Fundamental Characteristics of AAA+ Protein Family Structure and Function.

PubMed

Miller, Justin M; Enemark, Eric J

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

Purity-activity relationships of natural products: the case of anti-TB active ursolic acid.

PubMed

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.

Structure Elucidation of a Natural Product.

ERIC Educational Resources Information Center

Letcher, Roy M.

1983-01-01

Describes an experiment simulating a real-life structure elucidation problem through isolation, characterization, and chemical transformation of an "unknown," naturally occurring monoterpene, with extensive use being made of spectroscopy and aided by biogenetic considerations. Information given to students, procedures, results, and discussion of…

Fundamental Characteristics of AAA+ Protein Family Structure and Function

PubMed Central

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

Elucidating the role of surface chemistry on cationic phosphorus dendrimer-siRNA complexation.

PubMed

Deriu, Marco A; Tsapis, Nicolas; Noiray, Magali; Grasso, Gianvito; El Brahmi, Nabil; Mignani, Serge; Majoral, Jean-Pierre; Fattal, Elias; Danani, Andrea

2018-06-14

In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the flexibility/rigidity ratio, play a crucial role in the efficiency of complexation. However, advances in organic chemistry have enabled the development of dendrimers that differ only by a single atom on their surface terminals. This is the case for cationic phosphorus dendrimers functionalized with either pyrrolidinium (DP) or morpholinium (DM) terminal groups. This small change was shown to strongly affect the dendrimer-siRNA complexation, leading to more efficient anti-inflammatory effects in the case of DP. Reasons for this different behavior can hardly be inferred only by biological in vitro and in vivo experiments due to the high number of variables and complexity of the investigated biological system. However, an understanding of how small chemical surface changes may completely modify the overall dendrimer-siRNA complexation is a significant breakthrough towards the design of efficient dendrimers for nucleic acid delivery. Herein, we present experimental and computational approaches based on isothermal titration calorimetry and molecular dynamics simulations to elucidate the molecular reasons behind different efficiencies and activities of DP and DM. Results of the present research highlight how chemical surface modifications may drive the overall dendrimer-siRNA affinity by influencing enthalpic and entropic contributions of binding free energy. Moreover, this study elucidates molecular reasons related to complexation stoichiometry that may be crucial in determining the dendrimer complexation efficiency.

Relating color working memory and color perception.

PubMed

Allred, Sarah R; Flombaum, Jonathan I

2014-11-01

Color is the most frequently studied feature in visual working memory (VWM). Oddly, much of this work de-emphasizes perception, instead making simplifying assumptions about the inputs served to memory. We question these assumptions in light of perception research, and we identify important points of contact between perception and working memory in the case of color. Better characterization of its perceptual inputs will be crucial for elucidating the structure and function of VWM. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differences between amyloid-β aggregation in solution and on the membrane: insights into elucidation of the mechanistic details of Alzheimer's disease.

PubMed

Kotler, Samuel A; Walsh, Patrick; Brender, Jeffrey R; Ramamoorthy, Ayyalusamy

2014-10-07

The association of the amyloid-β (Aβ) peptide with cellular membranes is hypothesized to be the underlying phenomenon of neurotoxicity in Alzheimer's disease. Misfolding of proteins and peptides, as is the case with Aβ, follows a progression from a monomeric state, through intermediates, ending at long, unbranched amyloid fibers. This tutorial review offers a perspective on the association of toxic Aβ structures with membranes as well as details of membrane-associated mechanisms of toxicity.

Harnessing glycomics technologies: integrating structure with function for glycan characterization

PubMed Central

Robinson, Luke N.; Artpradit, Charlermchai; Raman, Rahul; Shriver, Zachary H.; Ruchirawat, Mathuros; Sasisekharan, Ram

2013-01-01

Glycans, or complex carbohydrates, are a ubiquitous class of biological molecules which impinge on a variety of physiological processes ranging from signal transduction to tissue development and microbial pathogenesis. In comparison to DNA and proteins, glycans present unique challenges to the study of their structure and function owing to their complex and heterogeneous structures and the dominant role played by multivalency in their sequence-specific biological interactions. Arising from these challenges, there is a need to integrate information from multiple complementary methods to decode structure-function relationships. Focusing on acidic glycans, we describe here key glycomics technologies for characterizing their structural attributes, including linkage, modifications, and topology, as well as for elucidating their role in biological processes. Two cases studies, one involving sialylated branched glycans and the other sulfated glycosaminoglycans, are used to highlight how integration of orthogonal information from diverse datasets enables rapid convergence of glycan characterization for development of robust structure-function relationships. PMID:22522536

Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems

PubMed Central

Fu, Yao; Kao, Weiyuan John

2010-01-01

Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

Model systems in heterogeneous catalysis: towards the design and understanding of structure and electronic properties.

PubMed

Pan, Q; Li, L; Shaikhutdinov, S; Fujimori, Y; Hollerer, M; Sterrer, M; Freund, H-J

2018-05-29

We discuss in this paper two case studies related to nano-particle catalyst systems. One concerns a model system for the Cr/SiO2 Phillips catalyst for ethylene polymerization and here we present XPS data to complement the previously published TPD, IRAS and reactivity studies to elucidate the electronic structure of the system in some detail. The second case study provides additional information on Au nano-particles supported on ultrathin MgO(100)/Ag(100) films where we had observed a specific activity of the particle's rim at the metal-oxide interface with respect to CO2 activation and oxalate formation, obviously connected to electron transfer through the MgO film from the metal substrate underneath. Here we present XPS and Auger data, which allows detailed analysis of the observed chemical shifts. This analysis corroborates previous findings deduced via STM.

iSpec: A Web-Based Activity for Spectroscopy Teaching

ERIC Educational Resources Information Center

Vosegaard, Thomas

2018-01-01

Students' skills in structure elucidation of organic molecules are developed by training them to understand advanced spectroscopic measurements and elucidate structures of small organic molecules from mass spectrometry (MS) and infrared (IR), ultraviolet (UV), and [superscript 1]H and [superscript 13]C nuclear magnetic resonance (NMR)…

Catharanthus alkaloids XXXII: isolation of alkaloids from Catharanthus trichophyllus roots and structure elucidation of cathaphylline.

PubMed

Cordell, G A; Farnsworth, N R

1976-03-01

Further examination of the cytotoxic alkaloid fractions of Catharanthus trichophyllus roots afforded nine alkaloids. Two of these alkaloids, lochnericine and horhammericine, are responsible for part of the cytotoxic activity. The structure elucidation of cathaphylline, a new beta-anilino acrylate derivative, is described.

Lipidomics of glycosphingolipids.

PubMed

Farwanah, Hany; Kolter, Thomas

2012-02-02

Glycosphingolipids (GSLs) contain one or more sugars that are attached to a sphingolipid moiety, usually to a ceramide, but in rare cases also to a sphingoid base. A large structural heterogeneity results from differences in number, identity, linkage, and anomeric configuration of the carbohydrate residues, and also from structural differences within the hydrophobic part. GSLs form complex cell-type specific patterns, which change with the species, the cellular differentiation state, viral transformation, ontogenesis, and oncogenesis. Although GSL structures can be assigned to only a few series with a common carbohydrate core, their structural variety and the complex pattern are challenges for their elucidation and quantification by mass spectrometric techniques. We present a general overview of the application of lipidomics for GSL determination. This includes analytical procedures and instrumentation together with recent correlations of GSL molecular species with human diseases. Difficulties such as the structural complexity and the lack of standard substances for complex GSLs are discussed.

Lipidomics of Glycosphingolipids

PubMed Central

Farwanah, Hany; Kolter, Thomas

2012-01-01

Glycosphingolipids (GSLs) contain one or more sugars that are attached to a sphingolipid moiety, usually to a ceramide, but in rare cases also to a sphingoid base. A large structural heterogeneity results from differences in number, identity, linkage, and anomeric configuration of the carbohydrate residues, and also from structural differences within the hydrophobic part. GSLs form complex cell-type specific patterns, which change with the species, the cellular differentiation state, viral transformation, ontogenesis, and oncogenesis. Although GSL structures can be assigned to only a few series with a common carbohydrate core, their structural variety and the complex pattern are challenges for their elucidation and quantification by mass spectrometric techniques. We present a general overview of the application of lipidomics for GSL determination. This includes analytical procedures and instrumentation together with recent correlations of GSL molecular species with human diseases. Difficulties such as the structural complexity and the lack of standard substances for complex GSLs are discussed. PMID:24957371

Structural characteristics of the molecular species of tetraacylglycerols in lesquerella (Physaria fendleri) oil elucidated by mass spectrometry

USDA-ARS?s Scientific Manuscript database

The structure and ratios of regioisomers of the molecular species of tetraacylglycerols affect their physical properties. They were elucidated by ESI mass spectrometry of the lithium adducts of tetraacylglycerols from the HPLC fractions of lesquerella oil. The contents of acyl and acylacyl chains at...

Nature's Migraine Treatment: Isolation and Structure Elucidation of Parthenolide from "Tanacetum parthenium"

ERIC Educational Resources Information Center

Walsh, Emma L.; Ashe, Siobhan; Walsh, John J.

2012-01-01

The purpose of this experiment is to provide students with the essential skills and knowledge required to perform the extraction, isolation, and structural elucidation of parthenolide from "Tanacetum parthenium" or feverfew. Students are introduced to a background of the traditional medicinal uses of parthenolide, while more modern applications of…

Growth of carbon structured over Pd, Pt and Ni: A comparative DFT study

NASA Astrophysics Data System (ADS)

Quiroga, Matías Abel

2013-03-01

To elucidate the graphene-like structures mechanisms growth over the M(1 1 1) surface (M = Pd, Pt and Ni) we performed ab initio calculus in the frame of density functional theory with the exchange-correlation functional treated according to the Generalized Gradient Approximation (GGA). In order to avoid the problem that represent the complex interaction between the well formed graphene layer and the metallic surface, we recreate the carbon rings formation initial steps, by adding one by one carbon atoms over M(1 1 1) surface. With this strategy, the chemical bonding is always present until the graphene layer is well formed, in which case the GGA neglects van der Waals dispersive forces. We investigate the electronic properties by studying the band structure and the density of states.

Medicinal flowers. IV. Marigold. (2): Structures of new ionone and sesquiterpene glycosides from Egyptian Calendula officinalis.

PubMed

Marukami, T; Kishi, A; Yoshikawa, M

2001-08-01

Following the characterization of hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and the structure elucidation of calendasaponins A, B, C, and D, two new ionone glucosides (officinosides A and B), and two sesquiterpene oligoglycosides (officinosides C and D), were isolated from the flowers of Egyptian Calendula officinalis. The structures of the officinosides were elucidated on the basis of chemical and physicochemical evidence.

UPLC-QTOF-MS/MS-guided isolation and purification of sulfur-containing derivatives from sulfur-fumigated edible herbs, a case study on ginseng.

PubMed

Zhang, Li; Shen, Hong; Xu, Jun; Xu, Jin-Di; Li, Zhen-Ling; Wu, Jie; Zou, Ye-Ting; Liu, Li-Fang; Li, Song-Lin

2018-04-25

In this study, a novel ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-guidance strategy was proposed for preparation of sulfur-containing derivatives in sulfur-fumigated edible herbs. Being versatile in both chromatographic separation and mass spectrometric detection, UPLC-QTOF-MS/MS was inducted into each experimental step for multifaceted purposes including finding, tracking, purity determination and structural elucidation of targeted compounds as well as UPLC-HPLC chromatographic conditions transplantation, whereby the isolation and purification procedures were greatly facilitated. Using this strategy, a new sulfur-containing ginsenoside Rg 1 derivative (named compound I) was obtained from sulfur-fumigated ginseng. The chemical structure of compound I was elucidated to be (3β, 6α, 12β)-3, 12-dihydroxydammar-25-ene-6, 20-diylbis-β-d-glucopyranoside, 24-sulfonic acid by QTOF-MS/MS, 1 H-NMR and 13 C-NMR analysis, and its generation mechanisms by sulfur-fumigation were accordingly discussed. The research deliverable suggests that the UPLC-QTOF-MS/MS-guidance strategy is promising for targeted preparation of sulfur-containing derivatives from sulfur-fumigated edible herbs. Copyright © 2017 Elsevier Ltd. All rights reserved.

(3, 2)D 1H, 13C BIRDr,X-HSQC-TOCSY for NMR structure elucidation of mixtures: application to complex carbohydrates.

PubMed

Brodaczewska, Natalia; Košťálová, Zuzana; Uhrín, Dušan

2018-02-01

Overlap of NMR signals is the major cause of difficulties associated with NMR structure elucidation of molecules contained in complex mixtures. A 2D homonuclear correlation spectroscopy in particular suffers from low dispersion of 1 H chemical shifts; larger dispersion of 13 C chemical shifts is often used to reduce this overlap, while still providing the proton-proton correlation information e.g. in the form of a 2D 1 H, 13 C HSQC-TOCSY experiment. For this methodology to work, 13 C chemical shift must be resolved. In case of 13 C chemical shifts overlap, 1 H chemical shifts can be used to achieve the desired resolution. The proposed (3, 2)D 1 H, 13 C BIRD r,X -HSQC-TOCSY experiment achieves this while preserving singlet character of cross peaks in the F 1 dimension. The required high-resolution in the 13 C dimension is thus retained, while the cross peak overlap occurring in a regular HSQC-TOCSY experiment is eliminated. The method is illustrated on the analysis of a complex carbohydrate mixture obtained by depolymerisation of a fucosylated chondroitin sulfate isolated from the body wall of the sea cucumber Holothuria forskali.

Classification of the Pospiviroidae based on their structural hallmarks.

PubMed

Giguère, Tamara; Perreault, Jean-Pierre

2017-01-01

The simplest known plant pathogens are the viroids. Because of their non-coding single-stranded circular RNA genome, they depend on both their sequence and their structure for both a successful infection and their replication. In the recent years, important progress in the elucidation of their structures was achieved using an adaptation of the selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) protocol in order to probe viroid structures in solution. Previously, SHAPE has been adapted to elucidate the structures of all of the members of the family Avsunviroidae, as well as those of a few members of the family Pospiviroidae. In this study, with the goal of providing an entire compendium of the secondary structures of the various viroid species, a total of thirteen new Pospiviroidae members were probed in solution using the SHAPE protocol. More specifically, the secondary structures of eleven species for which the genus was previously known were initially elucidated. At this point, considering all of the SHAPE elucidated secondary structures, a classification system for viroids in their respective genera was proposed. On the basis of the structural classification reported here, the probings of both the Grapevine latent viroid and the Dahlia latent viroid provide sound arguments for the determination of their respective genera, which appear to be Apscaviroid and Hostuviroid, respectively. More importantly, this study provides the complete repertoire of the secondary structures, mapped in solution, of all of the accepted viroid species reported thus far. In addition, a classification scheme based on structural hallmarks, an important tool for many biological studies, is proposed.

Classification of the Pospiviroidae based on their structural hallmarks

PubMed Central

Giguère, Tamara

2017-01-01

The simplest known plant pathogens are the viroids. Because of their non-coding single-stranded circular RNA genome, they depend on both their sequence and their structure for both a successful infection and their replication. In the recent years, important progress in the elucidation of their structures was achieved using an adaptation of the selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE) protocol in order to probe viroid structures in solution. Previously, SHAPE has been adapted to elucidate the structures of all of the members of the family Avsunviroidae, as well as those of a few members of the family Pospiviroidae. In this study, with the goal of providing an entire compendium of the secondary structures of the various viroid species, a total of thirteen new Pospiviroidae members were probed in solution using the SHAPE protocol. More specifically, the secondary structures of eleven species for which the genus was previously known were initially elucidated. At this point, considering all of the SHAPE elucidated secondary structures, a classification system for viroids in their respective genera was proposed. On the basis of the structural classification reported here, the probings of both the Grapevine latent viroid and the Dahlia latent viroid provide sound arguments for the determination of their respective genera, which appear to be Apscaviroid and Hostuviroid, respectively. More importantly, this study provides the complete repertoire of the secondary structures, mapped in solution, of all of the accepted viroid species reported thus far. In addition, a classification scheme based on structural hallmarks, an important tool for many biological studies, is proposed. PMID:28783761

Novel benzothiophene 1,1-dioxide deoxygenation path for the microwave-assisted synthesis of substituted benzothiophene-fused pyrrole derivatives.

PubMed

Karakuş, Hamza; Dürüst, Yaşar

2017-02-01

The reaction of C-(4-substituted-phenyl)-N-(benzoyl)-N-methylglycines with benzo[b]thiophene 1,1-dioxide unexpectedly gave benzothiophene-fused pyrrole derivatives in toluene under microwave irradiation via a cycloaddition and metal-free Pummerer-type sulfone deoxygenation path. In order to obtain the desired sulfone derivatives, the sulfide group underwent oxidation with m-CPBA to afford sulfones. The structures of all the new products were elucidated by spectroscopic/physical methods and, in two cases, by X-ray diffraction.

Nature's Anti-Alzheimer's Drug: Isolation and Structure Elucidation of Galantamine from "Leucojum Aestivum"

ERIC Educational Resources Information Center

Halpin, Catherine M.; Reilly, Ciara; Walsh, John J.

2010-01-01

The discovery that galantamine penetrates the blood-brain barrier has led to its clinical use in the treatment of choline-deficiency conditions in the brain, such as Alzheimer's disease. This experiment involves the isolation and structure elucidation of galantamine from "Leucojum aestivum". Isolation of the alkaloid constituents in "L. aestivum"…

Influence of coating defects on the corrosion behavior of cold sprayed refractory metals

NASA Astrophysics Data System (ADS)

Kumar, S.; Rao, A. Arjuna

2017-02-01

The defects in the cold sprayed coatings are critical in the case of corrosion performances of the coatings in aggressive conditions. To understand the influence of coating defects on corrosion, immersion tests have been carried out in HF solution for the cold sprayed and heat treated Titanium, Tantalum and Niobium coatings. Long duration immersion tests reveal inhomogeneous weight losses of the samples prepared at different heat treatment conditions. The weight loss for different coatings has been well corroborated with the coating defects and microstructures. Chemical and micro structural analysis elucidates the reason behind the inhomogeneous performance of different type of cold sprayed coatings in corrosion medium. In the case of cold sprayed titanium, formation of stable oxide along the inter-splat boundary hinders the aggressive attack of the corrosion medium which is not so in other cases.

Liquid chromatography with mass spectrometry method based two-step precursor ion scanning for the structural elucidation of flavonoids.

PubMed

Li, Yong; Pang, Tao; Shi, Junli; Lu, Xiuping; Deng, Jianhua; Lin, Qian

2014-11-01

Plant flavonoids are very important secondary metabolites for insect and virus control of their host plant and are potent nutrients for humans. To be able to understand the bioavailability and functions of plant flavonoids, it is necessary to reveal their exact chemical structures. Liquid chromatography with tandem mass spectrometry is a powerful approach for structural elucidation of metabolites. In this report, a two-step precursor ion scanning based liquid chromatography with tandem mass spectrometry method was developed for the structural elucidation of plant flavonoids. The established method consists of the two-step precursor ions scanning for possible flavonoids extraction, MS(2) fragment spectra acquisition and comparison with an online database, liquid chromatography retention rules correction, and commercial standards verification. The developed method was used for the structure elucidation of flavonoids in flowers and leaves of tobacco (Nicotiana tabacum), and 17 flavonoids were identified in the tobacco variety Yunyan 97. Nine of the 17 identified flavonoids were considered to be found in tobacco flowers or/and leaves for the first time based on the available references. This method was proved to be very effective and can be used for the identification of flavonoids in other plants. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two new stilbene trimers from Cynodon dactylon.

PubMed

Li, Bi-Jun; Liu, Yao; Gu, Ai-Tong; Zhang, Qing; Chen, Lei; Wang, Shu-Mei; Wang, Feng

2017-11-01

Many naturally occurring oligostilbenes have drawn considerable attention because of their intricate structures and diverse bioactivities. Two new stilbene trimers, cystibenetrimerol A (1) and cystibenetrimerol B (2) were isolated from the dried grass of Cynodon dactylon (L.) Pers. The planar structures and stereo configurations of them were elucidated by spectroscopic and spectrometric methods. The isolation and structures elucidation of two new stilbene trimers suggested the ordinary grass belonging to the family Poaceae may be a rich source of stilbene oligomers.

Elucidation of the structure-property relationship of p-type organic semiconductors through rapid library construction via a one-pot, Suzuki-Miyaura coupling reaction.

PubMed

Fuse, Shinichiro; Matsumura, Keisuke; Wakamiya, Atsushi; Masui, Hisashi; Tanaka, Hiroshi; Yoshikawa, Susumu; Takahashi, Takashi

2014-09-08

The elucidation of the structure-property relationship is an important issue in the development of organic electronics. Combinatorial synthesis and the evaluation of systematically modified compounds is a powerful tool in the work of elucidating structure-property relationships. In this manuscript, D-π-A structure, 32 p-type organic semiconductors were rapidly synthesized via a one-pot, Suzuki-Miyaura coupling with subsequent Knoevenagel condensation. Evaluation of the solubility and photovoltaic properties of the prepared compounds revealed that the measured solubility was strongly correlated with the solubility parameter (SP), as reported by Fedors. In addition, the SPs were correlated with the Jsc of thin-film organic solar cells prepared using synthesized compounds. Among the evaluated photovoltaic properties of the solar cells, Jsc and Voc had strong correlations with the photoconversion efficiency (PCE).

pH-Controlled Oxidation of an Aromatic Ketone: Structural Elucidation of the Products of Two Green Chemical Reactions

ERIC Educational Resources Information Center

Ballard, C. Eric

2010-01-01

A laboratory experiment emphasizing the structural elucidation of organic compounds has been developed as a discovery exercise. The "unknown" compounds are the products of the pH-controlled oxidation of 4'-methoxyacetophenone with bleach. The chemoselectivity of this reaction is highly dependent on the pH of the reaction media: under basic…

Nature's Cholesterol-Lowering Drug: Isolation and Structure Elucidation of Lovastatin from Red Yeast Rice-Containing Dietary Supplements

ERIC Educational Resources Information Center

Nazri, Maisarah Mohd; Samat, Farah D.; Kavanagh, Pierce V.; Walsh, John J.

2012-01-01

Red yeast rice, produced by fermenting the fungus, "Monascus purpureus", on rice ("Oryza sativa" L. gramineae), is commonly used as a dietary supplement. It contains lovastatin, a member of the statin family of compounds, and is licensed for use as a cholesterol-lowering agent. This experiment involves the isolation and structure elucidation of…

Elucidating the electronic structure of supported gold nanoparticles and its relevance to catalysis by means of hard X-ray photoelectron spectroscopy

DOE PAGES

Reinecke, Benjamin N.; Kuhl, Kendra P.; Ogasawara, Hirohito; ...

2015-12-31

We report on the electronic structure of Au (gold) nanoparticles supported onto TiO 2 with a goal of elucidating the most important effects that contribute to their high catalytic activity. We synthesize and characterize with high resolution transmission electron microscopy (HRTEM) 3.4, 5.3, and 9.5 nm diameter TiO 2-supported Au nanoparticles with nearly spherical shape and measure their valence band using Au 5d subshell sensitive hard X-ray photoelectron spectroscopy (HAXPES) conducted at Spring-8. Based on density functional theory (DFT) calculations of various Au surface structures, we interpret the observed changes in the Au 5d valence band structure as a functionmore » of size in terms of an increasing percentage of Au atoms at corners/edges for decreasing particle size. Finally, this work elucidates how Au coordination number impacts the electronic structure of Au nanoparticles, ultimately giving rise to their well-known catalytic activity.« less

Identification of a novel structure in heparin generated by potassium permanganate oxidation

PubMed Central

Beccati, Daniela; Roy, Sucharita; Yu, Fei; Gunay, Nur Sibel; Capila, Ishan; Lech, Miroslaw; Linhardt, Robert J.; Venkataraman, Ganesh

2012-01-01

The worldwide heparin contamination crisis in 2008 led health authorities to take fundamental steps to better control heparin manufacture, including implementing appropriate analytical and bio-analytical methods to ensure production and release of high quality heparin sodium product. Consequently, there is an increased interest in the identification and structural elucidation of unusually modified structures that may be present in heparin. Our study focuses on the structural elucidation of species that give rise to a signal observed at 2.10 ppm in the N-acetyl region of the 1H NMR spectrum of some pharmaceutical grade heparin preparations. Structural elucidation experiments were carried out using homonuclear (COSY, TOSCY and NOESY) and heteronuclear (HSQC, HSQC-DEPT, HMQC-COSY, HSQC-TOCSY, and HMBC) 2D NMR spectroscopy on both heparin as well as heparin-like model compounds. Our results identify a novel type of oxidative modification of the heparin chain that results from a specific step in the manufacturing process used to prepare heparin. PMID:25147414

Aging mechanisms in amorphous phase-change materials.

PubMed

Raty, Jean Yves; Zhang, Wei; Luckas, Jennifer; Chen, Chao; Mazzarello, Riccardo; Bichara, Christophe; Wuttig, Matthias

2015-06-24

Aging is a ubiquitous phenomenon in glasses. In the case of phase-change materials, it leads to a drift in the electrical resistance, which hinders the development of ultrahigh density storage devices. Here we elucidate the aging process in amorphous GeTe, a prototypical phase-change material, by advanced numerical simulations, photothermal deflection spectroscopy and impedance spectroscopy experiments. We show that aging is accompanied by a progressive change of the local chemical order towards the crystalline one. Yet, the glass evolves towards a covalent amorphous network with increasing Peierls distortion, whose structural and electronic properties drift away from those of the resonantly bonded crystal. This behaviour sets phase-change materials apart from conventional glass-forming systems, which display the same local structure and bonding in both phases.

Mass Spectra-Based Framework for Automated Structural Elucidation of Metabolome Data to Explore Phytochemical Diversity

PubMed Central

Matsuda, Fumio; Nakabayashi, Ryo; Sawada, Yuji; Suzuki, Makoto; Hirai, Masami Y.; Kanaya, Shigehiko; Saito, Kazuki

2011-01-01

A novel framework for automated elucidation of metabolite structures in liquid chromatography–mass spectrometer metabolome data was constructed by integrating databases. High-resolution tandem mass spectra data automatically acquired from each metabolite signal were used for database searches. Three distinct databases, KNApSAcK, ReSpect, and the PRIMe standard compound database, were employed for the structural elucidation. The outputs were retrieved using the CAS metabolite identifier for identification and putative annotation. A simple metabolite ontology system was also introduced to attain putative characterization of the metabolite signals. The automated method was applied for the metabolome data sets obtained from the rosette leaves of 20 Arabidopsis accessions. Phenotypic variations in novel Arabidopsis metabolites among these accessions could be investigated using this method. PMID:22645535

Glucosinolate structures in evolution.

PubMed

Agerbirk, Niels; Olsen, Carl Erik

2012-05-01

By 2000, around 106 natural glucosinolates (GSLs) were probably documented. In the past decade, 26 additional natural GSL structures have been elucidated and documented. Hence, the total number of documented GSLs from nature by 2011 can be estimated to around 132. A considerable number of additional suggested structures are concluded not to be sufficiently documented. In many cases, NMR spectroscopy would have provided the missing structural information. Of the GSLs documented in the past decade, several are of previously unexpected structures and occur at considerable levels. Most originate from just four species: Barbarea vulgaris, Arabidopsis thaliana, Eruca sativa and Isatis tinctoria. Acyl derivatives of known GSLs comprised 15 of the 26 newly documented structures, while the remaining exhibited new substitution patterns or chain length, or contained a mercapto group or related thio-functionality. GSL identification methods are reviewed, and the importance of using authentic references and structure-sensitive detection methods such as MS and NMR is stressed, especially when species with relatively unknown chemistry are analyzed. An example of qualitative GSL analysis is presented with experimental details (group separation and HPLC of both intact and desulfated GSLs, detection and structure determination by UV, MS, NMR and susceptibility to myrosinase) with emphasis on the use of NMR for structure elucidation of even minor GSLs and GSL hydrolysis products. The example includes identification of a novel GSL, (R)-2-hydroxy-2-(3-hydroxyphenyl)ethylglucosinolate. Recent investigations of GSL evolution, based on investigations of species with well established phylogeny, are reviewed. From the relatively few such investigations, it is already clear that GSL profiles are regularly subject to evolution. This result is compatible with natural selection for specific GSL side chains. The probable existence of structure-specific GSL catabolism in intact plants suggests that biochemical evolution of GSLs has more complex implications than the mere liberation of a different hydrolysis product upon tissue disruption. Copyright © 2012 Elsevier Ltd. All rights reserved.

4D Origami by Smart Embroidery.

PubMed

Stoychev, Georgi; Razavi, Mir Jalil; Wang, Xianqiao; Ionov, Leonid

2017-09-01

There exist many methods for processing of materials: extrusion, injection molding, fibers spinning, 3D printing, to name a few. In most cases, materials with a static, fixed shape are produced. However, numerous advanced applications require customized elements with reconfigurable shape. The few available techniques capable of overcoming this problem are expensive and/or time-consuming. Here, the use of one of the most ancient technologies for structuring, embroidering, is proposed to generate sophisticated patterns of active materials, and, in this way, to achieve complex actuation. By combining experiments and computational modeling, the fundamental rules that can predict the folding behavior of sheets with a variety of stitch-patterns are elucidated. It is demonstrated that theoretical mechanics analysis is only suitable to predict the behavior of the simplest experimental setups, whereas computer modeling gives better predictions for more complex cases. Finally, the applicability of the rules by designing basic origami structures and wrinkling substrates with controlled thermal insulation properties is shown. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans.

PubMed

Xu, Bin; Woodroffe, Abigail; Rodriguez-Murillo, Laura; Roos, J Louw; van Rensburg, Elizabeth J; Abecasis, Gonçalo R; Gogos, Joseph A; Karayiorgou, Maria

2009-09-29

To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease.

Utility of surface enhanced Raman spectroscopy (SERS) for elucidation and simultaneous determination of some penicillins and penicilloic acid using hydroxylamine silver nanoparticles.

PubMed

El-Zahry, Marwa R; Refaat, Ibrahim H; Mohamed, Horria A; Rosenberg, Erwin; Lendl, Bernhard

2015-11-01

Elucidation and quantitative determination of some of commonly used penicillins (ampicillin, penicillin G and carbenicillin) in the presence of their main degradation product (penicilloic acid) were developed. Forced acidic and basic degradation processes were applied at different time intervals. The formed degradation products were elucidated and quantified using surface enhanced Raman spectroscopy (SERS). Silver nanoparticles (AgNPs) prepared by reduction of silver nitrate using hydroxylamine-HCl in alkaline medium were used as SERS substrate. The results obtained in SERS were confirmed by the application of LC/MS method. The concentration range was 100-600 ng/ml in case of the studied penicillins and 100-700 ng/ml in case of penicilloic acid. An excellent correlation coefficient was found in case of ampicillin (r=0.9993) and in the case of penicilloic acid (r=0.9997). Validation procedures were carried out including precision, robustness and accuracy by comparing F- and t-values of both the proposed and reported methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Regimes of Flow over Complex Structures of Endothelial Glycocalyx: A Molecular Dynamics Simulation Study.

PubMed

Jiang, Xi Zhuo; Feng, Muye; Ventikos, Yiannis; Luo, Kai H

2018-04-10

Flow patterns on surfaces grafted with complex structures play a pivotal role in many engineering and biomedical applications. In this research, large-scale molecular dynamics (MD) simulations are conducted to study the flow over complex surface structures of an endothelial glycocalyx layer. A detailed structure of glycocalyx has been adopted and the flow/glycocalyx system comprises about 5,800,000 atoms. Four cases involving varying external forces and modified glycocalyx configurations are constructed to reveal intricate fluid behaviour. Flow profiles including temporal evolutions and spatial distributions of velocity are illustrated. Moreover, streamline length and vorticity distributions under the four scenarios are compared and discussed to elucidate the effects of external forces and glycocalyx configurations on flow patterns. Results show that sugar chain configurations affect streamline length distributions but their impact on vorticity distributions is statistically insignificant, whilst the influence of the external forces on both streamline length and vorticity distributions are trivial. Finally, a regime diagram for flow over complex surface structures is proposed to categorise flow patterns.

Structure elucidation of a novel oligosaccharide (Medalose) from camel milk

NASA Astrophysics Data System (ADS)

Gangwar, Lata; Singh, Rinku; Deepak, Desh

2018-02-01

Free oligosaccharides are the third most abundant solid component in milk after lactose and lipids. The study of milk oligosaccharides indicate that nutrients are not only benefits the infant's gut but also perform a number of other functions which include stimulation of growth, receptor analogues to inhibit binding of pathogens and substances that promote postnatal brain development. Surveys reveal that camel milk oligosaccharides possess varied biological activities that help in the treatment of diabetes, asthma, anaemia, piles and also a food supplement to milking mothers. In this research, camel milk was selected for its oligosaccharide contents, which was then processed by Kobata and Ginsburg method followed by the HPLC and CC techniques. Structure elucidation of isolated compound was done by the chemical degradation, chemical transformation and comparison of chemical shift of NMR data of natural and acetylated oligosaccharide structure reporter group theory, the 1H, 13C NMR, 2D-NMR (COSY, TOCSY and HSQC) techniques, and mass spectrometry. The structure was elucidated as under: MEDALOSE

Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton.

PubMed

Naman, C Benjamin; Li, Jie; Moser, Arvin; Hendrycks, Jeffery M; Benatrehina, P Annécie; Chai, Heebyung; Yuan, Chunhua; Keller, William J; Kinghorn, A Douglas

2015-06-19

Melanodiol 4″-O-protocatechuate (1) and melanodiol (2) represent novel flavonoid derivatives isolated from a botanical dietary supplement ingredient, dried black chokeberry (Aronia melanocarpa) fruit juice. These noncrystalline compounds possess an unprecedented fused pentacyclic core with two contiguous hemiketals. Due to having significant hydrogen deficiency indices, their structures were determined using computer-assisted structure elucidation software. The in vitro hydroxyl radical-scavenging and quinone reductase-inducing activity of each compound are reported, and a plausible biogenetic scheme is proposed.

Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton

PubMed Central

Naman, C. Benjamin; Li, Jie; Moser, Arvin; Hendrycks, Jeffery M.; Benatrehina, P. Annécie; Chai, Heebyung; Yuan, Chunhua; Keller, William J.; Kinghorn, A. Douglas

2015-01-01

Melanodiol 4″-O-protocatechuate (1) and melanodiol (2) represent novel flavonoid derivatives isolated from a botanical dietary supplement ingredient, dried black chokeberry (Aronia melanocarpa) fruit juice. These non-crystalline compounds possess an unprecedented fused pentacyclic core with two contiguous hemiketals. Due to having significant hydrogen deficiency indices, their structures were determined using computer-assisted structure elucidation software. The in vitro hydroxyl radical-scavenging and quinone reductase-inducing activity of each compound are reported, and a plausible biogenetic scheme is proposed PMID:26030740

Combining density functional theory (DFT) and pair distribution function (PDF) analysis to solve the structure of metastable materials: the case of metakaolin.

PubMed

White, Claire E; Provis, John L; Proffen, Thomas; Riley, Daniel P; van Deventer, Jannie S J

2010-04-07

Understanding the atomic structure of complex metastable (including glassy) materials is of great importance in research and industry, however, such materials resist solution by most standard techniques. Here, a novel technique combining thermodynamics and local structure is presented to solve the structure of the metastable aluminosilicate material metakaolin (calcined kaolinite) without the use of chemical constraints. The structure is elucidated by iterating between least-squares real-space refinement using neutron pair distribution function data, and geometry optimisation using density functional modelling. The resulting structural representation is both energetically feasible and in excellent agreement with experimental data. This accurate structural representation of metakaolin provides new insight into the local environment of the aluminium atoms, with evidence of the existence of tri-coordinated aluminium. By the availability of this detailed chemically feasible atomic description, without the need to artificially impose constraints during the refinement process, there exists the opportunity to tailor chemical and mechanical processes involving metakaolin and other complex metastable materials at the atomic level to obtain optimal performance at the macro-scale.

Towards fully automated structure-based function prediction in structural genomics: a case study.

PubMed

Watson, James D; Sanderson, Steve; Ezersky, Alexandra; Savchenko, Alexei; Edwards, Aled; Orengo, Christine; Joachimiak, Andrzej; Laskowski, Roman A; Thornton, Janet M

2007-04-13

As the global Structural Genomics projects have picked up pace, the number of structures annotated in the Protein Data Bank as hypothetical protein or unknown function has grown significantly. A major challenge now involves the development of computational methods to assign functions to these proteins accurately and automatically. As part of the Midwest Center for Structural Genomics (MCSG) we have developed a fully automated functional analysis server, ProFunc, which performs a battery of analyses on a submitted structure. The analyses combine a number of sequence-based and structure-based methods to identify functional clues. After the first stage of the Protein Structure Initiative (PSI), we review the success of the pipeline and the importance of structure-based function prediction. As a dataset, we have chosen all structures solved by the MCSG during the 5 years of the first PSI. Our analysis suggests that two of the structure-based methods are particularly successful and provide examples of local similarity that is difficult to identify using current sequence-based methods. No one method is successful in all cases, so, through the use of a number of complementary sequence and structural approaches, the ProFunc server increases the chances that at least one method will find a significant hit that can help elucidate function. Manual assessment of the results is a time-consuming process and subject to individual interpretation and human error. We present a method based on the Gene Ontology (GO) schema using GO-slims that can allow the automated assessment of hits with a success rate approaching that of expert manual assessment.

Recent advances in jointed quantum mechanics and molecular mechanics calculations of biological macromolecules: schemes and applications coupled to ab initio calculations.

PubMed

Hagiwara, Yohsuke; Tateno, Masaru

2010-10-20

We review the recent research on the functional mechanisms of biological macromolecules using theoretical methodologies coupled to ab initio quantum mechanical (QM) treatments of reaction centers in proteins and nucleic acids. Since in most cases such biological molecules are large, the computational costs of performing ab initio calculations for the entire structures are prohibitive. Instead, simulations that are jointed with molecular mechanics (MM) calculations are crucial to evaluate the long-range electrostatic interactions, which significantly affect the electronic structures of biological macromolecules. Thus, we focus our attention on the methodologies/schemes and applications of jointed QM/MM calculations, and discuss the critical issues to be elucidated in biological macromolecular systems. © 2010 IOP Publishing Ltd

Edible oil structures at low and intermediate concentrations. II. Ultra-small angle X-ray scattering of in situ tristearin solids in triolein

NASA Astrophysics Data System (ADS)

Peyronel, Fernanda; Ilavsky, Jan; Mazzanti, Gianfranco; Marangoni, Alejandro G.; Pink, David A.

2013-12-01

Ultra-small angle X-ray scattering has been used for the first time to elucidate, in situ, the aggregation structure of a model edible oil system. The three-dimensional nano- to micro-structure of tristearin solid particles in triolein solvent was investigated using 5, 10, 15, and 20% solids. Three different sample preparation procedures were investigated: two slow cooling rates of 0.5°/min, case 1 (22 days of storage at room temperature) and case 2 (no storage), and one fast cooling of 30°/min, case 3 (no storage). The length scale investigated, by using the Bonse-Hart camera at beamline ID-15D at the Advanced Photon Source, Argonne National Laboratory, covered the range from 300 Å to 10 μm. The unified fit and the Guinier-Porod models in the Irena software were used to fit the data. The former was used to fit 3 structural levels. Level 1 structures showed that the primary scatterers were essentially 2-dimensional objects for the three cases. The scatterers possessed lateral dimensions between 1000 and 4300 Å. This is consistent with the sizes of crystalline nanoplatelets present which were observed using cryo-TEM. Level 2 structures were aggregates possessing radii of gyration, Rg2 between 1800 Å and 12000 Å and fractal dimensions of either D2=1 for case 3 or 1.8≤D2≤2.1 for case 1 and case 2. D2 = 1 is consistent with unaggregated 1-dimensional objects. 1.8 ≤ D2 ≤ 2.1 is consistent with these 1-dimensional objects (below) forming structures characteristic of diffusion or reaction limited cluster-cluster aggregation. Level 3 structures showed that the spatial distribution of the level 2 structures was uniform, on the average, for case 1, with fractal dimension D3≈3 while for case 2 and case 3 the fractal dimension was D3≈2.2, which suggested that the large-scale distribution had not come to equilibrium. The Guinier-Porod model showed that the structures giving rise to the aggregates with a fractal dimension given by D2 in the unified fit level 2 model were cylinders described by the parameter s ≈1 in the Guinier-Porod model. The size of the base of these cylinders was in agreement with the cryo-TEM observations as well as with the results of the level 1 unified fit model. By estimating the size of the nanoplatelets and understanding the structures formed via their aggregation, it will be possible to engineer novel lipids systems that embody desired functional characteristics.

Toward structural elucidation of the gamma-secretase complex

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

Li, H.; Wolfe, M. S.; Selkoe, D. J.

2009-03-11

{gamma}-Secretase is an intramembrane protease complex that mediates the Notch signaling pathway and the production of amyloid {beta}-proteins. As such, this enzyme has emerged as an important target for development of novel therapeutics for Alzheimer disease and cancer. Great progress has been made in the identification and characterization of the membrane complex and its biological functions. One major challenge now is to illuminate the structure of this fascinating and important protease at atomic resolution. Here, we review recent progress on biochemical and biophysical probing of the structure of the four-component complex and discuss obstacles and potential pathways toward elucidating itsmore » detailed structure.« less

Stance and strategy: post-structural perspective and post-colonial engagement to develop nursing knowledge.

PubMed

Sochan, Anne M

2011-07-01

How should nursing knowledge advance? This exploration contextualizes its evolution past and present. In addressing how it evolved in the past, a probable historical evolution of its development draws on the perspectives of Frank & Gills's World System Theory, Kuhn's treatise on Scientific Revolutions, and Foucault's notions of Discontinuities in scientific knowledge development. By describing plausible scenarios of how nursing knowledge evolved, I create a case for why nursing knowledge developers should adopt a post-structural stance in prioritizing their research agenda(s). Further, by adopting a post-structural stance, I create a case on how nurses can advance their disciplinary knowledge using an engaging post-colonial strategy. Given an interrupted history caused by influence(s) constraining nursing's knowledge development by power structures external, and internal, to nursing, knowledge development can evolve in the future by drawing on post-structural interpretation, and post-colonial strategy. The post-structural writings of Deleuze & Guattari's understanding of 'Nomadology' as a subtle means to resist being constrained by existing knowledge development structures, might be a useful stance to understanding the urgency of why nursing knowledge should advance addressing the structural influences on its development. Furthermore, Bhabha's post-colonial elucidation of 'Hybridity' as an equally discreet means to change the culture of those constraining structures is an appropriate strategy to enact how nursing knowledge developers can engage with existing power structures, and simultaneously influence that engagement. Taken together, 'post-structural stance' and 'post-colonial strategy' can refocus nursing scholarship to learn from its past, in order to develop relevant disciplinary knowledge in its future. © 2011 Blackwell Publishing Ltd.

Marvels of enzyme catalysis at true atomic resolution: distortions, bond elongations, hidden flips, protonation states and atom identities.

PubMed

Neumann, Piotr; Tittmann, Kai

2014-12-01

Although general principles of enzyme catalysis are fairly well understood nowadays, many important details of how exactly the substrate is bound and processed in an enzyme remain often invisible and as such elusive. In fortunate cases, structural analysis of enzymes can be accomplished at true atomic resolution thus making possible to shed light on otherwise concealed fine-structural traits of bound substrates, intermediates, cofactors and protein groups. We highlight recent structural studies of enzymes using ultrahigh-resolution X-ray protein crystallography showcasing its enormous potential as a tool in the elucidation of enzymatic mechanisms and in unveiling fundamental principles of enzyme catalysis. We discuss the observation of seemingly hyper-reactive, physically distorted cofactors and intermediates with elongated scissile substrate bonds, the detection of 'hidden' conformational and chemical equilibria and the analysis of protonation states with surprising findings. In delicate cases, atomic resolution is required to unambiguously disclose the identity of atoms as demonstrated for the metal cluster in nitrogenase. In addition to the pivotal structural findings and the implications for our understanding of enzyme catalysis, we further provide a practical framework for resolution enhancement through optimized data acquisition and processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural determinants of arrestin functions.

PubMed

Gurevich, Vsevolod V; Gurevich, Eugenia V

2013-01-01

Arrestins are a small protein family with only four members in mammals. Arrestins demonstrate an amazing versatility, interacting with hundreds of different G protein-coupled receptor (GPCR) subtypes, numerous nonreceptor signaling proteins, and components of the internalization machinery, as well as cytoskeletal elements, including regular microtubules and centrosomes. Here, we focus on the structural determinants that mediate various arrestin functions. The receptor-binding elements in arrestins were mapped fairly comprehensively, which set the stage for the construction of mutants targeting particular GPCRs. The elements engaged by other binding partners are only now being elucidated and in most cases we have more questions than answers. Interestingly, even very limited and imprecise identification of structural requirements for the interaction with very few other proteins has enabled the development of signaling-biased arrestin mutants. More comprehensive understanding of the structural underpinning of different arrestin functions will pave the way for the construction of arrestins that can link the receptor we want to the signaling pathway of our choosing. Copyright © 2013 Elsevier Inc. All rights reserved.

Structural Determinants of Arrestin Functions

PubMed Central

Gurevich, Vsevolod V.; Gurevich, Eugenia V.

2015-01-01

Arrestins are a small protein family with only four members in mammals. Arrestins demonstrate an amazing versatility, interacting with hundreds of different G protein-coupled receptor (GPCR) subtypes, numerous nonreceptor signaling proteins, and components of the internalization machinery, as well as cytoskeletal elements, including regular microtubules and centrosomes. Here, we focus on the structural determinants that mediate various arrestin functions. The receptor-binding elements in arrestins were mapped fairly comprehensively, which set the stage for the construction of mutants targeting particular GPCRs. The elements engaged by other binding partners are only now being elucidated and in most cases we have more questions than answers. Interestingly, even very limited and imprecise identification of structural requirements for the interaction with very few other proteins has enabled the development of signaling-biased arrestin mutants. More comprehensive understanding of the structural underpinning of different arrestin functions will pave the way for the construction of arrestins that can link the receptor we want to the signaling pathway of our choosing. PMID:23764050

The influence of air-filled structures on wave propagation and beam formation of a pygmy sperm whale (Kogia breviceps) in horizontal and vertical planes.

PubMed

Song, Zhongchang; Zhang, Yu; Thornton, Steven W; Li, Songhai; Dong, Jianchen

2017-10-01

The wave propagation, sound field, and transmission beam pattern of a pygmy sperm whale (Kogia breviceps) were investigated in both the horizontal and vertical planes. Results suggested that the signals obtained at both planes were similarly characterized with a high peak frequency and a relatively narrow bandwidth, close to the ones recorded from live animals. The sound beam measured outside the head in the vertical plane was narrower than that of the horizontal one. Cases with different combinations of air-filled structures in both planes were used to study the respective roles in controlling wave propagation and beam formation. The wave propagations and beam patterns in the horizontal and vertical planes elucidated the important reflection effect of the spermaceti and vocal chambers on sound waves, which was highly significant in forming intensive forward sound beams. The air-filled structures, the forehead soft tissues and skull structures formed wave guides in these two planes for emitted sounds to propagate forward.

Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway

NASA Astrophysics Data System (ADS)

Harada, Ryuhei; Kitao, Akio

2013-07-01

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

Two new phenylpropanoid glycosides with interesterification from Scrophularia dentata Royle ex Benth

NASA Astrophysics Data System (ADS)

Zhang, Liuqiang; Yang, Zhuo; Jia, Qi; Dorje, Gaawe; Zhao, Zhili; Guo, Fujiang; Li, Yiming

2013-10-01

Two new phenylpropanoid glycosides (1-2), along with seven known ones (3-9), were isolated from the whole plant of Scrophularia dentata Royle ex Benth. Their structures were elucidated by spectroscopic methods. Among them, compounds 1 and 2 failed to separated, because they can easily transform into each other by acyl migrant reaction. In this paper, the interesterification mechanism was discussed firstly and the rule can be used in the similar structure elucidation in future.

Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature

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

Ruiz, C.; Grubs, R.E.; Jewett, T.

Complex chromosome rearrangements (CCR) are rare structural rearrangements. Currently six cases of prenatally diagnosed balanced de novo CCR have been described. We present two new cases of prenatally ascertained balanced de novo CCR. In the first case, an amniocentesis revealed a balanced de novo three-way CCR involving chromosomes 5,6, and 11 with a pericentric inversion of chromosome 5 [four breaks]. In the second case a balanced de novo rearrangement was identified by amniocentesis which involved a reciprocal translocation between chromosomes 3 and 8 and a CCR involving chromosomes 6,7, and 18 [six breaks]. The use of whole chromosome painting helpedmore » elucidate the nature of these rearrangements. A review of the postnatally ascertained cases suggests that most patients have congenital anomalies, minor anomalies, and/or developmental delay/mental retardation. In addition, there appears to be a relationship between the number of chromosome breaks and the extent of phenotypic effects. The paucity of information regarding prenatally diagnosed CCR and the bias of ascertainment of postnatal CCR cases poses a problem in counseling families. 38 refs., 3 figs., 4 tabs.« less

Fibroblastic connective tissue nevus.

PubMed

Velez, Moises J; Billings, Steven D; Weaver, Joshua A

2016-01-01

Fibroblastic connective tissue nevus (FCTN) is a newly recognized, benign cutaneous mesenchymal lesion of fibroblasts/myofibroblastic lineage, which expands the classification of connective tissue nevi. We present three cases of FCTN and discuss significant clinical, morphologic and immunophenotypic overlap with dermatomyofibroma. Our cases were from young women, aged 32, 24 and 10, and presented as 1.2 and 1 cm nodules on the posterior neck and right upper flank, respectively while presenting as a linear plaque of the right posterior thigh in the latter case. The lesions showed a poorly circumscribed proliferation of hypercellular spindle cells arranged in short to longer intersecting fascicles entrapping adnexal structures. Superficial adipose tissue was also entrapped in one case. The spindle cells had fibroblastic features with pale eosinophilic cytoplasmic extensions and inconspicuous nucleoli. The spindle cells were positive for CD34 in two cases. One case was negative for CD34, smooth muscle actin (SMA), desmin and S100. The overall features were consistent with a diagnosis of FCTN. In two cases, we further elucidated the fibroblastic differentiation of the spindle cells in FCTN with electron microscopy, which has not been previously described. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hydration structure of the α-chymotrypsin substrate binding pocket: the impact of constrained geometry

NASA Astrophysics Data System (ADS)

Carey, Christina; Cheng, Yuen-Kit; Rossky, Peter J.

2000-08-01

The concave substrate binding pocket of α-chymotrypsin binds specifically hydrophobic side chains. In order to understand the hydration structure present in the absence of substrate, and elucidate the character of the solvent displaced on binding, molecular dynamics computer simulation of the solvent in a fully hydrated protein has been carried out and analyzed. The pocket is found to be characterized in terms of a mixed polar and apolar macromolecular surface. It is shown that the simulated solvent structure within it is spatially consistent with that seen via crystallography. The solvent structure is energetically characterized by large losses in hydrogen bonding among solvent molecules except at the mouth of the pocket where exposure to bulk-like solvent is possible. The loss in hydrogen bonding is attributed to the highly constrained geometry available to the solvent, preventing formation of a hydrogen bonding network, with only partial compensation by interactions with the macromolecular surface. The solvent displacement concomitant with substrate binding will therefore be associated with a large enthalpic driving force. This result is at the extreme of a continuum of variable cases of "hydrophobic" hydration, which differ most basically in surface curvature. These range from convex solute surfaces, inducing clathrate-like structures, with negligible hydrogen bond loss, to flat surfaces with significant interfacial loss, to the present concave case with hydrogen bonding losses exceeding 50%.

Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans

PubMed Central

Xu, Bin; Woodroffe, Abigail; Rodriguez-Murillo, Laura; Roos, J. Louw; van Rensburg, Elizabeth J.; Abecasis, Gonçalo R.; Gogos, Joseph A.; Karayiorgou, Maria

2009-01-01

To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease. PMID:19805367

Rehabilitation of a patient with amelogenesis imperfecta using porcelain veneers and CAD/CAM polymer restorations: A clinical report.

PubMed

Saeidi Pour, Reza; Edelhoff, Daniel; Prandtner, Otto; Liebermann, Anja

2015-01-01

The complete dental rehabilitation of patients with a vertical dimension loss (VDL) caused by structural enamel deficits associated with amelogenesis imperfecta (AI) represents a difficult challenge for restorative teams. Accurate analysis and treatment planning that includes esthetic and functional evaluations and adequate material selection are important prerequisites for successful results. Long-term provisional restorations play an important role in exploring and elucidating the patients' esthetic demands and functional needs. Restorative treatment options can vary from requiring only oral hygiene instructions to extensive dental restorations that include composite fillings, ceramic veneers, metal-ceramic, or all-ceramic crowns. This case report describes a full-mouth rehabilitation of a patient with amelogenesis imperfecta including the case planning, bite replacement, preparation, and restoration setting steps with an experimental CAD/CAM polymer and porcelain veneers.

Delusions and the Right Hemisphere: A Review of the Case for the Right Hemisphere as a Mediator of Reality-Based Belief.

PubMed

Gurin, Lindsey; Blum, Sonja

2017-01-01

Delusions are beliefs that remain fixed despite evidence that they are incorrect. Although the precise neural mechanism of delusional belief remains to be elucidated, there is a predominance of right-hemisphere lesions among patients with delusional syndromes accompanied by structural pathology, suggesting that right-hemisphere lesions, or networks with key nodes in the right hemisphere, may be playing a role. The authors discuss the potential theoretical basis and empiric support for a specific right-hemisphere role in delusion production, drawing on its roles in pragmatic communication; perceptual integration; attentional surveillance and anomaly/novelty detection; and belief updating.

The aggregation of the merocyanine dyes, depending of the type of the counterions.

PubMed

Kolev, Tsonko; Koleva, Bojidarka B; Stoyanov, Stanimir; Spiteller, Michael; Petkov, Ivan

2008-10-01

Counterions affect on the substructures formation in the case of the merocyanine dye, 1-methyl-4-[2-(4-hydroxyphenyl)ethenyl)]piridinium] hydrogensquarate both in gas and condense phase. Spectroscopically and structural elucidation of these aggregates have been performed, using solid-state conventional and linear-polarized IR-spectroscopy of oriented colloids as a nematic liquid crystal suspension, UV-vis spectroscopy, HPLC tandem ESI mass spectrometry, 1H and 13C NMR, TGV and DSC. Quantum chemical DFT calculations have been carried out as well. Experimental and theoretical data are compared with analogous ones of corresponding iodide salt of dye studied.

Distribution and incorporation mode of the herbicide MCPA in soil derived organo-clay complexes.

