the production of prostaglandins and decrease the deoxypyridinoline disposal. On the other hand, secondary products which are extracted and characterized from marine organisms such as mollusks, fungi, bacteria, sponges and coral reefs show anti-osteoporosis activities via the inhibition of osteoclast differentiation and the induction of apoptosis in osteoclasts like cells or stimulation of osteoblast differentiation. Although, several investigations have been done in this area, many of studies have been carried out on animal models, like ovariectomy-induced bone loss in mice. Hence, clinical investigations are warranted to develop marine natural products against bone loss and to prevent osteoporosis.
A brief history of the Delayed'' discovery of nuclear fission

Energy Technology Data Exchange (ETDEWEB)

Holden, N.E.

1989-08-01

This year marks the Fiftieth Anniversary of the discovery of Nuclear Fission. In the early 1930's, the neutron was discovered, followed by the discovery of artificial radioactivity and then the use of the neutron to produce artificial radioactivity. The first experiments resulting in the fission of uranium took place in 1934. A paper which speculated on fission as an explanation was almost immediately published, yet no one took it seriously not even the author herself. Why did it take an additional five years before anyone realized what had occurred This is an abnormally long time in a period when discoveries, particularly in nuclear physics, seemed to be almost a daily occurrence. The events which led up to the discovery are recounted, with an attempt made to put them into their historical perspective. The role played by Mendeleev's Periodic Table, the role of the natural radioactive decay chain of uranium, the discovery of protactinium, the apparent discovery of masurium (technetium) and a speculation on the reason why Irene Curie may have missed the discovery of nuclear fission will all be discussed. 43 refs.
Investigating the Structure-Activity Relationship of the Insecticidal Natural Product Rocaglamide.

Science.gov (United States)

Hall, Roger G; Bruce, Ian; Cooke, Nigel G; Diorazio, Louis J; Cederbaum, Fredrik; Dobler, Markus R; Irving, Ed

2017-12-01

The natural product Rocaglamide (1), isolated from the tree Aglaia elliptifolia, is a compelling but also challenging lead structure for crop protection. In laboratory assays, the natural product shows highly interesting insecticidal activity against chewing pests and beetles, but also phytotoxicity on some crop plants. Multi-step syntheses with control of stereochemistry were required to probe the structure-activity relationship (SAR), and seek simplified analogues. After a significant research effort, just two areas of the molecule were identified which allow modification whilst maintaining activity, as will be highlighted in this paper.
An agent-based peer-to-peer architecture for semantic discovery of manufacturing services across virtual enterprises

Science.gov (United States)

Zhang, Wenyu; Zhang, Shuai; Cai, Ming; Jian, Wu

2015-04-01

With the development of virtual enterprise (VE) paradigm, the usage of serviceoriented architecture (SOA) is increasingly being considered for facilitating the integration and utilisation of distributed manufacturing resources. However, due to the heterogeneous nature among VEs, the dynamic nature of a VE and the autonomous nature of each VE member, the lack of both sophisticated coordination mechanism in the popular centralised infrastructure and semantic expressivity in the existing SOA standards make the current centralised, syntactic service discovery method undesirable. This motivates the proposed agent-based peer-to-peer (P2P) architecture for semantic discovery of manufacturing services across VEs. Multi-agent technology provides autonomous and flexible problemsolving capabilities in dynamic and adaptive VE environments. Peer-to-peer overlay provides highly scalable coupling across decentralised VEs, each of which exhibiting as a peer composed of multiple agents dealing with manufacturing services. The proposed architecture utilises a novel, efficient, two-stage search strategy - semantic peer discovery and semantic service discovery - to handle the complex searches of manufacturing services across VEs through fast peer filtering. The operation and experimental evaluation of the prototype system are presented to validate the implementation of the proposed approach.
Utilization of Natural Products as Functional Feed

OpenAIRE

Stella Magdalena; Natadiputri G H; Nailufar; Purwadaria T

2013-01-01

The use of antibiotics as feed additive improves performance in livestock. However, scientific data related to the use of antibiotics in feed merge spreading of bacterial resistance in animal and human bodies, therefore the usage of antibiotics in animal production is restricted. This condition raise the utilization of natural antibiotic as functional feed such as phytogenics (essential oil, flavonoid, saponin, and tannin), enzyme, probiotic, and prebiotic to improve the livestock’s performan...
Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale.

Science.gov (United States)

Lemetre, Christophe; Maniko, Jeffrey; Charlop-Powers, Zachary; Sparrow, Ben; Lowe, Andrew J; Brady, Sean F

2017-10-31

Although bacterial bioactive metabolites have been one of the most prolific sources of lead structures for the development of small-molecule therapeutics, very little is known about the environmental factors associated with changes in secondary metabolism across natural environments. Large-scale sequencing of environmental microbiomes has the potential to shed light on the richness of bacterial biosynthetic diversity hidden in the environment, how it varies from one environment to the next, and what environmental factors correlate with changes in biosynthetic diversity. In this study, the sequencing of PCR amplicons generated using primers targeting either ketosynthase domains from polyketide biosynthesis or adenylation domains from nonribosomal peptide biosynthesis was used to assess biosynthetic domain composition and richness in soils collected across the Australian continent. Using environmental variables collected at each soil site, we looked for environmental factors that correlated with either high overall domain richness or changes in the domain composition. Among the environmental variables we measured, changes in biosynthetic domain composition correlate most closely with changes in latitude and to a lesser extent changes in pH. Although it is unclear at this time the exact mix of factors that may drive the relationship between biosynthetic domain composition and latitude, from a practical perspective the identification of a latitudinal basis for differences in soil metagenome biosynthetic domain compositions should help guide future natural product discovery efforts. Published under the PNAS license.
Historical sketch of the discovery, production, and application of radioisotopes

International Nuclear Information System (INIS)

Williams, C.

1975-01-01

The Joliot-Curies made the first artificial radioisotope ( 30 P) by bombarding aluminum with alpha particles. The development of the cyclotron and other high-energy particle accelerators in the early 1930's led to the production of numerous radioisotopes in measurable quantities. By the beginning of the 1950's, with the abundant neutron fluxes available at the U. S. Atomic Commission reactors, radioisotopes of many species really became abundant. Naturally occurring radioactive lead had been used very sparingly as tracers as far back as 1918 in determining chemical solubility and in 1923 in plant uptake from lead solutions. Now many new uses were developed and tested as tracers in medical diagnosis, agricultural, and industrial chemical and metallurigical processes. Many therapeutic applications were tested. The industrial labs developed thickness and level gauges for control of various manufacturing processes. Cobalt gamma-ray irradiators were developed for medical therapy and have also been used for sterilization of surgical instruments and materials, for food preservation, and for initiation of certain chemical reactions. The most significant development in the 1960's was the rapidly increasing role of private industry in taking over the development, production, sales, as well as research, into new methods of production and applications of radioisotopes
Natural products from Cuscuta reflexa Roxb. with antiproliferation activities in HCT116 colorectal cell lines.

Science.gov (United States)

Riaz, Muhammad; Bilal, Aishah; Ali, Muhammad Shaiq; Fatima, Itrat; Faisal, Amir; Sherkheli, Muhammad Azhar; Asghar, Adnan

2017-03-01

Parasitic Cuscuta reflexa Roxb. possesses many medicinal properties and is a rich source of a variety of biologically relevant natural products. Natural products are the prime source of leads, drugs, and drug templates, and many of the anticancer and antiviral drugs are either based on natural product or derived from them. Cancer is a devastating disease and one of the leading causes of death worldwide despite improvements in patient survival during the past 50 years; new and improved treatments for cancer are therefore actively sought. Colorectal cancer is the fourth most prevalent cancer worldwide and is responsible for nearly 9% of all cancer deaths. Our search for anticancer natural products from C. reflexa has yielded four natural products: Scoparone (1), p-coumaric acid (2), stigmasta-3,5-diene (3) and 1-O-p-hydroxycinnamoylglucose (4) and among them 1-O-p-hydroxycinnamoyldlucose (4) showed promising antiproliferative activities in HCT116 colorectal cell lines, whereas compounds 1-3 showed moderate activities.
State of the Art in Tumor Antigen and Biomarker Discovery

International Nuclear Information System (INIS)

Even-Desrumeaux, Klervi; Baty, Daniel; Chames, Patrick

2011-01-01

Our knowledge of tumor immunology has resulted in multiple approaches for the treatment of cancer. However, a gap between research of new tumors markers and development of immunotherapy has been established and very few markers exist that can be used for treatment. The challenge is now to discover new targets for active and passive immunotherapy. This review aims at describing recent advances in biomarkers and tumor antigen discovery in terms of antigen nature and localization, and is highlighting the most recent approaches used for their discovery including “omics” technology
Time series analysis of the behavior of brazilian natural rubber

Directory of Open Access Journals (Sweden)

