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Sample records for non-proline cis peptide

  1. PBOND: web server for the prediction of proline and non-proline cis/trans isomerization.

    Science.gov (United States)

    Exarchos, Konstantinos P; Exarchos, Themis P; Papaloukas, Costas; Troganis, Anastassios N; Fotiadis, Dimitrios I

    2009-09-01

    PBOND is a web server that predicts the conformation of the peptide bond between any two amino acids. PBOND classifies the peptide bonds into one out of four classes, namely cis imide (cis-Pro), cis amide (cis-nonPro), trans imide (trans-Pro) and trans amide (trans-nonPro). Moreover, for every prediction a reliability index is computed. The underlying structure of the server consists of three stages: (1) feature extraction, (2) feature selection and (3) peptide bond classification. PBOND can handle both single sequences as well as multiple sequences for batch processing. The predictions can either be directly downloaded from the web site or returned via e-mail. The PBOND web server is freely available at http://195.251.198.21/pbond.html.

  2. PBOND: Web Server for the Prediction of Proline and Non-Proline cis / trans Isomerization

    Institute of Scientific and Technical Information of China (English)

    Konstantinos P. Exarchos; Themis P. Exarchos; Costas Papaloukas; Anastassios N. Troganis; Dimitrios I. Fotiadis

    2009-01-01

    PBOND is a web server that predicts the conformation of the peptide bond be-tween any two amino acids. PBOND classifies the peptide bonds into one out of four classes, namely cis imide(cis-Pro), cis amide(cis-nonPro), trans imide (trans-Pro)and trans amide(trans-nonPro). Moreover, for every prediction a reliability index is computed. The underlying structure of the server consists of three stages:(1)feature extraction,(2)feature selection and(3)peptide bond clas-sification. PBOND can handle both single sequences as well as multiple sequences for batch processing. The predictions can either be directly downloaded from the web site or returned via e-mail. The PBOND web server is freely available at http://195.251.198.21/pbond.html.

  3. cis-Peptide Bonds: A Key for Intestinal Permeability of Peptides? .

    Science.gov (United States)

    Marelli, Udaya Kiran; Ovadia, Oded; Frank, Andreas Oliver; Chatterjee, Jayanta; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst

    2015-10-19

    Recent structural studies on libraries of cyclic hexapeptides led to the identification of common backbone conformations that may be instrumental to the oral availability of peptides. Furthermore, the observation of differential Caco-2 permeabilities of enantiomeric pairs of some of these peptides strongly supports the concept of conformational specificity driven uptake and also suggests a pivotal role of carrier-mediated pathways for peptide transport, especially for scaffolds of polar nature. This work presents investigations on the Caco-2 and PAMPA permeability profiles of 13 selected N-methylated cyclic pentaalanine peptides derived from the basic cyclo(-D-Ala-Ala4 -) template. These molecules generally showed moderate to low transport in intestinal epithelia with a few of them exhibiting a Caco-2 permeability equal to or slightly higher than that of mannitol, a marker for paracellular permeability. We identified that the majority of the permeable cyclic penta- and hexapeptides possess an N-methylated cis-peptide bond, a structural feature that is also present in the orally available peptides cyclosporine A and the tri-N-methylated analogue of the Veber-Hirschmann peptide. Based on these observations it appears that the presence of N-methylated cis-peptide bonds at certain locations may promote the intestinal permeability of peptides through a suitable conformational preorganization.

  4. Insect kinin analogs with cis-peptide bond motif 4-aminopyroglutamate: Optimal stereochemistry

    Science.gov (United States)

    The insect kinins are present in a wide variety of insects and function as potent diuretic peptides, though they are subject to rapid degradation by internal peptidases. Insect kinin analogs incorporating stereochemical variants of (2S,4S)-4-aminopyroglutamate (APy), a cis-peptide bond motif, demon...

  5. Triple Effect of Mimetic Peptides Interfering with Neural Cell Adhesion Molecule Homophilic Cis Interactions

    DEFF Research Database (Denmark)

    Li, S. Z.; Kolkova, Kateryna; Rudenko, Olga;

    2005-01-01

    The neural cell adhesion molecule (NCAM) is pivotal in neural development, regeneration, and learning. Here we characterize two peptides, termed P1-B and P2, derived from the homophilic binding sites in the first two N-terminal immunoglobulin (Ig) modules of NCAM, with regard to their effects...... on neurite extension and adhesion. To evaluate how interference of these mimetic peptides with NCAM homophilic interactions in cis influences NCAM binding in trans, we employed a coculture system in which PC12-E2 cells were grown on monolayers of fibroblasts with or without NCAM expression and the rate...... of neurite outgrowth subsequently was analyzed. P2, but not P1-B, induced neurite outgrowth in the absence of NCAM binding in trans. When PC12-E2 cells were grown on monolayers of NCAM-expressing fibroblasts, the effect of both P1-B and P2 on neurite outgrowth was dependent on peptide concentrations. P1-B...

  6. Multiple gas-phase conformations of proline-containing peptides: is it always cis/trans isomerization?

    Science.gov (United States)

    Lietz, Christopher B; Chen, Zhengwei; Yun Son, Chang; Pang, Xueqin; Cui, Qiang; Li, Lingjun

    2016-08-02

    Ion mobility-mass spectrometry (IM-MS) is often employed to look at the secondary, tertiary, and quaternary structures of naked peptides and proteins in the gas-phase. Recently, it has offered a unique glimpse into proline-containing peptides and their cis/trans Xxx-Pro isomers. An experimental "signature" has been identified wherein a proline-containing peptide has its Pro residues substituted with another amino acid and the presence or absence of conformations in the IM-MS spectra is observed. Despite the high probability that one could attribute these conformations to cis/trans isomers, it is also possible that cis/trans isomers are not the cause of the additional conformations in proline-containing peptides. However, the experimental evidence of such a system has not been demonstrated or reported. Herein, we present the IM-MS analysis of Neuropeptide Y's wild-type (WT) signal sequence and Leu7Pro (L7P) mutant. Although comparison of arrival times and collision cross-sections of [M + 4H](4+) ions yields the cis/trans "signature", molecular dynamics indicates that a cis-Pro7 is not very stable and that trans-Pro7 conformations of the same cross-section arise with equal frequency. We believe that this work further underscores the importance of theoretical calculations in IM-MS structural assignments.

  7. Multiple gas-phase conformations of proline-containing peptides: Is it always cis/trans isomerization?

    OpenAIRE

    Lietz, Christopher B.; Chen, Zhengwei; Son, Chang Yun; Pang, Xueqin; Cui, Qiang; Li, Lingjun

    2016-01-01

    Ion mobility-mass spectrometry (IM-MS) is often employed to look at the secondary, tertiary, and quaternary structure of naked peptides and proteins in the gas-phase. Recently, it has offered a unique glimpse into proline-containing peptides and their cis/trans Xxx-Pro isomers. An experimental “signature” has been identified wherein a proline-containing peptide has its Pro residues substituted with another amino acid and the presence or absence of conformations in the IM-MS spectra are observ...

  8. Detection of discriminative sequence patterns in the neighborhood of proline cis peptide bonds and their functional annotation

    Directory of Open Access Journals (Sweden)

    Papaloukas Costas

    2009-04-01

    Full Text Available Abstract Background Polypeptides are composed of amino acids covalently bonded via a peptide bond. The majority of peptide bonds in proteins is found to occur in the trans conformation. In spite of their infrequent occurrence, cis peptide bonds play a key role in the protein structure and function, as well as in many significant biological processes. Results We perform a systematic analysis of regions in protein sequences that contain a proline cis peptide bond in order to discover non-random associations between the primary sequence and the nature of proline cis/trans isomerization. For this purpose an efficient pattern discovery algorithm is employed which discovers regular expression-type patterns that are overrepresented (i.e. appear frequently repeated in a set of sequences. Four types of pattern discovery are performed: i exact pattern discovery, ii pattern discovery using a chemical equivalency set, iii pattern discovery using a structural equivalency set and iv pattern discovery using certain amino acids' physicochemical properties. The extracted patterns are carefully validated using a specially implemented scoring function and a significance measure (i.e. log-probability estimate indicative of their specificity. The score threshold for the first three types of pattern discovery is 0.90 while for the last type of pattern discovery 0.80. Regarding the significance measure, all patterns yielded values in the range [-9, -31] which ensure that the derived patterns are highly unlikely to have emerged by chance. Among the highest scoring patterns, most of them are consistent with previous investigations concerning the neighborhood of cis proline peptide bonds, and many new ones are identified. Finally, the extracted patterns are systematically compared against the PROSITE database, in order to gain insight into the functional implications of cis prolyl bonds. Conclusion Cis patterns with matches in the PROSITE database fell mostly into two

  9. Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?

    Science.gov (United States)

    Siltari, Aino; Viitanen, Riikka; Kukkurainen, Sampo; Vapaatalo, Heikki; Valjakka, Jarkko

    2014-01-01

    Background The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inhibition of angiotensin-converting enzyme 1 (ACE-1) has been suggested as the explanation for these antihypertensive and beneficial vascular effects. Previously, human umbilical vein endothelial cells (HUVEC) have not been used to test ACE-1 inhibiting properties of casein derived tripeptides in vasculature. Purpose We focused on the cis/trans configurations of the peptide bonds in proline-containing tripeptides in order to discover whether the different structural properties of these peptides influence their activity in ACE-1 inhibition. We hypothesized that the configuration of proline-containing peptides plays a significant role in enzyme inhibition. Methods AutoDock 4.2 docking software was used to predict suitable peptide bond configurations of the tripeptides. Besides modeling studies, we completed ACE-1 activity measurements in vitro using HUVEC cultures. Results In HUVEC cells, both IPP and VPP inhibited ACE-1. Based on molecular docking studies, we propose that in ACE-1 inhibition IPP and VPP share a similar cis configuration between the first aliphatic (isoleucine or valine) and the second (proline) amino acid residues and more different configurations between two proline residues. In vivo experiments are needed to validate the significance of the present findings. PMID:24596454

  10. Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?

    Directory of Open Access Journals (Sweden)

    Siltari A

    2014-02-01

    Full Text Available Aino Siltari,1 Riikka Viitanen,2 Sampo Kukkurainen,2 Heikki Vapaatalo,1 Jarkko Valjakka2 1Institute of Biomedicine, Pharmacology, University of Helsinki, Finland; 2BioMediTech, Institute of Biomedical Technology, University of Tampere, Finland Background: The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP and valine-proline-proline (VPP have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inhibition of angiotensin-converting enzyme 1 (ACE-1 has been suggested as the explanation for these antihypertensive and beneficial vascular effects. Previously, human umbilical vein endothelial cells (HUVEC have not been used to test ACE-1 inhibiting properties of casein derived tripeptides in vasculature. Purpose: We focused on the cis/trans configurations of the peptide bonds in proline-containing tripeptides in order to discover whether the different structural properties of these peptides influence their activity in ACE-1 inhibition. We hypothesized that the configuration of proline-containing peptides plays a significant role in enzyme inhibition. Methods: AutoDock 4.2 docking software was used to predict suitable peptide bond configurations of the tripeptides. Besides modeling studies, we completed ACE-1 activity measurements in vitro using HUVEC cultures. Results: In HUVEC cells, both IPP and VPP inhibited ACE-1. Based on molecular docking studies, we propose that in ACE-1 inhibition IPP and VPP share a similar cis configuration between the first aliphatic (isoleucine or valine and the second (proline amino acid residues and more different configurations between two proline residues. In vivo experiments are needed to validate the significance of the present findings. Keywords: ACE inhibition, Autodock modeling, Ile-Pro-Pro, Val-Pro-Pro, vascular function

  11. Interplay between metal binding and cis/trans isomerization in legume lectins: structural and thermodynamic study of P. angolensis lectin.

    Science.gov (United States)

    Garcia-Pino, Abel; Buts, Lieven; Wyns, Lode; Loris, Remy

    2006-08-04

    The interplay between metal binding, carbohydrate binding activity, stability and structure of the lectin from Pterocarpus angolensis was investigated. Removal of the metals leads to a more flexible form of the protein with significantly less conformational stability. Crystal structures of this metal-free form show significant structural rearrangements, although some structural features that allow the binding of sugars are retained. We propose that substitution of an asparagine residue at the start of the C-terminal beta-strand of the legume lectin monomer hinders the trans-isomerization of the cis-peptide bond upon demetallization and constitutes an intramolecular switch governing the isomer state of the non-proline bond and ultimately the lectin phenotype.

  12. CIS overtakes poly; CIS ueberholt Poly

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzburger, Heiko

    2013-10-01

    The price competition of polycrystalline solar modules makes life difficult for the manufacturers. But with innovations they are able to compete in the market. In Germany especially CIS plays a role. [German] Die Preiskonkurrenz der polykristallinen Solarmodule macht den Herstellern das Leben schwer. Doch mit Innovationen schaffen sie es, sich am Markt zu behaupten. In Deutschland spielt vor allem CIS eine Rolle.

  13. The twilight zone of cis element alignments.

    Science.gov (United States)

    Sebastian, Alvaro; Contreras-Moreira, Bruno

    2013-02-01

    Sequence alignment of proteins and nucleic acids is a routine task in bioinformatics. Although the comparison of complete peptides, genes or genomes can be undertaken with a great variety of tools, the alignment of short DNA sequences and motifs entails pitfalls that have not been fully addressed yet. Here we confront the structural superposition of transcription factors with the sequence alignment of their recognized cis elements. Our goals are (i) to test TFcompare (http://floresta.eead.csic.es/tfcompare), a structural alignment method for protein-DNA complexes; (ii) to benchmark the pairwise alignment of regulatory elements; (iii) to define the confidence limits and the twilight zone of such alignments and (iv) to evaluate the relevance of these thresholds with elements obtained experimentally. We find that the structure of cis elements and protein-DNA interfaces is significantly more conserved than their sequence and measures how this correlates with alignment errors when only sequence information is considered. Our results confirm that DNA motifs in the form of matrices produce better alignments than individual sequences. Finally, we report that empirical and theoretically derived twilight thresholds are useful for estimating the natural plasticity of regulatory sequences, and hence for filtering out unreliable alignments.

  14. COMPENDEX/TEXT-PAC: CIS.

    Science.gov (United States)

    Standera, Oldrich

    This report evaluates the engineering information services provided by the University of Calgary since implementation of the COMPENDEX (tape service of Engineering Index, Inc.) service using the IBM TEXT-PAC system. Evaluation was made by a survey of the users of the Current Information Selection (CIS) service, the interaction between the system…

  15. cis-Apa: a practical linker for the microwave-assisted preparation of cyclic pseudopeptides via RCM cyclative cleavage.

    Science.gov (United States)

    Baron, Alice; Verdié, Pascal; Martinez, Jean; Lamaty, Frédéric

    2011-02-04

    A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.

  16. Cis-Lunar Base Camp

    Science.gov (United States)

    Merrill, Raymond G.; Goodliff, Kandyce E.; Mazanek, Daniel D.; Reeves, John D., Jr.

    2012-01-01

    Historically, when mounting expeditions into uncharted territories, explorers have established strategically positioned base camps to pre-position required equipment and consumables. These base camps are secure, safe positions from which expeditions can depart when conditions are favorable, at which technology and operations can be tested and validated, and facilitate timely access to more robust facilities in the event of an emergency. For human exploration missions into deep space, cis-lunar space is well suited to serve as such a base camp. The outer regions of cis-lunar space, such as the Earth-Moon Lagrange points, lie near the edge of Earth s gravity well, allowing equipment and consumables to be aggregated with easy access to deep space and to the lunar surface, as well as more distant destinations, such as near-Earth Asteroids (NEAs) and Mars and its moons. Several approaches to utilizing a cis-lunar base camp for sustainable human exploration, as well as some possible future applications are identified. The primary objective of the analysis presented in this paper is to identify options, show the macro trends, and provide information that can be used as a basis for more detailed mission development. Compared within are the high-level performance and cost of 15 preliminary cis-lunar exploration campaigns that establish the capability to conduct crewed missions of up to one year in duration, and then aggregate mass in cis-lunar space to facilitate an expedition from Cis-Lunar Base Camp. Launch vehicles, chemical propulsion stages, and electric propulsion stages are discussed and parametric sizing values are used to create architectures of in-space transportation elements that extend the existing in-space supply chain to cis-lunar space. The transportation options to cis-lunar space assessed vary in efficiency by almost 50%; from 0.16 to 0.68 kg of cargo in cis-lunar space for every kilogram of mass in Low Earth Orbit (LEO). For the 15 cases, 5-year campaign

  17. A method for selecting cis-acting regulatory sequences that respond to small molecule effectors

    Directory of Open Access Journals (Sweden)

    Allas Ülar

    2010-08-01

    Full Text Available Abstract Background Several cis-acting regulatory sequences functioning at the level of mRNA or nascent peptide and specifically influencing transcription or translation have been described. These regulatory elements often respond to specific chemicals. Results We have developed a method that allows us to select cis-acting regulatory sequences that respond to diverse chemicals. The method is based on the β-lactamase gene containing a random sequence inserted into the beginning of the ORF. Several rounds of selection are used to isolate sequences that suppress β-lactamase expression in response to the compound under study. We have isolated sequences that respond to erythromycin, troleandomycin, chloramphenicol, meta-toluate and homoserine lactone. By introducing synonymous and non-synonymous mutations we have shown that at least in the case of erythromycin the sequences act at the peptide level. We have also tested the cross-activities of the constructs and found that in most cases the sequences respond most strongly to the compound on which they were isolated. Conclusions Several selected peptides showed ligand-specific changes in amino acid frequencies, but no consensus motif could be identified. This is consistent with previous observations on natural cis-acting peptides, showing that it is often impossible to demonstrate a consensus. Applying the currently developed method on a larger scale, by selecting and comparing an extended set of sequences, might allow the sequence rules underlying the activity of cis-acting regulatory peptides to be identified.

  18. cis-2,6-Dibenzylcyclohexanone

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available In the title compound, C20H22O, the molecule is a meso isomer with the two benzyl groups cis to each other. The central cyclohexanone ring adopts a chair conformation. The molecule lies on a noncrystallographic mirror plane and the dihedral angles of the benzyl groups with respect to the ketone moiety are 88.06 (6 and 89.07 (6°.

  19. The Community Intercomparison Suite (CIS)

    Science.gov (United States)

    Watson-Parris, Duncan; Schutgens, Nick; Cook, Nick; Kipling, Zak; Kershaw, Phil; Gryspeerdt, Ed; Lawrence, Bryan; Stier, Philip

    2017-04-01

    Earth observations (both remote and in-situ) create vast amounts of data providing invaluable constraints for the climate science community. Efficient exploitation of these complex and highly heterogeneous datasets has been limited however by the lack of suitable software tools, particularly for comparison of gridded and ungridded data, thus reducing scientific productivity. CIS (http://cistools.net) is an open-source, command line tool and Python library which allows the straight-forward quantitative analysis, intercomparison and visualisation of remote sensing, in-situ and model data. The CIS can read gridded and ungridded remote sensing, in-situ and model data - and many other data sources 'out-of-the-box', such as ESA Aerosol and Cloud CCI product, MODIS, Cloud CCI, Cloudsat, AERONET. Perhaps most importantly however CIS also employs a modular plugin architecture to allow for the reading of limitless different data types. Users are able to write their own plugins for reading the data sources which they are familiar with, and share them within the community, allowing all to benefit from their expertise. To enable the intercomparison of this data the CIS provides a number of operations including: the aggregation of ungridded and gridded datasets to coarser representations using a number of different built in averaging kernels; the subsetting of data to reduce its extent or dimensionality; the co-location of two distinct datasets onto a single set of co-ordinates; the visualisation of the input or output data through a number of different plots and graphs; the evaluation of arbitrary mathematical expressions against any number of datasets; and a number of other supporting functions such as a statistical comparison of two co-located datasets. These operations can be performed efficiently on local machines or large computing clusters - and is already available on the JASMIN computing facility. A case-study using the GASSP collection of in-situ aerosol observations

  20. Total synthesis and stereochemical assignment of cis-uvariamicin I and cis-reticulatacin.

    Science.gov (United States)

    Abdel Ghani, Sherif B; Chapman, James M; Figadère, Bruno; Herniman, Julie M; Langley, G John; Niemann, Scott; Brown, Richard C D

    2009-09-18

    Diastereoisomeric mixtures of cis-uvariamicin I (15R,16R,19S,20S,36S and 15S,16S,19R,20R,36S) and cis-reticulatacin (17R,18R,21S,22S,36S and 17S,18S,21R,22R,36S) were synthesized to determine the stereochemistry of the natural products isolated from Annona muricata. It was not possible to resolve a mixture of the four synthetic isomers using chiral HPLC, but the mixed isomers could be distinguished using chiral HPLC EIMS with extracted fragment ion analysis. Comparison of synthetic standards with the natural isolate revealed that cis-uvariamicin I and cis-reticulatacin are present in nature as mixtures of threo-cis-threo diastereoisomers. It is suggested that the nomenclature for the natural products is amended as follows: (15R,16R,19S,20S,36S)-cis-uvariamicin I (cis-uvariamicin IA); (15S,16S,19R,20R,36S)-cis-uvariamicin I (cis-uvariamicin IB); (17R,18R,21S,22S,36S)-cis-reticulatacin (cis-reticulatacin A); (17S,18S,21R,22R,36S)-cis-reticulatacin (cis-reticulatacin B).

  1. Feature ratification procedures in some CIS countries

    Directory of Open Access Journals (Sweden)

    Eldar R. Hisamov

    2011-04-01

    Full Text Available This article attempts a comparative analysis of legislative procedures for the ratification of international treaties in various countries of the Commonwealth of Independent States (CIS.

  2. A cis-dibromorhenium(V iminophenolato complex

    Directory of Open Access Journals (Sweden)

    Abubak’r Abrahams

    2008-08-01

    Full Text Available The complex cis-[ReOBr2(msa(PPh3](1 was prepared from trans-[ReOBr3(PPh32] and 2-(1-iminoethylphenol (Hmsa in acetonitrile. An X-ray crystallographic study shows that the two bromides are coordinated cis to each other in the equatorial plane cis to the oxo group. DFT calculations on 1 and its trans isomer show that the energy difference between the HOMO and LUMO in the cis isomer is smaller than that in the trans.

  3. Communications and Information Sharing (CIS) Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — TheCommunications and Information Sharing (CIS) Laboratory is a Public Safety interoperable communications technology laboratory with analog and digital radios, and...

  4. Disruption of the 11-cis-Retinol Dehydrogenase Gene Leads to Accumulation of cis-Retinols and cis-Retinyl Esters

    OpenAIRE

    Driessen, Carola A. G. G.; Winkens, Huub J.; Hoffmann, Kirstin; Kuhlmann, Leonoor D.; Janssen, Bert P. M.; van Vugt, Anke H M; Van Hooser, J. Preston; Wieringa, B. E.; Deutman, August F; Palczewski, Krzysztof; Ruether, Klaus; Janssen, Jacques J. M.

    2000-01-01

    To elucidate the possible role of 11-cis-retinol dehydrogenase in the visual cycle and/or 9-cis-retinoic acid biosynthesis, we generated mice carrying a targeted disruption of the 11-cis-retinol dehydrogenase gene. Homozygous 11-cis-retinol dehydrogenase mutants developed normally, including their retinas. There was no appreciable loss of photoreceptors. Recently, mutations in the 11-cis-retinol dehydrogenase gene in humans have been associated with fundus albipunctatus. In 11-cis-retinol deh...

  5. Cis phosphorylated tau as the earliest detectable pathogenic conformation in Alzheimer disease, offering novel diagnostic and therapeutic strategies.

    Science.gov (United States)

    Nakamura, Kazuhiro; Zhen Zhou, Xiao; Ping Lu, Kun

    2013-01-01

    After protein phosphorylation on certain serine or threonine residues preceding a proline (pSer/Thr-Pro), the function of certain phosphorylated protein is further regulated by cis-trans conformational change. Due to the lack of any tool to detect such two conformations in cells, however, it is not even known whether any cis or trans conformation exists in vivo, not to mention their conformation-specific functions or regulation. We developed a novel peptide chemistry technology to generate the first pair of antibodies that can distinguish cis from trans pThr231-Pro tau. Cis, but not trans, pThr231-tau appears early in mild cognitive impairment (MCI) neurons and further accumulates in only degenerating neurons as Alzheimer disease (AD) progresses, localizing to dystrophic neurites, which are known to correlate well with memory loss. Unlike trans p-tau, the cis cannot promote microtubule assembly, and is more resistant to dephosphorylation and degradation and more prone to aggregation. Pin1 accelerates cis to trans isomerization to prevent tau pathology in AD. Thus, during MCI and AD development, cis pThr231-Pro tau is the earliest detectable pathogenic tau conformation and antibodies and vaccines against the pathogenic cis p-tau may be used for the early diagnosis and treatment of AD. These findings offer in vivo approach to study conformational regulation of Pro-directed phosphorylation signaling.

  6. cis sequence effects on gene expression

    Directory of Open Access Journals (Sweden)

    Jacobs Kevin

    2007-08-01

    Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

  7. Conformational preferences and prolyl cis-trans isomerization of phosphorylated Ser/Thr-Pro motifs.

    Science.gov (United States)

    Byun, Byung Jin; Kang, Young Kee

    2010-04-01

    The conformational study on Ac-pSer-Pro-NHMe and Ac-pThr-Pro-NHMe peptides has been carried out using hybrid density functional methods with the implicit solvation reaction field theory at the B3LYP/ 6-311++G(d,p)//B3LYP/6-31+G(d) level of theory in the gas phase and in solution (chloroform and water). For both pSer-Pro and pThr-Pro peptides in the gas phase and in chloroform, the most preferred conformation has the alpha-helical structure for the pSer/pThr residue, the down-puckered polyproline I structure for the Pro residue, and the cis prolyl peptide bond between the two residues, in which two hydrogen bonds between the phosphate oxygens with the backbone N--H groups seem to play a role. However, the trans conformations that have a single hydrogen bond of the phosphate oxygen with either of two backbone N--H groups become most preferred for both peptides in water. This is because the hydration free energy of the anionic oxygen of the phosphate group is expected to dramatically decrease for the cis conformation upon formation of the hydrogen bond with the backbone N--H groups. These calculated results are consistent with the observations by NMR and IR experiments, suggesting the existence of hydrogen bonds between the charged phosphoryl group and the backbone amide protons in solution. The calculated cis populations of 14.7 and 14.2% and rotational barriers of 19.87 and 20.57 kcal/mol to the cis-to-trans isomerization for pSer-Pro and pThr-Pro peptides in water, respectively, are consistent with the observed values for pSer-Pro and pThr-Pro containing peptides from NMR experiments. However, the hydrogen bond between the prolyl nitrogen and the following amide N--H group, which was suggested to be capable of catalyzing the prolyl isomerization, does not play a role in stabilizing the preferred transition state for the pSer/pThr-Pro peptides in water. Instead, the amide hydrogen of the NHMe group is involved in a bifurcated hydrogen bond with the anionic oxygen

  8. Cis and Trans Isomers of Cycloalkenes

    Science.gov (United States)

    Barrows, Susan E.; Eberlein, Thomas H.

    2005-09-01

    As a rule, a trans disubstituted alkene is more stable than the corresponding cis isomer. For cycloalkenes of fewer than eleven members, cis isomers are more stable than their trans counterparts. Although this exception to the normal rule is occasionally noted in beginning organic chemistry textbooks, it is often done without a careful analysis of the reasons behind it. The purpose of this article is to provide that analysis. In order for a cycloalkene to accommodate a trans double bond one or more of the following nonideal geometries must occur: a twisted π bond; pyramidal sp 2 -carbon atoms; nonideal sp 3 bond angles; or longer than normal C C single and double bonds. This article provides a list of experimentally determined relative energies of the cis and trans isomers within the series cycloheptene cycloundecene, along with computationally derived energies at several levels of theory. It also examines the geometric distortions through which cycloalkenes relieve the strain introduced by a trans double bond.

  9. Cis-regulatory mutations in human disease.

    Science.gov (United States)

    Epstein, Douglas J

    2009-07-01

    Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant of human disease susceptibility. The diversity of human genetic diseases attributed, in whole or in part, to mutations in non-coding regulatory sequences is on the rise. Improvements in genome-wide methods of associating genetic variation with human disease and predicting DNA with cis-regulatory potential are two of the major reasons for these recent advances. This review will highlight select examples from the literature that have successfully integrated genetic and genomic approaches to uncover the molecular basis by which cis-regulatory mutations alter gene expression and contribute to human disease. The fine mapping of disease-causing variants has led to the discovery of novel cis-acting regulatory elements that, in some instances, are located as far away as 1.5 Mb from the target gene. In other cases, the prior knowledge of the regulatory landscape surrounding the gene of interest aided in the selection of enhancers for mutation screening. The success of these studies should provide a framework for following up on the large number of genome-wide association studies that have identified common variants in non-coding regions of the genome that associate with increased risk of human diseases including, diabetes, autism, Crohn's, colorectal cancer, and asthma, to name a few.

  10. Précis de grammaire

    CERN Document Server

    Chollet, Isabelle

    2009-01-01

    Le Précis de grammaire est tout particulièrement destiné aux apprenants de français langue étrangère, quel que soit leur niveau. Cet ouvrage propose de fournir une réponse claire à tous les problèmes grammaticaux que rencontrent les étudiants étrangers. Axées sur la communication, les explications sont accompagnées d'exemples simples et de mises en situation. La forme et le sens sont donc privilégiés pour faire de ce précis une véritable grammaire de référence. Le précis de grammaire est composé de cinq parties comprenant chacune plusieurs chapitres : La phrase ; Les phrases complexes ; Les parties du discours ; Les relations logiques ; Le système verbal. Les chapitres comportent de nombreux renvois à d'autres chapitres. En début d'ouvrage, un sommaire détaillé présente l'ensemble du précis et donne une indication de niveau (selon le classement du Cadre européen de référence pour les langues) : de A l à C l. En fin d'ouvrage, un index permet de trouver très facilement un mot (...

  11. Statistical significance of cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Smith Andrew D

    2007-01-01

    Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

  12. PDSS/IMC CIS user's guide

    Science.gov (United States)

    1984-01-01

    The Spacelab Payload Development Support System PDSS Image Motion Compensator (IMC) computer interface simulation (CIS) user's manual is given. The software provides a real time interface simulation for the following IMC subsystems: the Dry Rotor Reference Unit, the Advanced Star/Target Reference Optical sensor, the Ultra Violet imaging telescope, the Wisconson Ultraviolet Photopolarimetry Experiment, the Cruciform Power distributor, and the Spacelab Experiment Computer Operating System.

  13. Combinatorial Cis-regulation in Saccharomyces Species

    Directory of Open Access Journals (Sweden)

    Aaron T. Spivak

    2016-03-01

    Full Text Available Transcriptional control of gene expression requires interactions between the cis-regulatory elements (CREs controlling gene promoters. We developed a sensitive computational method to identify CRE combinations with conserved spacing that does not require genome alignments. When applied to seven sensu stricto and sensu lato Saccharomyces species, 80% of the predicted interactions displayed some evidence of combinatorial transcriptional behavior in several existing datasets including: (1 chromatin immunoprecipitation data for colocalization of transcription factors, (2 gene expression data for coexpression of predicted regulatory targets, and (3 gene ontology databases for common pathway membership of predicted regulatory targets. We tested several predicted CRE interactions with chromatin immunoprecipitation experiments in a wild-type strain and strains in which a predicted cofactor was deleted. Our experiments confirmed that transcription factor (TF occupancy at the promoters of the CRE combination target genes depends on the predicted cofactor while occupancy of other promoters is independent of the predicted cofactor. Our method has the additional advantage of identifying regulatory differences between species. By analyzing the S. cerevisiae and S. bayanus genomes, we identified differences in combinatorial cis-regulation between the species and showed that the predicted changes in gene regulation explain several of the species-specific differences seen in gene expression datasets. In some instances, the same CRE combinations appear to regulate genes involved in distinct biological processes in the two different species. The results of this research demonstrate that (1 combinatorial cis-regulation can be inferred by multi-genome analysis and (2 combinatorial cis-regulation can explain differences in gene expression between species.

  14. Nucleation Kinetics of Cis-Entacapone

    OpenAIRE

    Škalec Šamec, D.; Meštrović, E.; Sander, A.

    2012-01-01

    The solubility curve and the metastable zone width for the system cis-entacapone –2-propanol have been determined in defined process conditions. These results along with values of induction period for the constant feed concentration at different levels of supersaturation were used for evaluating interfacial energy according to the classical nucleation theory. The results obtained were used for calculation of the critical nucleus size, nucleation rate, and prediction of crystal growth mecha...

  15. Bioactive Peptides

    Directory of Open Access Journals (Sweden)

    Eric Banan-Mwine Daliri

    2017-04-01

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

  16. Bioactive Peptides.

    Science.gov (United States)

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

    2017-04-26

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

  17. Target Specific Tactics in Olefin Metathesis: Synthetic Approach to cis-syn-cis-Triquinanes and -Propellanes.

    Science.gov (United States)

    Kotha, Sambasivarao; Aswar, Vikas R

    2016-04-15

    A concise and simple synthetic approach to cis-syn-cis-triquinanes and -propellanes has been demonstrated via olefin metathesis starting with exo-nadic anhydride. This approach involves a ring-opening and ring-closing metathesis sequence of norbornene derivatives using Grubb's catalyst. Early-stage diallylation of norbornene derivatives is demonstrated followed by ring-closing metathesis that delivers propellanes exclusively. Surprisingly, ring-opening metathesis, late-stage diallylation, followed by ring-closing metathesis delivers triquinane as well as propellane derivatives.

  18. US/CIS integrated NTRE concept

    Energy Technology Data Exchange (ETDEWEB)

    Bulman, M.J.; Culver, D.W.; McIlwain, M.C. (Aerojet Propulsion Division, P.O. Box 13222, Sacramento, California 95813-6000 (United States)); D' yakov, E.K. (LUTCH, 24 Zheleznodorozhnaya St. Podolsk, Moscow Region, Russian 142100 (Russian Federation)); Smetannikov, V.P. (RDIPE, P.O.B. 788, Moscow, Russia 101000 (Russian Federation)); Rochow, R. (Babcock Wilcox Space Nuclear Systems, P.O. Box 11165, Lynchburg, Virginia 24506-1165 (United States))

    1993-01-10

    The team of Aerojet, Energopool and Babcock Wilcox has prepared a near-term Nuclear Thermal Rocket Engine (NTRE) concept that takes advantage of mature fuel technology developed in the former Soviet Union. This proven, advanced fuel appreciably shortens the development schedule of this engine for Moon and Mars exploration. Our near term engine has a number of features that provide safety, mission performance, cost and risk benefits, including: (1) High temperature, long life CIS fuel, (2) high pressure, recuperated topping cycle, (3) assured restart, (4) long life, cooled nozzle with thin inner wall, (5) long life turbopumps, (6) heat radiation and electrical power generation, and (7) component integration energy.

  19. Environmental testing of CIS based modules

    Energy Technology Data Exchange (ETDEWEB)

    Willett, D.

    1995-11-01

    This report describes environmental testing of Siemen`s CIS modules. Charts and diagrams are presented on data concerning: temporary power loss of laminated mini-modules; the 50 thermal cycle test; the 10 humidity freeze cycle test; results after 1000 hours of exposure to damp heat; and interconnect test structures in damp heat testing. It is concluded that moisture ingress causes permanent increases in the series resistance of modules, and that improved packaging is needed for better high humidity reliability. Also, dry dark heat caused temporary power losses which were recovered in sunlight.

  20. The CIS coal terminals guide 1994

    Energy Technology Data Exchange (ETDEWEB)

    1994-10-01

    IBJ's first annual CIS Coal Terminal Guide includes comprehensive details of loading and multi-user loading/discharge facilities in Estonia (Muuga), Georgia (Poti), Latvia (Riga), Russia (Viborg, St Petersburg, Tuapse, Vostochniy and Vanino) and Ukraine (Reni, Izmail, Yuzhniy, Mariupol), capable of handling vessels in excess of 10,000 dwt. Following IBJ's established format the guide sets out information alphabetically in country order for rapid and easy reference and comprises contact, full address and communication details as well as berth dimensions, inbound and outbound materials handling facilities, storage facilities and cargo throughput.

  1. Peptide identification

    Science.gov (United States)

    Jarman, Kristin H [Richland, WA; Cannon, William R [Richland, WA; Jarman, Kenneth D [Richland, WA; Heredia-Langner, Alejandro [Richland, WA

    2011-07-12

    Peptides are identified from a list of candidates using collision-induced dissociation tandem mass spectrometry data. A probabilistic model for the occurrence of spectral peaks corresponding to frequently observed partial peptide fragment ions is applied. As part of the identification procedure, a probability score is produced that indicates the likelihood of any given candidate being the correct match. The statistical significance of the score is known without necessarily having reference to the actual identity of the peptide. In one form of the invention, a genetic algorithm is applied to candidate peptides using an objective function that takes into account the number of shifted peaks appearing in the candidate spectrum relative to the test spectrum.

  2. Type VIa β-turn-fused helix N-termini: A novel helix N-cap motif containing cis proline.

    Science.gov (United States)

    Dasgupta, Rubin; Ganguly, Himal K; Modugula, E K; Basu, Gautam

    2017-01-01

    Helix N-capping motifs often form hydrogen bonds with terminal amide groups which otherwise would be free. Also, without an amide hydrogen, proline (trans) is over-represented at helix N-termini (N1 position) because this naturally removes the need to hydrogen bond one terminal amide. However, the preference of cisPro, vis-à-vis helix N-termini, is not known. We show that cisPro (αR or PPII ) often appears at the N-cap position (N0) of helices. The N-cap cisPro(αR ) is associated with a six-residue sequence motif - X(-2) -X(-1) -cisPro-X(1) -X(2) -X(3) - with preference for Glu/Gln at X(-1) , Phe/Tyr/Trp at X(1) and Ser/Thr at X(3) . The motif, formed by the fusion of a helix and a type VIa β-turn, contains a hydrogen bond between the side chain of X(-1) and the side chain/backbone of X(3) , a α-helical hydrogen bond between X(-2) and X(2) and stacking interaction between cisPro and an aromatic residue at X(1) . NMR experiments on peptides containing the motif and its variants showed that local interactions associated with the motif, as found in folded proteins, were not enough to significantly tilt the cis/trans equilibrium towards cisPro. This suggests that some other evolutionary pressure must select the cisPro motif (over transPro) at helix N-termini. Database analysis showed that >C = O of the pre-cisPro(αR ) residue at the helix N-cap, directed opposite to the N→C helical axis, participates in long-range interactions. We hypothesize that the cisPro(αR ) motif is preferred at helix N-termini because it allows the helix to participate in long-range interactions that may be structurally and functionally important.

  3. Regioselective trans-cis photoisomerization of m-styrylstilbenes

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Y.; Uozy, Y.; Dote, T.; Ueda, M.; Matsuura, T.

    1988-01-06

    Trans-cis photoisomerization of m-styrylstilbenes, i.e., 2,4,6-triisopropyl-3'-styrylstilbene (TISS), 2,4,6-trimethyl-3'-styrylstilbene (TMSS), and 3-styrylstilbene (SS), and of stilbenes, i.e., 2,4,6-triisopropylstilbene (TIS), 2,4,6-trimethylstilbene (TMS), and stilbene (S), are studied under direct of benzophenone-sensitized irradiation in hexane. Measurements of quantum yields of isomerization have revealed that although the styrylstilbene molecule bears two styryl groups, the reaction is highly regioselective, depending upon the excitation conditions and reactant structures. For example, isomerization of trans, trans-TISS and trans,cis-TISS occurred either at the 2,4,6-trisubstituted styryl side upon direct excitation or at the unstubstituted styryl side upon sensitized excitation. When the starting material carries an unsubstituted cis-styryl group, the major isomerization always occurred at this moiety by either direct or sensitized excitation, e.g., cis,trans-TISS ..-->.. trans,trans-TISS, cis,cis-TISS ..-->.. trans,cis-TISS, and cis,trans-SS ..-->.. trans,trans-SS. Furthermore, the photoisomerization of cis,cis-SS was found to be one-way. These results are interpreted in terms of the usual energy sink concept: the excited-state energies (E/sub S/ and E/sub T/) of the stilbene chromophores depend on molecular distortion in a subtle manner.

  4. The role of cis regulatory evolution in maize domestication.

    Science.gov (United States)

    Lemmon, Zachary H; Bukowski, Robert; Sun, Qi; Doebley, John F

    2014-11-01

    Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes) show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  5. The Role of cis Regulatory Evolution in Maize Domestication

    Science.gov (United States)

    Lemmon, Zachary H.; Bukowski, Robert; Sun, Qi; Doebley, John F.

    2014-01-01

    Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes) show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues. PMID:25375861

  6. The role of cis regulatory evolution in maize domestication.

    Directory of Open Access Journals (Sweden)

    Zachary H Lemmon

    2014-11-01

    Full Text Available Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem. Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  7. The role of cis regulatory evolution in maize domestication.

    Directory of Open Access Journals (Sweden)

    Zachary H Lemmon

    2014-11-01

    Full Text Available Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem. Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  8. Structural characterization of the HIV-1 Vpr N terminus: evidence of cis/trans-proline isomerism.

    Science.gov (United States)

    Bruns, Karsten; Fossen, Torgils; Wray, Victor; Henklein, Peter; Tessmer, Uwe; Schubert, Ulrich

    2003-10-31

    The 96-residue human immunodeficiency virus (HIV) accessory protein Vpr serves manifold functions in the retroviral life cycle including augmentation of viral replication in non-dividing host cells, induction of G2 cell cycle arrest, and modulation of HIV-induced apoptosis. Using a combination of dynamic light scattering, circular dichroism, and NMR spectroscopy the N terminus of Vpr is shown to be a unique domain of the molecule that behaves differently from the C-terminal domain in terms of self-association and secondary structure folding. Interestingly, the four highly conserved proline residues in the N terminus are predicted to have a high propensity for cis/trans isomerism. Thus the high resolution structure and folding of a synthetic N-terminal peptide (Vpr1-40) and smaller fragments thereof have been investigated. 1H NMR data indicate Vpr1-40 possesses helical structure between residues 17-32, and for the first time, this helix, which is bound by proline residues, was observed even in aqueous solution devoid of any detergent supplements. In addition, NMR data revealed that all of the proline residues undergo a cis/ trans isomerism to such an extent that approximately 40% of all Vpr molecules possess at least one proline in a cis conformation. This phenomenon of cis/trans isomerism, which is unprecedented for HIV-1 Vpr, not only provides an explanation for the molecular heterogeneity observed in the full-length molecule but also indicates that in vivo the folding and function of Vpr should depend on a cis/trans-proline isomerase activity, particularly as two of the proline residues in positions 14 and 35 show considerable amounts of cis isomers. This prediction correlates well with our recent observation (Zander, K., Sherman, M. P., Tessmer, U., Bruns, K., Wray, V., Prechtel, A. T., Schubert, E., Henklein, P., Luban, J., Neidleman, J., Greene, W. C., and Schubert, U. (2003) J. Biol. Chem. 278, 43170-43181) of a functional interaction between the major

  9. Influence of Hofmeister Ions on the Structure of Proline-Based Peptide Models: A Combined Experimental and Molecular Modeling Study.

    Science.gov (United States)

    Bröhl, Andreas; Albrecht, Benjamin; Zhang, Yong; Maginn, Edward; Giernoth, Ralf

    2017-02-23

    The influence of three sodium salts, covering a wide range of the Hofmeister series, on the conformation of three proline-based peptide models in aqueous solution is examined using a combination of nuclear magnetic resonance spectroscopy and molecular dynamics simulations. The anions preferentially interact with the cis conformers of the peptide models, which is rationalized by the respective electrostatic potential surfaces. These preferred interactions have a strong impact on the thermodynamics of the cis/trans equilibria, leading to a higher population of the cis conformers. In distinct cases, these equilibria are nearly independent of temperature, showing that the salts are also able to stabilize the conformers over wide temperature ranges.

  10. Prepare dispersed CIS nano-scale particles and spray coating CIS absorber layers using nano-scale precursors.

    Science.gov (United States)

    Liou, Jian-Chiun; Diao, Chien-Chen; Lin, Jing-Jenn; Chen, Yen-Lin; Yang, Cheng-Fu

    2014-01-01

    In this study, the Mo-electrode thin films were deposited by a two-stepped process, and the high-purity copper indium selenide-based powder (CuInSe2, CIS) was fabricated by hydrothermal process by Nanowin Technology Co. Ltd. From the X-ray pattern of the CIS precursor, the mainly crystalline phase was CIS, and the almost undetectable CuSe phase was observed. Because the CIS powder was aggregated into micro-scale particles and the average particle sizes were approximately 3 to 8 μm, the CIS power was ground into nano-scale particles, then the 6 wt.% CIS particles were dispersed into isopropyl alcohol to get the solution for spray coating method. Then, 0.1 ml CIS solution was sprayed on the 20 mm × 10 mm Mo/glass substrates, and the heat treatment for the nano-scale CIS solution under various parameters was carried out in a selenization furnace. The annealing temperature was set at 550°C, and the annealing time was changed from 5 to 30 min, without extra Se content was added in the furnace. The influences of annealing time on the densification, crystallization, resistivity (ρ), hall mobility (μ), and carrier concentration of the CIS absorber layers were well investigated in this study.

  11. C-Peptide Test

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities C-peptide Share this page: Was this page helpful? Also known as: Insulin C-peptide; Connecting Peptide Insulin; Proinsulin C-peptide Formal ...

  12. U.S./CIS eye joint nuclear rocket venture

    Science.gov (United States)

    Clark, John S.; Mcilwain, Melvin C.; Smetanikov, Vladimir; D'Yakov, Evgenij K.; Pavshuk, Vladimir A.

    1993-01-01

    An account is given of the significance for U.S. spacecraft development of a nuclear thermal rocket (NTR) reactor concept that has been developed in the (formerly Soviet) Commonwealth of Independent States (CIS). The CIS NTR reactor employs a hydrogen-cooled zirconium hydride moderator and ternary carbide fuels; the comparatively cool operating temperatures associated with this design promise overall robustness.

  13. U.S./CIS eye joint nuclear rocket venture

    Science.gov (United States)

    Clark, John S.; McIlwain, Melvin C.; Smetanikov, Vladimir; D'Yakov, Evgenij K.; Pavshuk, Vladimir A.

    1993-07-01

    An account is given of the significance for U.S. spacecraft development of a nuclear thermal rocket (NTR) reactor concept that has been developed in the (formerly Soviet) Commonwealth of Independent States (CIS). The CIS NTR reactor employs a hydrogen-cooled zirconium hydride moderator and ternary carbide fuels; the comparatively cool operating temperatures associated with this design promise overall robustness.

  14. Synthon preferences in cocrystals of cis-carboxamides:carboxylic acids

    NARCIS (Netherlands)

    Moragues-Bartolome, A.M.; Jones, W.; Cruz-Cabeza, A.J.

    2012-01-01

    We study synthon preferences in cocrystals of cis-carboxamides with carboxylic acids using a combination of database analyses, cocrystallisation experiments and theoretical calculations. We classify the cis-carboxamides into three families: primary amides, cyclic amides (lactams) and cyclic imides.

  15. Lowest energy excited singlet state of isolated cis-hexatriene

    NARCIS (Netherlands)

    Kohler, B.E.; Song, K.; Buma, W.J.

    1991-01-01

    In a previous letter [J. Chem. Phys. 92, 4622 (1990)] we reported the first observation of the 2 1Ag state of cis-hexatriene in a supersonic jet expansion by using resonance enhanced multiphoton ionization spectroscopy. Here, the vibrational analysis of the 1 1Ag2 1Ag excitation spectrum of cis-hexa

  16. Relative Stability of cis- and trans-Hydrindanones

    Directory of Open Access Journals (Sweden)

    Motoo Tori

    2015-01-01

    Full Text Available The relative stabilities of several cis- and trans-hydrindanones were compared using both isomerization experiments and MM2 calculations. The generally believed rule that cis-hydrindanones are more stable than trans-isomers is applicable, but is not always true. This review introduces examples, mainly from studies in our laboratory, to explain these facts.

  17. Optimization of Pseudomonas putida KT2440 as host for the production of cis, cis-muconate from benzoate

    NARCIS (Netherlands)

    Duuren, van J.B.J.H.

    2011-01-01

    Optimization of Pseudomonas putida KT2440 as host for the production of cis, cis-muconate from benzoate P. putida KT2440 was used as biocatalyst given its versatile and energetically robust metabolism. Therefore, a mutant was generated and a process developed based on which a life cycle assessment

  18. Germinating the 2050 Cis-Lunar Econosphere

    Science.gov (United States)

    Scott, David W.; Curreri, Peter A.; Ferguson, Cynthia K.; Nall, Mark E.; Tinker, Michael L.; Wright, Gregory M.

    2015-01-01

    In early 2013, Marshall Space Flight Center's upper management chartered a diverse team for a six-week 'sprint' to speculate (in a disciplined manner) and paint (with broad brush strokes) a picture of how earth, space, and public/private entities might be operating and relating to each other... in the year 2100. Two 12-person groups of civil servants, one with members having 15 years or less of NASA experience and the other with more senior members, worked independently and then compared and integrated their conclusions. In 2014, the 'Space 2100' team, with some new team members and different group boundaries, ran a longer sprint to a) develop more detailed estimates of the operations and economics of space activities in the vicinity of the Earth and Moon in the 2050 time frame, b) identify evolutionary paths, barriers, and opportunities, and c) suggest actions and philosophies to enable and invigorate progress towards the vision. This paper explores Space 2100's first two sprints and their projections of NASA's role in what will likely be a highly networked, international space industry and cis-lunar infrastructure.

  19. 21 CFR 573.637 - Methyl esters of conjugated linoleic acid (cis-9, trans-11 and trans-10, cis-12-octadecadienoic...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methyl esters of conjugated linoleic acid (cis-9... § 573.637 Methyl esters of conjugated linoleic acid (cis-9, trans-11 and trans-10, cis-12-octadecadienoic acids). The food additive, methyl esters of conjugated linoleic acid (cis-9, trans-11 and trans-10...

  20. PH-stat fed-batch process to enhance the production of cis, cis-muconate from benzoate by Pseudomonas putida KT2440-JD1

    NARCIS (Netherlands)

    Duuren, J.B.J.H. van; Wijte, D.; Karge, B.; Martins dos Santos, V.A.; Yang, Y.; Mars, A.E.; Eggink, G.

    2012-01-01

    Pseudomonas putida KT2440-JD1 is able to cometabolize benzoate to cis, cis-muconate in the presence of glucose as growth substrate. P. putida KT2440-JD1 was unable to grow in the presence of concentrations above 50 mM benzoate or 600 mM cis, cis-muconate. The inhibitory effects of both compounds wer

  1. pH-stat fed-batch process to enhance the production of cis, cis-muconate from benzoate by Pseudomonas putida KT2440-JD1

    NARCIS (Netherlands)

    Duuren, van J.B.J.H.; Wijte, D.; Karge, B.; Martins Dos Santos, V.A.P.; Yang, Y.; Mars, A.E.; Eggink, G.

    2012-01-01

    Pseudomonas putida KT2440-JD1 is able to cometabolize benzoate to cis, cis-muconate in the presence of glucose as growth substrate. P. putida KT2440-JD1 was unable to grow in the presence of concentrations above 50 mM benzoate or 600 mM cis, cis-muconate. The inhibitory effects of both compounds wer

  2. Crystal structure of 1,6-dithiacyclodeca-cis-3,cis-8-diene (DTCDD

    Directory of Open Access Journals (Sweden)

    Russell G. Baughman

    2014-11-01

    Full Text Available The title compound, C8H12S2 (trivial name DTCDD, was obtained as a side product of the reaction between cis-1,4-dichlorobut-2-ene and sodium sulfide. The asymmetric unit consists of one-quarter of the molecule (S site symmetry 2 and the complete molecule has 2/m (C2h point symmetry with the C=C bond in an E conformation. The geometry of the title compound is compared to those of a chloro derivative and a mercury complex.

  3. Competition in notch signaling with cis enriches cell fate decisions.

    Directory of Open Access Journals (Sweden)

    Pau Formosa-Jordan

    Full Text Available Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions can also trigger a cell-autonomous Notch signal (cis-signaling, whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability

  4. Peptide arrays for screening cancer specific peptides.

    Science.gov (United States)

    Ahmed, Sahar; Mathews, Anu Stella; Byeon, Nara; Lavasanifar, Afsaneh; Kaur, Kamaljit

    2010-09-15

    In this paper, we describe a novel method to screen peptides for specific recognition by cancer cells. Seventy peptides were synthesized on a cellulose membrane in an array format, and a direct method to study the peptide-whole cell interaction was developed. The relative binding affinity of the cells for different peptides with respect to a lead 12-mer p160 peptide, identified by phage display, was evaluated using the CyQUANT fluorescence of the bound cells. Screening allowed identification of at least five new peptides that displayed higher affinity (up to 3-fold) for MDA-MB-435 and MCF-7 human cancer cells compared to the p160 peptide. These peptides showed very little binding to the control (noncancerous) human umbilical vein endothelial cells (HUVECs). Three of these peptides were synthesized separately and labeled with fluorescein isothiocyanate (FITC) to study their uptake and interaction with the cancer and control cells using confocal laser scanning microscopy and flow cytometry. The results confirmed the high and specific affinity of an 11-mer peptide 11 (RGDPAYQGRFL) and a 10-mer peptide 18 (WXEAAYQRFL) for the cancer cells versus HUVECs. Peptide 11 binds different receptors on target cancer cells as its sequence contains multiple recognition motifs, whereas peptide 18 binds mainly to the putative p160 receptor. The peptide array-whole cell binding assay reported here is a complementary method to phage display for further screening and optimization of cancer targeting peptides for cancer therapy and diagnosis.