PubMed

Riefer, Patrick; Klausmeyer, Timm; Schmidt, Burkhard; Schäffer, Andreas; Schwarzbauer, Jan

2017-08-03

The incorporation of xenobiotics into soil, especially via covalent bonds or sequestration has a major influence on the environmental behavior including toxicity, mobility, and bioavailability. The incorporation mode of 4-chloro-2-methylphenoxyacetic acid (MCPA) into organo-clay complexes has been investigated under a low (8.5 mg MCPA/kg soil) and high (1000 mg MCPA/kg soil) applied concentration, during an incubation period of up to 120 days. Emphasis was laid on the elucidation of distinct covalent linkages between non-extractable MCPA residues and humic sub-fractions (humic acids, fulvic acids, and humin). The cleavage of compounds by a sequential chemical degradation procedure (OH - , BBr 3 , RuO 4 , TMAH thermochemolysis) revealed for both concentration levels ester/amide bonds as the predominate incorporation modes followed by ether linkages. A possible influence of the soil microbial activity on the mode of incorporation could be observed in case of the high level samples. Structure elucidation identified MCPA as the only nonextractable substance, whereas the metabolite 4-chloro-2-methylphenol was additionally found as bioavailable and bioaccessible compound.

Structure elucidation of the new citharoxazole from the Mediterranean deep-sea sponge Latrunculia (Biannulata) citharistae.

PubMed

Genta-Jouve, Grégory; Francezon, Nellie; Puissant, Alexandre; Auberger, Patrick; Vacelet, Jean; Pérez, Thierry; Fontana, Angelo; Mourabit, Ali Al; Thomas, Olivier P

2011-08-01

Citharoxazole (1), a new batzelline derivative featuring a benzoxazole moiety, was isolated from the Mediterranean deep-sea sponge Latrunculia (Biannulata) citharistae Vacelet, 1969, together with the known batzelline C (2). This is the first chemical study of a Mediterranean Latrunculia species and the benzoxazole moiety is unprecedented for this family of marine natural products. The structure was mainly elucidated by the interpretation of NMR spectra and especially HMBC correlations. Copyright © 2011 John Wiley & Sons, Ltd.

Structure elucidation of organic compounds aided by the computer program system SCANNET

NASA Astrophysics Data System (ADS)

Guzowska-Swider, B.; Hippe, Z. S.

1992-12-01

Recognition of chemical structure is a very important problem currently solved by molecular spectroscopy, particularly IR, UV, NMR and Raman spectroscopy, and mass spectrometry. Nowadays, solution of the problem is frequently aided by the computer. SCANNET is a computer program system for structure elucidation of organic compounds, developed by our group. The structure recognition of an unknown substance is made by comparing its spectrum with successive reference spectra of standard compounds, i.e. chemical compounds of known chemical structure, stored in a spectral database. The computer program system SCANNET consists of six different spectral databases for following the analytical methods: IR, UV, 13C-NMR, 1H-NMR and Raman spectroscopy, and mass spectrometry. A chemist, to elucidate a structure, can use one of these spectral methods or a combination of them and search the appropriate databases. As the result of searching each spectral database, the user obtains a list of chemical substances whose spectra are identical and/or similar to the spectrum input into the computer. The final information obtained from searching the spectral databases is in the form of a list of chemical substances having all the examined spectra, for each type of spectroscopy, identical or simlar to those of the unknown compound.

Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis.

PubMed

Chen, Xi

2015-01-01

The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. © 2015 Elsevier Inc. All rights reserved.

Novel pyrrolinones as N-methyl-D-aspartate receptor antagonists.

PubMed

Poschenrieder, Hermann; Stachel, Hans-Dietrich; Höfner, Georg; Mayer, Peter

2005-04-01

A series of oximes, deriving from 2-arylidene-pyrroline-3,4-diones (7, 8, 22, 23) has been prepared. The presence of tautomers in their solutions has been established by spectroscopic means. The compounds reacted with diazomethane chiefly by N-methylation forming nitrones (10, 11). The analogously prepared 2-arylidene-4-nitropyrrolin-3-ones (12, 13, 24, 25), formally derived from nitrotetramic acids, yielded nitronic acid esters (14, 15, 26) upon reaction with diazomethane. The structures were elucidated by spectral evidence and-in the case of compounds 10 and 20b-by X-ray diffraction analysis. The binding affinity of some of the new compounds toward the N-methyl-d-aspartate (NMDA) (glycine site) receptor has been measured thus providing the basis for further structure-activity relationship studies. Oxime 8b showed the highest binding potency (Ki= 9.2 microM).

Characterization of paliperidone photodegradation products by LC-Q-TOF multistage mass spectrometry.

PubMed

Skibiński, Robert; Komsta, Łukasz; Inglot, Tadeusz

2016-06-01

The photodegradation of paliperidone in aqueous and methanol media under UVA and UVC irradiation was investigated. The identification and structural elucidation of its photodegradation products were performed by the use of the reversed-phase liquid chromatography coupled with accurate mass hybrid Q-TOF mass spectrometry and an atmospheric pressure chemical ionization source. Five degradation products were found and their masses were obtained with high accuracy (1.10-5.26 ppm) based on the TOF (MS) spectra. For the structural elucidation of unknown degradation products MS/MS spectra were also registered. However, for the identification of the main photodegradation product (3-{2-[4-(6-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one) in-source fragmentation connected with collision-induced dissociation was used and MS(3) spectra were finally performed. The photodegradation of paliperidone yields the first-order kinetics in all tested conditions. The aqueous medium was in this case much less stable than the methanol solvent regardless of the irradiation source. Additionally, the toxicity of the analyzed photodegradation products was predicted by the use of ECOSAR software and comparable values of LC50 for the main degradants and the parent compound were obtained. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Computerized modeling techniques predict the 3D structure of H₄R: facts and fiction.

PubMed

Zaid, Hilal; Ismael-Shanak, Siba; Michaeli, Amit; Rayan, Anwar

2012-01-01

The functional characterization of proteins presents a daily challenge r biochemical, medical and computational sciences, especially when the structures are undetermined empirically, as in the case of the Histamine H4 Receptor (H₄R). H₄R is a member of the GPCR superfamily that plays a vital role in immune and inflammatory responses. To date, the concept of GPCRs modeling is highlighted in textbooks and pharmaceutical pamphlets, and this group of proteins has been the subject of almost 3500 publications in the scientific literature. The dynamic nature of determining the GPCRs structure was elucidated through elegant and creative modeling methodologies, implemented by many groups around the world. H₄R which belongs to the GPCR family was cloned in 2000; understandably, its biological activity was reported only 65 times in pubmed. Here we attempt to cover the fundamental concepts of H₄R structure modeling and its implementation in drug discovery, especially those that have been experimentally tested and to highlight some ideas that are currently being discussed on the dynamic nature of H₄R and GPCRs computerized techniques for 3D structure modeling.

Phenolic glycosides with antimalarial activity from Grevillea "Poorinda Queen".

PubMed

Ovenden, Simon P B; Cobbe, Melanie; Kissell, Rebecca; Birrell, Geoffrey W; Chavchich, Marina; Edstein, Michael D

2011-01-28

In search of new antimalarial compounds, three new phenolic glycosides, robustasides E (1), F (2), and G (3), in addition to the known compounds robustaside D (4) and quercetin-7-O-[α-l-rhamnopyranosyl(1→6)-β-d-galactopyranoside] (5), were identified during chemical investigations of the MeOH extract from the leaves and twigs of Grevillea "Poorinda Queen". The chemical structures of the new compounds were elucidated through 2D NMR spectroscopy, while the absolute configuration of the sugar was elucidated through chemical degradation and comparison with an authentic standard. Discussed in detail are the isolation and structure elucidation of 1-3, as well as the associated in vitro anitmalarial activities for 1-5. Also discussed are the in vivo anitmalarial and in vitro cytotoxic activities for 1, 3, and 4.

G.A.M.E.: GPU-accelerated mixture elucidator.

PubMed

Schurz, Alioune; Su, Bo-Han; Tu, Yi-Shu; Lu, Tony Tsung-Yu; Lin, Olivia A; Tseng, Yufeng J

2017-09-15

GPU acceleration is useful in solving complex chemical information problems. Identifying unknown structures from the mass spectra of natural product mixtures has been a desirable yet unresolved issue in metabolomics. However, this elucidation process has been hampered by complex experimental data and the inability of instruments to completely separate different compounds. Fortunately, with current high-resolution mass spectrometry, one feasible strategy is to define this problem as extending a scaffold database with sidechains of different probabilities to match the high-resolution mass obtained from a high-resolution mass spectrum. By introducing a dynamic programming (DP) algorithm, it is possible to solve this NP-complete problem in pseudo-polynomial time. However, the running time of the DP algorithm grows by orders of magnitude as the number of mass decimal digits increases, thus limiting the boost in structural prediction capabilities. By harnessing the heavily parallel architecture of modern GPUs, we designed a "compute unified device architecture" (CUDA)-based GPU-accelerated mixture elucidator (G.A.M.E.) that considerably improves the performance of the DP, allowing up to five decimal digits for input mass data. As exemplified by four testing datasets with verified constitutions from natural products, G.A.M.E. allows for efficient and automatic structural elucidation of unknown mixtures for practical procedures. Graphical abstract .

Elucidating the Nature of the Excited State of a Heteroleptic Copper Photosensitizer by using Time-Resolved X-ray Absorption Spectroscopy.

PubMed

Moonshiram, Dooshaye; Garrido-Barros, Pablo; Gimbert-Suriñach, Carolina; Picón, Antonio; Liu, Cunming; Zhang, Xiaoyi; Karnahl, Michael; Llobet, Antoni

2018-04-25

We report the light-induced electronic and geometric changes taking place within a heteroleptic Cu I photosensitizer, namely [(xant)Cu(Me 2 phenPh 2 )]PF 6 (xant=xantphos, Me 2 phenPh 2 =bathocuproine), by time-resolved X-ray absorption spectroscopy in the ps-μs time regime. Time-resolved X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis enabled the elucidation of the electronic and structural configuration of the copper center in the excited state as well as its decay dynamics in different solvent conditions with and without triethylamine acting as a sacrificial electron donor. A three-fold decrease in the decay lifetime of the excited state is observed in the presence of triethylamine, showing the feasibility of the reductive quenching pathway in the latter case. A prominent pre-edge feature is observed in the XANES spectrum of the excited state upon metal to charge ligand transfer transition, showing an increased hybridization of the 3d states with the ligand p orbitals in the tetrahedron around the Cu center. EXAFS and density functional theory illustrate a significant shortening of the Cu-N and an elongation of the Cu-P bonds together with a decrease in the torsional angle between the xantphos and bathocuproine ligand. This study provides mechanistic time-resolved understanding for the development of improved heteroleptic Cu I photosensitizers, which can be used for the light-driven production of hydrogen from water. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Levothyroxine sodium revisited: A wholistic structural elucidation approach of new impurities via HPLC-HRMS/MS, on-line H/D exchange, NMR spectroscopy and chemical synthesis.

PubMed

Ruggenthaler, M; Grass, J; Schuh, W; Huber, C G; Reischl, R J

2017-02-20

The structural elucidation of unknown pharmaceutical impurities plays an important role in the quality control of newly developed and well-established active pharmaceutical ingredients (APIs). The United States Pharmacopeia (USP) monograph for the API Levothyroxine Sodium, a synthetic thyroid hormone, features two high pressure liquid chromatography (HPLC) methods using UV-VIS absorption detection to determine organic impurities in the drug substance. The impurity profile of the first USP method ("Procedure 1") has already been extensively studied, however for the second method ("Procedure 2"), which exhibits a significantly different impurity profile, no wholistic structural elucidation of impurities has been performed yet. Applying minor modifications to the chromatographic parameters of USP "Procedure 2" and using various comprehensive structural elucidation methods such as high resolution tandem mass spectrometry with on-line hydrogen-deuterium (H/D) exchange or two-dimensional nuclear magnetic resonance spectroscopy (NMR) we gained new insights about the complex impurity profile of the synthetic thyroid hormone. This resulted in the characterization of 24 compounds previously unknown to literature and the introduction of two new classes of Levothyroxine Sodium impurities. Five novel compounds were unambiguously identified via isolation or synthesis of reference substances and subsequent NMR spectroscopic investigation. Additionally, Collision-Induced Dissociation (CID)-type fragmentation of identified major impurities as well as neutral loss fragmentation patterns of many characterized impurities were discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Amenorrhoea and reversible infertility due to obstructive hydrocephalus: literature review and case report.

PubMed

Hamilton, Kimberly; Iskandar, Bermans

2018-02-12

Endocrine abnormalities are well-recognized consequences of intracranial pathology such as pituitary tumours. Less commonly, hydrocephalus may lead to dysfunction of the endocrine system, presenting as amenorrhoea or precocious puberty. We present a case report and literature review of hydrocephalus causing endocrine abnormalities including reversible infertility. A 34 year-old female presented with amenorrhoea and infertility. MRI showed a third ventricular mass and hydrocephalus. The amenorrhoea resolved within weeks of endoscopic third ventriculostomy and tumour biopsy; pregnancy ensued within 6 months. Thirty-two cases of hydrocephalus-related amenorrhoea were reported between 1915 and 2007. All patients who underwent modern hydrocephalus treatment experienced partial or complete resolution of endocrine dysfunction. Successful pregnancy was reported in three patients, as in our case presentation. While mechanisms of dysfunction have not been completely elucidated, studies point toward loss of GnRH pulsatility due to compression of the medio-basal hypothalamic structures. Hydrocephalus can cause endocrine dysfunction, including amenorrhoea, which may reverse with CSF diversion. Therefore, cranial imaging is an important component in the evaluation of such endocrine abnormalities.

Finite temperature effects on the X-ray absorption spectra of energy related materials

NASA Astrophysics Data System (ADS)

Pascal, Tod; Prendergast, David

2014-03-01

We elucidate the role of room-temperature-induced instantaneous structural distortions in the Li K-edge X-ray absorption spectra (XAS) of crystalline LiF, Li2SO4, Li2O, Li3N and Li2CO3 using high resolution X-ray Raman spectroscopy (XRS) measurements and first-principles density functional theory calculations within the eXcited electron and Core Hole (XCH) approach. Based on thermodynamic sampling via ab-initio molecular dynamics (MD) simulations, we find calculated XAS in much better agreement with experiment than those computed using the rigid crystal structure alone. We show that local instantaneous distortion of the atomic lattice perturbs the symmetry of the Li 1 s core-excited-state electronic structure, broadening spectral line-shapes and, in some cases, producing additional spectral features. This work was conducted within the Batteries for Advanced Transportation Technologies (BATT) Program, supported by the U.S. Department of Energy Vehicle Technologies Program under Contract No. DE-AC02-05CH11231.

Non-destructive identification of green and yellow pigments: the case of some Sicilian Renaissance glazed pottery

NASA Astrophysics Data System (ADS)

Crupi, V.; Majolino, D.; Venuti, V.; Barone, G.; Mazzoleni, P.; Pezzino, A.; La Russa, M. F.; Ruffolo, S. A.; Bardelli, F.

2010-09-01

Selected decorated Renaissance ceramic fragments, found during the excavation of a Sicilian archaeological site (Caltagirone, Sicily, South Italy), have been studied by combining scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDS), and X-ray absorbance spectroscopy (XAS). The study was aimed at providing microchemical and microstructural characterization of the colored glazed coatings in order to elucidate the nature of the pigments in the decorative layers, and in the glaze itself. From the obtained results, the general perspective has been the identification of information to be used for a reliable recognition of the production techniques. In particular, XAS measurements, performed using synchrotron radiation (SR) as the source at the Cu K-edge, in the case of green decorations, provided structural information of the oxidation states and the local chemical environment of copper (neighboring atoms and bond distances).

LC MS analysis in the e-beam and gamma radiolysis of metoprolol tartrate in aqueous solution: Structure elucidation and formation mechanism of radiolytic products

NASA Astrophysics Data System (ADS)

Slegers, Catherine; Maquille, Aubert; Deridder, Véronique; Sonveaux, Etienne; Habib Jiwan, Jean-Louis; Tilquin, Bernard

2006-09-01

E-beam and gamma products from the radiolysis of aqueous solutions of (±)-metoprolol tartrate, saturated in nitrogen, are analyzed by HPLC with on-line mass and UV detectors. The structures of 10 radiolytic products common to e-beam and gamma irradiations are elucidated by comparing their fragmentation pattern to that of (±)-metoprolol. Two of the radiolytic products are also metabolites. Different routes for the formation of the radiolytic products are proposed.

Structure elucidation of nigricanoside A through enantioselective total synthesis† †Electronic supplementary information (ESI) available: Complete experimental details and characterization data. See DOI: 10.1039/c5sc00281h Click here for additional data file.

PubMed Central

Chen, Jie; Koswatta, Panduka; DeBergh, J. Robb; Fu, Peng; Pan, Ende

2015-01-01

Nigricanoside A was isolated from green alga, and its dimethyl ester was found to display potent cytotoxicity. Its scarcity prevented a full structure elucidation, leaving total synthesis as the only means to determine its relative and absolute stereochemistry and to explore its biological activity. Here we assign the stereochemistry of the natural product through enantioselective total synthesis and provide initial studies of its cytotoxicity. PMID:26877863

Isolation and structure elucidation of the nucleoside antibiotic strepturidin from Streptomyces albus DSM 40763.

PubMed

Pesic, Alexander; Steinhaus, Britta; Kemper, Sebastian; Nachtigall, Jonny; Kutzner, Hans Jürgen; Höfle, Gerhard; Süssmuth, Roderich D

2014-06-01

The antibiotic strepturidin (1) was isolated from the microorganism Streptomyces albus DSM 40763, and its structure elucidated by spectroscopic methods and chemical degradation studies. The determination of the relative and absolute stereocenters was partially achieved using chiral GC/EI-MS analysis and microderivatization by acetal ring formation and subsequent 2D-NMR analysis of key (1)H,(1)H-NOESY NMR correlations and extraction of (1)H,(13)C coupling constants from (1)H,(13)C-HMBC NMR spectra. Based on these results, a biosynthesis model was proposed.

Characterization of Trinuclear Oxo Bridged Cobalt Complexes in Isolation

NASA Astrophysics Data System (ADS)

Lang, Johannes; Fries, Daniela V.; Niedner-Schatteburg, Gereon

2018-05-01

This study elucidates molecular structures, fragmentation pathways and relative stabilities of isolated trinuclear oxo bridged cobalt complexes of the structural type [Co3O(OAc)6(Py)n]+ (OAc=acetate, Py=pyridine, n=0, 1, 2, 3). We present infrared multiple photon dissociation (IR-MPD) spectra in combination with quantum chemical calculations. They indicate that the coordination of axial pyridine ligands to the [Co3O(OAc)6]+ subunit disturbs the triangular geometry of the Co3O core. [Co3O(OAc)6]+ exhibits a nearly equilateral triangular Co3O core geometry. The coordination of one or two pyridine ligands disturbs this arrangement resulting in isosceles triangular Co3O core geometries (in the cases of n=1 and 2). Coordination of three pyridine ligands (n=3) results in an equilateral triangular Co3O core geometry as in the case of n=0. Collision induced dissociation (CID) studies reveal that the complexes undergo a consecutive elimination of pyridine and acetate ligands with increasing excitation energy. Relative stabilities of the complexes decrease with the number of coordinated pyridine ligands. The presented results help to gain a fundamental insight into the molecular structure of trinuclear oxo bridged cobalt complexes void of any external effects such as crystal packing or solvation.

Theoretical NMR correlations based Structure Discussion.

PubMed

Junker, Jochen

2011-07-28

The constitutional assignment of natural products by NMR spectroscopy is usually based on 2D NMR experiments like COSY, HSQC, and HMBC. The actual difficulty of the structure elucidation problem depends more on the type of the investigated molecule than on its size. The moment HMBC data is involved in the process or a large number of heteroatoms is present, a possibility of multiple solutions fitting the same data set exists. A structure elucidation software can be used to find such alternative constitutional assignments and help in the discussion in order to find the correct solution. But this is rarely done. This article describes the use of theoretical NMR correlation data in the structure elucidation process with WEBCOCON, not for the initial constitutional assignments, but to define how well a suggested molecule could have been described by NMR correlation data. The results of this analysis can be used to decide on further steps needed to assure the correctness of the structural assignment. As first step the analysis of the deviation of carbon chemical shifts is performed, comparing chemical shifts predicted for each possible solution with the experimental data. The application of this technique to three well known compounds is shown. Using NMR correlation data alone for the description of the constitutions is not always enough, even when including 13C chemical shift prediction.

Elucidation of peptide-directed palladium surface structure for biologically tunable nanocatalysts.

PubMed

Bedford, Nicholas M; Ramezani-Dakhel, Hadi; Slocik, Joseph M; Briggs, Beverly D; Ren, Yang; Frenkel, Anatoly I; Petkov, Valeri; Heinz, Hendrik; Naik, Rajesh R; Knecht, Marc R

2015-05-26

Peptide-enabled synthesis of inorganic nanostructures represents an avenue to access catalytic materials with tunable and optimized properties. This is achieved via peptide complexity and programmability that is missing in traditional ligands for catalytic nanomaterials. Unfortunately, there is limited information available to correlate peptide sequence to particle structure and catalytic activity to date. As such, the application of peptide-enabled nanocatalysts remains limited to trial and error approaches. In this paper, a hybrid experimental and computational approach is introduced to systematically elucidate biomolecule-dependent structure/function relationships for peptide-capped Pd nanocatalysts. Synchrotron X-ray techniques were used to uncover substantial particle surface structural disorder, which was dependent upon the amino acid sequence of the peptide capping ligand. Nanocatalyst configurations were then determined directly from experimental data using reverse Monte Carlo methods and further refined using molecular dynamics simulation, obtaining thermodynamically stable peptide-Pd nanoparticle configurations. Sequence-dependent catalytic property differences for C-C coupling and olefin hydrogenation were then elucidated by identification of the catalytic active sites at the atomic level and quantitative prediction of relative reaction rates. This hybrid methodology provides a clear route to determine peptide-dependent structure/function relationships, enabling the generation of guidelines for catalyst design through rational tailoring of peptide sequences.

Experimental Realization of Tunable Metamaterial Hyper-transmitter

PubMed Central

Yoo, Young Joon; Yi, Changhyun; Hwang, Ji Sub; Kim, Young Ju; Park, Sang Yoon; Kim, Ki Won; Rhee, Joo Yull; Lee, YoungPak

2016-01-01

We realized the tunable metamaterial hyper-transmitter in the microwave range utilizing simple planar meta-structure. The single-layer metamaterial hyper-transmitter shows that the transmission peak occurs at 14 GHz. In case of the dual-layer one, it is possible to control the transmission peak from 5 to 10 GHz. Moreover, all the transmission peaks reveal transmission over 100%. We experimentally and theoretically investigated these phenomena through 3-dimensional simulation and measurement. The reason for being over 100% is also elucidated. The suggested hyper-transmitter can be used, for example, in enhancing the operating distance of the electromagnetic wave in Wi-Fi, military radar, wireless power transfer and self-driving car. PMID:27629804

Airway Reflux, Cough and Respiratory Disease

PubMed Central

Molyneux, Ian D.; Morice, Alyn H.

2011-01-01

It is increasingly accepted that the effects of gastro-oesophageal reflux are not limited to the gastrointestinal tract. The adjacent respiratory structures are also at risk from material ejected from the proximal oesophagus as a result of the failure of anatomical and physiological barriers. There is evidence of the influence of reflux on several respiratory and otorhinological conditions and although in many cases the precise mechanism has yet to be elucidated, the association alone opens potential novel avenues of therapy to clinicians struggling to treat patients with apparently intractable respiratory complaints. This review provides a description of the airway reflux syndrome, its effects on the lung and current and future therapeutic options. PMID:23251752

Experimental Realization of Tunable Metamaterial Hyper-transmitter

NASA Astrophysics Data System (ADS)

Yoo, Young Joon; Yi, Changhyun; Hwang, Ji Sub; Kim, Young Ju; Park, Sang Yoon; Kim, Ki Won; Rhee, Joo Yull; Lee, Youngpak

2016-09-01

We realized the tunable metamaterial hyper-transmitter in the microwave range utilizing simple planar meta-structure. The single-layer metamaterial hyper-transmitter shows that the transmission peak occurs at 14 GHz. In case of the dual-layer one, it is possible to control the transmission peak from 5 to 10 GHz. Moreover, all the transmission peaks reveal transmission over 100%. We experimentally and theoretically investigated these phenomena through 3-dimensional simulation and measurement. The reason for being over 100% is also elucidated. The suggested hyper-transmitter can be used, for example, in enhancing the operating distance of the electromagnetic wave in Wi-Fi, military radar, wireless power transfer and self-driving car.

Self-amplified photo-induced gap quenching in a correlated electron material

PubMed Central

Mathias, S.; Eich, S.; Urbancic, J.; Michael, S.; Carr, A. V.; Emmerich, S.; Stange, A.; Popmintchev, T.; Rohwer, T.; Wiesenmayer, M.; Ruffing, A.; Jakobs, S.; Hellmann, S.; Matyba, P.; Chen, C.; Kipp, L.; Bauer, M.; Kapteyn, H. C.; Schneider, H. C.; Rossnagel, K.; Murnane, M. M.; Aeschlimann, M.

2016-01-01

Capturing the dynamic electronic band structure of a correlated material presents a powerful capability for uncovering the complex couplings between the electronic and structural degrees of freedom. When combined with ultrafast laser excitation, new phases of matter can result, since far-from-equilibrium excited states are instantaneously populated. Here, we elucidate a general relation between ultrafast non-equilibrium electron dynamics and the size of the characteristic energy gap in a correlated electron material. We show that carrier multiplication via impact ionization can be one of the most important processes in a gapped material, and that the speed of carrier multiplication critically depends on the size of the energy gap. In the case of the charge-density wave material 1T-TiSe2, our data indicate that carrier multiplication and gap dynamics mutually amplify each other, which explains—on a microscopic level—the extremely fast response of this material to ultrafast optical excitation. PMID:27698341

Phosphorescent Organic Light Emitting Diodes Implementing Platinum Complexes

NASA Astrophysics Data System (ADS)

Ecton, Jeremy Exton

Organic light emitting diodes (OLEDs) are a promising approach for display and solid state lighting applications. However, further work is needed in establishing the availability of efficient and stable materials for OLEDs with high external quantum efficiency's (EQE) and high operational lifetimes. Recently, significant improvements in the internal quantum efficiency or ratio of generated photons to injected electrons have been achieved with the advent of phosphorescent complexes with the ability to harvest both singlet and triplet excitons. Since then, a variety of phosphorescent complexes containing heavy metal centers including Os, Ni, Ir, Pd, and Pt have been developed. Thus far, the majority of the work in the field has focused on iridium based complexes. Platinum based complexes, however, have received considerably less attention despite demonstrating efficiency's equal to or better than their iridium analogs. In this study, a series of OLEDs implementing newly developed platinum based complexes were demonstrated with efficiency's or operational lifetimes equal to or better than their iridium analogs for select cases. In addition to demonstrating excellent device performance in OLEDs, platinum based complexes exhibit unique photophysical properties including the ability to form excimer emission capable of generating broad white light emission from a single emitter and the ability to form narrow band emission from a rigid, tetradentate molecular structure for select cases. These unique photophysical properties were exploited and their optical and electrical properties in a device setting were elucidated. Utilizing the unique properties of a tridentate Pt complex, Pt-16, a highly efficient white device employing a single emissive layer exhibited a peak EQE of over 20% and high color quality with a CRI of 80 and color coordinates CIE(x=0.33, y=0.33). Furthermore, by employing a rigid, tetradentate platinum complex, PtN1N, with a narrow band emission into a microcavity organic light emitting diode (MOLED), significant enhancement in the external quantum efficiency was achieved. The optimized MOLED structure achieved a light out-coupling enhancement of 1.35 compared to the non-cavity structure with a peak EQE of 34.2%. In addition to demonstrating a high light out-coupling enhancement, the microcavity effect of a narrow band emitter in a MOLED was elucidated.

A Comparative Study of the Effectiveness of Two Strategies of Etymological Elaboration and Pictorial Elucidation on Idiom Learning: A Case of Young EFL Iranian Learners

ERIC Educational Resources Information Center

Haghshenas, Mahsa Sadat Mousavi; Hashemian, Mahmood

2016-01-01

This study examined the effect of etymological elaboration, pictorial elucidation, and integration of these 2 strategies on idiom learning by L2 learners. A total number of 80 homogeneous intermediate learners studying English at 3 language institutes in Isfahan, Iran, were selected. The intermediate participants were selected as the result of…

Tannin structural elucidation and quantitative ³¹P NMR analysis. 1. Model compounds.

PubMed

Melone, Federica; Saladino, Raffaele; Lange, Heiko; Crestini, Claudia

2013-10-02

Tannins and flavonoids are secondary metabolites of plants that display a wide array of biological activities. This peculiarity is related to the inhibition of extracellular enzymes that occurs through the complexation of peptides by tannins. Not only the nature of these interactions, but more fundamentally also the structure of these heterogeneous polyphenolic molecules are not completely clear. This first paper describes the development of a new analytical method for the structural characterization of tannins on the basis of tannin model compounds employing an in situ labeling of all labile H groups (aliphatic OH, phenolic OH, and carboxylic acids) with a phosphorus reagent. The ³¹P NMR analysis of ³¹P-labeled samples allowed the unprecedented quantitative and qualitative structural characterization of hydrolyzable tannins, proanthocyanidins, and catechin tannin model compounds, forming the foundations for the quantitative structural elucidation of a variety of actual tannin samples described in part 2 of this series.

Conservative management of retrocaval Ureter: A case series.

PubMed

Yen, Jia Min; Lee, Lui Shiong; Cheng, Christopher Wai Sam

2015-01-01

Retrocaval ureter is a rare congenital anomaly with the ureter passage posterior to the inferior vena cava. Surgical repair is suggested for patients with significant functional obstruction. However, there is little literature to suggest the management of asymptomatic patients. Case 1 patient is a 29 year-old Indonesian man and case 2 patient is a 41 year-old Malay man. Both patients were asymptomatic and well. This report is the short follow-up, therefore making it impossible to elucidate the natural history of uncorrected retrocaval ureters. At 8 month and 6 month respectively, they remained well without symptoms. Our report suggests that immediate surgical repair is not always needed. Longer follow-up with larger patient population is needed to formally elucidate the natural history of this uncommon condition. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structure elucidation of two triterpenoid saponins from rhizome of Anemone raddeana Regel.

PubMed

Lu, Jincai; Xu, Beibei; Gao, Song; Fan, Li; Zhang, Hongfen; Liu, Runxiang; Kodama, Hiroyuki

2009-09-01

Two new 27-hydroxy-oleanolic acid type triterpenoid saponins, raddeanoside 20 (1) and raddeanoside 21(2) were isolated from the rhizome of Anemone raddeana Regel. The structures of the two compounds were elucidated as 27-hydroxy-oleanolic acid 3-O-alpha-L-rhamnopyranosyl(1-->2) [beta-D-glucopyranosyl (1-->4)]-alpha-L-arabinopyranoside (1) and 3-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranosyl-27-hydroxy-oleanolic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (2) on the basis of chemical and spectral evidence.

Detection of low-level PTFE contamination: An application of solid-state NMR to structure elucidation in the pharmaceutical industry.

PubMed

Pham, Tran N; Day, Caroline J; Edwards, Andrew J; Wood, Helen R; Lynch, Ian R; Watson, Simon A; Bretonnet, Anne-Sophie Z; Vogt, Frederick G

2011-01-25

We report a novel use of solid-state ¹⁹F nuclear magnetic resonance to detect and quantify polytetrafluoroethylene contamination from laboratory equipment, which due to low quantity (up to 1% w/w) and insolubility remained undetected by standard analytical techniques. Solid-state ¹⁹F NMR is shown to be highly sensitive to such fluoropolymers (detection limit 0.02% w/w), and is demonstrated as a useful analytical tool for structure elucidation of unknown solid materials. Copyright © 2010 Elsevier B.V. All rights reserved.

Structural characterisation of medically relevant protein assemblies by integrating mass spectrometry with computational modelling.

PubMed

Politis, Argyris; Schmidt, Carla

2018-03-20

Structural mass spectrometry with its various techniques is a powerful tool for the structural elucidation of medically relevant protein assemblies. It delivers information on the composition, stoichiometries, interactions and topologies of these assemblies. Most importantly it can deal with heterogeneous mixtures and assemblies which makes it universal among the conventional structural techniques. In this review we summarise recent advances and challenges in structural mass spectrometric techniques. We describe how the combination of the different mass spectrometry-based methods with computational strategies enable structural models at molecular levels of resolution. These models hold significant potential for helping us in characterizing the function of protein assemblies related to human health and disease. In this review we summarise the techniques of structural mass spectrometry often applied when studying protein-ligand complexes. We exemplify these techniques through recent examples from literature that helped in the understanding of medically relevant protein assemblies. We further provide a detailed introduction into various computational approaches that can be integrated with these mass spectrometric techniques. Last but not least we discuss case studies that integrated mass spectrometry and computational modelling approaches and yielded models of medically important protein assembly states such as fibrils and amyloids. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Structural elucidation of the O-antigen of the Shigella flexneri provisional serotype 88-893: structural and serological similarities with S. flexneri provisional serotype Y394 (1c).

PubMed

Foster, R A; Carlin, N I A; Majcher, M; Tabor, H; Ng, L-K; Widmalm, G

2011-05-01

The structure of the repeating unit of the O-antigen polysaccharide from Shigella flexneri provisional serotype 88-893 has been determined. (1)H and (13)C NMR spectroscopy as well as 2D NMR experiments were employed to elucidate the structure. The carbohydrate part of the hexasaccharide repeating unit is identical to the previously elucidated structure of the O-polysaccharide from S. flexneri prov. serotype Y394. The O-antigen of S. flexneri prov. serotype 88-893 carries 0.7 mol O-acetyl group per repeating unit located at O-2 of the 3-substituted rhamnosyl residue, as identified by H2BC and BS-CT-HMBC NMR experiments. The O-antigen polysaccharide is composed of hexasaccharide repeating units with the following structure: →2)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-α-L-Rhap2Ac-(1→3)[α-D-Glcp-(1→2)-α-D-Glcp-(1→4)]-β-D-GlcpNAc-(1→. Serological studies showed that type antigens for the two provisional serotypes are identical; in addition 88-893 expresses S. flexneri group factor 6 antigen. We propose that provisional serotypes Y394 and 88-893 be designated as two new serotypes 7a and 7b, respectively, in the S. flexneri typing scheme. Copyright © 2011 Elsevier Ltd. All rights reserved.

Product ion isotopologue pattern: A tool to improve the reliability of elemental composition elucidations of unknown compounds in complex matrices.

PubMed

Kaufmann, A; Walker, S; Mol, G

2016-04-15

Elucidation of the elemental compositions of unknown compounds (e.g., in metabolomics) generally relies on the availability of accurate masses and isotopic ratios. This study focuses on the information provided by the abundance ratio within a product ion pair (monoisotopic versus the first isotopic peak) when isolating and fragmenting the first isotopic ion (first isotopic mass spectrum) of the precursor. This process relies on the capability of the quadrupole within the Q Orbitrap instrument to isolate a very narrow mass window. Selecting only the first isotopic peak (first isotopic mass spectrum) leads to the observation of a unique product ion pair. The lighter ion within such an isotopologue pair is monoisotopic, while the heavier ion contains a single carbon isotope. The observed abundance ratio is governed by the percentage of carbon atoms lost during the fragmentation and can be described by a hypergeometric distribution. The observed carbon isotopologue abundance ratio (product ion isotopologue pattern) gives reliable information regarding the percentage of carbon atoms lost in the fragmentation process. It therefore facilitates the elucidation of the involved precursor and product ions. Unlike conventional isotopic abundances, the product ion isotopologue pattern is hardly affected by isobaric interferences. Furthermore, the appearance of these pairs greatly aids in cleaning up a 'matrix-contaminated' product ion spectrum. The product ion isotopologue pattern is a valuable tool for structural elucidation. It increases confidence in results and permits structural elucidations for heavier ions. This tool is also very useful in elucidating the elemental composition of product ions. Such information is highly valued in the field of multi-residue analysis, where the accurate mass of product ions is required for the confirmation process. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Adoption of the HPV vaccine: a case study of three emerging countries.

PubMed

Caro Martínez, Araceli; Espín Balbino, Jaime; Lemgruber, Alexandre; Martín Ruiz, Eva; Olry de Labry Lima, Antonio; García-Mochón, Leticia; Lessa, Fernanda

2017-05-01

The human papillomavirus (HPV) vaccine has recently attracted considerable attention in emerging countries, due to its potential to reduce the impact of HPV-related diseases. This case study sheds new light about the variety of HTA arrangements, methods and processes involved in the adoption and use of HPV vaccines in a selected sample of central, eastern and southern Europe and Latin America and the Caribbean, all of them emerging in the use of HTA. A multi-country case study was designed. Mixed methods, document review, semi-structured surveys and personal communication with experts, were used for data collection and triangulation. This study shows that common elements of good practice exist in the processes and methods used, with all countries arriving at the same appraisal recommendations. However, the influence of socio-politico-economic factors appears to be determinant on the final decisions and restrictions to access made. This case study intends to draw useful lessons for policymakers in emerging settings interested in the adoption of the HPV vaccine supported by evidence-informed processes, such as those offered by institutionalized HTA. Future studies are also recommended to elucidate the specific roles that social values and uncertainties play in vaccine decision-making across different societies.

Structure elucidation of the designer drug N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide and the relevance of predicted (13) C NMR shifts - a case study.

PubMed

Girreser, Ulrich; Rösner, Peter; Vasilev, Andrej

2016-07-01

The detailed structure elucidation process of the new cannabimimetic designer drug, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, with a highly substituted pyrazole skeleton, using nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric (MS) techniques is described. After a first analysis of the NMR spectra and comparison with 48 possible pyrazole and imidazole structures, a subset of six positional isomeric pyrazoles and six imidazoles remained conceivable. Four substituents of the heterocyclic skeleton were identified: a proton bound to a pyrazole ring carbon atom; a 5-fluoropentyl group; a 4-fluorophenyl substituent; and a carbamoyl group, which is N-substituted with a methyl residue carrying a tert.-butyl and a carbamoyl substituent. The 5-fluoropentyl residue is situated at the nitrogen ring atom. Additional NMR experiments like the (1) H,(13) C HMBC were performed, but due to the small number of signals based on long-range couplings, the comparison of predicted and observed (13) C chemical shifts became necessary. The open access Internet shift prediction programs NMRDB, NMRSHIFTDB2, and CSEARCH were employed for the prediction of (13) C shift values which allowed an efficient and unambiguous structure determination. For the identified N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, the best agreement between predicted (13) C shifts and the observed chemical shifts and long-range couplings for the pyrazole ring carbon atoms, with a standard error of about 2 ppm, was found with each of the predictions. For the comparison of measured and predicted chemical shifts model compounds with simple substituents proved helpful. The identified compound is a homologue of AZ-037 which is offered by Internet suppliers. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Molecular simulation of the adsorption of methane in Engelhard titanosilicate frameworks.

PubMed

Pillai, Renjith S; Gomes, José R B; Jorge, Miguel

2014-07-01

Molecular simulations were carried out to elucidate the influence of structural heterogeneity and of the presence of extra-framework cations and water molecules on the adsorption of methane in Engelhard titanosilicates, ETS-10 and ETS-4. The simulations employed three different modeling approaches, (i) with fixed cations and water at their single crystal positions, (ii) with fixed cations and water at their optimized positions, and (iii) with mobile extra-framework cations and water molecules. Simulations employing the final two approaches provided a more realistic description of adsorption in these materials, and showed that at least some cations and water molecules are displaced from the crystallographic positions obtained from single crystal data. Upon methane adsorption in the case of ETS-10, the cations move to the large rings, while in the case of ETS-4, the water molecules and cations migrate to more available space in the larger 12-membered ring channels for better accommodation of the methane molecules. For ETS-4, we also considered adsorption in all possible pure polymorph structures and then combined these to provide an estimate of adsorption in a real ETS-4 sample. By comparing simulated adsorption isotherms to experimental data, we were able to show that both the mobility of extra-framework species and the structural heterogeneity should be taken into account for realistic predictions of adsorption in titanosilicate materials.

How ligands improve the hydrothermal stability and affect the adsorption in the IRMOF family.

PubMed

Bellarosa, Luca; Gutiérrez-Sevillano, Juan J; Calero, Sofía; López, Núria

2013-10-28

Metal-Organic Frameworks are considered to be the next generation of sorbents both because of their synthetic versatility and high selectivity potential. In the first generation (IRMOF), the main drawback for commercial implementation is the lack of hydrothermal stability. Even if several studies have been conducted to elucidate the reasons behind their structural weakness in humid environments, how apparently small changes in the stoichiometry of the building units affect the stability of the lattice is still poorly understood. Using density functional theory and ab initio molecular dynamics we investigated the reason behind the different behaviour of several substituted IRMOF-1 structures. We show that hydrophilic variations in the organic linkers work as new basins of attraction for the incoming water molecules, thus depleting the water content at the metal center. To confirm this, we performed Monte Carlo simulations to provide insights into the adsorption energies and check the effectiveness of the adsorption sites in the substituted structures for a variety of polar and non-polar molecules. The results show that linker modification affects molecular adsorption and can improve the overall stability of the lattice redirecting water to the new sites in the case of hydrophilic units. Three key parameters have been singled out to rationalize this behaviour, and used to predict the favoured adsorption sites in the case of gas mixtures.

Arterial stiffness estimation based photoplethysmographic pulse wave analysis

NASA Astrophysics Data System (ADS)

Huotari, Matti; Maatta, Kari; Kostamovaara, Juha

2010-11-01

Arterial stiffness is one of the indices of vascular healthiness. It is based on pulse wave analysis. In the case we decompose the pulse waveform for the estimation and determination of arterial elasticity. Firstly, optically measured with photoplethysmograph and then investigating means by four lognormal pulse waveforms for which we can find very good fit between the original and summed decomposed pulse wave. Several studies have demonstrated that these kinds of measures predict cardiovascular events. While dynamic factors, e.g., arterial stiffness, depend on fixed structural features of the vascular wall. Arterial stiffness is estimated based on pulse wave decomposition analysis in the radial and tibial arteries. Elucidation of the precise relationship between endothelial function and vascular stiffness awaits still further study.

Antifungal Amide Alkaloids from the Aerial Parts of Piper flaviflorum and Piper sarmentosum.

PubMed

Shi, Yan-Ni; Liu, Fang-Fang; Jacob, Melissa R; Li, Xing-Cong; Zhu, Hong-Tao; Wang, Dong; Cheng, Rong-Rong; Yang, Chong-Ren; Xu, Min; Zhang, Ying-Jun

2017-01-01

Sixty-three amide alkaloids, including three new, piperflaviflorine A ( 1 ), piperflaviflorine B ( 2 ), and sarmentamide D ( 4 ), and two previously synthesized ones, (1 E ,3 S )-1-cinnamoyl-3- hydroxypyrrolidine ( 3 ) and N -[7'-(4'-methoxyphenyl)ethyl]-2-methoxybenzamide ( 5 ), were isolated from the aerial parts of Piper flaviflorum and Piper sarmentosum. Their structures were elucidated by detailed spectroscopic analysis and, in case of 3 , by single-crystal X-ray diffraction. Most of the isolates were tested for their antifungal and antibacterial activities. Ten amides ( 6 - 15 ) showed antifungal activity against Cryptococcus neoformans ATCC 90 113 with IC 50 values in the range between 4.7 and 20.0 µg/mL. Georg Thieme Verlag KG Stuttgart · New York.

Molecular dynamics simulations of the Bcl-2 protein to predict the structure of its unordered flexible loop domain.

PubMed

Raghav, Pawan Kumar; Verma, Yogesh Kumar; Gangenahalli, Gurudutta U

2012-05-01

B-cell lymphoma (Bcl-2) protein is an anti-apoptotic member of the Bcl-2 family. It is functionally demarcated into four Bcl-2 homology (BH) domains: BH1, BH2, BH3, BH4, one flexible loop domain (FLD), a transmembrane domain (TM), and an X domain. Bcl-2's BH domains have clearly been elucidated from a structural perspective, whereas the conformation of FLD has not yet been predicted, despite its important role in regulating apoptosis through its interactions with JNK-1, PKC, PP2A phosphatase, caspase 3, MAP kinase, ubiquitin, PS1, and FKBP38. Many important residues that regulate Bcl-2 anti-apoptotic activity are present in this domain, for example Asp34, Thr56, Thr69, Ser70, Thr74, and Ser87. The structural elucidation of the FLD would likely help in attempts to accurately predict the effect of mutating these residues on the overall structure of the protein and the interactions of other proteins in this domain. Therefore, we have generated an increased quality model of the Bcl-2 protein including the FLD through modeling. Further, molecular dynamics (MD) simulations were used for FLD optimization, to predict the flexibility, and to determine the stability of the folded FLD. In addition, essential dynamics (ED) was used to predict the collective motions and the essential subspace relevant to Bcl-2 protein function. The predicted average structure and ensemble of MD-simulated structures were submitted to the Protein Model Database (PMDB), and the Bcl-2 structures obtained exhibited enhanced quality. This study should help to elucidate the structural basis for Bcl-2 anti-apoptotic activity regulation through its binding to other proteins via the FLD.

Secondary metabolites of cyanobacteria Nostoc sp.

NASA Astrophysics Data System (ADS)

Kobayashi, Akio; Kajiyama, Shin-Ichiro

1998-03-01

Cyanobacteria attracted much attention recently because of their secondary metabolites with potent biological activities and unusual structures. This paper reviews some recent studies on the isolation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteria Nostoc species.

Polymer-Induced Heteronucleation for Protein Single Crystal Growth: Structural Elucidation of Bovine Liver Catalase and Concanavalin A Forms

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

Foroughi, Leila M.; Kang, You-Na; Matzger, Adam J.

Obtaining single crystals for X-ray diffraction remains a major bottleneck in structural biology; when existing crystal growth methods fail to yield suitable crystals, often the target rather than the crystallization approach is reconsidered. Here we demonstrate that polymer-induced heteronucleation, a powerful technique that has been used for small molecule crystallization form discovery, can be applied to protein crystallization by optimizing the heteronucleant composition and crystallization formats for crystallizing a wide range of protein targets. Applying these advances to two benchmark proteins resulted in dramatically increased crystal size, enabling structure determination, for a half century old form of bovine liver catalasemore » (BLC) that had previously only been characterized by electron microscopy, and the discovery of two new forms of concanavalin A (conA) from the Jack bean and accompanying structural elucidation of one of these forms.« less

Novel aldehyde and thiosemicarbazone derivatives: Synthesis, spectroscopic characterization, structural studies and molecular docking studies

NASA Astrophysics Data System (ADS)

Karakurt, Tuncay; Tahtaci, Hakan; Subasi, Nuriye Tuna; Er, Mustafa; Ağar, Erbil

2016-12-01

In this study our purpose is that, synthesis and characterization of compounds containing the aldehyde and thiosemicarbazone groups and comparison of the theoretical results with the experimental results. The structures of all synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analyses techniques. The structure of compound (4) (C9H8N4O2S) was also elucidated by X-ray diffraction analysis. In addition, the theoretical IR spectrum, 1H NMR and 13C NMR chemical shift values, frontier molecular orbital values (FMO) of these molecules were analyzed by using Becke-3- Lee-Yang-Parr (B3LYP) method with LanL2DZ basis set. Finally, molecular docking studies were performed on synthesized compounds using the 4DKI beta-lactam protein structure to determine the potential binding mode of inhibitors.

Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

PubMed

Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz

2014-10-10

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.

Interactions of structurally modified surfactants with reservoir minerals: Calorimetric, spectroscopic and electrokinetic study

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

Somasundaran, P.; Sivakumar, A.; Xu, Q.

1991-03-01

The objective of this project is to elucidate mechanisms of adsorption of structurally modified surfactants on reservoir minerals and to develop a full understanding of the effect of the surfactant structure on the nature of the adsorbed layers at the molecular level. An additional aim is to study the adsorption of surfactant mixtures on simple well-characterized minerals and on complex minerals representing real conditions. The practical goal of these studies is the identification of the optimum surfactant structures and their combinations for micellar flooding. In this work, the experiments on adsorption were focussed on the position of sulfonate and methylmore » groups on the aromatic ring of alkyl xylene sulfonates. A multi-pronged approach consisting of calorimetry, electrokinetics, wettability and spectroscopy is planned to elucidate the adsorption mechanism of surfactants and their mixtures on minerals such as alumina and kaolinite. 32 refs., 15 figs., 7 tabs.« less

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

NASA Astrophysics Data System (ADS)

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-Ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-02-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT.

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

PubMed Central

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-01-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator–activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT. PMID:25687586

Asymptotic behavior of the Kohn-Sham exchange potential at a metal surface

NASA Astrophysics Data System (ADS)

Qian, Zhixin

2012-03-01

The asymptotic structure of the Kohn-Sham exchange potential vx(r) in the classically forbidden region of a metal surface is investigated, together with that of the Slater exchange potential VxS(r) and those of the approximate Krieger-Li-Iafrate VxKLI(r) and Harbola-Sahni Wx(r) exchange potentials. Particularly, the former is shown to have the form of vx(z→∞)=-αx/z with αx a constant dependent only of bulk electron density. The same result in previous work is thus confirmed; in the meanwhile, a controversy raised recently gets resolved. The structure of the exchange hole ρx(r,r') is examined, and the delocalization of it in the metal bulk when the electron is at large distance from the metal surface is demonstrated with analytical expressions. The asymptotic structures of vx(r), VxS(r), VxKLI(r), and Wx(r) at a slab metal surface are also investigated. Particularly, vx(z→∞)=-1/z in the slab case. The distinction, in this respect, between the semi-infinite and the slab metal surfaces is elucidated.

Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and Predicting Residence Time.

PubMed

Guo, Dong; IJzerman, Adriaan P

2018-01-01

G protein-coupled receptors (GPCRs) are integral membrane proteins and represent the largest class of drug targets. During the past decades progress in structural biology has enabled the crystallographic elucidation of the architecture of these important macromolecules. It also provided atomic-level visualization of ligand-receptor interactions, dramatically boosting the impact of structure-based approaches in drug discovery. However, knowledge obtained through crystallography is limited to static structural information. Less information is available showing how a ligand associates with or dissociates from a given receptor, whose importance is in fact increasingly recognized by the drug research community. Owing to recent advances in computer power and algorithms, molecular dynamics stimulations have become feasible that help in analyzing the kinetics of the ligand binding process. Here, we review what is currently known about the dynamics of GPCRs in the context of ligand association and dissociation, as determined through both crystallography and computer simulations. We particularly focus on the molecular basis of ligand dissociation from GPCRs and provide case studies that predict ligand dissociation pathways and residence time.

Structural changes induced by lattice-electron interactions: SiO2 stishovite and FeTiO3 ilmenite.

PubMed

Yamanaka, Takamitsu

2005-09-01

The bright source and highly collimated beam of synchrotron radiation offers many advantages for single-crystal structure analysis under non-ambient conditions. The structure changes induced by the lattice-electron interaction under high pressure have been investigated using a diamond anvil pressure cell. The pressure dependence of electron density distributions around atoms is elucidated by a single-crystal diffraction study using deformation electron density analysis and the maximum entropy method. In order to understand the bonding electrons under pressure, diffraction intensity measurements of FeTiO3 ilmenite and gamma-SiO2 stishovite single crystals at high pressures were made using synchrotron radiation. Both diffraction studies describe the electron density distribution including bonding electrons and provide the effective charge of the cations. In both cases the valence electrons are more localized around the cations with increasing pressure. This is consistent with molecular orbital calculations, proving that the bonding electron density becomes smaller with pressure. The thermal displacement parameters of both samples are reduced with increasing pressure.

Genetic assessment of connectivity in the common reef sponge, Callyspongia vaginalis (Demospongiae: Haplosclerida) reveals high population structure along the Florida reef tract

NASA Astrophysics Data System (ADS)

Debiasse, M. B.; Richards, V. P.; Shivji, M. S.

2010-03-01

The genetic population structure of the common branching vase sponge, Callyspongia vaginalis, was determined along the entire length (465 km) of the Florida reef system from Palm Beach to the Dry Tortugas based on sequences of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene. Populations of C. vaginalis were highly structured (overall ΦST = 0.33), in some cases over distances as small as tens of kilometers. However, nonsignificant pairwise ΦST values were also found between a few relatively distant sampling sites suggesting that some long distance larval dispersal may occur via ocean currents or transport in sponge fragments along continuous, shallow coastlines. Indeed, sufficient gene flow appears to occur along the Florida reef tract to obscure a signal of isolation by distance, but not to homogenize COI haplotype frequencies. The strong genetic differentiation among most of the sampling locations suggests that recruitment in this species is largely local source-driven, pointing to the importance of further elucidating general connectivity patterns along the Florida reef tract to guide the spatial scale of management efforts.

Johann Deisenhofer, Crystallography, and Proteins

Science.gov Websites

research using X-ray crystallography to elucidate for the first time the three-dimensional structure of a large membrane-bound protein molecule. This structure helped explain the process of photosynthesis, by a protein structure determination that relied on complementary features of two different beam lines

Molecular Structures and Momentum Transfer Cross Sections: The Influence of the Analyte Charge Distribution.

PubMed

Young, Meggie N; Bleiholder, Christian

2017-04-01

Structure elucidation by ion mobility spectrometry-mass spectrometry methods is based on the comparison of an experimentally measured momentum transfer cross-section to cross-sections calculated for model structures. Thus, it is imperative that the calculated cross-section must be accurate. However, it is not fully understood how important it is to accurately model the charge distribution of an analyte ion when calculating momentum transfer cross-sections. Here, we calculate and compare momentum transfer cross-sections for carbon clusters that differ in mass, charge state, and mode of charge distribution, and vary temperature and polarizability of the buffer gas. Our data indicate that the detailed distribution of the ion charge density is intimately linked to the contribution of glancing collisions to the momentum transfer cross-section. The data suggest that analyte ions with molecular mass ~3 kDa or momentum transfer cross-section 400-500 Å 2 would be significantly influenced by the charge distribution in nitrogen buffer gas. Our data further suggest that accurate structure elucidation on the basis of IMS-MS data measured in nitrogen buffer gas must account for the molecular charge distribution even for systems as large as C 960 (~12 kDa) when localized charges are present and/or measurements are conducted under cryogenic temperatures. Finally, our data underscore that accurate structure elucidation is unlikely if ion mobility data recorded in one buffer gas is converted into other buffer gases when electronic properties of the buffer gases differ. Graphical Abstract ᅟ.