Antônio Donizette de Oliveira

2009-03-01

Full Text Available The natural rubber is a non-wood product obtained of the coagulation of some lattices of forest species, being Hevea brasiliensis the main one. Native from the Amazon Region, this species was already known by the Indians before the discovery of America. The natural rubber became a product globally valued due to its multiple applications in the economy, being its almost perfect substitute the synthetic rubber derived from the petroleum. Similarly to what happens with other countless products the forecast of future prices of the natural rubber has been object of many studies. The use of models of forecast of univariate timeseries stands out as the more accurate and useful to reduce the uncertainty in the economic decision making process. This studyanalyzed the historical series of prices of the Brazilian natural rubber (R$/kg, in the Jan/99 - Jun/2006 period, in order tocharacterize the rubber price behavior in the domestic market; estimated a model for the time series of monthly natural rubberprices; and foresaw the domestic prices of the natural rubber, in the Jul/2006 - Jun/2007 period, based on the estimated models.The studied models were the ones belonging to the ARIMA family. The main results were: the domestic market of the natural rubberis expanding due to the growth of the world economy; among the adjusted models, the ARIMA (1,1,1 model provided the bestadjustment of the time series of prices of the natural rubber (R$/kg; the prognosis accomplished for the series supplied statistically adequate fittings.
Privacy and User Experience in 21st Century Library Discovery

Directory of Open Access Journals (Sweden)

Shayna Pekala

2017-06-01

Full Text Available Over the last decade, libraries have taken advantage of emerging technologies to provide new discovery tools to help users find information and resources more efficiently. In the wake of this technological shift in discovery, privacy has become an increasingly prominent and complex issue for libraries. The nature of the web, over which users interact with discovery tools, has substantially diminished the library’s ability to control patron privacy. The emergence of a data economy has led to a new wave of online tracking and surveillance, in which multiple third parties collect and share user data during the discovery process, making it much more difficult, if not impossible, for libraries to protect patron privacy. In addition, users are increasingly starting their searches with web search engines, diminishing the library’s control over privacy even further. While libraries have a legal and ethical responsibility to protect patron privacy, they are simultaneously challenged to meet evolving user needs for discovery. In a world where “search” is synonymous with Google, users increasingly expect their library discovery experience to mimic their experience using web search engines. However, web search engines rely on a drastically different set of privacy standards, as they strive to create tailored, personalized search results based on user data. Libraries are seemingly forced to make a choice between delivering the discovery experience users expect and protecting user privacy. This paper explores the competing interests of privacy and user experience, and proposes possible strategies to address them in the future design of library discovery tools.
An introduction to planar chromatography and its application to natural products isolation.

Science.gov (United States)

Gibbons, Simon

2012-01-01

Thin-layer chromatography (TLC) is an easy, inexpensive, rapid, and the most widely used method for the analysis and isolation of small organic natural and synthetic products. It also has use in the biological evaluation of organic compounds, particularly in the areas of antimicrobial and antioxidant metabolites and for the evaluation of acetylcholinesterase inhibitors which have utility in the treatment of Alzheimer's disease. The ease and inexpensiveness of use of this technique, coupled with the ability to rapidly develop separation and bioassay protocols will ensure that TLC will be used for some considerable time alongside conventional instrumental methods. This chapter deals with the basic principles of TLC and describes methods for the analysis and isolation of natural products. Examples of methods for isolation of several classes of natural product are detailed and protocols for TLC bioassays are given.
Search strategy has influenced the discovery rate of human viruses.

Science.gov (United States)

Rosenberg, Ronald; Johansson, Michael A; Powers, Ann M; Miller, Barry R

2013-08-20

A widely held concern is that the pace of infectious disease emergence has been increasing. We have analyzed the rate of discovery of pathogenic viruses, the preeminent source of newly discovered causes of human disease, from 1897 through 2010. The rate was highest during 1950-1969, after which it moderated. This general picture masks two distinct trends: for arthropod-borne viruses, which comprised 39% of pathogenic viruses, the discovery rate peaked at three per year during 1960-1969, but subsequently fell nearly to zero by 1980; however, the rate of discovery of nonarboviruses remained stable at about two per year from 1950 through 2010. The period of highest arbovirus discovery coincided with a comprehensive program supported by The Rockefeller Foundation of isolating viruses from humans, animals, and arthropod vectors at field stations in Latin America, Africa, and India. The productivity of this strategy illustrates the importance of location, approach, long-term commitment, and sponsorship in the discovery of emerging pathogens.
Three Essays in the Public Economics of Offshore Hydrocarbon Investment and Production

Science.gov (United States)

Kearney, Owen P.

Offshore sources, in both shallow and deep waters, are increasingly important contributors to global oil and natural gas production. As both resource owner and taxing authority, national governments play an important role in the production of these offshore hydrocarbons. How the policy choices of these governments affect firm behavior, however, is not necessarily well understood. This dissertation contributes to our knowledge of how public policy influences offshore hydrocarbon investment and production. In the first essay, I estimate the investment responses of hydrocarbon producers to the suspension of the royalty, a type of production tax levied on production from federal lands. I find that the potential for a royalty payments waiver: (1) increases the probability that an individual tract is acquired by an average of 193% (a mean increase of 5.6 percentage points); (2) decreases the probability that a lease is ever drilled during its observed lease term by an average of 14.5% (a mean decrease of 1.3 percentage points); and (3) increases the expected number of explored leases by 150%. The introduction of DWRRA also increases the average winning bid per lease by 60%. These estimates quantify the magnitudes of the discouraging effects of production taxation on oil and natural gas investment. In the second essay, I quantify the implied value of information spillovers in oil and natural gas exploration using an event study design. I find that 25 trading days after a discovery, firms that own leases adjacent to the discovery lease (but not the discovery lease, itself) realize an average abnormal return translating to 315 million in market capitalization. This effect is quantitatively large compared to costs for drilling an exploratory well. In the final essay, I measure how oil price affects water injection, a method for prolonging the productive lifetime of oil fields. I find that a 1 rise in price increases the water injected into the well's reservoir by
Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes.

Science.gov (United States)

Kehr, Jan-Christoph; Gatte Picchi, Douglas; Dittmann, Elke

2011-01-01

Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially emphasize modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future.
Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

Directory of Open Access Journals (Sweden)

Jan-Christoph Kehr

2011-12-01

Full Text Available Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially emphasize modular nonribosomal peptide synthetase (NRPS and polyketide synthase (PKS pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future.
Higgs Discovery: Impact on Composite Dynamics Technicolor & eXtreme Compositeness Thinking Fast and Slow

Science.gov (United States)

Sannino, Francesco

I discuss the impact of the discovery of a Higgs-like state on composite dynamics starting by critically examining the reasons in favour of either an elementary or composite nature of this state. Accepting the standard model interpretation I re-address the standard model vacuum stability within a Weyl-consistent computation. I will carefully examine the fundamental reasons why what has been discovered might not be the standard model Higgs. Dynamical electroweak breaking naturally addresses a number of the fundamental issues unsolved by the standard model interpretation. However this paradigm has been challenged by the discovery of a not-so-heavy Higgs-like state. I will therefore review the recent discovery1 that the standard model top-induced radiative corrections naturally reduce the intrinsic non-perturbative mass of the composite Higgs state towards the desired experimental value. Not only we have a natural and testable working framework but we have also suggested specic gauge theories that can realise, at the fundamental level, these minimal models of dynamical electroweak symmetry breaking. These strongly coupled gauge theories are now being heavily investigated via first principle lattice simulations with encouraging results. The new findings show that the recent naive claims made about new strong dynamics at the electroweak scale being disfavoured by the discovery of a not-so-heavy composite Higgs are unwarranted. I will then introduce the more speculative idea of extreme compositeness according to which not only the Higgs sector of the standard model is composite but also quarks and leptons, and provide a toy example in the form of gauge-gauge duality.

Evaluation of antioxidant activity of natural products; Kosanka seibun no kino hyokaho

Energy Technology Data Exchange (ETDEWEB)

Miyazawa, T.; Nakagawa, K. [Tohoku Univ., Sendai (Japan)

1998-10-20

The methods for evaluating antioxidant property of natural products in in vitro and in vivo lipid peroxidation systems are reviewed. Antioxidant activity of tocopherols, carotenoids, flavonoids and curcuminoids have been demonstrated against lipid peroxidation induced in microsomes, erythrocytes, plasma lipoproteins and in animal trials. Recently, in vivo antioxidant function of natural products was extensively investigated in humans together with explanation of their absorbability and metabolic fate. 35 refs., 8 figs., 4 tabs.
Natural or Plant Products for the Treatment of Neurological Disorders: Current Knowledge.