  5. Crystal structure of cis-anti-cis-dicyclohexane-18-crown-6 acetonitrile disolvate

    Directory of Open Access Journals (Sweden)

    Alexander Nazarenko

    2015-07-01

    Full Text Available The title compound (systematic name: cis-anti-cis-2,5,8,15,18,21-hexaoxatricyclo[20.4.0.09,14]hexacosane acetonitrile disolvate, C20H36O6·2CH3CN, crystallizes from an acetonitrile solution of dicyclohexane-18-crown-6 on evaporation. The molecule is arranged around a center of symmetry with half the crown ether molecule and one molecule of acetonitrile symmetry independent. All O—C—C—O torsion angles are gauche while all C—O—C—C angles are trans. The sequence of torsion angles is [(tg+t(tg−t]3; the geometry of oxygen atoms is close to pseudo-D3d with three atoms below and three atoms above the mean plane, with an average deviation of ±0.16 (1 Å from the mean plane. This geometry is identical to that observed in metal ion complexes of dicyclohexane-18-crown-6 but differs significantly from the conformation of a free unsolvated molecule. Each acetonitrile molecule connects to a crown ether molecule via two of its methyl group H atoms (C—H...O. Weaker interactions exist between the third H atom of the acetonitrile methyl group and an O atom of a neighbouring crown ether molecule (C—H...O; and between the N atom of the acetonitrile molecule and a H atom of another neighbouring crown ether molecule. All these intermolecular interactions create a three-dimensional network stabilizing the disolvate.

  6. CisLunar Habitat Internal Architecture Design Criteria

    Science.gov (United States)

    Jones, R.; Kennedy, K.; Howard, R.; Whitmore, M.; Martin, C.; Garate, J.

    2017-01-01

    BACKGROUND: In preparation for human exploration to Mars, there is a need to define the development and test program that will validate deep space operations and systems. In that context, a Proving Grounds CisLunar habitat spacecraft is being defined as the next step towards this goal. This spacecraft will operate differently from the ISS or other spacecraft in human history. The performance envelope of this spacecraft (mass, volume, power, specifications, etc.) is being defined by the Future Capabilities Study Team. This team has recognized the need for a human-centered approach for the internal architecture of this spacecraft and has commissioned a CisLunar Phase-1 Habitat Internal Architecture Study Team to develop a NASA reference configuration, providing the Agency with a "smart buyer" approach for future acquisition. THE CISLUNAR HABITAT INTERNAL ARCHITECTURE STUDY: Overall, the CisLunar Habitat Internal Architecture study will address the most significant questions and risks in the current CisLunar architecture, habitation, and operations concept development. This effort is achieved through definition of design criteria, evaluation criteria and process, design of the CisLunar Habitat Phase-1 internal architecture, and the development and fabrication of internal architecture concepts combined with rigorous and methodical Human-in-the-Loop (HITL) evaluations and testing of the conceptual innovations in a controlled test environment. The vision of the CisLunar Habitat Internal Architecture Study is to design, build, and test a CisLunar Phase-1 Habitat Internal Architecture that will be used for habitation (e.g. habitability and human factors) evaluations. The evaluations will mature CisLunar habitat evaluation tools, guidelines, and standards, and will interface with other projects such as the Advanced Exploration Systems (AES) Program integrated Power, Avionics, Software (iPAS), and Logistics for integrated human-in-the-loop testing. The mission of the Cis

  7. Trans-cis molecular photoswitching in interstellar Space*

    Science.gov (United States)

    Cuadrado, S.; Goicoechea, J. R.; Roncero, O.; Aguado, A.; Tercero, B.; Cernicharo, J.

    2016-01-01

    As many organic molecules, formic acid (HCOOH) has two conformers (trans and cis). The energy barrier to internal conversion from trans to cis is much higher than the thermal energy available in molecular clouds. Thus, only the most stable conformer (trans) is expected to exist in detectable amounts. We report the first interstellar detection of cis-HCOOH. Its presence in ultraviolet (UV) irradiated gas exclusively (the Orion Bar photodissociation region), with a low trans-to-cis abundance ratio of 2.8 ± 1.0, supports a photoswitching mechanism: a given conformer absorbs a stellar photon that radiatively excites the molecule to electronic states above the interconversion barrier. Subsequent fluorescent decay leaves the molecule in a different conformer form. This mechanism, which we specifically study with ab initio quantum calculations, was not considered in Space before but likely induces structural changes of a variety of interstellar molecules submitted to UV radiation. PMID:28003686

  8. Trans-cis molecular photoswitching in interstellar Space

    CERN Document Server

    Cuadrado, S; Roncero, O; Aguado, A; Tercero, B; Cernicharo, J

    2016-01-01

    As many organic molecules, formic acid (HCOOH) has two conformers (trans and cis). The energy barrier to internal conversion from trans to cis is much higher than the thermal energy available in molecular clouds. Thus, only the most stable conformer (trans) is expected to exist in detectable amounts. We report the first interstellar detection of cis-HCOOH. Its presence in ultraviolet (UV) irradiated gas exclusively (the Orion Bar photodissociation region), with a low trans-to-cis abundance ratio of 2.8+-1.0, supports a photoswitching mechanism: a given conformer absorbs a stellar photon that radiatively excites the molecule to electronic states above the interconversion barrier. Subsequent fluorescent decay leaves the molecule in a different conformer form. This mechanism, which we specifically study with ab initio quantum calculations, was not considered in Space before but likely induces structural changes of a variety of interstellar molecules submitted to UV radiation.

  9. Abundant raw material for cis-regulatory evolution in humans

    Science.gov (United States)

    Rockman, Matthew V.; Wray, Gregory A.

    2002-01-01

    Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (human phenotypic variation.

  10. Abundant raw material for cis-regulatory evolution in humans

    Science.gov (United States)

    Rockman, Matthew V.; Wray, Gregory A.

    2002-01-01

    Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (human phenotypic variation.

  11. The tomato cis-prenyltransferase gene family.

    Science.gov (United States)

    Akhtar, Tariq A; Matsuba, Yuki; Schauvinhold, Ines; Yu, Geng; Lees, Hazel A; Klein, Samuel E; Pichersky, Eran

    2013-02-01

    cis-prenyltransferases (CPTs) are predicted to be involved in the synthesis of long-chain polyisoprenoids, all with five or more isoprene (C5) units. Recently, we identified a short-chain CPT, neryl diphosphate synthase (NDPS1), in tomato (Solanum lycopersicum). Here, we searched the tomato genome and identified and characterized its entire CPT gene family, which comprises seven members (SlCPT1-7, with NDPS1 designated as SlCPT1). Six of the SlCPT genes encode proteins with N-terminal targeting sequences, which, when fused to GFP, mediated GFP transport to the plastids of Arabidopsis protoplasts. The SlCPT3-GFP fusion protein was localized to the cytosol. Enzymatic characterization of recombinant SlCPT proteins demonstrated that SlCPT6 produces Z,Z-FPP, and SlCPT2 catalyzes the formation of nerylneryl diphosphate while SlCPT4, SlCPT5 and SlCPT7 synthesize longer-chain products (C25-C55). Although no in vitro activity was demonstrated for SlCPT3, its expression in the Saccharomyces cerevisiae dolichol biosynthesis mutant (rer2) complemented the temperature-sensitive growth defect. Transcripts of SlCPT2, SlCPT4, SlCPT5 and SlCPT7 are present at low levels in multiple tissues, SlCPT6 is exclusively expressed in red fruit and roots, and SlCPT1, SlCPT3 and SlCPT7 are highly expressed in trichomes. RNAi-mediated suppression of NDPS1 led to a large decrease in β-phellandrene (which is produced from neryl diphosphate), with greater reductions achieved with the general 35S promoter compared to the trichome-specific MKS1 promoter. Phylogenetic analysis revealed CPT gene families in both eudicots and monocots, and showed that all the short-chain CPT genes from tomato (SlCPT1, SlCPT2 and SlCPT6) are closely linked to terpene synthase gene clusters.

  12. Workstation Designs for a Cis-Lunar Deep Space Habitat

    Science.gov (United States)

    Howe, A. Scott

    2014-01-01

    Using the International Standard Payload Rack (ISPR) system, a suite of workstations required for deep space missions have been proposed to fill out habitation functions in an International Space Station (ISS) derived Cis-lunar Deep Space Habitat. This paper introduces the functional layout of the Cis-lunar habitat design, and describes conceptual designs for modular deployable work surfaces, General Maintenance Workstation (GMWS), In-Space Manufacturing Workstation (ISMW), Intra-Vehicular Activity Telerobotics Work Station (IVA-TRWS), and Galley / Wardroom.

  13. Dissecting cis regulation of gene expression in human metabolic tissues.

    Directory of Open Access Journals (Sweden)

    Radu Dobrin

    Full Text Available Complex diseases such as obesity and type II diabetes can result from a failure in multiple organ systems including the central nervous system and tissues involved in partitioning and disposal of nutrients. Studying the genetics of gene expression in tissues that are involved in the development of these diseases can provide insights into how these tissues interact within the context of disease. Expression quantitative trait locus (eQTL studies identify mRNA expression changes linked to proximal genetic signals (cis eQTLs that have been shown to affect disease. Given the high impact of recent eQTL studies, it is important to understand what role sample size and environment plays in identification of cis eQTLs. Here we show in a genotyped obese human population that the number of cis eQTLs obey precise scaling laws as a function of sample size in three profiled tissues, i.e. omental adipose, subcutaneous adipose and liver. Also, we show that genes (or transcripts with cis eQTL associations detected in a small population are detected at approximately 90% rate in the largest population available for our study, indicating that genes with strong cis acting regulatory elements can be identified with relatively high confidence in smaller populations. However, by increasing the sample size we allow for better detection of weaker and more distantly located cis-regulatory elements. Yet, we determined that the number of tissue specific cis eQTLs saturates in a modestly sized cohort while the number of cis eQTLs common to all tissues fails to reach a maximum value. Understanding the power laws that govern the number and specificity of eQTLs detected in different tissues, will allow a better utilization of genetics of gene expression to inform the molecular mechanism underlying complex disease traits.

  14. Autotransfusion performed on a patient with cis AB blood group.

    Science.gov (United States)

    Kawahito, S; Kitahata, H; Kimura, H; Tanaka, K; Oshita, S

    1999-09-01

    Cis AB blood group is a rare variant of the AB blood group resulting from inheritance of both A and B genes on one chromosome. It may lead to misclassification in ABO grouping and clinical misdiagnosis as a result of its divergence from the laws of Landsteiner and Mendel. We encountered a case of cis AB blood group, and we found that autotransfusion was useful during surgery in this patient with a rare blood group.

  15. Prolyl cis-trans isomerization as a molecular timer.

    Science.gov (United States)

    Lu, Kun Ping; Finn, Greg; Lee, Tae Ho; Nicholson, Linda K

    2007-10-01

    Proline is unique in the realm of amino acids in its ability to adopt completely distinct cis and trans conformations, which allows it to act as a backbone switch that is controlled by prolyl cis-trans isomerization. This intrinsically slow interconversion can be catalyzed by the evolutionarily conserved group of peptidyl prolyl cis-trans isomerase enzymes. These enzymes include cyclophilins and FK506-binding proteins, which are well known for their isomerization-independent role as cellular targets for immunosuppressive drugs. The significance of enzyme-catalyzed prolyl cis-trans isomerization as an important regulatory mechanism in human physiology and pathology was not recognized until the discovery of the phosphorylation-specific prolyl isomerase Pin1. Recent studies indicate that both phosphorylation-dependent and phosphorylation-independent prolyl cis-trans isomerization can act as a novel molecular timer to help control the amplitude and duration of a cellular process, and prolyl cis-trans isomerization might be a new target for therapeutic interventions.

  16. The Development History of CIS (China)%CIS(中国)发展历程简析

    Institute of Scientific and Technical Information of China (English)

    黎华

    2010-01-01

    @@ 一、什么是CI(CIS) 在CI论著或CI交流对话中,常常将CI与CIS并用.CI作为舶来品,在英文里有两种含义:一是Corporate Image,指企业形象;二是Corporate Identity,指企业识别.常有人问:CI与CIS是同一回事吗?CI的英文全称:Corporate Identity,译作企业识别.CIS的英文全称:Corporate Identity System,译作企业识别系统.CI与CIS大体上说应属于同一基本概念,但人们更习惯口语中用CI.

  17. The intriguing Cyclophilin A-HIV-1 Vpr interaction: prolyl cis/trans isomerisation catalysis and specific binding

    Directory of Open Access Journals (Sweden)

    Henklein Petra

    2010-10-01

    Full Text Available Abstract Background Cyclophilin A (CypA represents a potential target for antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1 replication, although the mechanism through which CypA modulates HIV-1 infectivity still remains unclear. The interaction of HIV-1 viral protein R (Vpr with the human peptidyl prolyl isomerase CypA is known to occur in vitro and in vivo. However, the nature of the interaction of CypA with Pro-35 of N-terminal Vpr has remained undefined. Results Characterization of the interactions of human CypA with N-terminal peptides of HIV-1 Vpr has been achieved using a combination of nuclear magnetic resonace (NMR exchange spectroscopy and surface plasmon resonance spectroscopy (SPR. NMR data at atomic resolution indicate prolyl cis/trans isomerisation of the highly conserved proline residues Pro-5, -10, -14 and -35 of Vpr are catalyzed by human CypA and require only very low concentrations of the isomerase relative to that of the peptide substrates. Of the N-terminal peptides of Vpr only those containing Pro-35 bind to CypA in a biosensor assay. SPR studies of specific N-terminal peptides with decreasing numbers of residues revealed that a seven-residue motif centred at Pro-35 consisting of RHFPRIW, which under membrane-like solution conditions comprises the loop region connecting helix 1 and 2 of Vpr and the two terminal residues of helix 1, is sufficient to maintain strong specific binding. Conclusions Only N-terminal peptides of Vpr containing Pro-35, which appears to be vital for manifold functions of Vpr, bind to CypA in a biosensor assay. This indicates that Pro-35 is essential for a specific CypA-Vpr binding interaction, in contrast to the general prolyl cis/trans isomerisation observed for all proline residues of Vpr, which only involve transient enzyme-substrate interactions. Previously suggested models depicting CypA as a chaperone that plays a role in HIV-1 virulence are

  18. Evaluating cis-2,6-Dimethylpiperidide (cis-DMP) as a Base Component in Lithium-Mediated Zincation Chemistry

    Science.gov (United States)

    Armstrong, David R; Garden, Jennifer A; Kennedy, Alan R; Leenhouts, Sarah M; Mulvey, Robert E; O'Keefe, Philip; O'Hara, Charles T; Steven, Alan

    2013-01-01

    Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N′,N′-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis

  19. Evaluating cis-2,6-dimethylpiperidide (cis-DMP) as a base component in lithium-mediated zincation chemistry.

    Science.gov (United States)

    Armstrong, David R; Garden, Jennifer A; Kennedy, Alan R; Leenhouts, Sarah M; Mulvey, Robert E; O'Keefe, Philip; O'Hara, Charles T; Steven, Alan

    2013-09-27

    Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N',N'-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78% and 48% following D2O quenching of zincated benzamide intermediates). An 88% yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis

  20. Synthesis and photoactivity of phenylazonaphthalene peptide nucleic acid monomers

    Institute of Scientific and Technical Information of China (English)

    Jin Du Li; Miao Chen; Sheng Liu; Hao Bo Zhang; Zhi Lu Liu

    2008-01-01

    Phenylazonaphthalene peptide nucleic acid (PNA) monomers were successfully synthesized,and their photoisomerization was examined.The new PNA monomers showed reversible trans-cis isomerization with UV and visible light irradiation,which might be the foundation of photo-regulating the hybridization between PNA containing phenylazonaphthalene unit and DNA.Simultaneously,the fluorescence of the new PNA monomers might make them especially useful as structural probes.

  1. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  2. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen;

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2...

  3. Russia and the CIS: Relations of Foreign or Domestic Policy?

    Directory of Open Access Journals (Sweden)

    Cesáreo R. Aguilera de Prat

    1998-09-01

    Full Text Available What role does the Community of Independent States (CIS currently have in the area that was once called the Soviet Union, in particular in Russia’s so-called “near abroad”? The CIS was, to start with, little more than a liquidating committee of Soviet inheritance.This hybrid entity may be defined as a specific type of union among officially sovereign States that have few decision making mechanisms. For Russia its policy towards the “near abroad” is a priority given this country’s geostrategic interests in this area. The paperanalyzes some of the economic imperatives and the military’s participation in peacekeeping missions that have favored, up to a point, a “russification” of the CIS.

  4. Alterações estruturais in vivo dos isômeros todo-trans, 9-cis e 13-cis do b-caroteno

    Directory of Open Access Journals (Sweden)

    Costa Maria Aparecida Lopes da

    2002-01-01

    Full Text Available Com o objetivo de verificar alterações estruturais nos isômeros todo-trans, 9- e 13-cis do beta-caroteno foi realizado um ensaio biológico baseado no modelo de esgotamento das reservas hepáticas de carotenóides em ratos. Animais depletados desses carotenóides receberam, durante quinze dias, os isômeros puros todo-trans, 9-cis e 13-cis do beta-caroteno. Ao final deste período, verificou-se a ocorrência de re-isomerização in vivo desses isômeros, a partir da quantificação dos mesmos depositados no fígado dos animais. Foi observada re-isomerização do 9-cis em todo-trans, do todo-trans em 9-cis, do 13-cis em 9-cis e todo-trans. O 13-cis foi mais susceptível à isomerização que o 9-cis, pois este último passou a todo-trans e nunca a 13-cis. Já o 13-cis, tanto pode se transformar em 9-cis quanto em todo-trans.

  5. The role of cis-carotenoids in abscisic acid biosynthesis.

    Science.gov (United States)

    Parry, A D; Babiano, M J; Horgan, R

    1990-08-01

    Evidence has been obtained which is consistent with 9'-cis-neoxanthin being a major precursor of abscisic acid (ABA) in higher plants. A mild, rapid procedure was developed for the extraction and analysis of carotenoids from a range of tissues. Once purified the carotenoids were identified from their light-absorbance properties, reactions with dilute acid, high-performance liquid chromatography Rts, mass spectra and the quasiequilibria resulting from iodine-catalysed or chlorophyllsensitised photoisomerisation. Two possible ABA precursors, 9'-cis-neoxanthin and 9-cis-violaxanthin, were identified in extracts of light-grown and etiolated leaves (of Lycopersicon esculentum, Phaseolus vulgaris, Vicia faba, Pisum sativum, Cicer arietinum, Zea mays, Nicotiana plumbaginifolia, Plantago lanceolata and Digitalis purpurea), and roots of light-grown and etiolated plants (Lycopersicon, Phaseolus and Zea). The 9,9'-di-cisisomer of violaxanthin was synthesised but its presence was not detected in any extracts. Levels of 9'-cis-neoxanthin and all-trans-violaxanthin were between 20- to 100-fold greater than those of ABA in light-grown leaves. The levels of 9-cis-violaxanthin were similar to those of ABA but unaffected by water stress. Etiolated Phaseolus leaves contained reduced amounts of carotenoids (15-20% compared with light-grown leaves) but retained the ability to synthesise large amounts of ABA. The amounts of ABA synthesised, measured as increases in ABA and its metabolites phaseic acid and dihydrophaseic acid, were closely matched by decreases in the levels of 9'-cis-neoxanthin and all-trans-violaxanthin. In etiolated seedlings grown on 50% D2O, deuterium incorporation into ABA was similar to that into the xanthophylls. Relative levels of carotenoids in roots and light-grown and etiolated leaves of the ABA-deficient mutants, notabilis, flacca and sitiens were the same as those found in wild-type tomato tissues.

  6. cis,trans,cis-1,2,3,4-Tetrakis[2-(ethylsulfanylphenyl]cyclobutane

    Directory of Open Access Journals (Sweden)

    Barbara Sohr

    2016-01-01

    Full Text Available The title cyclobutane derivative, C36H40S4, formed serendipitously through a photochemically initiated [2 + 2] cycloaddition. The asymmetric unit contains half a molecule with the 2-(ethylsulfanylphenyl substituents in a cis configuration, the other half of the molecule being generated by the application of a twofold rotation operation. The substituents in both halves of the molecules are in a trans arrangement relative to each other. The cyclobutane ring shows angular and torsional strains, with C—C—C bond angles of 89.80 (8 and 88.40 (8°, and an average absolute torsion angle of 14.28 (10°. The angle of pucker in the ring is 20.27 (12°. The Ccb—Ccb—Cb angles between the cyclobutane (cb ring atoms and the attached benzene (b ring atoms are widened and range from 115.19 (10 to 121.66 (10°. A weak intramolecular C—H...S hydrogen-bonding interaction between one of the cyclobutane ring H atoms and the S atom may help to establish the molecular conformation. No specific intermolecular interactions are found.

  7. CIS 534 Week 3 Case Study The Ethical Hacker

    OpenAIRE

    Laynebaril

    2017-01-01

    CIS 534 Week 3 Case Study The Ethical Hacker Click Link Below To Buy: http://hwcampus.com/shop/cis-534-week-3-case-study-the-ethical-hacker/     ase Study: The Ethical Hacker Due Week 3 and worth 70 points   Imagine for a moment that you are a hacker; an ethical one. You are called upon by law enforcement based on your expertise to hack into a network of a business known to be launching crimes against humanity as its primary mission for operation and capital ga...

  8. Structural features of peptoid-peptide hybrids in lipid-water interfaces

    DEFF Research Database (Denmark)

    Uggerhøj, Lars Erik; Munk, Jens K; Hansen, Paul R;

    2014-01-01

    The inclusion of peptoid monomers into antimicrobial peptides (AMPs) increases their proteolytic resistance, but introduces conformational flexibility (reduced hydrogen bonding ability and cis/trans isomerism). We here use NMR spectroscopy to answer how the insertion of a peptoid monomer influenc...

  9. Creating a Collaborative Learning Community in the CIS Sandbox

    Science.gov (United States)

    Frydenberg, Mark

    2013-01-01

    Purpose: The purpose of this paper is to investigate the impact of transforming a traditional university computer lab to create a collaborative learning community known as the CIS Sandbox, by remodeling a physical space and supporting it with a virtual presence through the use of social media tools. The discussion applies Selander's "designs for…

  10. cis- and trans-Stilbenes: Chromatographic Separation and Photochemical Isomerization.

    Science.gov (United States)

    Levine, Samuel G.; And Others

    1988-01-01

    Describes an experiment that is to be performed midway in the first semester of an undergraduate organic chemistry laboratory coinciding with the students' introduction to cis-trans isomerism in the study of alkenes. Discusses the apparatus, materials, experimental procedure, historical significance, and results. (CW)

  11. cis-parthenolid-9-one from Anvillea garcinii.

    Science.gov (United States)

    Abdel-Sattar, E; McPhail, A T

    2000-11-01

    The cis-isomer (2) of the previously isolated parthenolid-9-one (1) was isolated from Anvillea garcinii and the structures and relative stereochemistries of both were determined from NMR data in combination with single-crystal X-ray analysis. In vitro cytotoxicity and in vivo antitumor activity for both compounds are reported.

  12. MODULATION OF CIS-DIAMMINEDICHLOROPLATINUM(II) RESISTANCE - A REVIEW

    NARCIS (Netherlands)

    TIMMERBOSSCHA, H; MULDER, NH; DEVRIES, EGE

    1992-01-01

    In this review an inventory is made of agents used to circumvent cis-diamminedichloroplatinum(II) (CDDP) resistance in vitro and in vivo. Agents that affect CDDP accumulation and membrane related systems, cytoplasmic defense mechanisms, as well as DNA accessibility and repair are reviewed. In resist

  13. GRASP65 controls the cis Golgi integrity in vivo

    NARCIS (Netherlands)

    Veenendaal, T.; Jarvela, T.; Grieve, A.G.; van Es, J.H.; Linstedt, A.D.; Rabouille, C.

    2014-01-01

    GRASP65 and GRASP55 are peripheral Golgi proteins localized to cis and medial/trans cisternae, respectively. They are implicated in diverse aspects of protein transport and structure related to the Golgi complex, including the stacking of the Golgi stack and/or the linking of mammalian Golgi stacks

  14. Trans-cis molecular photoswitching in interstellar space

    Science.gov (United States)

    Cuadrado, S.; Goicoechea, J. R.; Roncero, O.; Aguado, A.; Tercero, B.; Cernicharo, J.

    2016-11-01

    As many organic molecules, formic acid (HCOOH) has two conformers (trans and cis). The energy barrier to internal conversion from trans to cis is much higher than the thermal energy available in molecular clouds. Thus, only the most stable conformer (trans) is expected to exist in detectable amounts. We report the first interstellar detection of cis-HCOOH. Its presence in ultraviolet (UV) irradiated gas exclusively (the Orion Bar photodissociation region), with a low trans-to-cis abundance ratio of 2.8 ± 1.0, supports a photoswitching mechanism: a given conformer absorbs a stellar photon that radiatively excites the molecule to electronic states above the interconversion barrier. Subsequent fluorescent decay leaves the molecule in a different conformer form. This mechanism, which we specifically study with ab initio quantum calculations, was not considered in Space before but likely induces structural changes of a variety of interstellar molecules submitted to UV radiation. This paper makes use of observations obtained with the IRAM-30 m telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain).

  15. Systematic identification of cis-silenced genes by trans complementation

    Science.gov (United States)

    Lee, Jae Hyun; Bugarija, Branimir; Millan, Enrique J.; Walton, Noah M.; Gaetz, Jedidiah; Fernandes, Croydon J.; Yu, Wei-Hua; Mekel-Bobrov, Nitzan; Vallender, Tammy W.; Snyder, Gregory E.; Xiang, Andy Peng; Lahn, Bruce T.

    2009-01-01

    A gene’s transcriptional output is the combined product of two inputs: diffusible factors in the cellular milieu acting in trans, and chromatin state acting in cis. Here, we describe a strategy for dissecting the relative contribution of cis versus trans mechanisms to gene regulation. Referred to as trans complementation, it entails fusing two disparate cell types and searching for genes differentially expressed between the two genomes of fused cells. Any differential expression can be causally attributed to cis mechanisms because the two genomes of fused cells share a single homogenized milieu in trans. This assay uncovered a state of transcriptional competency that we termed ‘occluded’ whereby affected genes are silenced by cis-acting mechanisms in a manner that blocks them from responding to the trans-acting milieu of the cell. Importantly, occluded genes in a given cell type tend to include master triggers of alternative cell fates. Furthermore, the occluded state is maintained during cell division and is extraordinarily stable under a wide range of physiological conditions. These results support the model that the occlusion of lineage-inappropriate genes is a key mechanism of cell fate restriction. The identification of occluded genes by our assay provides a hitherto unavailable functional readout of chromatin state that is distinct from and complementary to gene expression status. PMID:19050040

  16. cis Determinants of Promoter Threshold and Activation Timescale

    Directory of Open Access Journals (Sweden)

    Anders S. Hansen

    2015-08-01

    Full Text Available Although the relationship between DNA cis-regulatory sequences and gene expression has been extensively studied at steady state, how cis-regulatory sequences affect the dynamics of gene induction is not known. The dynamics of gene induction can be described by the promoter activation timescale (AcTime and amplitude threshold (AmpThr. Combining high-throughput microfluidics with quantitative time-lapse microscopy, we control the activation dynamics of the budding yeast transcription factor, Msn2, and reveal how cis-regulatory motifs in 20 promoter variants of the Msn2-target-gene SIP18 affect AcTime and AmpThr. By modulating Msn2 binding sites, we can decouple AmpThr from AcTime and switch the SIP18 promoter class from high AmpThr and slow AcTime to low AmpThr and either fast or slow AcTime. We present a model that quantitatively explains gene-induction dynamics on the basis of the Msn2-binding-site number, TATA box location, and promoter nucleosome organization. Overall, we elucidate the cis-regulatory logic underlying promoter decoding of TF dynamics.

  17. INVESTIGATION OF THE SOLVENT FREE ISOMERISATION OF cis ...

    African Journals Online (AJOL)

    Preferred Customer

    Thermal analysis of cis-Mo(CO)4L2 [L = PPh2Et, PPh3, PPh2Me and ... simpler systems could provide more fundamental information on the complex isomerisation and ..... Van Atta, S.L.; Duclos, B.A.; Green, D. Organometallics 2000, 19, 2397.

  18. Peer Tutoring in the CIS Sandbox: Does It Work?

    Science.gov (United States)

    Frydenberg, Mark

    2013-01-01

    This paper reports on a student-created and facilitated peer-tutoring activity to assist first-year students in preparing for their final exam in an introductory information technology course. Tutors at the CIS Sandbox, a collaborative learning lab at an American university, offered a series of "Crunch Sessions" to their peers. This…

  19. Structural brain network characteristics can differentiate CIS from early RRMS

    Directory of Open Access Journals (Sweden)

    Muthuraman eMuthuraman

    2016-02-01

    Full Text Available Focal demyelinated lesions, diffuse white matter (WM damage and grey matter (GM atrophy influence directly the disease progression in patients with multiple sclerosis. The aim of this study was to identify specific characteristics of GM and WM structural networks in subjects with clinically isolated syndrome (CIS in comparison to patients with early relapsing-remitting multiple sclerosis (RRMS.Twenty patients with CIS, thirty three with RRMS and forty healthy subjects were investigated using 3 T-MRI. Diffusion tensor imaging was applied, together with probabilistic tractography and fractional anisotropy (FA maps for WM and cortical thickness correlation analysis for GM, to determine the structural connectivity patterns. A network topology analysis with the aid of graph theoretical approaches was used to characterize the network at different community levels (modularity, clustering coefficient, global and local efficiencies. Finally, we applied support vector machines (SVM to automatically discriminate the two groups. .In comparison to CIS subjects, patients with RRMS were found to have increased modular connectivity and higher local clustering, highlighting increased local processing in both GM and WM. Both groups presented increased modularity and clustering coefficients in comparison to healthy controls. SVM algorithms achieved 97% accuracy using the clustering coefficient as classifier derived from GM and 65% using WM from probabilistic tractography and 67 % from modularity of FA maps to differentiate between CIS and RRMS patients. We demonstrate a clear increase of modular and local connectivity in patients with early RRMS in comparison to CIS and healthy subjects. Based only on a single anatomic scan and without a priori information, we developed an automated and investigator-independent paradigm that can accurately discriminate between patients with these clinically similar disease entities, and could thus complement the current

  20. Cis-trans isomerization in the S1 state of acetylene: identification of cis-well vibrational levels.

    Science.gov (United States)

    Merer, Anthony J; Steeves, Adam H; Baraban, Joshua H; Bechtel, Hans A; Field, Robert W

    2011-06-28

    A systematic analysis of the S(1)-trans (Ã(1)A(u)) state of acetylene, using IR-UV double resonance along with one-photon fluorescence excitation spectra, has allowed assignment of at least part of every single vibrational state or polyad up to a vibrational energy of 4200 cm(-1). Four observed vibrational levels remain unassigned, for which no place can be found in the level structure of the trans-well. The most prominent of these lies at 46 175 cm(-1). Its (13)C isotope shift, exceptionally long radiative lifetime, unexpected rotational selection rules, and lack of significant Zeeman effect, combined with the fact that no other singlet electronic states are expected at this energy, indicate that it is a vibrational level of the S(1)-cis isomer (Ã(1)A(2)). Guided by ab initio calculations [J. H. Baraban, A. R. Beck, A. H. Steeves, J. F. Stanton, and R. W. Field, J. Chem. Phys. 134, 244311 (2011)] of the cis-well vibrational frequencies, the vibrational assignments of these four levels can be established from their vibrational symmetries together with the (13)C isotope shift of the 46 175 cm(-1) level (assigned here as cis-3(1)6(1)). The S(1)-cis zero-point level is deduced to lie near 44 900 cm(-1), and the ν(6) vibrational frequency of the S(1)-cis well is found to be roughly 565 cm(-1); these values are in remarkably good agreement with the results of recent ab initio calculations. The 46 175 cm(-1) vibrational level is found to have a 3.9 cm(-1) staggering of its K-rotational structure as a result of quantum mechanical tunneling through the isomerization barrier. Such tunneling does not give rise to ammonia-type inversion doubling, because the cis and trans isomers are not equivalent; instead the odd-K rotational levels of a given vibrational level are systematically shifted relative to the even-K rotational levels, leading to a staggering of the K-structure. These various observations represent the first definite assignment of an isomer of

  1. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  2. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  3. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  4. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  5. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  6. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  7. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  8. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  9. cis-Dichloridobis(1,10-phenanthrolinechromium(III chloride

    Directory of Open Access Journals (Sweden)

    Xiaoli Gao

    2011-02-01

    Full Text Available In the title complex, [CrCl2(C12H8N22]Cl, the CrIII ion is situated on a twofold rotation axis and displays a slightly distorted octahedral CrCl2N4 coordination geometry. The Cr environment is composed of a cis arrangement of two 1,10-phenanthroline and two chloride ligands. The chloride counter-anion exhibits half-occupation and is equally disordered over two positions.

  10. Synthesis and Conformation of cis-1,2-Disubstituted Cyclododecene

    Institute of Scientific and Technical Information of China (English)

    HAN,Xiang-Yu(韩翔宇); WANG,Ming-An(王明安); LIANG,Xiao-Mei(梁晓梅); WANG,Dao-Quan(王道全)

    2004-01-01

    Eight 1,2-disubstituted cyclododecenes were synthesized from a-alkoxycarbonyl-cyclododecanone and alkyl chloroformate. Their configuration and conformation determined by IR, NMR spectroscopy and X-ray diftraction analysis showed that the carbon-carbon double bond of all of the synthesized compounds has cis-configuration, and the ring skeleton of their preferred conformation is [lene2333] in solid, and they may adopt two different [lene2333]conformations, which exist in a dynamic equilibrium in solution.

  11. Thermodynamic state ensemble models of cis-regulation.

    Directory of Open Access Journals (Sweden)

    Marc S Sherman

    Full Text Available A major goal in computational biology is to develop models that accurately predict a gene's expression from its surrounding regulatory DNA. Here we present one class of such models, thermodynamic state ensemble models. We describe the biochemical derivation of the thermodynamic framework in simple terms, and lay out the mathematical components that comprise each model. These components include (1 the possible states of a promoter, where a state is defined as a particular arrangement of transcription factors bound to a DNA promoter, (2 the binding constants that describe the affinity of the protein-protein and protein-DNA interactions that occur in each state, and (3 whether each state is capable of transcribing. Using these components, we demonstrate how to compute a cis-regulatory function that encodes the probability of a promoter being active. Our intention is to provide enough detail so that readers with little background in thermodynamics can compose their own cis-regulatory functions. To facilitate this goal, we also describe a matrix form of the model that can be easily coded in any programming language. This formalism has great flexibility, which we show by illustrating how phenomena such as competition between transcription factors and cooperativity are readily incorporated into these models. Using this framework, we also demonstrate that Michaelis-like functions, another class of cis-regulatory models, are a subset of the thermodynamic framework with specific assumptions. By recasting Michaelis-like functions as thermodynamic functions, we emphasize the relationship between these models and delineate the specific circumstances representable by each approach. Application of thermodynamic state ensemble models is likely to be an important tool in unraveling the physical basis of combinatorial cis-regulation and in generating formalisms that accurately predict gene expression from DNA sequence.

  12. History and Status of the CIS Customs Union

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, T.M.; Erickson, S.A.

    1999-08-31

    This report explores the history of the CIS Customs Union and the major obstacles the Union faces in its implementation. Investigation of the Customs Union is necessary as its implementation could effect the Second Line of Defense (SLD) Program. Russian Customs contends that radiation detectors should not be installed along the Customs Union members borders of as the borders will be dissolved when the Union is implemented.

  13. Cis-Selective Ring-Opening Metathesis Polymerization with Ruthenium Catalysts

    Science.gov (United States)

    Keitz, Benjamin K.; Fedorov, Alexey; Grubbs, Robert H.

    2012-01-01

    Using a C-H activated, ruthenium-based metathesis catalyst, the cis selective ROMP of several monocyclic alkenes, as well as norbornene and oxanorbornene-type monomers is reported. The cis content of the isolated polymers depended heavily on monomer structure and temperature. By lowering the temperature, cis content as high as 96% could be obtained. PMID:22239675

  14. Radiation chemistry of cis-syn-cis dicyclohexano-18-crown-6 (DCH18C6): Acidity and uranyl nitrate dependence

    Energy Technology Data Exchange (ETDEWEB)

    Draye, Micheline [Laboratoire de Chimie Moleculaire et Environnement (EA1651), Universite de Savoie-Polytech' Savoie, Campus Scientifique, 73376 Le Bourget du Lac Cedex (France)], E-mail: micheline.draye@univ-savoie.fr; Favre-Reguillon, Alain [Laboratoire de Chimie Organique (UMR7084), Conservatoire National des Arts et Metiers, 2 rue conte, 75003 Paris (France); Faure, Rene [Laboratoire des sciences analytiques, UMR CNRS 5180, Universite Claude Bernard, Lyon 1, 43 boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex (France); Lemaire, Marc [Laboratoire de Catalyse et Synthese Organique, UMR CNRS 5246, Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, Universite Lyon 1 CPE, 43 boulevard du 11 novembre 1918, Villeurbanne 69622 (France)

    2008-05-15

    The cis-syn-cis isomer of dicyclohexano-18-crown-6 (DCH18C6) has been shown to be an efficient extractant able to perform the separation of Pu(IV) and U(VI) from fission products and then the separation of Pu(IV) from U(VI) without valence exchange as required in the PUREX process. This macrocycle was irradiated in nitric acid with a {sup 137}Cs {gamma} source to study its radiation chemical stability. Radiation chemical yields (G) were determined by gas chromatography. The results show that the presence of uranyl nitrate has a strong influence on DCH18C6 radiation chemical stability. Indeed, the presence of this template ion increases the macrocycle stability by promoting fragments recombination.

  15. Estrogenicity of novel phase I and phase II metabolites of zearalenone and cis-zearalenone.

    Science.gov (United States)

    Drzymala, Sarah S; Binder, Jennifer; Brodehl, Antje; Penkert, Martin; Rosowski, Mark; Garbe, Leif-Alexander; Koch, Matthias

    2015-10-01

    Zearalenone and its cis-isomer, cis-zearalenone, are nonsteroidal mycotoxins that elicit an estrogenic response upon binding to the estrogen receptor. This study compares the estrogenicity of eleven congeners including novel metabolites as 15-OH-zearalenone, zearalenone-14-sulfate, α-cis-zearalenol and β-cis-zearalenol using the E-Screen assay. Overall, a change in the configuration from trans to cis retains significant estrogenic activity. In contrast, alterations of the aromatic moiety including hydroxylation and sulfation showed a markedly decreased estrogenicity when compared to zearalenone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Role of cis-Monounsaturated Fatty Acids in the Prevention of Coronary Heart Disease.

    Science.gov (United States)

    Joris, Peter J; Mensink, Ronald P

    2016-07-01

    The effects of cis-monounsaturated fatty acids (cis-MUFAs) on the risk of coronary heart disease (CHD) and on CHD mortality are not clear. Also, dietary recommendations for cis-MUFA as derived by various organizations are not in agreement. Earlier studies have mainly focused on the effects of cis-MUFA on serum lipids and lipoproteins. More recent studies, however, have also addressed effects of cis-MUFA on other non-traditional CHD risk markers such as vascular function markers, postprandial vascular function, and energy intake and metabolism. Although well-designed randomized controlled trials with CHD events as endpoints are missing, several large prospective cohort studies have recently been published on the relationship between cis-MUFA and CHD risk. The aim of this paper is to review these new studies that have been published in the last 3 years on the effects of cis-MUFA on cardiovascular risk markers and CHD.

  17. Enantioselective disruption of the endocrine system by Cis-Bifenthrin in the male mice.

    Science.gov (United States)

    Jin, Yuanxiang; Wang, Jiangcong; Pan, Xiuhong; Miao, Wenyu; Lin, Xiaojian; Wang, Linggang; Fu, Zhengwei

    2015-07-01

    Bifenthrin (BF), as a chiral pyrethroid, is widely used to control field and household pests in China. At present, the commercial BF is a mixed compound containing cis isomers (cis-BF) including two enantiomers of 1R-cis-BF and 1S-cis-BF. In the present study, the two individual cis-BF enantiomers were separated by a preparative supercritical fluid chromatography. Then, four week-old adolescent male ICR mice were orally administered 1R-cis-BF and 1S-cis-BF separately daily for 3 weeks at doses of 0, 7.5 and 15 mg/kg/day, respectively. Results showed that the transcription status of some genes involved in cholesterol synthesis and transport as well as testosterone (T) synthesis in the testes were influenced by cis-BF enantiomers. Especially, we observed that the transcription status of key genes on the pathway of T synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17α-hydroxysteroid dehydrogenase (P45017α)) were selectively altered in the testis of mice when treated with 1S-cis-BF, suggesting that it is the possible reason to explain why the lower serum T concentration in 1S-cis-BF treated group. Taken together, it concluded that both of the cis-BF enantiomers have the endocrine disruption activities, while 1S-cis-BF was higher than 1R-cis-BF in mice when exposed during the puberty. The data was helpful to understand the toxicity of cis-BF in mammals under enantiomeric level.

  18. Parallel evolution of chordate cis-regulatory code for development.

    Directory of Open Access Journals (Sweden)

    Laura Doglio

    2013-11-01

    Full Text Available Urochordates are the closest relatives of vertebrates and at the larval stage, possess a characteristic bilateral chordate body plan. In vertebrates, the genes that orchestrate embryonic patterning are in part regulated by highly conserved non-coding elements (CNEs, yet these elements have not been identified in urochordate genomes. Consequently the evolution of the cis-regulatory code for urochordate development remains largely uncharacterised. Here, we use genome-wide comparisons between C. intestinalis and C. savignyi to identify putative urochordate cis-regulatory sequences. Ciona conserved non-coding elements (ciCNEs are associated with largely the same key regulatory genes as vertebrate CNEs. Furthermore, some of the tested ciCNEs are able to activate reporter gene expression in both zebrafish and Ciona embryos, in a pattern that at least partially overlaps that of the gene they associate with, despite the absence of sequence identity. We also show that the ability of a ciCNE to up-regulate gene expression in vertebrate embryos can in some cases be localised to short sub-sequences, suggesting that functional cross-talk may be defined by small regions of ancestral regulatory logic, although functional sub-sequences may also be dispersed across the whole element. We conclude that the structure and organisation of cis-regulatory modules is very different between vertebrates and urochordates, reflecting their separate evolutionary histories. However, functional cross-talk still exists because the same repertoire of transcription factors has likely guided their parallel evolution, exploiting similar sets of binding sites but in different combinations.

  19. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

    NARCIS (Netherlands)

    Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

    2003-01-01

    Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention:

  20. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

    NARCIS (Netherlands)

    Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

    2003-01-01

    Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention: Seventy

  1. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

    NARCIS (Netherlands)

    Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

    2003-01-01

    Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention: Seventy

  2. Generation of a catR deficient mutant of P. putida KT2440 that produces cis, cis-muconate from benzoate at high rate and yield

    NARCIS (Netherlands)

    Duuren, J.B.J.H. van; Wijte, D.; Leprince, A.; Karge, B.; Puchalka, J.; Wery, J.; Dos Santos, V.A.P.M.; Eggink, G.; Mars, A.E.

    2011-01-01

    Pseudomonas putida KT2440-JD1 was derived from P. putida KT2440 after N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-mutagenesis and exposure to 3-fluorobenzoate (3-FB). The mutant was no longer able to grow using benzoate as a sole carbon source, but co-metabolized benzoate to cis, cis-muconate during

  3. Blade Weapons of the Perm Cis-Urals Region

    Directory of Open Access Journals (Sweden)

    Danich Andrei V.

    2012-06-01

    Full Text Available The article is devoted to the understudied problem of bladed weapons of the Perm Cis-Urals region. For the first time the work generalizes significant archaeological and museum material dated back to the 8th-15th centuries, including the recent finds not yet interpreted by scholars. Their comprehensive analysis has made it possible to provide a detailed typological and chronological characteristic of certain types and categories of blade weapons and trace their evolution. The data on the role and place of the saber (cavalry sword in the mortuary cult are analyzed.

  4. Graphene oxide catalyzed cis-trans isomerization of azobenzene

    Directory of Open Access Journals (Sweden)

    Dongha Shin

    2014-09-01

    Full Text Available We report the fast cis-trans isomerization of an amine-substituted azobenzene catalyzed by graphene oxide (GO, where the amine functionality facilitates the charge transfer from azobenzene to graphene oxide in contrast to non-substituted azobenzene. This catalytic effect was not observed in stilbene analogues, which strongly supports the existence of different isomerization pathways between azobenzene and stilbene. The graphene oxide catalyzed isomerization is expected to be useful as a new photoisomerization based sensing platform complementary to GO-based fluorescence quenching methods.

  5. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    peptides are similar in size and structure, but oppositely charged at physiological pH. Both peptides were acylated with linear acyl chains of systematically increasing length, where sCT was furthermore acylated at two different positions on the peptide backbone. For GLP-2, we found that increasing acyl...... stems from a synergy between the positive peptide charge and membrane-active acyl moiety, supported by its pH-dependency, whereby the effect increased with decreasing pH and concomitant charge increase. The extent of permeation enhancing effect was highly dependent on acylation chain length and position...

  6. Topical peptides as cosmeceuticals

    Directory of Open Access Journals (Sweden)

    Varadraj Vasant Pai

    2017-01-01

    Full Text Available Peptides are known to have diverse biological roles, most prominently as signaling/regulatory molecules in a broad variety of physiological processes including defense, immunity, stress, growth, homeostasis and reproduction. These aspects have been used in the field of dermatology and cosmetology to produce short, stable and synthetic peptides for extracellular matrix synthesis, pigmentation, innate immunity and inflammation. The evolution of peptides over the century, which started with the discovery of penicillin, has now extended to their usage as cosmeceuticals in recent years. Cosmeceutical peptides may act as signal modulators of the extracellular matrix component, as structural peptides, carrier peptides and neurotransmitter function modulators. Transdermal delivery of peptides can be made more effective by penetration enhancers, chemical modification or encapsulation of peptides. The advantages of using peptides as cosmeceuticals include their involvement in many physiological functions of the skin, their selectivity, their lack of immunogenicity and absence of premarket regulatory requirements for their use. However, there are disadvantages: clinical evidence for efficacy is often weak, absorption may be poor due to low lipophilicity, high molecular weight and binding to other ingredients, and prices can be quite high.

  7. [Synthesis and crystalline structure of cis-monochloro(dimenthylsulfoxide)].

    Science.gov (United States)

    Bentefrit, F; Viossat, B; Tomas, A; Nguyen Huy, D; Morgant, G

    2002-03-01

    The synthesis of cis-monochloro(dimethylsulfoxide)(metforminuro) platine(II) was investigated. It crystallizes in the monoclinic system, space group P 2(1)/c with Z=4. The cell parameters are: a=9.173(2); b=11.286( 2); c=12.556( 3) (A); b=99.69(2) degrees. The structure of this compound was refined to R=0.031 and wR=0.038 using 1461 independent reflexions with I>3 s(I). The platinum coordination is square planar, built up from one Cl, one O from the dimethylsulfoxide, and one bidentate chelating ligand (metforminure anion) via the two imine nitrogen atoms in cis position. The negative charge of the metforminure ligand ensures the electric neutrality in the complex. The crystal packing is characterized by four hydrogen bonds, one of which is bifurcated (involving Cl atom (intramolecular bonding) and O(i) (intermolecular bonding; symmetry code i: x, 3/2-y; 1/2+z).

  8. Theoretical study of trans-cis photoisomerism in polymethine cyanines

    Science.gov (United States)

    Momicchioli, Fabio; Baraldi, Ivan; Berthier, Gaston

    1988-06-01

    The trans-cis photoisomerism of polymethine dyes has been interpreted so far using different and rather inconsistent models of the potential energy surfaces. In order to search for a unified electronic model, we tackled the problem again from an intramolecular point of view. Our study consisted in qualitative MO considerations followed by explicit (CS INDO) calculations of the S 0, T 1 and S 1 potential energy curves for a proper model system: pentamethine cyanine isomerizing around the 2-3 and 3-4 bonds. Torsional energy levels for the calculated potential curves were also obtained. The main conclusions are: (i) the photoreaction proceeds through a "non-spectroscopic" (perp) S 1 minimum which exists also in the isolated molecule, (ii) this twisted excited species has charge transfer character (TICT), as opposed to the biradicaloid character of the "non-spectroscopic" S 1 minimum involved in the trans→cis photoisomerization of olefines (e.g., stilbene). The possible consequences on the dynamics of the excited state relaxation in non-polar solvents are envisaged.

  9. Polymorphic cis- and trans-regulation of human gene expression.

    Directory of Open Access Journals (Sweden)

    Vivian G Cheung

    Full Text Available Expression levels of human genes vary extensively among individuals. This variation facilitates analyses of expression levels as quantitative phenotypes in genetic studies where the entire genome can be scanned for regulators without prior knowledge of the regulatory mechanisms, thus enabling the identification of unknown regulatory relationships. Here, we carried out such genetic analyses with a large sample size and identified cis- and trans-acting polymorphic regulators for about 1,000 human genes. We validated the cis-acting regulators by demonstrating differential allelic expression with sequencing of transcriptomes (RNA-Seq and the trans-regulators by gene knockdown, metabolic assays, and chromosome conformation capture analysis. The majority of the regulators act in trans to the target (regulated genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past.

  10. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  11. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.......Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  12. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  13. Avian host defense peptides

    NARCIS (Netherlands)

    Cuperus, Tryntsje; Coorens, M.; van Dijk, A.; Haagsman, H.P.

    2013-01-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense

  14. Bacteriocin Inducer Peptides

    Science.gov (United States)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  15. APD: the Antimicrobial Peptide Database

    OpenAIRE

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophob...

  16. Introduction of CIS National Center for China%ILO-CIS在中国——CIS 中国国家中心概况

    Institute of Scientific and Technical Information of China (English)

    杨乃莲

    2010-01-01

    @@ 编者按:2010 年8 月30 日,第48 届"国际职业安全卫生信息中心(CIS)年会"将在北京召开,此次盛会是自国际劳工局职业安全卫生信息中心(ILO-CIS)成立51 年来,首次在中国举行. 经过51 年的发展,ILO-CIS 在全世界已有近160 个国家中心.1987 年,CIS 中国国家中心被ILO-CIS 正式接纳为成员单位,至今,已走过23 年的时光.借本届CIS 年会在北京召开之际,我们将简要介绍CIS 中国国家中心成立以来的工作情况.

  17. Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence.

    Science.gov (United States)

    Wittkopp, Patricia J; Kalay, Gizem

    2011-12-06

    Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.

  18. Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora.

    Science.gov (United States)

    Steige, Kim A; Laenen, Benjamin; Reimegård, Johan; Scofield, Douglas G; Slotte, Tanja

    2017-01-31

    Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species.

  19. Formation of cis-coniferin in cell-free extracts of Fagus grandifolia Ehrh bark

    Science.gov (United States)

    Yamamoto, E.; Inciong, E. J.; Davin, L. B.; Lewis, N. G.

    1990-01-01

    American beech (Fagus grandifolia Ehrh) bark exclusively accumulates cis-monolignols and their glucosidic conjugates; no evidence for the accumulation of trans-monolignols has been found. The glucosyltransferase from this source exhibits a very unusual substrate specificity for cis, and not trans, monolignols. This is further evidence that cis monolignols are involved in lignin formation in these plant tissues. Preliminary evidence for the existence of a novel trans-cis monolignol isomerase was obtained, in agreement with our contention that this isomerization is not photochemically mediated.

  20. First start toward nuclear disarmament: CIS openness and compliance. Research report, August 1991-April 1992

    Energy Technology Data Exchange (ETDEWEB)

    Casteel, B.

    1992-04-01

    In the last six months we have seen significant changes in the Soviet Union which have radically altered that way we have conducted business. Now, it is no longer the Soviet Union, but the Commonwealth of Independent States (CIS). We are now making wholesale unilateral cuts in our defense structure as the CIS is viewed as our friend and no longer the Evil Empire. We are supplying the CIS with food, loan credits, and even offering assistance to help them destroy nuclear weapons. Even though the world has changed, the CIS remains the only country on the face of the earth capable of destroying the United States in a nuclear holocaust.

  1. Enthalpy of ligand substitution in cis organopalladium complexes with monodentate ligands.

    Science.gov (United States)

    Salas, Gorka; Casares, Juan A; Espinet, Pablo

    2009-10-21

    The enthalpy for the substitution reaction cis-[PdRf(2)(THF)(2)] + 2 L -->cis-[PdRf(2)L(2)] + 2THF (THF = tetrahydrofuran) has been measured in THF by calorimetric methods for Rf = 3,5-dichloro-2,4,6-trifluorophenyl, L = PPh(3), AsPh(3), SbPh(3), PMePh(2), PCyPh(2), PMe(3), AsMePh(2), or L(2) = dppe (1,2-bis(diphenylphosphino)ethane), dppf (1,1'-bis(diphenylphosphino)ferrocene). The values determined show that the substitution enthalpy has a strong dependence on the electronic and steric properties of the ligand. The study of the consecutive substitution reactions cis-[PdRf(2)(THF)(2)] + L -->cis-[PdRf(2)L(THF)] + THF, and cis-[PdRf(2)L(THF)] + L -->cis-[PdRf(2)L(2)] + THF has been carried our for L = PPh(3) and L = PCyPh(2). The first substitution is clearly more favorable for the bulkier leaving ligand, but the second gives practically the same DeltaH value for both cases, indicating that the differences in steric hindrance happen to compensate the electronic differences for both ligands. The X-ray structures of cis-[PdRf(2)(PMePh(2))(2)], cis-[PdRf(2)(dppe)] and cis-[PdRf(2)(dppf)] are reported.