Irmpd Action Spectroscopy and Computational Approaches to Elucidate Gas-Phase Structures and Energetics of 2'-DEOXYCYTIDINE and Cytidine Sodium Complexes

NASA Astrophysics Data System (ADS)

Zhu, Yanlong; Hamlow, Lucas; He, Chenchen; Gao, Juehan; Oomens, Jos; Rodgers, M. T.

2016-06-01

The local structures of DNA and RNA are influenced by protonation, deprotonation and noncovalent interactions with cations. In order to determine the effects of Na+ cationization on the gas-phase structures of 2'-deoxycytidine, [dCyd+Na]+, and cytidine, [Cyd+Na]+, infrared multiple photon dissociation (IRMPD) action spectra of these sodium cationized nucleosides are measured over the range extending from 500 to 1850 wn using the FELIX free electron laser. Complementary electronic structure calculations are performed to determine the stable low-energy conformations of these complexes. Geometry optimizations, frequency analyses, and IR spectra of these species are determined at the B3LYP/6-311+G(d,p) level of theory. Single-point energies are calculated at the B3LYP/6-311+G(2d,2p) level of theory to determine the relative stabilities of these conformations. Comparison of the measure IRMPD action spectra and computed linear IR spectra enable the conformations accessed in the experiments to be elucidated. For both cytosine nucleosides, tridentate binding of the Na+ cation to the O2, O4' and O5' atoms of the nucleobase and sugar is observed. Present results for the sodium cationized nucleosides are compared to results for the analogous protonated forms of these nucleosides to elucidate the effects of multiple chelating interactions with the sodium cation vs. hydrogen bonding interactions in the protonated systems on the structures and stabilities of these nucleosides.

Lightning induced inappropriate ICD shock: an unusual case of electromagnetic interference.

PubMed

Anderson, Daniel R; Gillberg, Jeffrey M; Torrey, Jeffrey W; Koneru, Jayanthi N

2012-06-01

An unusual case of electromagnetic interference is presented. As a result of a lightning shock to a Shower House, our patient received two shocks. An elucidation of the different mechanisms for the two shocks is presented. ©2010, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Crystalline structure of the marketed form of Rifampicin: a case of conformational and charge transfer polymorphism

NASA Astrophysics Data System (ADS)

de Pinho Pessoa Nogueira, Luciana; de Oliveira, Yara S.; de C. Fonseca, Jéssica; Costa, Wendell S.; Raffin, Fernanda N.; Ellena, Javier; Ayala, Alejandro Pedro

2018-03-01

Rifampicin is a semi-synthetic drug derived from rifamycin B, and currently integrates the fixed dose combination tablet formulations used in the treatment of tuberculosis. It is also used in the leprosy polychemotherapy and prophylaxis, which are diseases classified as neglected according to the World Health Organization. Rifampicin is a polymorphic drug and its desirable polymorphic form is labeled as II, being the main goal of this study the elucidation of its crystalline structure. Polymorph II is characterized by two molecules with different conformations in the asymmetric unit and the following lattice parameters: a = 14.0760 (10) Å, b = 17.5450 (10) Å, c = 17.5270 (10) Å, β = 92.15°. Differently to the previously reported structures, a charge transference from the hydroxyl group of the naphthoquinone of one conformer to the nitrogen of the piperazine group of the second conformer was observed. The relevance of the knowledge of this crystalline structure, which is the preferred polymorph for pharmaceutical formulations, was evidenced by analyzing raw materials with polymorphic mixtures. Thus, the results presented in this contribution close an old information gap allowing the complete solid-state characterization of rifampicin.

Shock and Impact Response of Naval Composite Structures

DTIC Science & Technology

2010-08-09

elucidating physical mechanisms that control the survivability of composite structures under blast and impact. TECHNICAL APPROACH The Principal...the Proceedings of the 16th International Conference on Composite Structures , Kyoto, Japan, July 8-13, 2007. D. ONR Solid Mechanics Program...ONR Solid Mechanics Program Review, Marine Composites and Sandwich Structures , University of Maryland University College, Adelphi, MD, September 21

Structure and function of enzymes in heme biosynthesis.

PubMed

Layer, Gunhild; Reichelt, Joachim; Jahn, Dieter; Heinz, Dirk W

2010-06-01

Tetrapyrroles like hemes, chlorophylls, and cobalamin are complex macrocycles which play essential roles in almost all living organisms. Heme serves as prosthetic group of many proteins involved in fundamental biological processes like respiration, photosynthesis, and the metabolism and transport of oxygen. Further, enzymes such as catalases, peroxidases, or cytochromes P450 rely on heme as essential cofactors. Heme is synthesized in most organisms via a highly conserved biosynthetic route. In humans, defects in heme biosynthesis lead to severe metabolic disorders called porphyrias. The elucidation of the 3D structures for all heme biosynthetic enzymes over the last decade provided new insights into their function and elucidated the structural basis of many known diseases. In terms of structure and function several rather unique proteins were revealed such as the V-shaped glutamyl-tRNA reductase, the dipyrromethane cofactor containing porphobilinogen deaminase, or the "Radical SAM enzyme" coproporphyrinogen III dehydrogenase. This review summarizes the current understanding of the structure-function relationship for all heme biosynthetic enzymes and their potential interactions in the cell.

Annotation and structural elucidation of bovine milk oligosaccharides and determination of novel fucosylated structures

PubMed Central

Aldredge, Danielle L; Geronimo, Maria R; Hua, Serenus; Nwosu, Charles C; Lebrilla, Carlito B; Barile, Daniela

2013-01-01

Bovine milk oligosaccharides (BMOs) are recognized by the dairy and food industries, as well as by infant formula manufacturers, as novel, high-potential bioactive food ingredients. Recent studies revealed that bovine milk contains complex oligosaccharides structurally related to those previously thought to be present in only human milk. These BMOs are microbiotic modulators involved in important biological activities, including preventing pathogen binding to the intestinal epithelium and serving as nutrients for a selected class of beneficial bacteria. Only a small number of BMO structures are fully elucidated. To better understand the potential of BMOs as a class of biotherapeutics, their detailed structure analysis is needed. This study initiated the development of a structure library of BMOs and a comprehensive evaluation of structure-related specificity. The bovine milk glycome was profiled by high-performance mass spectrometry and advanced separation techniques to obtain a comprehensive catalog of BMOs, including several novel, lower abundant neutral and fucosylated oligosaccharides that are often overlooked during analysis. Structures were identified using isomer-specific tandem mass spectroscopy and targeted exoglycosidase digestions to produce a BMO library detailing retention time, accurate mass and structure to allow their rapid identification in future studies. PMID:23436288

X-ray Crystal Structures Elucidate the Nucleotidyl Transfer Reaction of Transcript Initiation Using Two Nucleotides

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

M Gleghorn; E Davydova; R Basu

2011-12-31

We have determined the X-ray crystal structures of the pre- and postcatalytic forms of the initiation complex of bacteriophage N4 RNA polymerase that provide the complete set of atomic images depicting the process of transcript initiation by a single-subunit RNA polymerase. As observed during T7 RNA polymerase transcript elongation, substrate loading for the initiation process also drives a conformational change of the O helix, but only the correct base pairing between the +2 substrate and DNA base is able to complete the O-helix conformational transition. Substrate binding also facilitates catalytic metal binding that leads to alignment of the reactive groupsmore » of substrates for the nucleotidyl transfer reaction. Although all nucleic acid polymerases use two divalent metals for catalysis, they differ in the requirements and the timing of binding of each metal. In the case of bacteriophage RNA polymerase, we propose that catalytic metal binding is the last step before the nucleotidyl transfer reaction.« less

Structure and synthesis of polyisoprenoids used in N-glycosylation across the three domains of life

PubMed Central

Jones, Meredith B.; Rosenberg, Julian N.; Betenbaugh, Michael J.; Krag, Sharon S.

2009-01-01

N-linked protein glycosylation was originally thought to be specific to eukaryotes, but evidence of this post-translational modification has now been discovered across all domains of life: Eucarya, Bacteria, and Archaea. In all cases, the glycans are first assembled in a step-wise manner on a polyisoprenoid carrier lipid. At some stage of lipid-linked oligosaccharide synthesis, the glycan is flipped across a membrane. Subsequently, the completed glycan is transferred to specific asparagine residues on the protein of interest. Interestingly, though the N-glycosylation pathway seems to be conserved, the biosynthetic pathways of the polyisoprenoid carriers, the specific structures of the carriers, and the glycan residues added to the carriers vary widely. In this review we will elucidate how organisms in each basic domain of life synthesize the polyisoprenoids that they utilize for N-linked glycosylation and briefly discuss the subsequent modifications of the lipid to generate a lipid-linked oligosaccharide. PMID:19348869

Mapping nonlinear receptive field structure in primate retina at single cone resolution

PubMed Central

Li, Peter H; Greschner, Martin; Gunning, Deborah E; Mathieson, Keith; Sher, Alexander; Litke, Alan M; Paninski, Liam

2015-01-01

The function of a neural circuit is shaped by the computations performed by its interneurons, which in many cases are not easily accessible to experimental investigation. Here, we elucidate the transformation of visual signals flowing from the input to the output of the primate retina, using a combination of large-scale multi-electrode recordings from an identified ganglion cell type, visual stimulation targeted at individual cone photoreceptors, and a hierarchical computational model. The results reveal nonlinear subunits in the circuity of OFF midget ganglion cells, which subserve high-resolution vision. The model explains light responses to a variety of stimuli more accurately than a linear model, including stimuli targeted to cones within and across subunits. The recovered model components are consistent with known anatomical organization of midget bipolar interneurons. These results reveal the spatial structure of linear and nonlinear encoding, at the resolution of single cells and at the scale of complete circuits. DOI: http://dx.doi.org/10.7554/eLife.05241.001 PMID:26517879

Self-amplified photo-induced gap quenching in a correlated electron material

DOE PAGES

Mathias, S.; Eich, S.; Urbancic, J.; ...

2016-10-04

Capturing the dynamic electronic band structure of a correlated material presents a powerful capability for uncovering the complex couplings between the electronic and structural degrees of freedom. When combined with ultrafast laser excitation, new phases of matter can result, since far-from-equilibrium excited states are instantaneously populated. Here, we elucidate a general relation between ultrafast non-equilibrium electron dynamics and the size of the characteristic energy gap in a correlated electron material. Here, we show that carrier multiplication via impact ionization can be one of the most important processes in a gapped material, and that the speed of carrier multiplication critically dependsmore » on the size of the energy gap. In the case of the charge-density wave material 1T-TiSe 2, our data indicate that carrier multiplication and gap dynamics mutually amplify each other, which explains—on a microscopic level—the extremely fast response of this material to ultrafast optical excitation.« less

Olefinic Thermoplastic Elastomer Gels: Combining Polymer Crystallization and Microphase Separation in a Selective Solvent

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

Armstrong, Daniel P.; Mineart, Kenneth P.; Lee, Byeongdu

Since selectively swollen thermoplastic elastomer gels (TPEGs) afford a wide range of beneficial properties that open new doors to developing elastomer-based technologies, in this study we examine the unique structure-property behavior of TPEGs composed of olefinic block copolymers (OBCs). Unlike their styrenic counterparts typically possessing two chemically different blocks, this class of multiblock copolymers consists of linear polyethylene hard blocks and poly(ethylene-co-α-octene) soft blocks, in which case, microphase separation between the hard and the soft blocks is accompanied by crystallization of the hard blocks. We prepare olefinic TPEGs (OTPEGs) through the incorporation of a primarily aliphatic oil that selectively swellsmore » the soft block and investigate the resultant morphological features through the use of polarized light microscopy and small-/wideangle X-ray scattering. These features are correlated with thermal and mechanical property measurements from calorimetry, rheology, and extensiometry to elucidate the roles of crystallization and self-assembly on gel characteristics and establish useful structure-property relationships.« less

Density change and viscous flow during structural relaxation of plasma-enhanced chemical-vapor-deposited silicon oxide films

NASA Astrophysics Data System (ADS)

Cao, Zhiqiang; Zhang, Xin

2004-10-01

The structural relaxation of plasma-enhanced chemical-vapor-deposited (PECVD) silane-based silicon oxide films during thermal cycling and annealing has been studied using wafer curvature measurements. These measurements, which determine stress in the amorphous silicon oxide films, are sensitive to both plastic deformation and density changes. A quantitative case study of such changes has been done based upon the experimental results. A microstructure-based mechanism elucidates seams as a source of density change and voids as a source of plastic deformation, accompanied by a viscous flow. This theory was then used to explain a series of experimental results that are related to thermal cycling as well as annealing of PECVD silicon oxide films including stress hysteresis generation and reduction and coefficient of thermal-expansion changes. In particular, the thickness effect was examined; PECVD silicon oxide films with a thickness varying from 1to40μm were studied, as certain demanding applications in microelectromechanical systems require such thick films serving as heat/electrical insulation layers.

Molecular structures guide the engineering of chromatin

PubMed Central

Tekel, Stefan J.

2017-01-01

Abstract Chromatin is a system of proteins, RNA, and DNA that interact with each other to organize and regulate genetic information within eukaryotic nuclei. Chromatin proteins carry out essential functions: packing DNA during cell division, partitioning DNA into sub-regions within the nucleus, and controlling levels of gene expression. There is a growing interest in manipulating chromatin dynamics for applications in medicine and agriculture. Progress in this area requires the identification of design rules for the chromatin system. Here, we focus on the relationship between the physical structure and function of chromatin proteins. We discuss key research that has elucidated the intrinsic properties of chromatin proteins and how this information informs design rules for synthetic systems. Recent work demonstrates that chromatin-derived peptide motifs are portable and in some cases can be customized to alter their function. Finally, we present a workflow for fusion protein design and discuss best practices for engineering chromatin to assist scientists in advancing the field of synthetic epigenetics. PMID:28609787

Olefinic Thermoplastic Elastomer Gels: Combining Polymer Crystallization and Microphase Separation in a Selective Solvent

DOE PAGES

Armstrong, Daniel P.; Mineart, Kenneth P.; Lee, Byeongdu; ...

2016-11-01

Since selectively swollen thermoplastic elastomer gels (TPEGs) afford a wide range of beneficial properties that open new doors to developing elastomer-based technologies, in this study we examine the unique structure-property behavior of TPEGs composed of olefinic block copolymers (OBCs). Unlike their styrenic counterparts typically possessing two chemically different blocks, this class of multiblock copolymers consists of linear polyethylene hard blocks and poly(ethylene-co-α-octene) soft blocks, in which case, microphase separation between the hard and the soft blocks is accompanied by crystallization of the hard blocks. We prepare olefinic TPEGs (OTPEGs) through the incorporation of a primarily aliphatic oil that selectively swellsmore » the soft block and investigate the resultant morphological features through the use of polarized light microscopy and small-/wideangle X-ray scattering. These features are correlated with thermal and mechanical property measurements from calorimetry, rheology, and extensiometry to elucidate the roles of crystallization and self-assembly on gel characteristics and establish useful structure-property relationships.« less

Elucidating the alkaline oxygen evolution reaction mechanism on platinum

DOE PAGES

Favaro, M.; Valero-Vidal, C.; Eichhorn, J.; ...

2017-03-07

Understanding the interplay between surface chemistry, electronic structure, and reaction mechanism of the catalyst at the electrified solid/liquid interface will enable the design of more efficient materials systems for sustainable energy production. The substantial progress in operando characterization, particularly using synchrotron based X-ray spectroscopies, provides the unprecedented opportunity to uncover surface chemical and structural transformations under various (electro)chemical reaction environments. In this work, we study a polycrystalline platinum surface under oxygen evolution conditions in an alkaline electrolyte by means of ambient pressure X-ray photoelectron spectroscopy performed at the electrified solid/liquid interface. We elucidate previously inaccessible aspects of the surface chemistrymore » and structure as a function of the applied potential, allowing us to propose a reaction mechanism for oxygen evolution on a platinum electrode in alkaline solutions.« less

Preservice and Experienced Biology Teachers' Global and Specific Subject Matter Structures: Implications for Conceptions of Pedagogical Content Knowledge

ERIC Educational Resources Information Center

Abd-El-Khalick, Fouad

2006-01-01

This study aimed to describe preservice and experienced secondary biology teachers' global and specific subject matter structures (SMSs) and elucidate the relationship between these structures and teaching experience. Teachers' global and specific SMSs respectively designate their conceptions and/or organization of their disciplines and of…

The Native Production of the Sesquiterpene Isopterocarpolone by Streptomyces sp. RM-14-6

PubMed Central

Shaaban, Khaled A.; Singh, Shanteri; Elshahawi, Sherif I.; Wang, Xiachang; Ponomareva, Larissa V.; Sunkara, Manjula; Copley, Gregory C.; Hower, James C.; Morris, Andrew J.; Kharel, Madan K.; Thorson, Jon S.

2013-01-01

We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, the current study highlights the first native bacterial production of isopterocarpolone and the first full characterization of isopterocarpolone using 1D and 2D NMR spectroscopy and HR-ESI mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery. PMID:24237421

Contrasting magmatic structures between small plutons and batholiths emplaced at shallow crustal level (Sierras de Córdoba, Argentina)

NASA Astrophysics Data System (ADS)

Pinotti, Lucio P.; D'Eramo, Fernando J.; Weinberg, Roberto F.; Demartis, Manuel; Tubía, José María; Coniglio, Jorge E.; Radice, Stefania; Maffini, M. Natalia; Aragón, Eugenio

2016-11-01

Processes like injection, magma flow and differentiation and influence of the regional strain field are here described and contrasted to shed light on their role in the formation of small plutons and large batholiths their magmatic structures. The final geometric and compositional arrangement of magma bodies are a complex record of their construction and internal flow history. Magma injection, flow and differentiation, as well as regional stresses, all control the internal nature of magma bodies. Large magma bodies emplaced at shallow crustal levels result from the intrusion of multiple magma batches that interact in a variety of ways, depending on internal and external dynamics, and where the early magmatic, growth-related structures are commonly overprinted by subsequent history. In contrast, small plutons emplaced in the brittle-ductile transition more likely preserve growth-related structures, having a relatively simple cooling history and limited internal magma flow. Outcrop-scale magmatic structures in both cases record a rich set of complementary information that can help elucidate their evolution. Large and small granitic bodies of the Sierra Pampeanas preserve excellent exposures of magmatic structures that formed as magmas stepped through different rheological states during pluton growth and solidification. These structures reveal not only the flow pattern inside magma chambers, but also the rheological evolution of magmas in response to temperature evolution.

Patient participation in discharge planning conference

PubMed Central

Bångsbo, Angela; Dunér, Anna; Lidén, Eva

2014-01-01

Introduction There is a need for individualized discharge planning to support frail older persons at hospital discharge. In this context, active participation on their behalf cannot be taken for granted. The aim of this study was to elucidate patient participation in discharge planning conferences, with a focus on frail older persons, supported by the theory of positioning described by Harré & van Langenhove. Methods The study was designed as a case study based on audio-recordings of multidisciplinary discharge planning conferences and interviews with health professionals elucidating their opinions on preconditions for patient participation in discharge planning. The analysis has been performed using qualitative content analysis and discourse analysis. Data collection took place during 2008–2009 and included 40 health professionals and 13 frail older persons in hospital or municipal settings. Results Findings revealed four different positions of participation, characterized by the older person's level of activity during the conference and his/her appearance as being reduced (patient) or whole (person). The positions varied dynamically from being an active person, passive person, active patient, or passive patient and the health professionals, next-of-kin, and the older persons themselves contributed to the positioning. Conclusions The findings showed how the institutional setting served as a purposeful structure or a confinement to patient participation. PMID:25411572

A systems biology approach for elucidating the interaction of curcumin with Fanconi anemia FANC G protein and the key disease targets of leukemia.

PubMed

Mahato, David; Samanta, Dipayan; Mukhopadhyay, Sudit S; Krishnaraj, R Navanietha

2017-06-01

Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia. However, its complete mechanism is not elucidated. Herein, a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia. The proteins namely DOT1L, farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK-2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid receptor alpha (RARA) were chosen as disease targets for leukemia and modeled structure of FANC G protein as the disease target for FA. The docking investigations showed that curcumin had a very high binding affinity of -8.1 kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed that they had the comparable binding affinities of -9.7 k cal/mol, -8.7 k cal/mol, and -8.6 k cal/mol, respectively with curcumin. Further, the percentage similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a clue to understand the structural relationships to an extent and to predict the binding affinity. This investigation shows that curcumin effectively interacts with the disease targets of both FA and leukemia.

Neutrophil migration into the placenta: Good, bad or deadly?

PubMed Central

Giaglis, Stavros; Stoikou, Maria; Grimolizzi, Franco; Subramanian, Bibin Y.; van Breda, Shane V.; Hoesli, Irene; Lapaire, Olav; Hasler, Paul; Than, Nandor Gabor; Hahn, Sinuhe

2016-01-01

ABSTRACT Almost 2 decades have passed since the discovery that pregnancy is associated with a basal inflammatory state involving neutrophil activation, and that this is more overt in cases with preeclampsia, than in instances with sepsis. This pivotal observation paved the way for our report, made almost a decade ago, describing the first involvement of neutrophil extracellular traps (NETs) in a non-infectious human pathology, namely preeclampsia, where an abundance of these structures were detected directly in the placental intervillous space. Despite these remarkable findings, there remains a paucity of interest among reproductive biologists in further exploring the role or involvement of neutrophils in pregnancy and related pathologies. In this review we attempt to redress this deficit by highlighting novel recent findings including the discovery of a novel neutrophil subset in the decidua, the interaction of placental protein 13 (PP13) and neutrophils in modulating spiral artery modification, as well as the use of animal model systems to elucidate neutrophil function in implantation, gestation and parturition. These model systems have been particularly useful in identifying key components implicated in recurrent fetal loss, preeclampsia or new signaling molecules such as sphingolipids. Finally, the recent discovery that anti-phospolipid antibodies can trigger NETosis, supports our hypothesis that these structures may contribute to placental dysfunction in pertinent cases with recurrent fetal loss. PMID:26933824

Small-angle neutron scattering reveals the assembly mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase

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

Appolaire, Alexandre; Girard, Eric; Colombo, Matteo

2014-11-01

The present work illustrates that small-angle neutron scattering, deuteration and contrast variation, combined with in vitro particle reconstruction, constitutes a very efficient approach to determine subunit architectures in large, symmetric protein complexes. In the case of the 468 kDa heterododecameric TET peptidase machine, it was demonstrated that the assembly of the 12 subunits is a highly controlled process and represents a way to optimize the catalytic efficiency of the enzyme. The specific self-association of proteins into oligomeric complexes is a common phenomenon in biological systems to optimize and regulate their function. However, de novo structure determination of these important complexesmore » is often very challenging for atomic-resolution techniques. Furthermore, in the case of homo-oligomeric complexes, or complexes with very similar building blocks, the respective positions of subunits and their assembly pathways are difficult to determine using many structural biology techniques. Here, an elegant and powerful approach based on small-angle neutron scattering is applied, in combination with deuterium labelling and contrast variation, to elucidate the oligomeric organization of the quaternary structure and the assembly pathways of 468 kDa, hetero-oligomeric and symmetric Pyrococcus horikoshii TET2–TET3 aminopeptidase complexes. The results reveal that the topology of the PhTET2 and PhTET3 dimeric building blocks within the complexes is not casual but rather suggests that their quaternary arrangement optimizes the catalytic efficiency towards peptide substrates. This approach bears important potential for the determination of quaternary structures and assembly pathways of large oligomeric and symmetric complexes in biological systems.« less

Protein Structures Revealed at Record Pace

ScienceCinema

Hura, Greg

2017-12-11

The structure of a protein in days -- not months or years -- ushers in a new era in genomics research. Berkeley Lab scientists have developed a high-throughput protein pipeline that could expedite the development of biofuels and elucidate how proteins carry out lifes vital functions.

Protein Structures Revealed at Record Pace

ScienceCinema

Greg Hura

2017-12-09

The structure of a protein in days -- not months or years -- ushers in a new era in genomics research. Berkeley Lab scientists have developed a high-throughput protein pipeline that could expedite the development of biofuels and elucidate how proteins carry out lifes vital functions.

Structural insights into selective agonist actions of tamoxifen on human estrogen receptor alpha.

PubMed

Chakraborty, Sandipan; Biswas, Pradip Kumar

2014-08-01

Tamoxifen-an anti-estrogenic ligand in breast tissues used as a first-line treatment in estrogen receptor (ER)-positive breast cancers-is associated with the development of resistance followed by resumption of tumor growth in about 30 % of cases. Whether tamoxifen assists in proliferation in such cases or whether any ligand-independent pathway to transcription exists is not fully understood; also, no ERα mutants have been detected so far that could lead to tamoxifen resistance. Using in silico conformational analysis of the ERα ligand binding domain (LBD), in the absence and presence of selective agonist (diethylstilbestrol; DES), antagonist (Faslodex; ICI), and selective estrogen receptor modulator (SERM; 4-hydroxy tamoxifen; 4-OHT) ligands, we have elucidated ligand-responsive structural modulations of the ERα-LBD dimer in its agonist and antagonist complexes to address the issue of "tamoxifen resistance". DES and ICI were found to stabilize the dimer in their agonist and antagonist conformations, respectively. The ERα-LBD dimer without the presence of any bound ligand also led to a stable structure in agonist conformation. However, binding of 4-OHT to the antagonist structure led to a flexible conformation allowing the protein to visit conformations populated by agonists as was evident from principal component analysis and radius of gyration plots. Further, the relaxed conformations of the 4-OHT bound protein exhibited a diminished size of the co-repressor binding pocket in the LBD, thus signaling a partial blockage of the co-repressor binding motif. Thus, the ability of 4-OHT-bound ERα-LBD to assume flexible conformations visited by agonists and reduced co-repressor binding surface at the LBD provide crucial structural insights into tamoxifen-resistance that complement our existing understanding.

Novel selective TOCSY method enables NMR spectral elucidation of metabolomic mixtures

NASA Astrophysics Data System (ADS)

MacKinnon, Neil; While, Peter T.; Korvink, Jan G.

2016-11-01

Complex mixture analysis is routinely encountered in NMR-based investigations. With the aim of component identification, spectral complexity may be addressed chromatographically or spectroscopically, the latter being favored to reduce sample handling requirements. An attractive experiment is selective total correlation spectroscopy (sel-TOCSY), which is capable of providing tremendous spectral simplification and thereby enhancing assignment capability. Unfortunately, isolating a well resolved resonance is increasingly difficult as the complexity of the mixture increases and the assumption of single spin system excitation is no longer robust. We present TOCSY optimized mixture elucidation (TOOMIXED), a technique capable of performing spectral assignment particularly in the case where the assumption of single spin system excitation is relaxed. Key to the technique is the collection of a series of 1D sel-TOCSY experiments as a function of the isotropic mixing time (τm), resulting in a series of resonance intensities indicative of the underlying molecular structure. By comparing these τm -dependent intensity patterns with a library of pre-determined component spectra, one is able to regain assignment capability. After consideration of the technique's robustness, we tested TOOMIXED firstly on a model mixture. As a benchmark we were able to assign a molecule with high confidence in the case of selectively exciting an isolated resonance. Assignment confidence was not compromised when performing TOOMIXED on a resonance known to contain multiple overlapping signals, and in the worst case the method suggested a follow-up sel-TOCSY experiment to confirm an ambiguous assignment. TOOMIXED was then demonstrated on two realistic samples (whisky and urine), where under our conditions an approximate limit of detection of 0.6 mM was determined. Taking into account literature reports for the sel-TOCSY limit of detection, the technique should reach on the order of 10 μ M sensitivity. We anticipate this technique will be highly attractive to various analytical fields facing mixture analysis, including metabolomics, foodstuff analysis, pharmaceutical analysis, and forensics.

Formability and thermal stability of phase in (Fe1-y Coy)-(B, C, N) films

NASA Astrophysics Data System (ADS)

Sunaga, K.; Kadowaki, S.; Tsunoda, M.; Takahashi, M.

2004-06-01

In order to find a way to obtain stable -Fe16X2 phase, the formability and thermal stability of (bct) phase were discussed. According to a rigid sphere model, we concluded that the less formability of B for the phase is due to its large atomic radius. We elucidated the difference of thermal stability of -Fe-X, taking into account their decomposition process. While, the decomposition of -Fe-N progresses only by the migration of N, without changing the bone structure of Fe lattice, the additional energy is needed to break the original α-Fe lattice in the cases of α-Fe-B and α-Fe-C. Therefore thermal stability of α-Fe-B and α-Fe-C is higher than that of α-Fe-N.

Pyrrole Oligoglycosides from the Starfish Acanthaster planci Suppress Lipopolysaccharide-Induced Nitric Oxide Production in RAW264.7 Macrophages.

PubMed

Vien, Le Thi; Hanh, Tran Thi Hong; Huong, Phan Thi Thanh; Dang, Nguyen Hai; Thanh, Nguyen Van; Lyakhova, Ekaterina; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Kiem, Phan Van; Kicha, Alla; Minh, Chau Van

2016-11-01

Two new pyrrole oligoglycosides, plancipyrrosides A and B (1 and 2), were isolated from methanol extract of the Vietnamese starfish Acanthaster planci using various chromatographic procedures. Their structures were elucidated by spectroscopic methods including one and two dimensional (1D- and 2D)-NMR and Fourier transform ion cyclotron resonance (FT-ICR)-MS. The finding of 1 and 2 represents the third case of pyrrole oligoglycosides obtaining reported to date. Moreover, plancipyrroside B (2) exhibits a potent inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells with IC 50 of 5.94±0.34 µM, whereas plancipyrroside A (1) shows this inhibitory activity with IC 50 of 16.61±1.85 µM.

Grain-boundary free energy in an assembly of elastic disks.

PubMed

Lusk, Mark T; Beale, Paul D

2004-02-01

Grain-boundary free energy is estimated as a function of misoriention for symmetric tilt boundaries in an assembly of nearly hard disks. Fluctuating cell theory is used to accomplish this since the most common techniques for calculating interfacial free energy cannot be applied to such assemblies. The results are analogous to those obtained using a Leonard-Jones potential, but in this case the interfacial energy is dominated by an entropic contribution. Disk assemblies colorized with free and specific volume elucidate differences between these two characteristics of boundary structure. Profiles are also provided of the Helmholtz and Gibbs free energies as a function of distance from the grain boundaries. Low angle grain boundaries are shown to follow the classical relationship between dislocation orientation/spacing and misorientation angle.

A coupled subsurface-boundary layer model of water on Mars

NASA Astrophysics Data System (ADS)

Zent, A. P.; Haberle, R. M.; Houben, H. C.; Jakosky, B. M.

1993-02-01

A 1D numerical model of the exchange of H2O between the atmosphere and subsurface of Mars through the PBL is employed to explore the mechanisms of H2O exchange and to elucidate the role played by the regolith in the local H2O budget. The atmospheric model includes effects of Coriolis, pressure gradient, and frictional forces for momentum: radiation, sensible heat flux, and advection for heat. It is suggested that in most cases, the flux through the Martian surface reverses twice in the course of each sol. The effects of surface albedo, thermal inertia, solar declination, atmospheric optical depth, and regolith pore structure are explored. It is proposed that higher thermal inertia forces more H2O into the atmosphere because the regolith is warmer at depth.

Congenital prosopagnosia: face-blind from birth.

PubMed

Behrmann, Marlene; Avidan, Galia

2005-04-01

Congenital prosopagnosia refers to the deficit in face processing that is apparent from early childhood in the absence of any underlying neurological basis and in the presence of intact sensory and intellectual function. Several such cases have been described recently and elucidating the mechanisms giving rise to this impairment should aid our understanding of the psychological and neural mechanisms mediating face processing. Fundamental questions include: What is the nature and extent of the face-processing deficit in congenital prosopagnosia? Is the deficit related to a more general perceptual deficit such as the failure to process configural information? Are any neural alterations detectable using fMRI, ERP or structural analyses of the anatomy of the ventral visual cortex? We discuss these issues in relation to the existing literature and suggest directions for future research.

Epigenomics.

PubMed

Gomase, Virendra S; Tagore, Somnath

2008-03-01

'Epigenomics' can be termed as the study of the effects of chromatin structure, including the higher order of chromatin folding and attachment to the nuclear matrix, packaging of DNA around nucleosomes, covalent modifications of histone tails and DNA methylation. This has evolved to include any process that alters gene activity without changing the DNA sequence, and leads to modifications that can be transmitted to daughter cells. It also leads to a better knowledge of the changes in the regulation of genes and genomes that occur in major psychosis. It may also aid in understanding why the same gene sequence may predispose an individual to schizophrenia or bipolar disorder and in other cases does not, and elucidate the molecular mechanisms of how harmful; environmental factors interact with the genome. Results from the work may further lead to new diagnostics and effective therapies.

Comprehensive 5-Year Study of Cytogenetic Aberrations in 668 Infertile Men

PubMed Central

Yatsenko, Alexander N.; Yatsenko, Svetlana A.; Weedin, John W.; Lawrence, Amy E.; Patel, Ankita; Peacock, Sandra; Matzuk, Martin M.; Lamb, Dolores J.; Cheung, Sau Wai; Lipshultz, Larry I.

2010-01-01

Purpose The causes of male infertility are heterogeneous but more than 50% of cases have a genetic basis. Specific genetic defects have been identified in less than 20% of infertile males and, thus, most causes remain to be elucidated. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions. To refine the incidence and nature of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 668 infertile men with oligozoospermia and azoospermia. Materials and Methods High resolution Giemsa banding chromosome analysis and/or fluorescence in situ hybridization were done in 668 infertile males referred for routine cytogenetic analysis between January 2004 and March 2009. Results The overall incidence of chromosomal abnormalities was about 8.2%. Of the 55 patients with abnormal cytogenetic findings sex chromosome aneuploidies were observed in 29 (53%), including Klinefelter syndrome in 27 (49%). Structural chromosome abnormalities involving autosomes (29%) and sex chromosomes (18%) were detected in 26 infertile men. Abnormal cytogenetic findings were observed in 35 of 264 patients (13.3%) with azoospermia and 19 of 365 (5.2%) with oligozoospermia. Conclusions Structural chromosomal defects and low level sex chromosome mosaicism are common in oligozoospermia cases. Extensive cytogenetic assessment and fluorescence in situ hybridization may improve the detection rate in males with oligozoospermia. These findings highlight the need for efficient genetic testing in infertile men so that couples may make informed decisions on assisted reproductive technologies to achieve parenthood. PMID:20172548

Single Molecule Study of Cellulase Hydrolysis of Crystalline Cellulose

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

Liu, Y.-S.; Luo, Y.; Baker, J. O.

This report seeks to elucidate the role of cellobiohydrolase-I (CBH I) in the hydrolysis of crystalline cellulose. A single-molecule approach uses various imaging techniques to investigate the surface structure of crystalline cellulose and changes made in the structure by CBH I.

Roles of water in protein structure and function studied by molecular liquid theory.

PubMed

Imai, Takashi

2009-01-01

The roles of water in the structure and function of proteins have not been completely elucidated. Although molecular simulation has been widely used for the investigation of protein structure and function, it is not always useful for elucidating the roles of water because the effect of water ranges from atomic to thermodynamic level. The three-dimensional reference interaction site model (3D-RISM) theory, which is a statistical-mechanical theory of molecular liquids, can yield the solvation structure at the atomic level and calculate the thermodynamic quantities from the intermolecular potentials. In the last few years, the author and coworkers have succeeded in applying the 3D-RISM theory to protein aqueous solution systems and demonstrated that the theory is useful for investigating the roles of water. This article reviews some of the recent applications and findings, which are concerned with molecular recognition by protein, protein folding, and the partial molar volume of protein which is related to the pressure effect on protein.

Glucansucrases: three-dimensional structures, reactions, mechanism, α-glucan analysis and their implications in biotechnology and food applications.

PubMed

Leemhuis, Hans; Pijning, Tjaard; Dobruchowska, Justyna M; van Leeuwen, Sander S; Kralj, Slavko; Dijkstra, Bauke W; Dijkhuizen, Lubbert

2013-01-20

Glucansucrases are extracellular enzymes that synthesize a wide variety of α-glucan polymers and oligosaccharides, such as dextran. These carbohydrates have found numerous applications in food and health industries, and can be used as pure compounds or even be produced in situ by generally regarded as safe (GRAS) lactic acid bacteria in food applications. Research in the recent years has resulted in big steps forward in the understanding and exploitation of the biocatalytic potential of glucansucrases. This paper provides an overview of glucansucrase enzymes, their recently elucidated crystal structures, their reaction and product specificity, and the structural analysis and applications of α-glucan polymers. Furthermore, we discuss key developments in the understanding of α-glucan polymer formation based on the recently elucidated three-dimensional structures of glucansucrase proteins. Finally we discuss the (potential) applications of α-glucans produced by lactic acid bacteria in food and health related industries. Copyright © 2012 Elsevier B.V. All rights reserved.

Predictive and Experimental Approaches for Elucidating Protein–Protein Interactions and Quaternary Structures

PubMed Central

Nealon, John Oliver; Philomina, Limcy Seby

2017-01-01

The elucidation of protein–protein interactions is vital for determining the function and action of quaternary protein structures. Here, we discuss the difficulty and importance of establishing protein quaternary structure and review in vitro and in silico methods for doing so. Determining the interacting partner proteins of predicted protein structures is very time-consuming when using in vitro methods, this can be somewhat alleviated by use of predictive methods. However, developing reliably accurate predictive tools has proved to be difficult. We review the current state of the art in predictive protein interaction software and discuss the problem of scoring and therefore ranking predictions. Current community-based predictive exercises are discussed in relation to the growth of protein interaction prediction as an area within these exercises. We suggest a fusion of experimental and predictive methods that make use of sparse experimental data to determine higher resolution predicted protein interactions as being necessary to drive forward development. PMID:29206185

Structural Elucidation of Enzymatically Synthesized Galacto-oligosaccharides Using Ion-Mobility Spectrometry-Tandem Mass Spectrometry.

PubMed

Carević, Milica; Bezbradica, Dejan; Banjanac, Katarina; Milivojević, Ana; Fanuel, Mathieu; Rogniaux, Hélène; Ropartz, David; Veličković, Dušan

2016-05-11

Galacto-oligosaccharides (GOS) represent a diverse group of well-characterized prebiotic ingredients derived from lactose in a reaction catalyzed with β-galactosidases. Enzymatic transgalactosylation results in a mixture of compounds of various degrees of polymerization and types of linkages. Because structure plays an important role in terms of prebiotic activity, it is of crucial importance to provide an insight into the mechanism of transgalactosylation reaction and occurrence of different types of β-linkages during GOS synthesis. Our study proved that a novel one-step method, based on ion-mobility spectrometry-tandem mass spectrometry (IMS-MS/MS), enables complete elucidation of GOS structure. It has been shown that β-galactosidase from Aspergillus oryzae has the highest affinity toward formation of β-(1→3) or β-(1→6) linkages. Additionally, it was observed that the occurrence of different linkages varies during the reaction course, indicating that tailoring favorable GOS structures with improved prebiotic activity can be achieved by adequate control of enzymatic synthesis.

The cingulum: A unique structure of some Dolichopodidae

Treesearch

Justin Runyon

2008-01-01

The cingulum is a U-shaped structure of unknown function which arises between abdominal sterna 4 and 5 and terminates in a pair of variously modified flag-like appendages. This structure is well developed only in males of the genus Scellus. Richard Hurley discovered that Hydatostega have a much reduced cingulum, a finding that had broad implications for elucidating...

Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

DOE PAGES

Boiteau, Rene M.; Hoyt, David W.; Nicora, Carrie D.; ...

2018-01-17

Here, we introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS 2), and NMR in a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS 2 approach is well suited for discovery ofmore » new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.« less

Isolation, Structural Modification, and HIV Inhibition of Pentacyclic Lupane-Type Triterpenoids from Cassine xylocarpa and Maytenus cuzcoina.

PubMed

Callies, Oliver; Bedoya, Luis M; Beltrán, Manuela; Muñoz, Alejandro; Calderón, Patricia Obregón; Osorio, Alex A; Jiménez, Ignacio A; Alcamí, José; Bazzocchi, Isabel L

2015-05-22

As a part of our investigation into new anti-HIV agents, we report herein the isolation, structure elucidation, and biological activity of six new (1-6) and 20 known (7-26) pentacyclic lupane-type triterpenoids from the stem of Cassine xylocarpa and root bark of Maytenus cuzcoina. Their stereostructures were elucidated on the basis of spectroscopic and spectrometric methods, including 1D and 2D NMR techniques. To gain a more complete understanding of the structural requirements for anti-HIV activity, derivatives 27-48 were prepared by chemical modification of the main secondary metabolites. Sixteen compounds from this series displayed inhibitory effects of human immunodeficiency virus type 1 replication with IC50 values in the micromolar range, highlighting compounds 12, 38, and 42 (IC50 4.08, 4.18, and 1.70 μM, respectively) as the most promising anti-HIV agents.

Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

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

Boiteau, Rene M.; Hoyt, David W.; Nicora, Carrie D.

Here, we introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS 2), and NMR in a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS 2 approach is well suited for discovery ofmore » new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.« less

Solid state compatibility study and characterization of a novel degradation product of tacrolimus in formulation.

PubMed

Rozman Peterka, Tanja; Grahek, Rok; Hren, Jure; Bastarda, Andrej; Bergles, Jure; Urleb, Uroš

2015-06-10

Tacrolimus is macrolide drug that is widely used as a potent immunosuppressant. In the present work compatibility testing was conducted on physical mixtures of tacrolimus with excipients and on compatibility mixtures prepared by the simulation of manufacturing process used for the final drug product preparation. Increase in one major degradation product was detected in the presence of magnesium stearate based upon UHPLC analysis. The degradation product was isolated by preparative HPLC and its structure was elucidated by NMR and MS studies. Mechanism of the formation of this degradation product is proposed based on complementary degradation studies in a solution and structural elucidation data. The structure was proven to be alpha-hydroxy acid which is formed from the parent tacrolimus molecule through a benzilic acid type rearrangement reaction in the presence of divalent metallic cations. Degradation is facilitated at higher pH values. Copyright © 2015 Elsevier B.V. All rights reserved.

Methods for isolation of marine-derived endophytic fungi and their bioactive secondary products.

PubMed

Kjer, Julia; Debbab, Abdessamad; Aly, Amal H; Proksch, Peter

2010-03-01

Marine-derived fungi have been shown in recent years to produce a plethora of new bioactive secondary metabolites, some of them featuring new carbon frameworks hitherto unprecedented in nature. These compounds are of interest as new lead structures for medicine as well as for plant protection. The aim of this protocol is to give a detailed description of methods useful for the isolation and cultivation of fungi associated with various marine organisms (sponges, algae and mangrove plants) for the extraction, characterization and structure elucidation of biologically active secondary metabolites produced by these marine-derived endophytic fungi, and for the preliminary evaluation of their pharmacological properties based on rapid 'in house' screening systems. Some results exemplifying the positive outcomes of the protocol are given at the end. From sampling in marine environment to completion of the structure elucidation and bioactivity screening, a period of at least 3 months has to be scheduled.

Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

PubMed Central

Hoyt, David W.; Nicora, Carrie D.; Kinmonth-Schultz, Hannah A.; Ward, Joy K.

2018-01-01

We introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS2), and NMR into a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter out the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture, and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS2 approach is well suited to the discovery of new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases. PMID:29342073

Breaking the icosahedra in boron carbide

PubMed Central

Xie, Kelvin Y.; An, Qi; Sato, Takanori; Breen, Andrew J.; Ringer, Simon P.; Goddard, William A.; Cairney, Julie M.; Hemker, Kevin J.

2016-01-01

Findings of laser-assisted atom probe tomography experiments on boron carbide elucidate an approach for characterizing the atomic structure and interatomic bonding of molecules associated with extraordinary structural stability. The discovery of crystallographic planes in these boron carbide datasets substantiates that crystallinity is maintained to the point of field evaporation, and characterization of individual ionization events gives unexpected evidence of the destruction of individual icosahedra. Statistical analyses of the ions created during the field evaporation process have been used to deduce relative atomic bond strengths and show that the icosahedra in boron carbide are not as stable as anticipated. Combined with quantum mechanics simulations, this result provides insight into the structural instability and amorphization of boron carbide. The temporal, spatial, and compositional information provided by atom probe tomography makes it a unique platform for elucidating the relative stability and interactions of primary building blocks in hierarchically crystalline materials. PMID:27790982

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

The Role of Prosody in a Case of Foreign Accent Syndrome (FAS)

ERIC Educational Resources Information Center

Katz, William F.; Garst, Diane M.; Levitt, June

2008-01-01

Foreign accent syndrome (FAS) is a rare disorder characterized by the emergence of a perceived foreign accent following brain damage. The symptomotology, functional bases, and neural substrates of this disorder are still being elucidated. In this case study, acoustic analyses were performed on the speech of a 46-year old monolingual female who…

Osteosarcoma

Cancer.gov

The TARGET Osteosarcoma (OS) project elucidates comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of high-risk or hard-to-treat childhood cancers.The OS project has produced comprehensive genomic profiles of nearly 100 clinically annotated patient cases within the discovery dataset. Each fully-characterized TARGET OS case includes data from nucleic acid samples extracted from tumor and normal tissue.

Use of musculoskeletal ultrasonography in the diagnosis of pes anserine tendinitis: a case report.

PubMed

Valley, V T; Shermer, C D

2001-01-01

A 45-year-old woman presented to the Emergency Department with a chief complaint of acute, nontraumatic medial knee pain. Musculoskeletal ultrasonography was performed, and the diagnosis of pes anserine tendinitis was elucidated. A discussion of this clinical entity, the characteristic ultrasonographic findings, and therapy follow in this case report.

Convection roll-driven generation of supra-wavelength periodic surface structures on dielectrics upon irradiation with femtosecond pulsed lasers

NASA Astrophysics Data System (ADS)

Tsibidis, George D.; Skoulas, Evangelos; Papadopoulos, Antonis; Stratakis, Emmanuel

2016-08-01

The significance of the magnitude of the Prandtl number of a fluid in the propagation direction of induced convection rolls is elucidated. Specifically, we report on the physical mechanism to account for the formation and orientation of previously unexplored supra-wavelength periodic surface structures in dielectrics, following melting and subsequent capillary effects induced upon irradiation with ultrashort laser pulses. Counterintuitively, it is found that such structures exhibit periodicities, which are markedly, even multiple times, higher than the laser excitation wavelength. It turns out that the extent to which the hydrothermal waves relax depends upon the laser beam energy, produced electron densities upon excitation with femtosecond pulsed lasers, the magnitude of the induced initial local roll disturbances, and the magnitude of the Prandtl number with direct consequences on the orientation and size of the induced structures. It is envisaged that this elucidation may be useful for the interpretation of similar, albeit large-scale periodic or quasiperiodic structures formed in other natural systems due to thermal gradients, while it can also be of great importance for potential applications in biomimetics.

Archaeal RNA polymerase and transcription regulation

PubMed Central

Jun, Sung-Hoon; Reichlen, Matthew J.; Tajiri, Momoko; Murakami, Katsuhiko S.

2010-01-01

To elucidate the mechanism of transcription by cellular RNA polymerases (RNAPs), high resolution X-ray crystal structures together with structure-guided biochemical, biophysical and genetics studies are essential. The recently-solved X-ray crystal structures of archaeal RNA polymerase (RNAP) allow a structural comparison of the transcription machinery among all three domains of life. The archaea were once thought of closely related to bacteria, but they are now considered to be more closely related to the eukaryote at the molecular level than bacteria. According to these structures, the archaeal transcription apparatus, which includes RNAP and general transcription factors, is similar to the eukaryotic transcription machinery. Yet, the transcription regulators, activators and repressors, encoded by archaeal genomes are closely related to bacterial factors. Therefore, archaeal transcription appears to possess an intriguing hybrid of eukaryotic-type transcription apparatus and bacterial-like regulatory mechanisms. Elucidating the transcription mechanism in archaea, which possesses a combination of bacterial and eukaryotic transcription mechanisms that are commonly regarded as separate and mutually exclusive, can provide data that will bring basic transcription mechanisms across all three domains of life. PMID:21250781

Molecular modeling of the AhR structure and interactions can shed light on ligand-dependent activation and transformation mechanisms.

PubMed

Bonati, Laura; Corrada, Dario; Tagliabue, Sara Giani; Motta, Stefano

2017-02-01

Molecular modeling has given important contributions to elucidation of the main stages in the AhR signal transduction pathway. Despite the lack of experimentally determined structures of the AhR functional domains, information derived from homologous systems has been exploited for modeling their structure and interactions. Homology models of the AhR PASB domain have provided information on the binding cavity and contributed to elucidate species-specific differences in ligand binding. Molecular Docking simulations of the ligand binding process have given insights into differences in binding of diverse agonists, antagonists, and selective AhR modulators, and their application to virtual screening of large databases of compounds have allowed identification of novel AhR ligands. Recently available structural information on protein-protein and protein-DNA complexes of other bHLH-PAS systems has opened the way for modeling the AhR:ARNT dimer structure and investigating the mechanisms of AhR transformation and DNA binding. Future research directions should include simulation of the protein dynamics to obtain a more reliable description of intermolecular interactions involved in signal transmission.

Mode of bindings of zinc oxide nanoparticles to myoglobin and horseradish peroxidase: A spectroscopic investigations

NASA Astrophysics Data System (ADS)

Mandal, Gopa; Bhattacharya, Sudeshna; Ganguly, Tapan

2011-07-01

The interactions between two heme proteins myoglobin (HMb) and horseradish peroxidase (HRP) with zinc oxide (ZnO) nanoparticles are investigated by using UV-vis absorption, steady state fluorescence, synchronous fluorescence, time-resolved fluorescence, FT-IR, atomic force microscopy (AFM) and circular dichroism (CD) techniques under physiological condition of pH˜7.4. The presence of mainly static mode in fluorescence quenching mechanism of HMb and HRP by ZnO nanoparticle indicates the possibility of formation of ground state complex. The processes of bindings of ZnO nanoparticles with the two proteins are spontaneous molecular interaction procedures. In both cases hydrogen bonding plays a major role. The circular dichroism (CD) spectra reveal that a helicity of the proteins is reduced by increasing ZnO nanoparticle concentration although the α-helical structures of HMb and HRP retain their identity. On binding to the ZnO nanoparticles the secondary structure of HRP molecules (or HMb molecules) remains unchanged while there is a substantial change in the environment of the tyrosin active site in case of HRP molecules and tryptophan active site in case of HMb molecules. Tapping mode atomic force microscopy (AFM) was applied for the investigation the structure of HRP adsorbed in the environment of nanoparticles on the silicon and on the bare silicon. HRP molecules adsorb and aggregate on the mica with ZnO nanoparticle. The aggregation indicates an attractive interaction among the adsorbed molecules. The molecules are randomly distributed on the bare silicon wafer. The adsorption of HRP in the environment of ZnO nanoparticle changes drastically the domains due to a strong interaction between HRP and ZnO nanoparticles. Similar situation is observed in case of HMb molecules. These findings demonstrate the efficacy of biomedical applications of ZnO nanoparticles as well as in elucidating their mechanisms of action as drugs in both human and plant systems.

Isolation, structural elucidation, MS profiling, and evaluation of triglyceride accumulation inhibitory effects of benzophenone C-glucosides from leaves of Mangifera indica L.

PubMed

Zhang, Yi; Han, Lifeng; Ge, Dandan; Liu, Xuefeng; Liu, Erwei; Wu, Chunhua; Gao, Xiumei; Wang, Tao

2013-02-27

Seventy percent ethanol-water extract from the leaves of Mangifera indica L. (Anacardiaceae) was found to show an inhibitory effect on triglyceride (TG) accumulation in 3T3-L1 cells. From the active fraction, six new benzophenone C-glucosides, foliamangiferosides A(3) (1), A(4) (2), C(4) (3), C(5) (4), C(6) (5), and C(7) (6) together with 11 known benzophenone C-glucosides (7-17) were obtained. In this paper, isolation, structure elucidation (1-6), and MS fragment cleavage pathways of all 17 isolates were studied. 1-6 showed inhibitory effects on TG and free fatty acid accumulation in 3T3-L1 cells at 10 μM.

[Studies on chemical constituents from herbs of Botrychium lanuginosum].

PubMed

Wang, Dong; Liu, Xiao-qiu; Yao, Chun-suo; Fang, Wei-shuo

2008-11-01

To study the chemical constituents of Botrychium lanuginosum. Various chromatographic techniques were used to isolate and purify the constituents. The structures were elucidated by chemical evidence and spectroscopic methods. Ten compounds were isolated from the 95% ethanol extract of the herb of B. lanuginosum and their structures were elucidated as 30-nor-21beta-hopan-22-one (1), beta-sitosterol (2), luteolin (3), thunberginol A (4), apigenin (5), (6'-O-palmitoyl)-sitosterol-3-O-beta-D-glucoside (6), daucosterol (7), 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2R-hydroxy hexadecanoyl) amino]-4, 8-octadecadiene-1, 3-diol (8), luteolin-7-O-glucoside (9), sucrose (10). Compounds 1-10 were isolated from this genus for the first time.

The current status of the Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) species complex

PubMed Central

Souza, Nataly A; Brazil, Reginaldo P; Araki, Alejandra S

2017-01-01

Lutzomyia longipalpis s.l. is a complex of sibling species and is the principal vector of American visceral leishmaniasis. The present review summarises the diversity of efforts that have been undertaken to elucidate the number of unnamed species in this species complex and the phylogenetic relationships among them. A wide variety of evidence, including chemical, behavioral and molecular traits, suggests very recent speciation events and complex population structure in this group. Although significant advances have been achieved to date, differential vector capacity and the correlation between structure of parasite and vector populations have yet to be elucidated. Furthermore, increased knowledge about recent epidemiological changes, such as urbanisation, is essential for pursuing effective strategies for sandfly control in the New World. PMID:28225906

The current status of the Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) species complex.

PubMed

Souza, Nataly A; Brazil, Reginaldo P; Araki, Alejandra S

2017-03-01

Lutzomyia longipalpis s.l. is a complex of sibling species and is the principal vector of American visceral leishmaniasis. The present review summarises the diversity of efforts that have been undertaken to elucidate the number of unnamed species in this species complex and the phylogenetic relationships among them. A wide variety of evidence, including chemical, behavioral and molecular traits, suggests very recent speciation events and complex population structure in this group. Although significant advances have been achieved to date, differential vector capacity and the correlation between structure of parasite and vector populations have yet to be elucidated. Furthermore, increased knowledge about recent epidemiological changes, such as urbanisation, is essential for pursuing effective strategies for sandfly control in the New World.

Isolation, structure elucidation and DFT study on two novel oligosaccharides from yak milk

NASA Astrophysics Data System (ADS)

Singh, Meenakshi; Kumar, Alok; Srivastava, Gaurav; Deepak, Desh; Singh, M. P. V. V.