Science.gov (United States)

Parvez, Mohammad Khalid

2018-01-01

In recent decades, complementary and alternative medicine (CAM) has become very popular in the treatment of several chronic diseases. Natural products as one of the CAM modalities offer potential opportunities to discover lead compounds for novel drug development. The use of CAM or natural products in the prevention of neurodegenerative diseases is comparatively a newer area. A structured online literature search for peer-reviewed research articles was conducted on the PubMed, Europe PMC, Medline and Google Scholar portals, using phrases: natural products for neurologic disorders, phytomedicine for neurodegenerative diseases, natural therapeutics for neurological symptopms etc. Results: The retrieved data showed the natural therapeutics with anti-oxidative and anti-inflammatory salutations evidently plays a crucial role in protecting neurons. Of these, the most promising are caffeine, trigonelline, shogaol, curcumin, resveratrol, baicalein, wogonin, ginsenosides, tanshinones, withanolides, picrosides, parthenolide, cannabinoids, Devil's claw and white willow bark, including Chinese formulations Renshen Shouwu and Shengmai San. Though several herbs and their active ingredients have been studied in laboratory and clinical settings, only a few have been investigated for their molecular mechanisms of action. Notably, despite the promising and safe therapeutic benefits of CAM/herbal medicines, there exists a possible risk when combining them with prescription drugs. As a result, many drugs have shown changes in blood pressure, hepatotoxicity, seizures etc. when combined with certain herbs. Certainly, extensive work is needed to make sure that patients should take a regimen of protective and restorative therapy under an experienced healthcare professional. This article updates on the current knowledge of promising natural products used in neurological disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Identification of PPARgamma partial agonists of natural origin (II: in silico prediction in natural extracts with known antidiabetic activity.

Directory of Open Access Journals (Sweden)

Laura Guasch

Full Text Available BACKGROUND: Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action. METHODOLOGY/PRINCIPAL FINDINGS: From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally, we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature. CONCLUSIONS/SIGNIFICANCE: Our results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused
EFFECTS OF OIL AND NATURAL GAS PRICES ON INDUSTRIAL PRODUCTION IN THE EUROZONE MEMBER COUNTRIES

Directory of Open Access Journals (Sweden)

Yılmaz BAYAR

2014-04-01

Full Text Available Industrial production is one of the leading indicators of gross domestic product which reflects the overall economic performance of a country. In other words decreases or increases in industrial production point out a contracting or expanding economy. Therefore, changes in prices of oil and natural gas which are the crucial inputs to the industrial production are also important for the overall economy. This study examines the effects of changes in oil and natural gas prices on the industrial production in the 18 Eurozone member countries during the period January 2001-September 2013 by using panel regression. We found that oil prices and natural gas prices had negative effect on industrial production in the Eurozone member countries.
Economic growth to raise U.S. oil products, natural gas demand

International Nuclear Information System (INIS)

Beck, R.J.

1994-01-01

An accelerating economy will raise consumption of oil products and natural gas in the US this year. Contributing to demand growth will be the slump that began late last year in prices for crude oil and petroleum products. Some price recovery is likely in 1994, but there's little reason to expect a major increase. With oil production falling and demand rising, imports will have to climb again this year. OGJ projects a 2.6% increase this year following a 6.6% increase last year. Imports are expected to fill a record high 49.3% of US oil demand this year. The paper discusses energy and the economy, overall energy use, energy by source, the electrification trend, energy supplies, imports, refining operations, the growth of margins, and the energy demand of motor gasoline, jet fuel, distillate fuels, residual fuel oils, other petroleum products, and natural gas
Petroleum and natural gas economy in Arab countries and in Iran, Angola, Gabon, Nigeria and Chad

International Nuclear Information System (INIS)

1993-01-01

This paper describes briefly main informations on petroleum prices and market trends, trade and contracts, petroleum exploration in Algeria, Chad, Gabon, Libya, Saudi Arabia and Tunisia, new crude oil discoveries in Nigeria. In Iran, a joint venture will be constituted with Gaz de France for natural gas export in Europe. In Egypt, National Bank has financed for the first time a Liquefied Petroleum Gas plant. Statistics on petroleum and natural gas reserves, production, seismic surveys, drilling operations and refining units are also given. 9 tabs
Topology Discovery Using Cisco Discovery Protocol

OpenAIRE

Rodriguez, Sergio R.

2009-01-01

In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology ...
Financing drug discovery for orphan diseases

OpenAIRE

Fagnan, David Erik; Gromatzky, Austin A.; Stein, Roger Mark; Fernandez, Jose-Maria; Lo, Andrew W.

2014-01-01

Recently proposed ‘megafund’ financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures...
Thomson, his discovery of the electron and the twentieth century science and technology

International Nuclear Information System (INIS)

Ahmad, N.

1997-01-01

Sir J. J. Thomson was the first to discover a subatomic particle i. e. electron. Due to this discovery he is remembered in the history as T he Atom Smasher . He was a great experimentalists and a devoted physicist. He himself, his son and his seven pupils earned Noble prizes on the basis of their scientific discoveries. The discovery of electron by Sir Thomson in 1897, at Cavendish Laboratory, has rewritten the entire physical science. Although electron has wide spread applications in almost every field, yet its exact nature is not fully known. This article briefly describes the life of Sir Thomson, his achievements and the impact of his discovery of electron on the twentieth century science and technology. (author)
Environmental review of natural gas production in Lake Erie

International Nuclear Information System (INIS)

O'Shea, K.

2002-01-01

The water of Lake Erie is used as a source of drinking water for Ontario, New York, Pennsylvania, Ohio and Michigan. An environmental review has been conducted to determine the impact of drilling operations on the overall ecology of the lake. Since 1913, 2000 natural gas wells have been drilled in Lake Erie, of which 550 currently produce gas and account for 75 per cent of Ontario's total gas production. 180 wells are shut-in or suspended and the remaining wells have been abandoned. The gas wells are connected to onshore production facilities by approximately 1,600 km of small diameter pipelines that lie buried near shore or on top of the lake bed. Nearly 90 per cent of the in-lake infrastructure is in water depths of more than 20 metres. Talisman Energy is actively involved with the Canadian Coast Guard, the Department of Fisheries and Oceans, and the Ministry of Natural Resources to ensure cooperation between regulators and off-shore personnel. The environmental assessment of natural gas production in Lake Erie included a review of regulatory and best management practices, a biophysical overview of the lake, and a review of drilling practices, well completions, handling of waste streams, materials management, operations inspections, wastewater discharge, air emissions, and oil spills. It was revealed that for most drilling programs, cuttings are washed and discharged to the Lake. Ongoing testing will determine the impact that this practice has on benthic populations. The drill muds used for drilling operations are water based, environmentally friendly, and re-used between well locations. For completion programs, all well activities are closed circuit operations. Wells are abandoned through plugging with cement, removing wellheads and casing below the lake bottom. There has been a reported volume of about 23,000 litres of spilled product from 1990 to 2001, of which 68 per cent has come from 3 industrial companies that operate near Lake Erie. The offshore gas
Marine actinobacteria associated with marine organisms and their potentials in producing pharmaceutical natural products.

Science.gov (United States)

Valliappan, Karuppiah; Sun, Wei; Li, Zhiyong

2014-09-01

Actinobacteria are ubiquitous in the marine environment, playing an important ecological role in the recycling of refractory biomaterials and producing novel natural products with pharmic applications. Actinobacteria have been detected or isolated from the marine creatures such as sponges, corals, mollusks, ascidians, seaweeds, and seagrass. Marine organism-associated actinobacterial 16S rRNA gene sequences, i.e., 3,003 sequences, deposited in the NCBI database clearly revealed enormous numbers of actinobacteria associated with marine organisms. For example, RDP classification of these sequences showed that 112 and 62 actinobacterial genera were associated with the sponges and corals, respectively. In most cases, it is expected that these actinobacteria protect the host against pathogens by producing bioactive compounds. Natural products investigation and functional gene screening of the actinobacteria associated with the marine organisms revealed that they can synthesize numerous natural products including polyketides, isoprenoids, phenazines, peptides, indolocarbazoles, sterols, and others. These compounds showed anticancer, antimicrobial, antiparasitic, neurological, antioxidant, and anti-HIV activities. Therefore, marine organism-associated actinobacteria represent an important resource for marine drugs. It is an upcoming field of research to search for novel actinobacteria and pharmaceutical natural products from actinobacteria associated with the marine organisms. In this review, we attempt to summarize the present knowledge on the diversity and natural products production of actinobacteria associated with the marine organisms, based on the publications from 1991 to 2013.
Natural gas: An essential source of energy in the Romanian economy

International Nuclear Information System (INIS)

Coconea, G.

1993-01-01

The Romanian natural gas industry has existed since the early 1900s. The share of natural gas in Romania's current energy consumption is around 40%. The state gas company Romgaz operates ca 150 gas fields and 3,600 producing wells, but only 20% of annual production is being replaced by new discoveries. Declining gas production is caused by such factors as improper well completion, delayed workovers, water encroachment, and sand consolidation. Romgaz also transports imported natural gas from Russia and provides transportation services to natural gas importers in neighboring countries. The gas transmission network comprises ca 11,000 km of pipelines and 82,800 kW of installed compressor capacity. The distribution system supplies gas to over 2.5 million customers over some 15,000 km of pipeline. Future projects include expansion of production and increasing recoverable reserves, modernization of equipment, constructing an interconnecting pipeline with the Ukraine, installing a liquefied natural gas terminal on the Black Sea, rehabilitating the gas transmission grid, and installing supervisory control and data acquisition systems. The gas consumption pattern of 1990 (57% industrial, 31% power generation, 8% households) is expected to change with a substantial increase in household and commercial supplies, as well as replacement of gas-fired generation with hydroelectric and nuclear generation. A governmental restructuring strategy is being implemented to enhance oil and gas production, to improve operational efficiency of the sector, and to address environmental pollution. Components of the strategy are outlined
Patent border wars: defining the boundary between scientific discoveries and patentable inventions.