  2. Reactivity of monofunctional cis-platinum adducts as a function of DNA sequence.

    OpenAIRE

    Malinge, J M; Leng, M

    1988-01-01

    The purpose of this work was to study the chemical reactivity of monofunctional cis-platinum-nucleic acid adducts as a function of nucleic acid sequence. The first part of the paper deals with the formation of these adducts. It is shown that the ternary nucleic acid-cis-platinum-ethidium bromide complexes in which ethidium bromide and nucleotide residues are cross-linked by cis-platinum, are relatively unstable at 37 degrees C. In the presence of acridine, ethidium bromide (but not cis-platin...

  3. 中国大学也需要CIS

    Institute of Scientific and Technical Information of China (English)

    黄孟芳; 林能超

    2003-01-01

    CIS(Corporate Identity System)作为企业组织的形象系统理论和实践,自从20世纪50年代在欧美及日本产生、引入、成熟并且在世界范围迅速发展起来,至今已有近半个世纪,在国内形象设计和传播界,CIS的三部分.即理念识别——MI(Mind Identity)、“行为识别——BI(Behavior Identity),“视觉识别”——VI(Visual Identity),作为业界形象传播系统的要素也已成为共识。

  4. The Uncommon Enzymology of Cis-Acyltransferase Assembly Lines.

    Science.gov (United States)

    Keatinge-Clay, Adrian T

    2017-04-26

    The enzymology of 135 assembly lines containing primarily cis-acyltransferase modules is comprehensively analyzed, with greater attention paid to less common phenomena. Diverse online transformations, in which the substrate and/or product of the reaction is an acyl chain bound to an acyl carrier protein, are classified so that unusual reactions can be compared and underlying assembly-line logic can emerge. As a complement to the chemistry surrounding the loading, extension, and offloading of assembly lines that construct primarily polyketide products, structural aspects of the assembly-line machinery itself are considered. This review of assembly-line phenomena, covering the literature up to 2017, should thus be informative to the modular polyketide synthase novice and expert alike.

  5. Patterns of cis regulatory variation in diverse human populations.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    Full Text Available The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for

  6. Clinical pharmacology and pharmacokinetics of cis-platinum and analogs.

    Science.gov (United States)

    Ribaud, P; Gouveia, J; Bonnay, M; Mathe, G

    1981-01-01

    cis-Platinum (DDP), the first metal coordination complex introduced into clinical trials, is remarkable for its therapeutic index. A short review of the numerator of this index, ie, the clinical activities of DDP given as a single agent or in combination therapy is presented. Toxicity of DDP, the denominator of the index, is given more attention, particularly nephrotoxicity, whose cumulative character and molecular mechanism are still in question and which can most often be prevented by following certain safety rules that are detailed in this paper. Pharmacokinetics data of free and filterable platinum are reviewed and discussed according to the different modalities of administration of DDP, and to what is known about its toxicity and its mechanism of cell kill. The rationale for using DDP in combination treatment is presented and the question of possible long-term toxicities is raised. cis-platinum analogs are sought for the purpose of enlarging the spectrum of activity, increasing selectivity and diminishing toxicity. Malonato-platinum has been shown not to be cross-resistant with DDP and to be clinically effective in adult acute leukemia. In a phase I study, malonato-platinum, which is poorly soluble, was administered in 6-24-hour infusions to 49 patients in doses ranging from 3 to 32 mg/kg. GI toxicity was universal. Hematological toxicity appeared to be mild and not clearly dose-related (the 3-32 mg/kg patients were not yet evaluable). Platinum pharmacokinetics in urine and plasma were performed using flameless absorption spectrophotometry. Preliminary results have suggested that malonato-platinum presented several pharmacokinetic features in common with DDP. Minor responses were seen in four solid tumor patients, three of whom were refractory to DDP. Other analogs soon to be introduced into clinical trials are listed.

  7. Phase I trials of WR-2721 and cis-platinum

    Energy Technology Data Exchange (ETDEWEB)

    Glover, D.; Glick, J.H.; Weiler, C.; Yuhas, J.; Kligerman, M.M.

    1984-09-01

    WR-2721 is a sulfhydryl compound which in the animal model improves renal tolerance to cis-platinum (DDP) by factors of 1.3 to 1.7. Phase I trials were initiated to establish the toxicity and dose modification factor when WR-2721 was given prior to escalating doses of DDP. Nineteen patients received 27 courses of WR-2721 (450-910 mg/m/sup 2/) 20 minutes prior to DDP (50-120 mg/m/sup 2/). Mild, transient nephrotoxicity was observed in only 2 of 15 courses of DDP 80-100 mg/m/sup 2/ when WR-2721 was given prior to DDP. Although 5 of 9 patients treated with WR-2721 prior to 120 mg/m/sup 2/ of DDP developed transient nephrotoxicity, their serum creatinines returned to normal baseline values within 1 to 2 weeks. Thirty-four courses of WR-2721 (740 mg/m/sup 2/) prior to DDP 120-150 mg/m/sup 2/ with mannitol diuresis were administered. Biweekly serum creatinine and monthly creatinine clearances have remained normal in all patients treated with 120 mg/m/sup 2/ of platinum and WR-2721. Four of 10 patients treated with 150 mg/m/sup 2/ of cis-platinum experienced transient nephrotoxicity 5-7 days after treatment. Mild ototoxicity was noted in 4 patients following 150 mg/m/sup 2/ of DDP. WR-2721 does not appear to protect against the antitumor efficacy of DDP. Compared to retrospective series, our data suggest that WR-2721 may provide some protection against platinum-induced nephrotoxicity, but the dose modification factors remain to be established.

  8. Patterns of cis regulatory variation in diverse human populations.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    Full Text Available The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for

  9. Options for Staging Orbits in Cis-Lunar Space

    Science.gov (United States)

    Whitley, Ryan; Martinez, Roland

    2015-01-01

    NASA has been studying options to conduct missions beyond Low Earth Orbit, but within the Earth-Moon system, in preparation for deep space exploration including human missions to Mars. Referred to as the Proving Ground, this arena of exploration activities will enable the development of human spaceflight systems and operations to satisfy future exploration objectives beyond the cis-lunar environment. One option being considered includes the deployment of a habitable element or elements, which could be used as a central location for aggregation of supplies and resources for human missions in cis-lunar space and beyond. Characterizing candidate orbit locations for this asset and the impacts on system design and mission operations is important in the overall assessment of the options being considered. The orbits described in this paper were initially selected by taking advantage of previous studies conducted by NASA and the work of other authors. In this paper orbits are assessed for their relative attractiveness based on various factors. First, a set of constraints related to the capability of the combined Orion and SLS system to deliver humans and cargo to and from the orbit are evaluated. Second, the ability to support potential lunar surface activities is considered. Finally, deployed assets intended to spend multiple years in the Proving Ground would ideally require minimal station keeping costs to reduce the mass budget allocated to this function. Additional mission design drivers include potential for uninterrupted communication with deployed assets, thermal, communications, and other operational implications. The results of the characterization and evaluation of the selected orbits indicate a Near Rectilinear Orbit (NRO) is an attractive candidate as an aggregation point or staging location for operations. In this paper, the NRO is further described in terms which balance a number of key attributes that favor a variety of mission classes to meet multiple

  10. Determination of the cis-trans isomerization barriers of L-alanyl-L-proline in aqueous solutions and at water/hydrophobic interfaces by on-line temperature-jump relaxation HPLC and dynamic on-column reaction HPLC.

    Science.gov (United States)

    Shibukawa, Masami; Miyake, Ayaka; Eda, Sayaka; Saito, Shingo

    2015-09-15

    Proline cis-trans isomerization is known to play a key role in the rate-determining steps of protein folding. It is thus very important to understand the influence of environments, not only bulk solutions but also microenvironments such as interfaces, on the isomerization reaction of proline peptides. Here we present two HPLC methods for measurements of kinetic and equilibrium parameters for the isomerization reactions in bulk solutions and at liquid/solid interfaces. On-line temperature-jump relaxation HPLC (T-jump HPLC) allows the determination of forward and reverse rate constants of the isomerization in a bulk solution by monitoring the whole time course of conversion of pure isomers from both sides of the reaction, in contrast to other HPLC and capillary zone electrophoresis as well as spectrometric and calorimetric methods, which use a mixture of the isomers. We can then determine cis-trans isomerization barriers of the peptide at liquid/solid interfaces from the kinetic data obtained by dynamic on-column reaction HPLC and T-jump HPLC. We observed that the interconversion around the peptide bond for l-alanyl-l-proline (Ala-Pro) in water is accelerated at the surfaces of an alkyl-bonded silica and a poly(styrene-divinylbenzene) copolymer resin, and this is caused by a remarkable decrease in the enthalpy of activation. The molecular structures of the cis and trans forms of Ala-Pro estimated by quantum mechanics calculation reveal that an equilibrium shift toward the cis form as well as the rapid isomerization of Ala-Pro at the water/hydrophobic interfaces can be attributed to the lower polarity of the interfacial water at the surfaces of the hydrophobic materials compared to that of bulk water.

  11. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class...... examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion. Expert opinion: Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge...

  12. 12/10-Helical β-Peptide with Dynamic Folding Propensity: Coexistence of Right- and Left-Handed Helices in an Enantiomeric Foldamer.

    Science.gov (United States)

    Shin, Seonho; Lee, Mihye; Guzei, Ilia A; Kang, Young Kee; Choi, Soo Hyuk

    2016-10-12

    We present the first examples of atomic-resolution crystal data for the β-peptide 12/10-helix from oligomers of cis-2-aminocyclohexane carboxylic acid (cis-ACHC) with alternating chirality. The local conformations of two enantiomeric cis-ACHC dimer units suggested that a chiral β-peptide may adopt both right-handed and left-handed helical conformations in solution. To probe the conformational behavior of 12/10-helical β-peptides, the two reference helices with a single handedness were synthesized with a more rigidified cis-ACHC derivative. Comparison with these reference helices at low temperature revealed that a chiral cis-ACHC oligomer with alternating chirality indeed displays 12/10-helical conformations with both handedness that equilibrate rapidly in solution. This is a very rare example of chiral oligomers with helix inversion ability. The 12/10-helical backbone should be a valuable addition to potential scaffolds for applications involving helices with dynamic folding propensity.

  13. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...

  14. Anti-antimicrobial Peptides

    Science.gov (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  15. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  16. Antimicrobial Peptides in Echinoderms

    OpenAIRE

    Li, C; Haug, T; K Stensvåg

    2010-01-01

    Antimicrobial peptides (AMPs) are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, d...

  17. Immunotherapy with Allergen Peptides

    OpenAIRE

    Larché Mark

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cro...

  18. Planning "and" Sprinting: Use of a Hybrid Project Management Methodology within a CIS Capstone Course

    Science.gov (United States)

    Baird, Aaron; Riggins, Frederick J.

    2012-01-01

    An increasing number of information systems projects in industry are managed using hybrid project management methodologies, but this shift in project management methods is not fully represented in our CIS curriculums. CIS capstone courses often include an applied project that is managed with traditional project management methods (plan first,…

  19. A CIS (Clinical Information System) Quality Evaluation Tool for Nursing Care Services

    Science.gov (United States)

    Lee, Seon Ah

    2010-01-01

    The purpose of this study was to develop a tool to evaluate the quality of a clinical information system (CIS) conceived by nurses and conduct a pilot test with the developed tool as an initial assessment. CIS quality is required for successful implementation in information technology (IT) environments. The study started with the realization that…

  20. PHARMACOKINETICS OF PARENTERAL 13-CIS-RETINOIC ACID FORMULATIONS IN RATS

    NARCIS (Netherlands)

    GUCHELAAR, HJ; BEUKEVELD, GJJ; MULDER, NH; OOSTERHUIS, JW; Wouda, S.

    1992-01-01

    The pharmacokinetics of three 13-cis-retinoic acid formulations were studied after intraperitoneal (ip) administration to rats. Rats were given ip injections of 2.5 mg of 13-cis-retinoic acid per 360 g of body weight; the drug was administered as an alkaline solution, suspended in corn oil, or as a

  1. Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum

    Directory of Open Access Journals (Sweden)

    Chen Y

    2014-06-01

    Full Text Available Yun Chen,1,* Qian Li,1,2,* Qingsheng Wu1 1Department of Chemistry, Key Laboratory of Yangtze River Water Environment, Ministry of Education, Tongji University, Shanghai; 2Shanghai Institute of Quality Inspection and Technical Research, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: cis-Diamminediiodoplatinum (cis-DIDP is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4 at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded. Keywords: stearic acid, emulsion solvent evaporation method, drug delivery, cis-DIDP, in vitro

  2. Columbia River Coordinated Information System (CIS), 1992-1993 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Rowe, Mike; Roger, Phillip B.; O' Connor, Dick

    1993-11-01

    The purposes of this report are to: (1) describe the project to date; (2) to document the work and accomplishments of the (CIS) project for Fiscal Year 1993; and (3) to provide a glimpse of future project direction. The concept of a Coordinated Information System (CIS) as an approach to meeting the growing needs for regionally standardized anadromous fish information.

  3. Bacterial degradation of 3-chloroacrylic acid and the characterization of cis- and trans-specific dehalogenases

    NARCIS (Netherlands)

    Hylckama Vlieg, Johan E.T. van; Janssen, Dick B.

    1992-01-01

    A coryneform bacterium that is able to utilize cis- and trans-3-chloroacrylic acid as sole carbon source for growth was isolated from freshwater sediment. The organism was found to produce two inducible dehalogenases, one specific for the cis- and the other for trans-3-chloroacrylic acid. Both dehal

  4. 9-cis -carotene Inhibits Atherosclerosis Development in Female LDLR-/- Mice

    Directory of Open Access Journals (Sweden)

    Noa Zolberg Relevy

    2015-02-01

    Full Text Available Background: Several epidemiological studies have shown that diets rich in carotenoids are associated with a reduced risk of cardiovascular disease. However, administration of synthetic all-trans -carotene was reported to have no effect on cardiovascular disease. We previously showed that the 9-cis -carotene-rich powder of the alga Dunaliella bardawil inhibits atherogenesis and reduces plasma non-HDL cholesterol levels in mice. Context and purpose of this study: We sought to study whether isolated 9-cis -carotene inhibits atherogenesis in a murine model of atherosclerosis. Results: Twelve-week-old female LDL receptor knockout mice (LDLR-/- were pretreated for 2 weeks with regular chow diet fortified with the alga Dunaliella powder, 9-cis β-carotene isomer, all-trans β-carotene isomer, or 9-cis retinoic acid, followed by 10 weeks of a high-fat diet with the same fortifications. In contrast to Dunaliella, 9-cis β-carotene did not inhibit the high fat dietinduced elevation of plasma cholesterol. In addition, diet fortification with Dunaliella powder, β-carotene isomers, or 9-cis retinoic acid did not change the plasma retinol or retinoic acid levels.Nevertheless, 9-cis β-carotene significantly inhibited atherogenesis compared to the control mice (39% reduction. Conclusions: The results suggest that 9-cis β-carotene should be considered as an antiatherogenic agent in the human diet

  5. Polar alicyclic rings: synthesis and structure of all cis-1,2,3,4-tetrafluorocyclopentane.

    Science.gov (United States)

    Fang, Zeguo; Al-Maharik, Nawaf; Slawin, Alexandra M Z; Bühl, Michael; O'Hagan, David

    2016-04-14

    The all-cis isomer of 1,2,3,4-tetrafluorocyclopentane is prepared and characterised by NMR and X-ray crystallography and the experimental structure compared with theory. The structure has a similarly high polarity to all-cis tetrafluorocyclohexanes despite the increased conformational flexibility of a cyclopentane.

  6. Planning "and" Sprinting: Use of a Hybrid Project Management Methodology within a CIS Capstone Course

    Science.gov (United States)

    Baird, Aaron; Riggins, Frederick J.

    2012-01-01

    An increasing number of information systems projects in industry are managed using hybrid project management methodologies, but this shift in project management methods is not fully represented in our CIS curriculums. CIS capstone courses often include an applied project that is managed with traditional project management methods (plan first,…

  7. Theoretical modeling of peptide α-helical circular dichroism in aqueous solution.

    Science.gov (United States)

    Kaminský, Jakub; Kubelka, Jan; Bour, Petr

    2011-03-10

    Reliable modeling of protein and peptide circular dichroism (CD) spectra in the far UV presents a challenge for current theoretical approaches. In this study, the time-dependent density functional theory (TDDFT), configuration interaction with single excitation (CIS), and transition dipole coupling (TDC) were used to assess the most important factors contributing to the CD spectra of the α-helical secondary structure. The dependence on the peptide chain length and also the role of the flexibility and solvent environment were investigated with a model oligopeptide Ac-(Ala)(N)-NH-Me, (N = 1, ..., 18). Both the TDDFT and TDC-like methods suggest that the CD curve typical for the α-helix arises gradually, but its basic characteristic is discernible already for peptides with 4-5 amino acid residues. The calculated dependence was in a qualitative agreement with experimental spectra of short α-helices stabilized by the histidine-metal binding. The TDDFT computations of the CD were found to be unusually sensitive to the basis set and solvent model. Explicit hydration and temperature fluctuations of the peptide geometry, simulated with the aid of molecular dynamics (MD), significantly influenced the CD and absorption spectral shapes. An extensive averaging over MD configurations is thus required to obtain a converged spectral profile in cluster simulations. On the other hand, both the TDDFT and TDC models indicate only a minor influence of the alanine side chains. The CIS and TDC calculations also point toward a relatively small effect of the helix-helix interaction on the CD spectral profiles. For a model system of two helices, the CIS method predicted larger changes in the spectra than TDC. This suggests other than interactions between peptide chains, such as mutual polarization, can have a minor, but measurable, effect on the CD spectrum.

  8. Biologically active cis-cinnamic acid occurs naturally in Brassica parachinensis

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The biologically active cis-cinnamic acid (cis-CA) has been perceived as a synthetic plant growth regulator for decades. However, in the present study, we found that cis-CA actually exists as a naturally occurring compound in a Brassica plant. This natural growth- regulating substance presents in both the sunlight-irradiated leaf tissue and the non-irradiated root tissue. The concentrations of cis-CA in both tissues are comparable to the biologically effective levels of those major plant hormones. The presence of cis-CA in root tissue suggests that it may be produced through both light-dependent and -independent path- ways or it can be transported from a plant organ to another.

  9. Cis-9, trans-11 and trans-10, cis-12 CLA mixture does not change body composition, induces insulin resistance and increases serum HDL cholesterol level in rats.

    Science.gov (United States)

    de Almeida, Mariana Macedo; de Souza, Yamara Oliveira; Dutra Luquetti, Sheila Cristina Potente; Sabarense, Céphora Maria; do Amaral Corrêa, José Otávio; da Conceição, Ellen Paula Santos; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar; Andrade Soares, Sara Malaguti; Moura Gualberto, Ana Cristina; Gameiro, Jacy; da Gama, Marco Antônio Sundfeld; Ferraz Lopes, Fernando César; González Garcia, Raúl Marcel

    2015-01-01

    Synthetic supplements of conjugated linoleic acid (CLA) containing 50:50 mixture of cis-9, trans-11 and trans-10, cis-12 CLA isomers have been commercialized in some places for reducing body fat. However the safety of this CLA mixture is controversial and in some countries the CLA usage as food supplement is not authorized. Changes in insulinemic control and serum lipids profile are potential negative effects related to consumption of CLA mixture. The present study aimed to evaluate the effects of a diet containing mixture of cis-9, trans-11 and trans-10, cis-12 CLA on prevention of obesity risk as well as on potential side effects such as insulin resistance and dyslipidemia in Wistar rats. Thirty male Wistar rats were randomly assigned to the following dietary treatments (n=10/group), for 60 days: Normolipidic Control (NC), diet containing 4.0% soybean oil (SO); High Fat-Control (HF-C), diet containing 24.0% SO; High Fat-synthetic CLA (HF-CLA), diet containing 1.5% of an isomeric CLA mixture (Luta-CLA 60) and 22.5% SO. Luta-CLA 60 (BASF) contained nearly 60% of CLA (cis-9, trans-11 and trans-10, cis-12 CLA at 50:50 ratio). The HF-CLA diet contained 0.3% of each CLA isomer. HF-CLA diet had no effect on dietary intake and body composition. HF-CLA-fed rats had lower levels of PPARγ protein in retroperitoneal adipose tissue, hyperinsulinemia compared to HF-C-fed rats, hyperglycemia compared to NC-fed rats while no differences in glycemia were observed between NC and HF-C groups, increased HOMA index and higher levels of serum HDL cholesterol. Thus, feeding rats with a high fat diet containing equal parts of cis-9, trans-11 and trans-10, cis-12 CLA isomers had no effect on body composition and induced insulin resistance. Despite HF-CLA-fed rats had increased serum HDL cholesterol levels, caution should be taken before synthetic supplements containing cis-9, trans-11 and trans-10, cis-12 CLA are recommended as a nutritional strategy for weight management.

  10. Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae.

    Science.gov (United States)

    Donohoe, Bryon S; Kang, Byung-Ho; Gerl, Mathias J; Gergely, Zachary R; McMichael, Colleen M; Bednarek, Sebastian Y; Staehelin, L Andrew

    2013-05-01

    The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (i) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3-5 COPII vesicles in contact with a C2 cis cisterna. (ii) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (iii) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (iv) C2-Cn cis cisternae grow through COPII vesicle fusion. (v) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (vi) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (vii) In plants, ∼90% of native α-mannosidase I localizes to medial Golgi cisternae. (viii) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells. © 2013 John Wiley & Sons A/S.

  11. Cis and trans effects of human genomic variants on gene expression.

    Directory of Open Access Journals (Sweden)

    Julien Bryois

    2014-07-01

    Full Text Available Gene expression is a heritable cellular phenotype that defines the function of a cell and can lead to diseases in case of misregulation. In order to detect genetic variations affecting gene expression, we performed association analysis of single nucleotide polymorphisms (SNPs and copy number variants (CNVs with gene expression measured in 869 lymphoblastoid cell lines of the Avon Longitudinal Study of Parents and Children (ALSPAC cohort in cis and in trans. We discovered that 3,534 genes (false discovery rate (FDR = 5% are affected by an expression quantitative trait locus (eQTL in cis and 48 genes are affected in trans. We observed that CNVs are more likely to be eQTLs than SNPs. In addition, we found that variants associated to complex traits and diseases are enriched for trans-eQTLs and that trans-eQTLs are enriched for cis-eQTLs. As a variant affecting both a gene in cis and in trans suggests that the cis gene is functionally linked to the trans gene expression, we looked specifically for trans effects of cis-eQTLs. We discovered that 26 cis-eQTLs are associated to 92 genes in trans with the cis-eQTLs of the transcriptions factors BATF3 and HMX2 affecting the most genes. We then explored if the variation of the level of expression of the cis genes were causally affecting the level of expression of the trans genes and discovered several causal relationships between variation in the level of expression of the cis gene and variation of the level of expression of the trans gene. This analysis shows that a large sample size allows the discovery of secondary effects of human variations on gene expression that can be used to construct short directed gene regulatory networks.

  12. Application of CIS to high-efficiency PV module fabrication. Phase 3 final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Basol, B M; Kapur, V K; Leidholm, C R; Halani, A; Roe, R; Norsworthy, G [International Solar Electric Technology, Inglewood, CA (United States)

    1998-08-01

    During this research period, researchers at International Solar Electric Technology (ISET) concentrated their efforts on three different areas of research. Within the National CIS R and D Team, ISET participated in the substrate/Mo interactions working group and investigated issues such as Na diffusion from the soda-lime glass substrate into the Mo layers and CIS films. Researchers determined that the Na content within the Mo layers was not a strong function of the nature of the Mo film. However, they found that diffusion through the Mo layers was a function of the Mo film characteristics as well as a very strong function of the CIS growth process itself. Researchers showed conclusively that the Na resided on the grain boundaries of CIS layers. Another team activity involved evaluation of CdS-free CIS solar cells. ZnO/CIS junctions prepared by the two-stage process showed light-soaking effects. Cells left under illumination improved in efficiency and were similar to the CdS/CIS junctions. After storage in the dark, however, efficiency deteriorated greatly for the ZnO/CIS device, most of the decline coming from the open-circuit voltage values. Much of the effort during this period was spent on developing a low-cost, non-vacuum CIS deposition technique. The method developed involves particulate deposition and formation of precursor layers followed by the conversion of these layers into CIS. Test modules of 40--60 cm{sup 2} were adapted to understand the issues involved in this novel technology. At the present time, the submodule efficiencies are 6--7%. Single-cell efficiencies are in the 10--13% range.

  13. Photosensitized cis/trans isomerization of 1-(1-propenyl)cycloalkenes

    Energy Technology Data Exchange (ETDEWEB)

    Inman, W.D.; Sanchez, K.A.J.; Chaidez, M.A.; Paulson, D.R. (California State Univ., Los Angeles (USA))

    1989-09-29

    The photosensitized cis/trans isomerization of a series of 1-(1-propenyl)cycloalkenes is reported. A plot of the photostationary state trans/cis ratio vs the sensitizer triplet energy for 1-(1-propenyl)cyclopentene shows a constant trans/cis ratio of {approx} 1.0 with high-energy sensitizers (E{sub T} > 61 kcal/mol). The plot shows one maxima at E{sub T} {approx} 55 kcal/mol with low-energy sensitizers (E{sub T} < 61 kcal/mol). This type of plot is very similar to those obtained with acyclic dienes such as piperylene. The 1-(1-propenyl)cyclohexene system shows a similar plot with high-energy sensitizers, but with low-energy sensitizers this system shows two maxima occurring at 56 and 47 kcal/mol, respectively. This double-maxima plot is rationalized by an unusually low trans/cis decay ratio for the s-cis relaxed triplet state of the 1-(1-propenyl)cyclohexene system. This double maxima is not observed in other diene systems due to a high trans/cis decay ratio for their s-cis relaxed triplet states. The photosensitized cis/trans isomerization of 2-ethylidene-10-methyl-1(9)-octalin was also studied as a model for a conformationally locked s-trans system. The 1-(1-propenyl)cycloheptene system undergoes photosensitized cis/trans isomerization, but photostationary cis/trans isomerization data could not be obtained due to a very efficient photosensitized dimerization of this diene system.

  14. 9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages

    Directory of Open Access Journals (Sweden)

    Sapir Bechor

    2016-07-01

    Full Text Available Cholesterol efflux from macrophages is a key process in reverse cholesterol transport and, therefore, might inhibit atherogenesis. 9-cis-β-carotene (9-cis-βc is a precursor for 9-cis-retinoic-acid (9-cis-RA, which regulates macrophage cholesterol efflux. Our objective was to assess whether 9-cis-βc increases macrophage cholesterol efflux and induces the expression of cholesterol transporters. Enrichment of a mouse diet with βc from the alga Dunaliella led to βc accumulation in peritoneal macrophages. 9-cis-βc increased the mRNA levels of CYP26B1, an enzyme that regulates RA cellular levels, indicating the formation of RA from βc in RAW264.7 macrophages. Furthermore, 9-cis-βc, as well as all-trans-βc, significantly increased cholesterol efflux to high-density lipoprotein (HDL by 50% in RAW264.7 macrophages. Likewise, food fortification with 9-cis-βc augmented cholesterol efflux from macrophages ex vivo. 9-cis-βc increased both the mRNA and protein levels of ABCA1 and apolipoprotein E (APOE and the mRNA level of ABCG1. Our study shows, for the first time, that 9-cis-βc from the diet accumulates in peritoneal macrophages and increases cholesterol efflux to HDL. These effects might be ascribed to transcriptional induction of ABCA1, ABCG1, and APOE. These results highlight the beneficial effect of βc in inhibition of atherosclerosis by improving cholesterol efflux from macrophages.

  15. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    NARCIS (Netherlands)

    J.H.W. Rutten (Joost)

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the f

  16. Identifying cis-regulatory sequences by word profile similarity.

    Directory of Open Access Journals (Sweden)

    Garmay Leung

    Full Text Available BACKGROUND: Recognizing regulatory sequences in genomes is a continuing challenge, despite a wealth of available genomic data and a growing number of experimentally validated examples. METHODOLOGY/PRINCIPAL FINDINGS: We discuss here a simple approach to search for regulatory sequences based on the compositional similarity of genomic regions and known cis-regulatory sequences. This method, which is not limited to searching for predefined motifs, recovers sequences known to be under similar regulatory control. The words shared by the recovered sequences often correspond to known binding sites. Furthermore, we show that although local word profile clustering is predictive for the regulatory sequences involved in blastoderm segmentation, local dissimilarity is a more universal feature of known regulatory sequences in Drosophila. CONCLUSIONS/SIGNIFICANCE: Our method leverages sequence motifs within a known regulatory sequence to identify co-regulated sequences without explicitly defining binding sites. We also show that regulatory sequences can be distinguished from surrounding sequences by local sequence dissimilarity, a novel feature in identifying regulatory sequences across a genome. Source code for WPH-finder is available for download at http://rana.lbl.gov/downloads/wph.tar.gz.

  17. Changes in Cis-regulatory Elements during Morphological Evolution

    Directory of Open Access Journals (Sweden)

    Yu-Lee Paul

    2012-10-01

    Full Text Available How have animals evolved new body designs (morphological evolution? This requires explanations both for simple morphological changes, such as differences in pigmentation and hair patterns between different Drosophila populations and species, and also for more complex changes, such as differences in the forelimbs of mice and bats, and the necks of amphibians and reptiles. The genetic changes and pathways involved in these evolutionary steps require identification. Many, though not all, of these events occur by changes in cis-regulatory (enhancer elements within developmental genes. Enhancers are modular, each affecting expression in only one or a few tissues. Therefore it is possible to add, remove or alter an enhancer without producing changes in multiple tissues, and thereby avoid widespread (pleiotropic deleterious effects. Ideally, for a given step in morphological evolution it is necessary to identify (i the change in phenotype, (ii the changes in gene expression, (iii the DNA region, enhancer or otherwise, affected, (iv the mutation involved, (v the nature of the transcription or other factors that bind to this site. In practice these data are incomplete for most of the published studies upon morphological evolution. Here, the investigations are categorized according to how far these analyses have proceeded.

  18. Low Thrust, Deep Throttling, US/CIS Integrated NTRE

    Science.gov (United States)

    Culver, Donald W.; Kolganov, Vyacheslav; Rochow, Richard F.

    1994-07-01

    In 1993 our international team performed a follow-on ``Nuclear Thermal Rocket Engine (NTRE) Extended Life Feasibility Assessment'' study for the Nuclear Propulsion Office (NPO) at NASAs Lewis Research Center. The main purpose of this study was to complete the 1992 study matrix to assess NTRE designs at thrust levels of 22.5, 11.3, and 6.8 tonnes, using Commonwealth of Independent States (CIS) reactor technology. An additional Aerojet goal was to continue improving the NTRE concept we had generated. Deep throttling, mission performance optimized engine design parametrics, and reliability/cost enhancing engine system simplifications were studied, because they seem to be the last three basic design improvements sorely needed by post-NERVA NTRE. Deep throttling improves engine life by eliminating damaging thermal and mechanical shocks caused by after-cooling with pulsed coolant flow. Alternately, it improves mission performance with steady flow after-cooling by minimizing reactor over-cooling. Deep throttling also provides a practical transition from high pressures and powers of the high thrust power cycle to the low pressures and powers of our electric power generating mode. Two deep throttling designs are discussed; a workable system that was studied and a simplified system that is recommended for future study. Mission-optimized engine thrust/weight (T/W) and Isp predictions are included along with system flow schemes and concept sketches.

  19. Computational methods for the detection of cis-regulatory modules.

    Science.gov (United States)

    Van Loo, Peter; Marynen, Peter

    2009-09-01

    Metazoan transcription regulation occurs through the concerted action of multiple transcription factors that bind co-operatively to cis-regulatory modules (CRMs). The annotation of these key regulators of transcription is lagging far behind the annotation of the transcriptome itself. Here, we give an overview of existing computational methods to detect these CRMs in metazoan genomes. We subdivide these methods into three classes: CRM scanners screen sequences for CRMs based on predefined models that often consist of multiple position weight matrices (PWMs). CRM builders construct models of similar CRMs controlling a set of co-regulated or co-expressed genes. CRM genome screeners screen sequences or complete genomes for CRMs as homotypic or heterotypic clusters of binding sites for any combination of transcription factors. We believe that CRM scanners are currently the most advanced methods, although their applicability is limited. Finally, we argue that CRM builders that make use of PWM libraries will benefit greatly from future advances and will prove to be most instrumental for the annotation of regulatory regions in metazoan genomes.

  20. Using hexamers to predict cis-regulatory motifs in Drosophila

    Directory of Open Access Journals (Sweden)

    Kibler Dennis

    2005-10-01

    Full Text Available Abstract Background Cis-regulatory modules (CRMs are short stretches of DNA that help regulate gene expression in higher eukaryotes. They have been found up to 1 megabase away from the genes they regulate and can be located upstream, downstream, and even within their target genes. Due to the difficulty of finding CRMs using biological and computational techniques, even well-studied regulatory systems may contain CRMs that have not yet been discovered. Results We present a simple, efficient method (HexDiff based only on hexamer frequencies of known CRMs and non-CRM sequence to predict novel CRMs in regulatory systems. On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF. After combining the results of the different algorithms, 10 putative CRMs were identified and are strong candidates for future study. The hexamers used by HexDiff to distinguish between CRMs and non-CRM sequence were also analyzed and were shown to be enriched in regulatory elements. Conclusion HexDiff provides an efficient and effective means for finding new CRMs based on known CRMs, rather than known binding sites.

  1. A Cis-Regulatory Map of the Drosophila Genome

    Science.gov (United States)

    Nègre, Nicolas; Brown, Christopher D.; Ma, Lijia; Bristow, Christopher Aaron; Miller, Steven W.; Wagner, Ulrich; Kheradpour, Pouya; Eaton, Matthew L.; Loriaux, Paul; Sealfon, Rachel; Li, Zirong; Ishii, Haruhiko; Spokony, Rebecca F.; Chen, Jia; Hwang, Lindsay; Cheng, Chao; Auburn, Richard P.; Davis, Melissa B.; Domanus, Marc; Shah, Parantu K.; Morrison, Carolyn A.; Zieba, Jennifer; Suchy, Sarah; Senderowicz, Lionel; Victorsen, Alec; Bild, Nicholas A.; Grundstad, A. Jason; Hanley, David; MacAlpine, David M.; Mannervik, Mattias; Venken, Koen; Bellen, Hugo; White, Robert; Russell, Steven; Grossman, Robert L.; Ren, Bing; Gerstein, Mark; Posakony, James W.; Kellis, Manolis; White, Kevin P.

    2011-01-01

    Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide 1,2 has successfully identified specific subtypes of regulatory elements 3. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb-Response Elements 4, chromatin states 5, transcription factor binding sites (TFBS) 6–9, PolII regulation 8, and insulator elements 10; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome based on more than 300 chromatin immuno-precipitation (ChIP) datasets for eight chromatin features, five histone deacetylases (HDACs) and thirty-eight site-specific transcription factors (TFs) at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and we validated a subset of predictions for promoters, enhancers, and insulators in vivo. We also identified nearly 2,000 genomic regions of dense TF binding associated with chromatin activity and accessibility. We discovered hundreds of new TF co-binding relationships and defined a TF network with over 800 potential regulatory relationships. PMID:21430782

  2. Synthesis and properties of stereoregular cyclic polysilanols: cis-[PhSi(O)OH](4), cis-[PhSi(O)OH](6), and tris-cis-tris-trans-[PhSi(O)OH](12).

    Science.gov (United States)

    Shchegolikhina, Olga I; Pozdnyakova, Yulia A; Molodtsova, Yulia A; Korkin, Sergey D; Bukalov, Sergey S; Leites, Larissa A; Lyssenko, Konstantin A; Peregudov, Alexandr S; Auner, Norbert; Katsoulis, Dimitris E

    2002-12-16

    New stereoregular cyclic polysilanols of the general formula [PhSi(O)OH]n (n = 6 and 12) have been selectively obtained in high yields by the reaction of cagelike oligophenylmetallasiloxanes with dilute solutions of hydrochloric acid at low temperatures. An alternative method was used to prepare cis-[PhSi(O)OH](4) from sodium phenylsiloxanolate, cis-[(Na(+))(4)[PhSi(O)O(-)](4)].(1-butanol)(x). All compounds were fully characterized by NMR and IR spectroscopy and molecular weight determinations. The structure of cis-[PhSi(O)OH](6) was confirmed by single-crystal X-ray analysis. Furthermore, a series of stereoregular cyclosiloxanes containing triorganylsiloxy groups at each silicon atom was prepared by the reactions of the cyclic polysilanols with triorganylchlorosilanes Me(3)SiCl, Me(2)ViSiCl, and Me(2)(CH(2)Cl)SiCl.

  3. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    OpenAIRE

    Rutten, Joost

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the fi rst natriuretic peptide to be discovered and in humans ANP is predominantly formed in the cardiomyocytes of the atria.2 B-type natriuretic peptide (BNP) was fi rst discovered in porcine brain hen...

  4. Structural Basis for High-Affinity Peptide Inhibition of Human Pin1

    Science.gov (United States)

    Zhang, Yan; Daum, Sebastian; Wildemann, Dirk; Zhou, Xiao Zhen; Verdecia, Mark A.; Bowman, Marianne E.; Lücke, Christian; Hunter, Tony; Lu, Kun-Ping; Fischer, Gunter; Noel, Joseph P.

    2009-01-01

    Human Pin1 is a key regulator of cell-cycle progression and plays growth-promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a unique opportunity for disrupting oncogenic pathways. Here we report two high-resolution X-ray crystal structures of human Pin1 bound to non-natural peptide inhibitors. The structures of the bound high-affinity peptides identify a type-I β-turn conformation for Pin1 prolyl peptide isomerase domain–peptide binding and an extensive molecular interface for high-affinity recognition. Moreover, these structures suggest chemical elements that may further improve the affinity and pharmacological properties of future peptide-based Pin inhibitors. Finally, an intramolecular hydrogen bond observed in both peptide complexes mimics the cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases. This comparative discovery suggests that a cyclic peptide polyketide bridge, like that found in FK506 and rapamycin or a similar linkage, may significantly improve the binding affinity of structure-based Pin1 inhibitors. PMID:17518432

  5. cis,cis-Muconic acid: separation and catalysis to bio-adipic acid for nylon-6,6 polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Vardon, Derek R.; Rorrer, Nicholas A.; Salvachúa, Davinia; Settle, Amy E.; Johnson, Christopher W.; Menart, Martin J.; Cleveland, Nicholas S.; Ciesielski, Peter N.; Steirer, K. Xerxes; Dorgan, John R.; Beckham, Gregg T.

    2016-01-01

    cis,cis-Muconic acid is a polyunsaturated dicarboxylic acid that can be produced renewably via the biological conversion of sugars and lignin-derived aromatic compounds. Subsequently, muconic acid can be catalytically converted to adipic acid -- the most commercially significant dicarboxylic acid manufactured from petroleum. Nylon-6,6 is the major industrial application for adipic acid, consuming 85% of market demand; however, high purity adipic acid (99.8%) is required for polymer synthesis. As such, process technologies are needed to effectively separate and catalytically transform biologically derived muconic acid to adipic acid in high purity over stable catalytic materials. To that end, this study: (1) demonstrates bioreactor production of muconate at 34.5 g L-1 in an engineered strain of Pseudomonas putida KT2440, (2) examines the staged recovery of muconic acid from culture media, (3) screens platinum group metals (e.g., Pd, Pt, Rh, Ru) for activity and leaching stability on activated carbon (AC) and silica supports, (4) evaluates the time-on-stream performance of Rh/AC in a trickle bed reactor, and (5) demonstrates the polymerization of bio-adipic acid to nylon-6,6. Separation experiments confirmed AC effectively removed broth color compounds, but subsequent pH/temperature shift crystallization resulted in significant levels of Na, P, K, S and N in the crystallized product. Ethanol dissolution of muconic acid precipitated bulk salts, achieving a purity of 99.8%. Batch catalysis screening reactions determined that Rh and Pd were both highly active compared to Pt and Ru, but Pd leached significantly (1-9%) from both AC and silica supports. Testing of Rh/AC in a continuous trickle bed reactor for 100 h confirmed stable performance after 24 h, although organic adsorption resulted in reduced steady-state activity. Lastly, polymerization of bio-adipic acid with hexamethyldiamine produced nylon-6,6 with comparable properties to its petrochemical counterpart

  6. Dual Toxic-Peptide-Coding Staphylococcus aureus RNA under Antisense Regulation Targets Host Cells and Bacterial Rivals Unequally

    Directory of Open Access Journals (Sweden)

    Marie-Laure Pinel-Marie

    2014-04-01

    Full Text Available Produced from the pathogenicity islands of Staphylococcus aureus clinical isolates, stable SprG1 RNA encodes two peptides from a single internal reading frame. These two peptides accumulate at the membrane, and inducing their expression triggers S. aureus death. Replacement of the two initiation codons by termination signals reverses this toxicity. During growth, cis-antisense RNA SprF1 is expressed, preventing mortality by reducing SprG1 RNA and peptide levels. The peptides are secreted extracellularly, where they lyse human host erythrocytes, a process performed more efficiently by the longer peptide. The two peptides also inactivate Gram-negative and -positive bacteria, with the shorter peptide more effective against S. aureus rivals. Two peptides are secreted from an individual RNA containing two functional initiation codons. Thus, we present an unconventional type I toxin-antitoxin system expressed from a human pathogen producing two hemolytic and antibacterial peptides from a dual-coding RNA, negatively regulated by a dual-acting antisense RNA.

  7. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  8. Thermal processing differentially affects lycopene and other carotenoids in cis-lycopene containing, tangerine tomatoes.

    Science.gov (United States)

    Cooperstone, Jessica L; Francis, David M; Schwartz, Steven J

    2016-11-01

    Tangerine tomatoes, unlike red tomatoes, accumulate cis-lycopenes instead of the all-trans isomer. cis-Lycopene is the predominating isomeric form of lycopene found in blood and tissues. Our objective was to understand how thermal processing and lipid concentration affect carotenoid isomerisation and degradation in tangerine tomatoes. We conducted duplicated factorial designed experiments producing tangerine tomato juice and sauce, varying both processing time and lipid concentration. Carotenoids were extracted and analysed using high-performance liquid chromatography with photodiode array detection. Phytoene, phytofluene, ζ-carotene, neurosporene, tetra-cis-lycopene, all-trans-lycopene and other-cis-lycopenes were quantified. Tetra-cis-lycopene decreased with increasing heating time and reached 80% of the original level in sauce after processing times of 180min. All-trans-lycopene and other-cis-lycopenes increased with longer processing times. Total carotenoids and total lycopene decreased with increased heating times while phytoene and phytofluene were unchanged. These data suggest limiting thermal processing of tangerine tomato products if delivery of tetra-cis-lycopene is desirable.

  9. Cis-trans isomerizations of beta-carotene and lycopene: a theoretical study.

    Science.gov (United States)

    Guo, Wen-Hsin; Tu, Cheng-Yi; Hu, Ching-Han

    2008-09-25

    The all-trans to mono-cis isomerizations of polyenes and two C40H56 carotenes, beta-carotene and lycopene, at the ground singlet (S0) and triplet (T1) states are studied by means of quantum chemistry computations. At the S0 state of polyenes containing n acetylene units (Pn), we find that the energy barrier of the central C=C rotation decreases with n. In contrast, however, at the T 1 state, the rotational barrier increases with n. For the C40H56 carotenes, the rotational barriers of lycopene are lower than those of their beta-carotene counterparts. This difference renders the rotational rates of lycopene to be 1-2 orders of magnitude higher than those of beta-carotene at room temperature. For both these carotenes, the barrier is lowest for the rotation toward the 13-cis isomer. The relative abundances are in the following order: all-trans > 9-cis > 13-cis > 15-cis. Although the 5-cis isomer of lycopene has the lowest energy among the cis isomers, its formation from the all-trans form is restricted, owing to a very large rotational barrier. The possible physiological implications of this study are discussed.

  10. Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework.

    Science.gov (United States)

    Maeso, Ignacio; Tena, Juan J

    2016-09-01

    Cis-regulatory changes are arguably the primary evolutionary source of animal morphological diversity. With the recent explosion of genome-wide comparisons of the cis-regulatory content in different animal species is now possible to infer general principles underlying enhancer evolution. However, these studies have also revealed numerous discrepancies and paradoxes, suggesting that the mechanistic causes and modes of cis-regulatory evolution are still not well understood and are probably much more complex than generally appreciated. Here, we argue that the mutational mechanisms and genomic regions generating new regulatory activities must comply with the constraints imposed by the molecular properties of cis-regulatory elements (CREs) and the organizational features of long-range chromatin interactions. Accordingly, we propose a new integrative evolutionary framework for cis-regulatory evolution based on two major premises for the origin of novel enhancer activity: (i) an accessible chromatin environment and (ii) compatibility with the 3D structure and interactions of pre-existing CREs. Mechanisms and DNA sequences not fulfilling these premises, will be less likely to have a measurable impact on gene expression and as such, will have a minor contribution to the evolution of gene regulation. Finally, we discuss current comparative cis-regulatory data under the light of this new evolutionary model, and propose that the two most prominent mechanisms for the evolution of cis-regulatory changes are the overprinting of ancestral CREs and the exaptation of transposable elements.

  11. Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods.

    Science.gov (United States)

    Frederiksen, Rikard; Boyer, Nicholas P; Nickle, Benjamin; Chakrabarti, Kalyan S; Koutalos, Yiannis; Crouch, Rosalie K; Oprian, Daniel; Cornwall, M Carter

    2012-06-01

    We report experiments designed to test the hypothesis that the aqueous solubility of 11-cis-retinoids plays a significant role in the rate of visual pigment regeneration. Therefore, we have compared the aqueous solubility and the partition coefficients in photoreceptor membranes of native 11-cis-retinal and an analogue retinoid, 11-cis 4-OH retinal, which has a significantly higher solubility in aqueous medium. We have then correlated these parameters with the rates of pigment regeneration and sensitivity recovery that are observed when bleached intact salamander rod photoreceptors are treated with physiological solutions containing these retinoids. We report the following results: (a) 11-cis 4-OH retinal is more soluble in aqueous buffer than 11-cis-retinal. (b) Both 11-cis-retinal and 11-cis 4-OH retinal have extremely high partition coefficients in photoreceptor membranes, though the partition coefficient of 11-cis-retinal is roughly 50-fold greater than that of 11-cis 4-OH retinal. (c) Intact bleached isolated rods treated with solutions containing equimolar amounts of 11-cis-retinal or 11-cis 4-OH retinal form functional visual pigments that promote full recovery of dark current, sensitivity, and response kinetics. However, rods treated with 11-cis 4-OH retinal regenerated on average fivefold faster than rods treated with 11-cis-retinal. (d) Pigment regeneration from recombinant and wild-type opsin in solution is slower when treated with 11-cis 4-OH retinal than with 11-cis-retinal. Based on these observations, we propose a model in which aqueous solubility of cis-retinoids within the photoreceptor cytosol can place a limit on the rate of visual pigment regeneration in vertebrate photoreceptors. We conclude that the cytosolic gap between the plasma membrane and the disk membranes presents a bottleneck for retinoid flux that results in slowed pigment regeneration and dark adaptation in rod photoreceptors.

  12. Isolation and characterization of tetrachloroethylene- and cis-1,2-dichloroethylene-dechlorinating propionibacteria.

    Science.gov (United States)

    Chang, Young-Cheol; Ikeutsu, Kaori; Toyama, Tadashi; Choi, Dubok; Kikuchi, Shintaro

    2011-10-01

    Two rapidly growing propionibacteria that could reductively dechlorinate tetrachloroethylene (PCE) and cis-1,2-dichloroethylene (cis-DCE) to ethylene were isolated from environmental sediments. Metabolic characterization and partial sequence analysis of their 16S rRNA genes showed that the new isolates, designated as strains Propionibacterium sp. HK-1 and Propionibacterium sp. HK-3, did not match any known PCE- or cis-DCE-degrading bacteria. Both strains dechlorinated relatively high concentrations of PCE (0.3 mM) and cis-DCE (0.52 mM) under anaerobic conditions without accumulating toxic intermediates during incubation. Cell-free extracts of both strains catalyzed PCE and cis-DCE dechlorination; degradation was accelerated by the addition of various electron donors. PCE dehalogenase from strain HK-1 was mediated by a corrinoid protein, since the dehalogenase was inactivated by propyl iodide only after reduction by titanium citrate. The amounts of chloride ions (0.094 and 0.103 mM) released after PCE (0.026 mM) and cis-DCE (0.05 mM) dehalogenation using the cell-free enzyme extracts of both strains, HK-1 and HK-3, were stoichiometrically similar (91 and 100%), indicating that PCE and cis-DCE were fully dechlorinated. Radiotracer studies with [1,2-¹⁴C] PCE and [1,2-¹⁴C] cis-DCE indicated that ethylene was the terminal product; partial conversion to ethylene was observed. Various chlorinated aliphatic compounds (PCE, trichloroethylene, cis-DCE, trans-1,2-dichloroethylene, 1,1-dichloroethylene, 1,1-dichloroethane, 1,2-dichloroethane, 1,2-dichloropropane, 1,1,2-trichloroethane, and vinyl chloride) were degraded by cell-free extracts of strain HK-1.

  13. Dicyclopropylmethyl peptide backbone protectant.

    Science.gov (United States)

    Carpino, Louis A; Nasr, Khaled; Abdel-Maksoud, Adel Ali; El-Faham, Ayman; Ionescu, Dumitru; Henklein, Peter; Wenschuh, Holger; Beyermann, Michael; Krause, Eberhard; Bienert, Michael

    2009-08-20

    The N-dicyclopropylmethyl (Dcpm) residue, introduced into amino acids via reaction of dicyclopropylmethanimine hydrochloride with an amino acid ester followed by sodium cyanoborohydride or triacetoxyborohydride reduction, can be used as an amide bond protectant for peptide synthesis. Examples which demonstrate the amelioration of aggregation effects include syntheses of the alanine decapeptide and the prion peptide (106-126). Avoidance of cyclization to the aminosuccinimide followed substitution of Fmoc-(Dcpm)Gly-OH for Fmoc-Gly-OH in the assembly of sequences containing the sensitive Asp-Gly unit.

  14. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  15. β-PEPTIDES CYCLOBUTANIQUES

    OpenAIRE

    Fernandez, Carlos

    2008-01-01

    The synthesis of β-amino acids, structural analogues of?-Amino acids, is an issue essential in the development of oligopeptides. A lot of work has been conducted on the behavior of β-peptide (sequence of β-amino acids) as well as peptides mixed (mixed β-and β- amino acids). As a result, the conformational preference of β-amino acids will induce the appearance of a three-dimensional structure of the oligopeptide ordered. Thus, several types of helices, sheets and elbows were observed in β-olig...

  16. Immunotherapy with Allergen Peptides

    Directory of Open Access Journals (Sweden)

    Larché Mark

    2007-06-01

    Full Text Available Specific allergen immunotherapy (SIT is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.

  17. Invertebrate FMRFamide related peptides.

    Science.gov (United States)

    Krajniak, Kevin G

    2013-06-01

    In 1977 the neuropeptide FMRFamide was isolated from the clam, Macrocallista nimbosa. Since then several hundred FMRFamide-related peptides (FaRPs) have been isolated from invertebrate animals. Precursors to the FaRPs likely arose in the cnidarians. With the transition to a bilateral body plan FaRPs became a fixture in the invertebrate phyla. They have come to play a critical role as neurotransmitters, neuromodulators, and neurohormones. FaRPs regulate a variety of body functions including, feeding, digestion, circulation, reproduction, movement. The evolution of the molecular form and function of these omnipresent peptides will be considered.

  18. Geometry matters: inverse cytotoxic relationship for cis/trans-Ru(ii) polypyridyl complexes from cis/trans-[PtCl2(NH3)2].

    Science.gov (United States)

    Wachter, Erin; Zamora, Ana; Heidary, David K; Ruiz, José; Glazer, Edith C

    2016-08-09

    Two thermally activated ruthenium(ii) polypyridyl complexes, cis-Ru(bpy)2Cl2 and trans-Ru(qpy)Cl2 were investigated to determine the impact of the geometric arrangement of the exchangable ligands on the potential of the compounds to act as chemotherapeutics. In contrast to the geometry requirements for cisplatin, trans-Ru(qpy)Cl2 was 7.1-9.5× more cytotoxic than cis-Ru(bpy)2Cl2. This discovery could open up a new area of metal-based chemotherapeutic research.

  19. Contents of conjugated linoleic acid isomers cis9,trans11 and trans10,cis12 in ruminant and non-ruminant meats available in the Italian market

    OpenAIRE

    Francesca M. Cicognini; Filippo Rossi; Samantha Sigolo; Antonio Gallo; Aldo Prandini

    2014-01-01

    Conjugated linoleic acid (CLA) isomers are considered healthy factors due to their anticarcinogenic, anti-atherosclerotic and lipolytic effect. A recommended daily intake from 0.8 to 3 g CLA/day/person has been proposed to obtain biological effects in humans. The aim of this work was to provide data on cis9,trans11 (c9,t11 CLA) and trans10,cis12 (t10,c12 CLA) contents in meats collected from Italian largescale retail trade and completing a food CLA database. In a first trial, beef loin meats ...

