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Sample records for histidine triad protein

  1. Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity

    International Nuclear Information System (INIS)

    Kwasnicka-Crawford, Dorota A.; Vincent, Steven R.

    2005-01-01

    Microsomal cytochrome P450 reductase catalyzes the one-electron transfer from NADPH via FAD and FMN to various electron acceptors, such as cytochrome P450s or to some anti-cancer quinone drugs. This results in generation of free radicals and toxic oxygen metabolites, which can contribute to the cytotoxicity of these compounds. Recently, a cytosolic NADPH-dependent flavin reductase, NR1, has been described which is highly homologous to the microsomal cytochrome P450 reductase. In this study, we show that over-expression of NR1 in human embryonic kidney cells enhances the cytotoxic action of the model quinone, menadione. Furthermore, we show that a novel human histidine triad protein DCS-1, which is expressed together with NR1 in many tissues, can significantly reduce menadione-induced cytotoxicity in these cells. We also show that DCS-1 binds NF1 and directly modulates its activity. These results suggest that NR1 may play a role in carcinogenicity and cell death associated with one-electron reductions

  2. The protein histidine phosphatase LHPP is a tumour suppressor.

    Science.gov (United States)

    Hindupur, Sravanth K; Colombi, Marco; Fuhs, Stephen R; Matter, Matthias S; Guri, Yakir; Adam, Kevin; Cornu, Marion; Piscuoglio, Salvatore; Ng, Charlotte K Y; Betz, Charles; Liko, Dritan; Quagliata, Luca; Moes, Suzette; Jenoe, Paul; Terracciano, Luigi M; Heim, Markus H; Hunter, Tony; Hall, Michael N

    2018-03-29

    Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase. Consistent with these observations, global histidine phosphorylation was significantly upregulated in the liver tumours. Sustained, hepatic expression of LHPP in the hepatocellular carcinoma mouse model reduced tumour burden and prevented the loss of liver function. Finally, in patients with hepatocellular carcinoma, low expression of LHPP correlated with increased tumour severity and reduced overall survival. Thus, LHPP is a protein histidine phosphatase and tumour suppressor, suggesting that deregulated histidine phosphorylation is oncogenic.

  3. A study by nitrogen-15 nuclear magnetic resonance spectroscopy of the state of histidine in the catalytic triad of α-lytic protease

    International Nuclear Information System (INIS)

    Bachovchin, W.W.; Roberts, J.D.

    1978-01-01

    The ionization behaviour of the histidine of the catalytic triad of α-lytic protease using N-15 NMR spectroscopy is studied. This technique is especially informative about the protonation, hydrogen-bond formation, and tautomeric equilibrium of imidazole rings. The efficient and specific incorporation of N-15 labelled histidine into α-lytic protease was achieved by inducing and isolating an auxotroph of myxobacter 495 for which histidine is an essential amino acid. The results show that histidine of the catalytic triad of α-lytic protease appears to have a base strength which is essentially normal for an imidazole derivative but, in the pH range where the enzymatic activity is high, the histidine tautomer is favoured with the hydrogen located on N3 (π), as the result of hydrogen bonding to the asparate anion and possible the serine hydroxyl. Thus, the N-15 NMR shifts support the general geometry postulated for the ''charge-relay'' mechanism but not the idea of an unusually weakly basic histidine or an unusually strongly basic asparate carboxylate anion. (A.G.)

  4. Protein-induced geometric constraints and charge transfer in bacteriochlorophyll-histidine complexes in LH2.

    Science.gov (United States)

    Wawrzyniak, Piotr K; Alia, A; Schaap, Roland G; Heemskerk, Mattijs M; de Groot, Huub J M; Buda, Francesco

    2008-12-14

    Bacteriochlorophyll-histidine complexes are ubiquitous in nature and are essential structural motifs supporting the conversion of solar energy into chemically useful compounds in a wide range of photosynthesis processes. A systematic density functional theory study of the NMR chemical shifts for histidine and for bacteriochlorophyll-a-histidine complexes in the light-harvesting complex II (LH2) is performed using the BLYP functional in combination with the 6-311++G(d,p) basis set. The computed chemical shift patterns are consistent with available experimental data for positive and neutral(tau) (N(tau) protonated) crystalline histidines. The results for the bacteriochlorophyll-a-histidine complexes in LH2 provide evidence that the protein environment is stabilizing the histidine close to the Mg ion, thereby inducing a large charge transfer of approximately 0.5 electronic equivalent. Due to this protein-induced geometric constraint, the Mg-coordinated histidine in LH2 appears to be in a frustrated state very different from the formal neutral(pi) (N(pi) protonated) form. This finding could be important for the understanding of basic functional mechanisms involved in tuning the electronic properties and exciton coupling in LH2.

  5. Protein-Protein Interactions Prediction Using a Novel Local Conjoint Triad Descriptor of Amino Acid Sequences

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    Jun Wang

    2017-11-01

    Full Text Available Protein-protein interactions (PPIs play crucial roles in almost all cellular processes. Although a large amount of PPIs have been verified by high-throughput techniques in the past decades, currently known PPIs pairs are still far from complete. Furthermore, the wet-lab experiments based techniques for detecting PPIs are time-consuming and expensive. Hence, it is urgent and essential to develop automatic computational methods to efficiently and accurately predict PPIs. In this paper, a sequence-based approach called DNN-LCTD is developed by combining deep neural networks (DNNs and a novel local conjoint triad description (LCTD feature representation. LCTD incorporates the advantage of local description and conjoint triad, thus, it is capable to account for the interactions between residues in both continuous and discontinuous regions of amino acid sequences. DNNs can not only learn suitable features from the data by themselves, but also learn and discover hierarchical representations of data. When performing on the PPIs data of Saccharomyces cerevisiae, DNN-LCTD achieves superior performance with accuracy as 93.12%, precision as 93.75%, sensitivity as 93.83%, area under the receiver operating characteristic curve (AUC as 97.92%, and it only needs 718 s. These results indicate DNN-LCTD is very promising for predicting PPIs. DNN-LCTD can be a useful supplementary tool for future proteomics study.

  6. Emerging roles for protein histidine phosphorylation in cellular signal transduction: lessons from the islet ?-cell

    OpenAIRE

    Kowluru, Anjaneyulu

    2008-01-01

    Protein phosphorylation represents one of the key regulatory events in physiological insulin secretion from the islet ?-cell. In this context, several classes of protein kinases (e.g. calcium-, cyclic nucleotide- and phospholipid-dependent protein kinases and tyrosine kinases) have been characterized in the ?-cell. The majority of phosphorylated amino acids identified include phosphoserine, phosphothreonine and phosphotyrosine. Protein histidine phosphorylation has been implicated in the prok...

  7. Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT tumour suppressor gene: characterization of a 2 Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles

    Directory of Open Access Journals (Sweden)

    Boussaha Mekki

    2006-05-01

    Full Text Available Abstract Background The Fragile Histidine Triad gene (FHIT is an oncosuppressor implicated in many human cancers, including vesical tumors. FHIT is frequently hit by deletions caused by fragility at FRA3B, the most active of human common fragile sites, where FHIT lays. Vesical tumors affect also cattle, including animals grazing in the wild on bracken fern; compounds released by the fern are known to induce chromosome fragility and may trigger cancer with the interplay of latent Papilloma virus. Results The bovine FHIT was characterized by assembling a contig of 78 BACs. Sequence tags were designed on human exons and introns and used directly to select bovine BACs, or compared with sequence data in the bovine genome database or in the trace archive of the bovine genome sequencing project, and adapted before use. FHIT is split in ten exons like in man, with exons 5 to 9 coding for a 149 amino acids protein. VISTA global alignments between bovine genomic contigs retrieved from the bovine genome database and the human FHIT region were performed. Conservation was extremely high over a 2 Mb region spanning the whole FHIT locus, including the size of introns. Thus, the bovine FHIT covers about 1.6 Mb compared to 1.5 Mb in man. Expression was analyzed by RT-PCR and Northern blot, and was found to be ubiquitous. Four cDNA isoforms were isolated and sequenced, that originate from an alternative usage of three variants of exon 4, revealing a size very close to the major human FHIT cDNAs. Conclusion A comparative genomic approach allowed to assemble a contig of 78 BACs and to completely annotate a 1.6 Mb region spanning the bovine FHIT gene. The findings confirmed the very high level of conservation between human and bovine genomes and the importance of comparative mapping to speed the annotation process of the recently sequenced bovine genome. The detailed knowledge of the genomic FHIT region will allow to study the role of FHIT in bovine cancerogenesis

  8. Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT) tumour suppressor gene: characterization of a 2 Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles.

    Science.gov (United States)

    Uboldi, Cristina; Guidi, Elena; Roperto, Sante; Russo, Valeria; Roperto, Franco; Di Meo, Giulia Pia; Iannuzzi, Leopoldo; Floriot, Sandrine; Boussaha, Mekki; Eggen, André; Ferretti, Luca

    2006-05-23

    The Fragile Histidine Triad gene (FHIT) is an oncosuppressor implicated in many human cancers, including vesical tumors. FHIT is frequently hit by deletions caused by fragility at FRA3B, the most active of human common fragile sites, where FHIT lays. Vesical tumors affect also cattle, including animals grazing in the wild on bracken fern; compounds released by the fern are known to induce chromosome fragility and may trigger cancer with the interplay of latent Papilloma virus. The bovine FHIT was characterized by assembling a contig of 78 BACs. Sequence tags were designed on human exons and introns and used directly to select bovine BACs, or compared with sequence data in the bovine genome database or in the trace archive of the bovine genome sequencing project, and adapted before use. FHIT is split in ten exons like in man, with exons 5 to 9 coding for a 149 amino acids protein. VISTA global alignments between bovine genomic contigs retrieved from the bovine genome database and the human FHIT region were performed. Conservation was extremely high over a 2 Mb region spanning the whole FHIT locus, including the size of introns. Thus, the bovine FHIT covers about 1.6 Mb compared to 1.5 Mb in man. Expression was analyzed by RT-PCR and Northern blot, and was found to be ubiquitous. Four cDNA isoforms were isolated and sequenced, that originate from an alternative usage of three variants of exon 4, revealing a size very close to the major human FHIT cDNAs. A comparative genomic approach allowed to assemble a contig of 78 BACs and to completely annotate a 1.6 Mb region spanning the bovine FHIT gene. The findings confirmed the very high level of conservation between human and bovine genomes and the importance of comparative mapping to speed the annotation process of the recently sequenced bovine genome. The detailed knowledge of the genomic FHIT region will allow to study the role of FHIT in bovine cancerogenesis, especially of vesical papillomavirus-associated cancers of

  9. Characterization of PhPRP1, a histidine domain arabinogalactan protein from Petunia hybrida pistils.

    Science.gov (United States)

    Twomey, Megan C; Brooks, Jenna K; Corey, Jillaine M; Singh-Cundy, Anu

    2013-10-15

    An arabinogalactan protein, PhPRP1, was purified from Petunia hybrida pistils and shown to be orthologous to TTS-1 and TTS-2 from Nicotiana tabacum and NaTTS from Nicotiana alata. Sequence comparisons among these proteins, and CaPRP1 from Capsicum annuum, reveal a conserved histidine-rich domain and two hypervariable domains. Immunoblots show that TTS-1 and PhPRP1 are also expressed in vegetative tissues of tobacco and petunia respectively. In contrast to the molecular mass heterogeneity displayed by the pistil proteins, the different isoforms found in seedlings, roots, and leaves each has a discrete size (37, 80, 160, and 200 kDa) on SDS-PAGE gels. On the basis of their chemistry, distinctive domain architecture, and the unique pattern of expression, we have named this group of proteins HD-AGPs (histidine domain-arabinogalactan proteins). Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. Increased adsorption of histidine-tagged proteins onto tissue culture polystyrene

    DEFF Research Database (Denmark)

    Holmberg, Maria; Hansen, Thomas Steen; Lind, Johan Ulrik

    2012-01-01

    and ethylenediaminetetraacetic acid (EDTA), as well as adsorption performed at different pH and ionic strength indicates that the high adsorption is caused by electrostatic interaction between negatively charged carboxylate groups on the TCPS surface and positively charged histidine residues in the proteins. Pre......In this study we compare histidine-tagged and native proteins with regards to adsorption properties. We observe significantly increased adsorption of proteins with an incorporated polyhistidine amino acid motif (HIS-tag) onto tissue culture polystyrene (TCPS) compared to similar proteins without...... a HIS-tag. The effect is not observed on polystyrene (PS). Adsorption experiments have been performed at physiological pH (7.4) and the effect was only observed for the investigated proteins that have pI values below or around 7.4. Competitive adsorption experiments with imidazole...

  11. Substantial conformational change mediated by charge-triad residues of the death effector domain in protein-protein interactions.

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    Edward C Twomey

    Full Text Available Protein conformational changes are commonly associated with the formation of protein complexes. The non-catalytic death effector domains (DEDs mediate protein-protein interactions in a variety of cellular processes, including apoptosis, proliferation and migration, and glucose metabolism. Here, using NMR residual dipolar coupling (RDC data, we report a conformational change in the DED of the phosphoprotein enriched in astrocytes, 15 kDa (PEA-15 protein in the complex with a mitogen-activated protein (MAP kinase, extracellular regulated kinase 2 (ERK2, which is essential in regulating ERK2 cellular distribution and function in cell proliferation and migration. The most significant conformational change in PEA-15 happens at helices α2, α3, and α4, which also possess the highest flexibility among the six-helix bundle of the DED. This crucial conformational change is modulated by the D/E-RxDL charge-triad motif, one of the prominent structural features of DEDs, together with a number of other electrostatic and hydrogen bonding interactions on the protein surface. Charge-triad motif promotes the optimal orientation of key residues and expands the binding interface to accommodate protein-protein interactions. However, the charge-triad residues are not directly involved in the binding interface between PEA-15 and ERK2.

  12. Human Neuronal Calcium Sensor-1 Protein Avoids Histidine Residues To Decrease pH Sensitivity.

    Science.gov (United States)

    Gong, Yehong; Zhu, Yuzhen; Zou, Yu; Ma, Buyong; Nussinov, Ruth; Zhang, Qingwen

    2017-01-26

    pH is highly regulated in mammalian central nervous systems. Neuronal calcium sensor-1 (NCS-1) can interact with numerous target proteins. Compared to that in the NCS-1 protein of Caenorhabditis elegans, evolution has avoided the placement of histidine residues at positions 102 and 83 in the NCS-1 protein of humans and Xenopus laevis, possibly to decrease the conformational sensitivity to pH gradients in synaptic processes. We used all-atom molecular dynamics simulations to investigate the effects of amino acid substitutions between species on human NCS-1 by substituting Arg102 and Ser83 for histidine at neutral (R102H and S83H) and acidic pHs (R102H p and S83H p ). Our cumulative 5 μs simulations revealed that the R102H mutation slightly increases the structural flexibility of loop L2 and the R102H p mutation decreases protein stability. Community network analysis illustrates that the R102H and S83H mutations weaken the interdomain and strengthen the intradomain communications. Secondary structure contents in the S83H and S83H p mutants are similar to those in the wild type, whereas the global structural stabilities and salt-bridge probabilities decrease. This study highlights the conformational dynamics effects of the R102H and S83H mutations on the local structural flexibility and global stability of NCS-1, whereas protonated histidine decreases the stability of NCS-1. Thus, histidines at positions 102 and 83 may not be compatible with the function of NCS-1 whether in the neutral or protonated state.