Science.gov (United States)

Holman, Christopher M

2007-12-01

Drawing an appropriate boundary between unpatentable natural phenomena and patentable inventions is crucial in preventing the patent laws from unduly restricting access to fundamental scientific discoveries. Some would argue that, particularly in the U.S., patents are being issued that purport to claim a novel product or process but that, in effect, encompass any practical application of a fundamental biological principle. Examples include gene patents, which Congress is considering banning, and patents relating to biological correlations and pathways, such as the patents at issue in the headline-grabbing LabCorp v. Metabolite and Ariad v. Eli Lilly litigations. In view of the mounting concern, it seems likely that Congress and/or the courts will address the issue, and perhaps substantially shift the boundary.
Naturally Occurring Wound Healing Agents: An Evidence-Based Review.

Science.gov (United States)

Karapanagioti, E G; Assimopoulou, A N

2016-01-01

Nature constitutes a pool of medicines for thousands of years. Nowadays, trust in nature is increasingly growing, as many effective medicines are naturally derived. Over the last decades, the potential of plants as wound healing agents is being investigated. Wounds and ulcers affect the patients' life quality and often lead to amputations. Approximately 43,000,000 patients suffer from diabetic foot ulcers worldwide. Annually, $25 billion are expended for the treatment of chronic wounds, with the number growing due to aging population and increased incidents of diabetes and obesity. Therefore a timely, orderly and effective wound management and treatment is crucial. This paper aims to systematically review natural products, mainly plants, with scientifically well documented wound healing activity, focusing on articles based on animal and clinical studies performed worldwide and approved medicinal products. Moreover, a brief description of the wound healing mechanism is presented, to provide a better understanding. Although a plethora of natural products are in vitro and in vivo evaluated for wound healing activity, only a few go through clinical trials and even fewer launch the market as approved medicines. Most of them rely on traditional medicine, indicating that ethnopharmacology is a successful strategy for drug development. Since only 6% of plants have been systematically investigated pharmacologically, more intensified efforts and emerging advancements are needed to exploit the potentials of nature for the development of novel medicines. This paper aims to provide a reliable database and matrix for thorough further investigation towards the discovery of wound healing agents.
Novel Natural Products for Healthy Ageing from the Mediterranean Diet and Food Plants of Other Global Sources-The MediHealth Project.

Science.gov (United States)

Waltenberger, Birgit; Halabalaki, Maria; Schwaiger, Stefan; Adamopoulos, Nicolas; Allouche, Noureddine; Fiebich, Bernd L; Hermans, Nina; Jansen-Dürr, Pidder; Kesternich, Victor; Pieters, Luc; Schönbichler, Stefan; Skaltsounis, Alexios-Leandros; Tran, Hung; Trougakos, Ioannis P; Viljoen, Alvaro; Wolfender, Jean-Luc; Wolfrum, Christian; Xynos, Nikos; Stuppner, Hermann

2018-05-06

There is a rapid increase in the percentage of elderly people in Europe. Consequently, the prevalence of age-related diseases will also significantly increase. Therefore, the main goal of MediHealth, an international research project, is to introduce a novel approach for the discovery of active agents of food plants from the Mediterranean diet and other global sources that promote healthy ageing. To achieve this goal, a series of plants from the Mediterranean diet and food plants from other origins are carefully selected and subjected to in silico, cell-based, in vivo (fly and mouse models), and metabolism analyses. Advanced analytical techniques complement the bio-evaluation process for the efficient isolation and identification of the bioactive plant constituents. Furthermore, pharmacological profiling of bioactive natural products, as well as the identification and synthesis of their metabolites, is carried out. Finally, optimization studies are performed in order to proceed to the development of innovative nutraceuticals, dietary supplements or herbal medicinal products. The project is based on an exchange of researchers between nine universities and four companies from European and non-European countries, exploiting the existing complementary multidisciplinary expertise. Herein, the unique and novel approach of this interdisciplinary project is presented.
Epoxide-Opening Cascades in the Synthesis of Polycyclic Polyether Natural Products

Science.gov (United States)

2009-01-01

The group of polycyclic polyether natural products is of special interest due to the fascinating structure and biological effects displayed by its members. The latter includes potentially therapeutic antibiotic, antifungal, and anticancer properties, as well as extreme lethality. The polycyclic structural features of this family can, in some cases, be traced to their biosynthetic origin, but in others that are less well understood, only to proposed biosynthetic pathways that feature dramatic, yet speculative, epoxide–opening cascades. In this review we summarize how such epoxide–opening cascade reactions have been used in the synthesis of polycyclic polyethers and related natural products. PMID:19572302
Production of hydrogen by thermocatalytic cracking of natural gas

Energy Technology Data Exchange (ETDEWEB)

Muradov, N. [Florida Solar Energy Center, Cocoa, FL (United States)

1996-10-01

The conventional methods of hydrogen production from natural gas (for example, steam reforming and partial oxidation) are complex, multi-step processes that produce large quantities of CO{sub 2}. The main goal of this project is to develop a technologically simple process for hydrogen production from natural gas (NG) and other hydrocarbon fuels via single-step decomposition of hydrocarbons. This approach eliminates or significantly reduces CO{sub 2} emission. Carbon is a valuable by-product of this process, whereas conventional methods of hydrogen production from NG produce no useful by-products. This approach is based on the use of special catalysts that reduce the maximum temperature of the process from 1400-1500{degrees}C (thermal non-catalytic decomposition of methane) to 500-900{degrees}C. Transition metal based catalysts and various forms of carbon are among the candidate catalysts for the process. This approach can advantageously be used for the development of compact NG reformers for on-site production of hydrogen-methane blends at refueling stations and, also, for the production of hydrogen-rich gas for fuel cell applications. The author extended the search for active methane decomposition catalysts to various modifications of Ni-, Fe-, Mo- and Co-based catalysts. Variation in the operational parameters makes it possible to produce H{sub 2}-CH{sub 4} blends with a wide range of hydrogen concentrations that vary from 15 to 98% by volume. The author found that Ni-based catalysts are more effective at temperatures below 750{degrees}C, whereas Fe-based catalysts are effective at temperatures above 800{degrees}C for the production of hydrogen with purity of 95% v. or higher. The catalytic pyrolysis of liquid hydrocarbons (pentane, gasoline) over Fe-based catalyst was conducted. The author observed the production of a hydrogen-rich gas (hydrogen concentration up to 97% by volume) at a rate of approximately 1L/min.mL of hydrocarbon fuel.
Search for bioactive natural products from medicinal plants of Bangladesh.

Science.gov (United States)

Ahmed, Firoj; Sadhu, Samir Kumar; Ishibashi, Masami

2010-10-01

In our continuous search for bioactive natural products from natural resources, we explored medicinal plants of Bangladesh, targeting cancer-related tumor necrosis factor-related apoptosis-inducing ligand-signaling pathway, along with some other biological activities such as prostaglandin inhibitory activity, 1,1-diphenyl-2-picrylhydrazyl free-radical-scavenging activity, and cell growth inhibitory activity. Along with this, we describe a short field study on Sundarbans mangrove forests, Bangladesh, in the review.
Natural or Induced: Identifying Natural and Induced Swarms from Pre-production and Co-production Microseismic Catalogs at the Coso Geothermal Field

Science.gov (United States)

Schoenball, Martin; Kaven, Joern; Glen, Jonathan M. G.; Davatzes, Nicholas C.