2016-08-01

Two novel oligosaccharides were isolated from yak milk. The milk was processed by the method of Kobata and Ginsberg involving deproteination, centrifugation and lyophilization followed by gel filtrate chromatography acetylation and silica gel column chromatography of derivatized oligosaccharides while their homogeneity was confirmed by HPLC. The structures of these isolated oligosaccharides were elucidated by chemical transformation, chemical degradation, 1H, 13C NMR, 2D NMR (COSY, TOCSY and HSQC) and mass spectrometry. The geometry of compound A (Bosiose) and B (Bovisose) have been optimized at B3LYP method and 6-311 + G(d,p) basis set. The difference between the energies of A and B is 1.269 a.u. or 796.309 kcal/mol.

[n-Butyl Alcohol-soluble Chemical Constituents of Psidium guajava Leaves].

PubMed

Chen, Gang; Wan, Kai-hua; Fu, Hui-zheng; Yan, Qing-wei

2015-03-01

To study the chemical constituents of the leaves of Psidium guajava. The chemical constituents were isolated by column chromatography on silica gel, Sephadex LH-20 and MPLC. Their chemical structures were elucidated on the basis of special analysis. Seven compounds were isolated from n-butyl alcohol fraction, whose structures were elucidated as morin-3-O-α-L-arabopyranoside (1), morin-3-O-α-L-iyxopyranoside (2), 2,6-dihydroxy-4-O-β-D-glucopyranosyl-benzophenone (3), casuarictin (4),2,6-dihydroxy-3,5-dimethyl-4-O-(6"-O-galloyl-β-D-glucopyranosyl)-benzophenone(5), globulusin A(6), and kaempferol-3-O-β-D-(6"-galloyl) galactopyranoside (7). Compounds 3 and 5 ~ 7 are isolated from this plant for the first time.

Drying-induced atomic structural rearrangements in sodium-based calcium-alumino-silicate-hydrate gel and the mitigating effects of ZrO 2 nanoparticles

DOE PAGES

Yang, Kengran; Özçelik, V. Ongun; Garg, Nishant; ...

2018-01-01

Drying-induced nanoscopic alterations to the local atomic structure of silicate-activated slag and the mitigated effects of nano-ZrO2 are elucidated using in situ X-ray pair distribution function analysis.

Drying-induced atomic structural rearrangements in sodium-based calcium-alumino-silicate-hydrate gel and the mitigating effects of ZrO 2 nanoparticles

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

Yang, Kengran; Özçelik, V. Ongun; Garg, Nishant

Drying-induced nanoscopic alterations to the local atomic structure of silicate-activated slag and the mitigated effects of nano-ZrO2 are elucidated using in situ X-ray pair distribution function analysis.

Addison's Disease Mimicking as Acute Pancreatitis: A Case Report.

PubMed

Chaudhuri, Sayani; Rao, Karthik N; Patil, Navin; Ommurugan, Balaji; Varghese, George

2017-04-01

Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison's disease. Adrenal insufficiency (Addison's disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison's disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis.

[Studies on chemical constituents of Heterosmilax yunnanensis].

PubMed

Qin, Wen-jie; Wang, Gang-li; Lin, Rui-chao

2007-08-01

To study the chemical constituents of Heterosmilax yunianensis. The compounds were isolated and repeatedly purified with chromatograph and the structures were elucidated by physico-chemical properties and spectral analysis. Eight compounds were obtained and elucidated as beta-sitosterol (I), glycerol monopalmitate (II), daucosterol (IIl), hexacosanoic acid (IV), 5-hydroxymethyl furaldehyde (V), hergapen (VI), ursolic acid (VII), liquiritigenin (VIII). They have been isolated from this plant for the first time, and IV - VIII are obtained from the plants of Heterosmilax for the first time.

Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach.

PubMed

Zhang, Xiangyu; Jiang, Hailun; Li, Wei; Wang, Jian; Cheng, Maosheng

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors.

Topological characteristics of helical repeat proteins.

PubMed

Groves, M R; Barford, D

1999-06-01

The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem repeats of an alpha-helical structural unit, creating extended superhelical structures that are ideally suited to create a protein recognition interface.

Polymorphism in phenobarbital: discovery of a new polymorph and crystal structure of elusive form V.

PubMed

Roy, Saikat; Goud, N Rajesh; Matzger, Adam J

2016-03-21

This report highlights the discovery of a new polymorph of the anticonvulsant drug phenobarbital (PB) using polymer-induced heteronucleation (PIHn) and unravelling the crystal structure of the elusive form V. Both forms are characterized by structural, thermal and VT-Raman spectroscopy methods to elucidate phase transformation behavior and shed light on stability relationships.

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins

PubMed Central

Cremonez, Caroline M.; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A. A.; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M. C.; Arantes, Eliane C.; Tytgat, Jan

2016-01-01

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx. PMID:27706049

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins.

PubMed

Cremonez, Caroline M; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A A; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M C; Arantes, Eliane C; Tytgat, Jan

2016-09-30

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx.

Analytic studies on satellite detection of severe, two-cell tornadoes

NASA Technical Reports Server (NTRS)

Carrier, G. F.; Dergarabedian, P.; Fendell, F. E.

1979-01-01

It is argued that a two-cell structure is likely to be the unique property, and potentially satellite-accessible observable, of the exceptionally severe tornado. Analysis elucidating the dynamic, thermodynamic, and geometric properties of this two-cell structure is described. The analysis ultimately will furnish instrumentation requirements.

Using Jigsaw-Style Spectroscopy Problem-Solving to Elucidate Molecular Structure through Online Cooperative Learning

ERIC Educational Resources Information Center

Winschel, Grace A.; Everett, Renata K.; Coppola, Brian P.; Shultz, Ginger V.

2015-01-01

Cooperative learning was employed as an instructional approach to facilitate student development of spectroscopy problem solving skills. An interactive online environment was used as a framework to structure weekly discussions around spectroscopy problems outside of class. Weekly discussions consisted of modified jigsaw-style problem solving…

Isolation and structure determination of a lignan from the bark of Salix alba.

PubMed

Du, Qizhen; Jerz, Gerold; Shen, Lianqing; Xiu, Lili; Winterhalter, Peter

2007-05-01

A lignan, sisymbrifolin (1) found in the fruits of Solanum sisymbriflolium has been isolated from the bark extract of Salix alba (Salicaceae). Its structure was elucidated by its direct spectrum data of ESI-MS and one- and two-dimensional NMR spectroscopy for the first time.

Determination of absolute configuration of natural products: theoretical calculation of electronic circular dichroism as a tool

USDA-ARS?s Scientific Manuscript database

Determination of absolute configuration (AC) is one of the most challenging features in the structure elucidation of chiral natural products, especially those with complex structures. With revolutionary advancements in the area of quantum chemical calculations of chiroptical spectroscopy over the pa...

Ultra(high)-pressure liquid chromatography-electrospray ionization-time-of-flight-ion mobility-high definition mass spectrometry for the rapid identification and structural characterization of flavonoid glycosides from cauliflower waste.

PubMed

Gonzales, Gerard Bryan; Raes, Katleen; Coelus, Sofie; Struijs, Karin; Smagghe, Guy; Van Camp, John

2014-01-03

In this paper, a strategy for the detection and structural elucidation of flavonoid glycosides from a complex matrix in a single chromatographic run using U(H)PLC-ESI-IMS-HDMS/MS(E) is presented. This system operates using alternative low and high energy voltages that is able to perform the task of conventional MS/MS in a data-independent way without re-injection of the sample, which saves analytical time. Also, ion mobility separation (IMS) was employed as an additional separation technique for compounds that are co-eluting after U(H)PLC separation. First, the fragmentation of flavonoid standards were analyzed and criteria was set for structural elucidation of flavonoids in a plant extract. Based on retention times, UV spectra, exact mass, and MS fragment characteristics, such as abundances of daughter ions and the presence of radical ions ([Y0-H](-)), a total 19 flavonoid glycosides, of which 8 non-acylated and 11 acylated, were detected and structurally characterized in a cauliflower waste extract. Kaempferol and quercetin were the main aglycones detected while sinapic and ferulic acid were the main phenolic acids. C-glycosides were also found although their structure could not be elucidated. The proposed method can be used as a rapid screening test for flavonoid identification and for routine analysis of plant extracts, such as these derived from cauliflower waste. The study also confirms that agroindustrial wastes, such as cauliflower leaves, could be seen as a valuable source of different bioactive phenolic compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

Phytochemical study of Helichrysum italicum (Roth) G. Don: Spectroscopic elucidation of unusual amino-phlorogucinols and antimicrobial assessment of secondary metabolites from medium-polar extract.

PubMed

D'Abrosca, Brigida; Buommino, Elisabetta; Caputo, Pina; Scognamiglio, Monica; Chambery, Angela; Donnarumma, Giovanna; Fiorentino, Antonio

2016-12-01

Three unusual amino-phloroglucinols, named helichrytalicines A-C, along with seventeen known compounds including acetophenones, tremetrone derivatives, low-molecular weight phenols, flavonol glucosides, have been isolated from the medium-polar extract of Helichrysum italicum (Roth) G. Don, a medicinal plant typical of the Mediterranean vegetation. The structures of the compounds have been elucidated based on extensive 2D-NMR spectroscopic analyses, including COSY, TOCSY, HSQC, CIGAR-HMBC, H2BC and HSQC-TOCSY, along with Q-TOF HRMS 2 analysis. Stereostructure of the new compounds has been elucidated by Mosher's method and NOESY experiment. Antimicrobial properties against Staphylococcus epidermidis of selected compounds have been evaluated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia

PubMed Central

Minici, Claudia; Gounari, Maria; Übelhart, Rudolf; Scarfò, Lydia; Dühren-von Minden, Marcus; Schneider, Dunja; Tasdogan, Alpaslan; Alkhatib, Alabbas; Agathangelidis, Andreas; Ntoufa, Stavroula; Chiorazzi, Nicholas; Jumaa, Hassan; Stamatopoulos, Kostas; Ghia, Paolo; Degano, Massimo

2017-01-01

Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR–BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones. The diversity of homotypic BcR contacts leading to cell-autonomous signalling reconciles the existence of a shared pathogenic mechanism with the biological and clinical heterogeneity of CLL and offers opportunities for innovative treatment strategies. PMID:28598442

New dihydro-β-agarofuran sesquiterpenes from Parnassia wightiana wall: isolation, identification and cytotoxicity against cancer cells.

PubMed

Lv, Chao; Zheng, Zuo-Lue; Miao, Fang; Geng, Hui-Ling; Zhou, Le; Liu, La-Ping

2014-06-20

Five new (4-8) and three known (1-3) dihydro-β-agarofuran sesquiterpene polyesters were isolated from the whole plants of Parnassia wightiana. The structures of all compounds were elucidated through spectroscopic analysis including 2D-NMR and HR-MS. The absolute configuration of these compounds was established by X-ray diffraction analysis, comparison of NOESY spectra and biogenetic means. The cytotoxities of compounds 2-8 were evaluated in vitro against HL-60, SMMC-7721, A549, MCF-7 and SW480 cell lines. Compounds 5-7 exhibited the highest activities with IC₅₀ values of 11.8-30.1 μM in most cases. The SAR revealed that the introduction of hydroxyl group was able to significantly improve the activities of the compounds for most of the cell lines.

Effects of diagnostic ionizing radiation on pregnancy via TEM

NASA Astrophysics Data System (ADS)

Mohammed, W. H.; Artoli, A. M.

2008-08-01

In Sudan, X-rays are routinely used at least once for measurements of pelvis during the gestation period, though this is highly prohibited worldwide, except for a few life threatening cases. To demonstrate the effect of diagnostic ionizing radiation on uterus, fetus and neighboring tissues to the ovaries, two independent experiments on pregnant rabbits were conducted. The first experiment was a proof of concept that diagnostic ionizing radiation is hazardous throughout the gestation period. The second experiment was done through Transmission Electron Microscopy (TEM) to elucidate the morphological changes in the ultra structure of samples taken from irradiated pregnant rabbits. This study uses TEM to test the effect of diagnostic radiation of less than 0.6 Gray on the cellular level. Morphological changes have been captured and the images were analyzed to quantify these effects.

Stochasticity and determinism in models of hematopoiesis.

PubMed

Kimmel, Marek

2014-01-01

This chapter represents a novel view of modeling in hematopoiesis, synthesizing both deterministic and stochastic approaches. Whereas the stochastic models work in situations where chance dominates, for example when the number of cells is small, or under random mutations, the deterministic models are more important for large-scale, normal hematopoiesis. New types of models are on the horizon. These models attempt to account for distributed environments such as hematopoietic niches and their impact on dynamics. Mixed effects of such structures and chance events are largely unknown and constitute both a challenge and promise for modeling. Our discussion is presented under the separate headings of deterministic and stochastic modeling; however, the connections between both are frequently mentioned. Four case studies are included to elucidate important examples. We also include a primer of deterministic and stochastic dynamics for the reader's use.

Effect of shell corrections on the beta decay isobaric mass parabolas

NASA Astrophysics Data System (ADS)

Kaur, Sarbjeet; Kaur, Manpreet; Singh, Bir Bikram

2018-05-01

The beta decay isobaric mass parabolas have been studied for isobaric families in di erent mass regions. The mass parabolas have been studied using the semi empirical mass formula of Seeger to find the most stable isobar for a particular isobaric family. In addition to liquid drop part VLDM, the shell correction part δU to give binding energy B. E. = VLDM + δU, defined within Strutinsky renormalization procedure, has been used. To elucidate the role of shell e ects on the structure shape of mass parabola, we have made comparison for the δU = 0 and δU ≠ 0 cases. For a particular mass value of isobaric family, the results show that with the inclusion of shell corrections i.e. δU ≠ 0, the minimum for the most stable isobar is strongly pronounced compared to the case without shell corrections. In other words, shell corrections significantly enhance the stability of stable isobar. The study reveals that the role of shell effects on the mass minima is more pronounced in heavy mass region compared to light and intermediate mass regions.

Evidence of dengue virus replication in a non-traumatic spleen rupture case.

PubMed

de Souza, Luiz José; de Azevedo, João; Kohler, Liza Ingride Acha; Barros, Lorena de Freitas; Lima, Mariana Arêdes; Silva, Emiliana Mandarano; Mohana-Borges, Ronaldo; Nunes, Priscila Conrado Guerra; Paes, Marciano Viana

2017-11-01

The present report describes a case of splenic rupture due to dengue, a rare complication of dengue that should be considered in any patient with suspected dengue disease who started with left upper quadrant abdominal pain and hypotension. The pathophysiology of this entity is not yet well elucidated, but one of the theories present in the literature is that it is due to a depletion of coagulation factors and platelets leading to intra-splenic hemorrhage and rupture. The RT-PCR technique detected serotype 1 and histopathological studies of the spleen revealed significant atrophy of lymphoid follicles and extensive hemorrhage areas. Besides histopathological observations, virus replication was investigated by detection of dengue antigens, especially the non-structural 3 protein (NS3) in endothelial cells and splenic macrophages. This important complication has serious clinical repercussions and high mortality, due to the diagnostic difficulty and many factors that usually confuse or delay its diagnosis. Therefore, it is of the utmost importance to recognize their manifestations and their management to try to best minimize their consequences and mortality.

Generation of field-aligned current (FAC) and convection through the formation of pressure regimes: Correction for the concept of Dungey's convection

NASA Astrophysics Data System (ADS)

Tanaka, T.; Watanabe, M.; Den, M.; Fujita, S.; Ebihara, Y.; Kikuchi, T.; Hashimoto, K. K.; Kataoka, R.

2016-09-01

In this paper, we try to elucidate the generation mechanism of the field-aligned current (FAC) and coexisting convection. From the comparison between the theoretical prediction and the state of numerical solution from the high-resolution global simulation, we obtain the following conclusions about the distribution of dynamo, the magnetic field structure along the flow path that diverges Poynting flux, and energy conversion promoting the generation of electromagnetic energy. The dynamo for the region 1 FAC, which is in the high-latitude-side cusp-mantle region, has a structure in which magnetic field is compressed along the convection path by the slow mode motion. The dynamo for the region 2 FAC is in the ring current region at the inner edge of the plasma sheet, and has a structure in which magnetic field is curved outward along the convection path. Under these structures, electromagnetic energy is generated from the work done by pressure gradient force, in both dynamos for the region 1 and region 2 FACs. In these generation processes of the FACs, the excitation of convection and the formation of pressure regimes occur as interdependent processes. This structure leads to a modification in the way of understanding the Dungey's convection. Generation of the FAC through the formation of pressure regimes is essential even for the case of substorm onset.

Functional response of osteoblasts in functionally gradient titanium alloy mesh arrays processed by 3D additive manufacturing.

PubMed

Nune, K C; Kumar, A; Misra, R D K; Li, S J; Hao, Y L; Yang, R

2017-02-01

We elucidate here the osteoblasts functions and cellular activity in 3D printed interconnected porous architecture of functionally gradient Ti-6Al-4V alloy mesh structures in terms of cell proliferation and growth, distribution of cell nuclei, synthesis of proteins (actin, vinculin, and fibronectin), and calcium deposition. Cell culture studies with pre-osteoblasts indicated that the interconnected porous architecture of functionally gradient mesh arrays was conducive to osteoblast functions. However, there were statistically significant differences in the cellular response depending on the pore size in the functionally gradient structure. The interconnected porous architecture contributed to the distribution of cells from the large pore size (G1) to the small pore size (G3), with consequent synthesis of extracellular matrix and calcium precipitation. The gradient mesh structure significantly impacted cell adhesion and influenced the proliferation stage, such that there was high distribution of cells on struts of the gradient mesh structure. Actin and vinculin showed a significant difference in normalized expression level of protein per cell, which was absent in the case of fibronectin. Osteoblasts present on mesh struts formed a confluent sheet, bridging the pores through numerous cytoplasmic extensions. The gradient mesh structure fabricated by electron beam melting was explored to obtain fundamental insights on cellular activity with respect to osteoblast functions. Copyright © 2016 Elsevier B.V. All rights reserved.

A Library of the Nanoscale Self-Assembly of Amino Acids on Metal Surfaces

NASA Astrophysics Data System (ADS)

Iski, Erin; Yitamben, Esmeralda; Guisinger, Nathan

2012-02-01

The investigation of the hierarchical self-assembly of amino acids on surfaces represents a unique test-bed for the origin of enantio-favoritism in biology and the transmission of chirality from single molecules to complete surface layers. These chiral systems, in particular the assembly of isoleucine and alanine on Cu(111), represent a direct link to the understanding of certain biological processes, specifically the preference for some amino acids to form alpha helices vs. beta-pleated sheets in the secondary structure of proteins. Low temperature, ultra-high vacuum, scanning tunneling microscopy (LT UHV-STM) is used to study the hierarchical self-assembly of different amino acids on a Cu(111) single crystal in an effort to build a library of their two-dimensional structure with molecular-scale resolution for enhanced protein and peptide studies. Both enantiopure and racemic structures are studied in order to elucidate how chirality can affect the self-assembly of the amino acids. In some cases, density functional theory (DFT) models can be used to confirm the experimental structure. The advent of such a library with fully resolved, two-dimensional structures at different molecular coverages would address some of the complex questions surrounding the preferential formation of alpha helices vs. beta-pleated sheets in proteins and lead to a better understanding of the key role played by these amino acids in protein sequencing.

The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis.

PubMed

Improta, Roberto; Vitagliano, Luigi; Esposito, Luciana

2015-11-01

The elucidation of the mutual influence between peptide bond geometry and local conformation has important implications for protein structure refinement, validation, and prediction. To gain insights into the structural determinants and the energetic contributions associated with protein/peptide backbone plasticity, we here report an extensive analysis of the variability of the peptide bond angles by combining statistical analyses of protein structures and quantum mechanics calculations on small model peptide systems. Our analyses demonstrate that all the backbone bond angles strongly depend on the peptide conformation and unveil the existence of regular trends as function of ψ and/or φ. The excellent agreement of the quantum mechanics calculations with the statistical surveys of protein structures validates the computational scheme here employed and demonstrates that the valence geometry of protein/peptide backbone is primarily dictated by local interactions. Notably, for the first time we show that the position of the H(α) hydrogen atom, which is an important parameter in NMR structural studies, is also dependent on the local conformation. Most of the trends observed may be satisfactorily explained by invoking steric repulsive interactions; in some specific cases the valence bond variability is also influenced by hydrogen-bond like interactions. Moreover, we can provide a reliable estimate of the energies involved in the interplay between geometry and conformations. © 2015 Wiley Periodicals, Inc.

Interaction of parenting experiences and brain structure in the prediction of depressive symptoms in adolescents.

PubMed

Yap, Marie B H; Whittle, Sarah; Yücel, Murat; Sheeber, Lisa; Pantelis, Christos; Simmons, Julian G; Allen, Nicholas B

2008-12-01

Although some evidence suggests that neuroanatomic abnormalities may confer risk for major depressive disorder, findings are inconsistent. One potential explanation for this is the moderating role of environmental context, with individuals differing in their biological sensitivity to context. To examine the influence of adverse parenting as an environmental moderator of the association between brain structure and depressive symptoms. Cross-sectional measurement of brain structure, adverse parenting, and depressive symptoms in early adolescents. General community. A total of 106 students aged 11 to 13 years (55 males [51%]), recruited from primary schools in Melbourne, Australia, and their mothers. Selection was based on affective temperament, aimed at producing a sample representing a broad range of risk for major depressive disorder. No participant evidenced current or past case-level depressive, substance use, or eating disorder. (1) Volumetric measures of adolescents' amygdala, hippocampus, and anterior cingulate cortex (ACC); (2) frequency of observed maternal aggressive behavior during a mother-adolescent conflict-resolution interaction; and (3) adolescent depressive symptoms. Boys with smaller right amygdalas reported more depressive symptoms. However, neither hippocampal volume nor asymmetry measures of limbic or paralimbic ACC were directly related to level of depressive symptoms. Importantly, frequency of maternal aggressive behaviors moderated the associations between both the amygdala and ACC, and adolescent symptoms. Particularly, in conditions of low levels of maternal aggressiveness, boys with larger right amygdalas, girls with smaller bilateral amygdalas, and both boys and girls with smaller left paralimbic ACC reported fewer symptoms. These findings help elucidate the complex relationships between brain structure, environmental factors, and depressive symptoms. Further longitudinal research is required to examine how these factors contribute to the onset of case-level disorder, but given that family context risk factors are modifiable, our findings do suggest the potential utility of targeted early parenting interventions.

Thermodynamic properties of antiferromagnetic ordered states of π -d interacting systems of κ -(BETS) 2Fe X4(X =Br ,Cl )

NASA Astrophysics Data System (ADS)

Fukuoka, Shuhei; Yamashita, Satoshi; Nakazawa, Yasuhiro; Yamamoto, Takashi; Fujiwara, Hideki; Shirahata, Takashi; Takahashi, Kazuko

2016-06-01

The results are presented for systematic heat capacity measurements of π-d interacting systems of κ -(BETS) 2Fe Br4 and κ -(BETS) 2FeC l4 [BETS = bis(ethylenedithio)tetraselenafulvalene] performed under in-plane magnetic fields. We observed sharp thermal anomalies at 2.47 K for κ -(BETS) 2FeB r4 and at 0.47 K for κ -(BETS) 2FeC l4 at 0 T that are associated with antiferromagnetic transitions of the 3 d electrons in the anion layers. From analyses of the magnetic heat capacity data, we indicate that the two compounds show unconventional thermodynamic behaviors inherent in the π-d interacting layered system. In the case of κ -(BETS) 2FeB r4 , a small hump structure was observed in the magnetic heat capacity below the transition temperature when a magnetic field was applied parallel to the a axis. In the case of κ -(BETS) 2FeC l4 , a similar hump structure was observed at 0 T that remained in the data with magnetic fields applied parallel to the a axis. We demonstrate that the temperature dependencies of the magnetic heat capacities scale well by normalizing the temperatures with dominant one-dimensional direct interactions (Jdd/kB) of each compound. The field dependencies of the transition temperatures and the hump structures are elucidated in one simple magnetic field vs temperature (H -T ) phase diagram. These results indicate that the thermodynamic features of both κ-type BETS salts are essentially equivalent, and the observed hump structures are derived from the one-dimensional Jdd interaction characters, which are still influential for magnetic features even in the long-range magnetic ordered states.

Advances in structure elucidation of small molecules using mass spectrometry

PubMed Central

Fiehn, Oliver

2010-01-01

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules. Electronic supplementary material The online version of this article (doi:10.1007/s12566-010-0015-9) contains supplementary material, which is available to authorized users. PMID:21289855

Novel IgE Inhibitors for the Treatment of Food Allergies

DTIC Science & Technology

2015-10-01

currently the only FDA approved monoclonal anti-IgE therapy. We solved the IgE:omalizumab crystal structure to 2.54 Å. This structure elucidates the...Surprisingly, the complex structure shares significant similarity with the disruptive IgE inhibitor E2_79, and provides mechanistic insight into the...efficiency with which disruptive inhibitors are able to bind to, and accelerate FcεRIα dissociation from preformed IgE:FcεRIα complexes. Structural

The role of metals in protein conformational disorders - The case of prion protein and Aβ -peptide

NASA Astrophysics Data System (ADS)

De Santis, E.; Minicozzi, V.; Morante, S.; Rossi, G. C.; Stellato, F.

2016-02-01

Protein conformational disorders are members of a vast class of pathologies in which endogenous proteins or peptides undergo a misfolding process by switching from the physiological soluble configuration to a pathological fibrillar insoluble state. An important, but not yet fully elucidated, role in the process appears to be played by transition metal ions, mainly copper and zinc. X-ray absorption spectroscopy is one of the most suitable techniques for the structural characterization of biological molecules in complex with metal. Owing to its chemical selectivity and sensitivity to the local atomic geometry around the absorber, it can be successfully used to study the environment of metal ions in complex with proteins and peptides in physiological conditions. In this paper we present X-ray absorption spectroscopy studies of the metal ions coordination modes in systems where metals are complexed with specific amyloidogenic proteins and peptides. In particular, we show results concerning the Amyloid β peptide, that is involved in Alzheimer's disease, and the Prion protein, that is responsible for the Transmissible Spongiform Encephalopathy. Our findings suggest that the copper and zinc ions may play a crucial role in the aggregation and fibril formation process of these two biomolecules. Elucidating this kind of interaction could be a key preliminary step before any viable therapy can be conceived or designed.

Structural insight into catalytic mechanism of PET hydrolase.

PubMed

Han, Xu; Liu, Weidong; Huang, Jian-Wen; Ma, Jiantao; Zheng, Yingying; Ko, Tzu-Ping; Xu, Limin; Cheng, Ya-Shan; Chen, Chun-Chi; Guo, Rey-Ting

2017-12-13

PET hydrolase (PETase), which hydrolyzes polyethylene terephthalate (PET) into soluble building blocks, provides an attractive avenue for the bioconversion of plastics. Here we present the structures of a novel PETase from the PET-consuming microbe Ideonella sakaiensis in complex with substrate and product analogs. Through structural analyses, mutagenesis, and activity measurements, a substrate-binding mode is proposed, and several features critical for catalysis are elucidated.

Characterizing highly dynamic conformational states: The transcription bubble in RNAP-promoter open complex as an example

NASA Astrophysics Data System (ADS)

Lerner, Eitan; Ingargiola, Antonino; Weiss, Shimon

2018-03-01

Bio-macromolecules carry out complicated functions through structural changes. To understand their mechanism of action, the structure of each step has to be characterized. While classical structural biology techniques allow the characterization of a few "structural snapshots" along the enzymatic cycle (usually of stable conformations), they do not cover all (and often fast interconverting) structures in the ensemble, where each may play an important functional role. Recently, several groups have demonstrated that structures of different conformations in solution could be solved by measuring multiple distances between different pairs of residues using single-molecule Förster resonance energy transfer (smFRET) and using them as constrains for hybrid/integrative structural modeling. However, this approach is limited in cases where the conformational dynamics is faster than the technique's temporal resolution. In this study, we combine existing tools that elucidate sub-millisecond conformational dynamics together with hybrid/integrative structural modeling to study the conformational states of the transcription bubble in the bacterial RNA polymerase-promoter open complex (RPo). We measured microsecond alternating laser excitation-smFRET of differently labeled lacCONS promoter dsDNA constructs. We used a combination of burst variance analysis, photon-by-photon hidden Markov modeling, and the FRET-restrained positioning and screening approach to identify two conformational states for RPo. The experimentally derived distances of one conformational state match the known crystal structure of bacterial RPo. The experimentally derived distances of the other conformational state have characteristics of a scrunched RPo. These findings support the hypothesis that sub-millisecond dynamics in the transcription bubble are responsible for transcription start site selection.

Turbulent Heat Transfer in Curved Pipe Flow

NASA Astrophysics Data System (ADS)

Kang, Changwoo; Yang, Kyung-Soo

2013-11-01

In the present investigation, turbulent heat transfer in fully-developed curved pipe flow with axially uniform wall heat flux has been numerically studied. The Reynolds numbers under consideration are Reτ = 210 (DNS) and 1,000 (LES) based on the mean friction velocity and the pipe radius, and the Prandtl number (Pr) is 0.71. For Reτ = 210 , the pipe curvature (κ) was fixed as 1/18.2, whereas three cases of κ (0.01, 0.05, 0.1) were computed in the case of Reτ = 1,000. The mean velocity, turbulent intensities and heat transfer rates obtained from the present calculations are in good agreement with the previous numerical and experimental results. To elucidate the secondary flow structures due to the pipe curvature, the mean quantities and rms fluctuations of the flow and temperature fields are presented on the pipe cross-sections, and compared with those of the straight pipe flow. To study turbulence structures and their influence on turbulent heat transfer, turbulence statistics including but not limited to skewness and flatness of velocity fluctuations, cross-correlation coefficients, an Octant analysis, and turbulence budgets are presented and discussed. Based on our results, we attempt to clarify the effects of Reynolds number and the pipe curvature on turbulent heat transfer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0008457).

Structural and optical properties of Tb and Na-Tb co-doped Ca3V2O8 phosphors prepared by sol-gel process

NASA Astrophysics Data System (ADS)

Parab, Shambhu S.; Salker, A. V.

2018-01-01

A malic acid assisted sol-gel route was successfully employed to prepare two distinct series of green emitting Ca3V2O8 phosphors. In the first series, Tb was solely doped whereas in the second series Na and Tb were doped simultaneously in the Ca3V2O8 crystal lattice. X-ray diffraction studies proved the utility of adopted preparative method by confirming the monophasic formation of all compounds from both the series. Spectral analysis like Raman spectroscopy, UV-DRS were undertaken to analyse the local structure, crystallinity and absorptive characteristics. XPS validated the presence of desired oxidation states of all the elements present. Finally, photoluminescence studies were done to elucidate the scope of prepared compounds as green emitting phosphors and also to understand the effect of both doping schemes on the luminescence. Intense green emission was observed in both the cases. Tb concentration of 0.08 was found to be optimum in case of Tb singly doped compounds whereas Tb = 0.12 showed highest intensity among the Na-Tb co-doped samples. Moreover, a red shift in the excitation wavelength was observed after Na doping signifying a change in the local electronic environment which in turn has affected the luminescence pattern. Local crystallinity and vacancy concentrations were found to have a major say on the emission intensities.

[Forensic entomology].

PubMed

Açikgöz, Halide Nihal

2010-01-01

Odour of the animal or human corpses immediately after death is very attractive for insects and other invertebrates. Blue and green bottle flies from the Calliphoridae family are the first colonizers of cadaver and immediately later necrophagous Diptera from the Sarcophagidae family settle on the same corpse. It is essential to determine the time past after death for elucidating the event in case of the homicide or suspicious death, and it is directly proportional to the post mortem interval expected time, which is based upon the speed of the larval growth. In this article, we purposed to stress the special interest of forensic entomology for the scientists who will apply this science in their forensic researches and case studies, and also to provide information to our judges, prosecutors and law enforcement agents in order to consider the entomological samples to be reliable and applicable evidences as biological stains and hairs. We are of the opinion that if any forensic entomologist is called to the crime scene or if the evidences are collected and then delivered to an entomologist, the forensic cases will be elucidated faster and more accurately.

Antifungal diterpenes from Hypoestes serpens (Acanthaceae).

PubMed

Rasoamiaranjanahary, Lalao; Marston, Andrew; Guilet, David; Schenk, Kurt; Randimbivololona, Fanantenanirainy; Hostettmann, Kurt

2003-02-01

Two new diterpenes, fusicoserpenol A and dolabeserpenoic acid A, with antifungal activity, were isolated from leaves of Hypoestes serpens (Acanthaceae). Their structures were elucidated by means of spectrometric methods including 1D and 2D NMR experiments and MS analysis. X-ray crystallographic analysis confirmed the structure of fusicoserpenol A and established the relative configuration.

Genetic and Biochemical Map for the Biosynthesis of Occidiofungin, an Antifungal Produced by Burkholderia contaminans Strain MS14 ▿†

PubMed Central

Gu, Ganyu; Smith, Leif; Liu, Aixin; Lu, Shi-En

2011-01-01

A striking feature of Burkholderia contaminans strain MS14 is the production of a glycolipopeptide named occidiofungin. Occidiofungin has a broad range of antifungal activities against plant and animal pathogens. In this study, a complete covalent structure characterization and identification of the whole genomic DNA region for the occidiofungin gene (ocf) cluster are described. Discovery of the presence of 2,4-diaminobutyric acid and 3-chloro-β-hydroxytyrosine and elucidation of the structure of a novel C18 fatty amino acid residue have been achieved. In addition, seven additional putative open reading frames (the genes from ocfI to ocfN [ocfI-N] and ORF16) were identified. Transcription of all the putative genes ocfI-N identified in the region except ORF16 was regulated by both ambR1 and ambR2. Elucidation of the structure and the ocf gene cluster provides insight into the biosynthesis of occidiofungin and promotes future aims at understanding the biosynthetic machinery. This work provides new avenues for optimizing the production and synthesis of structural analogs of occidiofungin. PMID:21742901

Synthesis, liquid chromatographic fractionation and partial characterization of polybrominated dibenzofuran congeners.

PubMed

Gallistl, Christoph; Vetter, Walter

2016-04-15

Polybrominated dibenzofurans (PBDFs) are a class of highly toxic environmental contaminants which comprises 135 structurally different congeners. While the gas chromatographic separation and analysis of the most polychlorinated dibenzofurans (PCDFs) are well-documented, comparably little data is currently available in the case of PBDFs. In this study dibenzofuran was brominated to give a mixture of ∼40 PBDFs with one to seven bromine atoms. This synthesis mixture was fractionated by both countercurrent chromatography (CCC) with the solvent system n-hexane/toluene/acetonitrile and non-aqueous reversed-phase high performance liquid chromatography (RP-HPLC) with acetonitrile as the mobile phase. All together 80 consecutive CCC fractions and 40 HPLC fractions were taken and analyzed for PBDFs by gas chromatography coupled to mass spectrometry (GC/MS). CCC and RP-HPLC offered orthogonal separation of the PBDF mixture. As a consequence, selected CCC fractions were further fractionated by RP-HPLC. In this way, eight PBDFs could be isolated and the structures of twelve PBDFs were elucidated by proton magnetic resonance spectroscopy ((1)H NMR). Copyright © 2016 Elsevier B.V. All rights reserved.

Geocode of River Networks in Global Plateaus

NASA Astrophysics Data System (ADS)

Ni, J.; Wang, Y.; Wang, T.

2017-12-01

As typical hierarchical systems, river networks are of great significance to aquatic organisms and its diversity. Different aspects of river networks have been investigated in previous studies such as network structure, formation cause, material transport, nutrient cycle and habitat variation. Nevertheless, river networks function as biological habitat is far from satisfactory in plateau areas. This paper presents a hierarchical method for habitat characterization of plateau river networks with the geocode extracted from abiotic factors including historical geologic period, climate zone, water source and geomorphic process at different spatial scales. As results, characteristics of biological response with vertical differentiation within typical plateau river networks are elucidated. Altitude, climate and landform are of great influence to habitat and thereby structure of aquatic community, while diverse water source and exogenic action would influence biological abundance or spatiotemporal distribution. Case studies are made in the main stream of the Yellow River and the Yangtze River, respectively extended to the river source to Qinghai-Tibet Plateau, which demonstrate high potentials for decision making support to river protection, ecological rehabilitation and sustainable management of river ecosystems.

(+)-Meyeniins A-C, Novel Hexahydroimidazo[1,5-c]thiazole Derivatives from the Tubers of Lepidium meyenii: Complete Structural Elucidation by Biomimetic Synthesis and Racemic Crystallization.

PubMed

Zhou, Min; Ma, Hang-Ying; Liu, Zhi-Hua; Yang, Guang-Yu; Du, Gang; Ye, Yan-Qing; Li, Gan-Peng; Hu, Qiu-Fen

2017-03-08

(+)-Meyeniins A-C (1-3), a novel class of sulfur-containing hexahydroimidazo[1,5-c]thiazole derivatives, were isolated from the tubers of Lepidium meyenii (maca) cultivated in Lijiang, Yunnan province, China. Guided by their biosynthetic hypothesis, a stereocontrolled biomimetic synthesis of meyeniins A-C and their individual enantiomers was efficiently accomplished by a combination of a condensation reaction and Edman degradation. The formation of high-quality crystals for X-ray crystallography occurred much more readily from a racemic mixture of (±)-meyeniin A than with the single enantiomer alone in this case. These extensive strategies, combined with circular dichroism (CD) spectra, allowed the complete structural assignments of (+)-meyeniins A-C. Among them, (+)-meyeniin A showed moderate selective cytotoxicities against the HL-60, A549 and MCF-7 human cell lines with IC 50 values of 14.41, 32.22, and 33.14 μM, respectively. To some extent, these findings support traditional applications of maca as healthy nutritional supplements or functional foods for cancer prevention.

Molecular structures guide the engineering of chromatin.

PubMed

Tekel, Stefan J; Haynes, Karmella A

2017-07-27

Chromatin is a system of proteins, RNA, and DNA that interact with each other to organize and regulate genetic information within eukaryotic nuclei. Chromatin proteins carry out essential functions: packing DNA during cell division, partitioning DNA into sub-regions within the nucleus, and controlling levels of gene expression. There is a growing interest in manipulating chromatin dynamics for applications in medicine and agriculture. Progress in this area requires the identification of design rules for the chromatin system. Here, we focus on the relationship between the physical structure and function of chromatin proteins. We discuss key research that has elucidated the intrinsic properties of chromatin proteins and how this information informs design rules for synthetic systems. Recent work demonstrates that chromatin-derived peptide motifs are portable and in some cases can be customized to alter their function. Finally, we present a workflow for fusion protein design and discuss best practices for engineering chromatin to assist scientists in advancing the field of synthetic epigenetics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Improper ferroelectricity: A theoretical and experimental investigation

NASA Astrophysics Data System (ADS)

Hardy, J. R.; Ullman, F. G.

1984-02-01

A combined theoretical and experimental study has been made of the origins and properties of the improper ferroelectricity associated with structural modulations of non-zero wavelengths. Two classes of materials have been studied: rare earth molybdates (specifically, gadolinium molybdate: GMO), and potassium selenate and its isomorphs. In the former, the modulation is produced by a zone boundary phonon instability, and in the latter by the instability of a phonon of wave vector approximately two-thirds of the way to the zone-boundary. In the second case the initial result is a modulated structure whose repeat distance is not a rational multiple of the basic lattice repeat distance. This result is a modulated polarization which, when the basic modulation locks in to a rational multiple of the lattice spacing, becomes uniform, and improper ferroelectricity results. The origins of these effects have been elucidated by theoretical studies, initially semi-empirical, but subsequently from first-principles. These complemented the experimental work, which primarily used inelastic light scattering, uniaxial stress, and hydrostatic pressure, to probe the balance between the interionic forces through the effects on the phonons and dielectric properties.

Antioxidant and anticoagulant activity of polyphenol and polysaccharides from fermented Sargassum sp.

PubMed

Shobharani, P; Nanishankar, V H; Halami, P M; Sachindra, N M

2014-04-01

The current investigation was carried out with an objective of determining the structural characteristic of polysaccharides extracted from fermented Sargassum sp. to be used as potent natural heparin substitute anticoagulant compound. Sargassum sp. fermented with marine lactic acid bacteria was initially subjected to ethanol precipitation for the recovery of bioactive compounds. Antioxidant activity was maximum in the soluble fraction whereas anticoagulant activity was observed to be high in the precipitate which correlated with the increased polyphenols and total sugars respectively. The precipitate was purified by anion exchange chromatography and the fractions collected were analyzed for total sugars and anticoagulant activity. There was 2.6-3.9-folds increase in anticoagulant activity in the final purified fractions, with a maximum activity in case of sample fermented with Enterococcus faecium (6.7±0.22 IU/mg). Structural elucidation of potential anticoagulant polysaccharide by Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (NMR) analysis indicated the presence of alginate rich in mannuronic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

Crystal structure of an EfPDF complex with Met-Ala-Ser based on crystallographic packing.

PubMed

Nam, Ki Hyun; Kim, Kook-Han; Kim, Eunice Eun Kyeong; Hwang, Kwang Yeon

2009-04-17

PDF (peptide deformylase) plays a critical role in the production of mature proteins by removing the N-formyl polypeptide of nascent proteins in the prokaryote cell system. This protein is essential for bacterial growth, making it an attractive target for the design of new antibiotics. Accordingly, PDF has been evaluated as a drug target; however, architectural mechanism studies of PDF have not yet fully elucidated its molecular function. We recently reported the crystal structure of PDF produced by Enterococcus faecium [K.H. Nam, J.I. Ham, A. Priyadarshi, E.E. Kim, N. Chung, K.Y. Hwang, "Insight into the antibacterial drug design and architectural mechanism of peptide recognition from the E. faecium peptide deformylase structure", Proteins 74 (2009) 261-265]. Here, we present the crystal structure of the EfPDF complex with MAS (Met-Ser-Ala), thereby not only delineating the architectural mechanism for the recognition of mimic-peptides by N-terminal cleaved expression peptide, but also suggesting possible targets for rational design of antibacterial drugs. In addition to their implications for drug design, these structural studies will facilitate elucidation of the architectural mechanism responsible for the peptide recognition of PDF.

Structural basis of DNA sequence recognition by the response regulator PhoP in Mycobacterium tuberculosis.

PubMed

He, Xiaoyuan; Wang, Liqin; Wang, Shuishu

2016-04-15

The transcriptional regulator PhoP is an essential virulence factor in Mycobacterium tuberculosis, and it presents a target for the development of new anti-tuberculosis drugs and attenuated tuberculosis vaccine strains. PhoP binds to DNA as a highly cooperative dimer by recognizing direct repeats of 7-bp motifs with a 4-bp spacer. To elucidate the PhoP-DNA binding mechanism, we determined the crystal structure of the PhoP-DNA complex. The structure revealed a tandem PhoP dimer that bound to the direct repeat. The surprising tandem arrangement of the receiver domains allowed the four domains of the PhoP dimer to form a compact structure, accounting for the strict requirement of a 4-bp spacer and the highly cooperative binding of the dimer. The PhoP-DNA interactions exclusively involved the effector domain. The sequence-recognition helix made contact with the bases of the 7-bp motif in the major groove, and the wing interacted with the adjacent minor groove. The structure provides a starting point for the elucidation of the mechanism by which PhoP regulates the virulence of M. tuberculosis and guides the design of screening platforms for PhoP inhibitors.

Methyl phenlactonoates are efficient strigolactone analogs with simple structure

PubMed Central

Jamil, Muhammad; Kountche, Boubacar A; Haider, Imran; Guo, Xiujie; Ntui, Valentine O; Jia, Kun-Peng; Hameed, Umar S; Nakamura, Hidemitsu; Lyu, Ying; Jiang, Kai; Hirabayashi, Kei; Tanokura, Masaru; Arold, Stefan T; Asami, Tadao

2018-01-01

abstract Strigolactones (SLs) are a new class of phytohormones that also act as germination stimulants for root parasitic plants, such as Striga spp., and as branching factors for symbiotic arbuscular mycorrhizal fungi. Sources for natural SLs are very limited. Hence, efficient and simple SL analogs are needed for elucidating SL-related biological processes as well as for agricultural applications. Based on the structure of the non-canonical SL methyl carlactonoate, we developed a new, easy to synthesize series of analogs, termed methyl phenlactonoates (MPs), evaluated their efficacy in exerting different SL functions, and determined their affinity for SL receptors from rice and Striga hermonthica. Most of the MPs showed considerable activity in regulating plant architecture, triggering leaf senescence, and inducing parasitic seed germination. Moreover, some MPs outperformed GR24, a widely used SL analog with a complex structure, in exerting particular SL functions, such as modulating Arabidopsis roots architecture and inhibiting rice tillering. Thus, MPs will help in elucidating the functions of SLs and are promising candidates for agricultural applications. Moreover, MPs demonstrate that slight structural modifications clearly impact the efficiency in exerting particular SL functions, indicating that structural diversity of natural SLs may mirror a functional specificity. PMID:29300919

Ravynic acid, an antibiotic polyeneyne tetramic acid from Penicillium sp. elucidated through synthesis.

PubMed

Myrtle, J D; Beekman, A M; Barrow, R A

2016-09-21

A new antibiotic natural product, ravynic acid, has been isolated from a Penicillium sp. of fungus, collected from Ravensbourne National Park. The 3-acylpolyenyne tetramic acid structure was definitively elucidated via synthesis. Highlights of the synthetic method include the heat induced formation of the 3-acylphosphorane tetramic acid and a selective Wittig cross-coupling to efficiently prepare the natural compounds carbon skeleton. The natural compound was shown to inhibit the growth of Staphylococcus aureus down to concentrations of 2.5 µg mL(-1).

Implementing interorganizational cooperation in labour market reintegration: a case study.

PubMed

Ståhl, Christian

2012-06-01

To bring people with complex medical, social and vocational needs back to the labour market, interorganizational cooperation is often needed. Yet, studies of processes and strategies for achieving sustainable interorganizational cooperation are sparse. The aim of this study was to analyse the implementation processes of Swedish legislation on financial coordination, with specific focus on different strategies for and perspectives on implementing interorganizational cooperation. A multiple-case study was used, where two local associations for financial coordination were studied in order to elucidate and compare the development of cooperative work in two settings. The material, collected during a 3-year period, consisted of documents, individual interviews with managers, and focus groups with officials. Two different implementation strategies were identified. In case 1, a linear strategy was used to implement cooperative projects, which led to difficulties in maintaining cooperative work forms due to a fragmented and time-limited implementation process. In case 2, an interactive strategy was used, where managers and politicians were continuously involved in developing a central cooperation team that became a central part of a developing structure for interorganizational cooperation. An interactive cooperation strategy with long-term joint financing was here shown to be successful in overcoming organizational barriers to cooperation. It is suggested that a strategy based on adaptation to local conditions, flexibility and constant evaluation is preferred for developing sustainable interorganizational cooperation when implementing policies or legislation affecting interorganizational relationships.

Imperanene, a novel phenolic compound with platelet aggregation inhibitory activity from Imperata cylindrica.

PubMed

Matsunaga, K; Shibuya, M; Ohizumi, Y

1995-01-01

Imperanene, a novel phenolic compound [1] has been isolated from Imperata cylindrica. Its structure was elucidated by spectroscopic evidence. Imperanene showed platelet aggregation inhibitory activity.

New biflavonoids from dragon's blood of Dracaena cinnabari.

PubMed

Masaoud, M; Himmelreich, U; Ripperger, H; Adam, G

1995-08-01

The new biflavonoids 2'-methoxysocotrin-5'-ol, socotrin-4'-ol, and homoisosocotrin-4'-ol were isolated from dragon's blood of Dracaena cinnabari and their structures elucidated mainly by NMR spectroscopy.

Addison’s Disease Mimicking as Acute Pancreatitis: A Case Report

PubMed Central

Chaudhuri, Sayani; Rao, Karthik N; Ommurugan, Balaji; Varghese, George

2017-01-01

Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison’s disease. Adrenal insufficiency (Addison’s disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison’s disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis. PMID:28571196

Actin Cross-link Assembly and Disassembly Mechanics for α-Actinin and Fascin*

PubMed Central

Courson, David S.; Rock, Ronald S.

2010-01-01

Self-assembly of complex structures is commonplace in biology but often poorly understood. In the case of the actin cytoskeleton, a great deal is known about the components that include higher order structures, such as lamellar meshes, filopodial bundles, and stress fibers. Each of these cytoskeletal structures contains actin filaments and cross-linking proteins, but the role of cross-linking proteins in the initial steps of structure formation has not been clearly elucidated. We employ an optical trapping assay to investigate the behaviors of two actin cross-linking proteins, fascin and α-actinin, during the first steps of structure assembly. Here, we show that these proteins have distinct binding characteristics that cause them to recognize and cross-link filaments that are arranged with specific geometries. α-Actinin is a promiscuous cross-linker, linking filaments over all angles. It retains this flexibility after cross-links are formed, maintaining a connection even when the link is rotated. Conversely, fascin is extremely selective, only cross-linking filaments in a parallel orientation. Surprisingly, bundles formed by either protein are extremely stable, persisting for over 0.5 h in a continuous wash. However, using fluorescence recovery after photobleaching and fluorescence decay experiments, we find that the stable fascin population can be rapidly competed away by free fascin. We present a simple avidity model for this cross-link dissociation behavior. Together, these results place constraints on how cytoskeletal structures assemble, organize, and disassemble in vivo. PMID:20551315

Evolutionary origin of the Asteraceae capitulum: Insights from Calyceraceae.

PubMed

Pozner, Raúl; Zanotti, Christian; Johnson, Leigh A

2012-01-01

Phylogenies based on molecular data are revealing that generalizations about complex morphological structures often obscure variation and developmental patterns important for understanding the evolution of forms, as is the case for inflorescence morphology within the well-supported MGCA clade (Menyanthaceae + Goodeniaceae + Calyceraceae + Asteraceae). While the basal families share a basic thyrsic/thyrsoid structure of their inflorescences, Asteraceae possesses a capitulum that is widely interpreted as a racemose, condensed inflorescence. Elucidating the poorly known inflorescence structure of Calyceraceae, sister to Asteraceae, should help clarify how the Asteraceae capitulum evolved from thyrsic/thyrsoid inflorescences. The early development and structure of the inflorescence of eight species (five genera) of Calyceraceae were studied by SEM, and patterns of evolutionary change were interpreted via phylogenetic character mapping. The basic inflorescence structure of Calyceraceae is a cephalioid (a very condensed botryoid/thyrsoid). Optimization of inflorescence characters on a DNA sequence-derived tree suggests that the Asteraceae capitulum derives from a simple cephalioid through two morphological changes: loss of the terminal flower and suppression of the cymose branching pattern in the peripheral branches. Widely understood as a condensed raceme, the Asteraceae capitulum is the evolutionary result of a very reduced, condensed thyrsoid. Starting from that point, evolution worked separately only on the racemose developmental control/pattern within Asteraceae and mainly on the cymose developmental control/pattern within Calyceraceae, producing head-like inflorescences in both groups but with very different diversification potential. We also discuss possible remnants of the ancestral cephalioid structure in some Asteraceae.

Computational prediction of hinge axes in proteins

PubMed Central

2014-01-01

Background A protein's function is determined by the wide range of motions exhibited by its 3D structure. However, current experimental techniques are not able to reliably provide the level of detail required for elucidating the exact mechanisms of protein motion essential for effective drug screening and design. Computational tools are instrumental in the study of the underlying structure-function relationship. We focus on a special type of proteins called "hinge proteins" which exhibit a motion that can be interpreted as a rotation of one domain relative to another. Results This work proposes a computational approach that uses the geometric structure of a single conformation to predict the feasible motions of the protein and is founded in recent work from rigidity theory, an area of mathematics that studies flexibility properties of general structures. Given a single conformational state, our analysis predicts a relative axis of motion between two specified domains. We analyze a dataset of 19 structures known to exhibit this hinge-like behavior. For 15, the predicted axis is consistent with a motion to a second, known conformation. We present a detailed case study for three proteins whose dynamics have been well-studied in the literature: calmodulin, the LAO binding protein and the Bence-Jones protein. Conclusions Our results show that incorporating rigidity-theoretic analyses can lead to effective computational methods for understanding hinge motions in macromolecules. This initial investigation is the first step towards a new tool for probing the structure-dynamics relationship in proteins. PMID:25080829

Structural Elucidation of Novel Saponins in the Sea Cucumber Holothuria lessoni

PubMed Central

Bahrami, Yadollah; Zhang, Wei; Chataway, Tim; Franco, Chris

2014-01-01

Sea cucumbers are prolific producers of a wide range of bioactive compounds. This study aimed to purify and characterize one class of compound, the saponins, from the viscera of the Australian sea cucumber Holothuria lessoni. The saponins were obtained by ethanolic extraction of the viscera and enriched by a liquid-liquid partition process and adsorption column chromatography. A high performance centrifugal partition chromatography (HPCPC) was applied to the saponin-enriched mixture to obtain saponins with high purity. The resultant purified saponins were profiled using MALDI-MS/MS and ESI-MS/MS which revealed the structure of isomeric saponins to contain multiple aglycones and/or sugar residues. We have elucidated the structure of five novel saponins, Holothurins D/E and Holothurinosides X/Y/Z, along with seven reported triterpene glycosides, including sulfated and non-sulfated saponins containing a range of aglycones and sugar moieties, from the viscera of H. lessoni. The abundance of novel compounds from this species holds promise for biotechnological applications. PMID:25110919

Recent progress in elucidating the structure, function and evolution of disease resistance genes in plants.

PubMed

Liu, Jinling; Liu, Xionglun; Dai, Liangying; Wang, Guoliang

2007-09-01

Plants employ multifaceted mechanisms to fight with numerous pathogens in nature. Resistance (R) genes are the most effective weapons against pathogen invasion since they can specifically recognize the corresponding pathogen effectors or associated protein(s) to activate plant immune responses at the site of infection. Up to date, over 70 R genes have been isolated from various plant species. Most R proteins contain conserved motifs such as nucleotide-binding site (NBS), leucine-rich repeat (LRR), Toll-interleukin-1 receptor domain (TIR, homologous to cytoplasmic domains of the Drosophila Toll protein and the mammalian interleukin-1 receptor), coiled-coil (CC) or leucine zipper (LZ) structure and protein kinase domain (PK). Recent results indicate that these domains play significant roles in R protein interactions with effector proteins from pathogens and in activating signal transduction pathways involved in innate immunity. This review highlights an overview of the recent progress in elucidating the structure, function and evolution of the isolated R genes in different plant-pathogen interaction systems.

Molecular simulation and mathematical modelling of glass transition temperature depression induced by CO2 plasticization in Polysulfone membranes

NASA Astrophysics Data System (ADS)

Lock, S. S. M.; Lau, K. K.; Lock Sow Mei, Irene; Shariff, A. M.; Yeong, Y. F.; Bustam, A. M.