  13. Involvement of C-Terminal Histidines in Soybean PM1 Protein Oligomerization and Cu2+ Binding.

    Science.gov (United States)

    Liu, Guobao; Liu, Ke; Gao, Yang; Zheng, Yizhi

    2017-06-01

    Late embryogenesis abundant (LEA) proteins are widely distributed among plant species, where they contribute to abiotic stress tolerance. LEA proteins can be classified into seven groups according to conserved sequence motifs. The PM1 protein from soybean, which belongs to the Pfam LEA_1 group, has been shown previously to be at least partially natively unfolded, to bind metal ions and potentially to stabilize proteins and membranes. Here, we investigated the role of the PM1 C-terminal domain and in particular the multiple histidine residues in this half of the protein. We constructed recombinant plasmids expressing full-length PM1 and two truncated forms, PM1-N and PM1-C, which represent the N- and C-terminal halves of the protein, respectively. Immunoblotting and cross-linking experiments showed that full-length PM1 forms oligomers and high molecular weight (HMW) complexes in vitro and in vivo, while PM1-C, but not PM1-N, also formed oligomers and HMW complexes in vitro. When the histidine residues in PM1 and PM1-C were chemically modified, oligomerization was abolished, suggesting that histidines play a key role in this process. Furthermore, we demonstrated that high Cu2+ concentrations promote oligomerization and induce PM1 and PM1-C to form HMW complexes. Therefore, we speculate that PM1 proteins not only maintain ion homeostasis in the cytoplasm, but also potentially stabilize and protect other proteins during abiotic stress by forming a large, oligomeric molecular shield around biological targets. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Increased adsorption of histidine-tagged proteins onto tissue culture polystyrene.

    Science.gov (United States)

    Holmberg, Maria; Hansen, Thomas Steen; Lind, Johan Ulrik; Hjortø, Gertrud Malene

    2012-04-01

    In this study we compare histidine-tagged and native proteins with regards to adsorption properties. We observe significantly increased adsorption of proteins with an incorporated polyhistidine amino acid motif (HIS-tag) onto tissue culture polystyrene (TCPS) compared to similar proteins without a HIS-tag. The effect is not observed on polystyrene (PS). Adsorption experiments have been performed at physiological pH (7.4) and the effect was only observed for the investigated proteins that have pI values below or around 7.4. Competitive adsorption experiments with imidazole and ethylenediaminetetraacetic acid (EDTA), as well as adsorption performed at different pH and ionic strength indicates that the high adsorption is caused by electrostatic interaction between negatively charged carboxylate groups on the TCPS surface and positively charged histidine residues in the proteins. Pre-adsorption of bovine serum albumin (BSA) does not decrease the adsorption of HIS-tagged proteins onto TCPS. Our findings identify a potential problem in using HIS-tagged signalling molecule in assays with cells cultured on TCPS, since the concentration of the molecule in solution might be affected and this could critically influence the assay outcome. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Enzyme-linked immunosorbent assays for insulin-like growth factor-I using six-histidine tag fused proteins

    International Nuclear Information System (INIS)

    Huang Yong; Shi Ruina; Zhong Xuefei; Wang Dan; Zhao Meiping; Li Yuanzong

    2007-01-01

    The fusion proteins of insulin-like growth factor-I (IGF-I) and six-histidine tag (IGF-I-6H, 6H-IGF-I-6H) were cloned, expressed, purified and renatured, with their immunoreaction properties and biological activities intact. The binding kinetics between these fusion proteins and anti-IGF-I antibody or anti-6H antibody were studied using surface plasmon resonance (SPR). Two enzyme-linked immunosorbent assay (ELISA) modes, which proved feasible in the measurement of human serum samples, were used to detect IGF-I with the help of the six-histidine tagged proteins. Furthermore, combining the production technique of the six-histidine tagged fusion protein with the competitive sandwich ELISA mode, using an enzyme labeled anti-6H antibody as a tracer, can be a universal immunochemical method to quantitate other polypeptides or proteins

  16. Reduction in the copy number and expression level of the recurrent human papillomavirus integration gene fragile histidine triad (FHIT predicts the transition of cervical lesions.

    Directory of Open Access Journals (Sweden)

    Liming Wang

    Full Text Available Cervical cancer is the second most common cancer and the third leading cause of cancer death in females worldwide, especially in developing countries. High risk human papillomavirus (HR-HPV infection causes cervical cancer and precancerous cervical intraepithelial neoplasia (CIN. Integration of the HR-HPV genome into the host chromatin is an important step in cervical carcinogenesis. The detection of integrated papillomavirus sequences-PCR (DIPS-PCR allowed us to explore HPV integration in the human genome and to determine the pattern of this integration. We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and 40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the clinical samples and the HeLa and SiHa cell lines. Among all the integration loci, we identified three recurrent integration loci: 3p14.2 (3 samples, 13q22.1 (2 samples and a SiHa cell line and 8q24 (1 sample and a HeLa cell line. To further explore the effect of HR-HPV integration in the 3p14.2 locus, we used fluorescence in situ hybridization (FISH to determine the copy number of the 3p14.2 locus and immunohistochemistry (IHC to determine the protein expression levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus copy number and FHIT protein expression levels showed significant decreases when CIN transitioned to cervical cancer. HPV copy number was also evaluated in these clinical samples, and the copy number of HPV increased significantly between CIN and cervical cancer samples. Finally, we employed receiver operating characteristic curve (ROC curve analysis to evaluate the potential of all these indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT copy number and FHIT protein expression levels have good diagnostic efficiencies.

  17. Facile and high-efficient immobilization of histidine-tagged multimeric protein G on magnetic nanoparticles

    Science.gov (United States)

    Lee, Jiho; Chang, Jeong Ho

    2014-12-01

    This work reports the high-efficient and one-step immobilization of multimeric protein G on magnetic nanoparticles. The histidine-tagged (His-tag) recombinant multimeric protein G was overexpressed in Escherichia coli BL21 by the repeated linking of protein G monomers with a flexible linker. High-efficient immobilization on magnetic nanoparticles was demonstrated by two different preparation methods through the amino-silane and chloro-silane functionalization on silica-coated magnetic nanoparticles. Three kinds of multimeric protein G such as His-tag monomer, dimer, and trimer were tested for immobilization efficiency. For these tests, bicinchoninic acid (BCA) assay was employed to determine the amount of immobilized His-tag multimeric protein G. The result showed that the immobilization efficiency of the His-tag multimeric protein G of the monomer, dimer, and trimer was increased with the use of chloro-silane-functionalized magnetic nanoparticles in the range of 98% to 99%, rather than the use of amino-silane-functionalized magnetic nanoparticles in the range of 55% to 77%, respectively.

  18. Glassin, a histidine-rich protein from the siliceous skeletal system of the marine sponge Euplectella, directs silica polycondensation.

    Science.gov (United States)

    Shimizu, Katsuhiko; Amano, Taro; Bari, Md Rezaul; Weaver, James C; Arima, Jiro; Mori, Nobuhiro

    2015-09-15

    The hexactinellids are a diverse group of predominantly deep sea sponges that synthesize elaborate fibrous skeletal systems of amorphous hydrated silica. As a representative example, members of the genus Euplectella have proved to be useful model systems for investigating structure-function relationships in these hierarchically ordered siliceous network-like composites. Despite recent advances in understanding the mechanistic origins of damage tolerance in these complex skeletal systems, the details of their synthesis have remained largely unexplored. Here, we describe a previously unidentified protein, named "glassin," the main constituent in the water-soluble fraction of the demineralized skeletal elements of Euplectella. When combined with silicic acid solutions, glassin rapidly accelerates silica polycondensation over a pH range of 6-8. Glassin is characterized by high histidine content, and cDNA sequence analysis reveals that glassin shares no significant similarity with any other known proteins. The deduced amino acid sequence reveals that glassin consists of two similar histidine-rich domains and a connecting domain. Each of the histidine-rich domains is composed of three segments: an amino-terminal histidine and aspartic acid-rich sequence, a proline-rich sequence in the middle, and a histidine and threonine-rich sequence at the carboxyl terminus. Histidine always forms HX or HHX repeats, in which most of X positions are occupied by glycine, aspartic acid, or threonine. Recombinant glassin reproduces the silica precipitation activity observed in the native proteins. The highly modular composition of glassin, composed of imidazole, acidic, and hydroxyl residues, favors silica polycondensation and provides insights into the molecular mechanisms of skeletal formation in hexactinellid sponges.

  19. Deletion of Plasmodium falciparum Histidine-Rich Protein 2 (pfhrp2) and Histidine-Rich Protein 3 (pfhrp3) Genes in Colombian Parasites.

    Science.gov (United States)

    Murillo Solano, Claribel; Akinyi Okoth, Sheila; Abdallah, Joseph F; Pava, Zuleima; Dorado, Erika; Incardona, Sandra; Huber, Curtis S; Macedo de Oliveira, Alexandre; Bell, David; Udhayakumar, Venkatachalam; Barnwell, John W

    2015-01-01

    A number of studies have analyzed the performance of malaria rapid diagnostic tests (RDTs) in Colombia with discrepancies in performance being attributed to a combination of factors such as parasite levels, interpretation of RDT results and/or the handling and storage of RDT kits. However, some of the inconsistencies observed with results from Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-based RDTs could also be explained by the deletion of the gene that encodes the protein, pfhrp2, and its structural homolog, pfhrp3, in some parasite isolates. Given that pfhrp2- and pfhrp3-negative P. falciparum isolates have been detected in the neighboring Peruvian and Brazilian Amazon regions, we hypothesized that parasites with deletions of pfhrp2 and pfhrp3 may also be present in Colombia. In this study we tested 100 historical samples collected between 1999 and 2009 from six Departments in Colombia for the presence of pfhrp2, pfhrp3 and their flanking genes. Seven neutral microsatellites were also used to determine the genetic background of these parasites. In total 18 of 100 parasite isolates were found to have deleted pfhrp2, a majority of which (14 of 18) were collected from Amazonas Department, which borders Peru and Brazil. pfhrp3 deletions were found in 52 of the 100 samples collected from all regions of the country. pfhrp2 flanking genes PF3D7_0831900 and PF3D7_0831700 were deleted in 22 of 100 and in 1 of 100 samples, respectively. pfhrp3 flanking genes PF3D7_1372100 and PF3D7_1372400 were missing in 55 of 100 and in 57 of 100 samples. Structure analysis of microsatellite data indicated that Colombian samples tested in this study belonged to four clusters and they segregated mostly based on their geographic region. Most of the pfhrp2-deleted parasites were assigned to a single cluster and originated from Amazonas Department although a few pfhrp2-negative parasites originated from the other three clusters. The presence of a high proportion of pfhrp2

  20. Slow Histidine H/D Exchange Protocol for Thermodynamic Analysis of Protein Folding and Stability using Mass Spectrometry

    OpenAIRE

    Tran, Duc T.; Banerjee, Sambuddha; Alayash, Abdu I.; Crumbliss, Alvin L.; Fitzgerald, Michael C.

    2012-01-01

    Described here is a mass spectrometry based protocol to study the thermodynamic stability of proteins and protein-ligand complexes using the slow H/D exchange reaction of the imidazole C2 proton in histidine side chains. The protocol, which involves evaluating the denaturant dependence of this slow H/D exchange reaction in proteins, allows the global and/or subglobal unfolding/refolding properties of proteins and protein-ligand complexes to be probed. The protocol is developed using several m...

  1. Chiral recognition of proteins having L-histidine residues on the surface with lanthanide ion complex incorporated-molecularly imprinted fluorescent nanoparticles.

    Science.gov (United States)

    Uzun, Lokman; Uzek, Recep; Senel, Serap; Say, Ridvan; Denizli, Adil

    2013-08-01

    In this study, lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles were synthesized. A combination of three novel approaches was applied for the purpose. First, lanthanide ions [Terbium(III)] were complexed with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine amino acid, in order to incorporate the complex directly into the polymeric backbone. At the second stage, L-histidine molecules imprinted nanoparticles were utilized instead of whole protein imprinting in order to avoid whole drawbacks such as fragility, complexity, denaturation tendency, and conformation dependency. At the third stage following the first two steps mentioned above, imprinted L-histidine was coordinated with cupric ions [Cu(II)] to conduct the study under mild conditions. Then, molecularly imprinted fluorescent nanoparticles synthesized were used for L-histidine adsorption from aqueous solution to optimize conditions for adsorption and fluorimetric detection. Finally, usability of nanoparticles was investigated for chiral biorecognition using stereoisomer, D-histidine, racemic mixture, D,L-histidine, proteins with surface L-histidine residue, lysozyme, cytochrome C, or without ribonuclease A. The results revealed that the proposed polymerization strategy could make significant contribution to the solution of chronic problems of fluorescent component introduction into polymers. Additionally, the fluorescent nanoparticles reported here could be used for selective separation and fluorescent monitoring purposes. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase

    Science.gov (United States)

    2012-01-01

    Background The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons. Results The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatography-tandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAi-technique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells. Conclusions We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer's disease. PMID:22436051

  3. A histidine-rich protein 2-based malaria drug sensitivity assay for field use.

    Science.gov (United States)

    Noedl, Harald; Attlmayr, Bernhard; Wernsdorfer, Walther H; Kollaritsch, Herwig; Miller, Robert S

    2004-12-01

    With the spread of antimalarial drug resistance, simple and reliable tools for the assessment of antimalarial drug resistance, particularly in endemic regions and under field conditions, have become more important than ever before. We therefore developed a histidine-rich protein 2 (HRP2)-based drug sensitivity assay for testing of fresh isolates of Plasmodium falciparum in the field. In contrast to the HRP2 laboratory assay, the field assay uses a procedure that further simplifies the handling and culturing of malaria parasites by omitting centrifugation, washing, the use of serum, and dilution with uninfected red blood cells. A total of 40 fresh Plasmodium falciparum isolates were successfully tested for their susceptibility to dihydroartemisinin, mefloquine, quinine, and chloroquine (50% inhibitory concentration [IC50] = 3.43, 61.89, 326.75, and 185.31 nM, respectively). Results very closely matched those obtained with a modified World Health Organization schizont maturation assay (R2 = 0.96, P < 0.001; mean log difference at IC50 = 0.054).