  20. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    . An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  1. Synthesis of Stereoisomers of 3-Aminocyclohexanecarboxylic Acid and cis-3-Aminocyclohexene-5-carboxylic Acid

    Institute of Scientific and Technical Information of China (English)

    HU Yu; YU Sheng-Liang; YANG Yu-Jin; ZHU Jin; DENG Jin-Gen

    2006-01-01

    A practical synthesis of stereoisomers of 3-aminocyclohexanecarboxylic acid and cis-3-aminocyclohexene-5-carboxylic acid was achieved from cyclohexene-4-carboxylic acid via a key resolving approach with chiral 1-phenylethylamine.

  2. Isolation and characteristics analysis of a novel high bacterial cellulose producing strain Gluconacetobacter intermedius CIs26.

    Science.gov (United States)

    Yang, Ying; Jia, Jingjing; Xing, Jianrong; Chen, Jianbing; Lu, Shengmin

    2013-02-15

    A strain producing bacterial cellulose (BC) screened from rotten mandarin fruit was identified as Gluconacetobacter intermedius CIs26 by the examination of general taxonomical characteristics and 16S rDNA sequence analysis. Furthermore, Fourier transform infrared (FT-IR) spectrum showed that pellicle produced by strain CIs26 was composed of glucan, and had the same functional group as a typical BC. X-ray diffractometry (XRD) analysis indicated that the BC was type I in structure with crystallinity index of 75%. BC yields of strain CIs26 in Hestrin-Schramn (HS), citrus waste modified HS (CMHS) and citrus waste solution (CWS) mediums were 2.1 g/L, 5.7 g/L, and 7.2 g/L, respectively. It was shown that citrus waste could stimulate BC production of strain CIs26 efficiently. Based on the ability of utilization of citrus waste, this strain appeared to have potential in BC manufacture on an industrial scale.

  3. Identification of a Positive Cis-Element Upstream of Human NKX3.1 Gene

    Institute of Scientific and Technical Information of China (English)

    An-Li JIANG; Peng-Ju ZHANG; Xiao-Yan HU; Wei-Wen CHEN; Feng KONG; Zhi-Fang LIU; Hui-Qing YUAN; Jian-Ye ZHANG

    2005-01-01

    NKX3.1 is a prostate-specific homeobox gene related to prostate development and prostate cancer. In this work, we aimed to identify precisely the functional cis-element in the 197 bp region (from -1032 to -836 bp) of the NKX3.1 promoter (from -1032 to +8 bp), which was previously identified to present positive regulatory activity on NKX3.1 expression, by deletion mutagenesis analysis and electrophoretic mobility shift assay (EMSA). A 16 bp positive cis-element located between -920 and -905 bp upstream of the NKX3.1 gene was identified by deletion mutation analysis and proved to be a functional positive cis-element by EMSA. It will be important to further study the functions and regulatory mechanisms of this positive cis-element in NKX3.1 gene expression.

  4. Microwave Spectrum and Molecular Structure of the ARGON-CIS-1,2-DICHLOROETHYLENE Complex

    Science.gov (United States)

    Marshall, Mark D.; Leung, Helen O.; Nelson, Craig J.; Yoon, Leonard H.

    2016-06-01

    The non-planar molecular structure of the complex formed between the argon atom and cis-1,2-dichloroethylene is determined via analysis of its microwave spectrum. Spectra of the 35Cl and 37Cl isotopologues are observed in natural abundance and the nuclear quadrupole splitting due to the two chlorine nuclei is fully resolved. In addition, the complete quadrupole coupling tensor for the cis-1,2-dichloroethylene molecule, including the single non-zero off-diagonal element, has been determined. Unlike the argon-cis-1,2-difluoroethylene and the argon-vinyl chloride complexes, tunneling between the two equivalent non-planar configurations of argon-cis-1,2-dichloroethylene is not observed.

  5. Enantioselective Synthesis of cis-Decalins Using Organocatalysis and Sulfonyl Nazarov Reagents

    Directory of Open Access Journals (Sweden)

    Javier Peña

    2015-04-01

    Full Text Available The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov reagents is reported. The Jørgensen’s catalyst directs this highly enantioselective synthesis using different cyclohexenal derivatives.

  6. Comprehensive NASA Cis-Lunar Earth Moon Libration Orbit Reference and Web Application Project

    Data.gov (United States)

    National Aeronautics and Space Administration — To finalize a comprehensive NASA Cis-Lunar / Earth-Moon Libration Orbit Reference and Web Application begun using FY13 IRAD funding approved in May 2013. This GSFC...

  7. Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells.

    Science.gov (United States)

    Freire-Pritchett, Paula; Schoenfelder, Stefan; Várnai, Csilla; Wingett, Steven W; Cairns, Jonathan; Collier, Amanda J; García-Vílchez, Raquel; Furlan-Magaril, Mayra; Osborne, Cameron S; Fraser, Peter; Rugg-Gunn, Peter J; Spivakov, Mikhail

    2017-03-23

    Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells.

  8. Divergence in cis-regulatory sequences surrounding the opsin gene arrays of African cichlid fishes

    National Research Council Canada - National Science Library

    O'Quin, Kelly E; Smith, Daniel; Naseer, Zan; Schulte, Jane; Engel, Samuel D; Loh, Yong-Hwee E; Streelman, J Todd; Boore, Jeffrey L; Carleton, Karen L

    2011-01-01

    .... We use phylogenetic footprinting and shadowing to examine divergence in conserved non-coding elements, promoter sequences, and 3'-UTRs surrounding each opsin in search of candidate cis-regulatory...

  9. cis-Dihydroxylation and Epoxidation of Alkenes by Manganese Catalysts - Selectivity, Reactivity and Mechanism

    NARCIS (Netherlands)

    Boer, Johannes Wietse de

    2008-01-01

    Oxidation reactions are among the most elementary of organic transformations and are essential in biology, chemical industry and (synthetic organic) chemistry. Selective oxidation of hydrocarbons, such as cis-dihydroxylation and epoxidation of alkenes, introduces functional groups and yields useful

  10. Peptide vectors for gene delivery: from single peptides to multifunctional peptide nanocarriers.

    Science.gov (United States)

    Raad, Markus de; Teunissen, Erik A; Mastrobattista, Enrico

    2014-07-01

    The therapeutic use of nucleic acids relies on the availability of sophisticated delivery systems for targeted and intracellular delivery of these molecules. Such a gene delivery should possess essential characteristics to overcome several extracellular and intracellular barriers. Peptides offer an attractive platform for nonviral gene delivery, as several functional peptide classes exist capable of overcoming these barriers. However, none of these functional peptide classes contain all the essential characteristics required to overcome all of the barriers associated with successful gene delivery. Combining functional peptides into multifunctional peptide vectors will be pivotal for improving peptide-based gene delivery systems. By using combinatorial strategies and high-throughput screening, the identification of multifunctional peptide vectors will accelerate the optimization of peptide-based gene delivery systems.

  11. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  12. Annual report of the project CIS-03-95, `evaluation of actinide nuclear data`

    Energy Technology Data Exchange (ETDEWEB)

    Maslov, V.M. [Radiation Physics and Chemistry Problems Inst., Minsk-Sosny (Belarus)

    1997-03-01

    The evaluation of neutron data for {sup 243}Cm, {sup 245}Cm and {sup 246}Cm is made in the energy region from 10-5 eV up to 20 MeV. The results of the evaluation are compiled in the ENDF/B-VI format. This work is performed under the Project Agreement CIS-03-95 with the International Science and Technology Center (Moscow). This is the annual report of the project CIS-03-95. (author)

  13. Photosensitization of trans-Vitamin D3 to cis-Vitamin D3 in Heterogeneous System

    Institute of Scientific and Technical Information of China (English)

    Yong Bin HAN; Jin Ping CHEN; Yun Yan GAO; Bai Ning LIU; Guo Qiang YANG; Yi LI

    2005-01-01

    Two modes of heterogeneous photoisomerization of trans-vitamin D3 to cis-vitamin D3are described. The occurrence of isomerization on the substrate bounded to the polymeric support gives us the possibility in succession synthesis of 1α-hydroxyvitamin D3. The polymer-bound anthracene can sensitize isomerization of trans-vitamin D3 to cis-vitamin D3 efficiently and ease the separation process.

  14. The Clinical Interview Schedule-Revised (CIS-R)–Malay Version, Clinical Validation

    OpenAIRE

    Subramaniam, Kavitha; Krishnaswamy, Saroja; Jemain, Abdul Aziz; Hamid, Abdul; Patel, Vikram

    2006-01-01

    Use of instruments or questionnaires in different cultural settings without proper validation can result in inaccurate results. Issues like reliability, validity, feasibility and acceptability should be considered in the use of an instrument. The study aims to determine the usefulness of the CIS-R Malay version in detecting common mental health problems specifically to establish the validity. The CIS-R instrument (PROQSY* format) was translated through the back translation process into Malay....

  15. Trans-cis photoisomerization of azobenzene by n→π* excitation:A semiclassical dynamics study

    Institute of Scientific and Technical Information of China (English)

    Shuai Yuan; Wei Feng Wu; Yusheng Dou; Jian She Zhao

    2008-01-01

    A realistic dynamics simulation study is reported for the trans-cis photoisomerization of azobenzene triggered by the n→π*excitation and the results show that the formation of cis isomer follows the rotational motion around the N=N bond.The simulation find that the CNN bond angle bending vibrations also play a significant role in the vibronic coupling between the HOMO and LUMO,which essentially leads a nonadiabatic transition of the molecule to the electronic ground state.

  16. Annual report of the project CIS-03-95, `evaluation of actinide nuclear data`

    Energy Technology Data Exchange (ETDEWEB)

    Maslov, V.M. [Radiation Physics and Chemistry Problems Inst., Minsk-Sosny (Belarus)

    1997-03-01

    The evaluation of neutron data for {sup 243}Cm, {sup 245}Cm and {sup 246}Cm is made in the energy region from 10-5 eV up to 20 MeV. The results of the evaluation are compiled in the ENDF/B-VI format. This work is performed under the Project Agreement CIS-03-95 with the International Science and Technology Center (Moscow). This is the annual report of the project CIS-03-95. (author)

  17. Developmental and stress regulation of gene expression for a 9-cis-epoxycarotenoid dioxygenase, CstNCED, isolated from Crocus sativus stigmas.

    Science.gov (United States)

    Ahrazem, Oussama; Rubio-Moraga, Angela; Trapero, Almudena; Gómez-Gómez, Lourdes

    2012-01-01

    Oxidative cleavage of cis-epoxycarotenoids by 9-cis-epoxycarotenoid dioxygenase (NCED) is the critical step in the regulation of abscisic acid (ABA) synthesis in higher plants. ABA has been associated with dormancy and flower senescence, while also regulating plant adaptive responses to various environmental stresses. An NCED gene, CstNCED, was cloned from Crocus sativus stigmas. The deduced amino acid sequence of the CstNCED protein shared high identity with other monocot NCEDs, and was closely related to the liliopsida enzymes. At the N-terminus of CstNCED a chloroplast transit peptide sequence is located. However, its expression in chloroplast-free tissues suggested localization in other plastid types. The relationship between expression of CstNCED and the endogenous ABA level was investigated in the stigma and corms, where it was developmentally regulated. The senescence of the unpollinated stigma is preceded by an increase in ABA levels and CstNCED expression. In corms, a correlation was observed between CstNCED expression and dormancy. Furthermore, CstNCED expression was correlated with the presence of zeaxanthin in the dormant corms. When detached C. sativus leaves and stigmas were water and salt stressed, increases in CstNCED mRNA were observed. The results provided evidence of the involvement of CstNCED in the regulation of ABA-associated processes such as flower senescence and corm dormancy in monocotyledonous saffron.

  18. Photochemical trans-/cis-isomerization and quantitation of zearalenone in edible oils.

    Science.gov (United States)

    Köppen, Robert; Riedel, Juliane; Proske, Matthias; Drzymala, Sarah; Rasenko, Tatjana; Durmaz, Vedat; Weber, Marcus; Koch, Matthias

    2012-11-28

    The emphasis of the present work was to investigate the photochemical conversion of trans- to cis-zearalenone in edible oils under real-life conditions. For quantitation purposes a cis-zearalenone standard was synthesized and characterized for its identity and purity (≥95%) by (1)H NMR, X-ray crystallography, HPLC fluorescence and mass spectrometric detection. In a sample survey of 12 edible oils (9 corn oils, 3 hempseed oils) from local supermarkets all corn oils contained trans-zearalenone (median 194 μg/kg), but no cis-zearalenone was detected. For alteration studies trans-zearalenone contaminated corn oils were exposed to sunlight over 4 and 30 weeks, revealing an obvious shift toward cis-zearalenone up to a cis/trans ratio of 9:1 by storage in colorless glass bottles. Irradiation experiments of trans-zearalenone in different organic solvents confirmed the preferred formation of cis-zearalenone possibly caused by entropic effects rather than by enthalpic entities as investigated by quantum chemical and classical force field simulations.

  19. The Clinical Interview Schedule-Revised (CIS-R)-Malay Version, Clinical Validation.

    Science.gov (United States)

    Subramaniam, Kavitha; Krishnaswamy, Saroja; Jemain, Abdul Aziz; Hamid, Abdul; Patel, Vikram

    2006-01-01

    Use of instruments or questionnaires in different cultural settings without proper validation can result in inaccurate results. Issues like reliability, validity, feasibility and acceptability should be considered in the use of an instrument. The study aims to determine the usefulness of the CIS-R Malay version in detecting common mental health problems specifically to establish the validity. The CIS-R instrument (PROQSY* format) was translated through the back translation process into Malay. Inter rater reliability was established for raters who were medical students. Cases and controls for the study were psychiatric in patients, out patient and relatives or friends accompanying the patients to the clinic or visiting the inpatients. The Malay version of CIS-R was administered to all cases and controls. All cases and controls involved in the study were rated by psychiatrists for psychiatric morbidity using the SCID as a guideline. Specificity and sensitivity of the CIS-R to the assessment by the psychiatrist were determined. The Malay version of CIS-R showed 100% sensitivity and 96.15% specificity at a cut off score of 9. The CIS-R can be a useful instrument for clinical and research use in the Malaysian population for diagnosing common mental disorders like depression and anxiety.

  20. An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h

    Directory of Open Access Journals (Sweden)

    Ranjan V. Mannige

    2017-05-01

    Full Text Available The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom—the backbone dihedral angles φ and ψ (Ramachandran, Ramakrishnan & Sasisekharan, 1963. Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of φ and ψ has not been completely described for both cis and trans backbones. Additionally, little intuitive understanding is available about a peptide’s conformation simply from knowing the φ and ψ values of a peptide (e.g., is the regular peptide defined by φ = ψ =  − 100°  left-handed or right-handed?. This report provides a new metric for backbone handedness (h based on interpreting a peptide backbone as a helix with axial displacement d and angular displacement θ, both of which are derived from a peptide backbone’s internal coordinates, especially dihedral angles φ, ψ and ω. In particular, h equals sin(θd∕|d|, with range [−1, 1] and negative (or positive values indicating left(or right-handedness. The metric h is used to characterize the handedness of every region of the Ramachandran plot for both cis (ω = 0° and trans (ω = 180° backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ, ψ space. These maps fill in the ‘dead space’ within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013, this report presents a new plot based on d and θ that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone

  1. Synthesis of trans- and cis-4'-hydroxylomustine and development of validated analytical method for lomustine and trans- and cis-4'-hydroxylomustine in canine plasma.

    Science.gov (United States)

    Dirikolu, L; Chakkath, T; Fan, T; Mente, Nolan R

    2009-01-01

    In veterinary medicine, lomustine has been successfull used primarily for the treatment of resistant lymphoma and also for the treatment of mast cell tumors, intracranial meningioma, epitheliotropic lymphoma, and histiocytic sarcoma in dogs either alone or in combination with other chemotherapeutic agents. Even though lomustine is commonly used in dogs primarily for the treatment of resistant lymphoma, there is no pharmacokinetics information available regarding this compound in dogs. In the present study, we developed and validated a simple high-performance liquid chromatography (HPLC) method with a one-step liquid-liquid extraction procedure to detect and quantify lomustine and its two monohydroxylated metabolites (trans- and cis-4'-hydroxylomustine) in canine plasma for future pharmacokinetic studies. The HPLC-diode-array detection method reported here readily detects lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine in canine plasma with a limit of detection of lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine in plasma of about 10 ng/120 microL, 5 ng/120 microL, and 5 ng/120 microL, respectively. The mean extraction efficiency values for lomustine, cis-4'-hydroxylomustine, and trans-4'-hydroxylomustine were 73%, 90%, and 89%, respectively, from canine plasma samples on HPLC. The present study also provides stability information about lomustine and its two monohydroxylated metabolites in canine plasma and methanol solution stored at various conditions.

  2. APD: the Antimicrobial Peptide Database.

    Science.gov (United States)

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophobic percentage, key residue, unique sequence motif, structure and activity. APD is a useful tool for studying the structure-function relationship of antimicrobial peptides. The database can be accessed via a web-based browser at the URL: http://aps.unmc.edu/AP/main.html.

  3. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

  4. Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers.

    Science.gov (United States)

    Ochoa, Julio J; Farquharson, Andrew J; Grant, Ian; Moffat, L E; Heys, Steven D; Wahle, Klaus W J

    2004-07-01

    The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers. The trans-10, cis-12 CLA was the most effective isomer (55% inhibition). This isomer was also able to decrease bcl-2 gene expression and to increase p21(WAF1/Cip1) mRNA levels (60% increase at highest concentration). In contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their constituent isomers are not equivalent, due to the different pathways involved for individual isomers. Trans-10, cis-12 seems to work preferentially through modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects arachidonic acid metabolism.

  5. Avian host defense peptides.

    Science.gov (United States)

    Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

    2013-11-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds.

  6. Antimicrobial peptides in Echinoderms

    Directory of Open Access Journals (Sweden)

    C Li

    2010-05-01

    Full Text Available Antimicrobial peptides (AMPs are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, dissimilar to other known AMPs. A family of heterodimeric AMPs, named centrocins, are also present in S. droebachiensis. Lysozymes and fragments of larger proteins, such as beta-thymocins, actin, histone 2A and filamin A have also been shown to display antimicrobial activities in echinoderms. Future studies on AMPs should be aimed in revealing how echinoderms use these AMPs in the immune response against microbial pathogens.

  7. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  8. Peptides and Food Intake

    OpenAIRE

    Carmen Sobrino Crespo; Aranzazu Perianes Cachero; Lilian Puebla Jiménez; Vicente eBarrios; Eduardo eArilla

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the r...

  9. Proton Mobility in b2 Ion Formation and Fragmentation Reactions of Histidine-Containing Peptides

    Science.gov (United States)

    Nelson, Carissa R.; Abutokaikah, Maha T.; Harrison, Alex G.; Bythell, Benjamin J.

    2016-03-01

    A detailed energy-resolved study of the fragmentation reactions of protonated histidine-containing peptides and their b2 ions has been undertaken. Density functional theory calculations were utilized to predict how the fragmentation reactions occur so that we might discern why the mass spectra demonstrated particular energy dependencies. We compare our results to the current literature and to synthetic b2 ion standards. We show that the position of the His residue does affect the identity of the subsequent b2 ion (diketopiperazine versus oxazolone versus lactam) and that energy-resolved CID can distinguish these isomeric products based on their fragmentation energetics. The histidine side chain facilitates every major transformation except trans-cis isomerization of the first amide bond, a necessary prerequisite to diketopiperazine b2 ion formation. Despite this lack of catalyzation, trans-cis isomerization is predicted to be facile. Concomitantly, the subsequent amide bond cleavage reaction is rate-limiting.

  10. [C-peptide physiological effects].

    Science.gov (United States)

    Shpakov, A O; Granstrem, O K

    2013-02-01

    In the recent years there were numerous evidences that C-peptide, which was previously considered as a product of insulin biosynthesis, is one of the key regulators of physiological processes. C-peptide via heterotrimeric G(i/o) protein-coupled receptors activates a wide range of intracellular effector proteins and transcription factors and, thus, controls the inflammatory and neurotrophic processes, pain sensitivity, cognitive function, macro- and microcirculation, glomerular filtration. These effects of C-peptide are mainly expressed in its absolute or relative deficiency occurred in type 1 diabetes mellitus and they are less pronounced when the level of C-peptide is close to normal. Replacement therapy with C-peptide prevents many complications of type 1 diabetes, such as atherosclerosis, diabetic peripheral neuropathy, and nephropathy. C-peptide interacts with the insulin hexamer complexes and induces their dissociation and, as a result, regulates the functional activity of the insulin signaling system. At the same time, C-peptide at the concentrations above physiological may demonstrate pro-inflammatory effects on the endothelial cells and cause atherosclerotic changes in the vessels, which should be considered in the study of pathogenic mechanisms of complications of type 2 diabetes mellitus, where the level of C peptide is increased, as well as in the development of approaches for C-peptide application in clinic. This review is devoted contemporary achievements and unsolved problems in the study of C-peptide, as an important regulator of physiological and biochemical processes.

  11. Cationic iridium(III) complexes with two carbene-based cyclometalating ligands: cis versus trans isomers.

    Science.gov (United States)

    Monti, Filippo; La Placa, Maria Grazia I; Armaroli, Nicola; Scopelliti, Rosario; Grätzel, Michael; Nazeeruddin, Mohammad Khaja; Kessler, Florian

    2015-03-16

    A series of cationic iridium(III) complexes with two carbene-based cyclometalating ligands and five different N^N bipyridine and 1,10-phenanthroline ancillary ligands is presented. For the first time--in the frame of a rarely studied class of bis(heteroleptic) iridium complexes with two carbene-based cyclometalating ligands--a pair of cis and trans isomers has been isolated. All complexes (trans-1-5 and cis-3) were characterized by (1)H NMR, (13)C NMR, (31)P NMR, and HRMS (ESI-TOF); in addition, crystal structures of cis-3 and trans-4 are reported and discussed. Cyclic voltammetric studies show that the whole series exhibits highly reversible oxidation and reduction processes, suggesting promising potential for optoelectronic applications. Ground-state DFT and TD-DFT calculations nicely predict the blue shift experimentally observed in the room-temperature absorption and emission spectra of cis-3, compared to the trans complexes. In CH3CN, cis-3 displays a 4-fold increase in photoluminescence quantum yield (PLQY) with respect to trans-3, as a consequence of drastically slower nonradiative rate constant. By contrast, at 77 K, the emission properties of all the compounds, including the cis isomer, are much more similar, with a pronounced hypsochromic shift for the trans complexes. A similar behavior is found in solid state (1% w/w poly(methyl methacrylate) matrix), with all complexes displaying PLQY of ∼70-80%, comparable emission lifetimes (τ ≈ 1.3 μs), and a remarkable rigidochromic shift. To rationalize the more pronounced nonradiative deactivation (and smaller PLQY) observed for photoexcited trans complexes, comparative temperature-dependent emission studies in the range of 77-450 K for cis-3 and trans-3 were made in propylene glycol, showing that solvation effects are primarily responsible for the observed behavior.

  12. Hazard identification of cis/trans-zearalenone through the looking-glass.

    Science.gov (United States)

    Dellafiora, Luca; Galaverna, Gianni; Dall'Asta, Chiara; Cozzini, Pietro

    2015-12-01

    Among the food-related health issues, the presence of contaminants has a prominent role, due to the wide range of exogenous compounds that can occur in food commodities and to their large differences in structure and biological activity. A comprehensive assessment of the related risk is thus actually demanding in terms of time and facilities involved. In this context, the use of computational strategies can be an effective choice for supporting the hazard identification procedure at the early stage. In this work, we focused on the food contaminant zearalenone by comparing the trans and cis isomers, respectively the well-known mycoestrogen and its still largely understudied isomer. We estimated the possible effects exerted by human metabolism on the xenoestrogenicity of cis-ZEN by using a validated in silico strategy based on docking simulations and rescoring procedures. Similarly, the exploitation of the most promising enzymatic detoxifying routes designed for trans-ZEN - which relies on the enzyme lactono hydrolase from Clonostachys rosea - has been assessed for the cis-isomer as well. Our results showed that both isomers can act as functional analogues with respect to xenoestrogenic activity, and several cis-ZEN metabolites with high biological potential have been identified. On the contrary, in spite of the high degree of structural analogy, the cis isomer showed a pattern of interaction with the degrading enzyme in stark contrast with that observed for trans-ZEN. For these reasons, the outcomes presented herein strongly support the inclusion of cis-ZEN in further studies of occurrence, metabolism and bioactivity assessment, and suggest the need for a dedicated handling for the cis isomer in risk assessment studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. CIS-based registration of quality of life in a single source approach

    Directory of Open Access Journals (Sweden)

    Riek Markus

    2011-04-01

    Full Text Available Abstract Background Documenting quality of life (QoL in routine medical care and using it both for treatment and for clinical research is not common, although such information is absolutely valuable for physicians and patients alike. We therefore aimed at developing an efficient method to integrate quality of life information into the clinical information system (CIS and thus make it available for clinical care and secondary use. Methods We piloted our method in three different medical departments, using five different QoL questionnaires. In this setting we used structured interviews and onsite observations to perform workflow and form analyses. The forms and pertinent data reports were implemented using the integrated tools of the local CIS. A web-based application for mobile devices was developed based on XML schemata to facilitate data import into the CIS. Data exports of the CIS were analysed with statistical software to perform an analysis of data quality. Results The quality of life questionnaires are now regularly documented by patients and physicians. The resulting data is available in the Electronic Health Record (EHR and can be used for treatment purposes and communication as well as research functionalities. The completion of questionnaires by the patients themselves using a mobile device (iPad and the import of the respective data into the CIS forms were successfully tested in a pilot installation. The quality of data is rendered high by the use of automatic score calculations as well as the automatic creation of forms for follow-up documentation. The QoL data was exported to research databases for use in scientific analysis. Conclusion The CIS-based QoL is technically feasible, clinically accepted and provides an excellent quality of data for medical treatment and clinical research. Our approach with a commercial CIS and the web-based application is transferable to other sites.

  14. On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

    Science.gov (United States)

    Tarpine, Ryan; Istrail, Sorin

    The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

  15. Statistically significant dependence of the Xaa-Pro peptide bond conformation on secondary structure and amino acid sequence

    Directory of Open Access Journals (Sweden)

    Leitner Dietmar

    2005-04-01

    Full Text Available Abstract Background A reliable prediction of the Xaa-Pro peptide bond conformation would be a useful tool for many protein structure calculation methods. We have analyzed the Protein Data Bank and show that the combined use of sequential and structural information has a predictive value for the assessment of the cis versus trans peptide bond conformation of Xaa-Pro within proteins. For the analysis of the data sets different statistical methods such as the calculation of the Chou-Fasman parameters and occurrence matrices were used. Furthermore we analyzed the relationship between the relative solvent accessibility and the relative occurrence of prolines in the cis and in the trans conformation. Results One of the main results of the statistical investigations is the ranking of the secondary structure and sequence information with respect to the prediction of the Xaa-Pro peptide bond conformation. We observed a significant impact of secondary structure information on the occurrence of the Xaa-Pro peptide bond conformation, while the sequence information of amino acids neighboring proline is of little predictive value for the conformation of this bond. Conclusion In this work, we present an extensive analysis of the occurrence of the cis and trans proline conformation in proteins. Based on the data set, we derived patterns and rules for a possible prediction of the proline conformation. Upon adoption of the Chou-Fasman parameters, we are able to derive statistically relevant correlations between the secondary structure of amino acid fragments and the Xaa-Pro peptide bond conformation.

  16. Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sagara, Chiaki; Takahashi, Katsuhiko [Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, Shinagawa, Tokyo 142-8501 (Japan); Kagechika, Hiroyuki [School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda, Tokyo 101-0062 (Japan); Takahashi, Noriko, E-mail: t-noriko@hoshi.ac.jp [Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, Shinagawa, Tokyo 142-8501 (Japan)

    2013-03-29

    Highlights: ► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1. ► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells. ► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis. ► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells. ► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation. -- Abstract: Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. The complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA’s inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner.

  17. Possible involvement of an extracellular superoxide dismutase (SodA) as a radical scavenger in poly(cis-1,4-isoprene) degradation.

    Science.gov (United States)

    Schulte, Carina; Arenskötter, Matthias; Berekaa, Mahmoud M; Arenskötter, Quyen; Priefert, Horst; Steinbüchel, Alexander

    2008-12-01

    Gordonia westfalica Kb1 and Gordonia polyisoprenivorans VH2 induce the formation of an extracellular superoxide dismutase (SOD) during poly(cis-1,4-isoprene) degradation. To investigate the function of this enzyme in G. polyisoprenivorans VH2, the sodA gene was disrupted. The mutants exhibited reduced growth in liquid mineral salt media containing poly(cis-1,4-isoprene) as the sole carbon and energy source, and no SOD activity was detectable in the supernatants of the cultures. Growth experiments revealed that SodA activity is required for optimal growth on poly(cis-1,4-isoprene), whereas this enzyme has no effect on aerobic growth in the presence of water-soluble substrates like succinate, acetate, and propionate. This was detected by activity staining, and proof of expression was by antibody detection of SOD. When SodA from G. westfalica Kb1 was heterologously expressed in the sodA sodB double mutant Escherichia coli QC779, the recombinant mutant exhibited increased resistance to paraquat, thereby indicating the functionality of the G. westfalica Kb1 SodA and indirectly protection of G. westfalica cells by SodA from oxidative damage. Both sodA from G. polyisoprenivorans VH2 and sodA from G. westfalica Kb1 coded for polypeptides comprising 209 amino acids and having approximately 90% and 70% identical amino acids, respectively, to the SodA from Mycobacterium smegmatis strain MC(2) 155 and Micrococcus luteus NCTC 2665. As revealed by activity staining experiments with the wild type and the disruption mutant of G. polyisoprenivorans, this bacterium harbors only one active SOD belonging to the manganese family. The N-terminal sequences of the extracellular SodA proteins of both Gordonia species showed no evidence of leader peptides for the mature proteins, like the intracellular SodA protein of G. polyisoprenivorans VH2, which was purified under native conditions from the cells. In G. westfalica Kb1 and G. polyisoprenivorans VH2, SodA probably provides protection

  18. Conjugated linoleic acid (CLA. Cis 9, trans 11 and trans 10, cis 12 isomer detection in crude and refined corn oils by capillary GC

    Directory of Open Access Journals (Sweden)

    Özlem Tokuşoğlu

    2008-06-01

    Full Text Available Conjugated linoleic acids (CLAs exhibit protective effects against various types of cancer and heart diseases. With the newly developed capillary gas chromatographic method (GC, cis9, trans11 and trans10, cis12 octadecadienoic acid isomers of CLA (C18:2 were determined in crude and refined corn oils as qualitative and quantitative measurements. Cis 9, trans11 C18:2 (c9, t11 CLA was the major CLA isomer in both oils. It was found that c9, t11 CLA was 0.62% of the total lipid in crude oil and 1.24% of the total lipid in refined oil. Using the refining process, the total CLA was 1.38% whereas that of crude corn oil was 0.62%. An approximate 2.2 fold increase in the total CLA was found in refined oil (n = 9 (p y = 2.782x + 0.046 (R2 = 0.9999] were performed (p El ácido linoleico conjugado (CLA parece exhibir efecto protector frente a enfermedades cardiovasculares y varios tipos de cáncer. En este trabajo, se establece un mátodo analítico mediante cromatografía de gases con columna capilar para la determinación cualitativa y cuantitativa de los isómeros cis 9,trans 11 y trans 10, cis 12 en aceites de maiz crudo y refinado. El isómero cis 9, trans11 C18:2 fue el mayoritario encontrándose en concentraciones de 0.62% en el aceite cru,do y de 1.24 % en el aceite refinado. La cantidad total de CLA encontrada en el aceite refinado (n = 9 (p 2 = 0.9999 y de recuperación [y = 2.782x+0.046 (R2 = 0.9999]. El método cromatográfico propuesto podría ser usado para el control de calidad de los aceites vegetales.

  19. Correlation between the molecular structure and trans←→ cis isomerization characteristics of azobenzenes

    Institute of Scientific and Technical Information of China (English)

    HAN Mina; HONDA Takumu

    2012-01-01

    Photochemical and thermal isomerization of various azobenzenes was systematically investigated to understand the correlation between the molecular structure and trans←→cis isomerization characteristics of azobenzenes.A blue shift in π-π* absorption band of ortho-alkylated azobenzenes (1o and 2o) was observed together with a reduction in molar extinction coefficient (ε) in comparison with both meta-alkylated azobenzenes (4m and 5m) and 7p lacking the meta and ortho substituents.For ortho-alkylated azobenzene,photochemical trans-to-cis isomerization and thermal back cis-to-trans isomerization in solution occurred slowly when compared with 4m,5m and 7p.The half-life time of the cis form of 2o was found to be 380 h,which is about 8-50 times longer than those of comparable 4m,5m (43-13 h) and 7p (7h).Furthermore,comparison of the molecular structure and isomerization characteristics of azobenzene thiol (2oand 5m) self-assembled monolayers on flat gold surfaces indicates that the trans-to-cis photoconversion in monolayer systems is influenced by steric hindrance and strong intermolecular interaction between azobenzene units.

  20. Extensive cis-regulatory variation robust to environmental perturbation in Arabidopsis.

    Science.gov (United States)

    Cubillos, Francisco A; Stegle, Oliver; Grondin, Cécile; Canut, Matthieu; Tisné, Sébastien; Gy, Isabelle; Loudet, Olivier

    2014-11-01

    cis- and trans-acting factors affect gene expression and responses to environmental conditions. However, for most plant systems, we lack a comprehensive map of these factors and their interaction with environmental variation. Here, we examined allele-specific expression (ASE) in an F1 hybrid to study how alleles from two Arabidopsis thaliana accessions affect gene expression. To investigate the effect of the environment, we used drought stress and developed a variance component model to estimate the combined genetic contributions of cis- and trans-regulatory polymorphisms, environmental factors, and their interactions. We quantified ASE for 11,003 genes, identifying 3318 genes with consistent ASE in control and stress conditions, demonstrating that cis-acting genetic effects are essentially robust to changes in the environment. Moreover, we found 1618 genes with genotype x environment (GxE) interactions, mostly cis x E interactions with magnitude changes in ASE. We found fewer trans x E interactions, but these effects were relatively less robust across conditions, showing more changes in the direction of the effect between environments; this confirms that trans-regulation plays an important role in the response to environmental conditions. Our data provide a detailed map of cis- and trans-regulation and GxE interactions in A. thaliana, laying the ground for mechanistic investigations and studies in other plants and environments.

  1. Extensive cis-Regulatory Variation Robust to Environmental Perturbation in Arabidopsis[W

    Science.gov (United States)

    Cubillos, Francisco A.; Stegle, Oliver; Grondin, Cécile; Canut, Matthieu; Tisné, Sébastien; Gy, Isabelle

    2014-01-01

    cis- and trans-acting factors affect gene expression and responses to environmental conditions. However, for most plant systems, we lack a comprehensive map of these factors and their interaction with environmental variation. Here, we examined allele-specific expression (ASE) in an F1 hybrid to study how alleles from two Arabidopsis thaliana accessions affect gene expression. To investigate the effect of the environment, we used drought stress and developed a variance component model to estimate the combined genetic contributions of cis- and trans-regulatory polymorphisms, environmental factors, and their interactions. We quantified ASE for 11,003 genes, identifying 3318 genes with consistent ASE in control and stress conditions, demonstrating that cis-acting genetic effects are essentially robust to changes in the environment. Moreover, we found 1618 genes with genotype x environment (GxE) interactions, mostly cis x E interactions with magnitude changes in ASE. We found fewer trans x E interactions, but these effects were relatively less robust across conditions, showing more changes in the direction of the effect between environments; this confirms that trans-regulation plays an important role in the response to environmental conditions. Our data provide a detailed map of cis- and trans-regulation and GxE interactions in A. thaliana, laying the ground for mechanistic investigations and studies in other plants and environments. PMID:25428981

  2. Coevolution within a transcriptional network by compensatory trans and cis mutations

    KAUST Repository

    Kuo, D.

    2010-10-26

    Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA sequences near genes as the main cause of divergence. What is less clear is how these changes interact with trans-acting changes occurring elsewhere in the genetic circuit. Here, we report the discovery of a system of compensatory trans and cis mutations in the yeast AP-1 transcriptional network that allows for conserved transcriptional regulation despite continued genetic change. We pinpoint a single species, the fungal pathogen Candida glabrata, in which a trans mutation has occurred very recently in a single AP-1 family member, distinguishing it from its Saccharomyces ortholog. Comparison of chromatin immunoprecipitation profiles between Candida and Saccharomyces shows that, despite their different DNA-binding domains, the AP-1 orthologs regulate a conserved block of genes. This conservation is enabled by concomitant changes in the cis-regulatory motifs upstream of each gene. Thus, both trans and cis mutations have perturbed the yeast AP-1 regulatory system in such a way as to compensate for one another. This demonstrates an example of “coevolution” between a DNA-binding transcription factor and its cis-regulatory site, reminiscent of the coevolution of protein binding partners.

  3. cis p-tau: early driver of brain injury and tauopathy blocked by antibody

    Science.gov (United States)

    Mannix, Rebekah; Qiu, Jianhua; Moncaster, Juliet; Chen, Chun-Hau; Yao, Yandan; Lin, Yu-Min; Driver, Jane A; Sun, Yan; Wei, Shuo; Luo, Man-Li; Albayram, Onder; Huang, Pengyu; Rotenberg, Alexander; Ryo, Akihide; Goldstein, Lee E; Pascual-Leone, Alvaro; McKee, Ann C.; Meehan, William; Zhou, Xiao Zhen; Lu, Kun Ping

    2015-01-01

    Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD), whose defining pathologic features include tauopathy made of phosphorylated tau (p-tau). However, tauopathy has not been detected in early stages after TBI and how TBI leads to tauopathy is unknown. Here we find robust cis p-tau pathology after sport- and military-related TBI in humans and mice. Acutely after TBI in mice and stress in vitro, neurons prominently produce cis p-tau, which disrupts axonal microtubule network and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, termed “cistauosis”, appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis p-tau is a major early driver after TBI and leads to tauopathy in CTE and AD, and cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury. PMID:26176913

  4. Reactivity of monofunctional cis-platinum adducts as a function of DNA sequence.

    Science.gov (United States)

    Malinge, J M; Leng, M

    1988-08-11

    The purpose of this work was to study the chemical reactivity of monofunctional cis-platinum-nucleic acid adducts as a function of nucleic acid sequence. The first part of the paper deals with the formation of these adducts. It is shown that the ternary nucleic acid-cis-platinum-ethidium bromide complexes in which ethidium bromide and nucleotide residues are cross-linked by cis-platinum, are relatively unstable at 37 degrees C. In the presence of acridine, ethidium bromide (but not cis-platinum) is slowly released which leads to the formation of monofunctional cis-platinum-nucleic acid adducts. After removal of acridine, the monofunctional adducts react further to become bifunctional. The second part of the paper deals with the kinetics of disappearance of the monofunctional adducts in several polynucleotides but not in poly(dG).poly(dC). When the adducts possess a chloride ligand, the limiting step in the cross-linking is the rate of aquation reaction of the chloride ligand. The rate constants are an order of magnitude larger when the monofunctional adducts do not possess a chloride ligand. In both the cases, the rate constants are apparently independent of the nucleic acid sequence.

  5. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  6. Transition Metal Donor-Peptide-Acceptor Complexes: From Intramolecular Electron Transfer Reactions to the Study of Reactive Intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Isied, Stephan S.

    2003-03-11

    The trans-polyproline (PII) oligomers (Figure 1) are unusually rigid peptide structures which have been extensively studied by our group for peptide mediated intramolecular electron transfer (ET) at long distances. We have previously studied ET across a series of metal ion donor (D) acceptor (A) oligoproline peptides with different distances, driving forces and reorganizational energies. The majority of these experiments involve generating the ET intermediate using pulse radiolysis methods, although more recently photochemical methods are also used. Results of these studies showed that ET across peptides can vary by more than twelve orders of magnitude. Using ruthenium bipyridine donors, ET reaction rate constants across several proline residues (n = 4 - 9) occurred in the millisecond (ms) to {micro}s timescale, thus limiting the proline peptide conformational motions to only minor changes (far smaller than the large changes that occur on the ms to sec timescale, such as trans to cis proline isomerization). The present report describes our large data base of experimental results for D-peptide-A complexes in terms of a model where the involvement of both superexchange and hopping (hole and electron) mechanisms account for the long range ET rate constants observed. Our data shows that the change from superexchange to hopping mechanisms occurs at different distances depending on the type of D and A and their interactions with the peptides. Our model is also consistent with generalized models for superexchange and hopping which have been put forward by a number of theoretical groups to account for long range ET phenomena.

  7. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  8. The Pig PeptideAtlas

    DEFF Research Database (Denmark)

    Hesselager, Marianne Overgaard; Codrea, Marius; Sun, Zhi;

    2016-01-01

    underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within...... the veterinary proteomics domain, and this article demonstrates how the expression of isoform-unique peptides can be observed across distinct tissues and body fluids. The Pig PeptideAtlas is a unique resource for use in animal proteome research, particularly biomarker discovery and for preliminary design of SRM...

  9. Biodiscovery of aluminum binding peptides

    Science.gov (United States)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Hurley, Margaret M.; Stratis-Cullum, Dimitra

    2013-05-01

    Cell surface peptide display systems are large and diverse libraries of peptides (7-15 amino acids) which are presented by a display scaffold hosted by a phage (virus), bacteria, or yeast cell. This allows the selfsustaining peptide libraries to be rapidly screened for high affinity binders to a given target of interest, and those binders quickly identified. Peptide display systems have traditionally been utilized in conjunction with organic-based targets, such as protein toxins or carbon nanotubes. However, this technology has been expanded for use with inorganic targets, such as metals, for biofabrication, hybrid material assembly and corrosion prevention. While most current peptide display systems employ viruses to host the display scaffold, we have recently shown that a bacterial host, Escherichia coli, displaying peptides in the ubiquitous, membrane protein scaffold eCPX can also provide specific peptide binders to an organic target. We have, for the first time, extended the use of this bacterial peptide display system for the biodiscovery of aluminum binding 15mer peptides. We will present the process of biopanning with macroscopic inorganic targets, binder enrichment, and binder isolation and discovery.

  10. Antitumor Peptides from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Mi Sun

    2011-10-01

    Full Text Available The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.

  11. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective.......This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  12. Combining anti-cancer drugs with artificial sweeteners: synthesis and anti-cancer activity of saccharinate (sac) and thiosaccharinate (tsac) complexes cis-[Pt(sac)2(NH3)2] and cis-[Pt(tsac)2(NH3)2].

    Science.gov (United States)

    Al-Jibori, Subhi A; Al-Jibori, Ghassan H; Al-Hayaly, Lamaan J; Wagner, Christoph; Schmidt, Harry; Timur, Suna; Baris Barlas, F; Subasi, Elif; Ghosh, Shishir; Hogarth, Graeme

    2014-12-01

    The new platinum(II) complexes cis-[Pt(sac)2(NH3)2] (sac=saccharinate) and cis-[Pt(tsac)2(NH3)2] (tsac=thiosaccharinate) have been prepared, the X-ray crystal structure of cis-[Pt(sac)2(NH3)2] x H2O reveals that both saccharinate anions are N-bound in a cis-arrangement being inequivalent in both the solid-state and in solution at room temperature. Preliminary anti-cancer activity has been assessed against A549 human alveolar type-II like cell lines with the thiosaccharinate complex showing good activity.

  13. Property study of poly nitro compounds of cis-syn-cis-2, 6-dioxodecahydro-lH, 5H-diimidazo [4, 5-b: 4', 5'-e] pyrazine

    Science.gov (United States)

    Liu, Yang; Xu, Zhibin; Xu, Yudong; Xu, Liang; Meng, Zihui

    2017-03-01

    Poly nitro group substituted cis-syn-cis-2, 6-dioxodecahydro-lH, 5H-diimidazo [4, 5-b: 4', 5'-e] pyrazine derivatives are synthesized by modified method and adequately characterized. All compounds have good performance both in density (ρ> 1.85 g/cm3) and high detonation velocity (vD > 8800 m/s, calculated). Some representative compounds, for example, 4 (vD: 9405 ms-1; P: 41.6 GPa) and 5 (vD:9781 ms-1; P: 45.6 GPa) exhibit excellent detonation performances, which are comparable with current energetic compounds such as RDX (vD: 8724 ms-1; P: 35.2 GPa) and HMX (vD:9059 ms-1; P: 39.2 GPa). Considering the sensitivity increasing with the number of nitro group, two componds with tetranitro groups (2 and 3) are worthy of deep research.

  14. Peptides and Food Intake

    Science.gov (United States)

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  15. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  16. Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, A.; Fedorov, A; Fedorov, E; Schnoes, A; Glasner, M; Burley, S; Babbitt, P; Almo, S; Gerlt, J

    2009-01-01

    The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature's strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the a-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the e-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologous MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, gi 70731221; anti, Mycobacterium smegmatis, gi 118470554) document that the conserved Lys at the end of the second e-strand in the (e/a)7e-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of 'pseudoconvergent' evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction.

  17. Examining the Influence of Phosphorylation on Peptide Ion Structure by Ion Mobility Spectrometry-Mass Spectrometry

    Science.gov (United States)

    Glover, Matthew S.; Dilger, Jonathan M.; Acton, Matthew D.; Arnold, Randy J.; Radivojac, Predrag; Clemmer, David E.

    2016-05-01

    Ion mobility spectrometry-mass spectrometry (IMS-MS) techniques are used to study the general effects of phosphorylation on peptide structure. Cross sections for a library of 66 singly phosphorylated peptide ions from 33 pairs of positional isomers, and unmodified analogues were measured. Intrinsic size parameters (ISPs) derived from these measurements yield calculated collision cross sections for 85% of these phosphopeptide sequences that are within ±2.5% of experimental values. The average ISP for the phosphoryl group (0.64 ± 0.05) suggests that in general this moiety forms intramolecular interactions with the neighboring residues and peptide backbone, resulting in relatively compact structures. We assess the capability of ion mobility to separate positional isomers (i.e., peptide sequences that differ only in the location of the modification) and find that more than half of the isomeric pairs have >1% difference in collision cross section. Phosphorylation is also found to influence populations of structures that differ in the cis/ trans orientation of Xaa-Pro peptide bonds. Several sequences with phosphorylated Ser or Thr residues located N-terminally adjacent to Pro residues show fewer conformations compared to the unmodified sequences.

  18. Temperature- and Photocontrolled Unfolding/Folding of a Triple-Helical Azobenzene-Stapled Collagen Peptide Monitored by Infrared Spectroscopy.

    Science.gov (United States)

    Lorenz, Lisa; Kusebauch, Ulrike; Moroder, Luis; Wachtveitl, Josef

    2016-05-04

    The triple-helical structure of a model collagen peptide possessing azobenzene-derived clamps integrated in all three strands as side-chain-to-side-chain crosslinks is analyzed by IR spectroscopy in comparative thermal excursion experiments with the triple helix of a typical reference collagen peptide consisting of only glycine-proline-hydroxyproline repeats. By exploiting the known stabilizing effects of aqueous alcoholic solvents on the unique collagen fold, deuterated ethylene glycol/water (1:1) is used as a solvent to investigate the effect of the light-switchable trans/cis-azobenzene clamp on the stability of the triple helix in terms of H/D exchange rates and thermal unfolding. Results of this comparative analysis clearly reveal only a minor destabilization of the triple helix by the hydrophobic azobenzene moieties compared to the reference collagen peptide as reflected by a lower midpoint of the thermal unfolding and higher rates of H/D exchange. However, it also reveals that the driving force exerted by the trans-to-cis photoisomerization of the azobenzene moieties is insufficient for unfolding of the compact triple-helical collagen fold. Only temperature-dependent untightening of this fold with heating results in a reversible photomodulated unfolding and refolding of the azo-collagen peptide into the original triple helix.

  19. Cis-, intra-, subgenesis, genome editing as modern technologies for modifying the crop genomes (review

    Directory of Open Access Journals (Sweden)

    Н. Е. Волкова

    2016-02-01

    Full Text Available Purpose. Reviewing the literature on modern technologies of genetic modification of crop genomes. Results. The current state of genetically modified plants creation is analyzed. The information on cis-, intra- and subgenic plants and their comparison with transgenic crops is given. Examples of cis- and intragenesis application for improving characteristics of crops are provided. Such state-of-the-art technology of crop genome modification as genome editing is considered. Conclusions. Technologies for producing cis-, intra-, subgenic plants are rapidly developing and resulting in crops of the 21st century that can solve the problem of food provision for a constantly growing world population with the least contrary to the public interest.

  20. Managing the competitiveness in CIS countries and Ukraine: the goal and conditions

    Directory of Open Access Journals (Sweden)

    Anna KUKHARUK

    2017-06-01

    Full Text Available The study is focused on the analysis of conditions for business development and the industrial enterprises’ competitiveness formation in Commonwealth of Independent States (CIS. The study is based on several concepts – sustainable development, macroeconomic stability, “green economy”, and competitiveness. The article analyses the level of macroeconomic instability in a sample of CIS countries and Ukraine following the statistical approach and using the variation coefficient. The authors suggest calculating the indicators of stable development (SD-indicator and business simplicity (SB-indicator based on the international analytical reports data. Several CIS countries are visualized in SD and SB coordinates. The study defines the countries where the conditions for business competitiveness are to be improved due to the comparatively higher level of macroeconomic instability. The article will be interesting to scientists whose subject of research is the competitiveness of enterprises or the economic instability phenomena.

  1. Siemens solar CIS photovoltaic module and system performance at the National Renewable Energy Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Strand, T.; Kroposki, B.; Hansen, R. [National Renewable Energy Lab., Golden, CO (United States); Willett, D. [Siemens Solar Industries, Camarillo, CA (United States)

    1996-05-01

    This paper evaluates the individual module and array performance of Siemens Solar Industries copper indium diselenide (CIS) polycrystalline thin-film technology. This is accomplished by studying module and array performance over time. Preliminary temperature coefficients for maximum power, maximum-power voltage, maximum-power current, open-circuit voltage, short-circuit current, and fill factor are determined at both the module and array level. These coefficients are used to correct module/array performance to 25{degrees}C to evaluate stability. The authors show that CIS exhibits a strong inverse correlation between array power and back-of-module temperature. This is due mainly to the narrow bandgap of the CIS material, which results in a strong inverse correlation between voltage and temperature. They also show that the temperature-corrected module and array performance has been relatively stable over the evaluation interval ({approx}2 years).

  2. [Role of genes and their cis-regulatory elements during animal morphological evolution].

    Science.gov (United States)

    Sun, Boyuan; Tu, Jianbo; Li, Ying; Yang, Mingyao

    2014-06-01

    Cis-regulatory hypothesis is one of the most important theories in evolutionary developmental biology (evo-devo), which claims that evolution of cis-regulatory elements (CREs) plays a key role during evolution of morphology. However, an increasing number of experimental results show that cis-regulatory hypothesis alone is not far enough to explain the complexity of evo-devo processes. Other modifications, including mutations of protein coding, gene and genome duplications, and flexibility of homeodomains and CREs, also cause the morphological changes in animals. In this review, we retrospect the recent results of evolution of CREs and genes associated with CREs and discuss new methods and trends for research in evo-devo.

  3. The cis-trans Isomerisation of Homologous 2-Hydroxycycloalkanecarboxylic Acids under Basic Conditions

    Institute of Scientific and Technical Information of China (English)

    GYARMATI, Cs. Zsuzsanna; P(A)LINK(O), István; BOKROS, Attila; MARTINEK, A. Tamás; BERN(A)TH, Gábor

    2006-01-01

    The cis→trans isomerisation of homologous 2-hydroxycycloalkanecarboxylic acids in strongly basic aqueous solution was studied starting from the cis isomers. It was found that the cyclopentane, cyclohexane and cycloheptane homologues afforded synthetically useful amounts of the trans acids and the procedure resulted in relatively small quantities of the corresponding olefinic acids. In contrast, the isomerisation of the cis-2-hydroxycyclooctanecarboxylic acid produced roughly equal amounts of the cis and trans isomers and the 1-cyclooctenecarboxylic acid at equilibrium. Molecular modelling with the PM3 semiempirical method of the reactants, products and the intermediates applying explicit water molecules as reaction medium gave a fair estimate for the rate sequence of the idealised (dehydration-free) isomerisation reactions in aqueous base solution.

  4. MOLDOVA’S CHANCE TO INNOVATION: CAN THE CIS SURVEY HELP A DEVELOPING COUNTRYSUCCEED?

    Directory of Open Access Journals (Sweden)

    Daniela DUCA

    2013-06-01

    Full Text Available The Republic of Moldova is one of the few remaining countries in Europe that has not yet taken the Community Innovation Survey (CIS. Can this survey help Moldova identify the drawbacks and advantages of its national innovation system? This article establishes that CIS is indeed a useful tool for an initial diagnostic study. However, in a transitional economy, where little is known about innovation, CIS results must be complemented with open-ended questionnaires. It is found that, even though the innovation output is relatively high compared to other developing countries, Moldova is stuck in Rothwell’s first generation model of innovation. Moreover, as resources are not readily available for purchasing new technologies, the government and private companies can work towards encouraging a knowledge infrastructure that promotes organizational and management innovations.