2017-08-01

A sequence of molecular modelling procedure has been proposed to simulate experimentally validated membrane structure characterizing the effect of CO2 plasticization, whereby it can be subsequently employed to elucidate the depression in glass transition temperature (Tg ). Based on the above motivation, unswollen and swollen Polysulfone membrane structures with different CO2 loadings have been constructed, whereby the accuracy has been validated through good compliance with experimentally measured physical properties. It is found that the presence of CO2 constitutes to enhancement in polymeric chain relaxation, which consequently promotes the enlargement of molecular spacing and causes dilation in the membrane matrix. A series of glass transition temperature treatment has been conducted on the verified molecular structure to elucidate the effect of CO2 loadings to the depression in Tg induced by plasticization. Subsequently, a modified Michealis-Menten (M-M) function has been implemented to quantify the effect of CO2 loading attributed to plasticization towards Tg .

Structural elucidation of a novel phosphoglycolipid isolated from six species of Halomonas.

PubMed

Giordano, Assunta; Vella, Filomena M; Romano, Ida; Gambacorta, Agata

2007-08-01

The structure of a new phosphoglycolipid from the halophilic Gram-negative bacteria Halomonas elongata ATCC 33173(T), Halomonas eurihalina ATCC 49336(T), Halomonas almeriensis CECT 7050(T), strain Sharm (AM238662), Halomonas halophila DSM 4770(T), and Halomonas salina ATCC 49509(T) was elucidated by NMR and mass spectroscopy studies. In all of the species examined, the polar lipid composition consisted of 1,2-diacylglycero-3-phosphorylethanolamine, 1,2-diacylglycero-3-phosphoryl-glycerol, bisphosphatidyl glycerol, and the new phosphoglycolipid PGL1. The structure of PGL1 was established to be (2-(alpha-D-glucopyranosyloxy)-3-hydroxy-propyl)-phosphatidyl diacylglycerol. C16:0;C18:1 and C16:0;C19:cyclopropane are the most abundant acyl chains linked to the phosphatidylglycerol moiety of each isolated PGL1. All of the species presenting the lipid PGL1 belong to Halomonas rRNA group 1, suggesting that the new phosphoglycolipid could be a chemotaxonomic marker of this phylogenetic group.

Solar Cycle Fine Structure and Surface Rotation from Ca II K-Line Time Series Data

NASA Technical Reports Server (NTRS)

Scargle, Jeff; Keil, Steve; Worden, Pete

2011-01-01

Analysis of three and a half decades of data from the NSO/AFRL/Sac Peak K-line monitoring program yields evidence for four components to the variation: (a) the solar cycle, with considerable fine structure and a quasi-periodicity of 122.4 days; (b) a stochastic process, faster than (a) and largely independent of it, (c) a quasi-periodic signal due to rotational modulation, and of course (d) observational errors (shown to be quite small). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these chromospheric parameters. Time-frequency analysis is especially useful for extracting information about differential rotation, and in particular elucidates the connection between its behavior and fine structure of the solar cycle on approximately one-year time scales. These results further suggest that similar analyses will be useful at detecting and characterizing differential rotation in stars from stellar light-curves such as those being produced at NASA's Kepler observatory.

Relationship among visual field, blood flow, and neural structure measurements in glaucoma.

PubMed

Hwang, John C; Konduru, Ranjith; Zhang, Xinbo; Tan, Ou; Francis, Brian A; Varma, Rohit; Sehi, Mitra; Greenfield, David S; Sadda, Srinivas R; Huang, David

2012-05-17

To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma. Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale. Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P < 0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03). There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.

Lipopolysaccharide Antigens of Pseudomonas aeruginosa and Design of Novel Vaccines.

DTIC Science & Technology

1987-09-01

Pseudomonas aeruginosa, OA 1-C LChemical structure, Fisher immunotypes, M; ig0-Chain polysaccharide , and Synthetic antigens 19. ABSTRACT (Conu on rftvm if...have been characterized in our laboratories. Partial structures for the remaining two types have been elucidated. The O-chain polysaccharides of the... polysaccharide antigens for native structure, and (5) binding-site xa[lJ11:, of the antibodies using the synthetic antigens. b% B.. Sirmificance: General

NMR studies of protein-nucleic acid interactions.

PubMed

Varani, Gabriele; Chen, Yu; Leeper, Thomas C

2004-01-01

Protein-DNA and protein-RNA complexes play key functional roles in every living organism. Therefore, the elucidation of their structure and dynamics is an important goal of structural and molecular biology. Nuclear magnetic resonance (NMR) studies of protein and nucleic acid complexes have common features with studies of protein-protein complexes: the interaction surfaces between the molecules must be carefully delineated, the relative orientation of the two species needs to be accurately and precisely determined, and close intermolecular contacts defined by nuclear Overhauser effects (NOEs) must be obtained. However, differences in NMR properties (e.g., chemical shifts) and biosynthetic pathways for sample productions generate important differences. Chemical shift differences between the protein and nucleic acid resonances can aid the NMR structure determination process; however, the relatively limited dispersion of the RNA ribose resonances makes the process of assigning intermolecular NOEs more difficult. The analysis of the resulting structures requires computational tools unique to nucleic acid interactions. This chapter summarizes the most important elements of the structure determination by NMR of protein-nucleic acid complexes and their analysis. The main emphasis is on recent developments (e.g., residual dipolar couplings and new Web-based analysis tools) that have facilitated NMR studies of these complexes and expanded the type of biological problems to which NMR techniques of structural elucidation can now be applied.

Psychosis associated with usage of herbal slimming products adulterated with sibutramine: a case series.

PubMed

Chen, Sammy P L; Tang, Magdalene H Y; Ng, Sau Wah; Poon, Wing Tat; Chan, Albert Y W; Mak, Tony W L

2010-10-01

Sibutramine, or its structurally related analogs, is often found as an adulterant in proprietary herbal slimming products in Hong Kong. A few solitary case reports of sibutramine-associated psychosis have been published since 2000. As the only tertiary referral center for clinical toxicology analysis in Hong Kong, we noticed that psychosis was an unusually common feature in patients taking "herbal slimming products" adulterated with sibutramine or its structurally related analogs over the past 5 years. To examine the association between psychosis and the use of sibutramine-adulterated herbal products, in an attempt to elucidate this possible adverse drug reaction. This retrospective study reviewed all cases hospitalized with psychotic symptoms confirmed to have used herbal slimming products adulterated with sibutramine, or its analogs, between January 2004 and October 2009. The cases' clinical features, outcome, drug history, and analytical findings of the offending slimming products were studied. Results. Among the 16 confirmed cases, 15 (94%) were female; the median age was 19 years (range: 15-47). Auditory hallucination was documented in 10 (63%), visual hallucination in 6 (38%), persecutory ideas in 6 (38%), delusions in 4 (25%), and suicidal ideation in 2 (13%). For 20 "herbal" slimming products analyzed, 16 were found to have been adulterated with sibutramine, 2 with N-desmethyl-sibutramine, and 1 with N-bisdesmethyl-sibutramine. Other concomitant adulterants were also found and included phenolphthalein in 9, fenfluramine, mazindol, animal thyroid tissue in 2, hydrochlorothiazide and spironolactone in 1. Eight patients disclosed the source of the products: four through the Internet, one obtained over-the-counter locally, with three acquired outside Hong Kong. Slimming products claimed "herbal" in origin could often be adulterated with sibutramine and other Western medications. We observed an association between the use of these products and psychotic features. Further studies are warranted to study whether these adverse events are an uncommon adverse drug reaction of sibutramine.

A Trachylobane Diterpenoid from Xylopia aethiopica

PubMed

Ngouela; Nyassé; Tsamo; Brochier; Morin

1998-02-27

A new trachylobane derivative identified as 7alpha-hydroxytrachyloban-19beta-oic acid (1) has been isolated from the bark of Xylopia aethiopica and its structure elucidated by various NMR techniques and molecular modeling.

A new triterpene from callus of Pterocarpus santalinus.

PubMed

Krishnaveni, K S; Srinivasa Rao, J V

2000-02-01

A new pentacyclic triterpene was isolated from the callus induced from the stem cuttings of Pterocarpus santalinus. Based on spectral methods, the structure of the new compound was elucidated as 3-ketooleanane (1).

Online structural elucidation of alkaloids and other constituents in crude extracts and cultured cells of Nandina domestica by combination of LC-MS/MS, LC-NMR, and LC-CD analyses.

PubMed

Iwasa, Kinuko; Takahashi, Teturo; Nishiyama, Yumi; Moriyasu, Masataka; Sugiura, Makiko; Takeuchi, Atsuko; Tode, Chisato; Tokuda, Harukuni; Takeda, Kazuyoshi

2008-08-01

The combination of NMR, MS, and CD data permitted the structural elucidation including the absolute configuration of the known alkaloids and unknown components in the extract matrix solution of Nandina domestica without isolation and sample purification prior to the coupling experiments. Unstable natural stereoisomers were identified by LC-NMR and LC-MS. Five known alkaloids, (S)-isoboldine, (S)-domesticine, (S)-nantenine, sinoacutine, and menispermine, were identified from N. domestica. O-Methylpallidine and (E, E)-, (E, Z)-, and (Z, Z)-terrestribisamide were also characterized for the first time from this plant. Known jatrorrhizine, palmatine, and berberine and unknown (R)-carnegine and (E, E)-, (E, Z)-, and (Z, Z)-terrestribisamide were identified in the callus of N. domestica.

Surfactants tailored by the class Actinobacteria

PubMed Central

Kügler, Johannes H.; Le Roes-Hill, Marilize; Syldatk, Christoph; Hausmann, Rudolf

2015-01-01

Globally the change towards the establishment of a bio-based economy has resulted in an increased need for bio-based applications. This, in turn, has served as a driving force for the discovery and application of novel biosurfactants. The class Actinobacteria represents a vast group of microorganisms with the ability to produce a diverse range of secondary metabolites, including surfactants. Understanding the extensive nature of the biosurfactants produced by actinobacterial strains can assist in finding novel biosurfactants with new potential applications. This review therefore presents a comprehensive overview of the knowledge available on actinobacterial surfactants, the chemical structures that have been completely or partly elucidated, as well as the identity of the biosurfactant-producing strains. Producer strains of not yet elucidated compounds are discussed, as well as the original habitats of all the producer strains, which seems to indicate that biosurfactant production is environmentally driven. Methodology applied in the isolation, purification and structural elucidation of the different types of surface active compounds, as well as surfactant activity tests, are also discussed. Overall, actinobacterial surfactants can be summarized to include the dominantly occurring trehalose-comprising surfactants, other non-trehalose containing glycolipids, lipopeptides and the more rare actinobacterial surfactants. The lack of structural information on a large proportion of actinobacterial surfactants should be considered as a driving force to further explore the abundance and diversity of these compounds. This would allow for a better understanding of actinobacterial surface active compounds and their potential for biotechnological application. PMID:25852670

Elucidation of the structure and reaction mechanism of Sorghum bicolor hydroxycinnamoyltransferase and its structural relationship to other CoA-dependent transferases and synthases

USDA-ARS?s Scientific Manuscript database

Hydroxycinnamoyltransferase (SbHCT) from Sorghum bicolor participates in an early step of the phenylpropanoid pathway, exchanging CoA esterified to p-coumaric acid with shikimic or quinic acid, as intermediates in the biosynthesis of the monolignols coniferyl alcohol and sinapyl alcohol. In order to...

Real-Time Imaging of Plant Cell Wall Structure at Nanometer Scale, with Respect to Cellulase Accessibility and Degradation Kinetics (Presentation)

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

Ding, S. Y.

Presentation on real-time imaging of plant cell wall structure at nanometer scale. Objectives are to develop tools to measure biomass at the nanometer scale; elucidate the molecular bases of biomass deconstruction; and identify factors that affect the conversion efficiency of biomass-to-biofuels.

[Liability of pediatric nurses for professional negligence in Taiwan: a case study].

PubMed

Huang, Hui-Man; Sun, Fan-Ko

2014-04-01

Liability attribution and professional negligence in pediatric nursing are topics that have been neglected in Taiwan. (1) Identify the definitions of related criminal activities in accordance with domestic criminal law; (2) Elucidate the facts and the dispute in a current case involving a pediatric nurse; (3) Elucidate the principle of 'no punishment without law'; (4) Explore the reasons why the pediatric nurse in the current case received a verdict of 'not guilty'. A literature review and case study approach were used to analyze a sentence reconsideration of the first instance No. 1 (2011) issued by the Taiwan high court, Kaohsiung branch court. The conditions for the scrutiny of criminal activity under Taiwan criminal law are statement of facts, illegality (justifiable cause), and liability (excuse). In this case, the pediatric nurse was accused of failing to prevent an infant from suffocation and of not discharging her obligations as a nurse. The pediatric nurse rebutted the charge of criminal negligence. The intervening behaviors of the pediatric nurse were found to be legal and not culpable. In this case, the High Court and Supreme Court made a final criminal judgment based on the presumption of innocence, and the pediatric nurse was pronounced innocent of the charge. This article intends to assist pediatric nurses understand their liabilities under Taiwan's criminal law. Pediatric nurses should gain a better understanding of the nature of liability for professional negligence in order to clarify how actions that may be illegal do not necessarily make nurses culpable.

Bioethics education in clinical settings: theory and practice of the dilemma method of moral case deliberation.

PubMed

Stolper, Margreet; Molewijk, Bert; Widdershoven, Guy

2016-07-22

Moral Case Deliberation is a specific form of bioethics education fostering professionals' moral competence in order to deal with their moral questions. So far, few studies focus in detail on Moral Case Deliberation methodologies and their didactic principles. The dilemma method is a structured and frequently used method in Moral Case Deliberation that stimulates methodological reflection and reasoning through a systematic dialogue on an ethical issue experienced in practice. In this paper we present a case-study of a Moral Case Deliberation with the dilemma method in a health care institution for people with an intellectual disability, describing the theoretical background and the practical application of the dilemma method. The dilemma method focuses on moral experiences of participants concerning a concrete dilemma in practice. By an in-depth description of each of the steps of the deliberation process, we elucidate the educational value and didactics of this specific method. The didactics and methodical steps of the dilemma method both supported and structured the dialogical reflection process of the participants. The process shows that the participants learned to recognize the moral dimension of the issue at stake and were able to distinguish various perspectives and reasons in a systematic manner. The facilitator played an important role in the learning process of the participants, by assisting them in focusing on and exploring moral aspects of the case. The reflection and learning process, experienced by the participants, shows competency-based characteristics. The role of the facilitator is that of a Socratic teacher with specific knowledge and skills, fostering reflection, inquiry and dialogue. The specific didactics of the dilemma method is well suited for teaching bioethics in clinical settings. The dilemma method follows an inductive learning approach through a dialogical moral inquiry in which participants develop not only knowledge but also skills, attitude and character. The role of a trained facilitator and a specific view on teaching and practicing ethics are essential when using the dilemma method in teaching health care professionals how to reflect on their own moral issues in practice.

Structural elucidation and identification of a new derivative of phenethylamine using quadrupole time-of-flight mass spectrometry.

PubMed

Sekuła, Karolina; Zuba, Dariusz

2013-09-30

In recent years, the phenomenon of uncontrolled distribution of new psychoactive substances that were marketed without prior toxicological studies has been observed. Because many designer drugs are related in chemical structure, the potential for misidentifying them is an important problem. It is therefore essential to develop an analytical procedure for unequivocal elucidation of the structures of these compounds. The issue has been discussed in the context of 25I-NBMD [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2,3-methylenedioxyphenyl)methyl]ethanamine], a psychoactive substance first discovered on the drug market in 2012. The substance was extracted from blotter papers with methanol. Separation was achieved via liquid chromatography. Analysis was conducted by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS). Identification of the psychoactive component was supported by electron impact gas chromatography/mass spectrometry (GC/EI-MS). The high accuracy of the LC/ESI-QTOFMS method allowed the molecular mass of the investigated substance (M(exp) = 441.0438 Da; mass error, ∆m = 0.2 ppm) and the formulae of ions formed during fragmentation to be determined. The main ions were recorded at m/z = 135.0440, 290.9876 and 305.9981. Structures of the obtained ions were elucidated in the tandem mass spectrometry (MS/MS) experiments by comparing them to mass spectra of previously detected derivatives of phenethylamine. The performed study indicated the potential for using LC/QTOFMS method to identify new designer drugs. This technique can be used supplementary to standard GC/MS. Prior knowledge of the fragmentation mechanisms of phenethylamines allowed to predict the mass spectra of the novel substance--25I-NBMD. Copyright © 2013 John Wiley & Sons, Ltd.

Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides.

PubMed

Zitnay, Jared L; Li, Yang; Qin, Zhao; San, Boi Hoa; Depalle, Baptiste; Reese, Shawn P; Buehler, Markus J; Yu, S Michael; Weiss, Jeffrey A

2017-03-22

Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.

Model of critical diagnostic reasoning: achieving expert clinician performance.

PubMed

Harjai, Prashant Kumar; Tiwari, Ruby

2009-01-01

Diagnostic reasoning refers to the analytical processes used to determine patient health problems. While the education curriculum and health care system focus on training nurse clinicians to accurately recognize and rescue clinical situations, assessments of non-expert nurses have yielded less than satisfactory data on diagnostic competency. The contrast between the expert and non-expert nurse clinician raises the important question of how differences in thinking may contribute to a large divergence in accurate diagnostic reasoning. This article recognizes superior organization of one's knowledge base, using prototypes, and quick retrieval of pertinent information, using similarity recognition as two reasons for the expert's superior diagnostic performance. A model of critical diagnostic reasoning, using prototypes and similarity recognition, is proposed and elucidated using case studies. This model serves as a starting point toward bridging the gap between clinical data and accurate problem identification, verification, and management while providing a structure for a knowledge exchange between expert and non-expert clinicians.

New Dihydro-β-agarofuran Sesquiterpenes from Parnassia wightiana Wall: Isolation, Identification and Cytotoxicity against Cancer Cells

PubMed Central

Lv, Chao; Zheng, Zuo-Lue; Miao, Fang; Geng, Hui-Ling; Zhou, Le; Liu, La-Ping

2014-01-01

Five new (4–8) and three known (1–3) dihydro-β-agarofuran sesquiterpene polyesters were isolated from the whole plants of Parnassia wightiana. The structures of all compounds were elucidated through spectroscopic analysis including 2D-NMR and HR-MS. The absolute configuration of these compounds was established by X-ray diffraction analysis, comparison of NOESY spectra and biogenetic means. The cytotoxities of compounds 2–8 were evaluated in vitro against HL-60, SMMC-7721, A549, MCF-7 and SW480 cell lines. Compounds 5–7 exhibited the highest activities with IC50 values of 11.8–30.1 μM in most cases. The SAR revealed that the introduction of hydroxyl group was able to significantly improve the activities of the compounds for most of the cell lines. PMID:24955789

The role of interactions along the flood process chain and implications for risk assessment

NASA Astrophysics Data System (ADS)

Vorogushyn, Sergiy; Apel, Heiko; Viet Nguyen, Dung; Guse, Björn; Kreibich, Heidi; Lüdtke, Stefan; Schröter, Kai; Merz, Bruno

2017-04-01

Floods with their manifold characteristics are shaped by various processes along the flood process chain - from triggering meteorological extremes through catchment and river network process down to impacts on societies. In flood risk systems numerous interactions and feedbacks along the process chain may occur which finally shape spatio-temporal flood patterns and determine the ultimate risk. In this talk, we review some important interactions in the atmosphere-catchment, river-dike-floodplain and vulnerability compartments of the flood risk system. We highlight the importance of spatial interactions for flood hazard and risk assessment. For instance, the role of spatial rainfall structure or wave superposition in river networks is elucidated with selected case studies. In conclusion, we show the limits of current methods in assessment of large-scale flooding and outline the approach to more comprehensive risk assessment based on our regional flood risk model (RFM) for Germany.

Spectral analysis based on fast Fourier transformation (FFT) of surveillance data: the case of scarlet fever in China.

PubMed

Zhang, T; Yang, M; Xiao, X; Feng, Z; Li, C; Zhou, Z; Ren, Q; Li, X

2014-03-01

Many infectious diseases exhibit repetitive or regular behaviour over time. Time-domain approaches, such as the seasonal autoregressive integrated moving average model, are often utilized to examine the cyclical behaviour of such diseases. The limitations for time-domain approaches include over-differencing and over-fitting; furthermore, the use of these approaches is inappropriate when the assumption of linearity may not hold. In this study, we implemented a simple and efficient procedure based on the fast Fourier transformation (FFT) approach to evaluate the epidemic dynamic of scarlet fever incidence (2004-2010) in China. This method demonstrated good internal and external validities and overcame some shortcomings of time-domain approaches. The procedure also elucidated the cycling behaviour in terms of environmental factors. We concluded that, under appropriate circumstances of data structure, spectral analysis based on the FFT approach may be applicable for the study of oscillating diseases.

Solution NMR Spectroscopy for the Study of Enzyme Allostery

PubMed Central

Lisi, George P.; Loria, J. Patrick

2016-01-01

Allostery is a ubiquitous biological regulatory process in which distant binding sites within a protein or enzyme are functionally and thermodynamically coupled. Allosteric interactions play essential roles in many enzymological mechanisms, often facilitating formation of enzyme-substrate complexes and/or product release. Thus, elucidating the forces that drive allostery is critical to understanding the complex transformations of biomolecules. Currently, a number of models exist to describe allosteric behavior, taking into account energetics as well as conformational rearrangements and fluctuations. In the following review, we discuss the use of solution NMR techniques designed to probe allosteric mechanisms in enzymes. NMR spectroscopy is unequaled in its ability to detect structural and dynamical changes in biomolecules, and the case studies presented herein demonstrate the range of insights to be gained from this valuable method. We also provide a detailed technical discussion of several specialized NMR experiments that are ideally suited for the study of enzymatic allostery. PMID:26734986

Cosmology solved? Maybe

NASA Astrophysics Data System (ADS)

Turner, Michael S.

1999-03-01

For two decades the hot big-bang model as been referred to as the standard cosmology - and for good reason. For just as long cosmologists have known that there are fundamental questions that are not answered by the standard cosmology and point to a grander theory. The best candidate for that grander theory is inflation + cold dark matter. It holds that the Universe is flat, that slowly moving elementary particles left over from the earliest moments provide the cosmic infrastructure, and that the primeval density inhomogeneities that seed all the structure arose from quantum fluctuations. There is now prima facie evidence that supports two basic tenets of this paradigm. An avalanche of high-quality cosmological observations will soon make this case stronger or will break it. Key questions remain to be answered; foremost among them are: identification and detection of the cold dark matter particles and elucidation of the dark-energy component. These are exciting times in cosmology!

Insights into the molecular mechanism of dehalogenation catalyzed by D-2-haloacid dehalogenase from crystal structures.

PubMed

Wang, Yayue; Feng, Yanbin; Cao, Xupeng; Liu, Yinghui; Xue, Song

2018-01-23

D-2-haloacid dehalogenases (D-DEXs) catalyse the hydrolytic dehalogenation of D-2-haloacids, releasing halide ions and producing the corresponding 2-hydroxyacids. A structure-guided elucidation of the catalytic mechanism of this dehalogenation reaction has not been reported yet. Here, we report the catalytic mechanism of a D-DEX, HadD AJ1 from Pseudomonas putida AJ1/23, which was elucidated by X-ray crystallographic analysis and the H 2 18 O incorporation experiment. HadD AJ1 is an α-helical hydrolase that forms a homotetramer with its monomer including two structurally axisymmetric repeats. The product-bound complex structure was trapped with L-lactic acid in the active site, which is framed by the structurally related helices between two repeats. Site-directed mutagenesis confirmed the importance of the residues lining the binding pocket in stabilizing the enzyme-substrate complex. Asp205 acts as a key catalytic residue and is responsible for activating a water molecule along with Asn131. Then, the hydroxyl group of the water molecule directly attacks the C2 atom of the substrate to release the halogen ion instead of forming an enzyme-substrate ester intermediate as observed in L-2-haloacid dehalogenases. The newly revealed structural and mechanistic information on D-DEX may inspire structure-based mutagenesis to engineer highly efficient haloacid dehalogenases.

What We Know About the Brain Structure-Function Relationship.

PubMed

Batista-García-Ramó, Karla; Fernández-Verdecia, Caridad Ivette

2018-04-18

How the human brain works is still a question, as is its implication with brain architecture: the non-trivial structure–function relationship. The main hypothesis is that the anatomic architecture conditions, but does not determine, the neural network dynamic. The functional connectivity cannot be explained only considering the anatomical substrate. This involves complex and controversial aspects of the neuroscience field and that the methods and methodologies to obtain structural and functional connectivity are not always rigorously applied. The goal of the present article is to discuss about the progress made to elucidate the structure–function relationship of the Central Nervous System, particularly at the brain level, based on results from human and animal studies. The current novel systems and neuroimaging techniques with high resolutive physio-structural capacity have brought about the development of an integral framework of different structural and morphometric tools such as image processing, computational modeling and graph theory. Different laboratories have contributed with in vivo, in vitro and computational/mathematical models to study the intrinsic neural activity patterns based on anatomical connections. We conclude that multi-modal techniques of neuroimaging are required such as an improvement on methodologies for obtaining structural and functional connectivity. Even though simulations of the intrinsic neural activity based on anatomical connectivity can reproduce much of the observed patterns of empirical functional connectivity, future models should be multifactorial to elucidate multi-scale relationships and to infer disorder mechanisms.

Experimental studies of transplutonium metals and compounds under pressure

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

Peterson, J.R.; Haire, R.G.; Benedict, U.

1986-01-01

The structural behavior of the first four transplutonium metals and two Bk-Cf alloys as a function of pressure has been studied in diamond anvil cells via x-ray diffraction. The sequence of structures exhibited as pressure is increased is dhcp ..-->.. ccp ..-->.. orthorhombic. In addition a distorted ccp phase is observed in Am, Bk/sub 0.40/Cf/sub 0.60/, and Cf between the ccp and orthorhombic phases. Diamond anvil cells have also been used to contain AmI/sub 3/, CfBr/sub 3/, and CfCl/sub 3/ under pressure for investigation by absorption spectrophotometry. Both AmI/sub 3/ and CfBr/sub 3/ exhibit pressure-induced, irreversible phase transformations to themore » PuBr/sub 3/-type orthorhombic structure, a more dense form of these compounds. Thus the driving force for these transformations is more efficient crystal packing. Both hexagonal (to 22 GPa) and orthorhombic (to 35 GPa) CfCl/sub 3/ exhibit only reversible spectral changes with pressure. This probably reflects their nearly identical RTP unit cell volumes. In both cases the spectra obtained are consistent with a continuous alteration of the RTP structure with pressure; physical compression seems to make a given f-f transition easier. Additional data are being sought to elucidate more completely the behavior of CfCl/sub 3/ under pressure. 23 refs., 4 figs.« less

Structure and engineering of celluloses.

PubMed

Pérez, Serge; Samain, Daniel

2010-01-01

This chapter collates the developments and conclusions of many of the extensive studies that have been conducted on cellulose, with particular emphasis on the structural and morphological features while not ignoring the most recent results derived from the elucidation of unique biosynthetic pathways. The presentation of structural and morphological data gathered together in this chapter follows the historical development of our knowledge of the different structural levels of cellulose and its various organizational levels. These levels concern features such as chain conformation, chain polarity, chain association, crystal polarity, and microfibril structure and organization. This chapter provides some historical landmarks related to the evolution of concepts in the field of biopolymer science, which parallel the developments of novel methods for characterization of complex macromolecular structures. The elucidation of the different structural levels of organization opens the way to relating structure to function and properties. The chemical and biochemical methods that have been developed to dissolve and further modify cellulose chains are briefly covered. Particular emphasis is given to the facets of topochemistry and topoenzymology where the morphological features play a key role in determining unique physicochemical properties. A final chapter addresses what might be considered tomorrow's goal in amplifying the economic importance of cellulose in the context of sustainable development. Selected examples illustrate the types of result that can be obtained when cellulose fibers are no longer viewed as inert substrates, and when the polyhydroxyl nature of their surfaces, as well as their entire structural complexity, are taken into account. Copyright © 2010 Elsevier Inc. All rights reserved.

Effects of chemical fuel composition on energy generation from thermopower waves

NASA Astrophysics Data System (ADS)

Yeo, Taehan; Hwang, Hayoung; Jeong, Dong-Cheol; Lee, Kang Yeol; Hong, Jongsup; Song, Changsik; Choi, Wonjoon

2014-11-01

Thermopower waves, which occur during combustion within hybrid structures formed from nanomaterials and chemical fuels, result in a self-propagating thermal reaction and concomitantly generate electrical energy from the acceleration of charge carriers along the nanostructures. The hybrid structures for thermopower waves are composed of two primary components: the core thermoelectric material and the combustible fuel. So far, most studies have focused on investigating various nanomaterials for improving energy generation. Herein, we report that the composition of the chemical fuel used has a significant effect on the power generated by thermopower waves. Hybrid nanostructures consisting of mixtures of picric acid and picramide with sodium azide were synthesized and used to generate thermopower waves. A maximum voltage of ˜2 V and an average peak specific power as high as 15 kW kg-1 were obtained using the picric acid/sodium azide/multiwalled carbon nanotubes (MWCNTs) array composite. The average reaction velocity and the output voltage in the case of the picric acid/sodium azide were 25 cm s-1 and 157 mV, while they were 2 cm s-1 and 3 mV, in the case of the picramide/sodium azide. These marked differences are attributable to the chemical and structural differences of the mixtures. Mixing picric acid and sodium azide in deionized water resulted in the formation of 2,4,6-trinitro sodium phenoxide and hydrogen azide (H-N3), owing to the exchange of H+ and Na+ ions, as well as the formation of fiber-like structures, because of benzene π stacking. The negative enthalpy of formation of the new compounds and the fiber-like structures accelerate the reaction and increase the output voltage. Elucidating the effects of the composition of the chemical fuel used in the hybrid nanostructures will allow for the control of the combustion process and help optimize the energy generated from thermopower waves, furthering the development of thermopower waves as an energy source.

An isoflavone from Pterocarpus santalinus.

PubMed

Krishnaveni, K S; Rao, J V

2000-03-01

A new isoflavone together with liquiritigenin and isoliquiritigenin has been isolated from the heartwood of Pterocarpus santalinus. Based on spectral methods, the structure of the new compound was elucidated as 6-hydroxy,7,2',4',5'-tetramethoxyisoflavone.

Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

NASA Astrophysics Data System (ADS)

Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

2016-05-01

Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated.

Understanding the Basis of Auriculocondylar Syndrome: Insights From Human and Mouse Genetic Studies

PubMed Central

Clouthier, David E.; Passos Bueno, Maria Rita; Tavares, Andre L.P.; Lyonnet, Stanislas; Amiel, Jeanne; Gordon, Christopher T.

2014-01-01

Among human birth defect syndromes, malformations affecting the face are perhaps the most striking due to cultural and psychological expectations of facial shape. One such syndrome is auriculocondylar syndrome (ACS), in which patients present with defects in ear and mandible development. Affected structures arise from cranial neural crest cells, a population of cells in the embryo that reside in the pharyngeal arches and give rise to most of the bone, cartilage and connective tissue of the face. Recent studies have found that most cases of ACS arise from defects in signaling molecules associated with the endothelin signaling pathway. Disruption of this signaling pathway in both mouse and zebrafish results in loss of identity of neural crest cells of the mandibular portion of the first pharyngeal arch and the subsequent repatterning of these cells, leading to homeosis of lower jaw structures into more maxillary-like structures. These findings illustrate the importance of endothelin signaling in normal human craniofacial development and illustrate how clinical and basic science approaches can coalesce to improve our understanding of the genetic basis of human birth syndromes. Further, understanding the genetic basis for ACS that lies outside of known endothelin signaling components may help elucidate unknown aspects critical to the establishment of neural crest cell patterning during facial morphogenesis. PMID:24123988

On the use of atomistic simulations to aid bulk metallic glasses structural elucidation with solid-state NMR.

PubMed

Ferreira, Ary R; Rino, José P

2017-08-24

Solid-state nuclear magnetic resonance (ssNMR) experimental 27 Al metallic shifts reported in the literature for bulk metallic glasses (BMGs) were revisited in the light of state-of-the-art atomistic simulations. In a consistent way, the Gauge-Including Projector Augmented-Wave (GIPAW) method was applied in conjunction with classical molecular dynamics (CMD). A series of Zr-Cu-Al alloys with low Al concentrations were selected as case study systems, for which realistic CMD derived structural models were used for a short- and medium-range order mining. That initial procedure allowed the detection of trends describing changes on the microstructure of the material upon Al alloying, which in turn were used to guide GIPAW calculations with a set of abstract systems in the context of ssNMR. With essential precision and accuracy, the ab initio simulations also yielded valuable trends from the electronic structure point of view, which enabled an overview of the bonding nature of Al-centered clusters as well as its influence on the experimental ssNMR outcomes. The approach described in this work might promote the use of ssNMR spectroscopy in research on glassy metals. Moreover, the results presented demonstrate the possibility to expand the applications of this technique, with deeper insight into nuclear interactions and less speculative assignments.

Structural evolution under uniaxial drawing of Poly(D, L-lactide) Films

NASA Astrophysics Data System (ADS)

Stoclet, Grégory; Lefebvre, Jean-Marc; Seguela, Roland

2009-03-01

Aliphatic polyesters are an important class of biodegradable polymers. They have drawn particular attention in the last few years as food packaging materials because they can be derived from renewable resources. Among this family, polylactide (PLA) is considered as one of the most promising ``green'' polymer for use as a substitute to petroleum-based polymers. In the present work, we investigate the mechanical behaviour of amorphous poly(D, L-lactide) films in relation to the structural evolution upon stretching at various draw temperatures (Td) above the glass transition temperature. Examination of the drawing behaviour shows that PLA initially behaves like a rubbery material until a true strain of the order of 1. Strain hardening occurs beyond this strain level, up to film fracture. Such strain hardening is generally ascribed to a strain induced crystallization phenomenon. In the present case, it is clearly more pronounced for Td = 90 C than for Td = 70 C. The corresponding structural evolutions are investigated by means of WAXS. The diffraction patterns reveal the marked influence of draw temperature. Indeed for Td = 70 C a mesophase is induced whereas strain-induced crystallisation takes place at Td = 90 C. Further work is in progress, in order to elucidate mesophase development and mechanical response.

Influence of CO annealing in metal-oxide-semiconductor capacitors with SiO2 films thermally grown on Si and on SiC

NASA Astrophysics Data System (ADS)

Pitthan, E.; dos Reis, R.; Corrêa, S. A.; Schmeisser, D.; Boudinov, H. I.; Stedile, F. C.

2016-01-01

Understanding the influence of SiC reaction with CO, a by-product of SiC thermal oxidation, is a key point to elucidate the origin of electrical defects in SiC metal-oxide-semiconductor (MOS) devices. In this work, the effects on electrical, structural, and chemical properties of SiO2/Si and SiO2/SiC structures submitted to CO annealing were investigated. It was observed that long annealing times resulted in the incorporation of carbon from CO in the Si substrate, followed by deterioration of the SiO2/Si interface, and its crystallization as SiC. Besides, this incorporated carbon remained in the Si surface (previous SiO2/Si region) after removal of the silicon dioxide film by HF etching. In the SiC case, an even more defective surface region was observed due to the CO interaction. All MOS capacitors formed using both semiconductor materials presented higher leakage current and generation of positive effective charge after CO annealings. Such results suggest that the negative fixed charge, typically observed in SiO2/SiC structures, is not originated from the interaction of the CO by-product, formed during SiC oxidation, with the SiO2/SiC interfacial region.

Crystal structure of the avilamycin resistance-conferring methyltransferase AviRa from Streptomyces viridochromogenes.

PubMed

Mosbacher, Tanja G; Bechthold, Andreas; Schulz, Georg E

2003-05-23

The emergence of antibiotic-resistant bacterial strains is a widespread problem in contemporary medical practice and drug design. It is therefore important to elucidate the underlying mechanism in each case. The methyltransferase AviRa from Streptomyces viridochromogenes mediates resistance to the antibiotic avilamycin, which is closely related to evernimicin, an oligosaccharide antibiotic that has been used in medical studies. The structure of AviRa was determined by X-ray diffraction at 1.5A resolution. Phases were obtained from one selenomethionine residue introduced by site-directed mutagenesis. The chain-fold is similar to that of most methyltransferases, although AviRa contains two additional helices as a specific feature. A putative-binding site for the cofactor S-adenosyl-L-methionine was derived from homologous structures. It agrees with the conserved pattern of interacting amino acid residues. AviRa methylates a specific guanine base within the peptidyltransferase loop of the 23S ribosomal RNA. Guided by the target, the enzyme was docked to the cognate ribosomal surface, where it fit well into a deep cleft without contacting any ribosomal protein. The two additional alpha-helices of AviRa filled a depression in the surface. Since the transferred methyl group of the cofactor is in a pocket beneath the enzyme surface, the targeted guanine base has to flip out for methylation.

[Study on chemical constituents from Schisandra chinensis stem].

PubMed

Zheng, Li-shi; Du, Shu-shan; Cai, Qian

2014-10-01

To separate and identify the chemical constituents from the stem of Schisandra chinensis. Various chromatographic techniques were used to separate and purify the chemical constituents from 95% ethanol extraction of the stem of Schisandra chinensis. Their structures were elucidated based on the physico-chemical properties and spectral data. Ten compounds were obtained and elucidated as (+)-deoxyschizandrin (1), γ-schizandrin (2), wuweizisu C (3), gomisin N (4), schizandrin (5), anwuweizic acid (6), (-)-dihydroguaiaretic acid (7), tetradecanoic acid (8), β-sitosterol (9) and daucosterol (10). Compounds 6-8 are obtained from the stem of Schisandra chinensis for the first time.

Brocaenols A-C: novel polyketides from a marine derived Penicillium brocae.

PubMed

Bugni, Tim S; Bernan, Valerie S; Greenstein, Michael; Janso, Jeffrey E; Maiese, William M; Mayne, Charles L; Ireland, Chris M

2003-03-07

Chemical investigation of a Penicillium brocae, obtained from a tissue sample of a Fijian Zyzyya sp. sponge, yielded two known diketopiperazines and three novel cytotoxic polyketides, brocaenols A-C. The brocaenols contain an unusual enolized oxepine lactone ring system that to the best of our knowledge is unprecedented in the literature. The structures were elucidated by using 2D-NMR methods including an INADEQUATE experiment. The absolute stereochemistry of brocaenol A was established by using a modified Mosher method. The taxonomy of the producing fungus was elucidated by using both morphological and rDNA sequence analysis.

Preparation and characterization of polyclonal antibodies against human chaperonin 10

PubMed Central

Somodevilla-Torres, Maria J.; Hillyard, Narelle C.; Morton, Halle; Alewood, Dianne; Halliday, Judy A.; Alewood, Paul F.; Vesey, David A.; Walsh, Michael D.; Cavanagh, Alice C.

2000-01-01

Abstract Early pregnancy factor (EPF) has been identified as an extracellular homologue of chaperonin 10 (Cpn10), a heat shock protein that functions within the cell as a molecular chaperone. Here, we report the production of polyclonal antibodies directed against several different regions of the human Cpn10 molecule and their application to specific protein quantitation and localization techniques. These antibodies will be valuable tools in further studies to elucidate the mechanisms underlying the differential spatial and temporal localization of EPF and Cpn10 and in studies to elucidate structure and function. PMID:10701835

[Studies on flavonoids of Oxytropis falcata].

PubMed

Lu, Fang; Xu, Xiao-Jie

2007-02-01

To investigate the flavonoids of Oxytropisfalcata. Compounds were isolated by column chromatography using silica gel, Sephadex LH -20 and ODS as the adsorbents. Their structures were elucidated by NMR and MS spectroscopic data. Eight compounds were isolated and elucidated as 2', 4'-dihydroxy-4-methoxy chalcone (1), 2', 4'-dihydroxy chalcone (2), 5,7-dihydroxy-4'-methoxy flavonol (3), 7-hydroxy-4'-methoxy flavanones (4), 3', 7-dihydroxy-2',4'-dimethoxy isoflavan (5), 2'-hydroxy-4'-methoxy chalcone (6), 2'-methoxy-4'-hydroxy chalcone (7), 2',4'-dihydroxy dihydrochalcone (8). All compounds were obtained from O. falcata for the first time.

Real-time elucidation of catalytic pathways in CO hydrogenation on Ru

DOE PAGES

LaRue, Jerry; Krejci, Ondrej; Yu, Liang; ...

2017-07-31

Here, the direct elucidation of the reaction pathways in heterogeneous catalysis has been challenging due the short-lived nature of reaction intermediates. Here, we directly measured on ultrafast timescales the initial hydrogenation steps of adsorbed CO on a Ru catalyst surface, which is known as the bottleneck reaction in syngas and CO 2 reforming processes. We initiated the hydrogenation of CO with an ultrafast laser temperature jump and probed transient changes in the electronic structure using real-time x-ray spectroscopy. In combination with theoretical simulations, we verified the formation of CHO during CO hydrogenation.

Subnanopore filling during water vapor adsorption on microporous silica thin films as seen by low-energy positron annihilation

NASA Astrophysics Data System (ADS)

Ito, Kenji; Yoshimoto, Shigeru; O'Rourke, Brian E.; Oshima, Nagayasu; Kumagai, Kazuhiro

2018-02-01

Positron annihilation lifetime spectroscopy (PALS) using a low-energy positron microbeam extracted into air was applied to elucidating molecular-level pore structures formed in silicon-oxide-backboned microporous thin films under controlled humidity conditions; as a result, a direct observation of the interstitial spaces in the micropores filled with water molecules was achieved. It was demonstrated that PALS using a microbeam extracted into air in combination with water vapor adsorption is a powerful tool for the in-situ elucidation of both open and closed subnanoscaled pores of functional thin materials under practical conditions.

The One-carbon Carrier Methylofuran from Methylobacterium extorquens AM1 Contains a Large Number of α- and γ-Linked Glutamic Acid Residues*

PubMed Central

Hemmann, Jethro L.; Saurel, Olivier; Ochsner, Andrea M.; Stodden, Barbara K.; Kiefer, Patrick; Milon, Alain; Vorholt, Julia A.

2016-01-01

Methylobacterium extorquens AM1 uses dedicated cofactors for one-carbon unit conversion. Based on the sequence identities of enzymes and activity determinations, a methanofuran analog was proposed to be involved in formaldehyde oxidation in Alphaproteobacteria. Here, we report the structure of the cofactor, which we termed methylofuran. Using an in vitro enzyme assay and LC-MS, methylofuran was identified in cell extracts and further purified. From the exact mass and MS-MS fragmentation pattern, the structure of the cofactor was determined to consist of a polyglutamic acid side chain linked to a core structure similar to the one present in archaeal methanofuran variants. NMR analyses showed that the core structure contains a furan ring. However, instead of the tyramine moiety that is present in methanofuran cofactors, a tyrosine residue is present in methylofuran, which was further confirmed by MS through the incorporation of a 13C-labeled precursor. Methylofuran was present as a mixture of different species with varying numbers of glutamic acid residues in the side chain ranging from 12 to 24. Notably, the glutamic acid residues were not solely γ-linked, as is the case for all known methanofurans, but were identified by NMR as a mixture of α- and γ-linked amino acids. Considering the unusual peptide chain, the elucidation of the structure presented here sets the basis for further research on this cofactor, which is probably the largest cofactor known so far. PMID:26895963

A rare case of extra-nasopharyngeal angiofibroma of the septum in a female child.

PubMed

Singh, G B; Shukla, S; Kumari, P; Shukla, I

2018-02-01

Extra-nasopharyngeal angiofibroma is a rare but distinct clinical entity, different from juvenile angiofibroma. This clinical record elucidates the only case of extra-nasopharyngeal angiofibroma arising from the septum in a female child, who presented with epistaxis. The histopathological diagnosis was confirmed by immunohistochemistry, and the case was managed surgically with no recurrence. In a female paediatric patient presenting with epistaxis, extra-nasopharyngeal angiofibroma (of the inferior turbinate) is a rare albeit important differential diagnosis, as it challenges the hormonal theory of angiofibroma aetiopathogenesis.

[Study on chemical constituents of Orobanche coerulescens].

PubMed

Zhao, Jun; Yan, Ming; Huang, Yi; He, Wen-yi; Zhao, Yu

2007-10-01

Six compounds were isolated and purified from Orobanche coerulescens by extraction and different kinds of column chromatography. The structures were determined on the basis of spectral analysis. The structures were elucidated as D-mannitol(I), beta-sitosterol(II), succinic acid(III), caffeic acid(IV), protocatechuic aldehyde(V) and daucosterol(VI). All compounds are obtained from this plant for the first time.

Structural characterization of product ions by electrospray ionization and quadrupole time-of-flight mass spectrometry to support regulatory analysis of veterinary drug residues in foods Part 2: Benzimidazoles nitromidaz.....

USDA-ARS?s Scientific Manuscript database

RATIONALE: Analysis for identification and quantification of regulated veterinary drug residues in foods are usually achieved by liquid chromatography coupled to tandem mass spectrometry. The instrument method requires the selection of characteristic ions, but structure elucidation is seldom perform...

Organic Spectroscopy Laboratory: Utilizing IR and NMR in the Identification of an Unknown Substance

ERIC Educational Resources Information Center

Glagovich, Neil M.; Shine, Timothy D.

2005-01-01

A laboratory experiment that emphasizes the interpretation of both infrared (IR) and nuclear magnetic resonance (NMR) spectra in the elucidation of the structure of an unknown compound was developed. The method helps students determine [to the first power]H- and [to the thirteenth power]C-NMR spectra from the structures of compounds and to…

Guaiane dimers from Xylopia vielana.

PubMed

Kamperdick, C; Phuong, N M; Van Sung, T; Adam, G

2001-02-01

From the leaves of Xylopia vielana (Annonaceae) the three dimeric guaianes vielanin A-C were isolated and structurally elucidated by mass and NMR spectroscopy as 1-3. The structure of 1 contains a bridged ring system formed probably via a Diels-Alder reaction of two different guaiane monomers. Compounds 2 and 3 represent symmetric cyclobutanes formally generated from two equal guaiane moieties by [2 + 2] cycloaddition.

Cybastacines A and B: Antibiotic Sesterterpenes from a Nostoc sp. Cyanobacterium.

PubMed

Cabanillas, Alfredo H; Tena Pérez, Víctor; Maderuelo Corral, Santiago; Rosero Valencia, Diego Fernando; Martel Quintana, Antera; Ortega Doménech, Montserrat; Rumbero Sánchez, Ángel

2018-02-23

Cybastacines A (1) and B (2) were discovered as a novel pentacyclic sesterterpenoid-alkaloid skeleton structure, with a guanidinium group. These molecules were isolated from a Nostoc sp. cyanobacterium collected in the Canary Islands. Their structures were elucidated primarily by a combination of spectroscopic analyses and X-ray diffraction. These compounds showed antibiotic activities against several clinically relevant bacterial strains.

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: structural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

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

Green, E.D.; Baenziger, J.U.

1988-01-05

The authors have elucidated the structures of the anionic asparagine-linked oligosaccharides present on the glycoprotein hormones lutropin (luteinizing hormone), follitropin (follicle-stimulating hormone), and thyrotropin (thyroid-stimulating hormone). Purified hormones, isolated from bovine, ovine, and human pituitaries, were digested with N-glycanase, and the released oligosaccharides were reduced with NaB(/sup 3/H)/sub 4/. The /sup 3/H-labeled oligosaccharides from each hormone were then fractionated by anion-exchange high performance liquid chromatography (HPLC) into populations differing in the number of sulfate and/or sialic acid moieties. The sulfated, sialylated, and sulfated/sialylated structures, which together comprised 67-90% of the asparagine-linked oligosaccharides on the pituitary glycoprotein hormones, were highly heterogeneousmore » and displayed hormone- as well as animal species-specific features. A previously uncharacterized dibranched oligosaccharide, bearing one residue each of sulfate and sialic acid, was found on all of the hormones except bovine lutropin. In this study, they describe the purification and detailed structural characterizations of the sulfated, sialylated, and sulfated/sialylated oligosaccharides found on lutropin, follitropin, and thyrotropin from several animal species.« less

Elucidation of Peptide-Directed Palladium Surface Structure for Biologically Tunable Nanocatalysts

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

Bedford, Nicholas M.; Ramezani-Dakhel, Hadi; Slocik, Joseph M.

Peptide-enabled synthesis of inorganic nanostructures represents an avenue to access catalytic materials with tunable and optimized properties. This is achieved via peptide complexity and programmability that is missing in traditional ligands for catalytic nanomaterials. Unfortunately, there is limited information available to correlate peptide sequence to particle structure and catalytic activity to date. As such, the application of peptide-enabled nanocatalysts remains limited to trial and error approaches. In this paper, a hybrid experimental and computational approach is introduced to systematically elucidate biomolecule-dependent structure/function relationships for peptide-capped Pd nanocatalysts. Synchrotron X-ray techniques were used to uncover substantial particle surface structural disorder, whichmore » was dependent upon the amino acid sequence of the peptide capping ligand. Nanocatalyst configurations were then determined directly from experimental data using reverse Monte Carlo methods and further refined using molecular dynamics simulation, obtaining thermodynamically stable peptide-Pd nanoparticle configurations. Sequence-dependent catalytic property differences for C-C coupling and olefin hydrogenation were then eluddated by identification of the catalytic active sites at the atomic level and quantitative prediction of relative reaction rates. This hybrid methodology provides a clear route to determine peptide-dependent structure/function relationships, enabling the generation of guidelines for catalyst design through rational tailoring of peptide sequences« less

Molecular understanding of mutagenicity using potential energy methods. Progress report, July 1, 1992--September 30, 1993

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

Broyde, S.; Shapiro, R.

1993-09-01

Our objective has been to elucidate on a molecular level, at atomic resolution, the structures of DNAs modified by highly mutagenic aromatic amines and hydrocarbons. The underlying hypothesis is that DNA replicates with reduced fidelity when its normal right-handed B-structure is altered, and one result is a higher mutation rate. This change in structure may occur normally at a low incidence but it may be enhanced greatly after covalent modification by a mutagenic substance. The methods that we use to elucidate structures are computational, but we keep in close contact with experimental developments, and we incorporate data from NMR studiesmore » in our calculations when they are available. X-ray and low resolution spectroscopic studies have not succeeded in producing atomic resolution views of mutagen and carcinogen-oligonucleotide adducts. Even the high resolution NMR method cannot alone yield molecular views, though it does so in combination with our computations. The specific methods that we employ are minimized potential energy calculations using the torsion angle space molecular mechanics program DUPLEX to yield static views. Molecular dynamics simulations of static structures with solvent and salt can be carried out with the program AMBER; this yields mobile views in a medium that mimics aspects of the natural aqueous environment of the cell.« less

Structure elucidation of metabolite x17299 by interpretation of mass spectrometric data.

PubMed

Zhang, Qibo; Ford, Lisa A; Evans, Anne M; Toal, Douglas R

2017-01-01

A major bottleneck in metabolomic studies is metabolite identification from accurate mass spectrometric data. Metabolite x17299 was identified in plasma as an unknown in a metabolomic study using a compound-centric approach where the associated ion features of the compound were used to determine the true molecular mass. The aim of this work is to elucidate the chemical structure of x17299, a new compound by de novo interpretation of mass spectrometric data. An Orbitrap Elite mass spectrometer was used for acquisition of mass spectra up to MS 4 at high resolution. Synthetic standards of N,N,N -trimethyl-l-alanyl-l-proline betaine (l,l-TMAP), a diastereomer, and an enantiomer were chemically prepared. The planar structure of x17299 was successfully proposed by de novo mechanistic interpretation of mass spectrometric data without any laborious purification and nuclear magnetic resonance spectroscopic analysis. The proposed structure was verified by deuterium exchanged mass spectrometric analysis and confirmed by comparison to a synthetic standard. Relative configuration of x17299 was determined by direct chromatographic comparison to a pair of synthetic diastereomers. Absolute configuration was assigned after derivatization of x17299 with a chiral auxiliary group followed by its chromatographic comparison to a pair of synthetic standards. The chemical structure of metabolite x17299 was determined to be l,l-TMAP.

[About a fortuitous representation of a case of intestinal malrotation by Wilhem His (1880)].

PubMed

Louryan, S

2011-06-01

In a textbook published in 1882, His exhibits drawings devoted to intestine development. The last figure depicts a typical case of gut malrotation, but there is no comment about this in the text. It could be possible that this omission should be due to the fact that mechanisms of gut development were not totally elucidated at this time. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Change

DTIC Science & Technology

2013-10-01

burden of ovarian cancer through prevention. Finally, it is important to note that clear cell, endometrioid and mucinous carcinomas are clinically...were cut onto PEN membrane slides (Leica), and immediately stored on dry ice. An entire cross-section of fallopian tubes for each case underwent LCM...containing BRCA1, BRCA2 and non-BRCA cases, utilizing the following exclusion criteria: o Systemic steroid treatment for other conditions (ie SLE/ankylosing

2,3-Dihydrobiflavone from Ginkgo biloba.

PubMed

Krauze-Baranowska, M; Sowiński, P

1999-06-01

From the yellow leaves of Ginkgo biloba 2,3-dihydrosciadopitysin (5,5'',7''-trihydroxy-7,4',4'''-trimethoxy-3',8''-flavanone/flavone) was isolated as a mixture of two diastereomers. Its structure was elucidated employing 2D NMR techniques.

Mumic acids A-E: new diterpenoids from mumiyo.

PubMed

Kiren, Yuko; Nugroho, Alfarius Eko; Hirasawa, Yusuke; Shirota, Osamu; Bekenova, Myrzaim; Narbekovich, Narbekov Omorbay; Shapilova, Marina; Maeno, Hiromichi; Morita, Hiroshi

2014-01-01

Five new diterpenoids belonging to labdane and isopimarane skeletons, mumic acids A-E (1-5), have been isolated from mumiyo. Their structures and absolute configurations were elucidated on the basis of spectroscopic data and chemical derivatization.

Grasshopper ketone 3-O-primveroside from Sinocrassula indica.

PubMed

Xie, Hai-Hui; Yoshikawa, Masayuki

2012-01-01

A new megastigmane glycoside, grasshopper ketone 3-O-primveroside (1), was isolated from the methanolic extract of the whole herbs of Sinocrassula indica (Crassulaceae). Its structure was elucidated on the basis of spectral and chemical evidence.

Hirsutane-type sesquiterpenes with uncommon modifications from three basidiomycetes.

PubMed

Liermann, Johannes C; Schüffler, Anja; Wollinsky, Beate; Birnbacher, Judith; Kolshorn, Heinz; Anke, Timm; Opatz, Till

2010-05-07

From three basidiomycetes, Xeromphalina sp., Stereum sp., and Pleurocybella porrigens, six triquinane sesquiterpenes with unprecendented modifications and a rearranged sesquiterpene related to coriolin C have been isolated. Their isolation, structure elucidation, and biological evaluation are described.