  4. Introduction of a covalent histidine-heme linkage in a hemoglobin: a promising tool for heme protein engineering.

    Science.gov (United States)

    Rice, Selena L; Preimesberger, Matthew R; Johnson, Eric A; Lecomte, Juliette T J

    2014-12-01

    The hemoglobins of the cyanobacteria Synechococcus and Synechocystis (GlbNs) are capable of spontaneous and irreversible attachment of the b heme to the protein matrix. The reaction, which saturates the heme 2-vinyl by addition of a histidine residue, is reproduced in vitro by preparing the recombinant apoprotein, adding ferric heme, and reducing the iron to the ferrous state. Spontaneous covalent attachment of the heme is potentially useful for protein engineering purposes. Thus, to explore whether the histidine-heme linkage can serve in such applications, we attempted to introduce it in a test protein. We selected as our target the heme domain of Chlamydomonas eugametos LI637 (CtrHb), a eukaryotic globin that exhibits less than 50% sequence identity with the cyanobacterial GlbNs. We chose two positions, 75 in the FG corner and 111 in the H helix, to situate a histidine near a vinyl group. We characterized the proteins with gel electrophoresis, absorbance spectroscopy, and NMR analysis. Both T111H and L75H CtrHbs reacted upon reduction of the ferric starting material containing cyanide as the distal ligand to the iron. With L75H CtrHb, nearly complete (>90%) crosslinking was observed to the 4-vinyl as expected from the X-ray structure of wild-type CtrHb. Reaction of T111H CtrHb also occurred at the 4-vinyl, in a 60% yield indicating a preference for the flipped heme orientation in the starting material. The work suggests that the His-heme modification will be applicable to the design of proteins with a non-dissociable heme group. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Carney's triad

    International Nuclear Information System (INIS)

    Pignatelli, V.; Grassi, L.; Campani, D.; Pingitore, R.

    1988-01-01

    Carney's triad is a rare syndrome characterized by gastric leiomyosarcoma, functioning extraadrenal paraganglioma, and pulmonary chondroma. Twenty-seven cases are reported in literature: the most commonly observed neoplasm is gastric leiomyosarcoma (26/27),followed by lung tumor (22/27), and gastric paraganglioma (15/27). Three patients bearing a gastric leiomysarcoma developed liver metastases, and 6 had a local recurrence after some years. The occurence of paraganglioma makes the prognosis wors: 4 deaths from local infiltration, metastases or severe hypertension. The triad only accured in 9/27 cases, mostly young female patients. A common embryologic origin is difficult to assess. The case of a young female patients. A common embryologic origin is difficult to assess. The case of a young female patient with recurrent gastric leiomyosarcoma (12 years later) and bilateral pulmonary chondroma as described. It is important that patients with any of the tree tumors be periodically examined

  6. Chiral recognition of proteins having L-histidine residues on the surface with lanthanide ion complex incorporated-molecularly imprinted fluorescent nanoparticles

    International Nuclear Information System (INIS)

    Uzun, Lokman; Uzek, Recep; Şenel, Serap; Say, Ridvan; Denizli, Adil

    2013-01-01

    In this study, lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles were synthesized. A combination of three novel approaches was applied for the purpose. First, lanthanide ions [Terbium(III)] were complexed with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine amino acid, in order to incorporate the complex directly into the polymeric backbone. At the second stage, L-histidine molecules imprinted nanoparticles were utilized instead of whole protein imprinting in order to avoid whole drawbacks such as fragility, complexity, denaturation tendency, and conformation dependency. At the third stage following the first two steps mentioned above, imprinted L-histidine was coordinated with cupric ions [Cu(II)] to conduct the study under mild conditions. Then, molecularly imprinted fluorescent nanoparticles synthesized were used for L-histidine adsorption from aqueous solution to optimize conditions for adsorption and fluorimetric detection. Finally, usability of nanoparticles was investigated for chiral biorecognition using stereoisomer, D-histidine, racemic mixture, D,L-histidine, proteins with surface L-histidine residue, lysozyme, cytochrome C, or without ribonuclease A. The results revealed that the proposed polymerization strategy could make significant contribution to the solution of chronic problems of fluorescent component introduction into polymers. Additionally, the fluorescent nanoparticles reported here could be used for selective separation and fluorescent monitoring purposes. Highlights: • Lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles • Direct incorporation of the fluorescent complex into polymeric backbone. • Imprinting by assistance of cupric ion coordination into nanoparticles • Evaluation of the chiral biorecognition ability of nanoparticles • Simultaneous selective separation and fluorescent monitoring

  7. Chiral recognition of proteins having L-histidine residues on the surface with lanthanide ion complex incorporated-molecularly imprinted fluorescent nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Uzun, Lokman, E-mail: lokman@hacettepe.edu.tr [Hacettepe University, Department of Chemistry, 06381, Ankara (Turkey); Uzek, Recep; Şenel, Serap [Hacettepe University, Department of Chemistry, 06381, Ankara (Turkey); Say, Ridvan [Anadolu University, Department of Chemistry, 26470, Eskisehir (Turkey); Denizli, Adil [Hacettepe University, Department of Chemistry, 06381, Ankara (Turkey)

    2013-08-01

    In this study, lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles were synthesized. A combination of three novel approaches was applied for the purpose. First, lanthanide ions [Terbium(III)] were complexed with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine amino acid, in order to incorporate the complex directly into the polymeric backbone. At the second stage, L-histidine molecules imprinted nanoparticles were utilized instead of whole protein imprinting in order to avoid whole drawbacks such as fragility, complexity, denaturation tendency, and conformation dependency. At the third stage following the first two steps mentioned above, imprinted L-histidine was coordinated with cupric ions [Cu(II)] to conduct the study under mild conditions. Then, molecularly imprinted fluorescent nanoparticles synthesized were used for L-histidine adsorption from aqueous solution to optimize conditions for adsorption and fluorimetric detection. Finally, usability of nanoparticles was investigated for chiral biorecognition using stereoisomer, D-histidine, racemic mixture, D,L-histidine, proteins with surface L-histidine residue, lysozyme, cytochrome C, or without ribonuclease A. The results revealed that the proposed polymerization strategy could make significant contribution to the solution of chronic problems of fluorescent component introduction into polymers. Additionally, the fluorescent nanoparticles reported here could be used for selective separation and fluorescent monitoring purposes. Highlights: • Lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles • Direct incorporation of the fluorescent complex into polymeric backbone. • Imprinting by assistance of cupric ion coordination into nanoparticles • Evaluation of the chiral biorecognition ability of nanoparticles • Simultaneous selective separation and fluorescent monitoring.

  8. Investigation of the Copper Binding Site And the Role of Histidine As a Ligand in Riboflavin Binding Protein

    Energy Technology Data Exchange (ETDEWEB)

    Smith, S.R.; Bencze, K.Z.; Russ, K.A.; Wasiukanis, K.; Benore-Parsons, M.; Stemmler, T.L.

    2009-05-26

    Riboflavin Binding Protein (RBP) binds copper in a 1:1 molar ratio, forming a distinct well-ordered type II site. The nature of this site has been examined using X-ray absorption and pulsed electron paramagnetic resonance (EPR) spectroscopies, revealing a four coordinate oxygen/nitrogen rich environment. On the basis of analysis of the Cambridge Structural Database, the average protein bound copper-ligand bond length of 1.96 {angstrom}, obtained by extended x-ray absorption fine structure (EXAFS), is consistent with four coordinate Cu(I) and Cu(II) models that utilize mixed oxygen and nitrogen ligand distributions. These data suggest a Cu-O{sub 3}N coordination state for copper bound to RBP. While pulsed EPR studies including hyperfine sublevel correlation spectroscopy and electron nuclear double resonance show clear spectroscopic evidence for a histidine bound to the copper, inclusion of a histidine in the EXAFS simulation did not lead to any significant improvement in the fit.

  9. Protonation states of histidine and other key residues in deoxy normal human adult hemoglobin by neutron protein crystallography

    International Nuclear Information System (INIS)

    Kovalevsky, Andrey; Chatake, Toshiyuki; Shibayama, Naoya; Park, Sam-Yong; Ishikawa, Takuya; Mustyakimov, Marat; Fisher, S. Zoe; Langan, Paul; Morimoto, Yukio

    2010-01-01

    Using neutron diffraction analysis, the protonation states of 35 of 38 histidine residues were determined for the deoxy form of normal human adult hemoglobin. Distal and buried histidines may contribute to the increased affinity of the deoxy state for hydrogen ions and its decreased affinity for oxygen compared with the oxygenated form. The protonation states of the histidine residues key to the function of deoxy (T-state) human hemoglobin have been investigated using neutron protein crystallography. These residues can reversibly bind protons, thereby regulating the oxygen affinity of hemoglobin. By examining the OMIT F o − F c and 2F o − F c neutron scattering maps, the protonation states of 35 of the 38 His residues were directly determined. The remaining three residues were found to be disordered. Surprisingly, seven pairs of His residues from equivalent α or β chains, αHis20, αHis50, αHis58, αHis89, βHis63, βHis143 and βHis146, have different protonation states. The protonation of distal His residues in the α 1 β 1 heterodimer and the protonation of αHis103 in both subunits demonstrates that these residues may participate in buffering hydrogen ions and may influence the oxygen binding. The observed protonation states of His residues are compared with their ΔpK a between the deoxy and oxy states. Examination of inter-subunit interfaces provided evidence for interactions that are essential for the stability of the deoxy tertiary structure

  10. Immobilised metal-ion affinity chromatography purification of histidine-tagged recombinant proteins : a wash step with a low concentration of EDTA

    NARCIS (Netherlands)

    Westra, DF; Welling, GW; Koedijk, DGAM; Scheffer, AJ; The, TH; Welling-Wester, S

    2001-01-01

    Immobilised metal-ion affinity chromatography (IMAC) is widely used for the purification of recombinant proteins in which a poly-histidine tag is introduced. However, other proteins may also bind to IMAC columns. We describe the use of a washing buffer with a low concentration of EDTA (0.5 mM) for

  11. Immobilized palladium(II) ion affinity chromatography for recovery of recombinant proteins with peptide tags containing histidine and cysteine.

    Science.gov (United States)

    Kikot, Pamela; Polat, Aise; Achilli, Estefania; Fernandez Lahore, Marcelo; Grasselli, Mariano

    2014-11-01

    Fusion of peptide-based tags to recombinant proteins is currently one of the most used tools for protein production. Also, immobilized metal ion affinity chromatography (IMAC) has a huge application in protein purification, especially in research labs. The combination of expression systems of recombinant tagged proteins with this robust chromatographic system has become an efficient and rapid tool to produce milligram-range amounts of proteins. IMAC-Ni(II) columns have become the natural partners of 6xHis-tagged proteins. The Ni(II) ion is considered as the best compromise of selectivity and affinity for purification of a recombinant His-tagged protein. The palladium(II) ion is also able to bind to side chains of amino acids and form ternary complexes with iminodiacetic acid and free amino acids and other sulfur-containing molecules. In this work, we evaluated two different cysteine- and histidine-containing six amino acid tags linked to the N-terminal group of green fluorescent protein (GFP) and studied the adsorption and elution conditions using novel eluents. Both cysteine-containing tagged GFPs were able to bind to IMAC-Pd(II) matrices and eluted successfully using a low concentration of thiourea solution. The IMAC-Ni(II) system reaches less than 20% recovery of the cysteine-containing tagged GFP from a crude homogenate of recombinant Escherichia coli, meanwhile the IMAC-Pd(II) yields a recovery of 45% with a purification factor of 13. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Proton NMR Studies of a Large Protein. pH, Substrate Titrations, and NOESY Experiments with Perdeuterated Yeast Phosphoglycerate Kinase Containing [ 1H]Histidine Residues

    Science.gov (United States)

    Pappu, K. M.; Serpersu, E. H.

    Fully deuterated yeast phosphoglycerate kinase ([ 2H]PGK) was prepared biosynthetically with only histidine side chains of normal ( 1H) isotopic composition. The 1H NMR spectrum of this enzyme([ 1H]His[ 2H]PGK) showed that the histidine side chains are clearly visible as sharp signals. Thus detailed structural studies by 1H NMR became feasible with isotope-hybrid phosphoglycerate kinase which is otherwise too large ( Mr ˜ 46,000) for conventional 1H NMR studies. Proton signals of bound substrates were visible in the 1H NMR spectrum even with a substrate-to-enzyme ratio of less than 1/2 (mol/mol). The 2D NOESY spectrum of enzyme-MgdATP-glycerol 3-phosphate complex showed that, although protein concentration was very high (1.5 m M), no intraprotein cross peaks were observed other than those of intraresidue histidine NOE cross peaks. In addition, intrasubstrate NOEs and intermolecular NOEs between histidine and substrate protons were visible at a 1.5/1 substrate/enzyme (mol/mol) ratio. Paramagnetic effects of a substrate analog, Cr(III)ATP, on some of the histidine side chains indicated that the formation of the ternary enzyme-substrate complex causes large conformational changes in the enzyme.

  13. Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+ in Settings of Tissue Injury

    Directory of Open Access Journals (Sweden)

    Kristin M. Priebatsch

    2017-03-01

    Full Text Available Divalent metal ions are essential nutrients for all living organisms and are commonly protein-bound where they perform important roles in protein structure and function. This regulatory control from metals is observed in the relatively abundant plasma protein histidine-rich glycoprotein (HRG, which displays preferential binding to the second most abundant transition element in human systems, Zinc (Zn2+. HRG has been proposed to interact with a large number of protein ligands and has been implicated in the regulation of various physiological and pathological processes including the formation of immune complexes, apoptotic/necrotic and pathogen clearance, cell adhesion, antimicrobial activity, angiogenesis, coagulation and fibrinolysis. Interestingly, these processes are often associated with sites of tissue injury or tumour growth, where the concentration and distribution of Zn2+ is known to vary. Changes in Zn2+ levels have been shown to modify HRG function by altering its affinity for certain ligands and/or providing protection against proteolytic disassembly by serine proteases. This review focuses on the molecular interplay between HRG and Zn2+, and how Zn2+ binding modifies HRG-ligand interactions to regulate function in different settings of tissue injury.

  14. The triad value function

    DEFF Research Database (Denmark)

    Vedel, Mette

    2016-01-01

    the triad value function. Next, the applicability and validity of the concept is examined in a case study of four closed vertical supply chain triads. Findings - The case study demonstrates that the triad value function facilitates the analysis and understanding of an apparent paradox; that distributors...... are not dis-intermediated in spite of their limited contribution to activities in the triads. The results indicate practical adequacy of the triad value function. Research limitations/implications - The triad value function is difficult to apply in the study of expanded networks as the number of connections...... expands exponentially with the number of ties in the network. Moreover, it must be applied in the study of service triads and open vertical supply chain triads to further verify the practical adequacy of the concept. Practical implications - The triad value function cannot be used normatively...