  5. A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors

    Directory of Open Access Journals (Sweden)

    Michael A. White

    2016-10-01

    Full Text Available Transcription factors often activate and repress different target genes in the same cell. How activation and repression are encoded by different arrangements of transcription factor binding sites in cis-regulatory elements is poorly understood. We investigated how sites for the transcription factor CRX encode both activation and repression in photoreceptors by assaying thousands of genomic and synthetic cis-regulatory elements in wild-type and Crx−/− retinas. We found that sequences with high affinity for CRX repress transcription, whereas sequences with lower affinity activate. This rule is modified by a cooperative interaction between CRX sites and sites for the transcription factor NRL, which overrides the repressive effect of high affinity for CRX. Our results show how simple rearrangements of transcription factor binding sites encode qualitatively different responses to a single transcription factor and explain how CRX plays multiple cis-regulatory roles in the same cell.

  6. A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis

    Energy Technology Data Exchange (ETDEWEB)

    Keys, David N.; Lee, Byung-in; Di Gregorio, Anna; Harafuji, Naoe; Detter, Chris; Wang, Mei; Kahsai, Orsalem; Ahn, Sylvia; Arellano, Andre; Zhang, Quin; Trong, Stephan; Doyle, Sharon A.; Satoh, Noriyuki; Satou, Yutaka; Saiga, Hidetoshi; Christian, Allen; Rokhsar, Dan; Hawkins, Trevor L.; Levine, Mike; Richardson, Paul

    2005-01-05

    A screen for the systematic identification of cis-regulatory elements within large (>100 kb) genomic domains containing Hox genes was performed by using the basal chordate Ciona intestinalis. Randomly generated DNA fragments from bacterial artificial chromosomes containing two clusters of Hox genes were inserted into a vector upstream of a minimal promoter and lacZ reporter gene. A total of 222 resultant fusion genes were separately electroporated into fertilized eggs, and their regulatory activities were monitored in larvae. In sum, 21 separable cis-regulatory elements were found. These include eight Hox linked domains that drive expression in nested anterior-posterior domains of ectodermally derived tissues. In addition to vertebrate-like CNS regulation, the discovery of cis-regulatory domains that drive epidermal transcription suggests that C. intestinalis has arthropod-like Hox patterning in the epidermis.

  7. Hydrogenation of fluoroarenes: Direct access to all-cis-(multi)fluorinated cycloalkanes.

    Science.gov (United States)

    Wiesenfeldt, Mario P; Nairoukh, Zackaria; Li, Wei; Glorius, Frank

    2017-09-01

    All-cis-multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular, they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Very few such motifs have been prepared, as their syntheses require multistep sequences from diastereoselectively prefunctionalized precursors. Herein we report a synthetic strategy to access these valuable materials via the rhodium-cyclic (alkyl)(amino)carbene (CAAC)-catalyzed hydrogenation of readily available fluorinated arenes in hexane. This route enables the scalable single-step preparation of an abundance of multisubstituted and multifluorinated cycloalkanes, including all-cis-1,2,3,4,5,6-hexafluorocyclohexane as well as cis-configured fluorinated aliphatic heterocycles. Copyright © 2017, American Association for the Advancement of Science.

  8. Exhaustive Search for Over-represented DNA Sequence Motifs with CisFinder

    Science.gov (United States)

    Sharov, Alexei A.; Ko, Minoru S.H.

    2009-01-01

    We present CisFinder software, which generates a comprehensive list of motifs enriched in a set of DNA sequences and describes them with position frequency matrices (PFMs). A new algorithm was designed to estimate PFMs directly from counts of n-mer words with and without gaps; then PFMs are extended over gaps and flanking regions and clustered to generate non-redundant sets of motifs. The algorithm successfully identified binding motifs for 12 transcription factors (TFs) in embryonic stem cells based on published chromatin immunoprecipitation sequencing data. Furthermore, CisFinder successfully identified alternative binding motifs of TFs (e.g. POU5F1, ESRRB, and CTCF) and motifs for known and unknown co-factors of genes associated with the pluripotent state of ES cells. CisFinder also showed robust performance in the identification of motifs that were only slightly enriched in a set of DNA sequences. PMID:19740934

  9. Trans- and cis-resveratrol concentration in wines produced in Serbia

    Directory of Open Access Journals (Sweden)

    SANJA DJEKIC

    2008-10-01

    Full Text Available Resveratrol, which occurs in two isomeric forms, trans and cis, is a phytoalexin with numerous pharmacological activities, such as anti-cancer, antiviral, neuroprotective and anti-aging. Red wine is the main source of the compound and an easy way of including resveratrol in the human diet. In this study, the most popular commercial Serbian wines (red, white and rosé-type were analyzed for their content of trans- and cis-resveratrol. The analysis was performed by HPLC with a UV detector. Prior to the injection, phenolic compounds were extracted onto a LiChrolut RP18 bonded silica cartridge. The concentration of trans-resveratrol ranged from 0.11 to 1.69 mg L-1 and cis-resveratrol from 0.12 to 1.49 mg L-1.

  10. Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.

    Directory of Open Access Journals (Sweden)

    Arnab Bhattacherjee

    2013-10-01

    Full Text Available The binding of short disordered peptide stretches to globular protein domains is important for a wide range of cellular processes, including signal transduction, protein transport, and immune response. The often promiscuous nature of these interactions and the conformational flexibility of the peptide chain, sometimes even when bound, make the binding specificity of this type of protein interaction a challenge to understand. Here we develop and test a Monte Carlo-based procedure for calculating protein-peptide binding thermodynamics for many sequences in a single run. The method explores both peptide sequence and conformational space simultaneously by simulating a joint probability distribution which, in particular, makes searching through peptide sequence space computationally efficient. To test our method, we apply it to 3 different peptide-binding protein domains and test its ability to capture the experimentally determined specificity profiles. Insight into the molecular underpinnings of the observed specificities is obtained by analyzing the peptide conformational ensembles of a large number of binding-competent sequences. We also explore the possibility of using our method to discover new peptide-binding pockets on protein structures.

  11. Kinetics and mechanism of interaction of some bioactive ligands with cis-diaqua(cis-1,2-diaminocyclohexane)platinum(II) in aqueous medium

    Indian Academy of Sciences (India)

    P Karmakar; S Ray; S Mallick; B K Bera; A Mandal; S Mondal; A K Ghosh

    2013-09-01

    The substitution reaction of cis-[Pt(cis-dach)(H2O)2]2+ (where `dach’ is cis-1,2-diaminocyclohexane) with 2-thiouracil (S, N), 1,2-cyclohexanedionedioxime (N, N) and acetylacetone (O, O) were studied in aqueous solution in 0.10 M NaClO4 under pseudo-first order conditions as a functions of concentration, pH and temperature using UV-Vis spectrophotometry. The substitution reaction proceeds via rapid outer sphere association complex formation, followed by two slow consecutive steps. The first of these involves ligand-assisted deaquation, while second involves chelation as the second aqua ligand is displaced. The association equilibrium constant (KE) for the outer sphere complex formation has been evaluated together with rate constants for the two subsequent steps. The rate constants increase with increasing ligand concentration and the evaluated activation parameters for all reactions suggest an associative substitution mechanism for both the aqua ligand substitution processes. The product of the reaction has been characterized by IR, NMR and ESI-MS spectral analysis; which throws more light on the mechanistic behaviour of platinum(II) antitumour complexes.

  12. Comparative toxicity of cis-cypermethrin in rainbow trout, frog, mouse, and quail.

    Science.gov (United States)

    Edwards, R; Millburn, P; Hutson, D H

    1986-07-01

    The synthetic alpha-cyano-phenoxybenzyl-containing pyrethroid insecticides act on the CNS of vertebrates and show a species-selective toxicity in the order fish greater than amphibians much greater than mammals greater than birds. Concentrations of [14C]cis-cypermethrin in the brains of representative members of each of these classes of chordates were measured at toxic signs (an onset of hyperactivity followed by seizures and loss of balance/equilibrium) as an indicator of target organ sensitivity. The concentration of cis-cypermethrin in brain, associated with toxic signs, in micrograms per gram (mean +/- SE) as determined by high-performance liquid chromatography was 0.08 +/- 0.03 (frog), 0.23 +/- 0.05 (trout), 1.71 +/- 0.33 (mouse), and 3.94 +/- 0.88 (quail). Trout brain was equally sensitive to the cis and trans isomers of cypermethrin. In both mouse and quail, some 90% of the radioactivity in the brain was parent pyrethroid. Trout and frog, however, afforded only 56 and 32%, respectively, of the brain 14C as cypermethrin, with the remaining radioactivity in both extractable and nonextractable metabolites, including 4'-hydroxy-cis-cypermethrin, which is potentially neuroactive. Following oral administration, cis-cypermethrin was readily absorbed and metabolized by quail. Intestinal uptake was far less rapid in trout and mouse, with unchanged cypermethrin dispersed in secreted bile, being readily eliminated from the intestines of fish. The uptake and metabolism of cis-cypermethrin and the brain sensitivities of these animals to the pyrethroid account for the observed differences in acute toxicity.

  13. Dietary linseed oil increases trans-10,cis-15 18:2 in caprine milk fat.

    Science.gov (United States)

    Gómez-Cortés, P; Cívico, A; de la Fuente, M A; Juárez, M; Sánchez, N Núñez; Blanco, F Peña; Marín, A L Martínez

    2017-06-01

    Trans-10,cis-15 18:2 has been recently detected and characterized in digestive contents and meat and adipose tissue of ruminants, but its presence in milk and dairy products is hardly known. The aim of this study was to quantify trans-10,cis-15 18:2 in milk fat, better understand its metabolic origin, and help to elucidate the mechanisms of rumen biohydrogenation when the diet composition might affect ruminal environment. To address these objectives, 16 dairy goats were allocated to 2 simultaneous experiments (2 groups of goats and 2 treatments in each experiment). Experimental treatments consisted of basal diets with the same forage-to-concentrate ratio (33/67) and 2 starch-to-nonforage neutral detergent fiber (NDF) ratios (0.8 and 3.1), which were supplemented or not with 30 g/d of linseed oil for 25 d in a crossover design. Trans-10,cis-15 18:2 contents in milk fat were determined by gas chromatography fitted with an extremely polar capillary column (SLB-IL111). Levels of trans-10,cis-15 18:2 in individual milk fat samples ranged from 0 to 0.2% of total fatty acids, and its content in milk fat increased 8 fold due to linseed oil supplementation, substantiating the predominant role of α-linolenic acid in its formation. The trans-10,cis-15 18:2 levels in milk fat were similar in both experiments, despite the fact starch-to-nonforage NDF ratio of their respective basal diets greatly differed. In conclusion, trans-10,cis-15 18:2 was clearly related to linseed oil supplementation, and its increase in milk fat was comparable when the basal diets were rich in either nonforage NDF or starch. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Computational identification of new structured cis-regulatory elements in the 3'-untranslated region of human protein coding genes.

    Science.gov (United States)

    Chen, Xiaowei Sylvia; Brown, Chris M

    2012-10-01

    Messenger ribonucleic acids (RNAs) contain a large number of cis-regulatory RNA elements that function in many types of post-transcriptional regulation. These cis-regulatory elements are often characterized by conserved structures and/or sequences. Although some classes are well known, given the wide range of RNA-interacting proteins in eukaryotes, it is likely that many new classes of cis-regulatory elements are yet to be discovered. An approach to this is to use computational methods that have the advantage of analysing genomic data, particularly comparative data on a large scale. In this study, a set of structural discovery algorithms was applied followed by support vector machine (SVM) classification. We trained a new classification model (CisRNA-SVM) on a set of known structured cis-regulatory elements from 3'-untranslated regions (UTRs) and successfully distinguished these and groups of cis-regulatory elements not been strained on from control genomic and shuffled sequences. The new method outperformed previous methods in classification of cis-regulatory RNA elements. This model was then used to predict new elements from cross-species conserved regions of human 3'-UTRs. Clustering of these elements identified new classes of potential cis-regulatory elements. The model, training and testing sets and novel human predictions are available at: http://mRNA.otago.ac.nz/CisRNA-SVM.

  15. trans and cis Chromophore structures in the kindling fluorescent protein asFP595

    Science.gov (United States)

    Grigorenko, Bella; Savitsky, Alexander; Topol, Igor; Burt, Stanley; Nemukhin, Alexander

    2006-06-01

    The ab initio QM/MM calculations are used to optimize geometry configurations of the chromophore and surrounding residues for the kindling protein asFP595. The time-dependent DFT method is applied to estimate parameters of the S 0-S 1 vertical transition of the chromophore at the protein geometry taking into account effects from the nearest residues. The results of simulations provide a theoretical support to the hypothesis on the possibility of trans-cis izomerization of the chromophore in the mechanism of kindling. The system can absorb light in the trans anion form of the chromophore and emit at longer wavelength in the cis anion form.

  16. 抗HIV活性物质三取代(+)-cis-Khellactone衍生物的合成

    Institute of Scientific and Technical Information of China (English)

    赵春红; 谢蓝

    2003-01-01

      具有(+)-cis-Khellactone骨架结构的天然产物Suksdorfin具有明显的抗HIV活性.在对Suksdorfin进行系统的结构修饰和优化过程中发现(3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone(DCK)的类似物对HIV-1在H9细胞中的复制有非常强的抑制活性.……

  17. Spatially separated polar samples of the cis and trans conformers of 3-fluorophenol

    CERN Document Server

    Kierspel, Thomas; Chang, Yuan-Pin; Küpper, Jochen

    2013-01-01

    We demonstrate the spatial separation of the cis- and trans-conformers of 3-fluorophenol in the gas phase based on their distinct electric dipole moments. For both conformers we create very polar samples of their lowest-energy rotational quantum states. A >95 % pure beam of trans-3-fluorophenol and a >90 % pure beam of the lowest-energy rotational states of the less polar cis-3-fluorophenol were obtained for helium and neon supersonic expansions, respectively. This is the first demonstration of the spatial separation of the lowest-energy rotational states of the least polar conformer, which is necessary for strong alignment and orientation of all individual conformers.

  18. Local structure in the disordered solid solution of cis- and trans-perinones

    DEFF Research Database (Denmark)

    Teteruk, Jaroslav L.; Glinnemann, Juergen; Heyse, Winfried;

    2016-01-01

    The cis- and trans-isomers of the polycyclic aromatic compound perinone, C26H12N4O2, form a solid solution (Vat Red 14). This solid solution is isotypic to the crystal structures of cis-perinone (Pigment Red 194) and trans-perinone (Pigment Orange 34) and exhibits a combined positional....... The crystal structure of the solid solution was determined by single-crystal X-ray analysis. Extensive lattice-energy minimizations with force-field and DFT-D methods were carried out on combinatorially complete sets of ordered models. For the disordered systems, local structures were calculated, including...

  19. The Role of Cis-Lunar Space in Future Global Space Exploration

    Science.gov (United States)

    Bobskill, Marianne R.; Lupisella, Mark L.

    2012-01-01

    Cis-lunar space offers affordable near-term opportunities to help pave the way for future global human exploration of deep space, acting as a bridge between present missions and future deep space missions. While missions in cis-lunar space have value unto themselves, they can also play an important role in enabling and reducing risk for future human missions to the Moon, Near-Earth Asteroids (NEAs), Mars, and other deep space destinations. The Cis-Lunar Destination Team of NASA's Human Spaceflight Architecture Team (HAT) has been analyzing cis-lunar destination activities and developing notional missions (or "destination Design Reference Missions" [DRMs]) for cis-lunar locations to inform roadmap and architecture development, transportation and destination elements definition, operations, and strategic knowledge gaps. The cis-lunar domain is defined as that area of deep space under the gravitational influence of the earth-moon system. This includes a set of earth-centered orbital locations in low earth orbit (LEO), geosynchronous earth orbit (GEO), highly elliptical and high earth orbits (HEO), earth-moon libration or "Lagrange" points (E-ML1 through E-ML5, and in particular, E-ML1 and E-ML2), and low lunar orbit (LLO). To help explore this large possibility space, we developed a set of high level cis-lunar mission concepts in the form of a large mission tree, defined primarily by mission duration, pre-deployment, type of mission, and location. The mission tree has provided an overall analytical context and has helped in developing more detailed design reference missions that are then intended to inform capabilities, operations, and architectures. With the mission tree as context, we will describe two destination DRMs to LEO and GEO, based on present human space exploration architectural considerations, as well as our recent work on defining mission activities that could be conducted with an EML1 or EML2 facility, the latter of which will be an emphasis of this

  20. Trans- and cis-resveratrol concentration in wines produced in Serbia

    OpenAIRE

    SANJA DJEKIC; SLOBODAN MILOSAVLJEVIC; VLATKA VAJS; SLOBODAN JOVIC; ALEKSANDAR PETROVIC; NINOSLAV NIKICEVIC; VERICA MANOJLOVIC; VIKTOR NEDOVIC; VELE TESEVIC

    2008-01-01

    Resveratrol, which occurs in two isomeric forms, trans and cis, is a phytoalexin with numerous pharmacological activities, such as anti-cancer, antiviral, neuroprotective and anti-aging. Red wine is the main source of the compound and an easy way of including resveratrol in the human diet. In this study, the most popular commercial Serbian wines (red, white and rosé-type) were analyzed for their content of trans- and cis-resveratrol. The analysis was performed by HPLC with a UV detector. Prio...

  1. Facile synthesis of 1',2'-cis-beta-pyranosyladenine nucleosides.

    Science.gov (United States)

    Ando, Takayuki; Shinohara, Hisashi; Luo, Xiong; Kandeel, Mahmoud; Kitade, Yukio

    2007-12-10

    1',2'-cis-beta-Glycosyladenine nucleosides, such as beta-altroside, beta-mannoside, and beta-idoside, were efficiently synthesized from the corresponding 1',2'-trans-beta-6-chloropurine derivatives, beta-glucoside, and beta-galactoside. Nucleophilic substitution of the O-trifluoromethanesulfonyl groups at the C-2' and/or 3' was carried out using tetrabutylammonium acetate or cesium acetate under mild conditions. Subsequent deprotection and amidation afforded the desired compounds, 1',2'-cis-beta-pyranosyladenine nucleosides.

  2. Low plasma levels of cholecalciferol and 13-cis-retinoic acid in tuberculosis

    DEFF Research Database (Denmark)

    Srinivasan, Anand; Syal, Kirtimaan; Banerjee, Dibyajyoti

    2013-01-01

    Objective: The aim of this study was to estimate the concentration of cholecalciferol and 13-. cis-retinoic acid (RA) in the plasma and pleural fluid of patients with tuberculosis (TB) against controls. Methods: Plasma levels of cholecalciferol and 13-. cis-RA were measured in 22 patients with TB...... with active ingredients of vitamins A and D, we feel that there is a combined deficiency of these vitamins in patients with TB. There is an evidence that concomitant vitamin A and D supplementation can kill intracellular Mycobacterium tuberculosis invitro. Therefore, the observations made in this study can...

  3. Endogenous opioid peptides and epilepsy

    NARCIS (Netherlands)

    J. Haffmans (Judith)

    1985-01-01

    textabstractIn recent years a large number of pept:ides, many of which were originall.y characterized in non-neural tissues, have been reported to be present in the central nervous system ( CNS) . The detection of these peptides within the CNS has raised many questions regarding their source and mec

  4. Endocrine cells producing regulatory peptides.

    Science.gov (United States)

    Solcia, E; Usellini, L; Buffa, R; Rindi, G; Villani, L; Zampatti, C; Silini, E

    1987-07-15

    Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

  5. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  6. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...

  7. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the uni

  8. Expression, subcellular localization, and cis-regulatory structure of duplicated phytoene synthase genes in melon (Cucumis melo L.).

    Science.gov (United States)

    Qin, Xiaoqiong; Coku, Ardian; Inoue, Kentaro; Tian, Li

    2011-10-01

    Carotenoids perform many critical functions in plants, animals, and humans. It is therefore important to understand carotenoid biosynthesis and its regulation in plants. Phytoene synthase (PSY) catalyzes the first committed and rate-limiting step in carotenoid biosynthesis. While PSY is present as a single copy gene in Arabidopsis, duplicated PSY genes have been identified in many economically important monocot and dicot crops. CmPSY1 was previously identified from melon (Cucumis melo L.), but was not functionally characterized. We isolated a second PSY gene, CmPSY2, from melon in this work. CmPSY2 possesses a unique intron/exon structure that has not been observed in other plant PSYs. Both CmPSY1 and CmPSY2 are functional in vitro, but exhibit distinct expression patterns in different melon tissues and during fruit development, suggesting differential regulation of the duplicated melon PSY genes. In vitro chloroplast import assays verified the plastidic localization of CmPSY1 and CmPSY2 despite the lack of an obvious plastid target peptide in CmPSY2. Promoter motif analysis of the duplicated melon and tomato PSY genes and the Arabidopsis PSY revealed distinctive cis-regulatory structures of melon PSYs and identified gibberellin-responsive motifs in all PSYs except for SlPSY1, which has not been reported previously. Overall, these data provide new insights into the evolutionary history of plant PSY genes and the regulation of PSY expression by developmental and environmental signals that may involve different regulatory networks.

  9. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  10. A theoretical view of 1,3-butadiene selective hydrogenation toward cis-2-butene on Pdsbnd Ni layered catalyst

    Science.gov (United States)

    Gómez, Guillermina; Belelli, Patricia G.; Cabeza, Gabriela F.; Castellani, Norberto J.

    2015-10-01

    The production of cis-2-butene (cis-2B) on Pd/Ni(1 1 1) bimetallic model was evaluated considering two possible reactions: through the hydrogenation of 1,3-butadiene (13BD) adsorbed on a cis-geometry site and through the isomerization of trans-2-butene (trans-2B). For that purpose, density functional theory (DFT) calculations were performed following the corresponding Horiuti-Polanyi mechanisms. In the hydrogenation, two competitive pathways produce cis-2B and trans-2B from 13BD species adsorbed on di-π-cis and 1,2,3,4-tetra-σ sites, respectively. The cis-2B is obtained with smaller energy requirements than the trans-2B isomer in spite of the adsorption of 13BD on the di-π-cis site is 0.10 eV less stable than on the 1,2,3,4-tetra-σ site. On the other hand, the trans-2B previously formed could be isomerized to cis-2B, and vice versa, trough the 2-butyl intermediates, but the elevated energetic barriers to hydrogenate/dehydrogenate both 2B isomers would avoid these processes. In fact, the dehydrogenation reaction is the limiting step of the isomerization reaction. From these results, we infer that on the Pd/Ni(1 1 1) surface the cis-2B isomer is easier to be formed via the 13BD hydrogenation on the di-π-cis site than via the trans/cis isomerization of 2B.

  11. Synthetic approaches to peptides containing the L-Gln-L-Val-D(S)-Dmt motif.

    Science.gov (United States)

    Suaifan, Ghadeer A R Y; Arafat, Tawfiq; Threadgill, Michael D

    2007-05-15

    The pseudoprolines S-Dmo (5,5-dimethyl-4-oxaproline) and R-Dmt (5,5-dimethyl-4-thiaproline) have been used to study the effects of forcing a fully cis conformation in peptides. Synthesis of peptides containing these (which have the same configuration as L-Pro) is straightforward. However, synthesis of peptides containing S-Dmt is difficult, owing to the rapid cyclisation of L-Aaa-S-Dmt amides and esters to form the corresponding diketopiperazines (DKP); thus the intermediacy of L-Aaa-S-Dmt amides and esters must be avoided in the synthetic sequence. Peptides containing the L-Gln-L-Val-D(S)-Dmt motif are particularly difficult, owing to the insolubility of coupling partners containing Gln. Introduction of Gln as N-Boc-pyroglutamate overcame the latter difficulty and the dipeptide active ester BocPygValOC(6)F(5) coupled in good yield with S-DmtOH. BocPygVal-S- DmtNH(CH(2))(2)C(6)H(4)NO(2) was converted quantitatively to BocGlnVal-S-DmtNH(CH(2))(2)C(6)H(4)NO(2) with ammonia, demonstrating the utility of this approach. Two peptide derivatives (CbzSerLysLeuGlnVal-S-DmtNH(CH(2))(2)C(6)H(4)NO(2) and CbzSerSerLysLeuGlnVal-S- DmtNH(CH(2))(2)C(6)H(4)NO(2)) were assembled, using these new methods of coupling a dipeptide acid active ester with S-DmtOH and introduction of Gln as Pyg, followed by conventional peptide couplings. The presence of the Val caused these peptides to be cleaved very slowly by prostate-specific antigen (PSA) at Leu Gln, rather than the expected Gln Val.

  12. Single amino acid mutation in alpha-helical peptide affect second harmonic generation hyperpolarizability

    Science.gov (United States)

    Wei, Jing; Wang, Jin-Yun; Zhang, Min-Yi; Chai, Guo-Liang; Lin, Chen-Sheng; Cheng, Wen-Dan

    2013-01-01

    We investigate the effect of side chain on the first-order hyperpolarizability in α-helical polyalanine peptide with the 10th alanine mutation (Acetyl(ala)9X(ala)7NH2). Structures of various substituted peptides are optimized by ONIOM (DFT: AM1) scheme, and then linear and nonlinear optical properties are calculated by SOS//CIS/6-31G∗ method. The polarizability and first-order hyperpolarizability increase obviously only when 'X' represents phenylalanine, tyrosine and tryptophan. We also discuss the origin of nonlinear optical response and determine what caused the increase of first-order hyperpolarizability. Our results strongly suggest that side chains containing benzene, phenol and indole have important contributions to first-order hyperpolarizability.

  13. Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.02,6]undeca-3,11-dione and its congeners via ring-closing metathesis

    Directory of Open Access Journals (Sweden)

    Sambasivarao Kotha

    2015-07-01

    Full Text Available We have developed a simple methodology to transform cis-syn-cis-triquinane derivative 2 into the diindole based macrocycle 6 involving Fischer indolization and ring-closing metathesis (RCM. Various spiro-polyquinane derivatives have been assembled via RCM as a key step.

  14. Purification and use of E. coli peptide deformylase for peptide deprotection in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia; Sonke, Theo; Quaedflieg, Peter J.; Janssen, Dick B.

    2013-01-01

    Peptide deformylases (PDFs) catalyze the removal of the formyl group from the N-terminal methionine residue in nascent polypeptide chains in prokaryotes. Its deformylation activity makes PDF an attractive candidate for the biocatalytic deprotection of formylated peptides that are used in chemoenzyma

  15. Cis-regulatory elements in the primate brain: from functional specialization to neurodegeneration

    NARCIS (Netherlands)

    Vermunt, Marit W.

    2017-01-01

    Over the last decade, the noncoding part of the genome has been shown to harbour thousands of cis-regulatory elements, such as enhancers, that activate well-defined gene expression programs. Here, we charted active enhancers in a multiplicity of human brain regions to understand the role of

  16. Role of Human DNA Polymerase kappa in Extension Opposite from a cis-syn Thymine Dimer

    Energy Technology Data Exchange (ETDEWEB)

    R Vasquez-Del Carpio; T Silverstein; S Lone; R Johnson; L Prakash; S Prakash; A Aggarwal

    2011-12-31

    Exposure of DNA to UV radiation causes covalent linkages between adjacent pyrimidines. The most common lesion found in DNA from these UV-induced linkages is the cis-syn cyclobutane pyrimidine dimer. Human DNA polymerase {Kappa} (Pol{Kappa}), a member of the Y-family of DNA polymerases, is unable to insert nucleotides opposite the 3'T of a cis-syn T-T dimer, but it can efficiently extend from a nucleotide inserted opposite the 3'T of the dimer by another DNA polymerase. We present here the structure of human Pol{Kappa} in the act of inserting a nucleotide opposite the 5'T of the cis-syn T-T dimer. The structure reveals a constrained active-site cleft that is unable to accommodate the 3'T of a cis-syn T-T dimer but is remarkably well adapted to accommodate the 5'T via Watson-Crick base pairing, in accord with a proposed role for Pol{Kappa} in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.

  17. Modular Access to N-Substituted cis-3,5-Diaminopiperidines

    NARCIS (Netherlands)

    Blond, Aurelie; Dockerty, Paul; Alvarez, Raquel; Turcaud, Serge; Lecourt, Thomas; Micouin, Laurent

    2013-01-01

    A sequence of oxidative cleavage/reductive amination/hydrogenolysis enables the preparation of N-substituted cis-3,5-diaminopiperidines from a readily available bicyclic hydrazine. This new synthetic route provides a simple and general access to RNA-friendly fragments with a good chemical diversity.

  18. Synthesis, structure and applications of [cis-dioxomolybdenum(VI)-(ONO)] type complexes

    Indian Academy of Sciences (India)

    Rajan Deepan Chakravarthy; Dillip Kumar Chand

    2011-03-01

    Oxo-molybdenum chemistry is of great interest since such units are found in the active sites of a majority of molybdo-enzymes. In order to mimic the biological systems, a number of oxo-molybdenum complexes have been synthesised and studied. This review describes synthesis, structure and applications of oxomolybdenum complexes particularly cis-MoO2(L)(D) where L stands for a dianionic tridentate ONO ligand and D for a donor solvent molecule/monodentate ligand. The ligand moieties are derived from Schiff base, hydrazide Schiff base and other related tridentate ligands L(H)2. The coordination geometry around the Mo center in these complexes can be best described as a distorted octahedron in which the ONO-tridentate ligand occupies meridional position with two anionic oxygen donors mutually trans and are cis to the oxygen centers of the cis-dioxo group. Mostly the applications of cis-MoO2-(ONO) type complexes seen in literature are oxo transfer reactions like epoxidation, sulfoxidation and phosphine oxidation reactions.

  19. High-pressure access to the Δ9-cis- and Δ9-trans-tetrahydrocannabinols family.

    Science.gov (United States)

    Minuti, Lucio; Ballerini, Eleonora

    2011-07-01

    Diels-Alder reactions of a range of 1-(alkoxy/alkyl-substituted phenyl)buta-1,3-dienes with methyl vinyl ketone and methyl acrylate carried out in ethanol as the reaction medium under 9 kbar pressure were investigated. The use of high pressure as the activating method of the Diels-Alder reactions allows the efficient and endodiastereoselective generation of a series of cis-cyclohexenyl-benzene cycloadducts, which are selectively converted into their trans-epimers. The cis-cyclohexenyl-benzenes and trans-cyclohexenyl-benzenes produced are useful precursors for accessing substituted privileged cis-6a,7,8,10a-tetrahydro-6H-benzo[c]chromene and trans-6a,7,8,10a-tetrahydro-6H-benzo[c]chromene skeletons. The total syntheses of Δ(9)-cis-tetrahydrocannabinol (THC) and Δ(9)-trans-THC, through the use of selected Diels-Alder adducts, are described. Finally, a route for obtaining Δ(9)-trans-THC in both enantiomeric pure forms based on the (S)-(-)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP)-hydrazone method is also reported.

  20. Conformer of the peroxynitrite ion formed under photolysis of crystalline alkali nitrates – cis or trans?

    Science.gov (United States)

    Pak, V. Kh; Anan’ev, V. A.; Dyagileva, E. P.; Lyrshchikov, S. Yu; Miklin, M. B.; Rezvova, M. A.

    2017-01-01

    The optical and infrared reflectance spectra of the crystalline powders prepared by co-crystallization of caesium nitrate, nitrite, and peroxynitrite from alkali solution have been studied. We find that the trans conformer forms under photolysis of crystalline pure caesium nitrate. Under its dissolution the trans conformer transforms to the cis conformer.

  1. Water-Promoted Kinetic Separation of trans- and cis-Limonene Oxides

    Institute of Scientific and Technical Information of China (English)

    徐招兵; 渠瑾

    2012-01-01

    The efficient hydrolytic kinetic separation of trans/cis-(R)-(+)-limonene oxides was realized in a 1 : 1 mixed solvent of water and 1,4-dioxane without additional catalyst. Optically pure trans-(R)-(+)-limonene oxide was recovered in high yield (77%).

  2. Systematic genetic analysis identifies Cis-eQTL target genes associated with glioblastoma patient survival.

    Directory of Open Access Journals (Sweden)

    Qing-Rong Chen

    Full Text Available Prior expression quantitative trait locus (eQTL studies have demonstrated heritable variation determining differences in gene expression. The majority of eQTL studies were based on cell lines and normal tissues. We performed cis-eQTL analysis using glioblastoma multiforme (GBM data sets obtained from The Cancer Genome Atlas (TCGA to systematically investigate germline variation's contribution to tumor gene expression levels. We identified 985 significant cis-eQTL associations (FDR<0.05 mapped to 978 SNP loci and 159 unique genes. Approximately 57% of these eQTLs have been previously linked to the gene expression in cell lines and normal tissues; 43% of these share cis associations known to be associated with functional annotations. About 25% of these cis-eQTL associations are also common to those identified in Breast Cancer from a recent study. Further investigation of the relationship between gene expression and patient clinical information identified 13 eQTL genes whose expression level significantly correlates with GBM patient survival (p<0.05. Most of these genes are also differentially expressed in tumor samples and organ-specific controls (p<0.05. Our results demonstrated a significant relationship of germline variation with gene expression levels in GBM. The identification of eQTLs-based expression associated survival might be important to the understanding of genetic contribution to GBM cancer prognosis.

  3. Management practices in Russian multinational subsidiaries: The case of Knauf CIS

    NARCIS (Netherlands)

    Gurkov, I.; Kossov, V.; Filippov, S.

    2013-01-01

    This paper analyzes the growth and evolution of Knauf CIS Group from 1992 to 2012. The study defines the features and characteristics of the firm’s corporate policies including production and operations, marketing, HR management, and societal engagement. These policies have enabled Russian industria

  4. RADIAL DISTRIBUTION FUNCTION OF cis-1,4-POLYBUTADIENE BY ELECTRON DIFFRACTION

    Institute of Scientific and Technical Information of China (English)

    ZHOU Enle; KAN Xianglan; ZHAO Xiaoguang

    1983-01-01

    The interatomic distance function of rareearth catalyzed cis-1,4-polybutadiene was studied by radial distribution function (RDF) derived from electron diffraction. Two intramolecular peaks and three intermolecular peaks have been found on the RDF. The appearance of such a number of intermolecular maxima on the RDF can be explained by the local parallel packing of long molecular chains of the amorphous polymers.

  5. Fluorescence behavior of cis-methyl orange stabilized in cationic premicelles.

    Science.gov (United States)

    Dutta, Anisha; Dutta, Robin K

    2014-05-21

    The cis-isomer of methyl orange (MO), stabilized in cationic premicelles, has been found to be fluorescence active when excited at wavelength ≤270nm. An intense fluorescence band with maximum at 575nm along with a broad moderate intensity band in the range of 370-530nm and a low intensity band at 361nm have been observed. The major band at 575nm has been attributed to S1→S0 (n-π(*)) fluorescence unlike the other azobenzenes where the S2→S0 (π-π(*)) fluorescence is usually reported. UV-Vis spectral and surface tension study indicate that the dye exists in the trans form in dye-surfactant ionpair (DSIP) at very dilute concentrations of the surfactant. But the polar cis-isomer is stabilized by micellization of the DSIPs as the concentration of the surfactant is increased. The fluorescence and hence the cis-isomer again disappear when normal micelles are formed above the normal CMC of the surfactant. It has been suggested that the symmetry forbidden S1→S0 (n-π(*)) transition of MO becomes allowed due to the formation of the twisted cis-form. TD-DFT calculations have been used as an auxiliary tool to identify the possible structures and electronic transitions responsible for the specific absorption and fluorescence properties of MO observed in presence of premicellar cationic surfactants.

  6. Hybrid CIS-DFT method to study electric field effects on electronic excited states of ethylene

    Institute of Scientific and Technical Information of China (English)

    Ma Mei-Zhong; Zhu Zheng-He; Chen Xiao-Jun; Xu Guo-Liang; Zhang Yong-Bin; Mao Hua-Ping; Shen Xiao-Hong

    2005-01-01

    The present work is devoted to the study of the effects of external dipole electric field on the molecular structure of ethylene using a hybrid method which combines the single-excitation configuration interactions (CIS) with density functional theory (DFT), i.e. CIS-DFT(B3LYP). It is found that the effects of electric dipole field on the molecular geometry (D2h, D2d and C2v), dipole moment, transition dipole moment, polarizability and, particularly, excitation energy of ethylene are remarkable. The advantages of the hybrid CIS-DFT method are that it can determine the symmetry of molecule and the correct order of excitation as well as the Molecular Orbital (MO) electron configuration;thereby the electronic excitation states of ethylene are easily derived, and most of them are in agreement with those obtained in experiments or references. It may be the first time the effects of external electric field on ethylene molecule have been considered. Compared with other ab initio methods, the CIS-DFT method is relatively accurate and low cost in computation. We expect that it can be used to study other closed-shell molecules.

  7. Mapping cis- and trans-regulatory effects across multiple tissues in twins

    Science.gov (United States)

    Grundberg, Elin; Small, Kerrin S.; Hedman, Åsa K.; Nica, Alexandra C.; Buil, Alfonso; Keildson, Sarah; Bell, Jordana T.; Yang, Tsun-Po; Meduri, Eshwar; Barrett, Amy; Nisbett, James; Sekowska, Magdalena; Wilk, Alicja; Shin, So-Youn; Glass, Daniel; Travers, Mary; Min, Josine L.; Ring, Sue; Ho, Karen; Thorleifsson, Gudmar; Kong, Augustine; Thorsteindottir, Unnur; Ainali, Chrysanthi; Dimas, Antigone S.; Hassanali, Neelam; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lowe, Christopher E.; Di Meglio, Paola; Montgomery, Stephen B.; Parts, Leopold; Potter, Simon; Surdulescu, Gabriela; Tsaprouni, Loukia; Tsoka, Sophia; Bataille, Veronique; Durbin, Richard; Nestle, Frank O.; O’Rahilly, Stephen; Soranzo, Nicole; Lindgren, Cecilia M.; Zondervan, Krina T.; Ahmadi, Kourosh R.; Schadt, Eric E.; Stefansson, Kari; Smith, George Davey; McCarthy, Mark I.; Deloukas, Panos; Dermitzakis, Emmanouil T.; Spector, Tim D.

    2013-01-01

    Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many eQTL studies typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis-effect on expression cannot be accounted for by common cis-variants, a finding which exposes the contribution of low frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene and identify several replicating trans-variants which act predominantly in a tissue-restricted manner and may regulate the transcription of many genes. PMID:22941192

  8. The Differences Between Cis- and Trans-Gene Inactivation Caused by Heterochromatin in Drosophila.

    Science.gov (United States)

    Abramov, Yuriy A; Shatskikh, Aleksei S; Maksimenko, Oksana G; Bonaccorsi, Silvia; Gvozdev, Vladimir A; Lavrov, Sergey A

    2016-01-01

    Position-effect variegation (PEV) is the epigenetic disruption of gene expression near the de novo-formed euchromatin-heterochromatin border. Heterochromatic cis-inactivation may be accompanied by the trans-inactivation of genes on a normal homologous chromosome in trans-heterozygous combination with a PEV-inducing rearrangement. We characterize a new genetic system, inversion In(2)A4, demonstrating cis-acting PEV as well as trans-inactivation of the reporter transgenes on the homologous nonrearranged chromosome. The cis-effect of heterochromatin in the inversion results not only in repression but also in activation of genes, and it varies at different developmental stages. While cis-actions affect only a few juxtaposed genes, trans-inactivation is observed in a 500-kb region and demonstrates а nonuniform pattern of repression with intermingled regions where no transgene repression occurs. There is no repression around the histone gene cluster and in some other euchromatic sites. trans-Inactivation is accompanied by dragging of euchromatic regions into the heterochromatic compartment, but the histone gene cluster, located in the middle of the trans-inactivated region, was shown to be evicted from the heterochromatin. We demonstrate that trans-inactivation is followed by de novo HP1a accumulation in the affected transgene; trans-inactivation is specifically favored by the chromatin remodeler SAYP and prevented by Argonaute AGO2.

  9. Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human.

    Science.gov (United States)

    Aumont, V; Krisa, S; Battaglia, E; Netter, P; Richard, T; Mérillon, J M; Magdalou, J; Sabolovic, N

    2001-09-15

    Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol present in wine, which has been reported to have anti-inflammatory, anti-platelet, and anti-carcinogenic effects. The glucuronidation of this compound and that of the cis-isomer also naturally present, has been investigated in human liver microsomes. Both isomers were actively glucuronidated. The reaction led to the formation of two glucuronides (3-O- and 4'-O-glucuronides), whose structure was characterized by LC-MS and proton NMR. Glucuronidation was regio- and stereoselective. It occurred at a faster rate with the cis-isomer and preferred the 3-position on both isomers. In addition, the glucuronidation of resveratrol was tested using several recombinant UDP-glucuronosyltransferase (UGT) isoforms. The reaction was catalyzed by UGT of the family 1A (UGT1A1, 1A6, 1A7, 1A9, 1A10). The bilirubin conjugating UGT1A1 was mainly involved in the 3-O-glucuronidation of trans-resveratrol, whereas the phenol conjugating UGT1A6 activity was restricted to cis-resveratrol. The UGT1A9 and 1A10 were active toward both isomers. The activity supported by UGT2B7 and UGT2B15 was very low and restricted to cis-resveratrol. UGT1A3, 1A4, 2B4, and 2B11 were unable to form resveratrol glucuronides.

  10. Evidence supporting a cis-enediol-based mechanism for Pyrococcus furiosus phosphoglucose isomerase

    NARCIS (Netherlands)

    Berrisford, J.M.; Hounslow, A.M.; Akerboom, A.P.; Hagen, W.R.; Brouns, S.J.J.; Oost, van der J.; Murray, I.A.; Blackburn, G.M.; Waltho, J.P.; Rice, D.W.; Baker, P.J.

    2006-01-01

    The enzymatic aldose ketose isomerisation of glucose and fructose sugars involves the transfer of a hydrogen between their C1 and C2 carbon atoms and, in principle, can proceed through either a direct hydride shift or via a cis-enediol intermediate. Pyrococcus furiosus phosphoglucose isomerase (PfPG

  11. Differences Between Asymmetric cis and trans Platinum Complexes. Applications in Cancer Chemotherapy

    NARCIS (Netherlands)

    Pantoja López, Elena

    2005-01-01

    This thesis describes a variety of asymmetric cis- and trans-platinum(II) complexes. The major aim of this research has been the design of complexes with high antitumor activity that may overcome cisplatin resistance, and to establish a comparison between complexes with both geometries. These new ty

  12. Probing the interactions between boronic acids and cis-diol-containing biomolecules by affinity capillary electrophoresis.

    Science.gov (United States)

    Lü, Chenchen; Li, Hengye; Wang, Heye; Liu, Zhen

    2013-02-19

    The affinity of boronic acids to cis-diol-containing biomolecules has found wide applications in many fields, such as sensing, separation, drug delivery, and functional materials. A sound understanding of the binding interactions will greatly facilitate exquisite applications of this chemistry. Although a few analytical tools have been available for the characterization of the interactions, these techniques are associated with some apparent drawbacks, so they are only applicable to a limited range of boronic acids and cis-diol-containing biomolecules. Therefore, a widely applicable method is still greatly needed. In this work, an affinity capillary electrophoresis (ACE) method was established and validated to probe the interactions between boronic acids and cis-diol-containing biomolecules. The method was proven to be applicable to almost all types of cis-diol-containing biomolecules and boronic acids. Based on this method, a quantitative, comparative study on the interactions between 14 boronic acids that have important potentials for application with 5 typical monosaccharides of biological importance was carried out. The findings provided new insights into boronate affinity interactions, particularly the relationship between the binding strength with the molecular structures of the binding species. Besides, effects of pH and temperature on the binding strength were also investigated. This method exhibited several significant advantages, including (1) possibility of simultaneous study of multiple interactions, (2) low requirement on the purity of the binding species, (3) wide applicability, and (4) high accuracy and precision.

  13. SYNTHESIS AND CHARACTERIZATION OF DVE-CO-MA DERIVATIVES OF CIS- PLATINUM COMPLEXES

    Institute of Scientific and Technical Information of China (English)

    WANG Zhuting

    1989-01-01

    Copolymer of divinyl ether and maleic anhydride (DVE- co - MA) derivatives of cis- platinum complexes were synthesized and characterized by elementary analysis, IR and XPS ( X- ray photoelectron spectroscopy). The behavior of the products in biological environment was also studied. UV- visible and fluorescence spectra show that these polymer derivatives are able to exchange ligands with selected nucleophilic groups in biological environment.

  14. cis-Dichloridobis(N,N,N′,N′-tetramethylethane-1,2-diamineplatinum(II

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2012-12-01

    Full Text Available In the title complex, [PtCl2(C6H16N2], the PtII atom adopts a distorted cis-PtN2Cl2 square-planar coordination geometry. The five-membered chelate ring adopts a twisted conformation. In the crystal, weak C—H...Cl hydrogen bonds link the molecules into (001 sheets.

  15. Local structure in the disordered solid solution of cis- and trans-perinones.

    Science.gov (United States)

    Teteruk, Jaroslav L; Glinnemann, Jürgen; Heyse, Winfried; Johansson, Kristoffer E; van de Streek, Jacco; Schmidt, Martin U

    2016-06-01

    The cis- and trans-isomers of the polycyclic aromatic compound perinone, C26H12N4O2, form a solid solution (Vat Red 14). This solid solution is isotypic to the crystal structures of cis-perinone (Pigment Red 194) and trans-perinone (Pigment Orange 34) and exhibits a combined positional and orientational disorder: In the crystal, each molecular position is occupied by either a cis- or trans-perinone molecule, both of which have two possible molecular orientations. The structure of cis-perinone exhibits a twofold orientational disorder, whereas the structure of trans-perinone is ordered. The crystal structure of the solid solution was determined by single-crystal X-ray analysis. Extensive lattice-energy minimizations with force-field and DFT-D methods were carried out on combinatorially complete sets of ordered models. For the disordered systems, local structures were calculated, including preferred local arrangements, ordering lengths, and probabilities for the arrangement of neighbouring molecules. The superposition of the atomic positions of all energetically favourable calculated models corresponds well with the experimentally determined crystal structures, explaining not only the atomic positions, but also the site occupancies and anisotropic displacement parameters.

  16. cis-Urocanic acid attenuates acute dextran sodium sulphate-induced intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Eric Albert

    Full Text Available On exposure to sunlight, urocanic acid (UCA in the skin is converted from trans to the cis form and distributed systemically where it confers systemic immunosuppression. The aim of this study was to determine if administration of cis-UCA would be effective in attenuating colitis and the possible role of IL-10. Colitis was induced in 129/SvEv mice by administering 5% dextran sodium sulfate (DSS for 7 days in drinking water. During this period mice received daily subcutaneously injections of cis-UCA or vehicle. To examine a role for IL-10, 129/SvEv IL-10(-/- mice were injected for 24 days with cis-UCA or vehicle. Clinical disease was assessed by measurement of body weight, stool consistency, and presence of blood. At sacrifice, colonic tissue was collected for histology and measurement of myeloperoxidase and cytokines. Splenocytes were analyzed for CD4+CD25+FoxP3+ T-regulatory cells via flow cytometry. Murine bone-marrow derived antigen-presenting cells were treated with lipopolysaccharide (LPS ± UCA and cytokine secretion measured. Our results demonstrated that cis-UCA at a dose of 50 µg was effective in ameliorating DSS-induced colitis as evidenced by reduced weight loss and attenuated changes in colon weight/length. This protection was associated with reduced colonic expression of CXCL1, an increased expression of IL-17A and a significant preservation of splenic CD4+CD25+FoxP3+ T-regulatory cells. cis-UCA decreased LPS induced CXCL1, but not TNFα secretion, from antigen-presenting cells in vitro. UCA reduced colonic levels of IFNγ in IL-10(-/- mice but did not attenuate colitis. In conclusion, this study demonstrates that cis-urocanic acid is effective in reducing the severity of colitis in a chemically-induced mouse model, indicating that pathways induced by ultraviolet radiation to the skin can influence distal sites of inflammation. This provides further evidence for a possible role for sunlight exposure in modulating inflammatory

  17. Potential of phage-displayed peptide library technology to identify functional targeting peptides

    Science.gov (United States)

    Krumpe, Lauren RH; Mori, Toshiyuki

    2010-01-01

    Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo. PMID:20150977

  18. Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

    DEFF Research Database (Denmark)

    Richards, Stephen; Liu, Yue; Bettencourt, Brian R.;

    2005-01-01

    between the species-but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence...

  19. 9-CIS-RETINOIC ACID REPRESSES ESTROGEN-INDUCED EXPRESSION OF THE VERY-LOW-DENSITY APOLIPOPROTEIN-II GENE

    NARCIS (Netherlands)

    SCHIPPERS, IJ; KLOPPENBURG, M; SNIPPE, L; AB, G

    1994-01-01

    The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concent

  20. Cis- and trans-regulatory mechanisms of gene expression in the ASJ sensory neuron of Caenorhabditis elegans

    NARCIS (Netherlands)

    M. González-Barrios (María); J.C. Fierro-González (Juan Carlos); E. Krpelanova (Eva); J.A. Mora-Lorca (José Antonio); J. Rafael Pedrajas (José); X. Peñate (Xenia); S. Chavez (Sebastián); P. Swoboda (Peter); G. Jansen (Gert); A. Miranda-Vizuet (Antonio)

    2015-01-01

    textabstractThe identity of a given cell type is determined by the expression of a set of genes sharing common cis-regulatory motifs and being regulated by shared transcription factors. Here, we identify cis and trans regulatory elements that drive gene expression in the bilateral sensory neuron ASJ

  1. Interactions of radiation and adriamycin, bleomycin, mitomycin C or cis-diamminedichloroplatinum II in intestinal crypt cells

    DEFF Research Database (Denmark)

    von der Maase, H

    1984-01-01

    The interactions of radiation and adriamycin (ADM), bleomycin (BLM), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) in mouse jejunal crypt cells were studied using the microcolony survival assay. ADM administered from 24 h before to 48 h after irradiation resulted in an almost...

  2. Induction of cell cycle arrest in human MCF-7 breast cancer cells by cis-stilbene derivatives related to VIOXX.

    NARCIS (Netherlands)

    Sangjun, S.; de Jong, E.; Nijmeijer, S.; Mutarapat, T.; Ruchirawat, S.; van den Berg, M.; van Duursen, M.B.M.

    2009-01-01

    In our present study, 12 new cis-stilbene derivatives (CRI-1-CRI-13) related to VIOXX((R)) were synthesized and studied for their inhibitory effects on cell cycle progression and anti-estrogenicity in human adenoma breast cancer MCF-7 cells. Based on the different substituents in the cis-stilbene mo

  3. Baker's Yeast Deficient in Storage Lipid Synthesis Uses cis-Vaccenic Acid to Reduce Unsaturated Fatty Acid Toxicity.

    Science.gov (United States)

    Sec, Peter; Garaiova, Martina; Gajdos, Peter; Certik, Milan; Griac, Peter; Hapala, Ivan; Holic, Roman

    2015-07-01

    The role of cis-vaccenic acid (18:1n-7) in the reduction of unsaturated fatty acids toxicity was investigated in baker's yeast Saccharomyces cerevisiae. The quadruple mutant (QM, dga1Δ lro1Δ are1Δ are2Δ) deficient in enzymes responsible for triacylglycerol and steryl ester synthesis has been previously shown to be highly sensitive to exogenous unsaturated fatty acids. We have found that cis-vaccenic acid accumulated during cultivation in the QM cells but not in the corresponding wild type strain. This accumulation was accompanied by a reduction in palmitoleic acid (16:1n-7) content in the QM cells that is consistent with the proposed formation of cis-vaccenic acid by elongation of palmitoleic acid. Fatty acid analysis of individual lipid classes from the QM strain revealed that cis-vaccenic acid was highly enriched in the free fatty acid pool. Furthermore, production of cis-vaccenic acid was arrested if the mechanism of fatty acids release to the medium was activated. We also showed that exogenous cis-vaccenic acid did not affect viability of the QM strain at concentrations toxic for palmitoleic or oleic acids. Moreover, addition of cis-vaccenic acid to the growth medium provided partial protection against the lipotoxic effects of exogenous oleic acid. Transformation of palmitoleic acid to cis-vaccenic acid is thus a rescue mechanism enabling S. cerevisiae cells to survive in the absence of triacylglycerol synthesis as the major mechanism for unsaturated fatty acid detoxification.

  4. 9-CIS-RETINOIC ACID REPRESSES ESTROGEN-INDUCED EXPRESSION OF THE VERY-LOW-DENSITY APOLIPOPROTEIN-II GENE

    NARCIS (Netherlands)

    SCHIPPERS, IJ; KLOPPENBURG, M; SNIPPE, L; AB, G

    1994-01-01

    The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concent

  5. HeliCis: a DNA motif discovery tool for colocalized motif pairs with periodic spacing

    Directory of Open Access Journals (Sweden)

    Mostad Petter

    2007-10-01

    Full Text Available Abstract Background Correct temporal and spatial gene expression during metazoan development relies on combinatorial interactions between different transcription factors. As a consequence, cis-regulatory elements often colocalize in clusters termed cis-regulatory modules. These may have requirements on organizational features such as spacing, order and helical phasing (periodic spacing between binding sites. Due to the turning of the DNA helix, a small modification of the distance between a pair of sites may sometimes drastically disrupt function, while insertion of a full helical turn of DNA (10–11 bp between cis elements may cause functionality to be restored. Recently, de novo motif discovery methods which incorporate organizational properties such as colocalization and order preferences have been developed, but there are no tools which incorporate periodic spacing into the model. Results We have developed a web based motif discovery tool, HeliCis, which features a flexible model which allows de novo detection of motifs with periodic spacing. Depending on the parameter settings it may also be used for discovering colocalized motifs without periodicity or motifs separated by a fixed gap of known or unknown length. We show on simulated data that it can efficiently capture the synergistic effects of colocalization and periodic spacing to improve detection of weak DNA motifs. It provides a simple to use web interface which interactively visualizes the current settings and thereby makes it easy to understand the parameters and the model structure. Conclusion HeliCis provides simple and efficient de novo discovery of colocalized DNA motif pairs, with or without periodic spacing. Our evaluations show that it can detect weak periodic patterns which are not easily discovered using a sequential approach, i.e. first finding the binding sites and second analyzing the properties of their pairwise distances.