Elucidation of the atomic-scale mechanism of the anisotropic oxidation rate of 4H-SiC between the (0001) Si-face and ( 000 1 ¯ ) C-face by using a new Si-O-C interatomic potential

NASA Astrophysics Data System (ADS)

Takamoto, So; Yamasaki, Takahiro; Ohno, Takahisa; Kaneta, Chioko; Hatano, Asuka; Izumi, Satoshi

2018-05-01

Silicon carbide (SiC) is an attractive semiconductor material for applications in power electronic devices. However, fabrication of a high-quality SiC/SiO2 interface has been a challenge. It is well-known that there is a great difference in the oxidation rate between the Si-face and the C-face and that the quality of oxide on the Si-face is greater than that on the C-face. However, the atomistic mechanism of the thermal oxidation of SiC remains to be solved. In this paper, a new Si-O-C interatomic potential was developed to reproduce the kinetics of the thermal oxidation of SiC. Using this newly developed potential, large-scale SiC oxidation simulations at various temperatures were performed. The results showed that the activation energy of the Si-face is much larger than that of the C-face. In the case of the Si-face, a flat and aligned interface structure including Si1+ was created. Based on the estimated activation energies of the intermediate oxide states, it is proposed that the stability of the flat interface structure is the origin of the high activation energy of the oxidation of the Si-face. In contrast, in the case of the C-face, it is found that the Si atom at the interface is easily pulled up by the O atoms. This process generates the disordered interface and decreases the activation energy of the oxidation. It is also proposed that many excess C atoms are created in the case of the C-face.

Computational mass spectrometry for small molecules

PubMed Central

2013-01-01

The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

Nanometer-scale mapping of irreversible electrochemical nucleation processes on solid Li-ion electrolytes

NASA Astrophysics Data System (ADS)

Kumar, Amit; Arruda, Thomas M.; Tselev, Alexander; Ivanov, Ilia N.; Lawton, Jamie S.; Zawodzinski, Thomas A.; Butyaev, Oleg; Zayats, Sergey; Jesse, Stephen; Kalinin, Sergei V.

2013-04-01

Electrochemical processes associated with changes in structure, connectivity or composition typically proceed via new phase nucleation with subsequent growth of nuclei. Understanding and controlling reactions requires the elucidation and control of nucleation mechanisms. However, factors controlling nucleation kinetics, including the interplay between local mechanical conditions, microstructure and local ionic profile remain inaccessible. Furthermore, the tendency of current probing techniques to interfere with the original microstructure prevents a systematic evaluation of the correlation between the microstructure and local electrochemical reactivity. In this work, the spatial variability of irreversible nucleation processes of Li on a Li-ion conductive glass-ceramics surface is studied with ~30 nm resolution. An increased nucleation rate at the boundaries between the crystalline AlPO4 phase and amorphous matrix is observed and attributed to Li segregation. This study opens a pathway for probing mechanisms at the level of single structural defects and elucidation of electrochemical activities in nanoscale volumes.

A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf.

PubMed

da Silva, Gustavo; Martinho, Ana; Soengas, Raquel González; Duarte, Ana Paula; Serrano, Rita; Gomes, Elsa Teixeira; Silva, Olga

2015-10-01

The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. The alkaloid revealed to be non-cytotoxic against both cell lines. The IC50 values from the cells were also determined. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural elucidation of polysaccharide containing 3-O-methyl galactose from fruiting bodies of Pleurotus citrinopileatus.

PubMed

He, Pengfei; Zhang, Anqiang; Zhou, Saijing; Zhang, Fuming; Linhardt, Robert J; Sun, Peilong

2016-11-03

A water-soluble polysaccharide containing 3-O-methyl galactose (PCP60W) was isolated from fruiting bodies of Pleurotus citrinopileatus and purified by anion-exchange and gel column chromatography. This polysaccharide has an average molecular weight of 2.74 × 10 4  Da and its structure was elucidated using monosaccharide composition and methylation analysis combined with one- and two-dimensional (COSY, TOCSY, NOESY, HMQC and HMBC) NMR spectroscopy. PCP60W was shown to be a linear partially 3-O-methylated α-galactopyranan comprised of 6-linked galactose, 6-linked 3-O-methyl galactose and 4-linked glucose in a ratio of 3.0:1.0:0.6. This work provides additional evidence for the view that 3-O-methyl galactose is common to the genus Pleurotus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanometer-scale mapping of irreversible electrochemical nucleation processes on solid Li-ion electrolytes.

PubMed

Kumar, Amit; Arruda, Thomas M; Tselev, Alexander; Ivanov, Ilia N; Lawton, Jamie S; Zawodzinski, Thomas A; Butyaev, Oleg; Zayats, Sergey; Jesse, Stephen; Kalinin, Sergei V

2013-01-01

Electrochemical processes associated with changes in structure, connectivity or composition typically proceed via new phase nucleation with subsequent growth of nuclei. Understanding and controlling reactions requires the elucidation and control of nucleation mechanisms. However, factors controlling nucleation kinetics, including the interplay between local mechanical conditions, microstructure and local ionic profile remain inaccessible. Furthermore, the tendency of current probing techniques to interfere with the original microstructure prevents a systematic evaluation of the correlation between the microstructure and local electrochemical reactivity. In this work, the spatial variability of irreversible nucleation processes of Li on a Li-ion conductive glass-ceramics surface is studied with ~30 nm resolution. An increased nucleation rate at the boundaries between the crystalline AlPO4 phase and amorphous matrix is observed and attributed to Li segregation. This study opens a pathway for probing mechanisms at the level of single structural defects and elucidation of electrochemical activities in nanoscale volumes.

Nanometer-scale mapping of irreversible electrochemical nucleation processes on solid Li-ion electrolytes

PubMed Central

Kumar, Amit; Arruda, Thomas M.; Tselev, Alexander; Ivanov, Ilia N.; Lawton, Jamie S.; Zawodzinski, Thomas A.; Butyaev, Oleg; Zayats, Sergey; Jesse, Stephen; Kalinin, Sergei V.

2013-01-01

Electrochemical processes associated with changes in structure, connectivity or composition typically proceed via new phase nucleation with subsequent growth of nuclei. Understanding and controlling reactions requires the elucidation and control of nucleation mechanisms. However, factors controlling nucleation kinetics, including the interplay between local mechanical conditions, microstructure and local ionic profile remain inaccessible. Furthermore, the tendency of current probing techniques to interfere with the original microstructure prevents a systematic evaluation of the correlation between the microstructure and local electrochemical reactivity. In this work, the spatial variability of irreversible nucleation processes of Li on a Li-ion conductive glass-ceramics surface is studied with ~30 nm resolution. An increased nucleation rate at the boundaries between the crystalline AlPO4 phase and amorphous matrix is observed and attributed to Li segregation. This study opens a pathway for probing mechanisms at the level of single structural defects and elucidation of electrochemical activities in nanoscale volumes. PMID:23563856

Structure elucidation of organic compounds from natural sources using 1D and 2D NMR techniques

NASA Astrophysics Data System (ADS)

Topcu, Gulacti; Ulubelen, Ayhan

2007-05-01

In our continuing studies on Lamiaceae family plants including Salvia, Teucrium, Ajuga, Sideritis, Nepeta and Lavandula growing in Anatolia, many terpenoids, consisting of over 50 distinct triterpenoids and steroids, and over 200 diterpenoids, several sesterterpenoids and sesquiterpenoids along with many flavonoids and other phenolic compounds have been isolated. For Salvia species abietanes, for Teucrium and Ajuga species neo-clerodanes for Sideritis species ent-kaurane diterpenes are characteristic while nepetalactones are specific for Nepeta species. In this review article, only some interesting and different type of skeleton having constituents, namely rearranged, nor- or rare diterpenes, isolated from these species will be presented. For structure elucidation of these natural diterpenoids intensive one- and two-dimensional NMR techniques ( 1H, 13C, APT, DEPT, NOE/NOESY, 1H- 1H COSY, HETCOR, COLOC, HMQC/HSQC, HMBC, SINEPT) were used besides mass and some other spectroscopic methods.

Rapid screening and structural elucidation of a novel sibutramine analogue in a weight loss supplement: 11-desisobutyl-11-benzylsibutramine.

PubMed

Mans, Daniel J; Gucinski, Ashley C; Dunn, Jamie D; Gryniewicz-Ruzicka, Connie M; Mecker-Pogue, Laura C; Kao, Jeff L-F; Ge, Xia

2013-09-01

A novel analogue of sibutramine, 11-desisobutyl-11-benzylsibutramine, has been discovered. During routine ion mobility spectrometry (IMS) screening of a weight loss supplement collected at an US FDA import operation facility an unknown peak was observed. Further analysis of the supplement by liquid chromatography-mass spectrometry (LC-MS) and high resolution mass spectrometry revealed an unknown peak with a relative retention time of 1.04 with respect to sibutramine and a predicted formula of C20H24NCl. In order to elucidate the analogue's structure, it was isolated from the supplement and characterized by tandem mass spectrometry and nuclear magnetic resonance (NMR), which revealed the analogue possessed a benzyl moiety at the 11 position in place of the isobutyl group associated with sibutramine. Copyright © 2013. Published by Elsevier B.V.

Dhilirolides E-N, meroterpenoids produced in culture by the fungus Penicillium purpurogenum collected in Sri Lanka: structure elucidation, stable isotope feeding studies, and insecticidal activity.

PubMed

Centko, Ryan M; Williams, David E; Patrick, Brian O; Akhtar, Yasmin; Garcia Chavez, Miguel Angel; Wang, Yan Alexander; Isman, Murray B; de Silva, E Dilip; Andersen, Raymond J

2014-04-18

Extracts of laboratory cultures of the fungus Penicilium purpurogenum obtained from rotting fruit of the tree Averrhoa bilimbi growing in Sri Lanka have yielded 10 new meroterpenoids, dhilirolides E-N (5-14). The structures of the new dhilirolides have been elucidated by analysis of spectroscopic data and a single-crystal X-ray diffraction analysis of dhilirolide L (12). Dhilirolides A-N (1-14) represent the four unprecedented and rearranged dhilirane, isodhilirane, 14,15-dinordhilirane, and 23,24-dinorisodhilirane meroterpenoid carbon skeletons. Stable isotope feeding studies have confirmed the meroterpenoid biogenetic origin of the dhilirolides and provided support for a proposed genesis of the new carbon skeletons. Dhilirolide L (12) showed significant feeding inhibition and sublethal developmental disruption in the cabbage looper Trichoplusia ni, an important agricultural pest, at low concentrations.

One-pot microwave assisted synthesis and structural elucidation of novel ethyl 3-substituted-7-methylindolizine-1-carboxylates with larvicidal activity against Anopheles arabiensis

NASA Astrophysics Data System (ADS)

Chandrashekharappa, Sandeep; Venugopala, Katharigatta N.; Nayak, Susanta K.; Gleiser, Raquel M.; García, Daniel A.; Kumalo, Hezekiel M.; Kulkarni, Rashmi S.; Mahomoodally, Fawzi M.; Venugopala, Rashmi; Mohan, Mahendra K.; Odhav, Bharti

2018-03-01

In the present investigation a series of novel ethyl 3-substituted-7-methylindolizine-1-carboxylates was achieved by microwave assisted one-pot method. The purity of the compounds was ascertained by HPLC and structural elucidation of the title compounds was achieved by FT-IR, NMR (1H and 13C), LC-MS and elemental analysis. One randomly selected compound from the series was further studied by single crystal X-ray method for intra and intermolecular interactions. Larvicidal properties of the characterized compounds were evaluated against Anopheles arabiensis and it was found that indolizine pharmacophore influences larvicidal activity as we can see larvicidal activity for all the analogues. The synthesized analogues (2j, 2m and 2f) were the most potent compounds based on the functional groups on the indolizine pharmacophore for larvicidal assay.

Structure Elucidation and Immunomodulatory Activity of A Beta Glucan from the Fruiting Bodies of Ganoderma sinense

PubMed Central

Yue, Rui-Qi; Dong, Cai-Xia; Chan, Chung-Lap; Ko, Chun-Hay; Cheung, Wing-Shing; Luo, Ke-Wang; Dai, Hui; Wong, Chun-Kwok; Leung, Ping-Chung; Han, Quan-Bin

2014-01-01

A polysaccharide named GSP-2 with a molecular size of 32 kDa was isolated from the fruiting bodies of Ganoderma sinense. Its structure was well elucidated, by a combined utilization of chemical and spectroscopic techniques, to be a β-glucan with a backbone of (1→4)– and (1→6)–Glcp, bearing terminal- and (1→3)–Glcp side-chains at O-3 position of (1→6)–Glcp. Immunological assay exhibited that GSP-2 significantly induced the proliferation of BALB/c mice splenocytes with target on only B cells, and enhanced the production of several cytokines in human peripheral blood mononuclear cells and derived dendritic cells. Besides, the fluorescent labeled GSP-2 was phagocytosed by the RAW 264.7 cells and induced the nitric oxide secretion from the cells. PMID:25014571

Nine New Gingerols from the Rhizoma of Zingiber officinale and Their Cytotoxic Activities.

PubMed

Li, Zezhi; Wang, Yanzhi; Gao, MeiLing; Cui, Wanhua; Zeng, Mengnan; Cheng, Yongxian; Li, Juan

2018-02-02

Nine new gingerols, including three 6-oxo-shogaol derivatives [( Z )-6-oxo-[6]-shogaol ( 1 ), ( Z )-6-oxo-[8]-shogaol ( 2 ), ( Z )-6-oxo-[10]-shogaol ( 3 )], one 6-oxoparadol derivative [6-oxo-[6]-paradol ( 4 )], one isoshogaol derivative [( E )-[4]-isoshogaol ( 5 )], and four paradoldiene derivatives [(4 E ,6 Z )-[4]-paradoldiene ( 8 ), (4 E ,6 E )-[6]-paradoldiene ( 9 ), (4 E ,6 E )-[8]-paradoldiene ( 10 ), (4 E ,6 Z )-[8]-paradoldiene ( 11 )], together with eight known analogues, were isolated from the rhizoma of Zingiber officinale . Their structures were elucidated on the basis of spectroscopic data. It was noted that the isolation of 6-oxo-shogaol derivatives represents the first report of gingerols containing one 1,4-enedione motif. Their structures were elucidated on the basis of spectroscopic and HRESIMS data. All the new compounds were evaluated for their cytotoxic activities against human cancer cells (MCF-7, HepG-2, KYSE-150).

Methodological proposal for studying suicide as a complex phenomenon.

PubMed

Minayo, Maria Cecília de Souza; Cavalcante, Fátima Gonçalves; de Souza, Edinilsa Ramos

2006-08-01

The authors present a methodological proposal for studying suicide and suicide attempts from a combined socio-anthropological, epidemiological, and psychosocial perspective. This interdisciplinary and complex research model simultaneously examined individual, socioeconomic, historical/cultural, and population data as few studies have succeeded to date. Considering that the present study was conducted in a specific social reality, the authors created a methodological approach to comprehend the effects of a crisis in an industrial restructuring process in a mining company town in the State of Minas Gerais, Brazil, that was associated with unusually high suicide rates. Since it referred to a small geographic area (with only 100,000 inhabitants), the research is considered an ideal case study. The authors created different strategies to trace the local epidemiological profile, adapted a psychosocial autopsy technique to elucidate suicide cases and a psychosocial harm assessment technique to comprehend suicide attempts, and conducted a local analysis of the socio-cultural context. The methods proposed here (with advantages and limitations) proved productive for elucidating the study hypothesis.

Convergent dysregulation of frontal cortical cognitive and reward systems in eating disorders.

PubMed

Stefano, George B; Ptáček, Radek; Kuželová, Hana; Mantione, Kirk J; Raboch, Jiří; Papezova, Hana; Kream, Richard M

2013-05-10

A substantive literature has drawn a compelling case for the functional involvement of mesolimbic/prefrontal cortical neural reward systems in normative control of eating and in the etiology and persistence of severe eating disorders that affect diverse human populations. Presently, we provide a short review that develops an equally compelling case for the importance of dysregulated frontal cortical cognitive neural networks acting in concert with regional reward systems in the regulation of complex eating behaviors and in the presentation of complex pathophysiological symptoms associated with major eating disorders. Our goal is to highlight working models of major eating disorders that incorporate complementary approaches to elucidate functionally interactive neural circuits defined by their regulatory neurochemical phenotypes. Importantly, we also review evidence-based linkages between widely studied psychiatric and neurodegenerative syndromes (e.g., autism spectrum disorders and Parkinson's disease) and co-morbid eating disorders to elucidate basic mechanisms involving dopaminergic transmission and its regulation by endogenously expressed morphine in these same cortical regions.

Biomarkers as tracers for life on early earth and Mars

NASA Technical Reports Server (NTRS)

Simoneit, B. R.; Summons, R. E.; Jahnke, L. L.

1998-01-01

Biomarkers in geological samples are products derived from biochemical (natural product) precursors by reductive and oxidative processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments and biomembranes are preserved best over longer geological times and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker compositions permits the assessment of the major contributing species of extinct and/or extant life. In the case of the early Earth, work has progressed to elucidate molecular structure and carbon isotropic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior and preservation potential of primitive microbial communities. This approach uses combined molecular and isotopic analyses to characterize lipids produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions which affect their biosynthesis. On considering Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) yr ago). Both oxidized and reduced products would be expected. This is based on the inferred occurrence of hydrothermal activity during that time with the concomitant preservation of biochemically-derived organic matter. Both known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) and novel, potentially unknown compounds should be characterized.

How Does Your Protein Fold? Elucidating the Apomyoglobin Folding Pathway

PubMed Central

Dyson, H. Jane; Wright, Peter E.

2017-01-01

Conspectus Although each type of protein fold and in some cases individual proteins within a fold classification can have very different mechanisms of folding, the underlying biophysical and biochemical principles that operate to cause a linear polypeptide chain to fold into a globular structure must be the same. In an aqueous solution, the protein takes up the thermodynamically most stable structure, but the pathway along which the polypeptide proceeds in order to reach that structure is a function of the amino acid sequence, which must be the final determining factor, not only in shaping the final folded structure, but in dictating the folding pathway. A number of groups have focused on a single protein or group of proteins, to determine in detail the factors that influence the rate and mechanism of folding in a defined system, with the hope that hypothesis-driven experiments can elucidate the underlying principles governing the folding process. Our research group has focused on the folding of the globin family of proteins, and in particular on the monomeric protein apomyoglobin. Apomyoglobin (apoMb) folds relatively slowly (~2 seconds) via an ensemble of obligatory intermediates that form rapidly after the initiation of folding. The folding pathway can be dissected using rapid-mixing techniques, which can probe processes in the millisecond time range. Stopped-flow measurements detected by circular dichroism (CD) or fluorescence spectroscopy give information on the rates of folding events. Quench-flow experiments utilize the differential rates of hydrogen-deuterium exchange of amide protons protected in parts of the structure that are folded early; protection of amides can be detected by mass spectrometry or proton nuclear magnetic resonance spectroscopy (NMR). In addition, apoMb forms an intermediate at equilibrium at pH ~ 4, which is sufficiently stable for it to be structurally characterized by solution methods such as CD, fluorescence and NMR spectroscopies, and the conformational ensembles formed in the presence of denaturing agents and low pH can be characterized as models for the unfolded states of the protein. Newer NMR techniques such as measurement of residual dipolar couplings in the various partly folded states, and relaxation dispersion measurements to probe invisible states present at low concentrations, have contributed to providing a detailed picture of the apomyoglobin folding pathway. The research summarized in this review was aimed at characterizing and comparing the equilibrium and kinetic intermediates both structurally and dynamically, as well as delineating the complete folding pathway at a residue-specific level, in order to answer the question “What is it about the amino acid sequence that causes each molecule in the unfolded protein ensemble to start folding, and, once started, to proceed towards the formation of the correctly folded three-dimensional structure?” PMID:28032989

Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

PubMed

Das, Jagabandhu; Kimball, S David; Hall, Steven E; Han, Wen Ching; Iwanowicz, Edwin; Lin, James; Moquin, Robert V; Reid, Joyce A; Sack, John S; Malley, Mary F; Chang, Chiehying Y; Chong, Saeho; Wang-Iverson, David B; Roberts, Daniel G M; Seiler, Steven M; Schumacher, William A; Ogletree, Martin L

2002-01-07

A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

Structure of water clusters on graphene: A classical molecular dynamics approach

NASA Astrophysics Data System (ADS)

Maekawa, Yuki; Sasaoka, Kenji; Yamamoto, Takahiro

2018-03-01

The microscopic structure of surface water adsorbed on graphene is elucidated theoretically by classical molecular dynamics simulation. At a low temperature (100 K), the main polygon consisting of hydrogen bonds in single-layered water on graphene is tetragonal, whereas the dominant polygons in double-layered water are tetragonal, pentagonal, and hexagonal. On the other hand, at room temperature, the tetragonal, pentagonal, and hexagonal water clusters are the main structures in both single- and double-layered water.

Elucidation of kinematical and dynamical structure of the Galactic bulge

NASA Astrophysics Data System (ADS)

Yano, T.; Gouda, N.; Ueda, H.; Koyama, H.; Kan-ya, Y.; Taruya, A.

2008-07-01

Future space mission of astrometric satellite, GAIA and JASMINE (Japan Astrometry Satellite Mission for Infrared Exploration), will produce astrometric parameter, such as positions, parallaxes, and proper motions of stars in the Galactic bulge. Then kinematical information will be obtained in the future. Accordingly it is expected that our understanding of the dynamical structure will be greatly improved. Therefore it is important to make a method to construct a kinematical and dynamical structure of the Galactic bulge immediately.

Structure Elucidation of New Acetylated Saponins, Lessoniosides A, B, C, D, and E, and Non-Acetylated Saponins, Lessoniosides F and G, from the Viscera of the Sea Cucumber Holothuria lessoni

PubMed Central

Bahrami, Yadollah; Franco, Christopher M. M.

2015-01-01

Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core), and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na]+ provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins, Lessoniosides A–E, along with two non-acetylated saponins Lessoniosides F and G at m/z 1477.7, which are promising candidates for future drug development. The presented strategy allows a rapid, reliable and complete analysis of native saponins. PMID:25603350

Public Health Nurses' Activities for Suicide Prevention in Japan.

PubMed

Marutani, Miki; Yamamoto-Mitani, Noriko; Kodama, Shimpei

2016-07-01

Suicide is a major health issue worldwide, including in Japan. Japanese public health nurses (PHNs) play a distinctive role in suicide prevention, although few studies have delineated this role. The purpose of this study was to develop a conceptual framework that elucidates PHNs' activities for suicide prevention. Semi-structured interviews were conducted in 2012-2013 with 15 PHNs who worked in Tokyo metropolitan regions. Data were analyzed qualitatively using grounded theory, and a conceptual framework with seven categories was developed. Three phases that depict the PHNs' suicide prevention activities emerged. Phase I, Pursuing to understand suicide cases, included two categories: tracing back individual suicide cases and raising consciousness among the general public. Phase II, Spreading a web of care, included three categories: knitting a caring network, weaving regular programs into the web, and continuing to be a member of the web. Phase III, Maintaining motivation and commitment, included two categories: legitimatizing suicide prevention and cultivating continued commitment in the community. The activities of suicide prevention by PHNs included a process of developing a caring network that lead to the enhancement of the caring capacity of the community as a whole. © 2016 Wiley Periodicals, Inc.

Breeding experiments and genome-wide association analysis elucidate two genetically different forms of non-syndromic congenital cleft lip and jaw in Vorderwald × Montbéliarde cattle.

PubMed

Reinartz, S; Distl, O

2017-10-01

Non-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in Vorderwald × Montbéliarde cattle. The objective of the present study was to perform a genome-wide association study (GWAS) for 10 CLJ-affected and 50 unaffected Vorderwald × Montbéliarde cattle using the bovine Illumina high density bead chip to identify loci for this condition. Phenotypic classification of CLJ was based on a detailed recording of orofacial structures using computed tomography. A breeding experiment among CLJ-affected Vorderwald × Montbéliarde cattle and CLJ-affected Vorderwald × Montbéliarde cattle with unaffected Holsteins confirmed recessive inheritance and different loci for bilateral or left-sided versus right-sided CLJ. The GWAS for the five cases with right-sided CLJ gave a genome-wide signal on bovine chromosome (BTA) 29 at 16 Mb. For the four left-sided and one bilateral CLJ case, a genome-wide significant association was identified on BTA4 at 32 Mb. Two different loci are very likely to be involved in CLJ in Vorderwald × Montbéliarde cattle because experimental matings among affected cows and bulls with different types of CLJ did not result in CLJ-affected progeny, and in addition, two different loci were also found through GWAS and mapped on two different bovine chromosomes. Validation in 346 Vorderwald × Montbéliarde cattle for the highly associated SNPs on BTA4 and 29 gave ratios of 33/346 (0.095, BTA4) and 6/346 (0.017, BTA29) homozygous mutant genotypes. Further studies should elucidate the responsible mutations underlying the different types of CLJ in Vorderwald × Montbéliarde cattle. © 2017 Stichting International Foundation for Animal Genetics.

Isolation and structure elucidation of avocado seed (Persea americana) lipid derivatives that inhibit Clostridium sporogenes endospore germination.

PubMed

Rodríguez-Sánchez, Dariana Graciela; Pacheco, Adriana; García-Cruz, María Isabel; Gutiérrez-Uribe, Janet Alejandra; Benavides-Lozano, Jorge Alejandro; Hernández-Brenes, Carmen

2013-07-31

Avocado fruit extracts are known to exhibit antimicrobial properties. However, the effects on bacterial endospores and the identity of antimicrobial compounds have not been fully elucidated. In this study, avocado seed extracts were tested against Clostridium sporogenes vegetative cells and active endospores. Bioassay-guided purification of a crude extract based on inhibitory properties linked antimicrobial action to six lipid derivatives from the family of acetogenin compounds. Two new structures and four compounds known to exist in nature were identified as responsible for the activity. Structurally, most potent molecules shared features of an acetyl moiety and a trans-enone group. All extracts produced inhibition zones on vegetative cells and active endospores. Minimum inhibitory concentrations (MIC) of isolated molecules ranged from 7.8 to 15.6 μg/mL, and bactericidal effects were observed for an enriched fraction at 19.5 μg/mL. Identified molecules showed potential as natural alternatives to additives and antibiotics used by the food and pharmaceutical industries to inhibit Gram-positive spore-forming bacteria.

Production and structural elucidation of exopolysaccharide from endophytic Pestalotiopsis sp. BC55.

PubMed

Mahapatra, Subhadip; Banerjee, Debdulal

2016-01-01

There is a little information on exopolysaccharide production by endophytic fungi. In this investigation endophytic Pestalotiopsis sp. BC55 was used for optimization of exopolysaccharide production. One variable at a time method and response surface methodology were adopted to find out the best culture conditions and medium compositions for maximum exopolysaccharide production. The organism produced maximum exopolysaccharide (4.320 ± 0.022 g/l EPS) in 250 ml Erlenmeyer flask containing 75 ml potato dextrose broth supplemented with (g%/l) glucose, 7.66; urea, 0.29; CaCl2, 0.05 with medium pH 6.93; after 3.76 days of incubation at 24°C. Exopolysaccharide [EPS (EP-I)] produced by this organism have Mw ∼2×10(5)Da with a melting point range of 122-124°C. Structural elucidation of the EPS (PS-I) was carried out after a series of experiments. Result indicated the presence of only (1→3)-linked β-d-glucopyranosyl moiety. The structure of the repeating unit was established as - →3)-β-d-Glcp-(1→. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure elucidation of two novel yak milk oligosaccharides and their DFT studies

NASA Astrophysics Data System (ADS)

Singh, Ashish Kumar; Ranjan, Ashok Kr.; Srivastava, Gaurav; Deepak, Desh

2016-03-01

Milk is a primary dynamic biological fluid responsible for development of neonates. Besides the other regular constituents it have oligosaccharides in it which are responsible for antitumor, anticancer, antigenic and immunostimulant activities. In our endeavor to find biologically active novel oligosaccharides, yak milk was taken, which is a rich source of oligosaccharide and its milk is used as antihypertensive, antioxidative and heart strengthening agent in folk medicine. For this purpose yak milk was processed by method of Kobata and Ginsburg followed by gel filtration HPLC and CC which resulted in the isolation of two novel milk oligosaccharides namely (I) Grunniose and (II) Vakose. The structure of purified milk oligosaccharides were elucidated with the help of chemical degradation, chemical transformation, spectroscopic techniques like NMR (1H, 13C and 2D-NMR), structure reporter group theory and mass spectrometry. The optimized geometry of compound Grunniose and Vakose, at B3LYP method and 6-311 + G basis set on Gaussian 09 program, show that the compound Grunniose is lower in energy as compared to compound Vakose.

Discovery and structural elucidation of the illegal azo dye Basic Red 46 in sumac spice.

PubMed

Ruf, J; Walter, P; Kandler, H; Kaufmann, A

2012-01-01

An unknown red dye was discovered in a sumac spice sample during routine analysis for Sudan dyes. LC-DAD and LC-MS/MS did not reveal the identity of the red substance. Nevertheless, using LC-high-resolution MS and isotope ratio comparisons the structure was identified as Basic Red 46. The identity of the dye was further confirmed by comparison with a commercial hair-staining product and two textile dye formulations containing Basic Red 46. Analogous to the Sudan dyes, Basic Red 46 is an azo dye. However, some of the sample clean-up methodology utilised for the analysis of Sudan dyes in food prevents its successful detection. In contrast to the Sudan dyes, Basic Red 46 is a cation. Its cationic properties make it bind strongly to gel permeation columns and silica solid-phase extraction cartridges and prevent elution with standard eluents. This is the first report of Basic Red 46 in food. The structure elucidation of this compound as well as the disadvantages of analytical methods focusing on a narrow group of targeted analytes are discussed.

Microgravity Foam Structure and Rheology

NASA Technical Reports Server (NTRS)

Durian, Douglas J.

1997-01-01

To exploit rheological and multiple-light scattering techniques, and ultimately microgravity conditions, in order to quantify and elucidate the unusual elastic character of foams in terms of their underlying microscopic structure and dynamics. Special interest is in determining how this elastic character vanishes, i.e. how the foam melts into a simple viscous liquid, as a function of both increasing liquid content and shear strain rate. The unusual elastic character of foams will be quantified macroscopically by measurement of the shear stress as a function of static shear strain, shear strain rate, and time following a step strain; such data will be analyzed in terms of a yield stress, a static shear modulus, and dynamical time scales. Microscopic information about bubble packing and rearrangement dynamics, from which these macroscopic non-Newtonian properties presumably arise, will be obtained non-invasively by novel multiple-light scattering diagnostics such as Diffusing-Wave Spectroscopy (DWS). Quantitative trends with materials parameters, such as average bubble size, and liquid content, will be sought in order to elucidate the fundamental connection between the microscopic structure and dynamics and the macroscopic rheology.

Study of the Stereochemistry and Oxidation Mechanism of Plant Polyphenols, Assisted by Computational Chemistry.

PubMed

Matsuo, Yosuke

2017-01-01

In recent years, plant polyphenols have attracted great attention due to their wide range of biological activities. Certain kinds of polyphenols have complex structures; therefore, it is difficult to elucidate their total structure, including stereochemistry. In this study, we reinvestigated the stereostructures of two major C-glycosidic ellagitannins contained in Quercus plants, vescalagin and castalagin, and revised their stereostructures based on theoretical calculations of spectroscopic data. We also determined the structures of quercusnins A and B, isolated from the sapwood of Quercus crispula, based on theoretical calculations of NMR data. The oxidation mechanism of polyphenols has not been entirely elucidated. Therefore, we have also studied the oxidation mechanism of tea catechins during black tea production. Our investigation of the oxidation mechanism of black tea pigment theaflavins revealed that the difference in the position of the galloyl ester affords different oxidation products of theaflavins. In addition, oxidation products of pyrogallol-type catechins could be classified into three types-dehydrotheasinensins, theacitrins, and proepitheaflagallins; their detailed production and degradation mechanisms were also examined.

Ensemble cryo-EM elucidates the mechanism of translation fidelity

PubMed Central

Loveland, Anna B.; Demo, Gabriel; Grigorieff, Nikolaus; Korostelev, Andrei A.

2017-01-01

SUMMARY Faithful gene translation depends on accurate decoding, whose structural mechanism remains a matter of debate. Ribosomes decode mRNA codons by selecting cognate aminoacyl-tRNAs delivered by EF-Tu. We present high-resolution structural ensembles of ribosomes with cognate or near-cognate aminoacyl-tRNAs delivered by EF-Tu. Both cognate and near-cognate tRNA anticodons explore the A site of an open 30S subunit, while inactive EF-Tu is separated from the 50S subunit. A transient conformation of decoding-center nucleotide G530 stabilizes the cognate codon-anticodon helix, initiating step-wise “latching” of the decoding center. The resulting 30S domain closure docks EF-Tu at the sarcin-ricin loop of the 50S subunit, activating EF-Tu for GTP hydrolysis and ensuing aminoacyl-tRNA accommodation. By contrast, near-cognate complexes fail to induce the G530 latch, thus favoring open 30S pre-accommodation intermediates with inactive EF-Tu. This work unveils long-sought structural differences between the pre-accommodation of cognate and near-cognate tRNA that elucidate the mechanism of accurate decoding. PMID:28538735

Separation and structural characterization of the new synthetic cannabinoid JWH-018 cyclohexyl methyl derivative "NE-CHMIMO" using flash chromatography, GC-MS, IR and NMR spectroscopy.

PubMed

Angerer, Verena; Bisel, Philippe; Moosmann, Bjoern; Westphal, Folker; Auwärter, Volker

2016-09-01

Synthetic cannabinoids have become an integral part of the drugs of abuse market since many years. The most frequent form of consumption for this class of substances is smoking of herbal mixtures purchased via the Internet. In this article the identification and structure elucidation of a new synthetic cannabinoid, [1-(cyclohexylmethyl)-1H-indol-3-yl](naphthalen-1-yl)methanone, is described. The compound was found along with 5F-ADB in a 'herbal mixture' called 'Jamaican Gold Extreme', which was sent to our laboratory in the context of a suspected intoxication. For isolation of the substance a flash chromatography separation was applied. Structure elucidation was performed using gas chromatography-mass spectrometry (GC-MS), gas chromatography solid-state infrared (GC-sIR) and nuclear magnetic resonance (NMR) analysis. The new compound can be described as the cyclohexyl methyl derivative of the first generation synthetic cannabinoid JWH-018, and the authors suggest to use "NE-CHMIMO" as a semisystematic name. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The importance of functional tests to assess the effect of a new CFTR variant when genotype-phenotype correlation is not possible.

PubMed

Hinzpeter, Alexandre; Reboul, Marie-Pierre; Callebaut, Isabelle; Zordan, Cécile; Costes, Bruno; Guichoux, Julie; Iron, Albert; Lacombe, Didier; Martin, Natacha; Arveiler, Benoit; Fanen, Pascale; Fergelot, Patricia; Girodon, Emmanuelle

2017-05-01

In vitro functional tests aimed to investigate CFTR dysfunction appear critical to help elucidate the functional impact of new variants of uncertain clinical significance and solve inconclusive cases, especially in early deceased newborns.

Holistic Analysis of the Urban Water Systems in Greater Cincinnati Region

EPA Science Inventory

Urban water and wastewater systems with two utilities in Greater Cincinnati region were evaluated as a case study to elucidates a bigger picture of a typical centralized urban water system. Two different integrated assessment metrics were used to analyze the same system. LCA an...

Ductilisation of tungsten (W): Tungsten laminated composites

DOE PAGES

Reiser, Jens; Garrison, Lauren M.; Greuner, Henri; ...

2017-08-02

Here we elucidate the mechanisms of plastic deformation and fracture of tungsten laminated composites. Furthermore our results suggest that the mechanical response of the laminates is governed by the plastic deformation of the tungsten plies. In most cases, the impact of the interlayer is of secondary importance.

Guajadial: an unusual meroterpenoid from guava leaves Psidium guajava.

PubMed

Yang, Xiao-Long; Hsieh, Kun-Lung; Liu, Ji-Kai

2007-11-22

Guajadial (1), a novel caryophyllene-based meroterpenoid, was isolated from the Leaves of Psidium guajava (guava). The structure and relative stereochemistry of guajadial (1) were elucidated by extensive spectroscopic analysis. A possible biosynthetic pathway for 1 was proposed.

Nature's Sedative: Isolation and Structural Elucidation of Valtrate from Centranthus Ruber

ERIC Educational Resources Information Center

Doyle, Andrea M.; Reilly, Joe; Murphy, Niamh; Kavanagh, Pierce V.; O'Brien, John E.; Walsh, Martin S.; Walsh, John J.

2004-01-01

A member of a related genus of the valerianaceae, Centranthus ruber, is used, that yields a higher percentage valtrate than other related species such as "Valeriana officinalis," there by making easier isolation in pure form.

Matteucens I-J, phenolics from the rhizomes of Matteuccia orientalis.

PubMed

Zhu, Ling-Juan; Song, Ying; Shao, Peng; Zhang, Xue; Yao, Xin-Sheng

2018-01-01

Two new phenolics, named matteucens I-J (1-2), were isolated from the 60% EtOH extract of the rhizomes of Matteuccia orientalis (HOOK.) TREV. Their structures were elucidated by means of extensive spectroscopic analysis (HRESIMS, NMR).

[Cause of death related to medical disputes in Yancheng area: a study of 60 autopsy cases].

PubMed

Peng, Ming-Qi; Chen, Rong-Yu; Zhou, Lan; Zhang, Kai-Qiao; Shi, Jian-Song

2014-04-01

To summarize the pattern and main characteristics of fatal cases related to medical disputes in Yancheng area. Sixty fatal cases of medical disputes were retrospectively analyzed to elucidate the annual incidence, characters of distribution of hospitals, gender and age of the decedents, types of diseases, and cause of death. Among 60 fatal cases, most cases happened in health clinics of county, township and village. There were more males than females. The major medical specialties involved included internal medicine, surgery, gynecology and pediatrics, with the internal medicine specialty having the highest incidence. Police institutions have advantages in investigation of these cases in their jurisdictions, which could enhance the ability of local medicolegal examination.

The use of C-near edge X-ray absorption fine structure spectroscopy for the elaboration of chemistry in lignocellulosics

Treesearch

Lucian A. Lucia; Hiroki Nanko; Alan W. Rudie; Doug G. Mancosky; Sue Wirick

2006-01-01

The research presented elucidates the oxidation chemistry occurring in hydrogen peroxide bleached kraft pulp fibers by employing carbon near edge x-ray absorption fine structure spectroscopy (C-NEXAFS). C-NEXAFS is a soft x-ray technique that selectively interrogates atomic moieties using photoelectrons (Xrays) of variable energies. The X1A beam line at the National...

Withanolides from Jaborosa caulescens var. bipinnatifida

PubMed Central

Zhang, Huaping; Cao, Cong-Mei; Gallagher, Robert J.; Day, Victor W.; Montenegro, Gloria; Timmermann, Barbara N.

2013-01-01

Two new withanolides 2,3-dihydrotrechonolide A (1) and 2,3-dihydro-21-hydroxytrechonolide A (2) were isolated along with two known withanolides trechonolide A (3) and jaborosalactone 39 (4) from Jaborosa caulescens var. bipinnatifida (Solanaceae). The structures of 1-2 were elucidated through 2D NMR and other spectroscopic techniques. In addition, the structure of withanolide 1 was confirmed by X-ray crystallographic analysis. PMID:24314746

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

Kamiya, Shoji; Sato, Hisashi; Nishida, Masahiro

Reliability of electronic devices has been an issue of serious importance. One of the potential factors to spoil the reliability is possible local drops of strength on the interface of multilayered structure. A new technique for the evaluation of local interface adhesion energy was applied to the interface between Cu and cap layer in a Cu damascene interconnect structure, in order to elucidate variation in adhesion strength as a function of measurement location.

Three new metabolites from Botrytis cinerea.

PubMed

Wang, Tian-Shan; Zhou, Jin-Yan; Tan, Hong

2008-01-01

Three new metabolites, gamma-abscisolactone (1), botrytisic acids A (3) and B (4) were isolated from the fermentation broth of Botrytis cinerea TB-3-H8. Their structures were elucidated on the basis of MS, IR, UV, and NMR spectroscopic data. Compound 2 was isolated from natural resource for the first time. The structure of 1 was further confirmed by single-crystal X-ray diffraction (CCDC-265897).

Structure, recognition and adaptive binding in RNA aptamer complexes.

PubMed

Patel, D J; Suri, A K; Jiang, F; Jiang, L; Fan, P; Kumar, R A; Nonin, S

1997-10-10

Novel features of RNA structure, recognition and discrimination have been recently elucidated through the solution structural characterization of RNA aptamers that bind cofactors, aminoglycoside antibiotics, amino acids and peptides with high affinity and specificity. This review presents the solution structures of RNA aptamer complexes with adenosine monophosphate, flavin mononucleotide, arginine/citrulline and tobramycin together with an example of hydrogen exchange measurements of the base-pair kinetics for the AMP-RNA aptamer complex. A comparative analysis of the structures of these RNA aptamer complexes yields the principles, patterns and diversity associated with RNA architecture, molecular recognition and adaptive binding associated with complex formation.

Structure Diversity, Synthesis, and Biological Activity of Cyathane Diterpenoids in Higher Fungi.

PubMed

Tang, Hao-Yu; Yin, Xia; Zhang, Cheng-Chen; Jia, Qian; Gao, Jin-Ming

2015-01-01

Cyathane diterpenoids, occurring exclusively in higher basidiomycete (mushrooms), represent a structurally diverse class of natural products based on a characteristic 5-6-7 tricyclic carbon scaffold, including 105 members reported to date. These compounds show a diverse range of biological activities, such as antimicrobial, anti-MRSA, agonistic toward the kappa-opioid receptor, antiinflammatory, anti-proliferative and nerve growth factor (NGF)-like properties. The present review focuses on the structure diversity, structure elucidation and biological studies of these compounds, including mechanisms of actions and structure-activity relationships (SARs). In addition, new progress in chemical synthesis of cyathane diterpenoids is discussed.

Interfacial Li-ion localization in hierarchical carbon anodes

DOE PAGES

McNutt, Nicholas W.; Rios, Orlando; Maroulas, Vasileios; ...

2016-10-24

An understanding of the nanoscale structure and energetics of carbon composites is critical for their applications in electric energy storage. Here, we study the properties of carbon anodes synthesized from low-cost renewable lignin biopolymers for use in energy storage applications such as Li-ion batteries. The anodes possess both nanoscale and mesoscale order, consisting of carbon nanocrystallites distributed within an amorphous carbon matrix. Molecular dynamics simulations of an experimentally validated model of the anode is used to elucidate the nature of Li-ion storage. We report the discovery of a novel mechanism of Li-ion storage, one in which Li+ is not intercalatedmore » between layers of carbon (as is the case in graphitic anodes), but rather is localized at the interface of crystalline carbon domains. In particular, the effects of Li-ion binding energy on the Li-Li, Li-H, and Li-C pair distribution functions are revealed, along with the effect on charge distribution. As a result, the atomic environments surrounding the Li-ions are grouped on the basis of ion energy and then convolved into archetypal structural motifs that reveal deep insight into the geometry of ion localization in disordered systems.« less

Characteristic conformation of Mosher's amide elucidated using the cambridge structural database.

PubMed

Ichikawa, Akio; Ono, Hiroshi; Mikata, Yuji

2015-07-16

Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ1 of -13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group.

Uncovering the Connection Between Low-Frequency Dynamics and Phase Transformation Phenomena in Molecular Solids

NASA Astrophysics Data System (ADS)

Ruggiero, Michael T.; Zhang, Wei; Bond, Andrew D.; Mittleman, Daniel M.; Zeitler, J. Axel

2018-05-01

The low-frequency motions of molecules in the condensed phase have been shown to be vital to a large number of physical properties and processes. However, in the case of disordered systems, it is often difficult to elucidate the atomic-level details surrounding these phenomena. In this work, we have performed an extensive experimental and computational study on the molecular solid camphor, which exhibits a rich and complex structure-dynamics relationship, and undergoes an order-disorder transition near ambient conditions. The combination of x-ray diffraction, variable temperature and pressure terahertz time-domain spectroscopy, ab initio molecular dynamics, and periodic density functional theory calculations enables a complete picture of the phase transition to be obtained, inclusive of mechanistic, structural, and thermodynamic phenomena. Additionally, the low-frequency vibrations of a disordered solid are characterized for the first time with atomic-level precision, uncovering a clear link between such motions and the phase transformation. Overall, this combination of methods allows for significant details to be obtained for disordered solids and the associated transformations, providing a framework that can be directly applied for a wide range of similar systems.

Application of hidden Markov models to biological data mining: a case study

NASA Astrophysics Data System (ADS)

Yin, Michael M.; Wang, Jason T.

2000-04-01

In this paper we present an example of biological data mining: the detection of splicing junction acceptors in eukaryotic genes. Identification or prediction of transcribed sequences from within genomic DNA has been a major rate-limiting step in the pursuit of genes. Programs currently available are far from being powerful enough to elucidate the gene structure completely. Here we develop a hidden Markov model (HMM) to represent the degeneracy features of splicing junction acceptor sites in eukaryotic genes. The HMM system is fully trained using an expectation maximization (EM) algorithm and the system performance is evaluated using the 10-way cross- validation method. Experimental results show that our HMM system can correctly classify more than 94% of the candidate sequences (including true and false acceptor sites) into right categories. About 90% of the true acceptor sites and 96% of the false acceptor sites in the test data are classified correctly. These results are very promising considering that only the local information in DNA is used. The proposed model will be a very important component of an effective and accurate gene structure detection system currently being developed in our lab.

Graphene quantum dots: effect of size, composition and curvature on their assembly

DOE PAGES

Elvati, Paolo; Baumeister, Elizabeth; Violi, Angela

2017-03-21

Graphene Quantum Dots (GQDs) are a relatively new class of molecules that have ignited tremendous research interest due to their extraordinary and tunable optical, electrical, chemical and structural properties. In this paper, we report a molecular-level elucidation of the key mechanisms and physical–chemical factors controlling the assembly and stability of nanostructures formed by GQDs in an aqueous environment, using molecular dynamics simulations. We observe the general tendency to form small aggregates and three recurring configurations, one of them with a single layer of water separating two GQDs. The type and characteristics of the structure are mostly determined by the hydrophobicitymore » of the GQDs as well as the steric hindrance of the dangling groups. The composition of the terminal groups plays a key role in determining the configuration of the GQDs, which is also markedly affected by the formation of clusters. Notably, the aggregated GQDs assume strongly correlated shapes and, in some cases, display a radically different conformation distribution compared to single molecules. This cooperative effect prolongs the lifetime of the GQD configurations and can explain the observed persistence of chiral conformations that are only marginally more stable than their specular images.« less

Uncovering the Connection Between Low-Frequency Dynamics and Phase Transformation Phenomena in Molecular Solids.

PubMed

Ruggiero, Michael T; Zhang, Wei; Bond, Andrew D; Mittleman, Daniel M; Zeitler, J Axel

2018-05-11

The low-frequency motions of molecules in the condensed phase have been shown to be vital to a large number of physical properties and processes. However, in the case of disordered systems, it is often difficult to elucidate the atomic-level details surrounding these phenomena. In this work, we have performed an extensive experimental and computational study on the molecular solid camphor, which exhibits a rich and complex structure-dynamics relationship, and undergoes an order-disorder transition near ambient conditions. The combination of x-ray diffraction, variable temperature and pressure terahertz time-domain spectroscopy, ab initio molecular dynamics, and periodic density functional theory calculations enables a complete picture of the phase transition to be obtained, inclusive of mechanistic, structural, and thermodynamic phenomena. Additionally, the low-frequency vibrations of a disordered solid are characterized for the first time with atomic-level precision, uncovering a clear link between such motions and the phase transformation. Overall, this combination of methods allows for significant details to be obtained for disordered solids and the associated transformations, providing a framework that can be directly applied for a wide range of similar systems.

Design, structural and spectroscopic elucidation of new nitroaromatic carboxylic acids and semicarbazones for the in vitro screening of anti-leishmanial activity

NASA Astrophysics Data System (ADS)

Dias, L. C.; de Lima, G. M.; Pinheiro, C. B.; Rodrigues, B. L.; Donnici, C. L.; Fujiwara, R. T.; Bartholomeu, D. C.; Ferreira, R. A.; Ferreira, S. R.; Mendes, T. A. O.; da Silva, J. G.; Alves, M. R. A.

2015-01-01

In this paper we report the synthesis and characterization of four new nitroaromatic compounds, 2-{6-nitrobenzo[1,3]dioxol-5-(methyleneamino)}benzoic acid (1), 2-{[5-(2-nitrophenyl)furan-2-yl]methylene-amino}benzoic acid (2), 2-{(6-nitrobenzo[1,3]dioxol-5-yl)methylene}hydrazinecarboxamide (3) and 2-{[5-(2-nitrophenyl)furan-2-yl]methylene}hydrazinecarboxamide (4). Compounds (1)-(4) have been authenticated by infrared and NMR spectroscopy, and the structure of (1), (2) and (4) have been determined by X-ray diffraction. In addition, the in vitro ability of compounds (1)-(4) to inhibit the growth of Leishmania infantum has been evaluated. Comparisons of the redox potential of the compounds and leishmanicidal activity indicate that the presence of the electroactive nitro group is important for the biological activity. The inhibition activity of compound (3) is comparable to that of the reference drug, SbCl3. Considering the important side effects and the low efficiency of SbCl3 in the case of resistance, compound (3) deserves further attention as a promising anti-leishmanicidal drug for veterinary use.

Employing Theories Far beyond Their Limits - Linear Dichroism Theory.

PubMed

Mayerhöfer, Thomas G

2018-05-15

Using linear polarized light, it is possible in case of ordered structures, such as stretched polymers or single crystals, to determine the orientation of the transition moments of electronic and vibrational transitions. This not only helps to resolve overlapping bands, but also assigning the symmetry species of the transitions and to elucidate the structure. To perform spectral evaluation quantitatively, a sometimes "Linear Dichroism Theory" called approach is very often used. This approach links the relative orientation of the transition moment and polarization direction to the quantity absorbance. This linkage is highly questionable for several reasons. First of all, absorbance is a quantity that is by its definition not compatible with Maxwell's equations. Furthermore, absorbance seems not to be the quantity which is generally compatible with linear dichroism theory. In addition, linear dichroism theory disregards that it is not only the angle between transition moment and polarization direction, but also the angle between sample surface and transition moment, that influences band shape and intensity. Accordingly, the often invoked "magic angle" has never existed and the orientation distribution influences spectra to a much higher degree than if linear dichroism theory would hold strictly. A last point that is completely ignored by linear dichroism theory is the fact that partially oriented or randomly-oriented samples usually consist of ordered domains. It is their size relative to the wavelength of light that can also greatly influence a spectrum. All these findings can help to elucidate orientation to a much higher degree by optical methods than currently thought possible by the users of linear dichroism theory. Hence, it is the goal of this contribution to point out these shortcomings of linear dichroism theory to its users to stimulate efforts to overcome the long-lasting stagnation of this important field. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluid Physics of Foam Evolution and Flow

NASA Technical Reports Server (NTRS)

Aref, H.; Thoroddsen, S. T.; Sullivan, J. M.

2003-01-01

The grant supported theoretical, numerical and experimental work focused on the elucidation of the fluid physics of foam structure, evolution and flow. The experimental work concentrated on these subject areas: (a) Measurements of the speed of reconnections within a foam; (b) statistics of bubble rearrangements; and (c) three-dimensional reconstruction of the foam structure. On the numerical simulation and theory side our efforts concentrated on the subjects: (a) simulation techniques for 2D and 3D foams; (b) phase transition in a compressible foam; and (c) TCP structures.

Disruption of Inhibitory Function in the Ts65Dn Mouse Hippocampus Through Overexpression of GIRK2

DTIC Science & Technology

2007-10-24

are prominent (Galdzicki and Siarey, 2003). We found that GIRK2 mRNA and protein subunits are highly overexpressed in multiple CNS structures ... STRUCTURE GIRK channels are members of the large family of potassium inward rectifiers (Kir). The seven subfamilies of Kir channels (Kir1-7) differ as...This ability to discriminate against the smaller Na+ (atomic radius: 0.95 Å) was elucidated by examining the pore structure of the bacterial KcsA

Effects of potentization in aqueous solutions.

PubMed

Schulte, J

1999-10-01

Over the past two decades, research into structure formation and structure conservation in water has created a significant interest among the homeopathy research community. The formation of sustained static and dynamic structures in aqueous solutions is thought to be synonymous with the possible storage of information in associated liquids. Prominent models and experiments considering this possibility are presented in this paper, and some of their subtleties, which were not given much room in the respective original publications, will be elucidated in more detail here.

Super-resolution optical microscopy for studying membrane structure and dynamics.

PubMed

Sezgin, Erdinc

2017-07-12

Investigation of cell membrane structure and dynamics requires high spatial and temporal resolution. The spatial resolution of conventional light microscopy is limited due to the diffraction of light. However, recent developments in microscopy enabled us to access the nano-scale regime spatially, thus to elucidate the nanoscopic structures in the cellular membranes. In this review, we will explain the resolution limit, address the working principles of the most commonly used super-resolution microscopy techniques and summarise their recent applications in the biomembrane field.

Re-Envisioning Scientific Literacy as Relational, Participatory Thinking and Doing

ERIC Educational Resources Information Center

Trauth-Nare, Amy

2016-01-01

This review explores Michelle Hollingsworth Koomen's "Inclusive science education: Learning from Wizard" (see EJ1102217), a case study of a middle school student with learning exceptionalities in a mainstream science classroom. The strength of Koomen's work lies in her elucidation of the ways in which normative science instruction fails…

Innovation in Education--Norway. Technical Report.

ERIC Educational Resources Information Center

Dalin, Per

One in a series of five descriptive case studies dealing with innovation, this study on Norway elucidates the functions of the National Council for Innovation in Education (NCIE), an advisory council which was formed to regulate experimentation and reform in the entire Norwegian school system. With major emphasis on democratization, the objectives…

Factors Influencing Teacher Appropriation of Professional Learning Focused on the Use of Technology in Science Classrooms

ERIC Educational Resources Information Center

Longhurst, Max L.; Jones, Suzanne H.; Campbell, Todd

2017-01-01

Understanding factors that impact teacher implementation of learning from professional development is critical in order to maximize the educational and financial investment in teacher professional learning. This multi-case qualitative investigation elucidates factors that influence the appropriation of instructional tools associated with…

Mode of action framework analysis for receptor-mediated toxicity: the Peroxisome Proliferator-Activated Receptor alpha (PPARα) as a case study

EPA Science Inventory

Therapeutic hypolipidemic agents and industrial chemicals that cause peroxisome proliferation and induce liver tumors in rodents activate the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα). Research has elucidated the cellular and molecular events by w...