  15. Transcription and expression of Plasmodium falciparum histidine-rich proteins in different stages and strains: implications for rapid diagnostic tests.

    Directory of Open Access Journals (Sweden)

    Joanne Baker

    Full Text Available BACKGROUND: Although rapid diagnostic tests (RDTs for Plasmodium falciparum infection that target histidine rich protein 2 (PfHRP2 are generally sensitive, their performance has been reported to be variable. One possible explanation for variable test performance is differences in expression level of PfHRP in different parasite isolates. METHODS: Total RNA and protein were extracted from synchronised cultures of 7 P. falciparum lines over 5 time points of the life cycle, and from synchronised ring stages of 10 falciparum lines. Using quantitative real-time polymerase chain reaction, Western blot analysis and ELISA we investigated variations in the transcription and protein levels of pfhrp2, pfhrp3 and PfHRP respectively in the different parasite lines, over the parasite intraerythrocytic life cycle. RESULTS: Transcription of pfhrp2 and pfhrp3 in different parasite lines over the parasite life cycle was observed to vary relative to the control parasite K1. In some parasite lines very low transcription of these genes was observed. The peak transcription was observed in ring-stage parasites. Pfhrp2 transcription was observed to be consistently higher than pfhrp3 transcription within parasite lines. The intraerythrocytic lifecycle stage at which the peak level of protein was present varied across strains. Total protein levels were more constant relative to total mRNA transcription, however a maximum 24 fold difference in expression at ring-stage parasites relative to the K1 strain was observed. CONCLUSIONS: The levels of transcription of pfhrp2 and pfhrp3, and protein expression of PfHRP varied between different P. falciparum strains. This variation may impact on the detection sensitivity of PfHRP2-detecting RDTs.

  16. Immobilized Metal Affinity Chromatography Co-Purifies TGF-β1 with Histidine-Tagged Recombinant Extracellular Proteins

    Science.gov (United States)

    Kaur, Jasvir; Reinhardt, Dieter P.

    2012-01-01

    Extracellular recombinant proteins are commonly produced using HEK293 cells as histidine-tagged proteins facilitating purification by immobilized metal affinity chromatography (IMAC). Based on gel analyses, this one-step purification typically produces proteins of high purity. Here, we analyzed the presence of TGF-β1 in such IMAC purifications using recombinant extracellular fibrillin-1 fragments as examples. Analysis of various purified recombinant fibrillin-1 fragments by ELISA consistently revealed the presence of picomolar concentrations of active and latent TGF-β1, but not of BMP-2. These quantities of TGF-β1 were not detectable by Western blotting and mass spectrometry. However, the amounts of TGF-β1 were sufficient to consistently trigger Smad2 phosphorylation in fibroblasts. The purification mechanism was analyzed to determine whether the presence of TGF-β1 in these protein preparations represents a specific or non-specific co-purification of TGF-β1 with fibrillin-1 fragments. Control purifications using conditioned medium from non-transfected 293 cells yielded similar amounts of TGF-β1 after IMAC. IMAC of purified TGF-β1 and the latency associated peptide showed that these proteins bound to the immobilized nickel ions. These data clearly demonstrate that TGF-β1 was co-purified by specific interactions with nickel, and not by specific interactions with fibrillin-1 fragments. Among various chromatographic methods tested for their ability to eliminate TGF-β1 from fibrillin-1 preparations, gel filtration under high salt conditions was highly effective. As various recombinant extracellular proteins purified in this fashion are frequently used for experiments that can be influenced by the presence of TGF-β1, these findings have far-reaching implications for the required chromatographic schemes and quality controls. PMID:23119075

  17. Efficiency of histidine rich protein II-based rapid diagnostic tests for monitoring malaria transmission intensities in an endemic area

    Science.gov (United States)

    Modupe, Dokunmu Titilope; Iyabo, Olasehinde Grace; Oladoke, Oladejo David; Oladeji, Olanrewaju; Abisola, Akinbobola; Ufuoma, Adjekukor Cynthia; Faith, Yakubu Omolara; Humphrey, Adebayo Abiodun

    2018-04-01

    In recent years there has been a global decrease in the prevalence of malaria due to scaling up of control measures, hence global control efforts now target elimination and eradication of the disease. However, a major problem associated with elimination is asymptomatic reservoir of infection especially in endemic areas. This study aims to determine the efficiency of histidine rich protein II (HRP-2) based rapid diagnostic tests (RDT) for monitoring transmission intensities in an endemic community in Nigeria during the pre-elimination stage. Plasmodium falciparum asymptomatic malaria infection in healthy individuals and symptomatic cases were detected using HRP-2. RDT negative tests were re-checked by microscopy and by primer specific PCR amplification of merozoite surface protein 2 (msp-2) for asexual parasites and Pfs25 gene for gametocytes in selected samples to detect low level parasitemia undetectable by microscopy. The mean age of the study population (n=280) was 6.12 years [95% CI 5.16 - 7.08, range 0.5 - 55], parasite prevalence was 44.6% and 36.3% by microscopy and RDT respectively (p =0.056). The parasite prevalence of 61.5% in children aged >2 - 10 years was significantly higher than 3.7% rate in adults >18years (p malaria in endemic areas.

  18. Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru

    Science.gov (United States)

    Akinyi, Sheila; Hayden, Tonya; Gamboa, Dionicia; Torres, Katherine; Bendezu, Jorge; Abdallah, Joseph F.; Griffing, Sean M.; Quezada, Wilmer Marquiño; Arrospide, Nancy; De Oliveira, Alexandre Macedo; Lucas, Carmen; Magill, Alan J.; Bacon, David J.; Barnwell, John W.; Udhayakumar, Venkatachalam

    2013-01-01

    The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. PMID:24077522

  19. Dual Mode Fluorophore-Doped Nickel Nitrilotriacetic Acid-Modified Silica Nanoparticles Combine Histidine-Tagged Protein Purification with Site-Specific Fluorophore Labeling

    OpenAIRE

    Kim, Sung Hoon; Jeyakumar, M.; Katzenellenbogen, John A.

    2007-01-01

    We present the first example of a fluorophore-doped nickel chelate surface- modified silica nanoparticle that functions in a dual mode, combining histidine-tagged protein purification with site-specific fluorophore labeling. Tetramethylrhodamine (TMR)-doped silica nanoparticles, estimated to contain 700–900 TMRs per ca. 23-nm particle, were surface modified with nitrilotriacetic acid (NTA), producing TMR-SiO2-NTA-Ni+2. Silica-embedded TMR retains very high quantum yield, is resistant to quenc...

  20. Immobilization of histidine-tagged proteins on monodisperse metallochelation liposomes: Preparation and study of their structure

    Czech Academy of Sciences Publication Activity Database

    Mašek, J.; Bartheldyová, E.; Korvasová, Z.; Škrabalová, J.; Koudelka, Š.; Kulich, P.; Kratochvílová, Irena; Miller, A. D.; Ledvina, Miroslav; Raška, M.; Turánek, J.

    2011-01-01

    Roč. 408, č. 1 (2011), s. 95-104 ISSN 0003-2697 R&D Projects: GA ČR(CZ) GAP304/10/1951 Institutional research plan: CEZ:AV0Z10100520; CEZ:AV0Z40550506 Keywords : liposome * proteoliposome * detergent removal method * recombinant protein * metallochelatation * AF microscopy * TEM * dynamic light scattering Subject RIV: CE - Biochemistry Impact factor: 2.996, year: 2011

  1. Synthesis of Ni-Zn ferrite nanoparticles in radiofrequency thermal plasma reactor and their use for purification of histidine-tagged proteins

    International Nuclear Information System (INIS)

    Feczko, Tivadar; Muskotal, Adel; Gal, Lorand; Szepvoelgyi, Janos; Sebestyen, Anett; Vonderviszt, Ferenc

    2008-01-01

    Superparamagnetic Ni-Zn ferrite nanoparticles were synthesized in radiofrequency thermal plasma reactor from aqueous solutions of Ni- and Zn-nitrates. The nanoparticles were studied for protein purification performance in both quantitative and qualitative terms. For comparison, experiments were also performed by Ni-charged affinity chromatography. It was proved that the Ni-Zn ferrite nanoparticles effectively purified histidine-tagged proteins with a maximum protein binding capacity of about 7% (w/w). Gel electrophoresis demonstrated better purification characteristics for magnetic nanoparticles than for affinity chromatography.

  2. Dual-mode fluorophore-doped nickel nitrilotriacetic acid-modified silica nanoparticles combine histidine-tagged protein purification with site-specific fluorophore labeling.

    Science.gov (United States)

    Kim, Sung Hoon; Jeyakumar, M; Katzenellenbogen, John A

    2007-10-31

    We present the first example of a fluorophore-doped nickel chelate surface-modified silica nanoparticle that functions in a dual mode, combining histidine-tagged protein purification with site-specific fluorophore labeling. Tetramethylrhodamine (TMR)-doped silica nanoparticles, estimated to contain 700-900 TMRs per ca. 23 nm particle, were surface modified with nitrilotriacetic acid (NTA), producing TMR-SiO2-NTA-Ni2+. Silica-embedded TMR retains very high quantum yield, is resistant to quenching by buffer components, and is modestly quenched and only to a certain depth (ca. 2 nm) by surface-attached Ni2+. When exposed to a bacterial lysate containing estrogen receptor alpha ligand binding domain (ERalpha) as a minor component, these beads showed very high specificity binding, enabling protein purification in one step. The capacity and specificity of these beads for binding a his-tagged protein were characterized by electrophoresis, radiometric counting, and MALDI-TOF MS. ERalpha, bound to TMR-SiO2-NTA-Ni++ beads in a site-specific manner, exhibited good activity for ligand binding and for ligand-induced binding to coactivators in solution FRET experiments and protein microarray fluorometric and FRET assays. This dual-mode type TMR-SiO2-NTA-Ni2+ system represents a powerful combination of one-step histidine-tagged protein purification and site-specific labeling with multiple fluorophore species.

  3. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  4. Chemical conversion of cisplatin and carboplatin with histidine in a model protein crystallized under sodium iodide conditions

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M.; Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    Crystals of HEWL with cisplatin and HEWL with carboplatin grown in sodium iodide conditions both show a partial chemical transformation of cisplatin or carboplatin to a transiodoplatin (PtI{sub 2}X{sub 2}) form. The binding is only at the N{sup δ} atom of His15. A further Pt species (PtI{sub 3}X) is also seen, in both cases bound in a crevice between symmetry-related protein molecules. Cisplatin and carboplatin are platinum anticancer agents that are used to treat a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine in hen egg-white lysozyme (HEWL) showed a partial chemical conversion of carboplatin to cisplatin owing to the high sodium chloride concentration used in the crystallization conditions. Also, the co-crystallization of HEWL with carboplatin in sodium bromide conditions resulted in the partial conversion of carboplatin to the transbromoplatin form, with a portion of the cyclobutanedicarboxylate (CBDC) moiety still present. The results of the co-crystallization of HEWL with cisplatin or carboplatin in sodium iodide conditions are now reported in order to determine whether the cisplatin and carboplatin converted to the iodo form, and whether this took place in a similar way to the partial conversion of carboplatin to cisplatin in NaCl conditions or to transbromoplatin in NaBr conditions as seen previously. It is reported here that a partial chemical transformation has taken place to a transplatin form for both ligands. The NaI-grown crystals belonged to the monoclinic space group P2{sub 1} with two molecules in the asymmetric unit. The chemically transformed cisplatin and carboplatin bind to both His15 residues, i.e. in each asymmetric unit. The binding is only at the N{sup δ} atom of His15. A third platinum species is also seen in both conditions bound in a crevice between symmetry-related molecules. Here, the platinum is bound to three I atoms identified based on their anomalous difference electron densities

  5. The Escherichia coli BolA Protein IbaG Forms a Histidine-Ligated [2Fe-2S]-Bridged Complex with Grx4.

    Science.gov (United States)

    Dlouhy, Adrienne C; Li, Haoran; Albetel, Angela-Nadia; Zhang, Bo; Mapolelo, Daphne T; Randeniya, Sajini; Holland, Ashley A; Johnson, Michael K; Outten, Caryn E

    2016-12-13

    Two ubiquitous protein families have emerged as key players in iron metabolism, the CGFS-type monothiol glutaredoxins (Grxs) and the BolA proteins. Monothiol Grxs and BolA proteins form heterocomplexes that have been implicated in Fe-S cluster assembly and trafficking. The Escherichia coli genome encodes members of both of these proteins families, namely, the monothiol glutaredoxin Grx4 and two BolA family proteins, BolA and IbaG. Previous work has demonstrated that E. coli Grx4 and BolA interact as both apo and [2Fe-2S]-bridged heterodimers that are spectroscopically distinct from [2Fe-2S]-bridged Grx4 homodimers. However, the physical and functional interactions between Grx4 and IbaG are uncharacterized. Here we show that co-expression of Grx4 with IbaG yields a [2Fe-2S]-bridged Grx4-IbaG heterodimer. In vitro interaction studies indicate that IbaG binds the [2Fe-2S] Grx4 homodimer to form apo Grx4-IbaG heterodimer as well as the [2Fe-2S] Grx4-IbaG heterodimer, altering the cluster stability and coordination environment. Additionally, spectroscopic and mutagenesis studies provide evidence that IbaG ligates the Fe-S cluster via the conserved histidine that is present in all BolA proteins and by a second conserved histidine that is present in the H/C loop of two of the four classes of BolA proteins. These results suggest that IbaG may function in Fe-S cluster assembly and trafficking in E. coli as demonstrated for other BolA homologues that interact with monothiol Grxs.

  6. Identifying the functional part of heparin-binding protein (HBP) as a monocyte stimulator and the novel role of monocytes as HBP producers

    DEFF Research Database (Denmark)

    Schou, Morten; Djurup, René; Norris, Kjeld

    2011-01-01

    Heparin-binding protein (HBP), an evolutionary ancient and biologically highly important molecule in inflammation, is an inactive serine protease due to mutations in the catalytic triad. The histidine (position 41) in the conserved sequence TAAHC is mutated to serine and this sequence (TAASC) pla...

  7. Affinity purification and partial characterization of a yeast multiprotein complex for nucleotide excision repair using histidine-tagged Rad14 protein

    International Nuclear Information System (INIS)

    Rodriguez, K.; Talamantez, J.; Huang, W.; Reed, S.H.; Wang, Z.; Chen, L.; Feaver, W.J.; Friedberg, E.C.; Tomkinson, A.E.