2015-01-01

Increased levels of seismicity coinciding with injection of reservoir fluids have prompted interest in methods to distinguish induced from natural seismicity. Discrimination between induced and natural seismicity is especially difficult in areas that have high levels of natural seismicity, such as the geothermal fields at the Salton Sea and Coso, both in California. Both areas show swarm-like sequences that could be related to natural, deep fluid migration as part of the natural hydrothermal system. Therefore, swarms often have spatio-temporal patterns that resemble fluid-induced seismicity, and might possibly share other characteristics. The Coso Geothermal Field and its surroundings is one of the most seismically active areas in California with a large proportion of its activity occurring as seismic swarms. Here we analyze clustered seismicity in and surrounding the currently produced reservoir comparatively for pre-production and co-production periods. We perform a cluster analysis, based on the inter-event distance in a space-time-energy domain to identify notable earthquake sequences. For each event j, the closest previous event i is identified and their relationship categorized. If this nearest neighbor’s distance is below a threshold based on the local minimum of the bimodal distribution of nearest neighbor distances, then the event j is included in the cluster as a child to this parent event i. If it is above the threshold, event j begins a new cluster. This process identifies subsets of events whose nearest neighbor distances and relative timing qualify as a cluster as well as a characterizing the parent-child relationships among events in the cluster. We apply this method to three different catalogs: (1) a two-year microseismic survey of the Coso geothermal area that was acquired before exploration drilling in the area began; (2) the HYS_catalog_2013 that contains 52,000 double-difference relocated events and covers the years 1981 to 2013; and (3) a
Personal-Care Products Formulated with Natural Antioxidant Extracts

Directory of Open Access Journals (Sweden)

Maria Luisa Soto

2018-01-01

Full Text Available The objective of this study was to evaluate the potential use of some vegetal raw materials in personal-care products. Four ethanolic extracts (grape pomace, Pinus pinaster wood chips, Acacia dealbata flowers, and Lentinus edodes were prepared and total phenolics, monomeric sugars, and antioxidant capacity were determined on alcoholic extracts. Six of the most important groups of cosmetics products (hand cream, body oil, shampoo, clay mask, body exfoliating cream, and skin cleanser were formulated. Participants evaluated some sensory attributes and overall acceptance by a 10-point scale; the results showed differences among age-intervals, but not between males and females. The results confirmed that all extracts presented characteristics appropriate for their use in cosmetic formulations and their good acceptability by consumers into all cosmetic products. Texture/appearance, spreadability, and skin feeling are important attributes among consumer expectations, but odor and color were the primary drivers and helped differentiate the natural extracts added into all personal-care products.

Technical review of coal gasifiers for production of synthetic natural gas

International Nuclear Information System (INIS)

Lee, Geun Woo; Shin, Yong Seung

2012-01-01

Because of the increasing cost of oil and natural gas, energy production technologies using coal, including synthetic natural gas (SNG) and integrated gasification combined cycle (IGCC), have attracted attention because of the relatively low cost of coal. During the early stage of a project, the developer or project owner has many options with regard to the selection of a gasifier. In particular, from the viewpoint of feasibility, the gasifier is a key factor in the economic evaluation. This study compares the technical aspects of gasifiers for a real SNG production project in an early stage. A fixed bed slagging gasifier, wet type entrained gasifier, and dry type entrained gasifier, all of which have specific advantages, can be used for the SNG production project. Base on a comparison of the process descriptions and performances of each gasifier, this study presents a selection guideline for a gasifier for an SNG production project that will be beneficial to project developers and EPC (Engineering, Procurement, Construction) contractors
Marine organisms: an alternative source of potentially valuable natural products

Directory of Open Access Journals (Sweden)

Alphonse Kelecom

1991-01-01

Full Text Available This paper recalls the outcoming of marine natural products research and reviews a selection of marirne bioactive metabolites in current use together with promising trends in marine pharmacology.
Natural gas for power production in Western Europe

International Nuclear Information System (INIS)

1993-01-01

The third and last part of the Sub-Committee's study on natural gas for power generation is reprinted in this issue. This part addresses gas consumption in electricity production until the year 2010. The first part of the study dealing with combined cycle power plants was published in September and the 2nd part on regulatory and environmental issues in October 1992
The rare fluorinated natural products and biotechnological prospects for fluorine enzymology.

Science.gov (United States)

Chan, K K Jason; O'Hagan, David

2012-01-01

Nature has hardly evolved a biochemistry of fluorine although there is a low-level occurrence of fluoroacetate found in selected tropical and subtropical plants. This compound, which is generally produced in low concentrations, has been identified in the plants due to its high toxicity, although to date the biosynthesis of fluoroacetate in plants remains unknown. After that, fluorinated entities in nature are extremely rare, and despite increasingly sophisticated screening and analytical methods applied to natural product extraction, it has been 25 years since the last bona fide fluorinated natural product was identified from an organism. This was the reported isolation of the antibiotic 4-fluorothreonine and the toxin fluoroacetate in 1986 from Streptomyces cattleya. This bacterium has proven amenable to biochemical investigation, the fluorination enzyme (fluorinase) has been isolated and characterized, and the biosynthetic pathway to these bacterial metabolites has been elucidated. Also the fluorinase gene has been cloned into a host bacterium (Salinispora tropica), and this has enabled the de novo production of a bioactive fluorinated metabolite from fluoride ion, by genetic engineering. Biotechnological manipulation of the fluorinase offers the prospects for the assembly of novel fluorinated metabolites by fermentation technology. This is particularly attractive, given the backdrop that about 15-20% of pharmaceuticals licensed each year (new chemical entities) contain a fluorine atom. Copyright © 2012 Elsevier Inc. All rights reserved.
Spontaneously Reported Adverse Reactions for Herbal Medicinal Products and Natural Remedies in Sweden 2007-15: Report from the Medical Products Agency.

Science.gov (United States)

Svedlund, Erika; Larsson, Maria; Hägerkvist, Robert

2017-06-01

In relation to the extensive use of herbal medicinal products in self-care, the safety information is limited and there is a need for improvement. This study describes spontaneously reported adverse reactions related to herbal medicinal products and natural remedies in Sweden. To evaluate the characteristics and frequency of adverse events recorded by the Swedish Medical Products Agency, where herbal medicinal products and natural remedies were suspected as causative agents. Adverse drug reactions reported to the Swedish Medical Product Agency during 2007-15 related to approved herbal medicinal products or natural remedies were included and analysed in the retrospective study. Reports had been assessed for causality when they were lodged and only reports that had been assessed as at least possible were included in the study. In total, 116 reports (concerning 259 adverse reactions) related to herbal medicinal products or natural remedies were found in the Swedish national pharmacovigilance database. The active ingredients most frequently suspected during the study period were black cohosh rhizome (15 reports), purple coneflower herb (14 reports) and a combination of extracts of pollen (13 reports). Adverse reactions related to skin and subcutaneous tissue were the most commonly reported reactions. No previously unknown safety problems have been discovered in the present study. This finding could be explained by a thorough pre-approval assessment of medicinal products and the fact that most herbal preparations in medicinal products have been in clinical use for many years (for traditional herbal medicinal products, the requirements are ≥30 years), i.e. adverse reactions are acknowledged and assessed before approval.
Organisms for biofuel production: natural bioresources and methodologies for improving their biosynthetic potentials.

Science.gov (United States)

Hu, Guangrong; Ji, Shiqi; Yu, Yanchong; Wang, Shi'an; Zhou, Gongke; Li, Fuli

2015-01-01

In order to relieve the pressure of energy supply and environment contamination that humans are facing, there are now intensive worldwide efforts to explore natural bioresources for production of energy storage compounds, such as lipids, alcohols, hydrocarbons, and polysaccharides. Around the world, many plants have been evaluated and developed as feedstock for bioenergy production, among which several crops have successfully achieved industrialization. Microalgae are another group of photosynthetic autotroph of interest due to their superior growth rates, relatively high photosynthetic conversion efficiencies, and vast metabolic capabilities. Heterotrophic microorganisms, such as yeast and bacteria, can utilize carbohydrates from lignocellulosic biomass directly or after pretreatment and enzymatic hydrolysis to produce liquid biofuels such as ethanol and butanol. Although finding a suitable organism for biofuel production is not easy, many naturally occurring organisms with good traits have recently been obtained. This review mainly focuses on the new organism resources discovered in the last 5 years for production of transport fuels (biodiesel, gasoline, jet fuel, and alkanes) and hydrogen, and available methods to improve natural organisms as platforms for the production of biofuels.
Regional air quality impacts of increased natural gas production and use in Texas.

Science.gov (United States)

Pacsi, Adam P; Alhajeri, Nawaf S; Zavala-Araiza, Daniel; Webster, Mort D; Allen, David T

2013-04-02

Natural gas use in electricity generation in Texas was estimated, for gas prices ranging from $1.89 to $7.74 per MMBTU, using an optimal power flow model. Hourly estimates of electricity generation, for individual electricity generation units, from the model were used to estimate spatially resolved hourly emissions from electricity generation. Emissions from natural gas production activities in the Barnett Shale region were also estimated, with emissions scaled up or down to match demand in electricity generation as natural gas prices changed. As natural gas use increased, emissions decreased from electricity generation and increased from natural gas production. Overall, NOx and SO2 emissions decreased, while VOC emissions increased as natural gas use increased. To assess the effects of these changes in emissions on ozone and particulate matter concentrations, spatially and temporally resolved emissions were used in a month-long photochemical modeling episode. Over the month-long photochemical modeling episode, decreases in natural gas prices typical of those experienced from 2006 to 2012 led to net regional decreases in ozone (0.2-0.7 ppb) and fine particulate matter (PM) (0.1-0.7 μg/m(3)). Changes in PM were predominantly due to changes in regional PM sulfate formation. Changes in regional PM and ozone formation are primarily due to decreases in emissions from electricity generation. Increases in emissions from increased natural gas production were offset by decreasing emissions from electricity generation for all the scenarios considered.
Plant natural products research in tuberculosis drug discovery and ...