  6. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  7. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming;

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...... to haemodynamic changes in the pro-peptides copeptin, proadrenomedullin and pro-atrial natriuretic peptide (proANP) in patients with cirrhosis. MATERIALS AND METHODS: Fifty-four cirrhotic patients and 15 controls were characterized haemodynamically during a liver vein catheterization. Copeptin, proadrenomedullin...... found no extraction of copeptin, proadrenomedullin or proANP over the liver. Copeptin correlated with portal pressure (R=0·50, P

  8. Next generation natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Goetze, Jens P

    2012-01-01

    Plasma measurement of natriuretic peptides is a "must" for clinical laboratories. For the next generation measurement, the unraveling of the molecular complexity of the peptides points toward a more qualitative assessment, as the posttranslational processing also changes with disease. Changes...... in the molecular heterogeneity could in itself contain valuable information of clinical status, and the time seems right for industry and dedicated researchers in the field to get together and discuss the next generation natriuretic peptide measurement. In such an environment, new strategies can be developed...

  9. Peptide primary messengers in plants

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The peptide primary messengers regulate embryonic development,cell growth and many other activities in animal cells. But recent evidence verified that peptide primary messengers are also involved in plant defense responses, the recognition between pollen and stigma and keep the balance between cell proliferation and differentiations in shoot apical meristems. Those results suggest that plants may actually make wide use of peptide primary messengers, both in embryonic development and late life when they rally their cells to defend against pathogens and insect pests. The recent advance in those aspects is reviewed.

  10. Use of cis-[18F] fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Kjaer, Andreas; Heinemeier, Katja Maria

    2011-01-01

    Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non-invasive assess......Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non......-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60...

  11. Determination of the valence-band offset of CdS/CIS solar cell devices by target factor analysis

    Energy Technology Data Exchange (ETDEWEB)

    Niles, D.W.; Contreras, M.; Ramanathan, K.; Noufi, R. [National Renewable Energy Lab., Golden, CO (United States)

    1996-05-01

    X-ray photoemission spectroscopy (XPS) is used to determine and compare the valence-band offsets ({Delta}E{sub v}) for CdS grown by chemical bath deposition on single-crystal and thin-film CuInSe{sub 2} (CIS). The thin-film CIS device was suitable for photovoltaic energy production. By sputtering through the CdS/CIS interface and reducing the depth profile with target factor analysis, the magnitude of {Delta}E{sub v} was determined to be {Delta}E{sub v} = 1.06 {+-} 0.15 eV for both the single-crystal and thin-film interfaces. This determination of {Delta}E{sub v} is about 0.25 eV larger than many previously reported estimations CdS grown by physical vapor deposition on CIS and helps explain the record performance of CdS/CIS photovoltaic devices.

  12. Targeting the Eph System with Peptides and Peptide Conjugates.

    Science.gov (United States)

    Riedl, Stefan J; Pasquale, Elena B

    2015-01-01

    Eph receptor tyrosine kinases and ephrin ligands constitute an important cell communication system that controls development, tissue homeostasis and many pathological processes. Various Eph receptors/ephrins are present in essentially all cell types and their expression is often dysregulated by injury and disease. Thus, the 14 Eph receptors are attracting increasing attention as a major class of potential drug targets. In particular, agents that bind to the extracellular ephrin-binding pocket of these receptors show promise for medical applications. This pocket comprises a broad and shallow groove surrounded by several flexible loops, which makes peptides particularly suitable to target it with high affinity and selectivity. Accordingly, a number of peptides that bind to Eph receptors with micromolar affinity have been identified using phage display and other approaches. These peptides are generally antagonists that inhibit ephrin binding and Eph receptor/ ephrin signaling, but some are agonists mimicking ephrin-induced Eph receptor activation. Importantly, some of the peptides are exquisitely selective for single Eph receptors. Most identified peptides are linear, but recently the considerable advantages of cyclic scaffolds have been recognized, particularly in light of potential optimization towards drug leads. To date, peptide improvements have yielded derivatives with low nanomolar Eph receptor binding affinity, high resistance to plasma proteases and/or long in vivo half-life, exemplifying the merits of peptides for Eph receptor targeting. Besides their modulation of Eph receptor/ephrin function, peptides can also serve to deliver conjugated imaging and therapeutic agents or various types of nanoparticles to tumors and other diseased tissues presenting target Eph receptors.

  13. Screening of TACE Peptide Inhibitors from Phage Display Peptide Library

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To obtain the recombinant tumor necrosis factor-α converting enzyme (TACE) ectodomain and use it as a selective molecule for the screening of TACE peptide inhibitors, the cDNA coding catalytic domain (T800) and full-length ectodomain (T1300) of TACE were amplified by RTPCR, and the expression plasmids were constructed by inserting T800 and T1300 into plasmid pET28a and pET-28c respectively. The recombinant T800 and T1300 were induced by IPTG, and SDSPAGE and Western blotting analysis results revealed that T800 and T1300 were highly expressed in the form of inclusion body. After Ni2+-NTA resin affinity chromatography, the recombinant proteins were used in the screening of TACE-binding peptides from phage display peptide library respectively. After 4 rounds of biopanning, the positive phage clones were analyzed by ELISA, competitive inhibition assay and DNA sequencing. A common amino acid sequence (TRWLVYFSRPYLVAT) was found and synthesized. The synthetic peptide could inhibit the TNF-α release from LPS-stimulated human peripheral blood mononuclear cells (PBMC) up to 60.3 %. FACS analysis revealed that the peptide mediated the accumulation of TNF-α on the cell surface. These results demonstrate that the TACE-binding peptide is an effective antagonist of TACE.

  14. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    on a novel three-step procedure that identifies any reactive viral O-glycosyl peptide epitope with respect to (i) relevant peptide sequence, (ii) the reactive glycoform out of several possible glycopeptide isomers of that peptide sequence, and (iii) possibly tolerated carbohydrate or peptide structural...

  15. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    The alarming increase in the prevalence of obesity and associated comorbidities such as type 2 diabetes emphasizes the urgent need for new drugs with both anorectic and antidiabetic eects. Several peptide hormones secreted from the gastrointestinal tract play an important role in the physiological...... regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs...... of food intake, which was enhanced compared to native NMU. Project II explored the design, synthesis, and characterization of neoglycolipidated analogs of glucagon-like peptide 1 (GLP-1). Neoglycolipidation reduced lipophilicity and maintained or even improved in vitro potency towards the GLP-1 receptor...

  16. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs...... of this thesis contribute to emphasize the tremendous therapeutic potential of gut peptides for treatment of obesity and diabetes.......The alarming increase in the prevalence of obesity and associated comorbidities such as type 2 diabetes emphasizes the urgent need for new drugs with both anorectic and antidiabetic eects. Several peptide hormones secreted from the gastrointestinal tract play an important role in the physiological...

  17. Therapeutical Potential of Venom Peptides

    Directory of Open Access Journals (Sweden)

    İlker Kelle

    2006-01-01

    Full Text Available The term of pharmazooticals is known as a few amount of drugs derived from natural sources such as plants, venomous species of snakes, spiders, scorpions, frogs, lizards and cone snails. Peptide components of venoms are directed against wide variety of pharmacological targets such as ion channels and receptors. At the beginning, a number of these peptides have been used in experimental studies for defining the physiological, biochemical and immunological activities of organisms like mammalians. In recent studies, it has been shown that venom peptides can be valuable in treatment of acute and chronic pain, autoimmune and cardiovascular diseases, neurological disorders and chronic inflammatory and tumoral processes. Therefore particularly in clinical approaches, these peptide molecules or their synthetic analogues are considered as alternative agents that can be used instead of classical drugs for many clinical disorders due to their potent activity besides very few side effects.

  18. Antimicrobial peptides from Capsicum sp.

    African Journals Online (AJOL)

    ajl yemi

    2011-12-30

    Dec 30, 2011 ... pathogens, it is a challenge to sustain food production. *Corresponding ... Genetically modified plants (GMPs) resistance to plant pathogens are an .... tically developed peptides have been tested in topic treatments during ...

  19. Peptides and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bachovchin, W.W.; Unkefer, C.J.

    1994-12-01

    Advances in magnetic resonance and vibrational spectroscopy make it possible to derive detailed structural information about biomolecular structures in solution. These techniques are critically dependent on the availability of labeled compounds. For example, NMR techniques used today to derive peptide and protein structures require uniformity {sup 13}C-and {sup 15}N-labeled samples that are derived biosynthetically from (U-6-{sup 13}C) glucose. These experiments are possible now because, during the 1970s, the National Stable Isotope Resource developed algal methods for producing (U-6-{sup 13}C) glucose. If NMR techniques are to be used to study larger proteins, we will need sophisticated labelling patterns in amino acids that employ a combination of {sup 2}H, {sup 13}C, and {sup 15}N labeling. The availability of these specifically labeled amino acids requires a renewed investment in new methods for chemical synthesis of labeled amino acids. The development of new magnetic resonance or vibrational techniques to elucidate biomolecular structure will be seriously impeded if we do not see rapid progress in labeling technology. Investment in labeling chemistry is as important as investment in the development of advanced spectroscopic tools.

  20. Antimicrobial peptides in crustaceans

    Directory of Open Access Journals (Sweden)

    RD Rosa

    2010-11-01

    Full Text Available Crustaceans are a large and diverse invertebrate animal group that mounts a complex and efficient innate immune response against a variety of microorganisms. The crustacean immune system is primarily related to cellular responses and the production and release of important immune effectors into the hemolymph. Antimicrobial proteins and/or peptides (AMPs are key components of innate immunity and are widespread in nature, from bacteria to vertebrate animals. In crustaceans, 15 distinct AMP families are currently recognized, although the great majority (14 families comes from members of the order Decapoda. Crustacean AMPs are generally cationic, gene-encoded molecules that are mainly produced by circulating immune-competent cells (hemocytes or are derived from unrelated proteins primarily involved in other biological functions. In this review, we tentatively classified the crustacean AMPs into four main groups based on their amino acid composition, structural features and multi-functionality. We also attempted to summarize the current knowledge on their implication both in an efficient response to microbial infections and in crustacean survival.

  1. Antimicrobial peptides in annelids

    Directory of Open Access Journals (Sweden)

    A Tasiemski

    2008-06-01

    Full Text Available Gene encoded antimicrobial peptides (AMPs are widely distributed among living organisms including plants, invertebrates and vertebrates. They constitute important effectors of the innate immune response by exerting multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis and immune induction. In invertebrates, most of the data describe the characterization and/or the function of AMPs in the numerically and economically most representative group which are arthropods. Annelids are among the first coelomates and are therefore of special phylogenetic interest. Compared to other invertebrate groups, data on annelid’s immunity reveal heavier emphasis on the cellular than on the humoral response suggesting that immune defense of annelids seems to be principally developed as cellular immunity.This paper gives an overview of the variety of AMPs identified in the three classes of annelids, i.e. polychaetes, oligochaetes and achaetes. Their functions, when they have been studied, in the humoral or cellular response of annelids are also mentioned.

  2. Asteropsin A: an unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2+ influx.

    Science.gov (United States)

    Li, Huayue; Bowling, John J; Fronczek, Frank R; Hong, Jongki; Jabba, Sairam V; Murray, Thomas F; Ha, Nam-Chul; Hamann, Mark T; Jung, Jee H

    2013-03-01

    Herein we report the discovery of a cystine-crosslinked peptide from Porifera along with high-quality spatial details accompanied by the description of its unique effect on neuronal calcium influx. Asteropsin A (ASPA) was isolated from the marine sponge Asteropus sp., and its structure was independently determined using X-ray crystallography (0.87 angstroms) and solution NMR spectroscopy. An N-terminal pyroglutamate modification, uncommon cis proline conformations, and absence of basic residues helped distinguish ASPA from other cystine-crosslinked knot peptides. ASPA enhanced Ca2+ influx in murine cerebrocortical neuron cells following the addition of the Na+ channel activator veratridine but did not modify the oscillation frequency or amplitude of neuronal Ca2+ currents alone. Allosterism at neurotoxin site 2 was not observed, suggesting an alternative to the known Na+ channel interaction. Together with a distinct biological activity, the origin of ASPA suggests a new subclass of cystine-rich knot peptides associated with Porifera. The discovery of ASPA represents a distinctive addition to an emerging subclass of cystine-crosslinked knot peptides from Porifera.

  3. EU-CIS joint study project 2. Intervention criteria in CIS, risk assessments and non-radiological factors in decision-making

    Energy Technology Data Exchange (ETDEWEB)

    Hedemann Jensen, P. [Risoe National Lab., Roskilde (Denmark); Demin, V.F. [Russian Reserch Centre `Kurchatov Inst.`, Moscow (Russian Federation); Konstantinov, Y.O. [Research Inst. of Radiation Hygiene, St. Petersburg (Russian Federation); Likhtarev, I.A. [Ukrainian Scientific Centre for Radiation Medicine, Kiev (Ukraine); Rolevich, I.V. [Chernobyl State Commiettee, Minsk (Belarus); Schneider, T. [Centre d`etudes sur l`Evaluation de la Protection dans le domaine Nucleaire, CEPN, Paris (France)

    1996-05-01

    An extensive radiation risk estimation methodology has recently been developed in Russia and used for estimates of risk in exposed populations in the republics of Russia, Belarus and Ukraine. Results based on demographic data for the three republics are presented and compared with risk estimates from the EU risk model ASQRAD. The intervention criteria in the CIS republics have been evolving since the Chernobyl accident. The development of criteria in each of the three republics has been analysed and the CIS-Criteria have been compared to international guidance on intervention. After a nuclear or radiological emergency both radiological and non-radiological protection factors will influence the level of protective actions being introduced. The role of non-radiological protection factors in the overall optimization of health protection is addressed. It is argued that optimization of the overall health protection is not a question of developing radiation radiation protection philosophy to fully include socio-psychological factors. It is rather a question of including these factors - in parallel with the radiological protection factors - in cooperation between radiation protection experts and psychological specialists under the responsibility of the decision maker. (au) 19 tabs., 10 ills., 45 refs.

  4. trans,cis,cis-bis(benzoato)dichlorido(cyclohexane-1R,2R-diamine)platinum(IV): a prodrug candidate for the treatment of oxaliplatin-refractory colorectal cancer.

    Science.gov (United States)

    Gandin, Valentina; Marzano, Cristina; Pelosi, Giorgio; Ravera, Mauro; Gabano, Elisabetta; Osella, Domenico

    2014-06-01

    The gold standard for the treatment of metastatic colorectal cancer consists of combination chemotherapy. Over time, however, the development of chemoresistant tumor clones leads to relapse. It may be possible to overcome oxaliplatin chemoresistance in colorectal cancer cells by exploiting a complex obtained from the insertion of the cyclohexane-1R,2R-diamine carrier ligand (the same diamine present in oxaliplatin) into an octahedral Pt(IV) scaffold with high lipophilicity conferred by two benzoate axial ligands. Herein we report the synthesis, characterization (including X-ray structure), biological activity, and cellular accumulation of trans,cis,cis-bis(benzoato)dichlorido(cyclohexane-1R,2R-diamine)platinum(IV) complex in a panel of several human cancer cell lines, including a colon carcinoma cell line resistant to oxaliplatin. The compound under investigation shows the best performance in terms of in vitro anti-proliferative activity and ability to overcome chemoresistance, with respect to oxaliplatin and some other Pt(II) reference complexes. This result is likely related to the high lipophilicity shown by the title compound that favors its cellular accumulation by passive diffusion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Engineering catechol 1, 2-dioxygenase by design for improving the performance of the cis, cis-muconic acid synthetic pathway in Escherichia coli

    Science.gov (United States)

    Han, Li; Liu, Pi; Sun, Jixue; Wu, Yuanqing; Zhang, Yuanyuan; Chen, Wujiu; Lin, Jianping; Wang, Qinhong; Ma, Yanhe

    2015-01-01

    Regulating and ameliorating enzyme expression and activity greatly affects the performance of a given synthetic pathway. In this study, a new synthetic pathway for cis, cis-muconic acid (ccMA) production was reconstructed without exogenous induction by regulating the constitutive expression of the important enzyme catechol 1,2-dioxygenase (CatA). Next, new CatAs with significantly improved activities were developed to enhance ccMA production using structure-assisted protein design. Nine mutations were designed, simulated and constructed based on the analysis of the CatA crystal structure. These results showed that mutations at Gly72, Leu73 and/or Pro76 in CatA could improve enzyme activity, and the activity of the most effective mutant was 10-fold greater than that of the wild-type CatA from Acinetobacter sp. ADP1. The most productive synthetic pathway with a mutated CatA increased the titer of ccMA by more than 25%. Molecular dynamic simulation results showed that enlarging the entrance of the substrate-binding pocket in the mutants contributed to their increased enzyme activities and thus improved the performance of the synthetic pathway. PMID:26306712

  6. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women

    DEFF Research Database (Denmark)

    Tholstrup, Tine; Raff, Marianne; Straarup, Ellen Marie

    2008-01-01

    . The plasma cytokines interleukin-6 and tumor necrosis factor-a were not affected by the treatments, nor were any of the other variables measured. In conclusion, oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease, whereas the c9, t11 CLA......A mixture of trans-10, cis-12 (t10,c12) and cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA mixture) reduced atherosclerosis in animals, thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest. We gave 75 healthy postmenopausal...

  7. The ruthenium complex cis-(dichloro)tetrammineruthenium(III) chloride induces apoptosis and damages DNA in murine sarcoma 180 cells

    Indian Academy of Sciences (India)

    Aliny Pereira De Lima; Flávia De Castro Pereira; Cesar Augusto Sam Tiago Vilanova-Costa; Alessandra De Santana Braga Barbosa Ribeiro; Luiz Alfredo Pavanin; Wagner Batista Dos Santos; Elisângela De Paula Silveira-Lacerda

    2010-09-01

    Ruthenium(III) complexes are increasingly attracting the interest of researchers due to their promising pharmacological properties. Recently, we reported that the cis-(dichloro)tetrammineruthenium(III) chloride compound has cytotoxic effects on murine sarcoma 180 (S-180) cells. In an effort to understand the mechanism responsible for their cytotoxicity, study we investigated the genotoxicity, cell cycle distribution and induction of apoptosis caused by cis-(dichloro)tetrammineruthenium(III) chloride in S-180 tumour cells. cis-(dichloro)tetrammineruthenium(III) chloride treatment induced significant DNA damage in S-180 cells, as detected by the alkaline comet assay. In the cell cycle analysis, cis-(dichloro)tetrammineruthenium(III) chloride caused an increase in the number of cells in G1 phase, accompanied by a decrease in the S and G2 phases after 24 h of treatment. In contrast, the cell cycle distribution of S-180 cells treated with cis-(dichloro)tetrammineruthenium(III) chloride for 48 h showed a concentration-dependent increase in the sub-G1 phase (indicating apoptosis), with a corresponding decrease in cells in the G1, S and G2 phases. In addition, cis-(dichloro)tetrammineruthenium(III) chloride treatment induced apoptosis in a time-dependent manner, as observed by the increased numbers of annexin V-positive cells. Taken together, these findings strongly demonstrate that DNA damage, cell cycle changes and apoptosis may correlate with the cytotoxic effects of cis-(dichloro)tetrammineruthenium(III) chloride on S-180 cells.

  8. Tangerine tomatoes increase total and tetra-cis-lycopene isomer concentrations more than red tomatoes in healthy adult humans.

    Science.gov (United States)

    Burri, Betty Jane Burri; Chapman, Mary H; Neidlinger, Terry R; Seo, Jung S; Ishida, Betty K

    2009-01-01

    Lycopene, or the foods that contain it, may prevent prostate cancer. Studies suggest that some cis-lycopene isomers are more bioavailable than the trans-lycopene isomer. We hypothesized that tangerine tomatoes, which predominantly contain the tetra-cis isomer, should be a good source of bioavailable lycopene. We fed lunches containing 300 g tangerine or red tomato sauce per day to 21 healthy adults in a double-blind crossover design. We collected blood at baseline and after each treatment and washout period. We measured tetra-cis, other cis, and trans lycopene, as well as other carotenoids, by reversed-phase high-performance liquid chromatography. Both tomato sauces increased lycopene concentrations in blood, but the tangerine tomato sauce caused a greater increase of total and tetra-cis-lycopene. The cis isomer(s) may also have facilitated absorption of the trans-lycopene isomer. Indices of oxidative damage decreased as serum lycopene concentrations increased. Our results suggest that total lycopene concentrations can be increased by substituting tetra-cis-lycopene-rich tangerine tomatoes for common red tomatoes in the diet.

  9. Photochromism of cis(z)-1,2-bispyrryl-substituted ethene derivatives

    Institute of Scientific and Technical Information of China (English)

    樊贵宝; 明阳福; 樊美公; 姚思德; 左志华

    1996-01-01

    Photochromism of two bispyrryl-substituted ethenes, 2, 3-bis-(1-p-methoxyphenyl-5-phenyl-2-methyl-3-pyrryl)-2-butene (BPE1) and 2,3-bis(1-p-bromophenyl-4-phenyl-2-methyl-3-pyrryl)-2-butene (BPE2), was studied by laser flash photolysis technique. The results indicate that photocyclization of these compounds proceeds mainly via the excited triplet state, and the cis-trans isomerization proceeds mainly via the excited singlet state. After UV laser pulse irradiation, both photocylization and cis-trans isomerization of BPEl occur, but photocydization is the main reaction. On the other hand, laser photolysis of BPE2 leads mainly to photocydization. The effects of the substituents on the photochromic mechanism are also discussed.

  10. High efficiency CIGS and CIS cells with CVD ZnO buffer layers

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, L.C.; Lei, W.; Addis, F.W. [Washington State Univ./Tri-Cities, Richland, WA (United States); Shafarman, W.N. [Univ. of Delaware, Newark, DE (United States). Inst. of Energy Conversion; Contreras, M.A.; Ramanathan, K. [National Renewable Energy Lab., Golden, CO (United States)

    1997-12-31

    This paper describes investigations of CIS and CIGS solar cells with ZnO buffer layers. These studies are a result of a team effort between investigators at Washington State University (WSU), the Institute of Energy Conversion (IEC) and the National Renewable Energy Laboratory (NREL). Cells with ZnO buffer layers were fabricated with both Siemens CIS and NREL CIGS substrates. An active area efficiency of 13.95% was achieved for a ZnO/CIGS cell. ZnO buffer layers are grown by reacting a zinc adduct with tetrahydrofuran using a two-step approach: growth of approximately 100 {angstrom} of ZnO at 250 C; and then growth of 500 to 700 {angstrom} of ZnO at 100 C. The high temperature step is necessary to achieve good cell performance. It appears that exposure of CIGS to hydrogen at 250 C may remove contaminants and/or passivate recombination centers on the surface and subsurface regions.

  11. Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees

    Directory of Open Access Journals (Sweden)

    Chen Xiaoyu

    2007-12-01

    Full Text Available Abstract Background In vertebrates, a large part of gene transcriptional regulation is operated by cis-regulatory modules. These modules are believed to be regulating much of the tissue-specificity of gene expression. Results We develop a Bayesian network approach for identifying cis-regulatory modules likely to regulate tissue-specific expression. The network integrates predicted transcription factor binding site information, transcription factor expression data, and target gene expression data. At its core is a regression tree modeling the effect of combinations of transcription factors bound to a module. A new unsupervised EM-like algorithm is developed to learn the parameters of the network, including the regression tree structure. Conclusion Our approach is shown to accurately identify known human liver and erythroid-specific modules. When applied to the prediction of tissue-specific modules in 10 different tissues, the network predicts a number of important transcription factor combinations whose concerted binding is associated to specific expression.

  12. Ring-opening of cis-3-Substituted-2-vinylaziridines with Heteroatom Nucleophiles

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gaeun; Shin, Miri; Kang, Hanyoung [Chungbuk National Univ., Cheongju (Korea, Republic of)

    2014-03-15

    The results of the ring opening reaction of N-protected-cis-2-vinyl-3-(benzyloxymethyl)aziridines as model compounds for cis-3-substituted-2-vinylaziridines with various heteroatom nucleophiles are summarized in Table 1. Methanol is a good nucleophile to provide the desired 1,2-amino-alcohol derivative as a single product in excellent yield. We analyzed briefly the effect of solvents with methanol. Although other solvents such as DMF and THF also gave the product, CH{sub 2}Cl{sub 2} was employed as a preferred solvent because of the high yield and ease of handling. All the reactions were, therefore, examined in CH{sub 2}Cl{sub 2} in the presence of BF{sub 3}·OEt{sub 2} as a Lewis acid unless mentioned otherwise. All alcohols behaved as good nucleophiles to exclusively give the desired products (entry 1-7)

  13. Crystal structure of cis-diamminebis(nitrito-κN)platinum(II).

    Science.gov (United States)

    Kahlenberg, Volker; Gelbrich, Thomas; Tessadri, Richard; Klauser, Frederik

    2015-04-01

    Single crystals of cis-[Pt(NO2)2(NH3)2], were obtained by means of hyper-saturation directly out of a plating electrolyte. The square-planar coordination environment of the divalent Pt(II) atom is formed by four N atoms belonging to two ammine and two monodentate nitrite ligands. The ligands adopt a cis configuration. The crystal structure contains stacks of close-packed mol-ecules which run parallel to [001]. There are nine crystallographically independent inter-molecular N-H⋯O hydrogen bonds, resulting in a hydrogen-bonded hxl-type framework in which each mol-ecule serves as an eight-connected node. Four of the nine distinct hydrogen bonds connect complexes which belong to the same close-packed column parallel to [001]. In contrast to the previously reported crystal structure of the trans isomer, the title structure does not display intra-molecular hydrogen bonding.

  14. Modelling of the cis-trans partitioning in the photoisomerizations of cyanines and stilbene derivatives

    Science.gov (United States)

    Caselli, M.; Momicchioli, F.; Ponterini, G.

    1993-12-01

    In the course of photoisomerization, polymethine cyanines as well as stilbene and its derivates decay from the S 1 potential energy minimum, corresponding to the perpendicular geometry, to yield either cis or trans ground-state molecules. The fraction of cis isomers obtained, α, spans a larger range of values for symmetric cyanines than for stilbene derivatives. It is argued that such different behaviour for the two classes of compounds should be traceable to the electronically different nature of their S 1 perp species. Making use of radiationless transition theory results, it is shown the relative location of the S 1 minimum and S 0 maximum along the internal rotation coordinate is crucial to the evaluation of α: even small differences between these critical twisting angles, which are more reasonably expected for polymethine cyanines than for stilbene-like compounds, may cause strong deviations from equipartitioning (α=0.5).

  15. Quantum chemical topology study on the electronic structure of cis- and trans-FONO.

    Science.gov (United States)

    Berski, Slawomir; Latajka, Zdzislaw; Gordon, Agnieszka J

    2010-07-21

    The electronic structure of cis- and trans-FONO has been studied using topological analysis of the electron localization function at the B3LYP/aug-cc-pVTZ computational level. In cis-FONO with "normal" F-O bond length (1.428-1.441 A), a protocovalent F-O bonding has been found. The central N-O bond is "drained off" with the electron density (0.40e and 0.42e) and the terminal N-O bond resembles an electron-rich single bond (2.13e-2.14e). The F...ONO form with a long F...O bond (1.719 and 1.696 A) has a diradical character and consists of F and NO(2) subunits without clear indications of the covalent bond in the F...O region.

  16. Time-resolved fluorescence spectra of cis-stilbene in hexane and acetonitrile

    Science.gov (United States)

    Sajadi, M.; Dobryakov, A. L.; Garbin, E.; Ernsting, N. P.; Kovalenko, S. A.

    2010-04-01

    Transient fluorescence spectra from cis-stilbene in solution are recorded with 0.24 ps instrument response by a Kerr-Shutter upon excitation at 283 and 267 nm. The fluorescence decay shows no dependence on the excitation wavelength and proceeds monoexponentially with 0.21 ps in acetonitrile and 0.75 ps in hexane. No spectral shift or distortion of the fluorescence band is observed during the decay. Fluorescence contribution from 4a,4b-dihydrophenanthrene (DHP), produced in a competing reaction channel, was not detectable. From comparison with trans-fluorescence, the emission oscillator strength of cis-stilbene is determined to be 0.19 in hexane and 0.21 in acetonitrile.

  17. Functional analysis of cis-acting sequences regulating root-specific expression in transgenic tobacco

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two different length fragments, RSF1 and RSF2 which contained the cis-acting sequences of root-spe- cific gene TobRB7, were isolated from tobacco genome. The abilities of these fragments to direct root-specific expression were studied by fusing them to the β-glucuronidase (GUS) report gene with different directions. After the recombined vectors were transformed into tobacco, the expression pattern was performed by histochemical staining and the quantitative analysis of GUS activity. The data suggested that the cis-acting element of TobRB7 gene direct GUS expression not only as root-specific but also as bidirectional. In our studies, the short fragment, RSF2, performed stronger activity than RSF1 with any direction. The stronger activity of GUS expression was determined by reverse inserting of RSF1 or RSF2 than positive inserting.

  18. Cis-trans isomerisation of azobenzenes studied by laser-coupled NMR spectroscopy and DFT calculations.

    Science.gov (United States)

    Wazzan, Nuha A; Richardson, Patricia R; Jones, Anita C

    2010-07-30

    In a combined experimental and computational study of a group of para-substituted azobenzenes, the effects of substituents and solvent on the kinetics of thermal cis-to-trans isomerisation have been examined and the success of DFT calculations in predicting kinetic parameters assessed. Mono-substituted species are predicted to isomerise by inversion in both non-polar and polar solvent, whereas for push-pull azobenzenes the mechanism is predicted to change from inversion to rotation on going from non-polar to polar solvent. Computed free energies of activation qualitatively reproduce experimental trends but do not quantitatively predict the kinetics of cis-trans isomerisation. The polarisable continuum model of solvation fails to predict the experimentally observed influence of solvent on the entropy of activation.

  19. Polarity controlled reaction path and kinetics of thermal cis-to-trans isomerization of 4-aminoazobenzene.

    Science.gov (United States)

    Joshi, Neeraj Kumar; Fuyuki, Masanori; Wada, Akihide

    2014-02-20

    Spectral and kinetic behavior of thermal cis-to-trans isomerization of 4-aminoazobenzene (AAB) is examined in various solvents of different polarities. In contrast to azobenzene (AB), it is found the rate of thermal isomerization of AAB is highly dependent on solvent polarity. Accelerated rates are observed in polar solvents as compared to nonpolar solvents. Moreover, a decrease in the barrier height with an increase in medium polarity is observed. Our observations suggest that inversion is the preferred pathway in cis-to-trans thermal isomerization in a nonpolar medium; however, in a polar medium, the isomerization path deviates from the inversion route and rotational behavior is incorporated. Differences in the kinetics and in mechanisms of isomerization in different media are rationalized in terms of modulation in barrier height by polarity of the medium and solute-solvent interaction. It is found that kinetics as well as the mechanism of thermal isomerization in AAB is controlled by the polarity of the medium.

  20. [Trypanocidal activity and plasma kinetics of cis-Pt(II) pentamidine in the parasitized sheep].

    Science.gov (United States)

    Dreyfuss, G; Penicaut, B; Parrondo-Iglesias, E; Craciunescu, D; Dubost, G; Nicolas, J A

    1990-01-01

    The trypanocidal activity of cis-Pt(II) pentamidine had been demonstrated during the first phase of Trypanosoma brucei brucei sheep experimental trypanosomiasis. But a subcutaneous treatment with 5 mg.kg-1 (+2 x 12 mg.kg-1) was not effective during the brain phase of trypanosomiasis. The blood pharmacokinetics of this compound had a plasmatic peak between 45 and 60 min, followed by a low decreasing phase along several days. The curve shape allowed an important interval before the following injection, and showed a compound storage in internal organs and extravascular sites. A model of cis-Pt(II) pentamidine metabolism had been studied: this product could be used as a chemoprophylactic medicine against African trypanosomiasis and American leishmaniasis.

  1. How Is cis-trans Isomerization Controlled in Dronpa Mutants? A Replica Exchange Molecular Dynamics Study.

    Science.gov (United States)

    Moors, Samuel L C; Michielssens, Servaas; Flors, Cristina; Dedecker, Peter; Hofkens, Johan; Ceulemans, Arnout

    2008-06-01

    The reversibly photoactivatable green fluorescent protein analog Dronpa holds great promise as a marker for various new cellular imaging applications. Using a replica exchange method which combines both Hamiltonian and temperature exchanges, the ground-state dynamics of Dronpa and two mutants with increased switching kinetics, Val157Gly and Met159Thr, were compared. The dominant chromophore state was found to be the cis isomer in all three proteins. The simulation data suggest that both mutations strongly increase the chromophore flexibility and cis-trans isomerization rate. We identify three key amino acids, Val157, Met159, and Phe173, which are able to impede the bottom hula-twist transition path, depending on their position and rotameric state. We believe our insights will help to understand the switching process and provide useful information for the design of new variants with improved fluorescence properties.

  2. Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

    Science.gov (United States)

    Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

    2016-01-01

    This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.

  3. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  4. Versatile Peptide C-Terminal Functionalization via a Computationally Engineered Peptide Amidase

    NARCIS (Netherlands)

    Wu, Bian; Wijma, Hein J.; Song, Lu; Rozeboom, Henriette J.; Poloni, Claudia; Tian, Yue; Arif, Muhammad I.; Nuijens, Timo; Quaedflieg, Peter J. L. M.; Szymanski, Wiktor; Feringa, Ben L.; Janssen, Dick B.

    2016-01-01

    The properties of synthetic peptides, including potency, stability, and bioavailability, are strongly influenced by modification of the peptide chain termini. Unfortunately, generally applicable methods for selective and mild C-terminal peptide functionalization are lacking. In this work, we explore

  5. Automated solid-phase peptide synthesis to obtain therapeutic peptides

    Directory of Open Access Journals (Sweden)

    Veronika Mäde

    2014-05-01

    Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

  6. Ab initio based Monte Carlo studies of Cu-depleted CIS phases for solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Christian; Gruhn, Thomas; Felser, Claudia [Institut fuer Anorganische and Analytische Chemie, Johannes Gutenberg-Universitaet Mainz (Germany); Windeln, Johannes [IBM Mainz (Germany)

    2011-07-01

    Thin film solar cells with a CuInSe{sub 2} (CIS) absorber layer have an increasing share of the solar cell market because of their low production costs and the high efficiency. One interesting aspect of CIS is the inherent resilience to defects and composition fluctuations. Beside the stable CuInSe{sub 2} phase, there are various Cu-poor phases along the Cu{sub 2}Se-In{sub 2}Se{sub 3} tie line, including the CuIn{sub 3}Se{sub 5} and the CuIn{sub 5}Se{sub 8} phase. We have used ab initio calculations of Cu-poor CIS configurations to make a cluster expansion of the configurational energy. In the configurations, Cu atoms, In atoms, and vacancies are distributed over the Cu and In sites of a CIS cell with fixed Se atoms. With the resulting energy expression, CuIn{sub 3}Se{sub 5} and CuIn{sub 5}Se{sub 8} systems have been studied in the canonical ensemble. By analyzing the free energy landscape the transition temperature between a low-temperature ordered and a high-temperature disordered CuIn{sub 5}Se{sub 8} phase has been determined. Furthermore, grandcanonical ensemble simulations have been carried out, which provide the equilibrium Cu and In concentrations as a function of the chemical potentials {mu}{sub Cu} and {mu}{sub In}. Plateau regions for the CuInSe{sub 2} and the CuIn{sub 5}Se{sub 8} phases have been found and analyzed for different temperatures.

  7. Marketing, Co-operatives and Price Heterogeneity: Evidence from the CIS Dairy Sector

    OpenAIRE

    Sauer, Johannes; Gorton, Matthew; White, John

    2011-01-01

    Drawing on survey data, this paper identifies the determinants of variations in farm gate milk prices for three CIS countries (Armenia, Moldova and Ukraine). We apply a multi-level modeling approach, specifically a bootstrapped and selectivity bias corrected mixed-effects linear regression model. The analysis suggests three main strategies for farmers to improve the price received for their output: consolidation, cooperation and stable supply chain relationships. While selling through a marke...

  8. Marketing, cooperatives and price heterogeneity: evidence from the CIS dairy sector

    OpenAIRE

    Sauer, Johannes; Gorton, Matthew; White, John

    2011-01-01

    Drawing on survey data, this paper identifies the determinants of variations in farm gate milk prices for three CIS countries (Armenia, Moldova and Ukraine). We apply a multi-level modeling approach, specifically a bootstrapped and selectivity bias corrected mixed-effects linear regression model. The analysis suggests three main strategies for farmers to improve the price received for their output: consolidation, cooperation and stable supply chain relationships. While selling through a marke...

  9. Phase, morphology, and dimension control of CIS powders prepared using a solvothermal process

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Chih-Hui [Department of Materials Science and Engineering, National Cheng Kung University, Tainan, Taiwan (China); Ting, Jyh-Ming, E-mail: jting@mail.ncku.edu.t [Department of Materials Science and Engineering, National Cheng Kung University, Tainan, Taiwan (China)

    2009-05-29

    Crystalline chalcopyrite semiconductor CuInSe{sub 2} nanostructures were prepared using a solvothermal route. Various amine organic agents were used as the solvents. Cupric chloride, indium chloride, and selenium powders were mixed in a solvent of ethylenediamine or diethylamine. Effects of reaction time, reaction temperature, solvent type, and reactant concentration were studied. The results show that through selective processing conditions, the phase, morphology, and dimensions of the obtained CIS nanostructures can be controlled.

  10. Cis-Antisense Transcription Gives Rise to Tunable Genetic Switch Behavior: A Mathematical Modeling Approach.

    Science.gov (United States)

    Bordoy, Antoni E; Chatterjee, Anushree

    2015-01-01

    Antisense transcription has been extensively recognized as a regulatory mechanism for gene expression across all kingdoms of life. Despite the broad importance and extensive experimental determination of cis-antisense transcription, relatively little is known about its role in controlling cellular switching responses. Growing evidence suggests the presence of non-coding cis-antisense RNAs that regulate gene expression via antisense interaction. Recent studies also indicate the role of transcriptional interference in regulating expression of neighboring genes due to traffic of RNA polymerases from adjacent promoter regions. Previous models investigate these mechanisms independently, however, little is understood about how cells utilize coupling of these mechanisms in advantageous ways that could also be used to design novel synthetic genetic devices. Here, we present a mathematical modeling framework for antisense transcription that combines the effects of both transcriptional interference and cis-antisense regulation. We demonstrate the tunability of transcriptional interference through various parameters, and that coupling of transcriptional interference with cis-antisense RNA interaction gives rise to hypersensitive switches in expression of both antisense genes. When implementing additional positive and negative feed-back loops from proteins encoded by these genes, the system response acquires a bistable behavior. Our model shows that combining these multiple-levels of regulation allows fine-tuning of system parameters to give rise to a highly tunable output, ranging from a simple-first order response to biologically complex higher-order response such as tunable bistable switch. We identify important parameters affecting the cellular switch response in order to provide the design principles for tunable gene expression using antisense transcription. This presents an important insight into functional role of antisense transcription and its importance towards

  11. Evaluation of combinatorial cis-regulatory elements for stable gene expression in chicken cells

    Directory of Open Access Journals (Sweden)

    Seo Hee W

    2010-09-01

    Full Text Available Abstract Background Recent successes in biotechnological application of birds are based on their unique physiological traits such as unlimited manipulability onto developing embryos and simple protein constituents of the eggs. However it is not likely that target protein is produced as kinetically expected because various factors affect target gene expression. Although there have been various attempts to minimize the silencing of transgenes, a generalized study that uses multiple cis-acting elements in chicken has not been made. The aim of the present study was to analyze whether various cis-acting elements can help to sustain transgene expression in chicken fibroblasts. Results We investigated the optimal transcriptional regulatory elements for enhancing stable transgene expression in chicken cells. We generated eight constructs that encode enhanced green fluorescent protein (eGFP driven by either CMV or CAG promoters (including the control, containing three types of key regulatory elements: a chicken lysozyme matrix attachment region (cMAR, 5'-DNase I-hypersensitive sites 4 (cHS4, and the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE. Then we transformed immortalized chicken embryonic fibroblasts with these constructs by electroporation, and after cells were expanded under G418 selection, analyzed mRNA levels and mean fluorescence intensity (MFI by quantitative real-time PCR and flow cytometry, respectively. We found that the copy number of each construct significantly decreased as the size of the construct increased (R2 = 0.701. A significant model effect was found in the expression level among various constructs in both mRNA and protein (P cis-acting elements decreased the level of gene silencing as well as the coefficient of variance of eGFP-expressing cells (P Conclusions Our current data show that an optimal combination of cis-acting elements and promoters/enhancers for sustaining gene expression in chicken cells

  12. Evolved tooth gain in sticklebacks is associated with a cis-regulatory allele of Bmp6.

    Science.gov (United States)

    Cleves, Phillip A; Ellis, Nicholas A; Jimenez, Monica T; Nunez, Stephanie M; Schluter, Dolph; Kingsley, David M; Miller, Craig T

    2014-09-23

    Developmental genetic studies of evolved differences in morphology have led to the hypothesis that cis-regulatory changes often underlie morphological evolution. However, because most of these studies focus on evolved loss of traits, the genetic architecture and possible association with cis-regulatory changes of gain traits are less understood. Here we show that a derived benthic freshwater stickleback population has evolved an approximate twofold gain in ventral pharyngeal tooth number compared with their ancestral marine counterparts. Comparing laboratory-reared developmental time courses of a low-toothed marine population and this high-toothed benthic population reveals that increases in tooth number and tooth plate area and decreases in tooth spacing arise at late juvenile stages. Genome-wide linkage mapping identifies largely separate sets of quantitative trait loci affecting different aspects of dental patterning. One large-effect quantitative trait locus controlling tooth number fine-maps to a genomic region containing an excellent candidate gene, Bone morphogenetic protein 6 (Bmp6). Stickleback Bmp6 is expressed in developing teeth, and no coding changes are found between the high- and low-toothed populations. However, quantitative allele-specific expression assays of Bmp6 in developing teeth in F1 hybrids show that cis-regulatory changes have elevated the relative expression level of the freshwater benthic Bmp6 allele at late, but not early, stages of stickleback development. Collectively, our data support a model where a late-acting cis-regulatory up-regulation of Bmp6 expression underlies a significant increase in tooth number in derived benthic sticklebacks.

  13. cis-Difluoridobis(1,10-phenanthroline)chromium(III) perchlorate monohydrate

    DEFF Research Database (Denmark)

    Birk, Torben; Bendix, Jesper; Weihe, Högni

    2008-01-01

    The title complex, [CrF(2)(C(12)H(8)N(2))(2)]ClO(4)·H(2)O, displays a slightly distorted octa-hedral coordination geometry around the central chromium(III) ion. The Cr environment is composed of a cis arrangement of two 1,10-phenanthroline [average Cr(III)-N = 2.0726 (10) Å] and two fluoride...

  14. Cis-cotranscription of two beta globin genes during chicken primitive hematopoiesis.

    Directory of Open Access Journals (Sweden)

    Hiroki Nagai

    Full Text Available Chicken beta globin locus contains four genes, two of which, rho and epsilon, are expressed from the earliest stage of primitive hematopoiesis. Here we show that the transcription of these two genes in the nucleus engages in "on/off" phases. During each "on" phase, cotranscription of rho and epsilon in cis is favored. We propose that these two chicken beta globin genes are transcribed not by competing for a transcription initiation complex, but in a cooperative way.

  15. cis-[3-(2-Chloro-6-methylquinolin-3-yloxiran-2-yl](p-tolylmethanone

    Directory of Open Access Journals (Sweden)

    Narasimhamurthy Preveena

    2017-03-01

    Full Text Available In the title compound, C20H16ClNO2, the dihedral angle between the quinolyl ring system and the p-tolyl ring is 65.80 (7°. The rings are bridged by a functionalized epoxide system, with the exocyclic bonds in a cis configuration. In the crystal, weak C—H...O and C—H...Cl interactions link the molecules into [100] chains.

  16. Synthesis of novel biscrown ethers with rigid cis/trans ethylene bridge

    Institute of Scientific and Technical Information of China (English)

    Jian Quan Fan; La Sheng Jiang; Min Zhang; Na Wei; Ya Hui Feng; Shu Juan Han; Hui Wang

    2008-01-01

    Two novel biscrown ethers with rigid cisltrans ethylene linker were synthesized v/a Wittig reaction in high yield (about 80%).Their pure cis/trans-isomers were obtained by column chromatography separation. And their structure/configuration was confirmedby 1H NMR, 13C NMR, ESI mass spectrum, elemental analysis and UV-vis spectra.? 2008 La Sheng Jiang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  17. Enhancing Natural Attenuation through Bioaugmentation with Aerobic Bacteria that Degrade cis-1,2-Dichloroethene

    Science.gov (United States)

    2010-05-01

    cDCE cis-1,2-dichloroethene cfu colony forming units CMO cyclohexanone monooxygenase DCA 1,2-dichloroethane DNA deoxyribonucleic acid...of JS666) and (2) cyclohexanone monooxygenase (CMO) (based on the cyclohexanone monooxygenase gene of JS666). Additionally, a putative universal (UNI...molecular probes (one based on the isocitrate lyase gene and one based on the cyclohexanone monooygenase gene). In addition, JS666 activity and

  18. Unusual cis-diprotonated forms and fluorescent aggregates of non-peripherally alkoxy-substituted metallophthalocyanines.

    Science.gov (United States)

    Kasprzycki, P; Sobotta, L; Lijewski, S; Wierzchowski, M; Goslinski, T; Mielcarek, J; Radzewicz, C; Fita, P

    2017-08-16

    Protonation and aggregation of two metallophthalocyanines (zinc and magnesium) non-peripherally substituted with 1,4,7-trioxanonyl moieties were studied by steady-state and time-resolved optical spectroscopy. Both compounds are easily protonated in organic solvents, but the central metal ion strongly affects the character of this process. In particular, the magnesium derivative forms the cis-diprotonated isomer observed for the first time in phthalocyanines, in contrast to its zinc counterpart which forms the typical trans-diprotonated isomer. In addition, studies performed on phthalocyanines substituted with n-butoxy groups at their non-peripheral positions indicated that the formation of the cis-diprotonated forms is a more common feature of alkoxy-substituted magnesium metallophthalocyanines, in contrast to derivatives with other metal ions. The cis-diprotonated forms of the magnesium derivatives are formed at much lower proton concentrations than the trans-diprotonated forms of their zinc counterparts. The cis-isomers were also found to have more advantageous photophysical properties for photoactive applications than the trans-isomers. Aggregation studies of the trioxanonyl phthalocyanines revealed that the magnesium derivative aggregates much more easily in non-coordinating solvents than its zinc counterpart. Both the derivatives form fluorescent aggregates, which is typically attributed to the presence of oxygen-to-metal intermolecular coordination preventing the formation of non-fluorescent face-to-face stacks. The results indicate that the oxygen-to-metal coordination plays a significant role in the studied systems and the stronger oxygen-coordination ability of magnesium ions compared to zinc ions may underlie the observed differences between the phthalocyanines metallated with these two ions.

  19. Exhaustive Search for Over-represented DNA Sequence Motifs with CisFinder

    OpenAIRE

    Sharov, Alexei A; Minoru S.H. Ko

    2009-01-01

    We present CisFinder software, which generates a comprehensive list of motifs enriched in a set of DNA sequences and describes them with position frequency matrices (PFMs). A new algorithm was designed to estimate PFMs directly from counts of n-mer words with and without gaps; then PFMs are extended over gaps and flanking regions and clustered to generate non-redundant sets of motifs. The algorithm successfully identified binding motifs for 12 transcription factors (TFs) in embryonic stem cel...

  20. Biotransformation of (S)-cis-verbenol with Nocardia corallina B-276

    Energy Technology Data Exchange (ETDEWEB)

    Manjarrez, Norberto; Perez, Herminia I.; Solis, Aida; Luna, Hector; Lievano, Ricardo; Ramirez, Mario [Universidad Autonoma Metropolitana, Mexico, D.F. (Mexico). Unidad Xochimilco. Dept. de Sistemas Biologicos]. E-mail: maan@correo.xoc.uam.mx

    2007-07-01

    The biotransformation of (S)-cis-verbenol with Nocardia corallina was investigated using two methods: Suspension of cells in a phosphate buffer (pH 7) with various substrate:cells ratios; and bioreactor of 3-L with cells in the culture media. Both gave (1S)-(-)-verbenone with excellent yields ranging from >99 to 98%, at scale of 0.7 and 7 mmol respectively. (author)

  1. THE BIMODAL MOLECULAR WEIGHT DISTRIBUTION OF cis-POLYBUTADIENE POLYMERIZED WITH LANTHANIDE COMPLEX CATALYSTS

    Institute of Scientific and Technical Information of China (English)

    CHENG Rongshi; HU Huizhen; JIANG Liansheng

    1987-01-01

    The variation of the molecular weight and molecular weight distribution of cis-polybutadiene in the course of polymerization catalyzed by lanthanide complex composed of triisobutyl aluminium or diisobutyl aluminium hydride was investigated by osmometry, viscometry and size exclusion chromatography. By analyzing the experimental data, the reasons of the appearance of bimodal molecular weight distribution were elucidated and the possible mechanisms of polymerization were discussed.

  2. Solid Phase Biosensors for Arsenic or Cadmium Composed of A trans Factor and cis Element Complex

    Directory of Open Access Journals (Sweden)

    Mohammad Shohel Rana Siddiki

    2011-10-01

    Full Text Available The presence of toxic metals in drinking water has hazardous effects on human health. This study was conducted to develop GFP-based-metal-binding biosensors for on-site assay of toxic metal ions. GFP-tagged ArsR and CadC proteins bound to a cis element, and lost the capability of binding to it in their As- and Cd-binding conformational states, respectively. Water samples containing toxic metals were incubated on a complex of GFP-tagged ArsR or CadC and cis element which was immobilized on a solid surface. Metal concentrations were quantified with fluorescence intensity of the metal-binding states released from the cis element. Fluorescence intensity obtained with the assay significantly increased with increasing concentrations of toxic metals. Detection limits of 1 μg/L for Cd(II and 5 μg/L for As(III in purified water and 10 µg/L for Cd(II and As(III in tap water and bottled mineral water were achieved by measurement with a battery-powered portable fluorometer after 15-min and 30-min incubation, respectively. A complex of freeze dried GFP-tagged ArsR or CadC binding to cis element was stable at 4 °C and responded to 5 μg/L As(III or Cd(II. The solid phase biosensors are sensitive, less time-consuming, portable, and could offer a protocol for on-site evaluation of the toxic metals in drinking water.

  3. cis-Tetrachloridobis(1H-imidazole-κN3platinum(IV

    Directory of Open Access Journals (Sweden)

    Vadim Yu. Kukushkin

    2012-05-01

    Full Text Available In the title complex, cis-[PtCl4(C3H4N22], the PtIV ion lies on a twofold rotation axis and is coordinated in a slightly distorted octahedral geometry. The dihedral angle between the imidazole rings is 69.9 (2°. In the crystal, molecules are linked by N—H...Cl hydrogen bonds, forming a three-dimensional network.

  4. Cluster Ion Spectrometry (CIS) data quality indexes as a support for analysing magnetospheric measurements

    Science.gov (United States)

    Dandouras, Iannis; Barthe, Alain; Brunato, Sylvain; Rème, Henri; Laakso, Harri

    2016-04-01

    The Cluster Science Archive (CSA) aims at preserving the complete set of the measurements collected by the four Cluster spacecraft, so that they are usable in the long-term by the world-wide scientific community as well as by the instrument teams. This implies that the instrument data, properly calibrated, are filed together with the descriptive and documentary elements making it possible to select and interpret them. The CIS (Cluster Ion Spectrometry) experiment is a comprehensive ionic plasma spectrometry package onboard the Cluster spacecraft, capable of obtaining full three-dimensional ion distributions (about 0 to 40 keV/e) with a time resolution of one spacecraft spin (4 sec) and with mass-per-charge composition determination. For the archival of the CIS data a multi-level approach has been adopted. The CSA archival includes processed raw data, moments of the ion distribution functions, and calibrated high-resolution data in a variety of physical units. The latter are 3-D ion distribution functions, 2-D pitch-angle distributions and 1-D omni-directional fluxes. The CIS data archive includes also experiment documentation, graphical products for browsing through the data, data caveats and data quality indexes. The later constitute a novel product, which has been prepared in order to help the user asses the quality of the data acquired in different magnetospheric regions and during various operational modes. It provides information on which are in each case the issues that can affect the data quality, which are the data products affected, and gives a simple quantitative measurement of the severity of these issues. The principle of the CIS data quality indexes will be described and the various issues, that can under some conditions affect the data quality and are thus taken into account in generating the data quality indexes, will be discussed.