    1998-01-01

    The nucleotide excision repair (NER) pathway of eukaryotes involves approximately 30 polypeptides. Reconstitution of this pathway with purified components is consistent with the sequential assembly of NER proteins at the DNA lesion. However, recent studies have suggested that NER proteins may be pre-assembled in a high molecular weight complex in the absence of DNA damage. To examine this model further, we have constructed a histidine-tagged version of the yeast DNA damage recognition protein Rad14. Affinity purification of this protein from yeast nuclear extracts resulted in the co-purification of Rad1, Rad7, Rad10, Rad16, Rad23, RPA, RPB1, and TFIIH proteins, whereas none of these proteins bound to the affinity resin in the absence of recombinant Rad14. Furthermore, many of the co-purifying proteins were present in approximately equimolar amounts. Co-elution of these proteins was also observed when the nuclear extract was fractionated by gel filtration, indicating that the NER proteins were associated in a complex with a molecular mass of >1000 kDa prior to affinity chromatography. The affinity purified NER complex catalyzed the incision of UV-irradiated DNA in an ATP-dependent reaction. We conclude that active high molecular weight complexes of NER proteins exist in undamaged yeast cells

  8. A novel mechanism of “metal gel-shift” by histidine-rich Ni2+-binding Hpn protein from Helicobacter pylori strain SS1

    Science.gov (United States)

    Ito, Yuki; Masumoto, Junya; Morita, Eugene Hayato; Hayashi, Hidenori

    2017-01-01

    Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) is a universally used method for determining approximate molecular weight (MW) in protein research. Migration of protein that does not correlate with formula MW, termed “gel shifting” appears to be common for histidine-rich proteins but not yet studied in detail. We investigated “gel shifting” in Ni2+-binding histidine-rich Hpn protein cloned from Helicobacter pylori strain SS1. Our data demonstrate two important factors determining “gel shifting” of Hpn, polyacrylamide-gel concentration and metal binding. Higher polyacrylamide-gel concentrations resulted in faster Hpn migration. Irrespective of polyacrylamide-gel concentration, preserved Hpn-Ni2+ complex migrated faster (3–4 kDa) than apo-Hpn, phenomenon termed “metal gel-shift” demonstrating an intimate link between Ni2+ binding and “gel shifting”. To examine this discrepancy, eluted samples from corresponding spots on SDS-gel were analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). The MW of all samples was the same (6945.66±0.34 Da) and identical to formula MW with or without added mass of Ni2+. MALDI-TOF-MS of Ni2+-treated Hpn revealed that monomer bound up to six Ni2+ ions non-cooperatively, and equilibrium between protein-metal species was reliant on Ni2+ availability. This corroborates with gradually increased heterogeneity of apo-Hpn band followed by compact "metal-gel shift" band on SDS-PAGE. In view of presented data metal-binding and “metal-gel shift” models are discussed. PMID:28207866

  9. Conceptualizing inter-organizational triads

    DEFF Research Database (Denmark)

    Vedel, Mette; Holma, Anne-Maria; Havila, Virpi

    2016-01-01

    of inter-organizational phenomena. However, not all studies involving a context of three actors are actually examining triads. This paper offers a robust definition of three-actor constellations qualifying as triads. Moreover, it elaborates on different types of inter-organizational triads, based on two...... aspects of collectivity; cohesion and the ability to act as a single entity. The definition of inter-organizational triads and the categorization of different types of triads will hopefully encourage further studies of triads; the smallest and simplest network which offers insights, which cannot...

  10. Alanine rich peptide from Populus trichocarpa inhibit growth of Staphylococcus aureus via targetting its extracellular domain of Sensor Histidine Kinase YycGex protein.

    Science.gov (United States)

    Al Akeel, Raid; Mateen, Ayesha; Syed, Rabbani; Al-Qahtani, Mohammed S; Alqahtani, A

    2018-05-11

    Due to growing concern towards microbial resistance, ongoing search for developing novel bioactive compounds such as peptides is on rise. The aim of this study was to evaluate antimicrobial effect of Populus trichocarpa extract, chemically identify the active peptide fraction and finds its target in Staphylococcus aureus. In this study the active fraction of P. trichocarpa crude extract was purified and characterized using MS/MS. This peptide PT13 antimicrobial activity was confirmed by in-vitro agar based disk diffusion and in-vivo infection model of G. mellonella. The proteomic expression analysis of S. aureus under influence of PT13 was studied using LTQ-Orbitrap-MS in-solution digestion and identity of target protein was acquired with their quantified expression using label-free approach of Progenesis QI software. Docking study was performed with peptide PT13 and its target YycG protein using CABS-dock. The active fraction PT13 sequence was identified as KVPVAAAAAAAAAVVASSMVVAAAK, with 25 amino acid including 13 alanine having M/Z 2194.2469. PT13 was uniformly inhibited growth S. aureus SA91 and MIC was determined 16 μg/mL for SA91 S. aureus strain. Sensor histidine kinase (YycG) was most significant target found differentially expressed under influence of PT13. G. mellonella larvae were killed rapidly due to S aureus infection, whereas death in protected group was insignificant in compare to control. The docking models showed ten docking models with RMSD value 1.89 for cluster 1 and RMSD value 3.95 for cluster 2 which is predicted to be high quality model. Alanine rich peptide could be useful in constructing as antimicrobial peptide for targeting extracellular Domain of Sensor Histidine Kinase YycG from S. aureus used in the study. Copyright © 2018. Published by Elsevier Ltd.

  11. Female athlete triad update.

    Science.gov (United States)

    Beals, Katherine A; Meyer, Nanna L

    2007-01-01

    The passage of Title IX legislation in 1972 provided enormous opportunities for women to reap the benefits of sports participation. For most female athletes, sports participation is a positive experience, providing improved physical fitness, enhanced self-esteem, and better physical and mental health. Nonetheless, for a few female athletes, the desire for athletic success combined with the pressure to achieve a prescribed body weight may lead to the development of a triad of medical disorders including disordered eating, menstrual dysfunction, and low bone mineral density (BMD)--known collectively as the female athlete triad. Alone or in combination, the disorders of the triad can have a negative impact on health and impair athletic performance.

  12. Ubiquitin specific peptidase 5 mediates Histidine-rich protein Hpn induced cell apoptosis in hepatocellular carcinoma through P14-P53 signaling.

    Science.gov (United States)

    Liu, Yi; Wang, Wei-Mao; Zou, Li-Yi; Li, Li; Feng, Lu; Pan, Ming-Zhu; Lv, Min-Yi; Cao, Ying; Wang, Hua; Kung, Hsiang-Fu; Pang, Jian-Xin; Fu, Wei-Ming; Zhang, Jin-Fang

    2017-06-01

    Hpn is a small histidine-rich cytoplasmic protein from Helicobacter pylori and has been recognized as a high-risk factor for several cancers including gastric cancer, colorectal cancer, and MALT lymphoma. However, the relationship between Hpn and cancers remains elusive. In this study, we discovered that Hpn protein effectively suppressed cell growth and induced apoptosis in hepatocellular carcinoma (HCC). A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics was performed to find the molecular targets of Hpn in HCC cells. It was identified that twelve proteins were differentially expressed, with USP5 being one of the most significantly downregulated protein. The P14 ARF -P53 signaling was activated by USP5 knockdown in HCC cells. Furthermore, USP5 overexpression significantly rescued the suppressive effect of Hpn on the viability of HCC cells. In conclusion, our study suggests that Hpn plays apoptosis-inducing roles through suppressing USP5 expression and activating the P14 ARF -P53 signaling. Therefore, Hpn may be a potential candidate for developing novel anti-HCC drugs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Histidine-rich protein 2 (pfhrp2) and pfhrp3 gene deletions in Plasmodium falciparum isolates from select sites in Brazil and Bolivia.

    Science.gov (United States)

    Rachid Viana, Giselle Maria; Akinyi Okoth, Sheila; Silva-Flannery, Luciana; Lima Barbosa, Danielle Regina; Macedo de Oliveira, Alexandre; Goldman, Ira F; Morton, Lindsay C; Huber, Curtis; Anez, Arletta; Dantas Machado, Ricardo Luiz; Aranha Camargo, Luís Marcelo; Costa Negreiros do Valle, Suiane; Marins Póvoa, Marinete; Udhayakumar, Venkatachalam; Barnwell, John W

    2017-01-01

    More than 80% of available malaria rapid diagnostic tests (RDTs) are based on the detection of histidine-rich protein-2 (PfHRP2) for diagnosis of Plasmodium falciparum malaria. Recent studies have shown the genes that code for this protein and its paralog, histidine-rich protein-3 (PfHRP3), are absent in parasites from the Peruvian Amazon Basin. Lack of PfHRP2 protein through deletion of the pfhrp2 gene leads to false-negative RDT results for P. falciparum. We have evaluated the extent of pfhrp2 and pfhrp3 gene deletions in a convenience sample of 198 isolates from six sites in three states across the Brazilian Amazon Basin (Acre, Rondonia and Para) and 25 isolates from two sites in Bolivia collected at different times between 2010 and 2012. Pfhrp2 and pfhrp3 gene and their flanking genes on chromosomes 7 and 13, respectively, were amplified from 198 blood specimens collected in Brazil. In Brazil, the isolates collected in Acre state, located in the western part of the Brazilian Amazon, had the highest percentage of deletions for pfhrp2 25 (31.2%) of 79, while among those collected in Rondonia, the prevalence of pfhrp2 gene deletion was only 3.3% (2 out of 60 patients). In isolates from Para state, all parasites were pfhrp2-positive. In contrast, we detected high proportions of isolates from all 3 states that were pfhrp3-negative ranging from 18.3% (11 out of 60 samples) to 50.9% (30 out of 59 samples). In Bolivia, only one of 25 samples (4%) tested had deleted pfhrp2 gene, while 68% (17 out of 25 samples) were pfhrp3-negative. Among the isolates tested, P. falciparum pfhrp2 gene deletions were present mainly in those from Acre State in the Brazilian Amazon. These results indicate it is important to reconsider the use of PfHRP2-based RDTs in the western region of the Brazilian Amazon and to implement appropriate surveillance systems to monitor pfhrp2 gene deletions in this and other parts of the Amazon region.

  14. A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad

    Science.gov (United States)

    2018-01-01

    One group of enzymes that confer resistance to aminoglycoside antibiotics through covalent modification belongs to the GCN5-related N-acetyltransferase (GNAT) superfamily. We show how a unique GNAT subfamily member uses a previously unidentified noncanonical catalytic triad, consisting of a glutamic acid, a histidine, and the antibiotic substrate itself, which acts as a nucleophile and attacks the acetyl donor molecule. Neutron diffraction studies allow for unambiguous identification of a low-barrier hydrogen bond, predicted in canonical catalytic triads to increase basicity of the histidine. This work highlights the role of this unique catalytic triad in mediating antibiotic resistance while providing new insights into the design of the next generation of aminoglycosides. PMID:29632894

  15. Oleic Acid, deglycosylated vitamin D-binding protein, nitric oxide: a molecular triad made lethal to cancer.

    Science.gov (United States)

    Ruggiero, Marco; Ward, Emma; Smith, Rodney; Branca, Jacopo J V; Noakes, David; Morucci, Gabriele; Taubmann, Margit; Thyer, Lynda; Pacini, Stefania

    2014-07-01

    Oleic Acid (OA) has been shown to have anticancer properties mediated by interaction with proteins such as α-lactalbumin and lactoferrins. Therefore, we synthesized complexes of OA and Gc protein-derived macrophage activating factor (GcMAF) that inhibits per se cancer cell proliferation and metastatic potential. We hypothesised that OA-GcMAF complexes could exploit the anticancer properties of both OA and GcMAF in a synergistic manner. We postulated that the stimulating effects of GcMAF on macrophages might lead to release of nitric oxide (NO). Patients with advanced cancer were treated at the Immuno Biotech Treatment Centre with OA-GcMAF-based integrative immunotherapy in combination with a low-carbohydrate, high-protein diet, fermented milk products containing naturally-produced GcMAF, Vitamin D3, omega-3 fatty acids and low-dose acetylsalicylic acid. Measuring the tumour by ultrasonographic techniques, we observed a decrease of tumour volume of about 25%. These observations demonstrate that OA, GcMAF and NO can be properly combined and specifically delivered to advanced cancer patients with significant effects on immune system stimulation and tumour volume reduction avoiding harmful side-effects. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    John T Murphy

    2011-03-01

    Full Text Available Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants that were resistant to zinc toxicity. Here we demonstrate that mutations of the C. elegans histidine ammonia lyase (haly-1 gene promote zinc tolerance. C. elegans haly-1 encodes a protein that is homologous to vertebrate HAL, an enzyme that converts histidine to urocanic acid. haly-1 mutant animals displayed elevated levels of histidine, indicating that C. elegans HALY-1 protein is an enzyme involved in histidine catabolism. These results suggest the model that elevated histidine chelates zinc and thereby reduces zinc toxicity. Supporting this hypothesis, we demonstrated that dietary histidine promotes zinc tolerance. Nickel is another metal that binds histidine with high affinity. We demonstrated that haly-1 mutant animals are resistant to nickel toxicity and dietary histidine promotes nickel tolerance in wild-type animals. These studies identify a novel role for haly-1 and histidine in zinc metabolism and may be relevant for other animals.

  17. The female athlete triad.

    Science.gov (United States)

    Kazis, Keren; Iglesias, Elba

    2003-02-01

    The female athlete triad is a syndrome consisting of disordered eating, amenorrhea, and osteoporosis. The syndrome is increasing in prevalence as more women are participating in sports at a competitive level. Behaviors such as intense exercise or disordered eating patterns can lead to dysregulation of the hypothalamic-pituitarian-ovarian (HPO) axis, resulting in amenorrhea. Hypothalamic amenorrhea can lead to osteoporosis and increased fracture risk. Adolescents may particularly be at risk because it is during this crucial time that females attain their peak bone mass. Prevention of the female athlete triad through education and identification of athletes at risk may decrease the incidence of long-term deleterious consequences. Treatment of the female athlete triad is initially aimed at increasing caloric intake and decreasing physical activity until there is resumption of normal menses. Treatment of decreased bone mineral density and osteoporosis in the adolescent population, however, is controversial, with new treatment modalities currently being investigated in order to aid in the management of this disorder.

  18. Understanding the self-assembly of proteins onto gold nanoparticles and quantum dots driven by metal-histidine coordination.

    Science.gov (United States)

    Aldeek, Fadi; Safi, Malak; Zhan, Naiqian; Palui, Goutam; Mattoussi, Hedi

    2013-11-26

    Coupling of polyhistidine-appended biomolecules to inorganic nanocrystals driven by metal-affinity interactions is a greatly promising strategy to form hybrid bioconjugates. It is simple to implement and can take advantage of the fact that polyhistidine-appended proteins and peptides are routinely prepared using well established molecular engineering techniques. A few groups have shown its effectiveness for coupling proteins onto Zn- or Cd-rich semiconductor quantum dots (QDs). Expanding this conjugation scheme to other metal-rich nanoparticles (NPs) such as AuNPs would be of great interest to researchers actively seeking effective means for interfacing nanostructured materials with biology. In this report, we investigated the metal-affinity driven self-assembly between AuNPs and two engineered proteins, a His7-appended maltose binding protein (MBP-His) and a fluorescent His6-terminated mCherry protein. In particular, we investigated the influence of the capping ligand affinity to the nanoparticle surface, its density, and its lateral extension on the AuNP-protein self-assembly. Affinity gel chromatography was used to test the AuNP-MPB-His7 self-assembly, while NP-to-mCherry-His6 binding was evaluated using fluorescence measurements. We also assessed the kinetics of the self-assembly between AuNPs and proteins in solution, using time-dependent changes in the energy transfer quenching of mCherry fluorescent proteins as they immobilize onto the AuNP surface. This allowed determination of the dissociation rate constant, Kd(-1) ∼ 1-5 nM. Furthermore, a close comparison of the protein self-assembly onto AuNPs or QDs provided additional insights into which parameters control the interactions between imidazoles and metal ions in these systems.