African Journals Online (AJOL)

SAM

2014-06-04

Jun 4, 2014 ... Department of Medicinal Chemistry and Quality Control (MCQC), National Institute for Pharmaceutical Research and. Development ..... Anticancer. Cannabis sativa L. ... National Cancer Research Institute (NCI) at Frederick,.
Gamma radiodecontamination of natural products uses in Cuban pharmaceutical industry

International Nuclear Information System (INIS)

Rodriguez, M.; Lopez, M.; Guerra, M.; Lastra, H.; Prieto, E.; Padron, E.

1997-01-01

The aim of the present paper was to carry out the gamma radiodecontamination of industrial productions from there medicinal plant species (C. officinalis, P. incarta and M. recuttia) and two pharmaceuticals forms (S. platensis and bee pollen tabs) which presented high levels of microbiological count. Adequate irradiation doses calculated for each product were used in decontamination. The results obtained showed the effectiveness of the process in the elimination of microbial contamination from theses natural products. No changes in nutritional constituents or physico-chemical properties were observed
Application of PBPK modelling in drug discovery and development at Pfizer.

Science.gov (United States)

Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

2012-01-01

Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.
Epothilones as lead structures for the synthesis-based discovery of new chemotypes for microtubule stabilization.

Science.gov (United States)

Feyen, Fabian; Cachoux, Frédéric; Gertsch, Jürg; Wartmann, Markus; Altmann, Karl-Heinz

2008-01-01

Epothilones are macrocyclic bacterial natural products with potent microtubule-stabilizing and antiproliferative activity. They have served as successful lead structures for the development of several clinical candidates for anticancer therapy. However, the structural diversity of this group of clinical compounds is rather limited, as their structures show little divergence from the original natural product leads. Our own research has explored the question of whether epothilones can serve as a basis for the development of new structural scaffolds, or chemotypes, for microtubule stabilization that might serve as a basis for the discovery of new generations of anticancer drugs. We have elaborated a series of epothilone-derived macrolactones whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of a conformationally constrained side chain, the removal of the C3-hydroxyl group, and the replacement of C12 with nitrogen. So far, this approach has yielded analogs 30 and 40 that are the most advanced, the most rigorously modified, structures, both of which are potent antiproliferative agents with low nanomolar activity against several human cancer cell lines in vitro. The synthesis was achieved through a macrolactone-based strategy or a high-yielding RCM reaction. The 12-aza-epothilone ("azathilone" 40) may be considered a "non-natural" natural product that still retains most of the overall structural characteristics of a true natural product but is structurally unique, because it lies outside of the general scope of Nature's biosynthetic machinery for polyketide synthesis. Like natural epothilones, both 30 and 40 promote tubulin polymerization in vitro and at the cellular level induce cell cycle arrest in mitosis. These
Natural Radiation in byproducts of the production of phosphoric acid

International Nuclear Information System (INIS)

Silveira, Marcilei A. Guazzelli da; Cardoso, L.L.; Medina, N.H.

2014-01-01

Natural radiation is the largest source of radiation exposure to which man is subject. It is formed basically by cosmic radiation and the radionuclides present in the Earth crust, as 40 K and the elements of the decay series of 232 Th and 238 U. Phosphate ores, which constitutes the raw material for the production of phosphoric acid, have a high rate of natural radiation from the decay series of 232 Th and 238 U. Phosphogypsum, which is naturally radioactivity, is a by-product of the production of phosphoric acid by the wet method. For each ton of phosphoric acid it is produced about 4.5 tons of phosphogypsum. This work presents the analysis of samples collected in all stages of the manufacturing process of phosphoric acid, which generates the phosphogypsum. Gamma-ray spectrometry was used to measure the concentration of the elements of the decay series of 232 Th and 238 U. All analyzed samples showed a high concentration of radionuclides, promoting the need for further steps in the process in order to reduce the presence of such radionuclides in the phosphogypsum. The results indicate the radionuclide 238 U has higher contribution in some samples of the intermediate stages of the process. All samples exceeded the international average range of human exposure to terrestrial gamma radiation, which is 0.3 to 1.0 mSv/year. (author)
Short history of natural product research in the CSIR

CSIR Research Space (South Africa)

Walwyn, D

2006-02-01

Full Text Available Natural product research has been a major component of the CSIR's bioscience activities for its entire history, and particularly in the 1960s and 1970s. This type of work is also strongly aligned with one of the objectives of the CSIR, namely...
Synthetic biology approaches for the production of plant metabolites in unicellular organisms.

Science.gov (United States)

Moses, Tessa; Mehrshahi, Payam; Smith, Alison G; Goossens, Alain

2017-07-10

Synthetic biology is the repurposing of biological systems for novel objectives and applications. Through the co-ordinated and balanced expression of genes, both native and those introduced from other organisms, resources within an industrial chassis can be siphoned for the commercial production of high-value commodities. This developing interdisciplinary field has the potential to revolutionize natural product discovery from higher plants, by providing a diverse array of tools, technologies, and strategies for exploring the large chemically complex space of plant natural products using unicellular organisms. In this review, we emphasize the key features that influence the generation of biorefineries and highlight technologies and strategic solutions that can be used to overcome engineering pitfalls with rational design. Also presented is a succinct guide to assist the selection of unicellular chassis most suited for the engineering and subsequent production of the desired natural product, in order to meet the global demand for plant natural products in a safe and sustainable manner. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Telomerase Inhibitors from Natural Products and Their Anticancer Potential

Directory of Open Access Journals (Sweden)

Kumar Ganesan

2017-12-01

Full Text Available Telomeres and telomerase are nowadays exploring traits on targets for anticancer therapy. Telomerase is a unique reverse transcriptase enzyme, considered as a primary factor in almost all cancer cells, which is mainly responsible to regulate the telomere length. Hence, telomerase ensures the indefinite cell proliferation during malignancy—a hallmark of cancer—and this distinctive feature has provided telomerase as the preferred target for drug development in cancer therapy. Deactivation of telomerase and telomere destabilization by natural products provides an opening to succeed new targets for cancer therapy. This review aims to provide a fundamental knowledge for research on telomere, working regulation of telomerase and its various binding proteins to inhibit the telomere/telomerase complex. In addition, the review summarizes the inhibitors of the enzyme catalytic subunit and RNA component, natural products that target telomeres, and suppression of transcriptional and post-transcriptional levels. This extensive understanding of telomerase biology will provide indispensable information for enhancing the efficiency of rational anti-cancer drug design.
14 CFR 406.143 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are...
Microbial production of natural gas from coal and organic-rich shale

Science.gov (United States)

Orem, William

2013-01-01

Natural gas is an important component of the energy mix in the United States, producing greater energy yield per unit weight and less pollution compared to coal and oil. Most of the world’s natural gas resource is thermogenic, produced in the geologic environment over time by high temperature and pressure within deposits of oil, coal, and shale. About 20 percent of the natural gas resource, however, is produced by microorganisms (microbes). Microbes potentially could be used to generate economic quantities of natural gas from otherwise unexploitable coal and shale deposits, from coal and shale from which natural gas has already been recovered, and from waste material such as coal slurry. Little is known, however, about the microbial production of natural gas from coal and shale.
Inseparability of science history and discovery

Directory of Open Access Journals (Sweden)

J. M. Herndon

2010-04-01

Full Text Available Science is very much a logical progression through time. Progressing along a logical path of discovery is rather like following a path through the wilderness. Occasionally the path splits, presenting a choice; the correct logical interpretation leads to further progress, the wrong choice leads to confusion. By considering deeply the relevant science history, one might begin to recognize past faltering in the logical progression of observations and ideas and, perhaps then, to discover new, more precise understanding. The following specific examples of science faltering are described from a historical perspective: (1 Composition of the Earth's inner core; (2 Giant planet internal energy production; (3 Physical impossibility of Earth-core convection and Earth-mantle convection, and; (4 Thermonuclear ignition of stars. For each example, a revised logical progression is described, leading, respectively, to: (1 Understanding the endo-Earth's composition; (2 The concept of nuclear georeactor origin of geo- and planetary magnetic fields; (3 The invalidation and replacement of plate tectonics; and, (4 Understanding the basis for the observed distribution of luminous stars in galaxies. These revised logical progressions clearly show the inseparability of science history and discovery. A different and more fundamental approach to making scientific discoveries than the frequently discussed variants of the scientific method is this: An individual ponders and through tedious efforts arranges seemingly unrelated observations into a logical sequence in the mind so that causal relationships become evident and new understanding emerges, showing the path for new observations, for new experiments, for new theoretical considerations, and for new discoveries. Science history is rich in "seemingly unrelated observations" just waiting to be logically and causally related to reveal new discoveries.
A Growing Disconnection From Nature Is Evident in Cultural Products.