  5. Zirconium-doped magnetic microspheres for the selective enrichment of cis-diol-containing ribonucleosides.

    Science.gov (United States)

    Fan, Hua; Chen, Peihong; Wang, Chaozhan; Wei, Yinmao

    2016-05-27

    Zirconium-doped magnetic microspheres (Zr-Fe3O4) for the selective enrichment of cis-diol-containing biomolecules were easily synthesized via a one-step hydrothermal method. Characterization of the microspheres revealed that zirconium was successfully doped into the lattice of Fe3O4 at a doping level of 4.0 at%. Zr-Fe3O4 possessed good magnetic properties and high specificity towards cis-diol molecules, as shown using 28 compounds. For ribonucleosides, the adsorbent not only has favorable anti-interferential abilities but also has a high adsorption capacity up to 159.4μmol/g. As an example of a real application, four ribonucleosides in urine were efficiently enriched and detected via magnetic solid-phase extraction coupled with high-performance liquid chromatography. Under the optimized extraction conditions, the detection limits were determined to be between 0.005 and 0.017μg/mL, and the linearities ranged from 0.02 to 5.00μg/mL (R≥0.996) for these analytes. The accuracy of the analytical method was examined by studying the relative recoveries of the analytes in real urine samples, with recoveries varying from 77.8% to 119.6% (RSDs<10.6%, n=6). The results indicate that Zr-Fe3O4 is a suitable adsorbent for the analysis of cis-diol-containing biomolecules in practical applications.

  6. Epistasis in tomato color mutations involves regulation of phytoene synthase 1 expression by cis-carotenoids.

    Science.gov (United States)

    Kachanovsky, David E; Filler, Shdema; Isaacson, Tal; Hirschberg, Joseph

    2012-11-13

    Tomato (Solanum lycopersicum) fruit accumulate the red carotenoid pigment lycopene. The recessive mutation yellow-flesh (locus r) in tomato eliminates fruit carotenoids by disrupting the activity of the fruit-specific phytoene synthase (PSY1), the first committed step in the carotenoid biosynthesis pathway. Fruits of the recessive mutation tangerine (t) appear orange due to accumulation of 7,9,7',9'-tetra-cis-lycopene (prolycopene) as a result of a mutation in the carotenoid cis-trans isomerase. It was established 60 y ago that tangerine is epistatic to yellow-flesh. This uncharacteristic epistasis interaction defies a paradigm in biochemical genetics arguing that mutations that disrupt enzymes acting early in a biosynthetic pathway are epistatic to other mutations that block downstream steps in the same pathway. To explain this conundrum, we have investigated the interaction between tangerine and yellow-flesh at the molecular level. Results presented here indicate that allele r(2997) of yellow-flesh eliminates transcription of PSY1 in fruits. In a genetic background of tangerine, transcription of PSY1 is partially restored to a level sufficient for producing phytoene and downstream carotenoids. Our results revealed the molecular mechanism underlying the epistasis of t over r and suggest the involvement of cis-carotenoid metabolites in a feedback regulation of PSY1 gene expression.

  7. Control of Biofilms with the Fatty Acid Signaling Molecule cis-2-Decenoic Acid

    Directory of Open Access Journals (Sweden)

    Cláudia N. H. Marques

    2015-11-01

    Full Text Available Biofilms are complex communities of microorganisms in organized structures attached to surfaces. Importantly, biofilms are a major cause of bacterial infections in humans, and remain one of the most significant challenges to modern medical practice. Unfortunately, conventional therapies have shown to be inadequate in the treatment of most chronic biofilm infections based on the extraordinary innate tolerance of biofilms to antibiotics. Antagonists of quorum sensing signaling molecules have been used as means to control biofilms. QS and other cell-cell communication molecules are able to revert biofilm tolerance, prevent biofilm formation and disrupt fully developed biofilms, albeit with restricted effectiveness. Recently however, it has been demonstrated that Pseudomonas aeruginosa produces a small messenger molecule cis-2-decenoic acid (cis-DA that shows significant promise as an effective adjunctive to antimicrobial treatment of biofilms. This molecule is responsible for induction of the native biofilm dispersion response in a range of Gram-negative and Gram-positive bacteria and in yeast, and has been shown to reverse persistence, increase microbial metabolic activity and significantly enhance the cidal effects of conventional antimicrobial agents. In this manuscript, the use of cis-2-decenoic acid as a novel agent for biofilm control is discussed. Stimulating the biofilm dispersion response as a novel antimicrobial strategy holds significant promise for enhanced treatment of infections and in the prevention of biofilm formation.

  8. Liquid-Phase Deposition of CIS Thin Layers: Final Report, February 2003--July 2005

    Energy Technology Data Exchange (ETDEWEB)

    Ernst, F.; Pirouz, P.

    2006-02-01

    The goal of this project was to fabricate single-phase CIS (a-Cu-In-Se, stoichiometric composition: CuInSe2) thin films for photovoltaic applications from a liquid phase - a Cu-In-Se melt of appropriate composition. This approach of liquid-phase deposition (LPD) is based on the new phase diagram we have established for Cu-In-Se, the first complete equilibrium phase diagram of this system. The liquidus projection exhibits four composition fields in which the primary solid phase, i.e., the first solid material that forms on cooling down from an entirely liquid state, is a-CuInSe2. Remarkably, none of the four composition fields is anywhere near the stoichiometric composition (CuInSe2) of a-CuInSe2. The results demonstrate that the proposed technique is indeed capable of producing films with a particularly large grain size and a correspondingly low density of grain boundaries. To obtain films sufficiently thin for solar cell applications and with a sufficiently smooth surface, it is advantageous to employ a sliding boat mechanism. Future work on liquid-phase deposition of CIS should focus on the interaction between the melt and the substrate surface, the resulting CIS interfaces, the surface morphology of the LPD-grown films, and, of course, the electronic properties of the material.

  9. Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element.

    Science.gov (United States)

    Mao, Grace; Brody, James P

    2007-11-09

    Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014s(-1). We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase.

  10. Beta-2-microglobulin excretion: an indicator of long term nephrotoxicity during cis-platinum treatment?

    DEFF Research Database (Denmark)

    Sørensen, P G; Nissen, Mogens Holst; Groth, S;

    1985-01-01

    To evaluate the value of beta-2-microglobulin as an indicator of acute and long-term cis-platinum-induced nephrotoxicity, 51Cr-EDTA clearance and serum concentration and urinary excretion of beta-2-microglobulin were measured in 18 patients treated with a regimen including cis-platinum. Before...... treatment all values were within the normal range. During treatment 51Cr-EDTA clearance decreased from 108 to 90 ml/min/1.73 m2 (P less than 0.02). The decrease was irreversible, while a transient 2 to 5-fold increase in beta-2-microglobulin excretion in the urine was seen during treatment. Serum beta-2......-microglobulin remained unchanged. The decrease in 51Cr-EDTA clearance was not correlated to either the peak increase in the beta-2-microglobulin excretion or to the time of occurrence of the peak (R = 0.3). Thus, it is not possible to predict the long-term nephrotoxicity of cis-platinum by measuring the beta-2...

  11. Concordant gene expression in leukemia cells and normal leukocytes is associated with germline cis-SNPs.

    Directory of Open Access Journals (Sweden)

    Deborah French

    Full Text Available The degree to which gene expression covaries between different primary tissues within an individual is not well defined. We hypothesized that expression that is concordant across tissues is more likely influenced by genetic variability than gene expression which is discordant between tissues. We quantified expression of 11,873 genes in paired samples of primary leukemia cells and normal leukocytes from 92 patients with acute lymphoblastic leukemia (ALL. Genetic variation at >500,000 single nucleotide polymorphisms (SNPs was also assessed. The expression of only 176/11,783 (1.5% genes was correlated (p<0.008, FDR = 25% in the two tissue types, but expression of a high proportion (20 of these 176 genes was significantly related to cis-SNP genotypes (adjusted p<0.05. In an independent set of 134 patients with ALL, 14 of these 20 genes were validated as having expression related to cis-SNPs, as were 9 of 20 genes in a second validation set of HapMap cell lines. Genes whose expression was concordant among tissue types were more likely to be associated with germline cis-SNPs than genes with discordant expression in these tissues; genes affected were involved in housekeeping functions (GSTM2, GAPDH and NCOR1 and purine metabolism.

  12. Long-term performance data and analysis of CIS/CIGS modules deployed outdoors

    Science.gov (United States)

    del Cueto, J. A.; Rummel, S.; Kroposki, B.; Anderberg, A.

    2008-08-01

    The long-term performance data of copper indium diselenide (CIS) and gallium-alloyed CIS (CIGS) photovoltaic (PV) modules are investigated to assess the reliability of this technology. We study and report on numerous PV modules acquired from two manufacturers (A and B), deployed at NREL's outdoor test facility (OTF) in various configurations in the field: some are free standing, loaded with a fixed resistance and periodically tested indoors at STC; other modules are connected to data acquisition systems with their performance continuously monitored. Performance is characterized using current-voltage (I-V) measurements obtained either at standard test conditions or under real-time monitoring conditions: the power parameters plus other factors relating to quality like diode quality factors or series resistance are analyzed for changes against time. Using standard diode analysis to determine the sources of degradation indicates that CIS modules can exhibit between moderate and negligible degradation, with the dominant loss mode being fill factor declines along with decreases in open-circuit voltage, for illumination intensities near 1-sun. At lower intensities, current losses can appear appreciable. The real-time performance data also indicate that fill factor loss is the primary degradation mode, generally as a result of increases in series resistance.

  13. A mixed-valent cyclodiphosphazane: Transition metal chemistry and cis/trans isomerisation

    Indian Academy of Sciences (India)

    Guddekoppa S Ananthnag; Joel T Mague; Maravanji S Balakrishna

    2015-06-01

    The hydrolysis of cis-{ClP(-NBu)2P(NHBu)} (1) produced a mixed PIII/PV derivative of cyclodiphosphazane, cis-{(BuNH)P(-NBu)2P(O)H} (2). The treatment of 2 with elemental selenium resulted in the formation of the monoselenide, trans-{(BuNH)P(Se)(-NBu)2P(O)H} (3) in good yield. The reactions of two equivalent of 2 with [Pd(-Cl)(3-C3H5)]2 or [Ru(6--cymene)(-Cl)Cl]2 in dichloromethane afforded corresponding mononuclear complexes, [(3-C3H5)PdCl{(BuNH)P(-NBu)2P(O)H}] (4) and [((6--cymene)RuCl2){(BuNH)P(-NBu)2P(O)H}] (5). The treatment of 2 with M(COD)Cl2 (M = Pd and Pt) in dichloromethane at room temperature gave [MCl2{(BuNH)P(-NBu)2P(O)H}2] (6 M = Pd; 7 M = Pt) in good yield. Owing to the cis/trans isomerisation of the cyclodiphosphazane rings, the complexes 6 and 7 exist as a mixture of two isomers. Various NMR spectroscopic techniques were employed for structural elucidation. The molecular structures of 5 and 7 were established by single crystal X-ray crystallographic studies.

  14. Isomerization of cis-1,2-dimethylcyclohexane in single-pulse shock tube experiments.

    Science.gov (United States)

    Rosado-Reyes, Claudette M; Tsang, Wing

    2014-09-11

    Cyclic hydrocarbons are major constituents of jet fuels and reference compounds in jet fuel surrogates. The kinetic and thermal stability and reaction mechanisms of fuel molecules are essential input parameters in the models and simulations used in the design of novel fuels, renewable energy technologies, and devices. A detailed study and analysis of the pyrolytic chemistry of cis-1,2-dimethylcyclohexane has been performed in single-pulse shock tube experiments. The investigations are carried out over the temperature range of 1100 to 1200 K at about 2.5 atm pressure. The isomeric products are trans-1,2-dimethylcyclohexane, 1-octene, and (cis + trans)-2-octene. The three octene isomers can be attributed to internal disproportionation processes. Assuming a diradical mechanism and that cis-1,2-dimethylcyclohexane is formed in equal amount with respect to its trans isomer, the total rate expression for isomerization is kC-C = 10(15.5±0.8) exp(-38,644 ± 2061 K/T) s(-1). The rate constants are over an order of magnitude smaller than the equivalent noncyclic hydrocarbon system. The presence of the isomeric octenes suggests that internal disproportionation is an important component of the isomerization process.

  15. Substrate selectivity of various lipases in the esterification of cis- and trans-9-octadecenoic acid.

    Science.gov (United States)

    Borgdorf, R; Warwel, S

    1999-04-01

    The substrate selectivity of numerous commercially available lipases from microorganisms, plants and animal tissue towards 9-octadecenoic acids with respect to the cis/trans configuration of the C=C double bond was examined by the esterification of cis- and trans-9-octadecanoic acid (oleic and elaidic acid respectively) with n-butanol in n-hexane. A great number of lipases studied, e.g. those from Pseudomonas sp., porcine pancreas or Carica papaya, were unable to discriminate between the isomeric 9-octadecenoic acids. However, lipases from Candida cylindracea and Mucor miehei catalysed the esterification of oleic acid 3-4 times faster than the corresponding reaction of elaidic acid and therefore have a high preference for the cis isomer. Of all biocatalysts examined, only recombinant lipases from Candida antarctica favoured elaidic acid as substrate. While the preference of Candida antarctica lipase B for the trans isomer was quite low, Candida antarctica lipase A had an extraordinary substrate selectivity and its immobilized enzyme preparation [Chirazyme L-5 (3) from Boehringer] esterified elaidic acid about 15 times faster than oleic acid.

  16. A Cis-Lunar Propellant Infrastructure for Flexible Path Exploration and Space Commerce

    Science.gov (United States)

    Oeftering, Richard C.

    2012-01-01

    This paper describes a space infrastructure concept that exploits lunar water for propellant production and delivers it to users in cis-lunar space. The goal is to provide responsive economical space transportation to destinations beyond low Earth orbit (LEO) and enable in-space commerce. This is a game changing concept that could fundamentally affect future space operations, provide greater access to space beyond LEO, and broaden participation in space exploration. The challenge is to minimize infrastructure development cost while achieving a low operational cost. This study discusses the evolutionary development of the infrastructure from a very modest robotic operation to one that is capable of supporting human operations. The cis-lunar infrastructure involves a mix of technologies including cryogenic propellant production, reusable lunar landers, propellant tankers, orbital transfer vehicles, aerobraking technologies, and electric propulsion. This cislunar propellant infrastructure replaces Earth-launched propellants for missions beyond LEO. It enables users to reach destinations with smaller launchers or effectively multiplies the user s existing payload capacity. Users can exploit the expanded capacity to launch logistics material that can then be traded with the infrastructure for propellants. This mutually beneficial trade between the cis-lunar infrastructure and propellant users forms the basis of in-space commerce.

  17. Electronic spectra and trans—cis isomerism of streptopolymethine cyanines. A CS INDO CI study

    Science.gov (United States)

    Momicchioli, Fabio; Baraldi, Ivan; Ponterini, Glauco; Berthier, Gaston

    The understanding of the role played by cyanine dyes in various fields of application calls for a thorough knowledge of the excited state properties of their parent chromophores, i.e. cationic streptopolymethyne cyanines. For this aim we performed a detailed CS INDO CI investigation on the electronic spectra of tri-, penta- and heptamethine cyanines, both unsubstituted (TC, PC, HC) and terminally substituted by methyl groups (BMTC, BMPC, BMHC). The study comprised S0 Sn, and S0 Tn transitions of the trans and all mono- cis isomers. CI expansions involved solely π orbitals of the polymethine chains and pseudo-π orbitals of the substituents and included all singly-excited and the most important doubly- and triply-excited configurations. The spectroscopic effects of methyl substitution are fairly well described and are shown to be especially important in the upper excited states. The identification of the photochemically formed stereoisomers is attempted in terms of mono- cis isomers. For BMPC, in particular, we report the absorption spectrum of the phototropic form and show that the photoisomer is identifiable as the 3-4 cis form.

  18. Cis-regulatory Mutations in the Caenorhabditis elegans Homeobox Gene Locus cog-1 Affect Neuronal Development

    Science.gov (United States)

    O'Meara, M. Maggie; Bigelow, Henry; Flibotte, Stephane; Etchberger, John F.; Moerman, Donald G.; Hobert, Oliver

    2009-01-01

    We apply here comparative genome hybridization as a novel tool to identify the molecular lesion in two Caenorhabditis elegans mutant strains that affect a neuronal cell fate decision. The phenotype of the mutant strains resembles those of the loss-of-function alleles of the cog-1 homeobox gene, an inducer of the fate of the gustatory neuron ASER. We find that both lesions map to the cis-regulatory control region of cog-1 and affect a phylogenetically conserved binding site for the C2H2 zinc-finger transcription factor CHE-1, a previously known regulator of cog-1 expression in ASER. Identification of this CHE-1-binding site as a critical regulator of cog-1 expression in the ASER in vivo represents one of the rare demonstrations of the in vivo relevance of an experimentally determined or predicted transcription-factor-binding site. Aside from the mutationally defined CHE-1-binding site, cog-1 contains a second, functional CHE-1-binding site, which in isolation is sufficient to drive reporter gene expression in the ASER but in an in vivo context is apparently insufficient for promoting appropriate ASER expression. The cis-regulatory control regions of other ASE-expressed genes also contain ASE motifs that can promote ASE neuron expression when isolated from their genomic context, but appear to depend on multiple ASE motifs in their normal genomic context. The multiplicity of cis-regulatory elements may ensure the robustness of gene expression. PMID:19189954

  19. cis-regulatory elements involved in ultraviolet light regulation and plant defense.

    Science.gov (United States)

    Wingender, R; Röhrig, H; Höricke, C; Schell, J

    1990-10-01

    An elicitor-regulated transient expression system was established in soybean protoplasts that allowed the identification of cis-regulatory elements involved in plant defense. The 5' region of an ultraviolet (UV) light-inducible and elicitor-inducible chs gene (chs1) of soybean was subjected to deletion analysis with the help of chimeric chs-nptII/gus gene constructs. This analysis delimited the sequences necessary for elicitor inducibility to -175 and -134 of the chs1 promoter. The same soybean sequences were able to direct elicitor inducibility in parsley protoplasts, suggesting a conserved function of cis-acting elements involved in plant defense. In addition, this region of the soybean promoter also promotes UV light inducibility in parsley protoplasts. However, in contrast to the elicitor induction, correct regulation was not observed after UV light induction when sequences downstream of -75 were replaced by a heterologous minimal promoter. This result indicates that at least two cis-acting elements are involved in UV light induction.

  20. Effects of cis- and trans-unsaturated lipids on an interdigitated membrane.

    Science.gov (United States)

    Smith, Eric A; Smith, Connor; Tanksley, Brian; Dea, Phoebe K

    2014-06-01

    The effects of adding cis- and trans-unsaturated lipid to a fully interdigitated membrane were examined using differential scanning calorimetry (DSC) and X-ray diffraction. A monofluorinated analog of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was used as the interdigitated lipid. The single fluorine atom on the end of the sn-2 chain allows 1-palmitoyl-2-(16-fluoropalmitoyl)sn-glycero-3-phosphocholine (F-DPPC) to spontaneously form the interdigitated gel phase (LβI) below the main transition temperature (Tm). The cis 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and equivalent trans lipid 1,2-dielaidoyl-sn-glycero-3-phosphocholine (DEPC) are strongly disfavored to form the LβI phase. Wide-angle X-ray scattering (WAXS) data demonstrate that the unsaturated lipids progressively disrupt the intermolecular packing at higher concentrations. Small-angle X-ray scattering (SAXS) data show that as the ratio of unsaturated lipid increases, the amount of interdigitated lipid decreases. The cis isomer is more disruptive and inhibits interdigitation more effectively than the trans isomer.

  1. Semiconductor photocatalysis. Cis-trans photoisomerization of simple alkenes induced by trapped holes at surface states

    Energy Technology Data Exchange (ETDEWEB)

    Yanagida, S.; Mizumoto, K.; Pac, C.

    1986-02-19

    The use of ZnS or CdS as photocatalysts induces an efficient cis-trans photoisomerization of simple alkenes, e.g., the 2-octenes, 3-hexen-1-ols, and methyl 9-octadecenoates in photostationary cis-trans ratios almost identical with the thermodynamic equilibrium ratios achieved by the phenylthio radical. Quantum yields for the cis-trans photoisomerization, phi/sub c-t/, exceed largely over unity. Mechanistic studies involving Stern-Volmer analyses, quenching effect of oxygen, and ESR analyses under band-gap irradiation of ZnS in methanol demonstrate that the photoisomerizations take place with high turnover numbers at active sites where trapped holes at surface states, i.e., sulfur radicals arising from Zn vacancies and/or interstitial sulfur on sulfide semiconductors, play decisive roles. A highly efficient catalysis occurs with ZnS sols prepared from polysulfide-containing Na/sub 2/S solution. The trapped-hole mechanism is further supported by the enhanced effect of water acting as a good electron acceptor as well as the quenching effect of diethylamine acting as an electron donor.

  2. Comparative genome sequencing of drosophila pseudoobscura: Chromosomal, gene and cis-element evolution

    Energy Technology Data Exchange (ETDEWEB)

    Richards, Stephen; Liu, Yue; Bettencourt, Brian R.; Hradecky, Pavel; Letovsky, Stan; Nielsen, Rasmus; Thornton, Kevin; Todd, Melissa J.; Chen, Rui; Meisel, Richard P.; Couronne, Olivier; Hua, Sujun; Smith, Mark A.; Bussemaker, Harmen J.; van Batenburg, Marinus F.; Howells, Sally L.; Scherer, Steven E.; Sodergren, Erica; Matthews, Beverly B.; Crosby, Madeline A.; Schroeder, Andrew J.; Ortiz-Barrientos, Daniel; Rives, Catherine M.; Metzker, Michael L.; Muzny, Donna M.; Scott, Graham; Steffen, David; Wheeler, David A.; Worley, Kim C.; Havlak, Paul; Durbin, K. James; Egan, Amy; Gill, Rachel; Hume, Jennifer; Morgan, Margaret B.; Miner, George; Hamilton, Cerissa; Huang, Yanmei; Waldron, Lenee; Verduzco, Daniel; Blankenburg, Kerstin P.; Dubchak, Inna; Noor, Mohamed A.F.; Anderson, Wyatt; White, Kevin P.; Clark, Andrew G.; Schaeffer, Stephen W.; Gelbart, William; Weinstock, George M.; Gibbs, Richard A.

    2004-04-01

    The genome sequence of a second fruit fly, D. pseudoobscura, presents an opportunity for comparative analysis of a primary model organism D. melanogaster. The vast majority of Drosophila genes have remained on the same arm, but within each arm gene order has been extensively reshuffled leading to the identification of approximately 1300 syntenic blocks. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 35 My since divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome wide average consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than control sequences between the species but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a picture of repeat mediated chromosomal rearrangement, and high co-adaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila.

  3. The identification of cis-regulatory elements: A review from a machine learning perspective.

    Science.gov (United States)

    Li, Yifeng; Chen, Chih-Yu; Kaye, Alice M; Wasserman, Wyeth W

    2015-12-01

    The majority of the human genome consists of non-coding regions that have been called junk DNA. However, recent studies have unveiled that these regions contain cis-regulatory elements, such as promoters, enhancers, silencers, insulators, etc. These regulatory elements can play crucial roles in controlling gene expressions in specific cell types, conditions, and developmental stages. Disruption to these regions could contribute to phenotype changes. Precisely identifying regulatory elements is key to deciphering the mechanisms underlying transcriptional regulation. Cis-regulatory events are complex processes that involve chromatin accessibility, transcription factor binding, DNA methylation, histone modifications, and the interactions between them. The development of next-generation sequencing techniques has allowed us to capture these genomic features in depth. Applied analysis of genome sequences for clinical genetics has increased the urgency for detecting these regions. However, the complexity of cis-regulatory events and the deluge of sequencing data require accurate and efficient computational approaches, in particular, machine learning techniques. In this review, we describe machine learning approaches for predicting transcription factor binding sites, enhancers, and promoters, primarily driven by next-generation sequencing data. Data sources are provided in order to facilitate testing of novel methods. The purpose of this review is to attract computational experts and data scientists to advance this field.

  4. Non-H[sub 2]Se, ultra-thin CIS devices. [CuInSe[sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Delahoy, A.E.; Britt, J.; Kiss, Z. (Energy Photovoltaics, Inc., Princeton, NJ (United States))

    1993-02-01

    This report describes work done during Phase I of a 3-phase, cost- shared contract. Objective of the subcontract is to demonstrate 12% total-area efficiency copper indium diselenide (CIS) solar cells and 50-W CIS modules average at least 8 W/ft[sup 2] in the third year. At the end of Phase I, EPV delivered to NREL a 1.1 cm[sup 2] CIS cell with an active area efficiency of 10.5%. the corresponding total-area efficiency is 7.9%.

  5. Strand-specific RNA-seq reveals widespread occurrence of novel cis-natural antisense transcripts in rice

    Directory of Open Access Journals (Sweden)

    Lu Tingting

    2012-12-01

    Full Text Available Abstract Background Cis-natural antisense transcripts (cis-NATs are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs, which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs. Results We applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa. Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set, 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. Among them, 503 cis-NATs seemed to be associated with specific conditions. The deep sequence data from isolated epidermal cells of rice seedlings further showed that 54.0% of cis-NATs were expressed simultaneously in a population of homogenous cells. Nearly 9.7% of rice transcripts were involved in one-to-one or many-to-many cis-NATs formation. Furthermore, only 17.4-34.7% of 223 many-to-many cis-NAT groups were all expressed and generated nat-siRNAs, indicating that only some cis-NAT groups may be involved in complex regulatory networks. Conclusions

  6. The contribution of cis-regulatory elements to head-to-head gene pairs’ co-expression pattern

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Transcription regulation is one of the most critical pipelines in biological process,in which cis-elements play the role as gene expression regulators.We attempt to deduce the principles underlying the co-expression of "head-to-head" gene pairs by analyzing activities or behaviors of the shared cis-elements.A network component analysis was performed to estimate the impact of cis-elements on gene promoters and their activities under different conditions.Our discoveries reveal how biological system uses those regulatory elements to control the expression pattern of "head-to-head" gene pairs and the whole transcription regulation system.

  7. Direct demonstration of NCAM cis-dimerization and inhibitory effect of palmitoylation using the BRET2 technique

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Grunnet, Lars Groth; Lundh, Morten

    2011-01-01

    Biological activity of the neural cell adhesion molecule (NCAM) depends on both adhesion and activation of intra-cellular signaling. Based on in vitro experiments with truncated extra-cellular domains, several models describing homophilic NCAM trans- and cis-interactions have been proposed. However......, cis-dimerization in living cells has not been shown directly and the role of the cytoplasmic part in NCAM dimerization is poorly understood. Here, we used the bioluminescence resonance energy transfer (BRET(2)) technique to directly demonstrate that full-length NCAM cis-homodimerizes in living cells...

  8. Perspectives and Peptides of the Next Generation

    Science.gov (United States)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  9. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk

    2009-07-01

    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  10. Exploration of the Medicinal Peptide Space.

    Science.gov (United States)

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

  11. Peptide synthesis using unprotected peptides through orthogonal coupling methods.

    Science.gov (United States)

    Tam, J P; Lu, Y A; Liu, C F; Shao, J

    1995-01-01

    We describe an approach to the synthesis of peptides from segments bearing no protecting groups through an orthogonal coupling method to capture the acyl segment as a thioester that then undergoes an intramolecular acyl transfer to the amine component with formation of a peptide bond. Two orthogonal coupling methods to give the covalent ester intermediate were achieved by either a thiol-thioester exchange mediated by a trialkylphosphine and an alkylthiol or a thioesterification by C alpha-thiocarboxylic acid reacting with a beta-bromo amino acid. With this approach, unprotected segments ranging from 4 to 37 residues were coupled to aqueous solution to give free peptides up to 54 residues long with high efficiency. Images Fig. 1 PMID:8618926

  12. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111; Estudio de biodistribucion de nanoesferas lipidicas cargadas con cis-diaminodicloroplatino (II) y marcadas con nucleos radioactivos de Indio-111

    Energy Technology Data Exchange (ETDEWEB)

    Lopez R, V.; Juarez O, C.; Medina L, A. [Unidad de Investigacion Biomedica en Cancer INCAN-UNAM, Mexico D.F. (Mexico); Perez C, E.; Garcia L, P. [Instituto nacional de cancerologia, Mexico D.F. (Mexico)

    2007-07-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  13. Twilight reloaded: the peptide experience

    Science.gov (United States)

    Weichenberger, Christian X.; Pozharski, Edwin; Rupp, Bernhard

    2017-01-01

    The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallo­graphic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein–peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided. PMID:28291756

  14. Divergence in cis-regulatory sequences surrounding the opsin gene arrays of African cichlid fishes

    Directory of Open Access Journals (Sweden)

    Streelman J Todd

    2011-05-01

    Full Text Available Abstract Background Divergence within cis-regulatory sequences may contribute to the adaptive evolution of gene expression, but functional alleles in these regions are difficult to identify without abundant genomic resources. Among African cichlid fishes, the differential expression of seven opsin genes has produced adaptive differences in visual sensitivity. Quantitative genetic analysis suggests that cis-regulatory alleles near the SWS2-LWS opsins may contribute to this variation. Here, we sequence BACs containing the opsin genes of two cichlids, Oreochromis niloticus and Metriaclima zebra. We use phylogenetic footprinting and shadowing to examine divergence in conserved non-coding elements, promoter sequences, and 3'-UTRs surrounding each opsin in search of candidate cis-regulatory sequences that influence cichlid opsin expression. Results We identified 20 conserved non-coding elements surrounding the opsins of cichlids and other teleosts, including one known enhancer and a retinal microRNA. Most conserved elements contained computationally-predicted binding sites that correspond to transcription factors that function in vertebrate opsin expression; O. niloticus and M. zebra were significantly divergent in two of these. Similarly, we found a large number of relevant transcription factor binding sites within each opsin's proximal promoter, and identified five opsins that were considerably divergent in both expression and the number of transcription factor binding sites shared between O. niloticus and M. zebra. We also found several microRNA target sites within the 3'-UTR of each opsin, including two 3'-UTRs that differ significantly between O. niloticus and M. zebra. Finally, we examined interspecific divergence among 18 phenotypically diverse cichlids from Lake Malawi for one conserved non-coding element, two 3'-UTRs, and five opsin proximal promoters. We found that all regions were highly conserved with some evidence of CRX transcription

  15. Peptide-enhanced oral delivery of therapeutic peptides and proteins

    DEFF Research Database (Denmark)

    Kristensen, Mie; Foged, Camilla; Berthelsen, Jens;

    2013-01-01

    throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed......Systemic therapy upon oral delivery of biologics, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients...

  16. Study on Preparation and Crystal Structure of cis-Propiconazole%cis-丙环唑的制备及其晶体结构的研究

    Institute of Scientific and Technical Information of China (English)

    罗金香; 杨春龙

    2006-01-01

    采用丙环唑与硝酸成盐法和硅胶柱层析法制备了cis-丙环唑,并培养出单晶,用X射线单晶衍射法确定了其立体结构.晶体属单斜晶系,P21/c空间群,晶胞参数a=1.065 3(3)nm,b=1.894 0(6)nm,c=0.810 4(3)nm,β=100.032(6)°,Z=4,V=1.610 0(9)nm3,Dc=1.412g/cm3,F(000)=712,u=0.413 mm-1,R=0.066 2,wR=0.136 9.

  17. Pharmacokinetic correlation between experimental and clinical effects on human non-small cell lung cancers of cis-diammineglycolatoplatinum (254-S) and cis-diamminedichloroplatinum.

    Science.gov (United States)

    Koenuma, M; Kasai, H; Uchida, N; Wada, T; Hattori, M; Oguma, T; Totani, T; Inaba, M

    1995-01-01

    We attempted to correlate the in vitro and in vivo antitumor activities of cis-diammineglycolatoplatinum (254-S), a novel platinum complex, and cis-diamminedichloro-platinum (CDDP) against the established culture cell lines and xenografts of human non-small cell lung cancer (NSCLC) with their clinical effects, based on the previous finding that the cytotoxicity of CDDP depends on the area under the curve (AUC). The concentration of 254-S and CDDP inhibiting the in vitro growth of 4 cultured NSCLC lines by 50% (IC50) was 0.82-7.8 and 0.53-4.2 micrograms/ml, respectively, showing a similar level. Of the 4 cell lines, only the most sensitive line, RERF-LC-AI, showed an IC50 close to a specific concentration (0.50 for 254-S and 0.32 micrograms/ml for CDDP) that reproduces in vitro the clinical AUCfree (24.8 and 5.34 micrograms-hr/ml) of the respective drugs. We treated 6 lines of human NSCLC xenografts implanted in nude mice with 254-S and CDDP at a particular dose (13.2 and 3.7 mg/kg) that is equivalent to the clinical doses with respect to the plasma AUCfree. 254-S and CDDP exhibited significant antitumor effects on 2 and 1 of the 6 lines, respectively. These in vitro and in vivo findings were considered to be relatively well correlated with the reported clinical response rates of 15-19% for 254-S and 14-15% for CDDP.

  18. Studies on mechanism of cis9,trans11-CLA and trans10,cis12-CLA inducing apoptosis of human breast cancer cell line MCF-7

    Institute of Scientific and Technical Information of China (English)

    Xianzi Wan; Xianlin Yuan; Xiangling Yang; Yichen Li; Ling Zhong

    2010-01-01

    Objective:The aim of the study was to explore the activities of cis9,trans11-CLA (C9,t11-CLA) and trans10,cis12-CLA (t10,c12-CLA)inhibiting tumor,and investigate their relationships with PPARy and apoptotic proteins,and mechanism of anti-cancer.Methods:The inhibitory rate,cell growth curve and apoptotic morphological observation of MCF-7 cells were obtained by MTT assay,trypan blue staining and Hoechst33342 fluorescence staining.The apoptotic rate and cell cycle were detected with flow cytometry.Transcriptional level of genes was detected with RT-PCR semi-quantitative method,and Western blot was performed to detect proteins levels.Results:The two CLA isomers could reduce cell proliferation (P<0.05),increase apoptotic rate (P<0.05),and increase obviously the transcriptional and protein levels of PPARy (P<0.01).The synchronism and correlation between the effects of CLA to PPARy and apoptotic proteins Bax,Bcl-2,Caspase 3 changes were found with the dose-and time-dependent manners.There was cooperative relation between the levels of PPARy and the rates of Bax/Bcl-2,Caspase 3 (small fragment) by experiments of PPARy inhibitor GW9662 and ligand Rosiglitazone.Conclusion:The apoptotic pathway of PPARy-Bcl-2-Caspase 3 signaling was found.The C9,t11-CLA and t10,c12-CLA could inhibit MCF-7 cell proliferation and promote apoptosis via activating PPARy-Bcl-2-Caspase 3 pathway.CLA may be a kind of activator of PPARy.

  19. Contents of conjugated linoleic acid isomers cis9,trans11 and trans10,cis12 in ruminant and non-ruminant meats available in the Italian market

    Directory of Open Access Journals (Sweden)

    Francesca M. Cicognini

    2014-04-01

    Full Text Available Conjugated linoleic acid (CLA isomers are considered healthy factors due to their anticarcinogenic, anti-atherosclerotic and lipolytic effect. A recommended daily intake from 0.8 to 3 g CLA/day/person has been proposed to obtain biological effects in humans. The aim of this work was to provide data on cis9,trans11 (c9,t11 CLA and trans10,cis12 (t10,c12 CLA contents in meats collected from Italian largescale retail trade and completing a food CLA database. In a first trial, beef loin meats were characterised for label information available for consumers: origin (i.e., Ireland, France- Italy, Piedmont and sex of animals. No differences were observed for c9,t11 and t10,c12 CLA contents (mg/g fat of loin meat from male or female. Piedmontese meat showed lower (P<0.05 c9,t11 CLA level (mg/g fat than Irish and French-Italian meats, whereas similar t10,c12 CLA contents were measured in Piedmontese, Irish and French-Italian meats. Successively, meat samples from different animal species (male and female beef, veal, suckling lamb, belly beef, canned beef meat, pork and horse were characterised for their contents in c9,t11 and t10,c12 CLA. Lamb meat had the highest (P<0.05 c9,t11 CLA content (mg/g fat. The c9,t11 CLA was lower than 2 mg/g fat in veal, pork and horse meats. Low t10,c12 CLA amounts were found in all analysed meat samples. These data provided information to estimate the average daily intake of CLA from meats in an Italian cohort, which can be used in epidemiological studies.

  20. Copper(II)-bis-histidine coordination structure in a fibrillar amyloid β-peptide fragment and model complexes revealed by electron spin echo envelope modulation spectroscopy.

    Science.gov (United States)

    Hernández-Guzmán, Jessica; Sun, Li; Mehta, Anil K; Dong, Jijun; Lynn, David G; Warncke, Kurt

    2013-09-23

    Truncated and mutated amyloid-β (Aβ) peptides are models for systematic study-in homogeneous preparations-of the molecular origins of metal ion effects on Aβ aggregation rates, types of aggregate structures formed, and cytotoxicity. The 3D geometry of bis-histidine imidazole coordination of Cu(II) in fibrils of the nonapetide acetyl-Aβ(13-21)H14A has been determined by powder (14) N electron spin echo envelope modulation (ESEEM) spectroscopy. The method of simulation of the anisotropic combination modulation is described and benchmarked for a Cu(II) -bis-cis-imidazole complex of known structure. The revealed bis-cis coordination mode, and the mutual orientation of the imidazole rings, for Cu(II) in Ac-Aβ(13-21)H14A fibrils are consistent with the proposed β-sheet structural model and pairwise peptide interaction with Cu(II) , with an alternating [-metal-vacancy-]n pattern, along the N-terminal edge. Metal coordination does not significantly distort the intra-β-strand peptide interactions, which provides a possible explanation for the acceleration of Ac-Aβ(13-21)H14A fibrillization by Cu(II) , through stabilization of the associated state and low-reorganization integration of β-strand peptide pair precursors.

  1. Intracellular peptides: From discovery to function

    Directory of Open Access Journals (Sweden)

    Emer S. Ferro

    2014-06-01

    Full Text Available Peptidomics techniques have identified hundreds of peptides that are derived from proteins present mainly in the cytosol, mitochondria, and/or nucleus; these are termed intracellular peptides to distinguish them from secretory pathway peptides that function primarily outside of the cell. The proteasome and thimet oligopeptidase participate in the production and metabolism of intracellular peptides. Many of the intracellular peptides are common among mouse tissues and human cell lines analyzed and likely to perform a variety of functions within cells. Demonstrated functions include the modulation of signal transduction, mitochondrial stress, and development; additional functions will likely be found for intracellular peptides.

  2. Recent development of peptide self-assembly

    Institute of Scientific and Technical Information of China (English)

    Xiubo Zhao; Fang Pan; Jian R. Lu

    2008-01-01

    Amino acids are the building blocks to build peptides and proteins. Recent development in peptide synthesis has however enabled us to mimic this natural process by preparing various long and short peptides possessing different conformations and biological functions. The self-assembly of short designed peptides into molecular nanostructures is becoming a growing interest in nanobiotechnology. Self-assembled peptides exhibit several attractive features for applications in tissue regeneration, drug delivery, biological surface engineering as well as in food science, cosmetic industry and antibiotics. The aim of this review is to introduce the readers to a number of representative studies on peptide self-assembly.

  3. Characterization of Synthetic Peptides by Mass Spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter;

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS an......Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI...

  4. Embryonic exposure to cis-bifenthrin enantioselectively induces the transcription of genes related to oxidative stress, apoptosis and immunotoxicity in zebrafish (Danio rerio).

    Science.gov (United States)

    Jin, Yuanxiang; Pan, Xiuhong; Cao, Limin; Ma, Bufang; Fu, Zhengwei

    2013-02-01

    Cis-bifenthrin (cis-BF) is used widely for agricultural and non-agricultural purpose. Thus, cis-BF is one of the most frequently detected insecticides in the aquatic ecosystem. As a chiral pesticide, the commercial cis-BF contained two enantiomers including 1R-cis-BF and 1S-cis-BF. However, the difference in inducing oxidative stress, apoptosis and immunotoxicity by the two enantiomers in zebrafish still remains unclear. In the present study, the zebrafish were exposed to environmental concentrations of cis-BF, 1R-cis-BF and 1S-cis-BF during the embryos developmental stage. We observed that the mRNA levels of the most genes related to oxidative stress, apoptosis and immunotoxicity including Cu/Zn-superoxide dismutase (Cu/Zn-Sod), catalase (Cat), P53, murine double minute 2 (Mdm2), B-cell lymphoma/leukaemia-2 gene (Bcl2), Bcl2 associated X protein (Bax), apoptotic protease activating factor-1 (Apaf1), Caspase 9 (Cas9), Caspase 3 (Cas3), interleukin-1 beta (IL-1β) and interleukin-8(Il-8) were much higher in 1S-cis-BF treated group than those in cis-BF or 1R-cis-BF treated ones, suggesting that 1S-cis-BF has higher risk to induced oxidative stress, apoptosis and immunotoxicity than 1R-cis-BF in zebrafish. The information presented in this study will help with elucidating the differences and environmental risk of the two enantiomers of cis-BF-induced toxicity in aquatic organisms.

  5. Studies on the synthesis, characterization, binding with DNA and activities of two cis-planaramineplatinum(II complexes of the form: cis-PtL(NH3Cl2 where L = 3-hydroxypyridine and 2,3-diaminopyridine

    Directory of Open Access Journals (Sweden)

    Tayyem Hasan

    2006-03-01

    Full Text Available Abstract Background Cis-planaramineplatinum(II complexes like their trans isomers are often found to be active against cancer cell lines. The present study deals with the synthesis, characterization and determination of activity of new cis-planaramineplatinum(II complexes. Results Two cis-planaramineplatinum(II complexes: cis-(3-hydroxypyridine(amminedichloroplatinum(II (code named AH3 and cis-(2,3-diaminopyridine(amminedichloroplatinum(II (code named AH7 have been prepared and characterised based on elemental analyses, IR, Raman, mass and 1H NMR spectral measurements. The interactions of the compounds with pBR322 plasmid DNA have been investigated and their activity against ovarian cancer cell lines: A2780, A2780cisR and A2780ZD047Rhave been determined. Like cisplatin, AH3 and AH7 are believed to form mainly monofunctional N7(G and bifunctional intrastrand N7(GN7(G adducts with DNA, causing a local distortion of a DNA strand. As a result, gel mobility of the DNA changes. Both AH3 and AH7 are found to be less active than cisplatin against the three cell lines with AH3 being the more active compound of the two. The higher activity of AH3 is in line with its lower molar conductivity value corresponding to a lower degree of dissociation. Conclusion The differences in activity of AH3, AH7 and cisplatin against the cell lines illustrate structure-activity relationship.

  6. Antimicrobial Peptides from Marine Proteobacteria

    Directory of Open Access Journals (Sweden)

    Yannick Fleury

    2013-09-01

    Full Text Available After years of inadequate use and the emergence of multidrug resistant (MDR strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs, synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs, obtained through the linkage of (unusual amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs.

  7. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster (Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10-5 kDa, 5-1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10?5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  8. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    pharmacological tools interfering with NCAM functions. Recent progress in our understanding of the structural basis of NCAM-mediated cell adhesion and signaling has allowed a structure-based design of NCAM mimetic peptides. Using this approach a number of peptides termed P2, P1-B, P-3-DE and P-3-G, whose...... sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling a number of peptides derived from NCAM and targeting NCAM heterophilic ligands such as the fibroblast growth factor receptor...... in vitro and in vivo, making them attractive pharmacological tools suitable for drug development for the treatment of neurodegenerative disorders and impaired memory....

  9. A double-blind clinical investigation of cis(Z)-clopenthixol and clopenthixol in chronic schizophrenic patients.

    Science.gov (United States)

    Heikkilä, L; Karsten, D; Valli, K

    1981-01-01

    The therapeutic effect of the neuroleptic cis(Z)-clopenthixol has been compared with that of clopenthixol in mainly chronic schizophrenic patients in a double-blind 8-week trial. Forty-nine of the 54 patients in the trial received clopenthixol in the pre-trial period. Ratings with CGI and a single side effects form were done at weeks 0, 2, 4, 6, and 8. The registration of therapeutic effect at week 8 indicated a symptomatological status quo in both groups of patients while there was a tendency of slightly less interference by cis(Z)-clopenthixol with patient's functioning than by clopenthixol. The ratio of therapeutically equipotent cis(Z)-clopenthixol/clopenthixol doses was found to be 1:2. It is suggested that long-term treatment with clopenthixol advantageously may be replaced by cis(Z)-clopenthixol.

  10. Enhanced cis-platinum ototoxicity in children with brain tumours who have received simultaneous or prior cranial irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Walker, D.A.; Pillow, J.; Waters, K.D.; Keir, E.

    1989-01-01

    We report on four children who received cis-platinum simultaneously with, or in one case 10 months after, cranial irradiation and experienced exaggerated ototoxicity affecting all audible frequencies. The hearing loss was severe, affecting the critical areas for speech perception, and necessitated the provision of bilateral hearing aids. The audiograms of these patients are shown and compared to those of four children who had received cis-platinum as part of their treatment for neuroblastoma but without cranial irradiation. The precipitation of the exaggerated hearing loss with the administration of cis-platinum in one patient 10 months after finishing cranial irradiation suggests that care should be taken in the timing of cis-platinum administration in relation to concurrent or previous cranial irradiation.

  11. Communication: An accurate calculation of the S1 C2H2 cis-trans isomerization barrier height.

    Science.gov (United States)

    Baraban, Joshua H; Matthews, Devin A; Stanton, John F

    2016-03-21

    A high level ab initio calculation of the cis-trans isomerization barrier height in the first excited singlet electronic state of acetylene is found to agree very well with a recent experimental determination.

  12. Synthesis and Structural Properties of Aza[n]helicene Platinum Complexes: Control of Cis and Trans Stereochemistry.

    Science.gov (United States)

    Mendola, Daniele; Saleh, Nidal; Hellou, Nora; Vanthuyne, Nicolas; Roussel, Christian; Toupet, Loïc; Castiglione, Franca; Melone, Federica; Caronna, Tullio; Fontana, Francesca; Martí-Rujas, Javier; Parisini, Emilio; Malpezzi, Luciana; Mele, Andrea; Crassous, Jeanne

    2016-03-07

    The synthesis and structural characterization of azahelicene platinum complexes obtained from cis-PtCl2(NCEt)(PPh3) and from ligands that differ in terms of both the position of the nitrogen atom and the number of fused rings are reported. These square-planar complexes of the general formula PtCl2(nHm)(PPh3) (n = 4, 5; m = 5, 6) display mainly a cis configuration. However, by X-ray crystallographic analysis, we show that for both PtCl2(4H6)(PPh3) and PtCl2(5H6)(PPh3) there is chirality control of the cis/trans stereochemistry. Indeed, starting from a racemic mixture of aza[6]helicene, platinum complexes with a cis configuration are invariably obtained, and the more thermodynamically stable trans isomers are formed when using enantiopure ligands. We further corroborated these results by NMR analysis in solution.

  13. Characterization of the binding strengths between boronic acids and cis-diol-containing biomolecules by affinity capillary electrophoresis.

    Science.gov (United States)

    Lü, Chenchen; Liu, Zhen

    2015-01-01

    The affinity of boronic acids toward cis-diol-containing biomolecules has found wide applications in many fields, such as sensing, separation, drug delivery, and functional materials. A sound understanding of the binding interactions will greatly facilitate exquisite applications of this chemistry. Traditional techniques are associated with some apparent drawbacks, so they are only applicable to a limited range of boronic acids and cis-diol-containing biomolecules. This chapter describes an affinity capillary electrophoresis (ACE) method for the characterization of the binding strengths between boronic acids and cis-diol-containing biomolecules. As compared with existing approaches, such as (11)B NMR, the ACE method exhibits several significant advantages: (1) possibility of simultaneous study of multiple interactions, (2) low requirement on the purity of the binding species, (3) widely applicable to almost all types of cis-diol-containing compounds and boronic acids, and (4) high accuracy and precision.

  14. Metabolomic fingerprinting of primed tobacco cells provide the first evidence for the biological origin of cis-chlorogenic acid

    CSIR Research Space (South Africa)

    Mhlongo, MI

    2015-01-01

    Full Text Available Previous studies suggest that only transisomers of chlorogenic acid (CGA) are naturally produced. Cis-isomers have been noted in some plant tissues exposed to different mechanical processes as well as untreated tobacco leaves exposed to sunlight...

  15. Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

    Directory of Open Access Journals (Sweden)

    Mohammed Salah Ayoup

    2015-12-01

    Full Text Available Palladium catalysed carbonylation reactions using the meta- and para-iodo derivatives of all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane (4 are illustrated as the start point for a variety of functional group interconversions. The resultant benzaldehyde and benzoic acids offer novel building blocks for further derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds.

  16. The inhibition of macrophage foam cell formation by 9-cis β-carotene is driven by BCMO1 activity.

    Directory of Open Access Journals (Sweden)

    Noa Zolberg Relevy

    Full Text Available Atherosclerosis is a major cause of morbidity and mortality in developed societies, and begins when activated endothelial cells recruit monocytes and T-cells from the bloodstream into the arterial wall. Macrophages that accumulate cholesterol and other fatty materials are transformed into foam cells. Several epidemiological studies have demonstrated that a diet rich in carotenoids is associated with a reduced risk of heart disease; while previous work in our laboratory has shown that the 9-cis β-carotene rich alga Dunaliella inhibits atherogenesis in mice. The effect of 9-cis β-carotene on macrophage foam cell formation has not yet been investigated. In the present work, we sought to study whether the 9-cis β-carotene isomer, isolated from the alga Dunaliella, can inhibit macrophage foam cell formation upon its conversion to retinoids. The 9-cis β-carotene and Dunaliella lipid extract inhibited foam cell formation in the RAW264.7 cell line, similar to 9-cis retinoic acid. Furthermore, dietary enrichment with the algal powder in mice resulted in carotenoid accumulation in the peritoneal macrophages and in the inhibition of foam cell formation ex-vivo and in-vivo. We also found that the β-carotene cleavage enzyme β-carotene 15,15'-monooxygenase (BCMO1 is expressed and active in macrophages. Finally, 9-cis β-carotene, as well as the Dunaliella extract, activated the nuclear receptor RXR in hepa1-6 cells. These results indicate that dietary carotenoids, such as 9-cis β-carotene, accumulate in macrophages and can be locally cleaved by endogenous BCMO1 to form 9-cis retinoic acid and other retinoids. Subsequently, these retinoids activate the nuclear receptor RXR that, along with additional nuclear receptors, can affect various metabolic pathways, including those involved in foam cell formation and atherosclerosis.

  17. Peptide Antibiotics for ESKAPE Pathogens

    DEFF Research Database (Denmark)

    Thomsen, Thomas Thyge

    a cecropin-mellitin hybrid peptide and proved effective in killing colistin resistant Gram-negative A. baumannii in vitro. The molecule was improved with regard to toxicity, as measured by hemolytic ability. Further, this peptide is capable of specifically killing non-growing cells of colistin resistant A......Multi-drug resistance to antibiotics represents a global health challenge that results in increased morbidity and mortality rates. The annual death-toll is >700.000 people world-wide, rising to ~10 million by 2050. New antibiotics are lacking, and few are under development as return on investment...

  18. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  19. Peptides and the new endocrinology

    Science.gov (United States)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  20. An enhancer peptide for membrane-disrupting antimicrobial peptides

    Directory of Open Access Journals (Sweden)

    Zhang Hong

    2010-02-01

    Full Text Available Abstract Background NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4 by substitution of all acidic amino acid residues with amides (i.e., Glu → Gln, and Asp → Asn. Results In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-α, polymyxin B, and nisin killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-α against Staphylococcus aureus, whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at ≤ 300 μg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-α permeabilized S. aureus membranes with enhanced efficacy in the presence of NP4P. Conclusions NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane.

  1. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies...... are powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors...... such as structure, accessibility and amino acid composition are crucial. Since small peptides tend not to be immunogenic, it may be necessary to conjugate them to carrier proteins in order to enhance immune presentation. Several strategies for conjugation of peptide-carriers applied for immunization exist...

  2. Histidine-Containing Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2000-01-01

    Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics.......Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics....

  3. Part 1. Antimicrobial and Immunomodulatory Peptides

    African Journals Online (AJOL)

    Furthermore, some peptides have been shown to have mineral ... immunopotentiating and antimicrobial properties including .... that this will give a clarion call to focus on the benefits ..... peptide could also be used in cosmetic, eye-care, oral.

  4. Recent advances in solid phase peptide synthesis

    OpenAIRE

    White, P.D.

    2016-01-01

    Since its introduction by Merrifield half a century ago, solid phase peptide synthesis has evolved to become the enabling technology for the development of peptide therapeutics. Using modern methods, 100 - 1000s of peptides can be routinely synthesised in parallel for screening as leads for drug development and peptide APIs are produced in ton scale. In this talk I consider the state of art and report on recent advances to overcome remaining issues such as aspartimide formation, racemisation ...