  19. Sedimentation equilibrium of a small oligomer-forming membrane protein: effect of histidine protonation on pentameric stability.

    Science.gov (United States)

    Surya, Wahyu; Torres, Jaume

    2015-04-02

    Analytical ultracentrifugation (AUC) can be used to study reversible interactions between macromolecules over a wide range of interaction strengths and under physiological conditions. This makes AUC a method of choice to quantitatively assess stoichiometry and thermodynamics of homo- and hetero-association that are transient and reversible in biochemical processes. In the modality of sedimentation equilibrium (SE), a balance between diffusion and sedimentation provides a profile as a function of radial distance that depends on a specific association model. Herein, a detailed SE protocol is described to determine the size and monomer-monomer association energy of a small membrane protein oligomer using an analytical ultracentrifuge. AUC-ES is label-free, only based on physical principles, and can be used on both water soluble and membrane proteins. An example is shown of the latter, the small hydrophobic (SH) protein in the human respiratory syncytial virus (hRSV), a 65-amino acid polypeptide with a single α-helical transmembrane (TM) domain that forms pentameric ion channels. NMR-based structural data shows that SH protein has two protonatable His residues in its transmembrane domain that are oriented facing the lumen of the channel. SE experiments have been designed to determine how pH affects association constant and the oligomeric size of SH protein. While the pentameric form was preserved in all cases, its association constant was reduced at low pH. These data are in agreement with a similar pH dependency observed for SH channel activity, consistent with a lumenal orientation of the two His residues in SH protein. The latter may experience electrostatic repulsion and reduced oligomer stability at low pH. In summary, this method is applicable whenever quantitative information on subtle protein-protein association changes in physiological conditions have to be measured.

  20. Evidence that muscle cells do not express the histidine-rich glycoprotein associated with AMP deaminase but can internalise the plasma protein

    Directory of Open Access Journals (Sweden)

    A.R.M. Sabbatini

    2011-02-01

    Full Text Available Histidine-rich glycoprotein (HRG is synthesized by liver and is present at relatively high concentration in the plasma of vertebrates. We have previously described the association of a HRG-like molecule to purified rabbit skeletal muscle AMP deaminase (AMPD. We also provided the first evidence for the presence of a HRG-like protein in human skeletal muscle where a positive correlation between HRG content and total determined AMPD activity has been shown. In the present paper we investigate the origin of skeletal muscle HRG. The screening of a human skeletal muscle cDNA expression library using an anti-HRG antibody failed to reveal any positive clone. The RT-PCR analysis, performed on human skeletal muscle RNA as well as on RNA from the rhabdomyosarcoma (RD cell line, failed to show any mRNA specific for the plasma HRG or for the putative muscle variant. When the RD cells were incubated with human plasma HRG, a time-dependent increase of the HRG immunoreactivity was detected both at the plasma membrane level and intracellularly. The internalisation of HRG was inhibited by the addition of heparin. The above data strongly suggest that skeletal muscle cells do not synthesize the muscle variant of HRG but instead can actively internalise it from plasma.

  1. Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot

    Science.gov (United States)

    Markwalter, Christine F.; Gibson, Lauren E.; Mudenda, Lwiindi; Kimmel, Danielle W.; Mbambara, Saidon; Thuma, Philip E.; Wright, David W.

    2018-01-01

    Abstract. A rapid, on-bead enzyme-linked immunosorbent assay for Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM (pLDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify pLDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment. Biomarker clearance patterns relative to parasite clearance were determined; pLDH clearance followed closely with parasite clearance, whereas most patients maintained detectable levels of HRP2 for 35–52 days after treatment. Furthermore, weak-to-moderate correlations between biomarker concentration and parasite densities were found for both biomarkers. This work demonstrates the utility of the developed assay for epidemiological study and surveillance of malaria. PMID:29557342

  2. Histidine in Continuum Electrostatics Protonation State Calculations

    Science.gov (United States)

    Couch, Vernon; Stuchebruckhov, Alexei

    2014-01-01

    A modification to the standard continuum electrostatics approach to calculate protein pKas which allows for the decoupling of histidine tautomers within a two state model is presented. Histidine with four intrinsically coupled protonation states cannot be easily incorporated into a two state formalism because the interaction between the two protonatable sites of the imidazole ring is not purely electrostatic. The presented treatment, based on a single approximation of the interrelation between histidine’s charge states, allows for a natural separation of the two protonatable sites associated with the imidazole ring as well as the inclusion of all protonation states within the calculation. PMID:22072521

  3. Triads of capital

    DEFF Research Database (Denmark)

    Svendsen, Gunnar Lind Haase

    of capital means a coherent stock of capital, including social, cultural and physical capital, which belongs to a local community. The case of civic organization in rural Denmark 1800-1900 shows how the three capitals successively acted as driving forces: physical capital about year 1800, social capital...... about year 1880, and cultural capital about year 1900. In each case, one form of capital changed the two others in a chain reaction process, which ultimately led to a major reorganization of the triads of capital in the local rural communities....

  4. The service triad

    DEFF Research Database (Denmark)

    Andersson-Cederholm, Erika; Gyimóthy, Szilvia

    2010-01-01

    Models of service encounters are often fraught with reductionism, describing business relationships as mathematical combinations of dyadic constellations. Metaphors of ideal social relationships (marriages or friendships) are highlighted to stress normative aspects of equal, balanced and long......-term business partnerships. However, these approaches are limited in their analytical sensitivity, as they cannot address the complexity of multipart relationships, where meanings, roles and relationships are continuously constructed and reconstructed. In order to understand the ambivalent quality of business...... interactions, this article analyses the corporate travel market by applying Simmel’s depiction of the triad as a specific social form. Triadic constellations and more complex service networks involve dialectic tensions, simultaneously exhibiting loyalty and disloyalty, trust and distrust, empowerment...

  5. Catalysis by Glomerella cingulata cutinase requires conformational cycling between the active and inactive states of its catalytic triad.

    Science.gov (United States)

    Nyon, Mun Peak; Rice, David W; Berrisford, John M; Hounslow, Andrea M; Moir, Arthur J G; Huang, Huazhang; Nathan, Sheila; Mahadi, Nor Muhammad; Bakar, Farah Diba Abu; Craven, C Jeremy

    2009-01-09

    Cutinase belongs to a group of enzymes that catalyze the hydrolysis of esters and triglycerides. Structural studies on the enzyme from Fusarium solani have revealed the presence of a classic catalytic triad that has been implicated in the enzyme's mechanism. We have solved the crystal structure of Glomerella cingulata cutinase in the absence and in the presence of the inhibitors E600 (diethyl p-nitrophenyl phosphate) and PETFP (3-phenethylthio-1,1,1-trifluoropropan-2-one) to resolutions between 2.6 and 1.9 A. Analysis of these structures reveals that the catalytic triad (Ser136, Asp191, and His204) adopts an unusual configuration with the putative essential histidine His204 swung out of the active site into a position where it is unable to participate in catalysis, with the imidazole ring 11 A away from its expected position. Solution-state NMR experiments are consistent with the disrupted configuration of the triad observed crystallographically. H204N, a site-directed mutant, was shown to be catalytically inactive, confirming the importance of this residue in the enzyme mechanism. These findings suggest that, during its catalytic cycle, cutinase undergoes a significant conformational rearrangement converting the loop bearing the histidine from an inactive conformation, in which the histidine of the triad is solvent exposed, to an active conformation, in which the triad assumes a classic configuration.

  6. Substitution of aspartic acid-686 by histidine or asparagine in the human androgen receptor leads to a functionally inactive protein with altered hormone-binding characteristics

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Trifiro, M. A.; Kuiper, G. G.; Jenster, G.; Romalo, G.; Sai, T.; van Rooij, H. C.; Kaufman, M.; Rosenfield, R. L.; Liao, S.

    1991-01-01

    We have identified two different single nucleotide alterations in codon 686 (GAC; aspartic acid) in exon 4 of the human androgen receptor gene in three unrelated families with the complete form of androgen insensitivity. One mutation (G----C) results in an aspartic acid----histidine substitution

  7. High performance of histidine-rich protein 2 based rapid diagnostic tests in French Guiana are explained by the absence of pfhrp2 gene deletion in P. falciparum.

    Directory of Open Access Journals (Sweden)

    Mélanie Trouvay

    Full Text Available BACKGROUND: Care for malaria patients in endemic areas has been improved through the increasing use of Rapid Diagnostic Tests (RDTs. Most RDTs target the histidine-rich protein-2 antigen (PfHRP2 to detect P. falciparum, as it is abundant and shows great heat stability. However, their use in South America has been widely questioned following a recent publication that pinpoints the high prevalence of Peruvian field isolates lacking the gene encoding this protein. In the remote rural health centers of French Guiana, RDTs are the main diagnosis tools. Therefore, a study of PfHRP2 RDT performances and pfhrp2 genotyping was conducted to determine whether a replacement of the current pLDH-based kit could be considered. METHODS: The performance study compared the SD Malaria Ag test P.f/Pan® kit with the current gold standard diagnosis by microscopy. The prevalence of pfhrp2 and pfhrp3 deletions were evaluated from 221 P. falciparum isolates collected between 2009 and 2011 in French Guiana. RESULTS: Between January 2010 and August 2011, 960 suspected cases of malaria were analyzed using microscopy and RDTs. The sensitivity of the SD Malaria Ag test P.f/Pan® for detection of P. falciparum was 96.8% (95% CI: 90.9-99.3, and 86.0% (95% CI: 78.9-91.5 for the detection of P. vivax. No isolates (95% CI: 0-4.5 lacking either exon of the pfhrp2 gene were identified among the 221 P. falciparum isolates analyzed, but 7.4% (95% CI: 2.8-15.4 lacked the exon 2 part of the pfhrp3 gene. CONCLUSIONS: Field isolates lacking either exon of the pfhrp2 gene are absent in this western part of South America. Despite its sensibility to detect P. vivax, the SD Malaria Ag test P.f/Pan® kit is a satisfying alternative to microscopy in remote health centers, where it is difficult to provide highly skilled microscopists and to maintain the necessary equipment.

  8. Salt effects on ionization equilibria of histidines in myoglobin.

    Science.gov (United States)

    Kao, Y H; Fitch, C A; Bhattacharya, S; Sarkisian, C J; Lecomte, J T; García-Moreno E, B

    2000-09-01

    The salt dependence of histidine pK(a) values in sperm whale and horse myoglobin and in histidine-containing peptides was measured by (1)H-NMR spectroscopy. Structure-based pK(a) calculations were performed with continuum methods to test their ability to capture the effects of solution conditions on pK(a) values. The measured pK(a) of most histidines, whether in the protein or in model compounds, increased by 0.3 pH units or more between 0.02 M and 1.5 M NaCl. In myoglobin two histidines (His(48) and His(36)) exhibited a shallower dependence than the average, and one (His(113)) showed a steeper dependence. The (1)H-NMR data suggested that the salt dependence of histidine pK(a) values in the protein was determined primarily by the preferential stabilization of the charged form of histidine with increasing salt concentrations rather than by screening of electrostatic interactions. The magnitude and salt dependence of interactions between ionizable groups were exaggerated in pK(a) calculations with the finite-difference Poisson-Boltzmann method applied to a static structure, even when the protein interior was treated with arbitrarily high dielectric constants. Improvements in continuum methods for calculating salt effects on pK(a) values will require explicit consideration of the salt dependence of model compound pK(a) values used for reference in the calculations.

  9. Prebiotic synthesis of histidine

    Science.gov (United States)

    Shen, C.; Yang, L.; Miller, S. L.; Oro, J.

    1990-01-01

    The prebiotic formation of histidine (His) has been accomplished experimentally by the reaction of erythrose with formamidine followed by a Strecker synthesis. In the first step of this reaction sequence, the formation of imidazole-4-acetaldehyde took place by the condensation of erythrose and formamidine, two compounds that are known to be formed under prebiotic conditions. In a second step, the imidazole-4-acetaldehyde was converted to His, without isolation of the reaction products by adding HCN and ammonia to the reaction mixture. LC, HPLC, thermospray liquid chromatography-mass spectrometry, and tandem mass spectrometry were used to identify the product, which was obtained in a yield of 3.5% based on the ratio of His/erythrose. This is a new chemical synthesis of one of the basic amino acids which had not been synthesized prebiotically until now.

  10. Rumen-protected lysine, methionine, and histidine increase milk protein yield in dairy cows fed a metabolizable protein-deficient diet.

    Science.gov (United States)

    Lee, C; Hristov, A N; Cassidy, T W; Heyler, K S; Lapierre, H; Varga, G A; de Veth, M J; Patton, R A; Parys, C

    2012-10-01

    The objective of this experiment was to evaluate the effect of supplementing a metabolizable protein (MP)-deficient diet with rumen-protected (RP) Lys, Met, and specifically His on dairy cow performance. The experiment was conducted for 12 wk with 48 Holstein cows. Following a 2-wk covariate period, cows were blocked by DIM and milk yield and randomly assigned to 1 of 4 diets, based on corn silage and alfalfa haylage: control, MP-adequate diet (ADMP; MP balance: +9 g/d); MP-deficient diet (DMP; MP balance: -317 g/d); DMP supplemented with RPLys (AminoShure-L, Balchem Corp., New Hampton, NY) and RPMet (Mepron; Evonik Industries AG, Hanau, Germany; DMPLM); and DMPLM supplemented with an experimental RPHis preparation (DMPLMH). The analyzed crude protein content of the ADMP and DMP diets was 15.7 and 13.5 to 13.6%, respectively. The apparent total-tract digestibility of all measured nutrients, plasma urea-N, and urinary N excretion were decreased by the DMP diets compared with ADMP. Milk N secretion as a proportion of N intake was greater for the DMP diets compared with ADMP. Compared with ADMP, dry matter intake (DMI) tended to be lower for DMP, but was similar for DMPLM and DMPLMH (24.5, 23.0, 23.7, and 24.3 kg/d, respectively). Milk yield was decreased by DMP (35.2 kg/d), but was similar to ADMP (38.8 kg/d) for DMPLM and DMPLMH (36.9 and 38.5kg/d, respectively), paralleling the trend in DMI. The National Research Council 2001model underpredicted milk yield of the DMP cows by an average (±SE) of 10.3 ± 0.75 kg/d. Milk fat and true protein content did not differ among treatments, but milk protein yield was increased by DMPLM and DMPLMH compared with DMP and was not different from ADMP. Plasma essential amino acids (AA), Lys, and His were lower for DMP compared with ADMP. Supplementation of the DMP diets with RP AA increased plasma Lys, Met, and His. In conclusion, MP deficiency, approximately 15% below the National Research Council requirements from 2001, decreased

  11. The Currarino triad: neurosurgical considerations

    NARCIS (Netherlands)

    Emans, P.J.; van Aalst, J.; van Heurn, L.W.E.; Marcelis, C.; Kootstra, G.; Beets-Tan, R.G.H.; Vles, J.S.; Beuls, E.A.