Science.gov (United States)

Kesebir, Selin; Kesebir, Pelin

2017-03-01

Human connection with nature is widely believed to be in decline even though empirical evidence is scarce on the magnitude and historical pattern of the change. Studying works of popular culture in English throughout the 20th century and later, we have documented a cultural shift away from nature that begins in the 1950s. Since then, references to nature have been decreasing steadily in fiction books, song lyrics, and film storylines, whereas references to the human-made environment have not. The observed temporal pattern is consistent with the explanatory role of increased virtual and indoors recreation options (e.g., television, video games) in the disconnect from nature, and it is inconsistent with a pure urbanization account. These findings are cause for concern, not only because they imply foregone physical and psychological benefits from engagement with nature, but also because cultural products are agents of socialization that can evoke curiosity, respect, and concern for the natural world.
Recent Advances in Substrate-Controlled Asymmetric Cyclization for Natural Product Synthesis

Directory of Open Access Journals (Sweden)

Jeyun Jo

2017-06-01

Full Text Available Asymmetric synthesis of naturally occurring diverse ring systems is an ongoing and challenging research topic. A large variety of remarkable reactions utilizing chiral substrates, auxiliaries, reagents, and catalysts have been intensively investigated. This review specifically describes recent advances in successful asymmetric cyclization reactions to generate cyclic architectures of various natural products in a substrate-controlled manner.

Medicinal plants and natural products in amelioration of arsenic toxicity: a short review.

Science.gov (United States)

Bhattacharya, Sanjib

2017-12-01

Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis. To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically. Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies. This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.
The importance of asking "how and why?" in natural product structure elucidation.

Science.gov (United States)

Brown, Patrick D; Lawrence, Andrew L

2017-10-18

Covering: up to 2017This review highlights why careful consideration of the biosynthetic origin (the how) and the biological function (the why) of a natural product can be so useful during the determination of its structure. Recent examples of structural reassignments inspired by biosynthetic and functional insights will be presented. This review will demonstrate the importance of viewing the origin, structure and function of a natural product as intertwined threads of a single story, best viewed as a whole rather than as discrete topics.
Chiral thiazoline and thiazole building blocks for the synthesis of peptide-derived natural products.

Science.gov (United States)

Just-Baringo, Xavier; Albericio, Fernando; Alvarez, Mercedes

2014-01-01

Thiazoline and thiazole heterocycles are privileged motifs found in numerous peptide-derived natural products of biological interest. During the last decades, the synthesis of optically pure building blocks has been addressed by numerous groups, which have developed a plethora of strategies to that end. Efficient and reliable methodologies that are compatible with the intricate and capricious architectures of natural products are a must to further develop their science. Structure confirmation, structure-activity relationship studies and industrial production are fields of paramount importance that require these robust methodologies in order to successfully bring natural products into the clinic. Today's chemist toolbox is assorted with many powerful methods for chiral thiazoline and thiazole synthesis. Ranging from biomimetic approaches to stereoselective alkylations, one is likely to find a suitable method for their needs.
Cell immobilization for production of lactic acid biofilms do it naturally.

Science.gov (United States)

Dagher, Suzanne F; Ragout, Alicia L; Siñeriz, Faustino; Bruno-Bárcena, José M

2010-01-01

Interest in natural cell immobilization or biofilms for lactic acid fermentation has developed considerably over the last few decades. Many studies report the benefits associated with biofilms as industrial methods for food production and for wastewater treatment, since the formation represents a protective means of microbial growth offering survival advantages to cells in toxic environments. The formation of biofilms is a natural process in which microbial cells adsorb to a support without chemicals or polymers that entrap the cells and is dependent on the reactor environment, microorganism, and characteristics of the support. These unique characteristics enable biofilms to cause chronic infections, disease, food spoilage, and devastating effects as in microbial corrosion. Their distinct resistance to toxicity, high biomass potential, and improved stability over cells in suspension make biofilms a good tool for improving the industrial economics of biological lactic acid production. Lactic acid bacteria and specific filamentous fungi are the main sources of biological lactic acid. Over the past two decades, studies have focused on improving the lactic acid volumetric productivity through reactor design development, new support materials, and improvements in microbial production strains. To illustrate the operational designs applied to the natural immobilization of lactic acid producing microorganisms, this chapter presents the results of a search for optimum parameters and how they are affected by the physical, chemical, and biological variables of the process. We will place particular emphasis upon the relationship between lactic acid productivity attained by various types of reactors, supports, media formulations, and lactic acid producing microorganisms. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Appreciation of symmetry in natural product synthesis.

Science.gov (United States)

Bai, Wen-Ju; Wang, Xiqing

2017-12-13

Covering: 2012 to June 2017This review aims to show that complex natural product synthesis can be streamlined by taking advantage of molecular symmetry. Various strategies to construct molecules with either evident or hidden symmetry are illustrated. Insights regarding the origins and adjustments of these strategies as well as inspiring new methodological developments are deliberated. When a symmetric strategy fails, the corresponding reason is analysed and an alternative approach is briefly provided. Finally, the importance of exploiting molecular symmetry and future research directions are discussed.
Petroleum and natural gas economy in Arab countries, Angola, Iran and Nigeria

International Nuclear Information System (INIS)

Anon.

1993-01-01

This paper describes briefly main informations on petroleum prices and market trends, trade and contracts, imports, demand, taxes. The Southern Oil Company has restored a production capacity of 1.8 Mb per day in the South of Iraq. In Iran, a joint venture between France and Iran (Iranian French Gas Co.) has been created and precedes the establishment of an european consortium for iranian gas import. In Jordan, in the natural gas field of Risha, a new discovery can give 633000 m 3 per day. Informations on petroleum exploration or production in Tunisia (Rhemoura oil field), in Syria (Dez ez Zor Petroleum Company), in Angola are also offered
Natural gas productive capacity for the lower 48 states 1984 through 1996, February 1996

International Nuclear Information System (INIS)

1996-01-01

This is the fourth wellhead productive capacity report. The three previous ones were published in 1991, 1993, and 1994. This report should be of particular interest to those in Congress, Federal and State agencies, industry, and the academic community, who are concerned with the future availability of natural gas. The EIA Dallas Field Office has prepared five earlier reports regarding natural gas productive capacity. These reports, Gas Deliverability and Flow Capacity of Surveillance Fields, reported deliverability and capacity data for selected gas fields in major gas producing areas. The data in the reports were based on gas-well back-pressure tests and estimates of gas-in-place for each field or reservoir. These reports use proven well testing theory, most of which has been employed by industry since 1936 when the Bureau of Mines first published Monograph 7. Demand for natural gas in the United States is met by a combination of natural gas production, underground gas storage, imported gas, and supplemental gaseous fuels. Natural gas production requirements in the lower 48 States have been increasing during the last few years while drilling has remained at low levels. This has raised some concern about the adequacy of future gas supplies, especially in periods of peak heating or cooling demand. The purpose of this report is to address these concerns by presenting a 3-year projection of the total productive capacity of natural gas at the wellhead for the lower 48 States. Alaska is excluded because Alaskan gas does not enter the lower-48 States pipeline system. The Energy Information Administration (EIA) generates this 3-year projection based on historical gas-well drilling and production data from State, Federal, and private sources. In addition to conventional gas-well gas, coalbed gas and oil-well gas are also included
Beyond The Prime Directive: The MAST Discovery Portal and High Level Science Products

Science.gov (United States)

Fleming, Scott W.; Abney, Faith; Donaldson, Tom; Dower, Theresa; Fraquelli, Dorothy A.; Koekemoer, Anton M.; Levay, Karen; Matuskey, Jacob; McLean, Brian; Quick, Lee; Rogers, Anthony; Shiao, Bernie; Thompson, Randy; Tseng, Shui-Ay; Wallace, Geoff; White, Richard L.

2015-01-01

The Mikulski Archive for Space Telescopes (MAST) is a NASA-funded archive for a wide range of astronomical missions, primarily supporting space-based UV and optical telescopes. What is less well-known is that MAST provides much more than just a final resting place for primary data products and documentation from these missions. The MAST Discovery Portal is our new search interface that integrates all the missions that MAST supports into a single interface, allowing users to discover (and retrieve) data from other missions that overlap with your targets of interest. In addition to searching MAST, the Portal allows users to search the Virtual Observatory, granting access to data from thousands of collections registered with the VO, including large missions spanning the electromagnetic spectrum (e.g., Chandra, SDSS, Spitzer, 2MASS, WISE). The Portal features table import/export, coordinate-based cross-matching, dynamic chart plotting, and the AstroView sky viewer with footprint overlays. We highlight some of these capabilities with science-driven examples. MAST also accepts High Level Science Products (HLSPs) from the community. These HLSPs are user-generated data products that can be related to a MAST-supported mission. MAST provides a permanent archive for these data with linked references, and integrates it within MAST infrastructure and services. We highlight some of the most recent HLSPs MAST has released, including the HST Frontier Fields, GALEX All-Sky Diffuse Radiation Mapping, a survey of the intergalactic medium with HST-COS, and one of the most complete line lists ever derived for a white dwarf using FUSE AND HST-STIS. These HLSPs generate substantial interest from the community, and are an excellent way to increase visibility and ensure the longevity of your data.
Natural Products as Adjunctive Treatment for Pancreatic Cancer: Recent Trends and Advancements

Directory of Open Access Journals (Sweden)