Elucidating public perceptions of environmental behavior: a case study of Lake Lanier

EPA Science Inventory

This paper investigates stakeholders' different perspectives on the environment over the short- (2-5 yrs) and long-term (25+ yrs). Stakeholders were surveyed to indicate their level of concern for a list of water quality indicators and water quality stressors over both time horiz...

A new benzylisoquinoline alkaloid from Leontice altaica.

PubMed

Jenis, Janar; Nugroho, Alfarius Eko; Hashimoto, Akiyo; Deguchi, Jun; Hirasawa, Yusuke; Wong, Chin Piow; Kaneda, Toshio; Shirota, Osamu; Morita, Hiroshi

2015-02-01

A new benzylisoquinoline alkaloid, lincangenine-4-β-D-glucopyranoside (1), has been isolated from the roots of Leontice altaica, together with 5 known alkaloids. Its structure was elucidated on the basis of 1D and 2D NMR data, and chemical means.

Monoterpene glycosides from Paeonia veitchii.

PubMed

Fu, Qiang; Tan, Mao-Ling; Yuan, Hai-Mei; Chen, Jiang; Fu, Jia

2017-01-01

The EtOH extract of the roots of Paeonia veitchii afforded two new monoterpene glycosides paeonidanin I (1) and paeonidanin J (2), and a new dimeric monoterpene glycoside paeonidanin K (3). Their structures were elucidated on the basis of spectroscopic means and hydrolysis products.

A New Triterpenoidal from Vernonia cinerea.

PubMed

Misra, T N; Singh, R S; Srivastava, R; Pandey, H S; Prasad, C; Singh, S

1993-10-01

From the roots of VERNONIA CINEREA Less. (Compositae) a new triterpenoid has been isolated and characterised as 3beta-acetoxyurs-19-ene ( 1). A further constituent has been identified as lupeol acetate. Structure elucidation has been made with the help of spectral analyses.

Secoiridoid components from Jasminum grandiflorum.

PubMed

Sadhu, Samir Kumar; Khan, Md Sojib; Ohtsuki, Takashi; Ishibashi, Masami

2007-07-01

Secoiridoid glucosides, 2''-epifraxamoside and demethyl-2''-epifraxamoside, and the secoiridoid, jasminanhydride were isolated from Jasminum grandiflorum together with four previously known phenolics and a triterpene. Structures were elucidated by detailed spectroscopic analysis. Stereochemistry of the compounds was determined by differential NOE experiment.

Overview of open resources to support automated structure verification and elucidation

EPA Science Inventory

Cheminformatics methods form an essential basis for providing analytical scientists with access to data, algorithms and workflows. There are an increasing number of free online databases (compound databases, spectral libraries, data repositories) and a rich collection of software...

Two new C19-diterpenoid alkaloids from Aconitum tsaii.

PubMed

Li, Gui-Qiong; Zhang, Li-Mei; Zhao, Da-Ke; Chen, Yan-Ping; Shen, Yong

2017-05-01

Two new C 19 -diterpenoid alkaloids, 14-benzoylliljestrandisine (1) and 14-anisoylliljestrandisine (2), were isolated from the roots of Aconitum tsaii. Their structures were elucidated by different spectroscopic (IR, UV, 1D and 2D NMR) and mass-spectrometric techniques.

Constituents of Andromeda polifolia.

PubMed

Pachaly, P; Klein, M

1987-10-01

A reinvestigation of the aerial parts of ANDROMEDA POLIFOLIA afforded in addition to the known compounds gardenoside ( 1), guaijaverine ( 2) and avicularine ( 3), a new flavonol-dipentoside named polifolioside ( 4). the compounds were isolated employing DCCC and their structures were elucidated by spectroscopic methods.

One new benzyldihydrophenanthrene from Arundina graminifolia.

PubMed

Liu, Mei-Feng; Han, Yun; Xing, Dong-Ming; Wang, Wei; Xu, Li-Zhen; Du, Li-Jun; Ding, Yi

2005-10-01

A novel benzyldihydrophenanthrene named arundinaol has been isolated from the rhizoma of Arundina graminifolia. The structure of has been elucidated as 7-hydroxy-1-(p-hydroxybenzyl)-2,4-dimethoxy-9,10-dihydrophenanthrene on the basis of physical and chemical evidence and spectral analysis.

Functional data analysis of sleeping energy expenditure

USDA-ARS?s Scientific Manuscript database

Adequate sleep is crucial during childhood for metabolic health, and physical and cognitive development. Inadequate sleep can disrupt metabolic homeostasis and alter sleeping energy expenditure (SEE). Functional data analysis methods were applied to SEE data to elucidate the population structure of ...

A new lignan from the seeds of Arctium lappa.

PubMed

Yong, Min; Kun, Gu; Qiu, Min-Hua

2007-01-01

A new compound, neoarctin A (1), together with nine known compounds (2-10), were obtained from the ethanolic extract of the seeds of Arctium lappa. The structure of 1 was elucidated on the basis of spectral and chemical evidence.

Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3-3 Protein-Protein Interactions.

PubMed

Cau, Ylenia; Fiorillo, Annarita; Mori, Mattia; Ilari, Andrea; Botta, Maurizo; Lalle, Marco

2015-12-28

Giardiasis is a gastrointestinal diarrheal illness caused by the protozoan parasite Giardia duodenalis, which affects annually over 200 million people worldwide. The limited antigiardial drug arsenal and the emergence of clinical cases refractory to standard treatments dictate the need for new chemotherapeutics. The 14-3-3 family of regulatory proteins, extensively involved in protein-protein interactions (PPIs) with pSer/pThr clients, represents a highly promising target. Despite homology with human counterparts, the single 14-3-3 of G. duodenalis (g14-3-3) is characterized by a constitutive phosphorylation in a region critical for target binding, thus affecting the function and the conformation of g14-3-3/clients interaction. However, to approach the design of specific small molecule modulators of g14-3-3 PPIs, structural elucidations are required. Here, we present a detailed computational and crystallographic study exploring the implications of g14-3-3 phosphorylation on protein structure and target binding. Self-Guided Langevin Dynamics and classical molecular dynamics simulations show that phosphorylation affects locally and globally g14-3-3 conformation, inducing a structural rearrangement more suitable for target binding. Profitable features for g14-3-3/clients interaction were highlighted using a hydrophobicity-based descriptor to characterize g14-3-3 client peptides. Finally, the X-ray structure of g14-3-3 in complex with a mode-1 prototype phosphopeptide was solved and combined with structure-based simulations to identify molecular features relevant for clients binding to g14-3-3. The data presented herein provide a further and structural understanding of g14-3-3 features and set the basis for drug design studies.

Glucosinolate diversity within a phylogenetic framework of the tribe Cardamineae (Brassicaceae) unraveled with HPLC-MS/MS and NMR-based analytical distinction of 70 desulfoglucosinolates.

PubMed

Olsen, Carl Erik; Huang, Xiao-Chen; Hansen, Cecilie I C; Cipollini, Don; Ørgaard, Marian; Matthes, Annemarie; Geu-Flores, Fernando; Koch, Marcus A; Agerbirk, Niels

2016-12-01

As a basis for future investigations of evolutionary trajectories and biosynthetic mechanisms underlying variations in glucosinolate structures, we screened members of the crucifer tribe Cardamineae by HPLC-MS/MS, isolated and identified glucosinolates by NMR, searched the literature for previous data for the tribe, and collected HPLC-MS/MS data for nearly all glucosinolates known from the tribe as well as some related structures (70 in total). This is a considerable proportion of the approximately 142 currently documented natural glucosinolates. Calibration with authentic references allowed distinction (or elucidation) of isomers in many cases, such as distinction of β-hydroxyls, methylthios, methylsulfinyls and methylsulfonyls. A mechanism for fragmentation of secondary β-hydroxyls in MS was elucidated, and two novel glucosinolates were discovered: 2-hydroxy-3-methylpentylglucosinolate in roots of Cardamine pratensis and 2-hydroxy-8-(methylsulfinyl)octylglucosinolate in seeds of Rorippa amphibia. A large number of glucosinolates (ca. 54 with high structural certainty and a further 28 or more suggested from tandem MS), representing a wide structural variation, is documented from the tribe. This included glucosinolates apparently derived from Met, Phe, Trp, Val/Leu, Ile and higher homologues. Normal side chain elongation and side chain decoration by oxidation or methylation was observed, as well as rare abnormal side chain decoration (hydroxylation of aliphatics at the δ rather than β-position). Some species had diverse profiles, e.g. R. amphibia and C. pratensis (19 and 16 individual glucosinolates, respectively), comparable to total diversity in literature reports of Armoracia rusticana (17?), Barbarea vulgaris (20-24), and Rorippa indica (>20?). The ancestor or the tribe would appear to have used Trp, Met, and homoPhe as glucosinolate precursor amino acids, and to exhibit oxidation of thio to sulfinyl, formation of alkenyls, β-hydroxylation of aliphatic chains and hydroxylation and methylation of indole glucosinolates. Two hotspots of apparent biochemical innovation and loss were identified: C. pratensis and the genus Barbarea. Diversity in other species mainly included structures also known from other crucifers. In addition to a role of gene duplication, two contrasting genetic/biochemical mechanisms for evolution of such combined diversity and redundancy are discussed: (i) involvement of widespread genes with expression varying during evolution, and (ii) mutational changes in substrate specificities of CYP79F and GS-OH enzymes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Casting Protocols for the Production of Open Cell Aluminum Foams by the Replication Technique and the Effect on Porosity

PubMed Central

Elizondo Luna, Erardo M.; Barari, Farzad; Woolley, Robert; Goodall, Russell

2014-01-01

Metal foams are interesting materials from both a fundamental understanding and practical applications point of view. Uses have been proposed, and in many cases validated experimentally, for light weight or impact energy absorbing structures, as high surface area heat exchangers or electrodes, as implants to the body, and many more. Although great progress has been made in understanding their structure-properties relationships, the large number of different processing techniques, each producing material with different characteristics and structure, means that understanding of the individual effects of all aspects of structure is not complete. The replication process, where molten metal is infiltrated between grains of a removable preform material, allows a markedly high degree of control and has been used to good effect to elucidate some of these relationships. Nevertheless, the process has many steps that are dependent on individual “know-how”, and this paper aims to provide a detailed description of all stages of one embodiment of this processing method, using materials and equipment that would be relatively easy to set up in a research environment. The goal of this protocol and its variants is to produce metal foams in an effective and simple way, giving the possibility to tailor the outcome of the samples by modifying certain steps within the process. By following this, open cell aluminum foams with pore sizes of 1–2.36 mm diameter and 61% to 77% porosity can be obtained. PMID:25548938

Gambling primates: reactions to a modified Iowa Gambling Task in humans, chimpanzees and capuchin monkeys

PubMed Central

Williamson, Rebecca A.; Latzman, Robert D.; de Waal, Frans B. M.; Brosnan, Sarah F.

2014-01-01

Humans will, at times, act against their own economic self-interest, for example, in gambling situations. To explore the evolutionary roots of this behavior, we modified a traditional human gambling task, the Iowa Gambling Task (IGT), for use with chimpanzees, capuchin monkeys and humans. We expanded the traditional task to include two additional payoff structures to fully elucidate the ways in which these primate species respond to differing reward distributions versus overall quantities of rewards, a component often missing in the existing literature. We found that while all three species respond as typical humans do in the standard IGT payoff structure, species and individual differences emerge in our new payoff structures. Specifically, when variance avoidance and reward maximization conflicted, roughly equivalent numbers of apes maximized their rewards and avoided variance, indicating that the traditional payoff structure of the IGT is insufficient to disentangle these competing strategies. Capuchin monkeys showed little consistency in their choices. To determine whether this was a true species difference or an effect of task presentation, we replicated the experiment but increased the intertrial interval. In this case, several capuchin monkeys followed a reward maximization strategy, while chimpanzees retained the same strategy they had used previously. This suggests that individual differences in strategies for interacting with variance and reward maximization are present in apes, but not in capuchin monkeys. The primate gambling task presented here is a useful methodology for disentangling strategies of variance avoidance and reward maximization. PMID:24504555

Phenotype- and Genotype-Specific Structural Alterations in Spasmodic Dysphonia

PubMed Central

Bianchi, Serena; Battistella, Giovanni; Huddleston, Hailey; Scharf, Rebecca; Fleysher, Lazar; Rumbach, Anna F.; Frucht, Steven J.; Blitzer, Andrew; Ozelius, Laurie J.; Simonyan, Kristina

2017-01-01

Background Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology. Methods Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes). Results Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus. Conclusions Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. PMID:28186656

Effect of D23N mutation on the dimer conformation of amyloid β-proteins: ab initio molecular simulations in water.

PubMed

Okamoto, Akisumi; Yano, Atsushi; Nomura, Kazuya; Higai, Shin'ichi; Kurita, Noriyuki

2014-05-01

The molecular pathogenesis of Alzheimer's disease (AD) is deeply involved in aggregations of amyloid β-proteins (Aβ) in a diseased brain. The recent experimental studies indicated that the mutation of Asp23 by Asn (D23N) within the coding sequence of Aβ increases the risk for the pathogeny of cerebral amyloid angiopathy and early-onset familial ADs. Fibrils of the D23N mutated Aβs can form both parallel and antiparallel structures, and the parallel one is considered to be associated with the pathogeny. However, the structure and the aggregation mechanism of the mutated Aβ fibrils are not elucidated at atomic and electronic levels. We here investigated solvated structures of the two types of Aβ dimers, each of which is composed of the wild-type or the D23N mutated Aβ, using classical molecular mechanics and ab initio fragment molecular orbital (FMO) methods, in order to reveal the effect of the D23N mutation on the structure of Aβ dimer as well as the specific interactions between the Aβ monomers. The results elucidate that the effect of the D23N mutation is significant for the parallel structure of Aβ dimer and that the solvating water molecules around the Aβ dimer have significant contribution to the stability of Aβ dimer. Copyright © 2014 Elsevier Inc. All rights reserved.

A new meroterpenoid, chrodrimanin C, from YO-2 of Talaromyces sp.

PubMed

Hayashi, Hideo; Oka, Yuki; Kai, Kenji; Akiyama, Kohki

2012-01-01

The new meroterpenoid, chrodrimanin C (3), together with chrodrimanins A (2) and B (1) were isolated from okara (the insoluble residue of whole soybean) that had been fermented with strain YO-2 of Talaromyces sp. Their structures were elucidated by spectroscopic methods. The partial structures of 1 essential for exhibiting insecticidal activity were investigated by using a silkworm assay. The absolute configuration of 1 was also determined.

Microgravity Foam Structure and Rheology

NASA Technical Reports Server (NTRS)

Durian, Douglas J.

1996-01-01

The objective of this research was to exploit rheological and multiple-light scattering techniques, and ultimately microgravity conditions, in order to quantify and elucidate the unusual elastic character of foams in terms of their underlying microscopic structure and dynamics. Special interest was in determining how this elastic character vanishes, i.e. how the foam melts into a simple viscous liquid, as a function of both increasing liquid content and shear strain rate.

Origin and development of plasma membrane derived invaginations in Vinca rosea l.

NASA Technical Reports Server (NTRS)

Mahlberg, P.; Walkinshaw, C.; Olson, K.

1971-01-01

The occurrence, morphology, and possible ontogeny of plasma-membrane-related structures are described which can develop into invaginations or intravacuolar formations. An underlying study of meristematic tissues from the shoot of Vinca rosea supports the interpretation that endocytosis does occur in plant cells and that it is appropriate to refer to these structures as endocytoses. The function of these invaginations or their content remains to be elucidated.

Withanolides from Jaborosa caulescens var. bipinnatifida.

PubMed

Zhang, Huaping; Cao, Cong-Mei; Gallagher, Robert J; Day, Victor W; Montenegro, Gloria; Timmermann, Barbara N

2014-02-01

Withanolides 2,3-dihydrotrechonolide A (1) and 2,3-dihydro-21-hydroxytrechonolide A (2) were isolated along with two known withanolides trechonolide A (3) and jaborosalactone 39 (4) from Jaborosa caulescens var. bipinnatifida (Solanaceae). The structures of 1-2 were elucidated through 2D NMR and other spectroscopic techniques. In addition, the structure of withanolide 1 was confirmed by X-ray crystallographic analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioactive constituents from Chinese natural medicines. XXII. Absolute structures of new megastigmane glycosides, sedumosides E1, E2, E3, F1, F2, and G, from Sedum sarmentosum (Crassulaceae).

PubMed

Morikawa, Toshio; Zhang, Yi; Nakamura, Seikou; Matsuda, Hisashi; Muraoka, Osamu; Yoshikawa, Masayuki

2007-03-01

Six new megastigmane glycosides, sedumosides E1, E2, E3, F1, F2, and G, were isolated from the whole plant of Sedum sarmentosum (Crassulaceae). The structures of new constituents including the absolute configuration were elucidated on the basis of chemical and physicochemical evidence.

3-Dimensional atomic scale structure of the ionic liquid-graphite interface elucidated by AM-AFM and quantum chemical simulations

NASA Astrophysics Data System (ADS)

Page, Alister J.; Elbourne, Aaron; Stefanovic, Ryan; Addicoat, Matthew A.; Warr, Gregory G.; Voïtchovsky, Kislon; Atkin, Rob

2014-06-01

In situ amplitude modulated atomic force microscopy (AM-AFM) and quantum chemical simulations are used to resolve the structure of the highly ordered pyrolytic graphite (HOPG)-bulk propylammonium nitrate (PAN) interface with resolution comparable with that achieved for frozen ionic liquid (IL) monolayers using STM. This is the first time that (a) molecular resolution images of bulk IL-solid interfaces have been achieved, (b) the lateral structure of the IL graphite interface has been imaged for any IL, (c) AM-AFM has elucidated molecular level structure immersed in a viscous liquid and (d) it has been demonstrated that the IL structure at solid surfaces is a consequence of both thermodynamic and kinetic effects. The lateral structure of the PAN-graphite interface is highly ordered and consists of remarkably well-defined domains of a rhomboidal superstructure composed of propylammonium cations preferentially aligned along two of the three directions in the underlying graphite lattice. The nanostructure is primarily determined by the cation. Van der Waals interactions between the propylammonium chains and the surface mean that the cation is enriched in the surface layer, and is much less mobile than the anion. The presence of a heterogeneous lateral structure at an ionic liquid-solid interface has wide ranging ramifications for ionic liquid applications, including lubrication, capacitive charge storage and electrodeposition.In situ amplitude modulated atomic force microscopy (AM-AFM) and quantum chemical simulations are used to resolve the structure of the highly ordered pyrolytic graphite (HOPG)-bulk propylammonium nitrate (PAN) interface with resolution comparable with that achieved for frozen ionic liquid (IL) monolayers using STM. This is the first time that (a) molecular resolution images of bulk IL-solid interfaces have been achieved, (b) the lateral structure of the IL graphite interface has been imaged for any IL, (c) AM-AFM has elucidated molecular level structure immersed in a viscous liquid and (d) it has been demonstrated that the IL structure at solid surfaces is a consequence of both thermodynamic and kinetic effects. The lateral structure of the PAN-graphite interface is highly ordered and consists of remarkably well-defined domains of a rhomboidal superstructure composed of propylammonium cations preferentially aligned along two of the three directions in the underlying graphite lattice. The nanostructure is primarily determined by the cation. Van der Waals interactions between the propylammonium chains and the surface mean that the cation is enriched in the surface layer, and is much less mobile than the anion. The presence of a heterogeneous lateral structure at an ionic liquid-solid interface has wide ranging ramifications for ionic liquid applications, including lubrication, capacitive charge storage and electrodeposition. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01219d

Structural models of antibody variable fragments: A method for investigating binding mechanisms

NASA Astrophysics Data System (ADS)

Petit, Samuel; Brard, Frédéric; Coquerel, Gérard; Perez, Guy; Tron, François

1998-03-01

The value of comparative molecular modeling for elucidating structure-function relationships was demonstrated by analyzing six anti-nucleosome autoantibody variable fragments. Structural models were built using the automated procedure developed in the COMPOSER software, subsequently minimized with the AMBER force field, and validated according to several standard geometric and chemical criteria. Canonical class assignment from Chothia and Lesk's [Chottin and Lesk, J. Mol. Biol., 196 (1987) 901; Chothia et al., Nature, 342 (1989) 877] work was used as a supplementary validation tool for five of the six hypervariable loops. The analysis, based on the hypothesis that antigen binding could occur through electrostatic interactions, reveals a diversity of possible binding mechanisms of anti-nucleosome or anti-histone antibodies to their cognate antigen. These results lead us to postulate that anti-nucleosome autoantibodies could have different origins. Since both anti-DNA and anti-nculeosome autoantibodies are produced during the course of systemic lupus erythematosus, a non-organ specific autoimmune disease, a comparative structural and electrostatic analysis of the two populations of autoantibodies may constitute a way to elucidate their origin and the role of the antigen in tolerance breakdown. The present study illustrates some interests, advantages and limits of a methodology based on the use of comparative modeling and analysis of molecular surface properties.

Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds

PubMed Central

Rahman, Mona N.; Vukomanovic, Dragic; Vlahakis, Jason Z.; Szarek, Walter A.; Nakatsu, Kanji; Jia, Zongchao

2013-01-01

The development of heme oxygenase (HO) inhibitors, especially those that are isozyme-selective, promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties and may play a role in several disease states, making it an enticing therapeutic target. Traditionally, the metalloporphyrins have been used as competitive HO inhibitors owing to their structural similarity with the substrate, heme. However, given heme's important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), non-selectivity is an unfortunate side-effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort to develop novel compounds as potent, selective inhibitors of HO. This resulted in the creation of non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated, which provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies. PMID:23097500

Structural elucidation of estrus urinary lipocalin protein (EULP) and evaluating binding affinity with pheromones using molecular docking and fluorescence study

PubMed Central

Rajesh, Durairaj; Muthukumar, Subramanian; Saibaba, Ganesan; Siva, Durairaj; Akbarsha, Mohammad Abdulkader; Gulyás, Balázs; Padmanabhan, Parasuraman; Archunan, Govindaraju

2016-01-01

Transportation of pheromones bound with carrier proteins belonging to lipocalin superfamily is known to prolong chemo-signal communication between individuals belonging to the same species. Members of lipocalin family (MLF) proteins have three structurally conserved motifs for delivery of hydrophobic molecules to the specific recognizer. However, computational analyses are critically required to validate and emphasize the sequence and structural annotation of MLF. This study focused to elucidate the evolution, structural documentation, stability and binding efficiency of estrus urinary lipocalin protein (EULP) with endogenous pheromones adopting in-silico and fluorescence study. The results revealed that: (i) EULP perhaps originated from fatty acid binding protein (FABP) revealed in evolutionary analysis; (ii) Dynamic simulation study shows that EULP is highly stable at below 0.45 Å of root mean square deviation (RMSD); (iii) Docking evaluation shows that EULP has higher binding energy with farnesol and 2-iso-butyl-3-methoxypyrazine (IBMP) than 2-naphthol; and (iv) Competitive binding and quenching assay revealed that purified EULP has good binding interaction with farnesol. Both, In-silico and experimental studies showed that EULP is an efficient binding partner to pheromones. The present study provides impetus to create a point mutation for increasing longevity of EULP to develop pheromone trap for rodent pest management. PMID:27782155

Structural elucidation of estrus urinary lipocalin protein (EULP) and evaluating binding affinity with pheromones using molecular docking and fluorescence study.

PubMed

Rajesh, Durairaj; Muthukumar, Subramanian; Saibaba, Ganesan; Siva, Durairaj; Akbarsha, Mohammad Abdulkader; Gulyás, Balázs; Padmanabhan, Parasuraman; Archunan, Govindaraju

2016-10-26

Transportation of pheromones bound with carrier proteins belonging to lipocalin superfamily is known to prolong chemo-signal communication between individuals belonging to the same species. Members of lipocalin family (MLF) proteins have three structurally conserved motifs for delivery of hydrophobic molecules to the specific recognizer. However, computational analyses are critically required to validate and emphasize the sequence and structural annotation of MLF. This study focused to elucidate the evolution, structural documentation, stability and binding efficiency of estrus urinary lipocalin protein (EULP) with endogenous pheromones adopting in-silico and fluorescence study. The results revealed that: (i) EULP perhaps originated from fatty acid binding protein (FABP) revealed in evolutionary analysis; (ii) Dynamic simulation study shows that EULP is highly stable at below 0.45 Å of root mean square deviation (RMSD); (iii) Docking evaluation shows that EULP has higher binding energy with farnesol and 2-iso-butyl-3-methoxypyrazine (IBMP) than 2-naphthol; and (iv) Competitive binding and quenching assay revealed that purified EULP has good binding interaction with farnesol. Both, In-silico and experimental studies showed that EULP is an efficient binding partner to pheromones. The present study provides impetus to create a point mutation for increasing longevity of EULP to develop pheromone trap for rodent pest management.

DYNAMICS OF MINERAL STRUCTURES AND THE FATE OF METALS IN SOILS AND SEDIMENTS

EPA Science Inventory

Significant progress has been made in elucidating sorption reactions that control the partitioning of metals from solution to mineral surfaces in contaminated soil/sediment systems. Surface complexation models have been developed to quantify the forward reaction with reasonable ...

Genetic structure of the fungal grapevine pathogen Eutypa lata from four continents

USDA-ARS?s Scientific Manuscript database

Deciphering the geographic origins of pathogens and elucidating the population biology of these microscopic organisms are necessary steps to establish effective disease-control strategies. The generalist ascomycete fungus Eutypa lata causes Eutypa dieback of grapevine (Vitis vinifera) worldwide. To ...

A new isoflavone glucoside from Pterocarpus santalinus.

PubMed

Krishnaveni, K S; Srinivasa Rao, J V

2000-01-01

A new isoflavone glucoside (1) together with the known santal has been isolated from the heartwood of Pterocarpus santalinus. Based on spectral methods, the structure of the new compound was elucidated as 4',5-dihydroxy 7-O-methyl isoflavone 3'-O-beta-D-glucoside.

The explicit form of the rate function for semi-Markov processes and its contractions

NASA Astrophysics Data System (ADS)

Sughiyama, Yuki; Kobayashi, Testuya J.

2018-03-01

We derive the explicit form of the rate function for semi-Markov processes. Here, the ‘random time change trick’ plays an essential role. Also, by exploiting the contraction principle of large deviation theory to the explicit form, we show that the fluctuation theorem (Gallavotti-Cohen symmetry) holds for semi-Markov cases. Furthermore, we elucidate that our rate function is an extension of the level 2.5 rate function for Markov processes to semi-Markov cases.

One drop chemical derivatization--DESI-MS analysis for metabolite structure identification.

PubMed

Lubin, Arnaud; Cabooter, Deirdre; Augustijns, Patrick; Cuyckens, Filip

2015-07-01

Structural elucidation of metabolites is an important part during the discovery and development process of new pharmaceutical drugs. Liquid Chromatography (LC) in combination with Mass Spectrometry (MS) is usually the technique of choice for structural identification but cannot always provide precise structural identification of the studied metabolite (e.g. site of hydroxylation and site of glucuronidation). In order to identify those metabolites, different approaches are used combined with MS data including nuclear magnetic resonance, hydrogen/deuterium exchange and chemical derivatization followed by LC-MS. Those techniques are often time-consuming and/or require extra sample pre-treatment. In this paper, a fast and easy to set up tool using desorption electrospray ionization-MS for metabolite identification is presented. In the developed method, analytes in solution are simply dried on a glass plate with printed Teflon spots and then a single drop of derivatization mixture is added. Once the spot is dried, the derivatized compound is analyzed. Six classic chemical derivatizations were adjusted to work as a one drop reaction and applied on a list of compounds with relevant functional groups. Subsequently, two successive reactions on a single spot of amoxicillin were tested and the methodology described was successfully applied on an in vitro incubated alprazolam metabolite. All reactions and analyses were performed within an hour and gave useful structural information by derivatizing functional groups, making the method a time-saving and efficient tool for metabolite identification if used in addition or in some cases as an alternative to common methods. Copyright © 2015 John Wiley & Sons, Ltd.

The One-carbon Carrier Methylofuran from Methylobacterium extorquens AM1 Contains a Large Number of α- and γ-Linked Glutamic Acid Residues.

PubMed

Hemmann, Jethro L; Saurel, Olivier; Ochsner, Andrea M; Stodden, Barbara K; Kiefer, Patrick; Milon, Alain; Vorholt, Julia A

2016-04-22

Methylobacterium extorquens AM1 uses dedicated cofactors for one-carbon unit conversion. Based on the sequence identities of enzymes and activity determinations, a methanofuran analog was proposed to be involved in formaldehyde oxidation in Alphaproteobacteria. Here, we report the structure of the cofactor, which we termed methylofuran. Using an in vitro enzyme assay and LC-MS, methylofuran was identified in cell extracts and further purified. From the exact mass and MS-MS fragmentation pattern, the structure of the cofactor was determined to consist of a polyglutamic acid side chain linked to a core structure similar to the one present in archaeal methanofuran variants. NMR analyses showed that the core structure contains a furan ring. However, instead of the tyramine moiety that is present in methanofuran cofactors, a tyrosine residue is present in methylofuran, which was further confirmed by MS through the incorporation of a (13)C-labeled precursor. Methylofuran was present as a mixture of different species with varying numbers of glutamic acid residues in the side chain ranging from 12 to 24. Notably, the glutamic acid residues were not solely γ-linked, as is the case for all known methanofurans, but were identified by NMR as a mixture of α- and γ-linked amino acids. Considering the unusual peptide chain, the elucidation of the structure presented here sets the basis for further research on this cofactor, which is probably the largest cofactor known so far. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

MS/MS analysis and imaging of lipids across Drosophila brain using secondary ion mass spectrometry.

PubMed

Phan, Nhu T N; Munem, Marwa; Ewing, Andrew G; Fletcher, John S

2017-06-01

Lipids are abundant biomolecules performing central roles to maintain proper functioning of cells and biological bodies. Due to their highly complex composition, it is critical to obtain information of lipid structures in order to identify particular lipids which are relevant for a biological process or metabolic pathway under study. Among currently available molecular identification techniques, MS/MS in secondary ion mass spectrometry (SIMS) imaging has been of high interest in the bioanalytical community as it allows visualization of intact molecules in biological samples as well as elucidation of their chemical structures. However, there have been few applications using SIMS and MS/MS owing to instrumental challenges for this capability. We performed MS and MS/MS imaging to study the lipid structures of Drosophila brain using the J105 and 40-keV Ar 4000 + gas cluster ion source, with the novelty being the use of MS/MS SIMS analysis of intact lipids in the fly brain. Glycerophospholipids were identified by MS/MS profiling. MS/MS was also used to characterize diglyceride fragment ions and to identify them as triacylglyceride fragments. Moreover, MS/MS imaging offers a unique possibility for detailed elucidation of biomolecular distribution with high accuracy based on the ion images of its fragments. This is particularly useful in the presence of interferences which disturb the interpretation of biomolecular localization. Graphical abstract MS/MS was performed during time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis of Drosophila melongaster (fruit fly) to elucidate the structure and origin of different chemical species in the brain including a range of different phospholipid classes (PC, PI, PE) and di- and triacylglycerides (DAG & TAG) species where reference MS/MS spectra provided a potential means of discriminating between the isobaric [M-OH] + ion of DAGs and the [M-RCO] + ion of TAGs.

Streamlined structure elucidation of an unknown compound in a pigment formulation.

PubMed

Yüce, Imanuel; Morlock, Gertrud E

2016-10-21

A fast and reliable quality control is important for ink manufacturers to ensure a constant production grade of mixtures and chemical formulations, and unknown components attract their attention. Structure elucidating techniques seem time-consuming in combination with column-based methods, but especially the low solubility of pigment formulations is challenging the analysis. In contrast, layer chromatography is more tolerant with regard to pigment particles. One PLC plate for NMR and FTIR analyses and one HPTLC plate for recording of high resolution mass spectra, MS/MS spectra and for gathering information on polarity and spectral properties were needed to characterize a structure, exemplarily shown for an unknown component in pigment Red 57:1 to be 3-hydroxy-2-naphtoic acid. A preparative layer chromatography (PLC) workflow was developed that used an Automated Multiple Development 2 (AMD 2) system. The 0.5-mm PLC plate could still be operated in the AMD 2 system and allowed a smooth switch from the analytical to the preparative gradient separation. Through automated gradient development and the resulting focusing of bands, the sharpness of the PLC bands was improved. For NMR, the necessary high load of the target compound on the PLC plate was achieved via a selective solvent extraction that discriminated the polar sample matrix and thus increased the application volume of the extract that could maximally be applied without overloading. By doing so, the yield for NMR analysis was improved by a factor of 9. The effectivity gain through a simple, but thoroughly chosen extraction solvent is often overlooked, and for educational purpose, it was clearly illustrated and demonstrated by an extended solvent screening. Thus, PLC using an automated gradient development after a selective extraction was proven to be a new powerful combination for structural elucidation by NMR. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations

PubMed Central

Ahlstrom, Logan S.; Vorontsov, Ivan I.; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations. PMID:28107510

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations.

PubMed

Ahlstrom, Logan S; Vorontsov, Ivan I; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.

Encapsulation of the Antioxidant R-(+)-α-Lipoic Acid in Permethylated α- and β-Cyclodextrins: Thermal and X-ray Structural Characterization of the 1:1 Inclusion Complexes.

PubMed

Caira, Mino R; Bourne, Susan A; Mzondo, Buntubonke

2017-05-23

The naturally occurring compound α-lipoic acid (ALA) is implicated in manifold critical biological roles and its potent antioxidant properties and potential for treatment of various diseases have led to its widespread use as a dietary supplement. However, shortcomings of poor aqueous solubility and low thermal stability have hampered its development as a medicinal agent, prompting the use of cyclodextrins (CDs) to address these problems. The paucity of published structural data on the nature of the interactions between ALA and CDs motivated the present study, which describes the synthesis and X-ray structural elucidation of crystalline inclusion complexes between the biologically relevant R-(+)-α-lipoic acid (RALA) and the host molecules permethylated α-CD (TMA) and permethylated β-CD (TMB). Single crystal X-ray diffraction of TMA·RALA·6H₂O and TMB·RALA revealed significantly different orientations of the RALA molecule within the TMA and TMB cavities, but in both cases the guest molecule is fully encapsulated by the respective parent host molecules and residues of CD molecules of neighboring complex units. While pure RALA melted at 46-48 °C, combined thermal analysis techniques indicated that on heating the respective complexes, the release of RALA occurred at significantly higher onset temperatures, in the range 150-170 °C.

Antibody Epitope Analysis to Investigate Folded Structure, Allosteric Conformation, and Evolutionary Lineage of Proteins.

PubMed

Wong, Sienna; Jin, J-P

2017-01-01

Study of folded structure of proteins provides insights into their biological functions, conformational dynamics and molecular evolution. Current methods of elucidating folded structure of proteins are laborious, low-throughput, and constrained by various limitations. Arising from these methods is the need for a sensitive, quantitative, rapid and high-throughput method not only analysing the folded structure of proteins, but also to monitor dynamic changes under physiological or experimental conditions. In this focused review, we outline the foundation and limitations of current protein structure-determination methods prior to discussing the advantages of an emerging antibody epitope analysis for applications in structural, conformational and evolutionary studies of proteins. We discuss the application of this method using representative examples in monitoring allosteric conformation of regulatory proteins and the determination of the evolutionary lineage of related proteins and protein isoforms. The versatility of the method described herein is validated by the ability to modulate a variety of assay parameters to meet the needs of the user in order to monitor protein conformation. Furthermore, the assay has been used to clarify the lineage of troponin isoforms beyond what has been depicted by sequence homology alone, demonstrating the nonlinear evolutionary relationship between primary structure and tertiary structure of proteins. The antibody epitope analysis method is a highly adaptable technique of protein conformation elucidation, which can be easily applied without the need for specialized equipment or technical expertise. When applied in a systematic and strategic manner, this method has the potential to reveal novel and biomedically meaningful information for structure-function relationship and evolutionary lineage of proteins. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Structural Investigations of the MnO-Bi3O3-CdO Glass System by IR and Raman Spectroscopies

NASA Astrophysics Data System (ADS)

Ardelean, I.; Todor, Ioana; PǍŞCUŢǍ, P.

Homogeneous glasses are formed in the MnO-Bi3O3-CdO system, up to 50 mol% MnO. For these glasses, IR and Raman spectral measurements are carried out in order to elucidate the local structure. We identify by IR spectroscopy both the structural units BiO3 and BiO6. The Raman investigation confirms the prevalence of BiO6 groups in the glass network for all concentrations. The number of these structural groups progressively increases with MnO content.

Genetic engineering combined with deep UV resonance Raman spectroscopy for structural characterization of amyloid-like fibrils.

PubMed

Sikirzhytski, Vitali; Topilina, Natalya I; Higashiya, Seiichiro; Welch, John T; Lednev, Igor K

2008-05-07

Elucidating the structure of the cross-beta core in large amyloid fibrils is a challenging problem in modern structural biology. For the first time, a set of de novo polypeptides was genetically engineered to form amyloid-like fibrils with similar morphology and yet different strand length. Differential ultraviolet Raman spectroscopy allowed for separation of the spectroscopic signatures of the highly ordered beta-sheet strands and turns of the fibril core. The relationship between Raman frequencies and Ramachandran dihedral angles of the polypeptide backbone indicates the nature of the beta-sheet and turn structural elements.

Phononic Band Gaps in 2D Quadratic and 3D Cubic Cellular Structures

PubMed Central

Warmuth, Franziska; Körner, Carolin

2015-01-01

The static and dynamic mechanical behaviour of cellular materials can be designed by the architecture of the underlying unit cell. In this paper, the phononic band structure of 2D and 3D cellular structures is investigated. It is shown how the geometry of the unit cell influences the band structure and eventually leads to full band gaps. The mechanism leading to full band gaps is elucidated. Based on this knowledge, a 3D cellular structure with a broad full band gap is identified. Furthermore, the dependence of the width of the gap on the geometry parameters of the unit cell is presented. PMID:28793713

Influence of Chemical Conditions on the Nanoporous Structure of Silicate Aerogels

PubMed Central

Sinkó, Katalin

2010-01-01

Silica or various silicate aerogels can be characterized by highly porous, open cell, low density structures. The synthesis parameters influence the three-dimensional porous structures by modifying the kinetics and mechanism of hydrolysis and condensation processes. Numerous investigations have shown that the structure of porous materials can be tailored by variations in synthesis conditions (e.g., the type of precursors, catalyst, and surfactants; the ratio of water/precursor; the concentrations; the medium pH; and the solvent). The objectives of this review are to summarize and elucidate the effects of chemical conditions on the nanoporous structure of sol-gel derived silicate aerogels.

A history of gap junction structure: hexagonal arrays to atomic resolution.

PubMed

Grosely, Rosslyn; Sorgen, Paul L

2013-02-01

Gap junctions are specialized membrane structures that provide an intercellular pathway for the propagation and/or amplification of signaling cascades responsible for impulse propagation, cell growth, and development. Prior to the identification of the proteins that comprise gap junctions, elucidation of channel structure began with initial observations of a hexagonal nexus connecting apposed cellular membranes. Concomitant with technological advancements spanning over 50 years, atomic resolution structures are now available detailing channel architecture and the cytoplasmic domains that have helped to define mechanisms governing the regulation of gap junctions. Highlighted in this review are the seminal structural studies that have led to our current understanding of gap junction biology.

Phononic Band Gaps in 2D Quadratic and 3D Cubic Cellular Structures.

PubMed

Warmuth, Franziska; Körner, Carolin

2015-12-02

The static and dynamic mechanical behaviour of cellular materials can be designed by the architecture of the underlying unit cell. In this paper, the phononic band structure of 2D and 3D cellular structures is investigated. It is shown how the geometry of the unit cell influences the band structure and eventually leads to full band gaps. The mechanism leading to full band gaps is elucidated. Based on this knowledge, a 3D cellular structure with a broad full band gap is identified. Furthermore, the dependence of the width of the gap on the geometry parameters of the unit cell is presented.

Identifying challenges and opportunities for improved nutrient management through U.S.D.A's Dairy Agroecosystem Working Group

USDA-ARS?s Scientific Manuscript database

Nutrient management is a priority of U.S. dairy farms, although specific concerns vary across regions and management systems. To elucidate challenges and opportunities to improving nutrient use efficiencies, the USDA’s Dairy Agroecosystems Working Group investigated 10 case studies of confinement (i...

Dyslexia from a Cross-Linguistic and Cross-Cultural Perspective: The Case of Russian and Russia

ERIC Educational Resources Information Center

Kornev, Aleksandr N.; Rakhlin, Natalia; Grigorenko, Elena L.

2010-01-01

An important goal of research on specific learning disorders (such as dyslexia, or specific reading disability, or dysgraphia, or specific writing disorder) is to elucidate the universal characteristics and cross-linguistic and cross-cultural differences of literacy acquisition and disability. However, despite the acknowledged necessity of…

ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TECHNIQUE FOR IDENTIFYING COMPOUNDS IN COMPLEX MIXTURES

EPA Science Inventory

When tentatively identifying compounds in complex mixtures using mass spectral libraries, multiple matches or no plausible matches due to a high level of chemical noise or interferences can occur. Worse yet, most analytes are not in the libraries. In each case, Ion Composition El...

Two new prenylflavonoids from Morus alba.

PubMed

Gao, Li; Li, Yuan-Dong; Zhu, Bao-Kun; Li, Zhi-Yu; Huang, Li-Bin; Li, Xian-Yi; Wang, Fei; Ren, Fu-Cai; Liao, Tou-Gen

2018-02-01

Two new prenylflavonoids, morusalbols A and B (1 and 2), were isolated from the branches and leaves of Morus alba, together with three known compounds, kuwanon C (3), morusin (4), morusinol (5). The structures of these two prenylflavonoids were elucidated by extensive analyzes of the spectroscopic data.

Three new alkaloids from the fruits of Morus alba.

PubMed

Wang, Xin; Kang, Jie; Wang, Hong-Qing; Liu, Chao; Li, Bao-Ming; Chen, Ruo-Yun

2014-01-01

From the fruits of Morus alba, three new alkaloids, mulbaines A (1), B (2), and C (3) were isolated. The structures of these compounds were elucidated on the basis of spectroscopic methods (UV, IR, HR-ESI-MS, 1D, and 2D NMR).

Sesquiterpenoids from Vernonia cinerea.

PubMed

Chen, Xin; Zhan, Zha-Jun; Yue, Jian-Min

2006-01-01

A new sesquiterpenoid, namely vernocinolide A, as well as ten known ones, were isolated from the ethyl acetate soluble fraction of the Vernoniacinerea. The structure of vernocinolide A was elucidated by spectroscopic methods. Among the known sesquiterpenoids, nine of them were isolated from this plant for the first time.

Isolation and synthesis of antibacterial prenylated acylphloroglu-cinols from Psorothamnus fremontii

USDA-ARS?s Scientific Manuscript database

Antibacterial assay-guided fractionation of the methanol extract of the native American plant Psorothamnus fremontii followed by structure elucidation afforded three prenylated acylphloroglucinol derivatives, psorothatins A-C (1-3). They feature a unique a,ß-epoxyketone functionality and an a,ß-hydr...

Critical ratios for structural analysis of triacylglycerols using mass spectrometry

USDA-ARS?s Scientific Manuscript database

Recent developments have finally allowed fragment behaviors using APCI-MS to be elucidated after twenty years of literature reports. Critical Ratios have been defined that correspond to various aspects of triacylglycerol (TAG) analysis, from overall degree of unsaturation to localization of fatty ac...

Graminone B, a novel lignan with vasodilative activity from Imperata cylindrica.

PubMed

Matsunaga, K; Shibuya, M; Ohizumi, Y

1994-12-01

Two novel lignans, graminones A [1] and B [2] have been isolated from Imperata cylindrica and their structures have been elucidated on the basis of their spectral data. Graminone B [2] showed inhibitory activity on the contraction of the rabbit aorta.

A new stilbenoid from Arundina graminifolia.

PubMed

Liu, Mei-Feng; Han, Yun; Xing, Dong-Ming; Shi, Yue; Xu, Li-Zhen; Du, Li-Jun; Ding, Yi

2004-09-01

A chemical investigation of the Orchidaceae Arundina gramnifolia has led to the isolation of a novel stilbenoid, named arundinan (1). The structure of 1 has been elucidated as 2-(p-hydroxybenzyl)-3-hydroxy-5-methoxybibenzyl on the basis of physical and chemical evidence and spectral analysis.

Mono- and multimeric ferrocene congeners of quinoline-based polyamines as potential antiparasitics

USDA-ARS?s Scientific Manuscript database

A series of mono- and multimeric polyamine-containing ferrocenyl complexes bearing a quinoline motif were prepared. The complexes were characterised by standard techniques. The molecular structure of the monomeric salicylaldimine derivative was elucidated using single crystal X-ray diffraction and w...

Novel dihydro-beta-agarofuran sesquiterpenes as potent modulators of human P-glycoprotein dependent multidrug resistance.

PubMed

Torres-Romero, David; Muñoz-Martínez, Francisco; Jiménez, Ignacio A; Castanys, Santiago; Gamarro, Francisco; Bazzocchi, Isabel L

2009-12-21

P-Glycoprotein (Pgp) overexpression is one factor contributing to multidrug resistance (MDR) in cancer cells and represents one drawback in the treatment of cancer. In an attempt to find more specific and less toxic anticancer MDR-reversal agents, we report herein the isolation, structure elucidation and biological activity of nine new (, and ) and seven known (, and ) dihydro-beta-agarofuran sesquiterpenes from the leaves of Celastrus vulcanicola. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, CD studies and biogenetic means. All the compounds were assayed on human MDR1-transfected NIH-3T3 cells, in order to determine their ability to reverse the MDR phenotype due to Pgp overexpression. Six compounds from these series (, , , , and ) showed an effectiveness that was similar to (or higher than) the classical Pgp reversal agent verapamil for the reversal of resistance to daunomycin and vinblastine. The structure-activity relationships are discussed.

Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme

PubMed Central

Bailey, Lucas J; Tan, Yong Zi; Wei, Hui; Wang, Andrew; Farcasanu, Mara; Woods, Virgil A; McCord, Lauren A; Lee, David; Shang, Weifeng; Deprez-Poulain, Rebecca; Deprez, Benoit; Liu, David R; Koide, Akiko; Koide, Shohei; Kossiakoff, Anthony A

2018-01-01

Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies. PMID:29596046

Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser

DOE PAGES

Popp, David; Loh, N. Duane; Zorgati, Habiba; ...

2017-06-02

A major goal for X-ray free-electron laser (XFEL) based science is to elucidate structures of biological molecules without the need for crystals. Filament systems may provide some of the first single macromolecular structures elucidated by XFEL radiation, since they contain one-dimensional translational symmetry and thereby occupy the diffraction intensity region between the extremes of crystals and single molecules. Here, we demonstrate flow alignment of as few as 100 filaments ( Escherichia coli pili, F-actin, and amyloid fibrils), which when intersected by femtosecond X-ray pulses result in diffraction patterns similar to those obtained from classical fiber diffraction studies. We also determinemore » that F-actin can be flow-aligned to a disorientation of approximately 5 degrees. Using this XFEL-based technique, we determine that gelsolin amyloids are comprised of stacked β-strands running perpendicular to the filament axis, and that a range of order from fibrillar to crystalline is discernable for individual α-synuclein amyloids.« less

Energetics and Structural Characterization of the large-scale Functional Motion of Adenylate Kinase

PubMed Central

Formoso, Elena; Limongelli, Vittorio; Parrinello, Michele

2015-01-01

Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great value to guide rationally the development of new medications. Here using a metadynamics-based computational protocol we elucidate the thermodynamics and structural properties underlying the AK functional transitions. The free energy estimation of the conformational motions of the enzyme allows characterizing the sequence of events that regulate its action. We reveal the atomistic details of the most relevant enzyme states, identifying residues such as Arg119 and Lys13, which play a key role during the conformational transitions and represent druggable spots to design enzyme inhibitors. Our study offers tools that open new areas of investigation on large-scale motion in proteins. PMID:25672826

Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser

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

Popp, David; Loh, N. Duane; Zorgati, Habiba

A major goal for X-ray free-electron laser (XFEL) based science is to elucidate structures of biological molecules without the need for crystals. Filament systems may provide some of the first single macromolecular structures elucidated by XFEL radiation, since they contain one-dimensional translational symmetry and thereby occupy the diffraction intensity region between the extremes of crystals and single molecules. Here, we demonstrate flow alignment of as few as 100 filaments ( Escherichia coli pili, F-actin, and amyloid fibrils), which when intersected by femtosecond X-ray pulses result in diffraction patterns similar to those obtained from classical fiber diffraction studies. We also determinemore » that F-actin can be flow-aligned to a disorientation of approximately 5 degrees. Using this XFEL-based technique, we determine that gelsolin amyloids are comprised of stacked β-strands running perpendicular to the filament axis, and that a range of order from fibrillar to crystalline is discernable for individual α-synuclein amyloids.« less

Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity.

PubMed

Steven, Alasdair C; Heymann, J Bernard; Cheng, Naiqian; Trus, Benes L; Conway, James F

2005-04-01

For many viruses, the final stage of assembly involves structural transitions that convert an innocuous precursor particle into an infectious agent. This process -- maturation -- is controlled by proteases that trigger large-scale conformational changes. In this context, protease inhibitor antiviral drugs act by blocking maturation. Recent work has succeeded in determining the folds of representative examples of the five major proteins -- major capsid protein, scaffolding protein, portal, protease and accessory protein -- that are typically involved in capsid assembly. These data provide a framework for detailed mechanistic investigations and elucidation of mutations that affect assembly in various ways. The nature of the conformational change has been elucidated: it entails rigid-body rotations and translations of the arrayed subunits that transfer the interactions between them to different molecular surfaces, accompanied by refolding and redeployment of local motifs. Moreover, it has been possible to visualize maturation at the submolecular level in movies based on time-resolved cryo-electron microscopy.

Purification and partial elucidation of the structure of an antioxidant carbohydrate biopolymer from the probiotic bacterium Bacillus coagulans RK-02.

PubMed

Kodali, Vidya P; Perali, Ramu S; Sen, R

2011-08-26

An exopolysaccharide (EPS) was isolated from Bacillus coagulans RK-02 and purified by size exclusion chromatography. The purified, homogeneous EPS had an average molecular weight of ∼3 × 10⁴ Da by comparison with FITC-labeled dextran standards. In vivo evaluations showed that, like other reported polysaccharides, this EPS displayed significant antioxidant activity. FTIR spectroscopy analysis showed the presence of hydroxy, carboxy, and α-glycosidic linkages and a mannose residue. GC analysis indicated that the EPS was a heteropolymer composed of glucose, mannose, galactose, glucosamine, and fucose as monomeric constituent units. Partial elucidation of the structure of the carbohydrate biopolymer based on GC-MS and NMR analysis showed the presence of two unique sets of tetrasaccharide repeating units that have 1→3 and 1→6 glycosidic linkages. This is also the first report of a Gram-positive bacterial polysaccharide with both fucose as a sugar monomer and 1→3 and 1→6 glycosidic linkages in the molecular backbone.

[Isolation and structural elucidation of secondary metabolites from marine Streptomyces sp. SCSIO 1934].

PubMed

Niu, Siwen; Li, Sumei; Tian, Xinpeng; Hu, Tao; Ju, Jianhua; Ynag, Xiaohong; Zhang, Si; Zhang, Changsheng

2011-07-01

Marine Actinobacteria are emerging as new resources for bioactive natural products with promise in novel drug discovery. In recent years, the richness and diversity of marine Actinobacteria from the South China Sea and their ability in producing bioactive products have been investigated. The objective of this work is to isolate and identify bioactive secondary metabolites from a marine actinobacterium SCSIO 1934 derived from sediments of South China Sea. The strain was identified as a Streptomyces spieces by analyzing its 16S rDNA sequence. Streptomyces sp. SCSIO 1934 was fermented under optimized conditions and seven bioactive secondary metabolites were isolated and purified by chromatographic methods including colum chromatography over silica gel and Sephadex LH-20. Their structures were elucidated as 17-O-demethylgeldanamycin (1), lebstatin (2), 17-O-demethyllebstatin (3), nigericin (4), nigericin sodium salt (5), abierixin (6), respectively, by detailed NMR spectroscopic data (1H, 13C, COSY, HSQC and HMBC). This work provided a new marine actinobacterium Streptomyces sp. SCSIO 1934, capable of producing diverse bioactive natural products.

Energetics and Structural Characterization of the large-scale Functional Motion of Adenylate Kinase

NASA Astrophysics Data System (ADS)

Formoso, Elena; Limongelli, Vittorio; Parrinello, Michele

2015-02-01

Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great value to guide rationally the development of new medications. Here using a metadynamics-based computational protocol we elucidate the thermodynamics and structural properties underlying the AK functional transitions. The free energy estimation of the conformational motions of the enzyme allows characterizing the sequence of events that regulate its action. We reveal the atomistic details of the most relevant enzyme states, identifying residues such as Arg119 and Lys13, which play a key role during the conformational transitions and represent druggable spots to design enzyme inhibitors. Our study offers tools that open new areas of investigation on large-scale motion in proteins.

Tiopronin Gold Nanoparticle Precursor Forms Aurophilic Ring Tetramer

PubMed Central

Simpson, Carrie A.; Farrow, Christopher L.; Tian, Peng; Billinge, Simon J.L.; Huffman, Brian J.; Harkness, Kellen M.; Cliffel, David E.

2010-01-01

In the two step synthesis of thiolate-monolayer protected clusters (MPCs), the first step of the reaction is a mild reduction of gold(III) by thiols that generates gold(I) thiolate complexes as intermediates. Using tiopronin (Tio) as the thiol reductant, the characterization of the intermediate Au4Tio4 complex was accomplished with various analytical and structural techniques. Nuclear magnetic resonance (NMR), elemental analysis, thermogravimetric analysis (TGA), and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) were all consistent with a cyclic gold(I)-thiol tetramer structure, and final structural analysis was gathered through the use of powder diffraction and pair distribution functions (PDF). Crystallographic data has proved challenging for almost all previous gold(I)-thiolate complexes. Herein, a novel characterization technique when combined with standard analytical assessment to elucidate structure without crystallographic data proved invaluable to the study of these complexes. This in conjunction with other analytical techniques, in particular mass spectrometry, can elucidate a structure when crystallographic data is unavailable. In addition, luminescent properties provided evidence of aurophilicity within the molecule. The concept of aurophilicity has been introduced to describe a select group of gold-thiolate structures, which possess unique characteristics, mainly red photoluminescence and a distinct Au-Au intramolecular distance indicating a weak metal-metal bond as also evidenced by the structural model of the tetramer. Significant features of both the tetrameric and aurophilic properties of the intermediate gold(I) tiopronin complex are retained after borohydride reduction to form the MPC, including gold(I) tiopronin partial rings as capping motifs, or “staples”, and weak red photoluminescence that extends into the Near Infrared region. PMID:21067183

Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli

PubMed Central

Napolitano, Michael G.; Landon, Matthieu; Gregg, Christopher J.; Lajoie, Marc J.; Govindarajan, Lakshmi; Mosberg, Joshua A.; Kuznetsov, Gleb; Goodman, Daniel B.; Vargas-Rodriguez, Oscar; Isaacs, Farren J.; Söll, Dieter; Church, George M.