    2006-01-01

    OBJECTIVES: The Currarino triad, a relatively uncommon hereditary disorder, is often associated with tethered cord and anterior myelomeningocele. Little is known of the implications of these neuroanatomic malformations or of the neurosurgical attitude. The objective of this study is to identify the

  12. Giddens’ Triad in Accounting Research

    OpenAIRE

    Edson Roberto Macohon; Carlos Eduardo Facin Lavarda

    2015-01-01

    To understand how the theory of Structuration has been investigated in Accounting, the objective was to analyze Giddens’ Triad in accounting research. Studies in the framework of the theory of Structuration (TS) were triangulated. The structural dimension of signification was conceived from a perceptive perspective, that is, when cognitive schemes are used to interpret the reality. Nevertheless, in the accounting information context, Accounting cannot be considered a monolithic tool to interp...

  13. 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....

  14. Immunolocalization of a Histidine-Rich Epidermal Differentiation Protein in the Chicken Supports the Hypothesis of an Evolutionary Developmental Link between the Embryonic Subperiderm and Feather Barbs and Barbules.

    Science.gov (United States)

    Alibardi, Lorenzo; Holthaus, Karin Brigit; Sukseree, Supawadee; Hermann, Marcela; Tschachler, Erwin; Eckhart, Leopold

    2016-01-01

    The morphogenesis of feathers is a complex process that depends on a tight spatiotemporal regulation of gene expression and assembly of the protein components of mature feathers. Recent comparative genomics and gene transcription studies have indicated that genes within the epidermal differentiation complex (EDC) encode numerous structural proteins of cornifying skin cells in amniotes including birds. Here, we determined the localization of one of these proteins, termed EDMTFH (Epidermal Differentiation Protein starting with a MTF motif and rich in Histidine), which belongs to a group of EDC-encoded proteins rich in aromatic amino acid residues. We raised an antibody against an EDMTFH-specific epitope and performed immunohistochemical investigations by light microscopy and immunogold labeling by electron microscopy of chicken embryos at days 14-18 of development. EDMTFH was specifically present in the subperiderm, a transient layer of the embryonic epidermis, and in barbs and barbules of feathers. In the latter, it partially localized to bundles of so-called feather beta-keratins (corneous beta-proteins, CBPs). Cells of the embryonic periderm, the epidermis proper, and the feather sheath were immunonegative for EDMTFH. The results of this study indicate that EDMTFH may contribute to the unique mechanical properties of feathers and define EDMTFH as a common marker of the subperiderm and the feather barbules. This expression pattern of EDMTFH resembles that of epidermal differentiation cysteine-rich protein (EDCRP) and feather CBPs and is in accordance with the hypothesis that a major part of the cyclically regenerating feather follicle is topologically, developmentally and evolutionarily related to the embryonic subperiderm.

  15. Immunolocalization of a Histidine-Rich Epidermal Differentiation Protein in the Chicken Supports the Hypothesis of an Evolutionary Developmental Link between the Embryonic Subperiderm and Feather Barbs and Barbules.

    Directory of Open Access Journals (Sweden)

    Lorenzo Alibardi

    Full Text Available The morphogenesis of feathers is a complex process that depends on a tight spatiotemporal regulation of gene expression and assembly of the protein components of mature feathers. Recent comparative genomics and gene transcription studies have indicated that genes within the epidermal differentiation complex (EDC encode numerous structural proteins of cornifying skin cells in amniotes including birds. Here, we determined the localization of one of these proteins, termed EDMTFH (Epidermal Differentiation Protein starting with a MTF motif and rich in Histidine, which belongs to a group of EDC-encoded proteins rich in aromatic amino acid residues. We raised an antibody against an EDMTFH-specific epitope and performed immunohistochemical investigations by light microscopy and immunogold labeling by electron microscopy of chicken embryos at days 14-18 of development. EDMTFH was specifically present in the subperiderm, a transient layer of the embryonic epidermis, and in barbs and barbules of feathers. In the latter, it partially localized to bundles of so-called feather beta-keratins (corneous beta-proteins, CBPs. Cells of the embryonic periderm, the epidermis proper, and the feather sheath were immunonegative for EDMTFH. The results of this study indicate that EDMTFH may contribute to the unique mechanical properties of feathers and define EDMTFH as a common marker of the subperiderm and the feather barbules. This expression pattern of EDMTFH resembles that of epidermal differentiation cysteine-rich protein (EDCRP and feather CBPs and is in accordance with the hypothesis that a major part of the cyclically regenerating feather follicle is topologically, developmentally and evolutionarily related to the embryonic subperiderm.

  16. 2-Fluoro-l-histidine

    Directory of Open Access Journals (Sweden)

    Kiran K. Andra

    2010-11-01

    Full Text Available The title compound, C6H8FN3O2, an analog of histidine, shows a reduced side-chain pKa (ca 1. The title structure exhibits a shortening of the bond between the proximal ring N atom and the F-substituted ring C atom, indicating an increase in π-bond character due to an inductive effect of fluorine.

  17. Classifying service triads to gain strategic insight

    NARCIS (Netherlands)

    Sengupta, Sourav; Niranjan, Tarikere T; van der Valk, Wendy; Humphreys, John

    2015-01-01

    Service triads refer to triadic relationships where a client firm (buying organization) outsources its service delivery to a third party supplier (vendor) who directly serves the client’s customer. Given the vast diversity of service triads, a one-size-fits-all approach of studying them is

  18. Histidine augments the suppression of hepatic glucose production by central insulin action.

    Science.gov (United States)

    Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-Ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

    2013-07-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

  19. Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane.

    Science.gov (United States)

    Weng, Haibo; Guo, Xinhua; Papoin, Julien; Wang, Jie; Coppel, Ross; Mohandas, Narla; An, Xiuli

    2014-01-01

    The malaria parasite Plasmodium falciparum exports a large number of proteins into the erythrocyte cytoplasm during the asexual intraerythrocytic stage of its life cycle. A subset of these proteins interacts with erythrocyte membrane skeletal proteins and grossly alters the structure and function of the membrane. Several of the exported proteins, such as PfEMP1, PfEMP3, RESA and KAHRP, interact with the preponderant erythrocyte skeleton protein, spectrin. Here we have searched for possible interaction of these four malaria proteins with another major erythrocyte skeleton protein, ankyrin R. We have shown that KAHRP, but none of the other three, binds to ankyrin R. We have mapped the binding site for ankyrin R to a 79-residue segment of the KAHRP sequence, and the reciprocal binding site for KAHRP in ankyrin R to a subdomain (D3) of the 89kDa ankyrin R membrane-binding domain. Interaction of intact ankyrin R with KAHRP was inhibited by the free D3 subdomain. When, moreover, red cells loaded with the soluble D3 subdomain were infected with P. falciparum, KAHRP secreted by the intraerythrocytic parasite no longer migrated to the host cell membrane, but remained diffusely distributed throughout the cytosol. Our findings suggest a potentially important role for interaction of KAHRP with red cell membrane skeleton in promoting the adhesion of malaria-infected red cells to endothelial surfaces, a central element in the pathophysiology of malaria. © 2013.

  20. A triad of lys12, lys41, arg78 spatial domain, a novel identified heparin binding site on tat protein, facilitates tat-driven cell adhesion.

    Directory of Open Access Journals (Sweden)

    Jing Ai

    Full Text Available Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.

  1. The Dark Triad across academic majors

    DEFF Research Database (Denmark)

    Vedel, Anna; Thomsen, Dorthe K.

    2017-01-01

    The Dark Triad traits (i.e., narcissism, psychopathy, and Machiavellianism) have been associated with the desire for power, status, and social dominance in the workplace, and these desires have been hypothesized to draw Dark Triad individuals towards occupations affording such outcomes. Following...... this reasoning, the Dark Triad may also influence educational choices. Research in other personality traits has shown that Big Five traits impact educational choices: Students in different academic majors differ on Big Five traits at enrollment. The aim of the present study was to explore whether there are also...

  2. The dark triad: Emotional and interpersonal characteristics

    Directory of Open Access Journals (Sweden)

    Tomić Katarina N.

    2016-01-01

    Full Text Available The Dark triad is a construct of pathological personality traits, which consists of three components conceptually different, but still with significant empirical overlap: narcissism, Machiavellianism and subclinical psychopathy. The concept of Dark Triad found its place in the current structural models of personality, such as the Big-five and HEXACO model, and also an Interpersonal circumplex, within which the personal qualities project itselves into certain patterns of interpersonal behavior. This paper provides a brief theoretical overview of the basic elements of the Dark Triad, and an overview of current research related to (un justified observation of the three constituent dimensions as a single construct in theoretical and empirical terms. Also, the paper presents an overview of the emotional dysfunctions typical for the triad, as well as the problems and consequences in the area of interpersonal and social relations.

  3. Controlling service delivery in service triads

    NARCIS (Netherlands)

    Iwaarden, van J.; Valk, van der W.; Aalders, L.; Virolainen, V.-M.

    2010-01-01

    Organizations are increasingly sourcing services that are directly delivered to their (end) customers by external providers. Buying organization, supplier and (end) customer operate in a triadic service relationship. In these triads, the buying organization lacks direct control over service delivery

  4. The New Triad, Disarmament and Strategic Stability

    International Nuclear Information System (INIS)

    Gruselle, Bruno

    2008-01-01

    After a comment of the evolution contained by the Nuclear Posture Review (NPR) published in 2001 by the US government and which proposed a new definition of the fundamentals of the US defence strategy, the author gives an overview of options, progress and perspectives of the new Triad. He discusses the progress status of American systems belonging to this new Triad (a global antimissile defence, development of a conventional strategic component, possible international cooperation and deployments), and the influence of arms control mechanisms on this new Triad (legal constraints, ambiguity of strategic missile conversion and alarm capacities, definition of a new framework for the conventional strategic strike programme). In the second part, the author analyses the consequences of the existence of this new Triad on strategic situations. He discusses the emergence of a new competition with Russia, the impact of Chinese modernisation, the impact on proliferating countries and on terrorist actions, and the perspective of a new paradigm for arms control

  5. Immobilised histidine tagged β2-adrenoceptor oriented by a diazonium salt reaction and its application in exploring drug-protein interaction using ephedrine and pseudoephedrine as probes.

    Science.gov (United States)

    Li, Qian; Bian, Liujiao; Zhao, Xinfeng; Gao, Xiaokang; Zheng, Jianbin; Li, Zijian; Zhang, Youyi; Jiang, Ru; Zheng, Xiaohui

    2014-01-01

    A new oriented method using a diazonium salt reaction was developed for linking β2-adrenoceptor (β2-AR) on the surface of macroporous silica gel. Stationary phase containing the immobilised receptor was used to investigate the interaction between β2-AR and ephedrine plus pseudoephedrine by zonal elution. The isotherms of the two drugs best fit the Langmuir model. Only one type of binding site was found for ephedrine and pseudoephedrine targeting β2-AR. At 37 °C, the association constants during the binding were (5.94±0.05)×103/M for ephedrine and (3.80±0.02) ×103/M for pseudoephedrine, with the binding sites of (8.92±0.06) ×10-4 M. Thermodynamic studies showed that the binding of the two compounds to β2-AR was a spontaneous reaction with exothermal processes. The ΔGθ, ΔHθ and ΔSθ for the interaction between ephedrine and β2-AR were -(22.33±0.04) kJ/mol, -(6.51±0.69) kJ/mol and 50.94±0.31 J/mol·K, respectively. For the binding of pseudoephedrine to the receptor, these values were -(21.17±0.02) kJ/mol, -(7.48±0.56) kJ/mol and 44.13±0.01 J/mol·K. Electrostatic interaction proved to be the driving force during the binding of the two drugs to β2-AR. The proposed immobilised method will have great potential for attaching protein to solid substrates and realizing the interactions between proteins and drugs.

  6. Immobilised histidine tagged β2-adrenoceptor oriented by a diazonium salt reaction and its application in exploring drug-protein interaction using ephedrine and pseudoephedrine as probes.

    Directory of Open Access Journals (Sweden)

    Qian Li

    Full Text Available A new oriented method using a diazonium salt reaction was developed for linking β2-adrenoceptor (β2-AR on the surface of macroporous silica gel. Stationary phase containing the immobilised receptor was used to investigate the interaction between β2-AR and ephedrine plus pseudoephedrine by zonal elution. The isotherms of the two drugs best fit the Langmuir model. Only one type of binding site was found for ephedrine and pseudoephedrine targeting β2-AR. At 37 °C, the association constants during the binding were (5.94±0.05×103/M for ephedrine and (3.80±0.02 ×103/M for pseudoephedrine, with the binding sites of (8.92±0.06 ×10-4 M. Thermodynamic studies showed that the binding of the two compounds to β2-AR was a spontaneous reaction with exothermal processes. The ΔGθ, ΔHθ and ΔSθ for the interaction between ephedrine and β2-AR were -(22.33±0.04 kJ/mol, -(6.51±0.69 kJ/mol and 50.94±0.31 J/mol·K, respectively. For the binding of pseudoephedrine to the receptor, these values were -(21.17±0.02 kJ/mol, -(7.48±0.56 kJ/mol and 44.13±0.01 J/mol·K. Electrostatic interaction proved to be the driving force during the binding of the two drugs to β2-AR. The proposed immobilised method will have great potential for attaching protein to solid substrates and realizing the interactions between proteins and drugs.

  7. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases Summary

    The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase

  8. Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action

    OpenAIRE

    Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime

    2013-01-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA le...