Qingxi Yue

2017-01-01

Full Text Available Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.
Deposits of naturally occurring radioactivity in production of oil and natural gas; Radioaktive avleiringer i olje- og gassproduksjon

Energy Technology Data Exchange (ETDEWEB)

Strand, T; Lysebo, I; Kristensen, D; Birovljev, A

1997-01-01

Deposits of naturally occurring radioactive materials is an increasing problem in Norwegian oil and gas production. Activity concentration in solid-state samples and production water, and doses to workers involved in different operations off-shore, have been measured. The report also includes a discussion of different methods of monitoring and alternatives for final disposal of wastes. 154 refs.
Usability Test Results for a Discovery Tool in an Academic Library

Directory of Open Access Journals (Sweden)

Jody Condit Fagan

2008-03-01

Full Text Available Discovery tools are emerging in libraries. These tools offer library patrons the ability to concurrently search the library catalog and journal articles. While vendors rush to provide feature-rich interfaces and access to as much content as possible, librarians wonder about the usefulness of these tools to library patrons. In order to learn about both the utility and usability of EBSCO Discovery Service, James Madison University conducted a usability test with eight students and two faculty members. The test consisted of nine tasks focused on common patron requests or related to the utility of specific discovery tool features. Software recorded participants’ actions and time on task, human observers judged the success of each task, and a post-survey questionnaire gathered qualitative feedback and comments from the participants. Overall, participants were successful at most tasks, but specific usability problems suggested some interface changes for both EBSCO Discovery Service and JMU’s customizations of the tool. The study also raised several questions for libraries above and beyond any specific discovery tool interface, including the scope and purpose of a discovery tool versus other library systems, working with the large result sets made possible by discovery tools, and navigation between the tool and other library services and resources. This article will be of interest to those who are investigating discovery tools, selecting products, integrating discovery tools into a library web presence, or performing evaluations of similar systems.
Scientific Prediction and Prophetic Patenting in Drug Discovery.

Science.gov (United States)

Curry, Stephen H; Schneiderman, Anne M

2015-01-01

Pharmaceutical patenting involves writing claims based on both discoveries already made, and on prophesy of future developments in an ongoing project. This is necessitated by the very different timelines involved in the drug discovery and product development process on the one hand, and successful patenting on the other. If patents are sought too early there is a risk that patent examiners will disallow claims because of lack of enablement. If patenting is delayed, claims are at risk of being denied on the basis of existence of prior art, because the body of relevant known science will have developed significantly while the project was being pursued. This review examines the role of prophetic patenting in relation to the essential predictability of many aspects of drug discovery science, promoting the concepts of discipline-related and project-related prediction. This is especially directed towards patenting activities supporting commercialization of academia-based discoveries, where long project timelines occur, and where experience, and resources to pay for patenting, are limited. The need for improved collaborative understanding among project scientists, technology transfer professionals in, for example, universities, patent attorneys, and patent examiners is emphasized.
Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced Genome Editing.

Science.gov (United States)

Weber, Jakob; Valiante, Vito; Nødvig, Christina S; Mattern, Derek J; Slotkowski, Rebecca A; Mortensen, Uffe H; Brakhage, Axel A

2017-01-20

Filamentous fungi produce varieties of natural products even in a strain dependent manner. However, the genetic basis of chemical speciation between strains is still widely unknown. One example is trypacidin, a natural product of the opportunistic human pathogen Aspergillus fumigatus, which is not produced among different isolates. Combining computational analysis with targeted gene editing, we could link a single nucleotide insertion in the polyketide synthase of the trypacidin biosynthetic pathway and reconstitute its production in a nonproducing strain. Thus, we present a CRISPR/Cas9-based tool for advanced molecular genetic studies in filamentous fungi, exploiting selectable markers separated from the edited locus.
The discovery of the periodic table as a case of simultaneous discovery.

Science.gov (United States)

Scerri, Eric

2015-03-13

The article examines the question of priority and simultaneous discovery in the context of the discovery of the periodic system. It is argued that rather than being anomalous, simultaneous discovery is the rule. Moreover, I argue that the discovery of the periodic system by at least six authors in over a period of 7 years represents one of the best examples of a multiple discovery. This notion is supported by a new view of the evolutionary development of science through a mechanism that is dubbed Sci-Gaia by analogy with Lovelock's Gaia hypothesis. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Recombinant organisms for production of industrial products

Science.gov (United States)

Adrio, Jose-Luis

2010-01-01

A revolution in industrial microbiology was sparked by the discoveries of ther double-stranded structure of DNA and the development of recombinant DNA technology. Traditional industrial microbiology was merged with molecular biology to yield improved recombinant processes for the industrial production of primary and secondary metabolites, protein biopharmaceuticals and industrial enzymes. Novel genetic techniques such as metabolic engineering, combinatorial biosynthesis and molecular breeding techniques and their modifications are contributing greatly to the development of improved industrial processes. In addition, functional genomics, proteomics and metabolomics are being exploited for the discovery of novel valuable small molecules for medicine as well as enzymes for catalysis. The sequencing of industrial microbal genomes is being carried out which bodes well for future process improvement and discovery of new industrial products. PMID:21326937
Recombinant organisms for production of industrial products.

Science.gov (United States)

Adrio, Jose-Luis; Demain, Arnold L

2010-01-01

A revolution in industrial microbiology was sparked by the discoveries of ther double-stranded structure of DNA and the development of recombinant DNA technology. Traditional industrial microbiology was merged with molecular biology to yield improved recombinant processes for the industrial production of primary and secondary metabolites, protein biopharmaceuticals and industrial enzymes. Novel genetic techniques such as metabolic engineering, combinatorial biosynthesis and molecular breeding techniques and their modifications are contributing greatly to the development of improved industrial processes. In addition, functional genomics, proteomics and metabolomics are being exploited for the discovery of novel valuable small molecules for medicine as well as enzymes for catalysis. The sequencing of industrial microbal genomes is being carried out which bodes well for future process improvement and discovery of new industrial products. © 2010 Landes Bioscience
Beyond Discovery

DEFF Research Database (Denmark)

Korsgaard, Steffen; Sassmannshausen, Sean Patrick

2017-01-01

In this chapter we explore four alternatives to the dominant discovery view of entrepreneurship; the development view, the construction view, the evolutionary view, and the Neo-Austrian view. We outline the main critique points of the discovery presented in these four alternatives, as well...
Cytotoxic Natural Products from Marine Sponge-Derived Microorganisms

Directory of Open Access Journals (Sweden)

Huawei Zhang

2017-03-01

Full Text Available A growing body of evidence indicates that marine sponge-derived microbes possess the potential ability to make prolific natural products with therapeutic effects. This review for the first time provides a comprehensive overview of new cytotoxic agents from these marine microbes over the last 62 years from 1955 to 2016, which are assorted into seven types: terpenes, alkaloids, peptides, aromatics, lactones, steroids, and miscellaneous compounds.
Collision-Induced Dissociation Mass Spectrometry: A Powerful Tool for Natural Product Structure Elucidation.

Science.gov (United States)

Johnson, Andrew R; Carlson, Erin E

2015-11-03

Mass spectrometry is a powerful tool in natural product structure elucidation, but our ability to directly correlate fragmentation spectra to these structures lags far behind similar efforts in peptide sequencing and proteomics. Often, manual data interpretation is required and our knowledge of the expected fragmentation patterns for many scaffolds is limited, further complicating analysis. Here, we summarize advances in natural product structure elucidation based upon the application of collision induced dissociation fragmentation mechanisms.
Plant volatile aldehydes as natural insecticides against stored-product beetles.

Science.gov (United States)

Hubert, Jan; Münzbergová, Zuzana; Santino, Angelo

2008-01-01

Infestation by stored-product pests causes serious losses in food and feed commodities. Among possible strategies against these pests, which aim to reduce the use of synthetic insecticides, including fumigants, natural insecticides produced by plants represent one of the most promising approaches for their ecochemical control. Three six-carbon and nine-carbon aldehydes, natural plant volatiles produced by the plant lipoxygenase pathway, were tested for their insecticidal activity against five species of stored-product beetles in feeding, fumigation and combined bioassays. The compounds (2E,6Z)-nonadienal, (2E)-nonenal and (2E)-hexenal were incorporated into feeding discs in feeding bioassays or evaporated from filter paper in closed glass chambers in fumigation tests. Beetle sensitivity to aldehydes differed according to the different treatments. The highest activity was obtained by (2E)-hexenal in fumigation tests, with the LC(50) ranging from 4 to 26 mg L(-1), while (2E, 6Z)-nonadienal was the most effective in feeding tests, giving LD(50)s ranging from 0.44 to 2.76 mg g(-1) when applied to feeding discs. Fumigation tests in the presence of wheat grains confirmed that (2E)-hexenal was the most effective compound, with a calculated LC(99) ranging from 33 to 166 mg L(-1). The results of both feeding and fumigation tests indicated that natural plant aldehydes are potential candidates to control stored-product beetles.

Some links on this page may take you to non-federal websites. Their policies may differ from this site.