  5. Development and use of engineered peptide deformylase in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia

    2012-01-01

    Deze thesis beschrijft het onderzoek naar potentieel van het gebruik van het peptide deformylase (PDF) in chemo enzymatische peptide synthese. PDF is geschikt voor selective N terminale deformylatie van bepaalde N-formyl-peptides zonder gelijktijdige hydrolyse van de peptide binding. Door de uitdagi

  6. Structural studies of polypeptides: Mechanism of immunoglobin catalysis and helix propagation in hybrid sequence, disulfide containing peptides

    Energy Technology Data Exchange (ETDEWEB)

    Storrs, Richard Wood [Univ. of California, Berkeley, CA (United States)

    1992-08-01

    Catalytic immunoglobin fragments were studied Nuclear Magnetic Resonance spectroscopy to identify amino acid residues responsible for the catalytic activity. Small, hybrid sequence peptides were analyzed for helix propagation following covalent initiation and for activity related to the protein from which the helical sequence was derived. Hydrolysis of p-nitrophenyl carbonates and esters by specific immunoglobins is thought to involve charge complementarity. The pK of the transition state analog P-nitrophenyl phosphate bound to the immunoglobin fragment was determined by 31P-NMR to verify the juxtaposition of a positively charged amino acid to the binding/catalytic site. Optical studies of immunoglobin mediated photoreversal of cis, syn cyclobutane thymine dimers implicated tryptophan as the photosensitizing chromophore. Research shows the chemical environment of a single tryptophan residue is altered upon binding of the thymine dimer. This tryptophan residue was localized to within 20 Å of the binding site through the use of a nitroxide paramagnetic species covalently attached to the thymine dimer. A hybrid sequence peptide was synthesized based on the bee venom peptide apamin in which the helical residues of apamin were replaced with those from the recognition helix of the bacteriophage 434 repressor protein. Oxidation of the disufide bonds occured uniformly in the proper 1-11, 3-15 orientation, stabilizing the 434 sequence in an α-helix. The glycine residue stopped helix propagation. Helix propagation in 2,2,2-trifluoroethanol mixtures was investigated in a second hybrid sequence peptide using the apamin-derived disulfide scaffold and the S-peptide sequence. The helix-stop signal previously observed was not observed in the NMR NOESY spectrum. Helical connectivities were seen throughout the S-peptide sequence. The apamin/S-peptide hybrid binded to the S-protein (residues 21-166 of ribonuclease A) and reconstituted enzymatic activity.

  7. Structural studies of polypeptides: Mechanism of immunoglobin catalysis and helix propagation in hybrid sequence, disulfide containing peptides

    Energy Technology Data Exchange (ETDEWEB)

    Storrs, R.W.

    1992-08-01

    Catalytic immunoglobin fragments were studied Nuclear Magnetic Resonance spectroscopy to identify amino acid residues responsible for the catalytic activity. Small, hybrid sequence peptides were analyzed for helix propagation following covalent initiation and for activity related to the protein from which the helical sequence was derived. Hydrolysis of p-nitrophenyl carbonates and esters by specific immunoglobins is thought to involve charge complementarity. The pK of the transition state analog P-nitrophenyl phosphate bound to the immunoglobin fragment was determined by [sup 31]P-NMR to verify the juxtaposition of a positively charged amino acid to the binding/catalytic site. Optical studies of immunoglobin mediated photoreversal of cis, syn cyclobutane thymine dimers implicated tryptophan as the photosensitizing chromophore. Research shows the chemical environment of a single tryptophan residue is altered upon binding of the thymine dimer. This tryptophan residue was localized to within 20 [Angstrom] of the binding site through the use of a nitroxide paramagnetic species covalently attached to the thymine dimer. A hybrid sequence peptide was synthesized based on the bee venom peptide apamin in which the helical residues of apamin were replaced with those from the recognition helix of the bacteriophage 434 repressor protein. Oxidation of the disufide bonds occured uniformly in the proper 1-11, 3-15 orientation, stabilizing the 434 sequence in an [alpha]-helix. The glycine residue stopped helix propagation. Helix propagation in 2,2,2-trifluoroethanol mixtures was investigated in a second hybrid sequence peptide using the apamin-derived disulfide scaffold and the S-peptide sequence. The helix-stop signal previously observed was not observed in the NMR NOESY spectrum. Helical connectivities were seen throughout the S-peptide sequence. The apamin/S-peptide hybrid binded to the S-protein (residues 21-166 of ribonuclease A) and reconstituted enzymatic activity.

  8. Water drives peptide conformational transitions

    CERN Document Server

    Nerukh, Dmitry

    2011-01-01

    Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that water is the main driving force of the conformational changes.

  9. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Deacon, C F; Holst, Jens Juul; Carr, R D

    1999-01-01

    Type 2 diabetes mellitus is a metabolic disease resulting in raised blood sugar which, if not satisfactorily controlled, can cause severe and often debilitating complications. Unfortunately, for many patients, the existing therapies do not give adequate control. Glucagon-like peptide-1 (GLP-1) is...

  10. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2006-01-01

    The incretin hormones are intestinal polypeptides that enhance postprandial insulin secretion. Gastric inhibitory polypeptide (GIP) was initially thought to regulate gastric acid secretion, whereas glucagon-like peptide-1 (GLP-1) was discovered as a result of a systematic search for intestinal...

  11. The evolution of peptide hormones.

    Science.gov (United States)

    Niall, H D

    1982-01-01

    Despite limitations in our present knowledge it is already possible to discern the main features of peptide hormone evolution, since the same mechanisms (and indeed the same hormone molecules) function in many different ways. This underlying unity of organization has its basis in the tendency of biochemical networks, once established, to survive and diversify. The most surprising recent findings in endocrinology have been the discovery of vertebrate peptide hormones in multiple sites within the same organism, and the reports, persuasive but requiring confirmation, of vertebrate hormones in primitive unicellular organisms (20, 20a). Perhaps the major challenge for the future is to define the roles and interactions of the many peptide hormones identified in brain (18). The most primitive bacteria and the human brain, though an enormous evolutionary distance apart, may have more in common than we have recognized until now. As Axelrod & Hamilton have pointed out in a recent provocative article, "The Evolution of Cooperation" (1), bacteria, though lacking a brain, are capable of adaptive behavior that can be analysed in terms of game theory. It is clear that we can learn a great deal about the whole evolutionary process from a study of the versatile and durable peptide hormones molecules.

  12. Discrimination of cis-trans sex pheromone components in two sympatric Lepidopteran species.

    Science.gov (United States)

    Zhang, Sufang; Kong, Xiangbo; Ze, Sangzi; Wang, Hongbin; Lin, Aizhu; Liu, Fu; Zhang, Zhen

    2016-06-01

    Pheromone-binding proteins (PBPs) play an important role in the recognition of pheromones by insects. However, the abilities of these PBPs to discriminate pheromone components and recognize the isomers are unclear. Dendrolimus houi and Dendrolimus kikuchii are two sympatric coniferous pests whose pheromones have cis-trans isomers. We used these insect species to detect the precise recognition abilities of PBPs. The four PBPs examined showed male-biased antenna-intensive expression patterns, whereas PBP1 showed higher expression than PBP2 in the antenna. DhouPBP1 only bound to a minor interspecific pheromone component, whereas DhouPBP2 bound to all three intraspecific components and another minor interspecific component. DkikPBP1 and DkikPBP2 could recognize all three intraspecific components with affinities negatively correlated with their ratios, and they bound to interspecific pheromones with affinity that was positively correlated with the ratios. The four PBPs have different cis-trans isomer discrimination abilities, i.e., DhouPBP1 and DkikPBP1 could not discriminate the two cis-trans isomer pairs of pheromones from the two species, whereas DhouPBP2 could discriminate between both pairs, and DkikPBP2 could only discriminate one pair. Overall, PBPs from D. houi and D. kikuchii use different strategies to help the moths to discriminate the intra- and interspecific pheromone components. Our work will contribute to better understanding of the sex pheromone recognition mechanism in these two sister species of moths and provide insights into more effective management practices of these pest species.

  13. A model for a statewide critical incident stress (CIS) debriefing program for emergency services personnel.

    Science.gov (United States)

    Neely, K W; Spitzer, W J

    1997-01-01

    Emergency services personnel are highly vulnerable to acute and cumulative critical incident stress (CIS) that can manifest as anger, guilt, depression, and impaired decision-making, and, in certain instances, job loss. Interventions designed to identify such distress and restore psychological functioning becomes imperative. A statewide debriefing team was formed in 1988 through a collaborative effort between an academic department of emergency medicine and a social work department of a teaching hospital, and a metropolitan area fire department and ambulance service. Using an existing CIS debriefing model, 84 prescreened, mental health professionals and emergency services personnel were provided with 16 hours of training and were grouped into regional teams. Debriefing requests are received through a central number answered by a communicator in a 24-hour communications center located within the emergency department. Debriefings are conducted 48-72 hours after the event for specific types of incidents. Follow-up telephone calls are made by the debriefing team leader two to three weeks following a debriefing. The teams rely on donations to pay for travel and meals. One hundred sixty-eight debriefings were conducted during the first four years. Rural agencies accounted for 116 (69%) requests. During this period, 1,514 individuals were debriefed: 744 (49%) firefighters, 460 (30%) EMTs, and 310 (21%) police officers, dispatchers, and other responders. Deaths of children, extraordinary events, and incidents involving victims known to the responders (35%, 14%, and 14% respectively) were the most common reasons for requesting debriefings. Feedback was received from 48 (28%) of the agencies that requested the debriefing. All of those who responded felt that the debriefing had a beneficial effect on its personnel. Specific individuals identified by agency representatives as having the greatest difficulty were observed to be returned to their pre-incident state. CIS

  14. Bounded search for de novo identification of degenerate cis-regulatory elements

    Directory of Open Access Journals (Sweden)

    Khetani Radhika S

    2006-05-01

    Full Text Available Abstract Background The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach. Results In this paper, we report PRISM, a degenerate motif finder that leverages the relationship between the statistical significance of a set of binding sites and that of the individual binding sites. PRISM first identifies overrepresented, non-degenerate consensus motifs, then iteratively relaxes each one into a high-scoring degenerate motif. This approach requires no tunable parameters, thereby lending itself to unbiased performance comparisons. We therefore compare PRISM's performance against nine popular motif finders on 28 well-characterized S. cerevisiae regulons. PRISM consistently outperforms all other programs. Finally, we use PRISM to predict the binding sites of uncharacterized regulons. Our results support a proposed mechanism of action for the yeast cell-cycle transcription factor Stb1, whose binding site has not been determined experimentally. Conclusion The relationship between statistical measures of the binding sites and the set as a whole leads to a simple means of identifying the diverse range of cis-regulatory elements to which a protein binds. This approach leverages the advantages of word-counting, in that position dependencies are implicitly accounted for and local optima are more easily avoided. While we sacrifice guaranteed optimality to prevent the exponential blowup of exhaustive search, we prove that the error

  15. Community Intercomparison Suite (CIS) v1.4.0: a tool for intercomparing models and observations

    Science.gov (United States)

    Watson-Parris, Duncan; Schutgens, Nick; Cook, Nicholas; Kipling, Zak; Kershaw, Philip; Gryspeerdt, Edward; Lawrence, Bryan; Stier, Philip

    2016-09-01

    The Community Intercomparison Suite (CIS) is an easy-to-use command-line tool which has been developed to allow the straightforward intercomparison of remote sensing, in situ and model data. While there are a number of tools available for working with climate model data, the large diversity of sources (and formats) of remote sensing and in situ measurements necessitated a novel software solution. Developed by a professional software company, CIS supports a large number of gridded and ungridded data sources "out-of-the-box", including climate model output in NetCDF or the UK Met Office pp file format, CloudSat, CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization), MODIS (MODerate resolution Imaging Spectroradiometer), Cloud and Aerosol CCI (Climate Change Initiative) level 2 satellite data and a number of in situ aircraft and ground station data sets. The open-source architecture also supports user-defined plugins to allow many other sources to be easily added. Many of the key operations required when comparing heterogenous data sets are provided by CIS, including subsetting, aggregating, collocating and plotting the data. Output data are written to CF-compliant NetCDF files to ensure interoperability with other tools and systems. The latest documentation, including a user manual and installation instructions, can be found on our website (http://cistools.net). Here, we describe the need which this tool fulfils, followed by descriptions of its main functionality (as at version 1.4.0) and plugin architecture which make it unique in the field.

  16. Expression-guided in silico evaluation of candidate cis regulatory codes for Drosophila muscle founder cells.

    Directory of Open Access Journals (Sweden)

    Anthony A Philippakis

    2006-05-01

    Full Text Available While combinatorial models of transcriptional regulation can be inferred for metazoan systems from a priori biological knowledge, validation requires extensive and time-consuming experimental work. Thus, there is a need for computational methods that can evaluate hypothesized cis regulatory codes before the difficult task of experimental verification is undertaken. We have developed a novel computational framework (termed "CodeFinder" that integrates transcription factor binding site and gene expression information to evaluate whether a hypothesized transcriptional regulatory model (TRM; i.e., a set of co-regulating transcription factors is likely to target a given set of co-expressed genes. Our basic approach is to simultaneously predict cis regulatory modules (CRMs associated with a given gene set and quantify the enrichment for combinatorial subsets of transcription factor binding site motifs comprising the hypothesized TRM within these predicted CRMs. As a model system, we have examined a TRM experimentally demonstrated to drive the expression of two genes in a sub-population of cells in the developing Drosophila mesoderm, the somatic muscle founder cells. This TRM was previously hypothesized to be a general mode of regulation for genes expressed in this cell population. In contrast, the present analyses suggest that a modified form of this cis regulatory code applies to only a subset of founder cell genes, those whose gene expression responds to specific genetic perturbations in a similar manner to the gene on which the original model was based. We have confirmed this hypothesis by experimentally discovering six (out of 12 tested new CRMs driving expression in the embryonic mesoderm, four of which drive expression in founder cells.

  17. The importance of being cis: evolution of orthologous fish and mammalian enhancer activity.

    Science.gov (United States)

    Ritter, Deborah I; Li, Qiang; Kostka, Dennis; Pollard, Katherine S; Guo, Su; Chuang, Jeffrey H

    2010-10-01

    Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers, but a critical issue is how well orthologous CNE sequences retain the same activity in their respective species, a characteristic important for generalization of model organism studies. To quantify how well CNE enhancer activity has been preserved, we compared the anatomy-specific activities of 41 zebra fish CNEs in zebra fish embryos with the activities of orthologous human CNEs in mouse embryos. We found that 13/41 (∼30%) of the orthologous CNE pairs exhibit conserved positive activity in zebra fish and mouse. Conserved positive activity is only weakly associated with either sequence conservation or the absence of bases undergoing accelerated evolution. A stronger effect is that disparate activity is associated with transcription factor binding site divergence. To distinguish the contributions of cis- versus trans-regulatory changes, we analyzed 13 CNEs in a three-way experimental comparison: human CNE tested in zebra fish, human CNE tested in mouse, and orthologous zebra fish CNE tested in zebra fish. Both cis- and trans-changes affect a significant fraction of CNEs, although human and zebra fish sequences exhibit disparate activity in zebra fish (indicating cis regulatory changes) twice as often as human sequences show disparate activity when tested in mouse and zebra fish (indicating trans regulatory changes). In all four cases where the zebra fish and human CNE display a similar expression pattern in zebra fish, the human CNE also displays a similar expression pattern in mouse. This suggests that the endogenous enhancer activity of ∼30% of human CNEs can be determined from experiments in zebra fish alone, and to identify these CNEs, both the zebra fish and the human sequences should be tested.

  18. Are Interactions between cis-Regulatory Variants Evidence for Biological Epistasis or Statistical Artifacts?

    Science.gov (United States)

    Fish, Alexandra E; Capra, John A; Bush, William S

    2016-10-06

    The importance of epistasis-or statistical interactions between genetic variants-to the development of complex disease in humans has been controversial. Genome-wide association studies of statistical interactions influencing human traits have recently become computationally feasible and have identified many putative interactions. However, statistical models used to detect interactions can be confounded, which makes it difficult to be certain that observed statistical interactions are evidence for true molecular epistasis. In this study, we investigate whether there is evidence for epistatic interactions between genetic variants within the cis-regulatory region that influence gene expression after accounting for technical, statistical, and biological confounding factors. We identified 1,119 (FDR = 5%) interactions that appear to regulate gene expression in human lymphoblastoid cell lines, a tightly controlled, largely genetically determined phenotype. Many of these interactions replicated in an independent dataset (90 of 803 tested, Bonferroni threshold). We then performed an exhaustive analysis of both known and novel confounders, including ceiling/floor effects, missing genotype combinations, haplotype effects, single variants tagged through linkage disequilibrium, and population stratification. Every interaction could be explained by at least one of these confounders, and replication in independent datasets did not protect against some confounders. Assuming that the confounding factors provide a more parsimonious explanation for each interaction, we find it unlikely that cis-regulatory interactions contribute strongly to human gene expression, which calls into question the relevance of cis-regulatory interactions for other human phenotypes. We additionally propose several best practices for epistasis testing to protect future studies from confounding. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. Double-Stranded Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2001-01-01

    A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  20. Peptides and metallic nanoparticles for biomedical applications.

    NARCIS (Netherlands)

    Kogan, M.J.; Olmedo, I.; Hosta, L.; Guerrero, A.R.; Cruz Ricondo, L.J.; Albericio, F.

    2007-01-01

    In this review, we describe the contribution of peptides to the biomedical applications of metallic nanoparticles. We also discuss strategies for the preparation of peptide-nanoparticle conjugates and the synthesis of the peptides and metallic nanoparticles. An overview of the techniques used for th

  1. Toxins and antimicrobial peptides: interactions with membranes

    Science.gov (United States)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  2. Diverse CLE peptides from cyst nematode species

    Science.gov (United States)

    Plant CLAVATA3/ESR (CLE)-like peptides play diverse roles in plant growth and development including maintenance of the stem cell population in the root meristem. Small secreted peptides sharing similarity to plant CLE signaling peptides have been isolated from several cyst nematode species including...

  3. Activity of Cathelicidin Peptides against Chlamydia spp.

    Science.gov (United States)

    Donati, Manuela; Di Leo, Korinne; Benincasa, Monica; Cavrini, Francesca; Accardo, Silvia; Moroni, Alessandra; Gennaro, Renato; Cevenini, Roberto

    2005-01-01

    The in vitro activity of six cathelicidin peptides against 25 strains of Chlamydia was investigated. SMAP-29 proved to be the most active peptide, reducing the inclusion numbers of all 10 strains of Chlamydia trachomatis tested by ≥50% at 10 μg/ml. This peptide was also active against C. pneumoniae and C. felis. PMID:15728927

  4. 11-cis retinal torsion: A QTAIM and stress tensor analysis of the S1 excited state

    Science.gov (United States)

    Maza, Julio R.; Jenkins, Samantha; Kirk, Steven R.

    2016-05-01

    We investigate torsion about the C11-C12 bond mid-point for the S1 state of 11-cis retinal, using a QTAIM and stress tensor analysis. The QTAIM and stress tensor responses to a torsion ±α increase at a faster rate for the preferred direction of torsion though the CI seam. A QTAIM and stress tensor vector-based analysis provides an alternative way of characterising the asymmetry of the S1 potential energy surface. In the vicinity of the CI seam the ellipticity ε attained minimum values. The application of this analysis to molecular rotary motors is briefly discussed.

  5. Kinetic model for the thermal rearrangement of cis- and trans-pinane.

    Science.gov (United States)

    Stolle, Achim; Bonrath, Werner; Ondruschka, Bernd; Kinzel, Daniel; González, Leticia

    2008-07-03

    On the basis of pyrolysis experiments with cis-pinane ( 1a), trans-pinane ( 1b), beta-citronellene ( 2), and isocitronellene ( 3), rate constants and activation parameters for the thermal rearrangement of the title compounds were calculated. Combining these with experimental parameters (residence time) allows for the kinetic modeling of the thermal rearrangement of 1a, 1b, 2, and 3. The chosen model of competitive first-order reactions describes the thermal behavior of the title compounds in a very good manner over a wide temperature range.

  6. Cis/trans Coordination in olefin metathesis by static and molecular dynamic DFT calculations

    KAUST Repository

    Poater, Albert

    2014-05-25

    In regard to [(N-heterocyclic carbene)Ru]-based catalysts, it is still a matter of debate if the substrate binding is preferentially cis or trans to the N-heterocyclic carbene ligand. By means of static and molecular dynamic DFT calculations, a simple olefin, like ethylene, is shown to be prone to the trans binding. Bearing in mind the higher reactivity of trans isomers in olefin metathesis, this insight helps to construct small alkene substrates with increased reactivity. © 2014 Springer Science+Business Media New York.

  7. Immunotoxicity of Dermal Permethrin and Cis-Urocanic Acid: Effects of Chemical Mixtures in Environmental Health

    OpenAIRE

    Prater, Mary Renee

    2002-01-01

    The present study examined adverse effects of sunlight exposure (mimicked by intradermal cis-urocanic acid, cUCA) on local and systemic immune responses, with or without co-exposure to the immunotoxic insecticide permethrin. A single exposure to cUCA caused diminished splenic macrophage phagocytosis that was persistent up to 30 days post-exposure. Five-day exposure to cUCA subtly increased splenocyte proliferation in response to the T cell mitogen Concanavalin A. Four-week exposure to cUCA c...

  8. Commercial Off-the-Shelf (COTS) Components and Enterprise Component Information System (eCIS)

    Energy Technology Data Exchange (ETDEWEB)

    John Minihan; Ed Schmidt; Greg Enserro; Melissa Thompson

    2008-06-30

    The purpose of the project was to develop the processes for using commercial off-the-shelf (COTS) parts for WR production and to put in place a system for implementing the data management tools required to disseminate, store, track procurement, and qualify vendors. Much of the effort was devoted to determining if the use of COTS parts was possible. A basic question: How does the Nuclear Weapons Complex (NWC) begin to use COTS in the weapon Stockpile Life Extension Programs with high reliability, affordability, while managing risk at acceptable levels? In FY00, it was determined that a certain weapon refurbishment program could not be accomplished without the use of COTS components. The elements driving the use of COTS components included decreased cost, greater availability, and shorter delivery time. Key factors that required implementation included identifying the best suppliers and components, defining life cycles and predictions of obsolescence, testing the feasibility of using COTS components with a test contractor to ensure capability, as well as quality and reliability, and implementing the data management tools required to disseminate, store, track procurement, and qualify vendors. The primary effort of this project then was to concentrate on the risks involved in the use of COTS and address the issues of part and vendor selection, procurement and acceptance processes, and qualification of the parts via part and sample testing. The Enterprise Component Information System (eCIS) was used to manage the information generated by the COTS process. eCIS is a common interface for both the design and production of NWC components and systems integrating information between SNL National Laboratory (SNL) and the Kansas City Plant (KCP). The implementation of COTS components utilizes eCIS from part selection through qualification release. All part related data is linked across an unclassified network for access by both SNL and KCP personnel. The system includes not

  9. Rapid evolution of cis-regulatory sequences via local point mutations

    Science.gov (United States)

    Stone, J. R.; Wray, G. A.

    2001-01-01

    Although the evolution of protein-coding sequences within genomes is well understood, the same cannot be said of the cis-regulatory regions that control transcription. Yet, changes in gene expression are likely to constitute an important component of phenotypic evolution. We simulated the evolution of new transcription factor binding sites via local point mutations. The results indicate that new binding sites appear and become fixed within populations on microevolutionary timescales under an assumption of neutral evolution. Even combinations of two new binding sites evolve very quickly. We predict that local point mutations continually generate considerable genetic variation that is capable of altering gene expression.

  10. Four new tetracyclic alkaloids with cis-decahydroquinoline motif from Myrioneuron effusum.

    Science.gov (United States)

    Zhang, Jia-Hui; Guo, Jing-Jing; Yuan, Yu-Xi; Fu, Yan-Hui; Gu, Yu-Cheng; Zhang, Yu; Chen, Duo-Zhi; Li, Shun-Lin; Di, Ying-Tong; Hao, Xiao-Jiang

    2016-07-01

    Four new Myrioneuron alkaloids, mysumamides A-D (1-4), along with three known ones were isolated from the twigs and leaves of Myrioneuron effusum. All of these alkaloids possessed the tetracyclic skeleton and contained the decahydroquinoline (cis-DHQ) moiety. Their structures and relative configurations were elucidated on the basis of spectroscopic methods, especially 2D NMR techniques. The absolute configuration of 1 was determined by single-crystal X-ray diffraction. The cytotoxic activities of these compounds were also evaluated in vitro.

  11. Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

    Directory of Open Access Journals (Sweden)

    Allan Andrew C

    2008-07-01

    Full Text Available Abstract Background Transcription factors (TFs co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1 leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA

  12. Thin-Film Solar Cells Based on the Polycrystalline Compound Semiconductors CIS and CdTe

    Directory of Open Access Journals (Sweden)

    Michael Powalla

    2007-01-01

    14% expected in the near future. The integrated interconnection of single cells into large-area modules of 0.6×1.2m2 enables low-cost mass production, so that thin-film modules will soon be able to compete with conventional silicon-wafer-based modules. This contribution provides an overview of the basic technologies for CdTe and CIS modules, the research and development (R&D issues, production technology and capacities, the module performance in long-term outdoor testing, and their use in installations.

  13. Chemometric analysis of mass spectra of cis and trans fatty acid picolinyl esters

    DEFF Research Database (Denmark)

    Leth, Torben

    1997-01-01

    Capillary GC of fatty acid methyl esters with MS detection only yields information about the molecular weight of the compound. However, if picolinyl esters of fatty acids are analysed in this way it is possible to obtain more information about their structure, perhaps even the cis or trans...... configuration. Picolinyl esters of fatty acids are prepared by adding carbonyl-diimidazole, 3-hydroxy-methylpyridine and 4-pyrrolidin-o-pyridine to a solution of free fatty acids in dichloromethane. The picolinyl esters dissolved in heptane are then separated by capillary GC on a CP Sil 88 column equipped...

  14. Identification of Distal cis-Regulatory Elements at Mouse Mitoferrin Loci Using Zebrafish Transgenesis▿

    OpenAIRE

    Amigo, J. D.; Yu, M.; Troadec, M.-B.; Gwynn, B; Cooney, J. D.; Lambert, A.J.; Chi, N. C.; Weiss, M J; Peters, L. L.; Kaplan, J; Cantor, Alan B.; Paw, Barry Htin

    2011-01-01

    Mitoferrin 1 (Mfrn1; Slc25a37) and mitoferrin 2 (Mfrn2; Slc25a28) function as essential mitochondrial iron importers for heme and Fe/S cluster biogenesis. A genetic deficiency of Mfrn1 results in a profound hypochromic anemia in vertebrate species. To map the cis-regulatory modules (CRMs) that control expression of the Mfrn genes, we utilized genome-wide chromatin immunoprecipitation (ChIP) datasets for the major erythroid transcription factor GATA-1. We identified the CRMs that faithfully dr...

  15. The (+)-cis- and (+)-trans-Olibanic Acids: Key Odorants of Frankincense.

    Science.gov (United States)

    Cerutti-Delasalle, Céline; Mehiri, Mohamed; Cagliero, Cecilia; Rubiolo, Patrizia; Bicchi, Carlo; Meierhenrich, Uwe J; Baldovini, Nicolas

    2016-10-24

    Frankincense (olibanum) is one of the oldest aromatic materials used by humans, but the key molecular constituents contributing to its characteristic odor remained unknown. Reported herein is the discovery that (1S,2S)-(+)-trans- and (1S,2R)-(+)-cis-2-octylcyclopropyl-1-carboxylic acids are highly potent and substantive odorants occurring in ppm amounts in all of the frankincense samples analyzed, even those showing radically different volatile compositions. These cyclopropyl-derived acids provide the very characteristic old churchlike endnote of the frankincense odor.

  16. Total synthesis of cis-reticulatacin-10-ones A and B: absolute stereochemical assignment.

    Science.gov (United States)

    Abdel Ghani, Sherif B; Brown, Lynda J; Figadère, Bruno; Brown, Richard C D

    2010-10-21

    cis-Reticulatacin-10-ones A and B were synthesised as a predefined mixture of diastereoisomers (dr ∼ 1 : 9) in nine steps from the acid chloride 8, and without the use of hydroxyl protecting groups. Comparison of the chiral HPLC chromatogram of the synthetic sample with that of the natural product isolated from the roots of the tropical fruit tree Annona muricata L. showed the natural product to be a mixture of A and B diastereoisomers (dr ∼ 1 : 1).

  17. Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis.

    Directory of Open Access Journals (Sweden)

    Michalis Barkoulas

    2016-09-01

    Full Text Available Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression.

  18. cis-4-Cyclohexene-1,2-dicarboximide: Inhibitor of phytochrome-promoted seed germination

    OpenAIRE

    BEWLEY, J. DEREK; Oaks, Ann

    1980-01-01

    cis-4-Cyclohexene-1,2-dicarboximide (CHDC) inhibits the germination of light-requiring seeds in both light and darkness but has no effect upon the germination of non-light-requiring seeds. In lettuce seeds, CHDC inhibits the action of far-red-absorbing form of phytochrome in breaking dormancy. This inhibition can be overcome by benzyladenine and red light together, but not by a combination of red light and gibberellic acid. Gibberellic acid-induced germination of lettuce seeds in darkness is ...

  19. Determinants of Chromosome Architecture: Insulator Pairing in cis and in trans.

    Directory of Open Access Journals (Sweden)

    Miki Fujioka

    2016-02-01

    Full Text Available The chromosomes of multicellular animals are organized into a series of topologically independent looped domains. This domain organization is critical for the proper utilization and propagation of the genetic information encoded by the chromosome. A special set of architectural elements, called boundaries or insulators, are responsible both for subdividing the chromatin into discrete domains and for determining the topological organization of these domains. Central to the architectural functions of insulators are homologous and heterologous insulator:insulator pairing interactions. The former (pairing between copies of the same insulator dictates the process of homolog alignment and pairing in trans, while the latter (pairing between different insulators defines the topology of looped domains in cis. To elucidate the principles governing these architectural functions, we use two insulators, Homie and Nhomie, that flank the Drosophila even skipped locus. We show that homologous insulator interactions in trans, between Homie on one homolog and Homie on the other, or between Nhomie on one homolog and Nhomie on the other, mediate transvection. Critically, these homologous insulator:insulator interactions are orientation-dependent. Consistent with a role in the alignment and pairing of homologs, self-pairing in trans is head-to-head. Head-to-head self-interactions in cis have been reported for other fly insulators, suggesting that this is a general principle of self-pairing. Homie and Nhomie not only pair with themselves, but with each other. Heterologous Homie-Nhomie interactions occur in cis, and we show that they serve to delimit a looped chromosomal domain that contains the even skipped transcription unit and its associated enhancers. The topology of this loop is defined by the heterologous pairing properties of Homie and Nhomie. Instead of being head-to-head, which would generate a circular loop, Homie-Nhomie pairing is head-to-tail. Head

  20. Single-molecule studies on individual peptides and peptide assemblies on surfaces.

    Science.gov (United States)

    Yang, Yanlian; Wang, Chen

    2013-10-13

    This review is intended to reflect the recent progress in single-molecule studies of individual peptides and peptide assemblies on surfaces. The structures and the mechanism of peptide assembly are discussed in detail. The contents include the following topics: structural analysis of single peptide molecules, adsorption and assembly of peptides on surfaces, folding structures of the amyloid peptides, interaction between amyloid peptides and dye or drug molecules, and modulation of peptide assemblies by small molecules. The explorations of peptide adsorption and assembly will benefit the understanding of the mechanisms for protein-protein interactions, protein-drug interactions and the pathogenesis of amyloidoses. The investigations on peptide assembly and its modulations could also provide a potential approach towards the treatment of the amyloidoses.

  1. Polycistronic peptide coding genes in eukaryotes--how widespread are they?

    Science.gov (United States)

    Tautz, Diethard

    2009-01-01

    The classical textbook assumption for the structure of an eukaryotic gene is that it codes for a single polypeptide of more than 100 amino acids in length. This is also the implicit assumption in most gene annotation pipelines. A gene family has now been discovered in insects that shows that an eukaryotic mRNA can code for peptides as short as eleven amino acids and that a single mRNA can code for several such peptides. This raises the question whether short open reading frames might also have a functional potential in other mRNAs, in particular those that occur in the 5'-UTR of many mRNAs. A number of these have been shown to act in cis to regulate the translation of the main open reading frame of the mRNA. But there may be others that could act in trans on other biological processes. The question of how many peptide-coding genes may exist is therefore worth revisiting. This poses new bioinformatic challenges that can only be resolved through multiple genome comparisons within a range of evolutionary distances.

  2. Peptide crosslinked micelles: a new strategy for the design and synthesis of peptide vaccines

    OpenAIRE

    Hao, Jihua; Kwissa, Marcin; Pulendran, Bali; Murthy, Niren

    2006-01-01

    This report presents a new and simple methodology for the synthesis of multicomponent peptide vaccines, named the peptide crosslinked micelles (PCMs). The PCMs are core shell micelles designed to deliver peptide antigens and immunostimulatory DNA to antigen-presenting cells (APCs). They are composed of immunostimulatory DNA, peptide antigen, and a thiopyridal derived poly(ethylene glycol)-polylysine block copolymer. The peptide antigen acts as a crosslinker in the PCM strategy, which allows t...

  3. Inducible Expression of the De-Novo Designed Antimicrobial Peptide SP1-1 in Tomato Confers Resistance to Xanthomonas campestris pv. vesicatoria

    Science.gov (United States)

    Herrera Diaz, Areli; Kovacs, Izabella; Lindermayr, Christian

    2016-01-01

    Antimicrobial peptides (AMPs) are small peptides with less than 50 amino acids and are part of the innate immune response in almost all organisms, including bacteria, vertebrates, invertebrates and plants. AMPs are active against a broad-spectrum of pathogens. The inducible expression of AMPs in plants is a promising approach to combat plant pathogens with minimal negative side effects, such as phytotoxicity or infertility. In this study, inducible expression of the de-novo designed AMP SP1-1 in Micro Tom tomato protected tomato fruits against bacterial spot disease caused by Xanthomonas campestris pv. vesicatoria. The peptide SP1-1 was targeted to the apoplast which is the primary infection site for plant pathogens, by fusing SP1-1 peptide to the signal peptide RsAFP1 of radish (Raphanus sativus). The pathogen inducibility of the expression was enabled by using an optimized inducible 4XW2/4XS promoter. As a result, the tomato fruits of independently generated SP1-1 transgenic lines were significantly more resistant to X. campestris pv. vesicatoria than WT tomato fruits. In transgenic lines, bacterial infection was reduced up to 65% in comparison to the infection of WT plants. Our study demonstrates that the combination of the 4XW2/4XS cis-element from parsley with the synthetic antimicrobial peptide SP1-1 is a good alternative to protect tomato fruits against infections with X. campestris pv. vesicatoria. PMID:27706237

  4. PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats.

    Science.gov (United States)

    Willemin, Marie-Emilie; Desmots, Sophie; Le Grand, Rozenn; Lestremau, François; Zeman, Florence A; Leclerc, Eric; Moesch, Christian; Brochot, Céline

    2016-03-01

    Permethrin, a pyrethroid insecticide, is suspected to induce neuronal and hormonal disturbances in humans. The widespread exposure of the populations has been confirmed by the detection of the urinary metabolites of permethrin in biomonitoring studies. Permethrin is a chiral molecule presenting two forms, the cis and the trans isomers. Because in vitro studies indicated a metabolic interaction between the trans and cis isomers of permethrin, we adapted and calibrated a PBPK model for trans- and cis-permethrin separately in rats. The model also describes the toxicokinetics of three urinary metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA), 3-phenoxybenzoic acid (3-PBA) and 4'OH-phenoxybenzoic acid (4'-OH-PBA). In vivo experiments performed in Sprague-Dawley rats were used to calibrate the PBPK model in a Bayesian framework. The model captured well the toxicokinetics of permethrin isomers and their metabolites including the rapid absorption, the accumulation in fat, the extensive metabolism of the parent compounds, and the rapid elimination of metabolites in urine. Average hepatic clearances in rats were estimated to be 2.4 and 5.7 L/h/kg for cis- and trans-permethrin, respectively. High concentrations of the metabolite 4'-OH-PBA were measured in urine compared to cis- and trans-DCCA and 3-PBA. The confidence in the extended PBPK model was then confirmed by good predictions of published experimental data obtained using the isomers mixture. The extended PBPK model could be extrapolated to humans to predict the internal dose of exposure to permethrin from biomonitoring data in urine.

  5. Peptide array-based characterization and design of ZnO-high affinity peptides.

    Science.gov (United States)

    Okochi, Mina; Sugita, Tomoya; Furusawa, Seiji; Umetsu, Mitsuo; Adschiri, Tadafumi; Honda, Hiroyuki

    2010-08-15

    Peptides with both an affinity for ZnO and the ability to generate ZnO nanoparticles have attracted attention for the self-assembly and templating of nanoscale building blocks under ambient conditions with compositional uniformity. In this study, we have analyzed the specific binding sites of the ZnO-binding peptide, EAHVMHKVAPRP, which was identified using a phage display peptide library. The peptide binding assay against ZnO nanoparticles was performed using peptides synthesized on a cellulose membrane using the spot method. Using randomized rotation of amino acids in the ZnO-binding peptide, 125 spot-synthesized peptides were assayed. The peptide binding activity against ZnO nanoparticles varied greatly. This indicates that ZnO binding does not depend on total hydrophobicity or other physical parameters of these peptides, but rather that ZnO recognizes the specific amino acid alignment of these peptides. In addition, several peptides were found to show higher binding ability compared with that of the original peptides. Identification of important binding sites in the EAHVMHKVAPRP peptide was investigated by shortened, stepwise sequence from both termini. Interestingly, two ZnO-binding sites were found as 6-mer peptides: HVMHKV and HKVAPR. The peptides identified by amino acid substitution of HKVAPR were found to show high affinity and specificity for ZnO nanoparticles.

  6. Fabrication of Odor Sensor Using Peptide

    Science.gov (United States)

    Hotokebuchi, Yuta; Hayashi, Kenshi; Toko, Kiyoshi; Chen, Ronggang; Ikezaki, Hidekazu

    We report fabrication of an odor sensor using peptides. Peptides were designed to acquire the specific reception for a target odor molecule. Au surface of the sensor electrode was coated by the designed peptide using the method of self assembled monolayers (SAMs). Functionalized Au surfaces by the peptides were confirmed by ellipsometry and cyclic voltammetry. The odorants of vanillin, phenethyl alcohol and hexanol were discriminated by QCM sensor with the peptide surface. Moreover, we verified specific interaction between amino acid (Trp) and vanillin by fluorescence assay.

  7. Brain natriuretic peptide measurement in pulmonary medicine.

    Science.gov (United States)

    Salerno, Daniel; Marik, Paul E

    2011-12-01

    Serum levels of natriuretic peptides are well established as important biomarkers in patients with cardiac disease. Less attention has been placed on the role of natriuretic peptides in patients with pulmonary conditions. In several well-defined groups of patients with pulmonary disease natriuretic peptides provide the clinician with clinically valuable information. A limitation of the interpretation of natriuretic peptides in pulmonary disease is the confounding effect of concurrent conditions such as heart failure, hypoxia, sepsis and renal failure. The present paper reviews the role of natriuretic peptides for diagnosis, risk stratification and prognosis of several pulmonary disorders.

  8. Engineering Synthetic cis-Regulatory Elements for Simultaneous Recognition of Three Transcriptional Factors in Bacteria.

    Science.gov (United States)

    Amores, Gerardo Ruiz; Guazzaroni, María-Eugenia; Silva-Rocha, Rafael

    2015-12-18

    Recognition of cis-regulatory elements by transcription factors (TF) at target promoters is crucial to gene regulation in bacteria. In this process, binding of TFs to their cognate sequences depends on a set of physical interactions between these proteins and specific nucleotides in the operator region. Previously, we showed that in silico optimization algorithms are able to generate short sequences that are recognized by two different TFs of Escherichia coli, namely, CRP and IHF, thus generating an AND logic gate. Here, we expanded this approach in order to engineer DNA sequences that can be simultaneously recognized by three unrelated TFs (CRP, IHF, and Fis). Using in silico optimization and experimental validation strategies, we were able to obtain a candidate promoter (Plac-CFI1) regulated by only two TFs with an AND logic, thus demonstrating a limitation in the design. Subsequently, we modified the algorithm to allow the optimization of extended sequences, and were able to design two synthetic promoters (PCFI20-1 and PCFI22-5) that were functional in vivo. Expression assays in E. coli mutant strains for each TF revealed that while CRP positively regulates the promoter activities, IHF and Fis are strong repressors of both the promoter variants. Taken together, our results demonstrate the potential of in silico strategies in bacterial synthetic promoter engineering. Furthermore, the study also shows how small modifications in cis-regulatory elements can drastically affect the final logic of the resulting promoter.

  9. Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes

    DEFF Research Database (Denmark)

    Obsen, Thomas; Faergeman, Nils J; Chung, Soonkyu;

    2012-01-01

    Conjugated linoleic acid (CLA) reduces adiposity in vivo. However, mechanisms mediating these changes are unclear. Therefore, we treated cultures of human adipocytes with trans-10, cis-12 (10,12) CLA, cis-9, trans-11 (9,11) CLA or other trans fatty acids (FA), and measured indices of lipid......]-oleic or [(14)C]-linoleic acids. When using [(14)C]-acetic acid and [(14)C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10......,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within...

  10. Dissection of cis-regulatory elements in the C. elegans Hox gene egl-5 promoter.

    Science.gov (United States)

    Teng, Yingqi; Girard, Lisa; Ferreira, Henrique B; Sternberg, Paul W; Emmons, Scott W

    2004-12-15

    Hox genes are highly conserved segmental identity genes well known for their complex expression patterns and divergent targets. Here we present an analysis of cis-regulatory elements in the Caenorhabditis elegans Hox gene egl-5, which is expressed in multiple tissues in the posterior region of the nematode. We have utilized phylogenetic footprinting to efficiently identify cis-regulatory elements and have characterized these with gfp reporters and tissue-specific rescue experiments. We have found that the complex expression pattern of egl-5 is the cumulative result of the activities of multiple tissue or local region-specific activator sequences that are conserved both in sequence and near-perfect order in the related nematode Caenorhabditis briggsae. Two conserved regulatory blocks analyzed in detail contain multiple sites for both positively and negatively acting factors. One of these regions may promote activation of egl-5 in certain cells via the Wnt pathway. Positively acting regions are repressed in inappropriate tissues by additional negative pathways acting at other sites within the promoter. Our analysis has allowed us to implicate several new regulatory factors significant to the control of egl-5 expression.

  11. CIS Modules Process R&D: Final Technical Report, October 2005 - June 2006

    Energy Technology Data Exchange (ETDEWEB)

    Tarrant, D. E.; Gay, R. R.

    2006-07-01

    The primary objectives of this subcontract were to: address key near-term technical R&D issues for continued improvement in thin-film PV products; continue process development for increased production capacity; pursue long-term R&D contributing to progress toward the MYTP goals for 2020 to increase the conversion efficiency to 15% and reduce module manufacturing costs to less than $50/m2, thus enabling PV systems with a 30-year lifetime at an installed cost of under $2.00/W; and advance the understanding of the requirements needed to achieve better thin-film PV cell and module performance, greater reliability and market acceptance, and investigate materials systems and new devices that can improve the cost/performance ratio of future thin-film PV factories. The demonstrated and maintained high production yield is a major accomplishment supporting attractive cost projections for CIS. Process R&D at successive levels of CIS production has led to the continued demonstration of the prerequisites for commitment to large-scale commercialization. Process and packaging R&D during this and previous subcontracts has demonstrated the potential for further cost and performance improvements.

  12. Plasticity of the cis-regulatory input function of a gene.

    Directory of Open Access Journals (Sweden)

    Avraham E Mayo

    2006-04-01

    Full Text Available The transcription rate of a gene is often controlled by several regulators that bind specific sites in the gene's cis-regulatory region. The combined effect of these regulators is described by a cis-regulatory input function. What determines the form of an input function, and how variable is it with respect to mutations? To address this, we employ the well-characterized lac operon of Escherichia coli, which has an elaborate input function, intermediate between Boolean AND-gate and OR-gate logic. We mapped in detail the input function of 12 variants of the lac promoter, each with different point mutations in the regulator binding sites, by means of accurate expression measurements from living cells. We find that even a few mutations can significantly change the input function, resulting in functions that resemble Pure AND gates, OR gates, or single-input switches. Other types of gates were not found. The variant input functions can be described in a unified manner by a mathematical model. The model also lets us predict which functions cannot be reached by point mutations. The input function that we studied thus appears to be plastic, in the sense that many of the mutations do not ruin the regulation completely but rather result in new ways to integrate the inputs.

  13. A cisão da fração ferrarista (1959-1960

    Directory of Open Access Journals (Sweden)

    Bombardelli, Maura

    2011-01-01

    Full Text Available O presente artigo propõe-se a examinar a cisão interna ocorrida no Partido Trabalhista Brasileiro (PTB na passagem para os anos 1960, da qual se originou, em 1959, o Movimento Trabalhista Renovador (MTR, transformado em partido político no ano seguinte. Orientados pelo estudo das subunidades partidárias desenvolvido por Giovanni Sartori (1982, procuramos compreender de que forma uma fração atuante no PTB, cuja principal liderança era Fernando Ferrari, demarcou posições político-ideológicas diante do grupo majoritário liderado por João Goulart. Primeiramente, recompusemos este evento e abordamos alguns aspectos da trajetória de Ferrari para, então, analisarmos a cisão ferrarista. As fontes utilizadas foram o jornal Correio do Povo, entre maio de 1959 e outubro de 1960 e um livro publicado por Ferrari após o pleito para a vice-presidência da República de 1960, intitulado Minha Campanha (1961, além de outras fontes bibliográficas

  14. Synthesis and Conformation Analysis of cis-1,2-Disubstituted Cyclododecanes

    Institute of Scientific and Technical Information of China (English)

    HAN Xiang-Yu; WANG Ming-An; LI Tai-Gong; LIANG Xiao-Mei; DONG Yan-Hong; CHEN Fu-Heng; WANG Dao-Quan

    2007-01-01

    cis-1,2-Disubstituted cyclododecanes 2 were synthesized by sodium borohydride reduction of 2-monosubstituted cyclododecanones and their structures were confirmed by 1HNMR, 13C NMR and elemental analysis. The higher cis-selectivity of NaBH4 reduction of 2- monosubstituted cyclododecanones was rationalized by the mode of "corner position carbonyl participation". Crystal data for 2c: Mr = 263.21, monoclinic, space group P21/c, a = 1.11140(7), b = 2.62590(17), c = 0.91360(6) nm, β= 106.1840(10)°, V = 2.5606(3) nm3, Dc = 1.366 g/cm3, Z = 8, F(000) = 1104, μ(MoKα= 3.182 mm-1, S = 0.837, the final R = 0.0460 and wR = 0.1033. Crystal X-ray diffraction analysis for 2c showed that its ring skeleton adopts [3333] conformation, in which the OH group presents at the side-exo position and the other one at the corner carbon. The 1H NMR data of 2 showed that 1-corner-R-2-side-exo-OH [3333] and 1-corner-OH-2-side-exo-R [3333] conformations coexist in dynamic equilibrium in the solution, but only the former presents in the crystal.

  15. Synthesis and Crystal Structure of cis-[meso-1, 3-Bis(propylsulfinyl)propane]dichloroplatinum(Ⅱ)

    Institute of Scientific and Technical Information of China (English)

    陈巍; 杜淼; 张若桦; 卜显和

    2002-01-01

    A mononuclear complex, cis-[meso-1, 3-bis(propylsulfinyl)propane]- dichloroplatinum(Ⅱ) (Pt(C9H20O2S2)Cl2) 1, has been prepared and structurally characterizated by single-crystal X-ray diffraction. The crystal belongs to orthorhombic system, space group Pna21 with a = 22.800(3), b = 11.7662(13), c = 5.8115(6) ?, V = 1559.0(3) ?3, Mr = 490.36, Dc = 2.089 g/cm3, Z = 4, F(000) = 936, ( (MoK() = 9.596 mm-1 and ( = 0.71073 ?. The structure was refined to R = 0.0204 and wR = 0.0473 for 2703 reflections with I > 2σ(I). It is revealed that the central Pt(Ⅱ) ion in the title complex is bonded to two Cl atoms in a cis-configuration and two S atoms of the ligand to form the coordination geometry deviating slightly from the square planar.

  16. Separation of cis- and trans-Asarone from Acorus tatarinowii by Preparative Gas Chromatography

    Directory of Open Access Journals (Sweden)

    H. L. Zuo

    2012-01-01

    Full Text Available A preparative gas chromatography (pGC method was developed for the separation of isomers (cis- and trans-asarone from essential oil of Acorus tatarinowii. The oil was primarily fractionated by silica gel chromatography using different ratios of petroleum ether and ethyl acetate as gradient elution solvents. And then the fraction that contains mixture of the isomers was further separated by pGC. The compounds were separated on a stainless steel column packed with 10% OV-101 (3 m × 6 mm, i.d., and then the effluent was split into two gas flows. One percent of the effluent passed to the flame ionization detector (FID for detection and the remaining 99% was directed to the fraction collector. Two isomers were collected after 90 single injections (5 uL with the yield of 178 mg and 82 mg, respectively. Furthermore, the structures of the obtained compounds were identified as cis- and trans-asarone by 1H- and 13C-NMR spectra, respectively.

  17. Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors.

    Science.gov (United States)

    Fleming, Michael S; Vysochan, Anna; Paixão, Sόnia; Niu, Jingwen; Klein, Rüdiger; Savitt, Joseph M; Luo, Wenqin

    2015-04-02

    RET can be activated in cis or trans by its co-receptors and ligands in vitro, but the physiological roles of trans signaling are unclear. Rapidly adapting (RA) mechanoreceptors in dorsal root ganglia (DRGs) express Ret and the co-receptor Gfrα2 and depend on Ret for survival and central projection growth. Here, we show that Ret and Gfrα2 null mice display comparable early central projection deficits, but Gfrα2 null RA mechanoreceptors recover later. Loss of Gfrα1, the co-receptor implicated in activating RET in trans, causes no significant central projection or cell survival deficit, but Gfrα1;Gfrα2 double nulls phenocopy Ret nulls. Finally, we demonstrate that GFRα1 produced by neighboring DRG neurons activates RET in RA mechanoreceptors. Taken together, our results suggest that trans and cis RET signaling could function in the same developmental process and that the availability of both forms of activation likely enhances but not diversifies outcomes of RET signaling.

  18. Innovative sputtering techniques for CIS and CdTe submodule fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, J.M.; Misra, M.S.; Lanning, B. (Martin Marietta Aerospace, Denver, CO (United States). Astronautics Group)

    1993-03-01

    This report describes work done during Phase 1 of the subject subcontract. The subcontract was designed to study innovative deposition techniques, such as the rotating cylindrical magnetron sputtering system and electrodeposition for large-area, low-cost copper indium diselenide (CIS) and cadmium telluride (CdTe) devices. A key issue for photovoltaics (PV) in terrestrial and future space applications is producibility, particularly for applications using a large quantity of PV. Among the concerns for fabrication of polycrystalline thin-film PV, such as CIS and CdTe, are production volume, cost, and minimization of waste. Both rotating cylindrical magnetron (C-Mag[trademark]) sputtering and electrodeposition have tremendous potential for the fabrication of polycrystalline thin-film PV due to scaleability, efficient utilization of source materials, and inherently higher deposition rates. In the case of sputtering, the unique geometry of the C-Mae facilitates innovative cosputtering and reactive sputtering that could lead to greater throughput reduced health and safety risks, and, ultimately, lower fabrication cost. Electrodeposited films appear to be adherent and comparable with low-cost fabrication techniques. Phase I involved the initial film and device fabrication using the two techniques mentioned herein. Devices were tested by both internal facilities, as well as NREL and ISET.

  19. Effects of cis and trans genetic ancestry on gene expression in African Americans.

    Directory of Open Access Journals (Sweden)

    Alkes L Price

    2008-12-01

    Full Text Available Variation in gene expression is a fundamental aspect of human phenotypic variation. Several recent studies have analyzed gene expression levels in populations of different continental ancestry and reported population differences at a large number of genes. However, these differences could largely be due to non-genetic (e.g., environmental effects. Here, we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that individuals from this population inherit variable proportions of two continental ancestries. We first relate gene expression levels in individual African Americans to their genome-wide proportion of European ancestry. The results provide strong evidence of a genetic contribution to expression differences between European and African populations, validating previous findings. Second, we infer local ancestry (0, 1, or 2 European chromosomes at each location in the genome and investigate the effects of ancestry proximal to the expressed gene (cis versus ancestry elsewhere in the genome (trans. Both effects are highly significant, and we estimate that 12+/-3% of all heritable variation in human gene expression is due to cis variants.

  20. Identification of distal cis-regulatory elements at mouse mitoferrin loci using zebrafish transgenesis.

    Science.gov (United States)

    Amigo, Julio D; Yu, Ming; Troadec, Marie-Berengere; Gwynn, Babette; Cooney, Jeffrey D; Lambert, Amy J; Chi, Neil C; Weiss, Mitchell J; Peters, Luanne L; Kaplan, Jerry; Cantor, Alan B; Paw, Barry H

    2011-04-01

    Mitoferrin 1 (Mfrn1; Slc25a37) and mitoferrin 2 (Mfrn2; Slc25a28) function as essential mitochondrial iron importers for heme and Fe/S cluster biogenesis. A genetic deficiency of Mfrn1 results in a profound hypochromic anemia in vertebrate species. To map the cis-regulatory modules (CRMs) that control expression of the Mfrn genes, we utilized genome-wide chromatin immunoprecipitation (ChIP) datasets for the major erythroid transcription factor GATA-1. We identified the CRMs that faithfully drive the expression of Mfrn1 during blood and heart development and Mfrn2 ubiquitously. Through in vivo analyses of the Mfrn-CRMs in zebrafish and mouse, we demonstrate their functional and evolutionary conservation. Using knockdowns with morpholinos and cell sorting analysis in transgenic zebrafish embryos, we show that GATA-1 directly regulates the expression of Mfrn1. Mutagenesis of individual GATA-1 binding cis elements (GBE) demonstrated that at least two of the three GBE within this CRM are functionally required for GATA-mediated transcription of Mfrn1. Furthermore, ChIP assays demonstrate switching from GATA-2 to GATA-1 at these elements during erythroid maturation. Our results provide new insights into the genetic regulation of mitochondrial function and iron homeostasis and, more generally, illustrate the utility of genome-wide ChIP analysis combined with zebrafish transgenesis for identifying long-range transcriptional enhancers that regulate tissue development.