2016-01-01

The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 “recalcitrant” AGRs required diversification to identify viable alternatives. Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional “safe replacement zone” (SRZ) within which alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we implemented a CRISPR/Cas9-based method to deplete a diversified population of a wild-type allele, allowing us to evaluate exhaustively the fitness impact of all 64 codon alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons that fall outside the SRZ are rapidly depleted from a growing population. Our unbiased and systematic strategy for identifying unpredicted design flaws in synthetic genomes and for elucidating rules governing codon choice will be crucial for designing genomes exhibiting radically altered genetic codes. PMID:27601680

Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6.

PubMed

Shaaban, Khaled A; Saunders, Meredith A; Zhang, Yinan; Tran, Tuan; Elshahawi, Sherif I; Ponomareva, Larissa V; Wang, Xiachang; Zhang, Jianjun; Copley, Gregory C; Sunkara, Manjula; Kharel, Madan K; Morris, Andrew J; Hower, James C; Tremblay, Matthew S; Prendergast, Mark A; Thorson, Jon S

2017-01-27

The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6-8] and 11 previously reported bacterial metabolites (1, 3, 9-12a, and 14-18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.

Effect of Substitution on the Aniline Moiety of the GPR88 Agonist 2-PCCA: Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies.

PubMed

Jin, Chunyang; Decker, Ann M; Harris, Danni L; Blough, Bruce E

2016-10-19

GPR88, an orphan receptor richly expressed in the striatum, is implicated in a number of basal ganglia-associated disorders. In order to elucidate the functions of GPR88, an in vivo probe appropriate for CNS investigation is required. We previously reported that 2-PCCA was able to modulate GPR88-mediated cAMP production through a Gα i -coupled pathway. Early structure-activity relationship (SAR) studies suggested that the aniline moiety of 2-PCCA is a suitable site for diverse modifications. Aimed at elucidating structural requirements in this region, we have designed and synthesized a series of analogues bearing a variety of substituents at the phenyl ring of the aniline moiety. Several compounds (e.g., 5j, 5o) showed improved or comparable potency, but have lower lipophilicity than 2-PCCA (clogP 6.19). These compounds provide the basis for further optimization to probe GPR88 in vivo functions. Computational studies confirmed the SAR trends and supported the notion that 4'-substituents on the biphenyl ring exit through a largely hydrophobic binding site to the extracellular loop.

Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins

PubMed Central

Yang, Aimin; Pantoom, Supansa; Wu, Yao-Wen

2017-01-01

Autophagy is a conserved cellular process involved in the elimination of proteins and organelles. It is also used to combat infection with pathogenic microbes. The intracellular pathogen Legionella pneumophila manipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to phosphatidylethanolamine (PE) on autophagosomal membranes. To understand how RavZ recognizes and deconjugates LC3-PE, we prepared semisynthetic LC3 proteins and elucidated the structures of the RavZ:LC3 interaction. Semisynthetic LC3 proteins allowed the analysis of structure-function relationships. RavZ extracts LC3-PE from the membrane before deconjugation. RavZ initially recognizes the LC3 molecule on membranes via its N-terminal LC3-interacting region (LIR) motif. The RavZ α3 helix is involved in extraction of the PE moiety and docking of the acyl chains into the lipid-binding site of RavZ that is related in structure to that of the phospholipid transfer protein Sec14. Thus, Legionella has evolved a novel mechanism to specifically evade host autophagy. DOI: http://dx.doi.org/10.7554/eLife.23905.001 PMID:28395732

Spatially and temporally resolved exciton dynamics and transport in single nanostructures and assemblies

NASA Astrophysics Data System (ADS)

Huang, Libai

2015-03-01

The frontier in solar energy conversion now lies in learning how to integrate functional entities across multiple length scales to create optimal devices. To address this new frontier, I will discuss our recent efforts on elucidating multi-scale energy transfer, migration, and dissipation processes with simultaneous femtosecond temporal resolution and nanometer spatial resolution. We have developed ultrafast microscopy that combines ultrafast spectroscopy with optical microscopy to map exciton dynamics and transport with simultaneous ultrafast time resolution and diffraction-limited spatial resolution. We have employed pump-probe transient absorption microscopy to elucidate morphology and structure dependent exciton dynamics and transport in single nanostructures and molecular assemblies. More specifically, (1) We have applied transient absorption microscopy (TAM) to probe environmental and structure dependent exciton relaxation pathways in sing-walled carbon nanotubes (SWNTs) by mapping dynamics in individual pristine SWNTs with known structures. (2) We have systematically measured and modeled the optical properties of the Frenkel excitons in self-assembled porphyrin tubular aggregates that represent an analog to natural photosynthetic antennae. Using a combination of ultrafast optical microscopy and stochastic exciton modeling, we address exciton transport and relaxation pathways, especially those related to disorder.

The major glucosinolate hydrolysis product in rocket (Eruca sativa L.), sativin, is 1,3-thiazepane-2-thione: Elucidation of structure, bioactivity, and stability compared to other rocket isothiocyanates.

PubMed

Fechner, Jana; Kaufmann, Martin; Herz, Corinna; Eisenschmidt, Daniela; Lamy, Evelyn; Kroh, Lothar W; Hanschen, Franziska S

2018-09-30

Rocket is rich in glucosinolates and valued for its hot and spicy taste. Here we report the structure elucidation, bioactivity, and stability of the mainly formed glucosinolate hydrolysis product, namely sativin, which was formerly thought to be 4-mercaptobutyl isothiocyanate. However, by NMR characterization we revealed that sativin is in fact 1,3-thiazepane-2-thione, a tautomer of 4-mercaptobutyl isothiocyanate with 7-membered ring structure and so far unknown. This finding was further substantiated by conformation sampling using molecular modeling and total enthalpy calculation with density functional theory. During aqueous heat treatment sativin in general was quite stable, while the isothiocyanates erucin and sulforaphane were labile, having half-lives of 132 min and 56 min (pH 5, 100 °C), respectively. Moreover, using a WST-1 assay, we found that sativin did not reduce cell viability of HepG2 cells in a range of 0.3-30 µM, and, therefore, exhibited no cytotoxic effects in this cell line. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Apolipoprotein ε7 allele in memory complaints: insights through protein structure prediction.

PubMed

Youn, Young Chul; Lim, Yong Kwan; Han, Su-Hyun; Giau, Vo Van; Lee, Mi-Kyung; Park, Kwang-Yeol; Kim, SangYun; Bagyinszky, Eva; An, Seong Soo A; Kim, Hye Ryoun

2017-01-01

APOE ε7 gene is a rare mutant form of APOE ε3 . The mutation occurs in the lipid-binding domain of APOE. Based on the protein's structure, APOE ε7 is expected to function in lipid and β-amyloid metabolism, similar to APOE ε4 . However, unlike that for APOE ε4 , the mechanisms responsible for Alzheimer's disease (AD) cases associated with APOE ε7 expression have not been elucidated. The present study aims to investigate the association between APOE ε7 expression and cognitive impairment. APOE was sequenced in DNA samples collected from 344 memory-complaint patients who visited the memory clinic, and from 345 non-memory-complaint individuals from the health promotion center. The protein structures of ApoE3, ApoE4, and ApoE7 were predicted. Three ε3 / ε7 heterozygote individuals who were all classified under the memory-complaint group were identified. Of these, two subjects were clinically diagnosed with AD with small vessel disease, and the remaining individual was diagnosed with subjective cognitive impairment. This study predicted the protein structures of ApoE3, ApoE4, and ApoE7 and determined the three-dimensional structure of the carboxy terminus of ApoE7, which participates in an electrostatic domain interaction similar to that of APOE ε4 . APOE K244 or K245 mutations for APOE ε7 were not found in the Korean reference genome database, which contains information (http://152.99.75.168/KRGDB/browser/mainBrowser.jsp) from 622 healthy individuals. As verified by the results of structural prediction, APOE ε7 could serve as another risk factor for cognitive impairment and is particularly associated with vascular disease. However, additional studies are required to validate the pathogenic nature of APOE ε7 .

The PELskin project: part II-investigating the physical coupling between flexible filaments in an oscillating flow.

PubMed

Revell, Alistair; O'Connor, Joseph; Sarkar, Abhishek; Li, Cuicui; Favier, Julien; Kamps, Laura; Brücker, Christoph

2017-01-01

The fluid-structure interaction mechanisms of a coating composed of flexible flaps immersed in a periodically oscillating channel flow is here studied by means of numerical simulation, employing the Euler-Bernoulli equations to account for the flexibility of the structures. A set of passively actuated flaps have previously been demonstrated to deliver favourable aerodynamic impact when attached to a bluff body undergoing periodic vortex shedding. As such, the present configuration is identified to provide a useful test-bed to better understand this mechanism, thought to be linked to experimentally observed travelling waves. Having previously validated and elucidated the flow mechanism in Paper 1 of this series, we hereby undertake a more detailed analysis of spectra obtained for different natural frequency of structures and different configurations, in order to better characterize the mechanisms involved in the organized motion of the structures. Herein, this wave-like behaviour, observed at the tips of flexible structures via interaction with the fluid flow, is characterized by examining the time history of the filaments motion and the corresponding effects on the fluid flow, in terms of dynamics and frequency of the fluid velocity. Results indicate that the wave motion behaviour is associated with the formation of vortices in the gaps between the flaps, which itself are a function of the structural resistance to the cross flow. In addition, formation of vortices upstream of the leading and downstream of the trailing flap is seen, which interact with the formation of the shear-layer on top of the row. This leads to a phase shift in the wave-type motion along the row that resembles the observation in the cylinder case.

[Studies on chemical constituents from roots of Craibiodendron henryi].

PubMed

Huang, Xiang-Zhong; Liu, Yue; Yu, Shi-Shan; Hu, You-Cai; Qu, Jing

2007-04-01

To study the chemical constituents from the roots of Craibiodendron henryi. Various chromatographic techniques were used to isolate and purify the constituents. The structures were elucidated by chemical evidence and spectral methods. Twelve compounds were isolated from the ethyl acetate soluble fraction of the 95% ethanolic extract and their struc- tures were elucidated as quercetin (1), quercetin-3-O-rhamnicoside (2), quercetin-3-O-arabinofuranoside (3), (-)-epicatechin (4), proanthocyanidin A-2 (5), procyanidin B-2 (6), (-)-isolariciresinol-2a-O-beta-D-xylopyranoside (7), lyoniside (8), sitoster-yl-3beta-glucoside-6'-O-palmitate (9), beta-sitosterol (10), daucosterol (11) and octacosanoic acid (12). Compounds 1-12 were isolated from this plant for the first time.

Statistical mechanics of protein structural transitions: Insights from the island model

PubMed Central

Kobayashi, Yukio

2016-01-01

The so-called island model of protein structural transition holds that hydrophobic interactions are the key to both the folding and function of proteins. Herein, the genesis and statistical mechanical basis of the island model of transitions are reviewed, by presenting the results of simulations of such transitions. Elucidating the physicochemical mechanism of protein structural formation is the foundation for understanding the hierarchical structure of life at the microscopic level. Based on the results obtained to date using the island model, remaining problems and future work in the field of protein structures are discussed, referencing Professor Saitô’s views on the hierarchic structure of science. PMID:28409078

Modulation of frontogenetic plankton production along a meandering jet by zonal wind forcing: An application to the Alboran Sea

NASA Astrophysics Data System (ADS)

Oguz, Temel; Mourre, Baptiste; Tintoré, Joaquin

2017-08-01

We present a coupled physical-biological modeling study to elucidate the changes in ageostrophic frontal dynamics and the frontogenetic plankton production characteristics of a meandering jet under the impacts of successive westerly/easterly wind events combined with seasonal variations in the upstream transport and buoyancy flux characteristics of the jet, using a case study for the Alboran Sea (Western Mediterranean). Their nonlinear coupling is shown to result in different forms of physical and biological characteristics of the background jet structure that follows a meandering path around two anticyclonic gyres in the western and eastern basins and a cyclonic eddy in between. The westerly, downfront wind events broaden the jet, and result in stronger cross-frontal density contrast and intensify ageostrophic cross-frontal secondary circulation. Thus, they improve the frontogenetic plankton production with respect to the no-wind case. They also support higher production along the northern coast in response to wind-induced coastal upwelling and spreading of resulting nutrient-rich, productive water by mesoscale stirring. These features weaken gradually as the jet transport reduces. In contrast, stronger and longer-lasting easterlies during the reduced jet transport phase weaken the currents and frontal density structure, change the circular Western Alboran Gyre to an elongated form, and shift the main axis of the jet towards the southern basin. Then, frontogenesis fails to contribute to phytoplankton production that becomes limited to the eddy pumping within cyclones. Apart from the frontogenetic production, eddy pumping, mesoscale stirring, and diapycnal mixing of nutrients support intermittent and localized phytoplankton patches over the basin.

Folding and unfolding pathway of chaperonin GroEL monomer and elucidation of thermodynamic parameters.

PubMed

Puri, Sarita; Chaudhuri, Tapan K

2017-03-01

The conformation and thermodynamic stability of monomeric GroEL were studied by CD and fluorescence spectroscopy. GroEL denaturation with urea and dilution in buffer leads to formation of a folded GroEL monomer. The monomeric nature of this protein was verified by size-exclusion chromatography and native PAGE. It has a well-defined secondary and tertiary structure, folding activity (prevention of aggregation) for substrate protein and is resistant to proteolysis. Being a properly folded and reversibly refoldable, monomeric GroEL is amenable for the study of thermodynamic stability by unfolding transition methods. We present the equilibrium unfolding of monomeric GroEL as studied by urea and heat mediated unfolding processes. The urea mediated unfolding shows two transitions and a single transition in the heat mediated unfolding process. In the case of thermal unfolding, some residual structure unfolds at a higher temperature (70-75°C). The process of folding/unfolding is reversible in both cases. Analysis of folding/unfolding data provides a measure of ΔG NU H 2 O , T m , ΔH van and ΔS van of monomeric GroEL. The thermodynamic stability parameter ΔG NU H 2 O is similar with both CD and intrinsic fluorescence i.e. 7.10±1.0kcal/mol. The calculated T m , ΔH van and ΔS van from the thermal unfolding transition is 46±0.5°C, 43.3±0.1kcal/mol and 143.9±0.1cal/mol/k respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Towards a New Framework for Interpreting Relations Between Mantle Dynamics and Processes at the Earth's Surface: A Case Study Involving the Deccan Traps

NASA Astrophysics Data System (ADS)

Glisovic, P.; Forte, A. M.

2017-12-01

An outstanding challenge in modern geodynamics is the utilization of mantle convection models and geophysical data to successfully explain geological events and processes that alter Earth's biosphere, climate, and surface. A key challenge in this modelling is the determination of the initial (and unknown) configuration of mantle heterogeneity in the geological past. The first step in addressing this challenge is recognizing that seismic tomography is our most powerful tool for mapping the present-day, internal structure of the mantle. We, therefore, implemented a new back-and-forth iterative method for time-reversed, tomography-based convection modelling to reconstruct Earth's internal 3-D structure and dynamics over the Cenozoic [Glisovic & Forte 2016 (JGR)]. This backward convection modelling also includes another key input - the depth variation of mantle viscosity inferred from joint inversions of the global convection-related observables and a suite of glacial isostatic adjustments (GIA) data [Mitrovica & Forte 2004 (EPSL), Forte et al. 2010 (EPSL)]. This state-of-the-art, time-reversed convection model is able to show that massive outpourings of basalt in west-central India, known as the Deccan Traps, about 65 million years ago can be directly linked to the presence of two different deep-mantle hotspots: Réunion and Comores [Glisovic & Forte 2017 (Science)]. This work constitutes case study showing how time-reversed convection modelling provides a new framework for interpreting the relations between mantle dynamics and changing paleogeography and it provides a roadmap for a new series of studies that will elucidate these linkages.

Bioactive natural compounds from the plant endophytic fungi Pestalotiopsis spp.

PubMed

Wang, Kuiwu; Lei, Jinxiu; Wei, Jiguang; Yao, Nan

2012-11-01

The plant-endophytic strains of the fungus Pestalotiopsis (Amphisphaeriaceae) are distributed throughout the world. Previous chemical investigation of members of the genus resulted in the discovery of various bioactive secondary metabolites including chromones, cytosporones, polyketides, terpenoids and coumarins with diverse structural features. The present report reviews the papers, which have appeared in the literature till now, concerning the isolation, structural elucidation, and biological activities of the secondary metabolites from Pestalotiopsis species.

A bis-bithiophene from Tridax procumbens L. (Asteraceae).

PubMed

Ali, Muhammad Shaiq; Jahangir, Muhammad

2002-08-01

The ethyl acetate soluble part of hexane extract of Tridax procumbens yielded a new bis-bithiophene named tridbisbithiophene along with four known terpenoids: taraxasteryl acetate, beta-amyrenone, lupeol and oleanolic acid, which have never been reported so far from Tridax procumbens. The structures of all the isolated constituents were elucidated with the aid of 1D-NMR spectroscopy whereas, the structure of new constituent tridbisbithiophene was confirmed via COSY and HMBC interactions.

Thermal degradation of Lewis acid complexed LDPE films

NASA Astrophysics Data System (ADS)

Sreelatha, K.; Predeep, P.

2017-06-01

The study highlights the thermal behavior of the semiconducting LDPE films synthesized by SbCl5 doping. The structural peculiarities and the responses of the structure to energetic modifications are studied. TGA and DTG curves are used to determine the thermal stability of the material. Degradation kinetics is elucidated. Activation energy and the entropy of activation for the degradation of the samples are calculated using Coats-Redfern plots and the samples show appreciable thermal stability.

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. II. Structure elucidation.

PubMed

Johnson, J H; Tymiak, A A; Bolgar, M S

1990-08-01

The structures of janthinocins A, B and C, three novel macrocyclic peptide lactone antibiotics isolated from fermentations of Janthinobacterium lividum, were determined. The janthinocins are of particular interest because they contain three amino acid residues that have not previously been reported in natural products: Each contains erythro-beta-hydroxy-D-leucine while janthinocins A and B also contain beta-hydroxytryptophan and beta-ketotryptophan, respectively.

Diterpenoid glycosides from the bitter fern Gleichenia quadripartita.

PubMed

Socolsky, Cecilia; Asakawa, Yoshinori; Bardón, Alicia

2007-12-01

Fifteen new diterpenoid glycosides (1a-n, 2) were isolated from an Argentine collection of the bitter fern Gleichenia quadripartita along with the known flavonoid glycoside afzelin. Structure elucidation was accomplished by 1D and 2D NMR spectroscopy and by high-resolution MS analyses. In addition, X-ray crystallographic analysis of a monocrystal of 1a as well as chemical derivatization of 1h and 1m were performed to confirm their structures.

Mammographic phenotypes of breast cancer risk driven by breast anatomy

NASA Astrophysics Data System (ADS)

Gastounioti, Aimilia; Oustimov, Andrew; Hsieh, Meng-Kang; Pantalone, Lauren; Conant, Emily F.; Kontos, Despina

2017-03-01

Image-derived features of breast parenchymal texture patterns have emerged as promising risk factors for breast cancer, paving the way towards personalized recommendations regarding women's cancer risk evaluation and screening. The main steps to extract texture features of the breast parenchyma are the selection of regions of interest (ROIs) where texture analysis is performed, the texture feature calculation and the texture feature summarization in case of multiple ROIs. In this study, we incorporate breast anatomy in these three key steps by (a) introducing breast anatomical sampling for the definition of ROIs, (b) texture feature calculation aligned with the structure of the breast and (c) weighted texture feature summarization considering the spatial position and the underlying tissue composition of each ROI. We systematically optimize this novel framework for parenchymal tissue characterization in a case-control study with digital mammograms from 424 women. We also compare the proposed approach with a conventional methodology, not considering breast anatomy, recently shown to enhance the case-control discriminatory capacity of parenchymal texture analysis. The case-control classification performance is assessed using elastic-net regression with 5-fold cross validation, where the evaluation measure is the area under the curve (AUC) of the receiver operating characteristic. Upon optimization, the proposed breast-anatomy-driven approach demonstrated a promising case-control classification performance (AUC=0.87). In the same dataset, the performance of conventional texture characterization was found to be significantly lower (AUC=0.80, DeLong's test p-value<0.05). Our results suggest that breast anatomy may further leverage the associations of parenchymal texture features with breast cancer, and may therefore be a valuable addition in pipelines aiming to elucidate quantitative mammographic phenotypes of breast cancer risk.

Revealing the Reaction Mechanism of Na–O 2 Batteries using Environmental Transmission Electron Microscopy

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

Kwak, Won -Jin; Luo, Langli; Jung, Hun -Gi

Due to its high energy efficiency, sodium-oxygen (Na-O 2) batteries have been extensively studied recently. One of the critical challenges for the development of the Na-O 2 battery is the elucidation of the reaction mechanism, the reaction products, and thestructural and chemical evolution of reaction product as well as their correlation with the battery performance. Herein, in-situ TEM was employed to probe the reaction mechanism and the structural evolution of the discharge products in Na-O 2 batteries. The discharge product is featured by the formation of both cubic and conformal NaO 2. It has been noticed that the impingement ofmore » reaction product (NaO 2) can lead to the coarsening of the particle through coalescence. We also investigated the stability of the discharge product, noticing that the reaction product NaO 2 is stable in the case of solid electrolyte. Here, the present work provide unprecedented insight for the development of the Na-O 2 batteries.« less

Revealing the Reaction Mechanism of Na–O 2 Batteries using Environmental Transmission Electron Microscopy

DOE PAGES

Kwak, Won -Jin; Luo, Langli; Jung, Hun -Gi; ...

2018-01-15

Due to its high energy efficiency, sodium-oxygen (Na-O 2) batteries have been extensively studied recently. One of the critical challenges for the development of the Na-O 2 battery is the elucidation of the reaction mechanism, the reaction products, and thestructural and chemical evolution of reaction product as well as their correlation with the battery performance. Herein, in-situ TEM was employed to probe the reaction mechanism and the structural evolution of the discharge products in Na-O 2 batteries. The discharge product is featured by the formation of both cubic and conformal NaO 2. It has been noticed that the impingement ofmore » reaction product (NaO 2) can lead to the coarsening of the particle through coalescence. We also investigated the stability of the discharge product, noticing that the reaction product NaO 2 is stable in the case of solid electrolyte. Here, the present work provide unprecedented insight for the development of the Na-O 2 batteries.« less

A Dynamic Analysis of Secretory Granules Containing Proteins Involved In Learning

NASA Astrophysics Data System (ADS)

Prahl, Louis; Simon, Alex; Jacobs, Conor; Fulwiler, Audrey; Hilken, Lindsay; Scalettar, Bethe; Lochner, Janis

2010-10-01

Formation and encoding of long-term memories requires a series of structural changes at synapses, or sites of neuronal communication, in the hippocampus; these changes are mediated by neuromodulatory proteins and serve to strengthen synapses to improve communication. Two prominent neuromodulators, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), are copackaged into secretory granules (SGs) in the body of nerve cells and are transported to distal synapses by motor proteins. At synapses, particularly presynaptic sites, the fate of tPA and BDNF is largely unknown. Motivated by this, and by recent data implicating presynaptic BDNF in early phases of learning, we used fluorescence microscopy to elucidate dynamic properties of presynaptic tPA and BDNF. We find that presynaptic SGs containing tPA and/or BDNF undergo Brownian and anomalous diffusive motion that, in 75% of cases, is so slow that it typically would be classified as immobility. These results suggest that tPA and BDNF are retained at presynaptic sites to facilitate their corelease and role in learning.

Potential of glucans as vaccine adjuvants: A review of the α-glucans case.

PubMed

Moreno-Mendieta, Silvia; Guillén, Daniel; Hernández-Pando, Rogelio; Sánchez, Sergio; Rodríguez-Sanoja, Romina

2017-06-01

α-Glucans are present in virtually all domains of life, and these glucose chains linked by α-1,4- and α-1,6-linked branches form the most important storage carbohydrates in cells. It is likely for this reason that α-glucans are not generally considered as bioactive molecules as β-glucans are. Nevertheless, it is known that depending on their source, many α-glucans play important roles as modulators of immune response. Recent efforts have attempted to elucidate the mechanisms through which α-glucans exert their immunostimulant effects; however, the main challenge is the accurate identification of the receptors of immune cells involved in their recognition. Here, we review the adjuvant properties reported for some polysaccharides and ultimately focus on α-glucans and how their structural characteristics, such as molecular weight, solubility and derivatization, influence their immunostimulatory properties. As a final point, we discuss the potential and associated challenges of using these polysaccharides as adjuvants, particularly in mucosal vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accounting for noise when clustering biological data.

PubMed

Sloutsky, Roman; Jimenez, Nicolas; Swamidass, S Joshua; Naegle, Kristen M

2013-07-01

Clustering is a powerful and commonly used technique that organizes and elucidates the structure of biological data. Clustering data from gene expression, metabolomics and proteomics experiments has proven to be useful at deriving a variety of insights, such as the shared regulation or function of biochemical components within networks. However, experimental measurements of biological processes are subject to substantial noise-stemming from both technical and biological variability-and most clustering algorithms are sensitive to this noise. In this article, we explore several methods of accounting for noise when analyzing biological data sets through clustering. Using a toy data set and two different case studies-gene expression and protein phosphorylation-we demonstrate the sensitivity of clustering algorithms to noise. Several methods of accounting for this noise can be used to establish when clustering results can be trusted. These methods span a range of assumptions about the statistical properties of the noise and can therefore be applied to virtually any biological data source.

Preliminary observations on the effects of milk fortification with conjugated linoleic acid in yogurt preparation

NASA Astrophysics Data System (ADS)

Salamon, R. V.; Albert, I.; András, C. D.; Csapó, J.; Ibănescu, C.

2015-04-01

The fortification and enrichment of food with health benefic natural or natural identical substances creating new functional foods became an important issue for food researchers and processors. However, often occurs that the obtained products (despite of their health benefic activity) cannot be marketed due to strange or accustomed taste and/or texture. The aim of the research was to elucidate the effect of conjugated linoleic acid (CLA) enrichment of raw milk on the rheological properties of the obtained yogurt. The results show that the values of the complex viscosity at 50 rad.s-1 (correlated with the thickness and sliminess of the food gel structures) of the CLA-enriched yogurt was the lowest among the studied samples, meaning the enriched yogurt is more creamy than the commercial products. These observations gave us the hope that, in this case, the texture of enriched product will not present any drawback related to consumer quality judgment.

Fluctuations and symmetries in two-dimensional active gels.

PubMed

Sarkar, N; Basu, A

2011-04-01

Motivated by the unique physical properties of biological active matter, e.g., cytoskeletal dynamics in eukaryotic cells, we set up effective two-dimensional (2d) coarse-grained hydrodynamic equations for the dynamics of thin active gels with polar or nematic symmetries. We use the well-known three-dimensional (3d) descriptions (K. Kruse et al., Eur. Phys. J. E 16, 5 (2005); A. Basu et al., Eur. Phys. J. E 27, 149 (2008)) for thin active-gel samples confined between parallel plates with appropriate boundary conditions to derive the effective 2d constitutive relations between appropriate thermodynamic fluxes and generalised forces for small deviations from equilibrium. We consider three distinct cases, characterised by spatial symmetries and boundary conditions, and show how such considerations dictate the structure of the constitutive relations. We use these to study the linear instabilities, calculate the correlation functions and the diffusion constant of a small tagged particle, and elucidate their dependences on the activity or nonequilibrium drive.

Chemical constituents from Piper hainanense and their cytotoxicities.

PubMed

Shi, Yan-Ni; Xin, Ying; Ling, Yi; Li, Xing-Cong; Hao, Chao-Yun; Zhu, Hong-Tao; Wang, Dong; Yang, Chong-Ren; Xu, Min; Zhang, Ying-Jun

2016-08-01

Two new compounds, (Z,R)-1-phenylethylcinnamate (1) and (1R,2R,3R,6S)-pipoxide (2) were isolated from the aerial part of Piper hainanense, along with 12 known compounds, including nine benzene derivatives (4-11), one isobutylamide (12), and two polyoxygenated cyclohexene derivatives (13-14). Their structures were elucidated on the basis of the HRESIMS, 1D and 2D NMR spectroscopic analyses, and ECD in cases of 2 and 3. The absolute configuration of ellipeiopsol B (3) was determined for the first time. All these compounds 1-14 were reported from the titled plant for the first time. Most of the isolates were tested for their cytotoxicities against five human cancer cell lines. Four of which, 2, 3, 9, 14 showed moderate bioactivities. Among them, the new compound 2 showed potential cytotoxicity against SMMC-7721, MCF-7, and SW-480 with IC50 values of 9.7, 15.0, and 13.2 μM, respectively.

Counting numbers of synaptic proteins: absolute quantification and single molecule imaging techniques

PubMed Central

Patrizio, Angela; Specht, Christian G.

2016-01-01

Abstract. The ability to count molecules is essential to elucidating cellular mechanisms, as these often depend on the absolute numbers and concentrations of molecules within specific compartments. Such is the case at chemical synapses, where the transmission of information from presynaptic to postsynaptic terminals requires complex interactions between small sets of molecules. Be it the subunit stoichiometry specifying neurotransmitter receptor properties, the copy numbers of scaffold proteins setting the limit of receptor accumulation at synapses, or protein packing densities shaping the molecular organization and plasticity of the postsynaptic density, all of these depend on exact quantities of components. A variety of proteomic, electrophysiological, and quantitative imaging techniques have yielded insights into the molecular composition of synaptic complexes. In this review, we compare the different quantitative approaches and consider the potential of single molecule imaging techniques for the quantification of synaptic components. We also discuss specific neurobiological data to contextualize the obtained numbers and to explain how they aid our understanding of synaptic structure and function. PMID:27335891

Counting numbers of synaptic proteins: absolute quantification and single molecule imaging techniques.

PubMed

Patrizio, Angela; Specht, Christian G

2016-10-01

The ability to count molecules is essential to elucidating cellular mechanisms, as these often depend on the absolute numbers and concentrations of molecules within specific compartments. Such is the case at chemical synapses, where the transmission of information from presynaptic to postsynaptic terminals requires complex interactions between small sets of molecules. Be it the subunit stoichiometry specifying neurotransmitter receptor properties, the copy numbers of scaffold proteins setting the limit of receptor accumulation at synapses, or protein packing densities shaping the molecular organization and plasticity of the postsynaptic density, all of these depend on exact quantities of components. A variety of proteomic, electrophysiological, and quantitative imaging techniques have yielded insights into the molecular composition of synaptic complexes. In this review, we compare the different quantitative approaches and consider the potential of single molecule imaging techniques for the quantification of synaptic components. We also discuss specific neurobiological data to contextualize the obtained numbers and to explain how they aid our understanding of synaptic structure and function.

Population trapping: The mechanism for the lost resonance lines in Pm-like ions

NASA Astrophysics Data System (ADS)

Kato, Daiji; Sakaue, Hiroyuki A.; Murakami, Izumi; Nakamura, Nobuyuki

2017-10-01

We report a population kinetics study on line emissions of the Pm-like Bi22+ performed by using a collisional-radiative (CR) model. Population rates of excited levels are analyzed to explain the population trapping in the 4f135s2 state which causes the loss of the 5s - 5p resonance lines in emission spectra. Based on the present analysis, we elucidate why the population trapping is not facilitated for a meta-stable excited level of the Sm-like Bi21+. The emission line spectra are calculated for the Pm-like isoelectronic sequence from Au18+ through W13+ and compared with experimental measurements by electron-beam-ion-traps (EBITs). Structures of the spectra are similar for all of the cases except for calculated W13+ spectra. The calculated spectra are hardly reconciled with the measured W13+ spectrum using the compact electron-beam-ion-trap (CoBIT) [Phys. Rev. A 92 (2015) 022510].

Plankton networks driving carbon export in the oligotrophic ocean

NASA Astrophysics Data System (ADS)

Guidi, L.; Chaffron, S.; Bittner, L.; Eveillard, D.; Raes, J.; Karsenti, E.; Bowler, C.; Gorsky, G.

2016-02-01

The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis that sinks to the deep ocean as particles where it is sequestered. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure and interactions driving the process remain largely uncharacterised. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of the underlying processes. We show that specific plankton communities correlate with carbon export and highlight unexpected and overlooked taxa such as Radiolaria, alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical oligotrophic ocean. Additionally, we show that the relative abundance of just a few bacterial and viral genes can predict most of the variability in carbon export in these regions. Together these results help elucidate ecosystem drivers of the biological carbon pump and present a case study for scaling from genes-to-ecosystems.

Electron solvation and localization at interfaces

NASA Astrophysics Data System (ADS)

Harris, Charles B.; Szymanski, Paul; Garrett-Roe, Sean; Miller, Andre D.; Gaffney, Kelly J.; Liu, Simon H.; Bezel, Ilya

2003-12-01

Two-photon photoemission of thiolate/Ag(111), nitrile/Ag(111), and alcohol/Ag(111) interfaces elucidates electron solvation and localization in two dimensions. For low coverages of thiolates on Ag(111), the occupied (HOMO) and unoccupied (LUMO) electronic states of the sulfer-silver bond are localized due to the lattice gas structure of the adsorbate. As the coverage saturates and the adsorbate-adsorbate nearest neighbor distance decreases, the HOMO and LUMO delocalize across many adsorbate molecules. Alcohol- and nitrile-covered Ag(111) surfaces solvate excess image potential state (IPS) electrons. In the case of alcohol-covered surfaces, this solvation is due to a shift in the local workfunction of the surface. For two-monolayer coverages of nitriles/Ag(111), localization accompanies solvation of the IPS. The size of the localized electron can be estimated by Fourier transformation of the wavefunction from momentum- to position-space. The IPS electron localizes to 15 +/- 4 angstroms full-width at half maximum in the plane of the surface, i.e., to a single lattice site.

Structure-Based Design of Highly Selective Inhibitors of the CREB Binding Protein Bromodomain.

PubMed

Denny, R Aldrin; Flick, Andrew C; Coe, Jotham; Langille, Jonathan; Basak, Arindrajit; Liu, Shenping; Stock, Ingrid; Sahasrabudhe, Parag; Bonin, Paul; Hay, Duncan A; Brennan, Paul E; Pletcher, Mathew; Jones, Lyn H; Chekler, Eugene L Piatnitski

2017-07-13

Chemical probes are required for preclinical target validation to interrogate novel biological targets and pathways. Selective inhibitors of the CREB binding protein (CREBBP)/EP300 bromodomains are required to facilitate the elucidation of biology associated with these important epigenetic targets. Medicinal chemistry optimization that paid particular attention to physiochemical properties delivered chemical probes with desirable potency, selectivity, and permeability attributes. An important feature of the optimization process was the successful application of rational structure-based drug design to address bromodomain selectivity issues (particularly against the structurally related BRD4 protein).

A theoretical probe of high-valence uranium and transuranium silylamides: Structural and redox properties

NASA Astrophysics Data System (ADS)

Zhong, Yu-Xi; Guo, Yuan-Ru; Pan, Qing-Jiang

2016-02-01

Relativistic density functional theory was used to explore the structural and redox properties of 18 prototypical actinyl silylamides including a variation of metals (U, Np and Pu), metal oxidation states (VI and V) and equatorial ligands. A theoretical approach associated with implicit solvation and spin-orbit/multiplet corrections was proved to be reliable. A marked shift of reduction potentials of actinyl silylamides caused by changes of equatorial coordination ligands and implicit solvation was elucidated by analyses of electronic structures and single-electron reduction mechanism.

Isolation and structure of palstatin from the Amazon tree Hymeneae palustris(1).

PubMed

Pettit, George R; Meng, Yanhui; Stevenson, Clare A; Doubek, Dennis L; Knight, John C; Cichacz, Zbigniew; Pettit, Robin K; Chapuis, Jean-Charles; Schmidt, Jean M

2003-02-01

Bioassay (P388 lymphocytic leukemia cell line and human cancer cell lines) guided separation of an extract prepared from the leaves of Hymenaea palustris Ducké led to the isolation of six cancer cell growth inhibitory flavonoids (1-6). The structures were elucidated by HRMS and 1D and 2D NMR spectral analysis. The new flavonolignan 1 designated palstatin proved to be a methoxy structural modification of 5'-methoxyhydnocarpin-D (2). Flavones 1-4 inhibited growth of the pathogenic bacteria Enterococcus faecalis and/or Neisseria gonorrhoeae.

Toward a structural understanding of turbulent drag reduction: nonlinear coherent states in viscoelastic shear flows.

PubMed

Stone, Philip A; Waleffe, Fabian; Graham, Michael D

2002-11-11

Nontrivial steady flows have recently been found that capture the main structures of the turbulent buffer layer. We study the effects of polymer addition on these "exact coherent states" (ECS) in plane Couette flow. Despite the simplicity of the ECS flows, these effects closely mirror those observed experimentally: Structures shift to larger length scales, wall-normal fluctuations are suppressed while streamwise ones are enhanced, and drag is reduced. The mechanism underlying these effects is elucidated. These results suggest that the ECS are closely related to buffer layer turbulence.

Theoretical Neuroanatomy:Analyzing the Structure, Dynamics,and Function of Neuronal Networks

NASA Astrophysics Data System (ADS)

Seth, Anil K.; Edelman, Gerald M.

The mammalian brain is an extraordinary object: its networks give rise to our conscious experiences as well as to the generation of adaptive behavior for the organism within its environment. Progress in understanding the structure, dynamics and function of the brain faces many challenges. Biological neural networks change over time, their detailed structure is difficult to elucidate, and they are highly heterogeneous both in their neuronal units and synaptic connections. In facing these challenges, graph-theoretic and information-theoretic approaches have yielded a number of useful insights and promise many more.

Solid-state NMR and computational studies of 4-methyl-2-nitroacetanilide.

PubMed

Harris, Robin K; Ghi, Phuong Y; Hammond, Robert B; Ma, Cai Yun; Roberts, Kevin J; Yates, Jonathan R; Pickard, Chris J

2006-03-01

Studies on the solid-state structure of two polymorphs of 4-methyl-2-nitroacetanilide (MNA) were conducted using magic-angle spinning (13)C, (15)N and (1)H NMR spectroscopy, together with first-principles computations of NMR shielding (including use of a program that takes explicit account of the translational symmetry inherent in crystalline structures). The effects on (13)C chemical shifts of side-chain rotations have been explored. Information derived from these studies was then incorporated within a systematic space-search methodology for elucidation of trial crystallographic structures from powder XRD.

Mapping magnetoelastic response of terfenol-D ring structure

NASA Astrophysics Data System (ADS)

Youssef, George; Newacheck, Scott; Lopez, Mario

2017-05-01

The magneto-elastic response of a Terfenol-D (Tb.3Dy.7Fe1.92) ring has been experimentally investigated and analyzed. Ring structures give rise to complex behavior based on the interaction of the magnetic field with the material, which is further compounded with anisotropies associated with mechanical and magnetic properties. Discrete strain measurements were used to construct magnetostriction maps, which are used to elucidate the non-uniformity of the strain distribution due to geometrical factors and magnetic field interactions, namely, magnetic shielding and stable onion state in the ring structure.

Self-assembly of chlorophenols in water

PubMed Central

Rogalska, Ewa; Rogalski, Marek; Gulik-Krzywicki, Tadeusz; Gulik, Annette; Chipot, Christophe

1999-01-01

In saturated solutions of some di- and trichlorophenols, structures with complex morphologies, consisting of thin, transparent sheets often coiling into helices and ultimately twisting into filaments, were observed under the optical microscope. Freeze-fracture electron microscopy, x-ray diffraction, phase diagrams, and molecular modeling were performed to elucidate the observed phenomena. Here, we present evidence that the chlorophenols studied, when interacting with water, self-assemble into bilayers. The fact that some chlorophenols form the same supramolecular structures as those described previously for structurally nonrelated surfactants sheds light on the mechanisms of self-assembly. PMID:10359753

Pestalotiopamide E, a new amide from the endophytic fungus Pestalotiopsis sp.

PubMed

Xu, Jing; Lin, Qiang; Wang, Bin; Wray, Victor; Lin, Wen-Han; Proksch, Peter

2011-04-01

Chemical examination of the endophytic fungus Pestalotiopsis sp., isolated from the leaves of the Chinese mangrove Rhizophora mucronata, yielded a new amide called pestalotiopamide E (1). The structure of the new compound was unambiguously elucidated on the basis of extensive spectroscopic data analysis.

Echinopsacetylenes A and B, new thiophenes from Echinops transiliensis

USDA-ARS?s Scientific Manuscript database

Two new polyacetylene thiophenes, echinopsacetylenes A and B (1 and 2), were isolated from the root of Echinops transiliensis. The structures of 1 and 2 were elucidated on the basis of spectroscopic analyses and chemical transformations. Echinopsacetylene A (1) is the first natural product possessin...

INVESTIGATING UNCERTAINTY AND SENSITIVITY IN INTEGRATED MULTIMEDIA ENVIRONMENTAL MODELS: TOOLS FOR 3MRA

EPA Science Inventory

Sufficiently elucidating uncertainty and sensitivity structures in environmental models can be a difficult task, even for low-order, single-media constructs driven by a unique set of site-specific data. The ensuing challenge of examining ever more complex, integrated, higher-ord...

INVESTIGATING UNCERTAINTY AND SENSITIVITY IN INTEGRATED, MULTIMEDIA ENVIRONMENTAL MODELS: TOOLS FOR FRAMES-3MRA

EPA Science Inventory

Elucidating uncertainty and sensitivity structures in environmental models can be a difficult task, even for low-order, single-medium constructs driven by a unique set of site-specific data. Quantitative assessment of integrated, multimedia models that simulate hundreds of sites...

Poecillastrin D: a new cytotoxin of the chondropsin class from marine sponge Jaspis serpentina.

PubMed

Takemoto, Daisaku; Takekawa, Yoshihiko; Soest, Rob W M van; Fusetani, Nobuhiro; Matsunaga, Shigeki

2007-11-01

Poecillastrin D (2) was isolated together with poecillastrin C (1) from the deep sea sponge, Japsis serpentina. Its structure was elucidated to be that of a macrolide lactam by spectroscopic methods. These compounds showed potent cytotoxicity against various tumor cell lines.

A new biflavonyloxymethane from Pongamia pinnata.

PubMed

Ghosh, Anindita; Mandal, Suvra; Banerji, Avijit; Banerji, Julie

2010-08-01

The root bark of Pongamia pinnata Pierre Syn Pongamia glabra (Family: Fabaceae) has afforded a new biflavonyloxymethane, karanjabiflavone, along with a known furanoflavone, pongapin. The structure of this new biflavonyloxymethane was elucidated from extensive spectral studies including 2D-NMR experiments. Both of these compounds possess antioxidant activity.

Modeling the Hydrogen Bond within Molecular Dynamics

ERIC Educational Resources Information Center

Lykos, Peter

2004-01-01

The structure of a hydrogen bond is elucidated within the framework of molecular dynamics based on the model of Rahman and Stillinger (R-S) liquid water treatment. Thus, undergraduates are exposed to the powerful but simple use of classical mechanics to solid objects from a molecular viewpoint.

Keggin-type polyoxometalate nanosheets: synthesis and characterization via scanning transmission electron microscopy.

PubMed

Hiyoshi, Norihito

2018-05-17

Polyoxometalate nanosheets were synthesized at the gas/liquid interface of an aqueous solution of Keggin-type silicotungstic acid, cesium chloride, and n-octylamine. The structure of the nanosheets was elucidated via aberration-corrected scanning transmission electron microscopy at the atomic and molecular levels.

Structural modeling of the AhR:ARNT complex in the bHLH-PASA-PASB region elucidates the key determinants of dimerization.

PubMed

Corrada, Dario; Denison, Michael S; Bonati, Laura

2017-05-02

Elucidation of the dimerization process of the aryl hydrocarbon receptor (AhR) with the AhR nuclear translocator (ARNT) is crucial for understanding the mechanisms underlying the functional activity of AhR, including mediation of the toxicity of environmental contaminants. In this work, for the first time a structural model of the AhR:ARNT dimer encompassing the entire bHLH-PASA-PASB domain region is proposed. It is developed by using a template-based modeling approach, relying on the recently available crystallographic structures of two dimers of homologous systems in the bHLH-PAS family of proteins: the CLOCK:BMAL1 and the HIF2α:ARNT heterodimers. The structural and energetic characteristics of the modeled AhR:ARNT protein-protein interface are determined by evaluating the variations in solvent accessible surface area, the total binding free energy and the per-residue free energy contributions obtained by the MM-GBSA method and the Energy Decomposition Analysis. The analyses of the intricate network of inter-domain interactions at the dimerization interfaces provide insights into the key determinants of dimerization. These are confirmed by comparison of the computational findings with the available experimental mutagenesis and functional analysis data. The results presented here on the AhR:ARNT dimer structure and interactions provide a framework to start analyzing the mechanism of AhR transformation into its functional DNA binding form.

Elucidating Molecular Motion through Structural and Dynamic Filters of Energy-Minimized Conformer Ensembles

PubMed Central

2015-01-01

Complex RNA structures are constructed from helical segments connected by flexible loops that move spontaneously and in response to binding of small molecule ligands and proteins. Understanding the conformational variability of RNA requires the characterization of the coupled time evolution of interconnected flexible domains. To elucidate the collective molecular motions and explore the conformational landscape of the HIV-1 TAR RNA, we describe a new methodology that utilizes energy-minimized structures generated by the program “Fragment Assembly of RNA with Full-Atom Refinement (FARFAR)”. We apply structural filters in the form of experimental residual dipolar couplings (RDCs) to select a subset of discrete energy-minimized conformers and carry out principal component analyses (PCA) to corroborate the choice of the filtered subset. We use this subset of structures to calculate solution T1 and T1ρ relaxation times for 13C spins in multiple residues in different domains of the molecule using two simulation protocols that we previously published. We match the experimental T1 times to within 2% and the T1ρ times to within less than 10% for helical residues. These results introduce a protocol to construct viable dynamic trajectories for RNA molecules that accord well with experimental NMR data and support the notion that the motions of the helical portions of this small RNA can be described by a relatively small number of discrete conformations exchanging over time scales longer than 1 μs. PMID:24479561

Preparation of zein nanoparticles by using solution-enhanced dispersion with supercritical CO2 and elucidation with computational fluid dynamics.

PubMed

Li, Sining; Zhao, Yaping

2017-01-01

Nanoparticles have attracted more and more attention in the medicinal field. Zein is a biomacromolecule and can be used as a carrier for delivering active ingredients to prepare controlled release drugs. In this article, we presented the preparation of zein nanoparticles by solution-enhanced dispersion by supercritical CO 2 (SEDS) approach. Scanning electron microscopy and transmission electron microscopy were applied to characterize the size and morphology of the obtained particles. The nozzle structure and the CO 2 flow rate greatly affected the morphology and the size of the particles. The size of zein was able to be reduced to 50-350 nm according to the different conditions. The morphologies of the resultant zein were either sphere or the filament network consisted of nanoparticles. The influence of the nozzle structure and the CO 2 flow rate on the velocity field was elucidated by using computational fluid dynamics. The nozzle structure and the CO 2 flow rate greatly affected the distribution of the velocity field. However, a similar velocity field could also be obtained when the nozzle structure or the CO 2 flow rate, or both were different. Therefore, the influence of the nozzle structure and the CO 2 flow rate on the size and morphology of the particles, can boil down to the velocity field. The results demonstrated that the velocity field can be a potential criterion for producing nanoparticles with controllable morphology and size, which is useful to scale-up the SEDS process.

SCIENCE FOR INTEGRATED WATERSHED MANAGEMENT: A MULTI-SCALE EXPERIMENTAL CASE STUDY LINKING LAND USE MANAGEMENT PRACTICES AND WATER QUALITY IN SOUTHERN OHIO

EPA Science Inventory

Although it is routine for watershed management programs to coincide the monitoring of land use impacts and water quality at different spatial scales, rarely are the data collected in a manner to elucidate the linkages among ecological systems across a drainage network. There rem...

Primary Discourse and Expressive Oral Language in a Kindergarten Student

ERIC Educational Resources Information Center

Fiano, Darcy A.

2014-01-01

This seven-month ethnographic case study elucidated a kindergarten student's navigation through her first formal schooling experience with relation to expressive oral language. Gee's theory of Discourses and methodology of discourse analysis were used to examine expressive oral language in use. Two discursive contexts germane to…

Asymptomatic Emphysematous Pyelonephritis - Positron Emission Tomography Computerized Tomography Aided Diagnostic and Therapeutic Elucidation

PubMed Central

Pathapati, Deepti; Shinkar, Pawan Gulabrao; kumar, Satya Awadhesh; Jha; Dattatreya, Palanki Satya; Chigurupati, Namrata; Chigurupati, Mohana Vamsy; Rao, Vatturi Venkata Satya Prabhakar

2017-01-01

The authors report an interesting coincidental unearthing by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of a potentially serious medical condition of emphysematous pyelonephritis in a case of nasopharyngeal carcinoma. The management by conservative ureteric stenting and antibiotics was done with gratifying clinical outcome. PMID:28242985

How Young Children Construe Pain Experienced by Self and Others: A Case of Naive Theory

ERIC Educational Resources Information Center

Eilam, Billie; Mattatia, Miri

2015-01-01

We investigated young children's construal of pain in relation to (a) the self, (b) other humans, and (c) animals, plants, and objects, to elucidate children's cognitive understanding of this complex, abstract, subjective concept. We interviewed 17 Kindergarten students using a variety of non-painful stimuli and procedures to prompt discussion of…

Physiological responses to prolonged bed rest in humans: A compendium of research, 1981-1988

NASA Technical Reports Server (NTRS)

Luu, Phuong B.; Ortiz, Vanessa; Barnes, Paul R.; Greenleaf, John E.

1990-01-01

Clinical observations and results form more basic studies that help to elucidate the physiological mechanisms of the adaptation of humans to prolonged bed rest. If the authors' abstract or summary was appropriate, it was included. In some cases a more detailed synopsis was provided under the subheadings of purpose, methods, results, and conclusions.

Corruption Risks of Private Tutoring: Case of Georgia

ERIC Educational Resources Information Center

Kobakhidze, Magda Nutsa

2014-01-01

The paper focuses on teacher-supplied private tutoring in the context of post-Soviet Georgia, and elucidates the ways in which teacher-supplied private tutoring can be related to educational corruption. The paper draws on data from in-depth interviews of 18 school teachers in different parts of Georgia in 2013. The findings of the qualitative…

Congenital dacryocystocele.

PubMed

Harris, G J; DiClementi, D

1982-11-01

Four cases of congenital lacrimal sac distention were managed in an initially conservative manner to further elucidate the natural history of the condition and to formulate a more systematic approach to its treatment. In three cases, the abnormality resolved without nasolacrimal duct probing, with no adverse sequelae. In one case, dacryocystitis caused by Serratia marcescens, corneal astigmatism, and severe canthal distortion prompted surgical intervention. The management of individual cases of dacryocystocele should be influenced by the presence of inflammation, the virulence of any infecting organisms, the induction of astigmatism and anisometropia, and the degree of canthal distortion. Dacryocystocele appears to be a more specific term for lacrimal sac distention than either amniotocele or mucocele, and is not restricted to only one source of its fluid contents.

Fungal and herbivore elicitation of a newly identified maize sesquiterpenoid, zealexin A4, is constrained by abiotic stress

USDA-ARS?s Scientific Manuscript database

The existence of microbe- or abiotic stress-inducible antimicrobials, termed phytoalexins, has only recently been discovered in maize. Identification and structural elucidation of the labdane-related diterpenoid kauralexins and sesquiterpenoid zealexins has collectively resulted in 10 novel pathogen...

Structural characteristics of the molecular species of tetraacylglycerols in lesquerella (Physaria fendleri) oil elucidated by mass spectrometry

USDA-ARS?s Scientific Manuscript database

Tetraacylglycerols (triacylglycerol estolides) contain an acylacyl chain (one fatty acid attached to the hydroxyl group of another fatty acid attached to the glycerol backbone) and have different physical properties from those of triacylglycerols. Tetraacylglycerols can be used in industry such as t...

Sesquiterpenoids from Vernonia cinerea.

PubMed

Chen, Xin; Zhan, Zha-Jun; Yue, Jian-Min

2006-02-01

A new sesquiterpenoid, vernocinolide A (1), as well as ten known ones (2-11), were isolated from the ethyl acetate soluble fraction of Vernonia cinerea. The structure of vernocinolide A (1) was elucidated by spectroscopic methods. Among the known sesquiterpenoids, nine of them were isolated from this plant for the first time.

Three new norsesquiterpenoids from the seeds of Alpinia galanga.

PubMed

Bian, Meng-Qin; Kang, Jie; Wang, Hong-Qing; Zhang, Qing-Jian; Liu, Chao; Chen, Ruo-Yun

2014-01-01

From the seeds of Alpinia galanga Willd., three new norsesquiterpenoid racemic mixtures, galanols A-C (1-3) were isolated, along with three known sesquiterpenoids (4-6). Their structures were elucidated by means of UV, IR, HR-ESI-MS, 1D NMR and 2D NMR spectroscopic data.

SORPTION OF LEAD ON A RUTHENIUM COMPOUND: A MACROSCOPIC AND MICROSCOPIC STUDY

EPA Science Inventory

The objective of this study was to elucidate the sorption mechanism of Pb on the high-affinity ruthenium compound with time at pH 6 employing batch methods and X-ray absorption fine structure (XAFS) and X-ray diffraction (XRD) spectroscopies. For the spectroscopic studies, Pb so...

Commentary: Elucidating the Neural Correlates of Early Childhood Memory

ERIC Educational Resources Information Center

Mullally, Sinead L.

2015-01-01

Both episodic memory and the key neural structure believed to support it, namely the hippocampus, are believed to undergo protracted periods of postnatal developmental. Critically however, the hippocampus is comprised of distinct subfields and circuits, and these circuits appear to mature at different rates (Lavenex and Banta Lavenex, 2013).…

Unveiling the complexity of the maize transcriptome by single-molecule long-read sequencing

USDA-ARS?s Scientific Manuscript database

Zea mays is an important crop species and genetic model for elucidating transcriptional networks in plants. Uncertainties about the complete structure of mRNA transcripts, particularly with respect to alternatively spliced isoforms, limit the progress of research in this system. In this study, we us...