  9. Ni nanoparticles decorated onto graphene oxide with SiO2 as interlayer for high performance on histidine-rich protein separation

    Science.gov (United States)

    Yang, Xiaodan; Zhang, Min; Zheng, Jing; Li, Weizhen; Gan, Wenjun; Xu, Jingli; Hayat, Tasawar; Alharbi, Njud S.; Yang, Fan

    2018-05-01

    Sandwich-like structure of graphene oxide (GO) @SiO2@C-Ni nanosheets were prepared by combining an extended stöber method with subsequent carbonization treatment, in which polydopamine was used as reducing agent and carbon source. Firstly, the GO nanosheets were covered with SiO2 interlayer and finally coated with a outer shell of nickel ion doped polydopamine (PDA-Ni2+) with an extended stöber method. Followed by a carbonization to produce the GO@SiO2@C-Ni sheets with metallic nickel nanoparticles embedded in PDA-derived thin graphic carbon layer. Notably, silica interlayer played a vital role in the formation of such GO@SiO2@C-Ni sheets. Without the protection of SiO2, the hydrophobic graphene@C-Ni composites were obtained instead. While with silica layer as the spacer, the obtained hydrophilic GO@SiO2@C-Ni composites were not only well dispersed in the solution, but also can be adjusted in terms of the size and density of Ni nanoparticles (NPs) on surface by changing the calcination temperature or the molar ratio between dopamine and nickel salt. Furthermore, nickel nanoparticles decorated on GO@SiO2 sheets were employed to enrich His-rich proteins (BHb and BSA) via specific metal affinity force between polyhistidine groups and nickel nanoparticles.

  10. Giddens’ Triad in Accounting Research

    Directory of Open Access Journals (Sweden)

    Edson Roberto Macohon

    2015-09-01

    Full Text Available To understand how the theory of Structuration has been investigated in Accounting, the objective was to analyze Giddens’ Triad in accounting research. Studies in the framework of the theory of Structuration (TS were triangulated. The structural dimension of signification was conceived from a perceptive perspective, that is, when cognitive schemes are used to interpret the reality. Nevertheless, in the accounting information context, Accounting cannot be considered a monolithic tool to interpret the information. From a constitutive perspective, there are the languages that provide for the social construction of reality. With a view to the systematic integration of social practices, the function of Accounting is to standardize the processes among the different organizational sectors. The legitimation structure based on the window-dressing device considers Accounting as a means to reflect the organization’s expectations. Nevertheless, Accounting needs to play a neutral role to conquer the reliability of the information disclosed. The perspective of the sanction mechanisms takes into account the assessments of the interaction forms. Hence, based on the standardization of rules and routines, Accounting can promote the processes of approval, or not, of organizational conducts. In the conception of the domination structure, the authoritative or allocative resources promote the exercise of power. Thus, Accounting can expand its activity sphere and, consequently, participate directly in organizational power disputes. Finally, the ideological mechanism is discussed that considers Accounting as a mechanism that can facilitate the understanding of the structural contradictions of society. Therefore, the accountants need to be agents of changes in the social transformation processes.

  11. Histidine-lysine peptides as carriers of nucleic acids.

    Science.gov (United States)

    Leng, Qixin; Goldgeier, Lisa; Zhu, Jingsong; Cambell, Patricia; Ambulos, Nicholas; Mixson, A James

    2007-03-01

    With their biodegradability and diversity of permutations, peptides have significant potential as carriers of nucleic acids. This review will focus on the sequence and branching patterns of peptide carriers composed primarily of histidines and lysines. While lysines within peptides are important for binding to the negatively charged phosphates, histidines are critical for endosomal lysis enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by either covalent or ionic bonds with liposomes augment transfection compared to liposome carriers alone. More recently, we have examined peptides as sole carriers of nucleic acids because of their intrinsic advantages compared to the bipartite HK/liposome carriers. With a protocol change and addition of a histidine-rich tail, HK peptides as sole carriers were more effective than liposomes alone in several cell lines. While four-branched polymers with a primary repeating sequence pattern of -HHK- were more effective as carriers of plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers in complex with plasmids encoding antiangiogenic proteins significantly decreased tumor growth. Furthermore, modification of HK polymers with polyethylene glycol and vascular-specific ligands increased specificity of the polyplex to the tumor by more than 40-fold. Together with further development and insight on the structure of HK polyplexes, HK peptides may prove to be useful as carriers of different forms of nucleic acids both in vitro and in vivo.

  12. Role of Reversible Histidine Coordination in Hydroxylamine Reduction by Plant Hemoglobins (Phytoglobins).

    Science.gov (United States)

    Athwal, Navjot Singh; Alagurajan, Jagannathan; Andreotti, Amy H; Hargrove, Mark S

    2016-10-18

    Reduction of hydroxylamine to ammonium by phytoglobin, a plant hexacoordinate hemoglobin, is much faster than that of other hexacoordinate hemoglobins or pentacoordinate hemoglobins such as myoglobin, leghemoglobin, and red blood cell hemoglobin. The reason for differences in reactivity is not known but could be intermolecular electron transfer between protein molecules in support of the required two-electron reduction, hydroxylamine binding, or active site architecture favoring the reaction. Experiments were conducted with phytoglobins from rice, tomato, and soybean along with human neuroglobin and soybean leghemoglobin that reveal hydroxylamine binding as the rate-limiting step. For hexacoordinate hemoglobins, binding is limited by the dissociation rate constant for the distal histidine, while leghemoglobin is limited by an intrinsically low affinity for hydroxylamine. When the distal histidine is removed from rice phytoglobin, a hydroxylamine-bound intermediate is formed and the reaction rate is diminished, indicating that the distal histidine imidazole side chain is critical for the reaction, albeit not for electron transfer but rather for direct interaction with the substrate. Together, these results demonstrate that phytoglobins are superior at hydroxylamine reduction because they have distal histidine coordination affinity constants near 1, and facile rate constants for binding and dissociation of the histidine side chain. Hexacoordinate hemoglobins such as neuroglobin are limited by tighter histidine coordination that blocks hydroxylamine binding, and pentacoordinate hemoglobins have intrinsically lower hydroxylamine affinities.

  13. The Creative Side of the Dark Triad

    Science.gov (United States)

    Kapoor, Hansika

    2015-01-01

    This study associates the subclinical dark triad (DT) of personality--narcissism, psychopathy, and Machiavellianism, and their composite--with negative creativity. An instrument developed by the author assessed the likelihood of engaging in creativity, where negative creativity was defined as an act that is original and useful to the individual.…

  14. MRI and radiographic findings in Currarino's triad

    International Nuclear Information System (INIS)

    Pfluger, T.; Czekalla, R.; Koletzko, S.; Muensterer, O.; Willemsen, U.F.; Hahn, K.

    1996-01-01

    Currarino's triad is a rare complex of a congential sacral bony abnormality, anorectal malformation and a presacral mass. Intractable constipation since birth is the leading symptom of this triad, which follows an autosomal dominant mode of heredity. We report conventional radiographic and MR findings in one family consisting of a mother and her two daughters. In all three cases, radiography revealed an abnormality of the os sacrum, the so-called scimitar sacrum. MR examination, undertaken next in our institution, was applied with T1-, T2- and proton density weighted sequences in all three orientations before and after i.v. application of gadolinium diethylene-triamine-pentaacetic acid (Gd-DTPA). In two patients we were able to diagnose the complete form of the triad and in one patient an incomplete form. In any case of a radiographically diagnosed scimitar sacrum in combination with constipation. Currarino's triad should be considered. MRI, as the method of choice, should be the next step to detect a presacral mass and any anomalies of the spinal canal. The importance of early recognition lies in the high morbidity and mortality rates resulting from this disorder. (orig.)

  15. Generation of a Proton Motive Force by Histidine Decarboxylation and Electrogenic Histidine/Histamine Antiport in Lactobacillus buchneri

    OpenAIRE

    Molenaar, Douwe; Bosscher, Jaap S.; Brink, Bart ten; Driessen, Arnold J.M.; Konings, Wil N.

    1993-01-01

    Lactobacillus buchneri ST2A vigorously decarboxylates histidine to the biogenic amine histamine, which is excreted into the medium. Cells grown in the presence of histidine generate both a transmembrane pH gradient, inside alkaline, and an electrical potential (delta psi), inside negative, upon addition of histidine. Studies of the mechanism of histidine uptake and histamine excretion in membrane vesicles and proteoliposomes devoid of cytosolic histidine decarboxylase activity demonstrate tha...

  16. Histidine-rich glycoprotein protects from systemic Candida infection.

    Directory of Open Access Journals (Sweden)

    Victoria Rydengård

    2008-08-01

    Full Text Available Fungi, such as Candida spp., are commonly found on the skin and at mucosal surfaces. Yet, they rarely cause invasive infections in immunocompetent individuals, an observation reflecting the ability of our innate immune system to control potentially invasive microbes found at biological boundaries. Antimicrobial proteins and peptides are becoming increasingly recognized as important effectors of innate immunity. This is illustrated further by the present investigation, demonstrating a novel antifungal role of histidine-rich glycoprotein (HRG, an abundant and multimodular plasma protein. HRG bound to Candida cells, and induced breaks in the cell walls of the organisms. Correspondingly, HRG preferentially lysed ergosterol-containing liposomes but not cholesterol-containing ones, indicating a specificity for fungal versus other types of eukaryotic membranes. Both antifungal and membrane-rupturing activities of HRG were enhanced at low pH, and mapped to the histidine-rich region of the protein. Ex vivo, HRG-containing plasma as well as fibrin clots exerted antifungal effects. In vivo, Hrg(-/- mice were susceptible to infection by C. albicans, in contrast to wild-type mice, which were highly resistant to infection. The results demonstrate a key and previously unknown antifungal role of HRG in innate immunity.

  17. The structure and dynamic properties of the complete histidine phosphotransfer domain of the chemotaxis specific histidine autokinase CheA from Thermotoga maritima

    International Nuclear Information System (INIS)

    Vu, Anh; Hamel, Damon J.; Zhou Hongjun; Dahlquist, Frederick W.

    2011-01-01

    The bacterial histidine autokinase CheA contains a histidine phosphotransfer (Hpt) domain that accepts a phosphate from the catalytic domain and donates the phosphate to either target response regulator protein, CheY or CheB. The Hpt domain forms a helix-bundle structure with a conserved four-helix bundle motif and a variable fifth helix. Observation of two nearly equally populated conformations in the crystal structure of a Hpt domain fragment of CheA from Thermotoga maritima containing only the first four helices suggests more mobility in a tightly packed helix bundle structure than previously thought. In order to examine how the structures of Hpt domain homologs may differ from each other particularly in the conformation of the last helix, and whether an alternative conformation exists in the intact Hpt domain in solution, we have solved a high-resolution, solution structure of the CheA Hpt from T. maritima and characterized the backbone dynamics of this protein. The structure contains a four-helix bundle characteristic of histidine phosphotransfer domains. The position and orientation of the fifth helix resembles those in known Hpt domain crystal and solution structures in other histidine kinases. The alternative conformation that was reported in the crystal structure of the CheA Hpt from T. maritima missing the fifth helix is not detected in the solution structure, suggesting a role for the fifth helix in providing stabilizing forces to the overall structure.

  18. [Ionization energies and infrared spectra studies of histidine using density functional theory].

    Science.gov (United States)

    Hu, Qiong; Wang, Guo-Ying; Liu, Gang; Ou, Jia-Ming; Wang, Rui-Li

    2010-05-01

    Histidines provide axial ligands to the primary electron donors in photosynthetic reaction centers (RCs) and play an important role in the protein environments of these donors. In this paper the authors present a systematic study of ionization energies and vibrational properties of histidine using hybrid density functional theory (DFT). All calculations were undertaken by using B3LYP method in combination with four basis sets: 6-31G(d), 6-31G(df, p), 6-31+G(d) and 6-311+G(2d, 2p) with the aim to investigate how the basis sets influence the calculation results. To investigate solvent effects and gain a detailed understanding of marker bands of histidine, the ionization energies of histidine and the vibrational frequencies of histidine which are unlabeled and 13C, 15N, and 2H labeled in the gas phase, CCl4, protein environment, THF and water solution, which span a wide range of dielectric constant, were also calculated. Our results showed that: (1) The main geometry parameters of histidine were impacted by basis sets and mediums, and C2-N3 and N3-C4 bond of imidazole ring of histidine side chain display the maximum bond lengths in the gas phase; (2) single point energies and frequencies calculated were decreased while ionization energies increased with the increasing level of basis sets and diffuse function applied in the same solvent; (3) with the same computational method, the higher the dielectric constant of the solvent used, the lower the ionization energy and vibrational frequency and the higher the intensity obtained. In addition, calculated ionization energy in the gas phase and marker bands of histidine as well as frequency shift upon 13C and 15N labeling at the computationally more expensive 6-311+G(2d, 2p) level are in good agreement with experimental observations available in literatures. All calculations indicated that the results calculated by using higher level basis set with diffuse function were more accurate and closer to the experimental value. In

  19. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

    Science.gov (United States)

    Hernández-Sánchez, Itzell E.; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P.; Jiménez-Bremont, Juan F.

    2015-01-01

    The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization. PMID:26442018

  20. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

    Directory of Open Access Journals (Sweden)

    Itzell Euridice Hernández-Sánchez

    2015-09-01

    Full Text Available The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine rich motif is proposed as a targeting element for OpsDHN1 nuclear localization.

  1. Capture and separation of l-histidine through optimized zinc-decorated magnetic silica spheres.

    Science.gov (United States)

    Cardoso, Vanessa F; Sebastián, Víctor; Silva, Carlos J R; Botelho, Gabriela; Lanceros-Méndez, Senentxu

    2017-09-01

    Zinc-decorated magnetic silica spheres were developed, optimized and tested for the capture and separation of l-histidine. The magnetic silica spheres were prepared using a simple sol-gel method and show excellent magnetic characteristics, adsorption capacity toward metal ions, and stability in aqueous solution in a wide pH range. The binding capacity of zinc-decorated magnetic silica spheres to histidine proved to be strongly influenced by the morphology, composition and concentration of metal at the surface of the magnetic silica spheres and therefore these parameters should be carefully controlled in order to maximize the performance for protein purification purposes. Optimized zinc-decorated magnetic silica spheres demonstrate a binding capacity to l-histidine of approximately 44mgg -1 at the optimum binding pH buffer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Feeding filaggrin: effects of L-histidine supplementation in atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Tan SP

    2017-10-01

    Full Text Available Siao Pei Tan,1,2 Simon B Brown,1,2 Christopher EM Griffiths,3 Richard B Weller,1,2 Neil K Gibbs3,4 1MRC Centre for Inflammation Research, 2Department of Dermatology, The University of Edinburgh, Edinburgh, 3Dermatology Centre, Division of Musculoskeletal and Dermatological Sciences, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, 4Curapel, Life Sciences Hub Wales, Cardiff, UK Abstract: Atopic dermatitis (AD, also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF. In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24. In vitro studies demonstrated that l-histidine significantly increased both filaggrin formation and skin barrier function (P<0.01, respectively. Data from the clinical study indicated that once daily oral l-histidine significantly reduced (P<0.003 AD disease severity by 34% (physician assessment using the SCORingAD tool and 39% (patient self-assessment using the Patient Oriented Eczema Measure tool after 4 weeks of treatment. No improvement was noted with the placebo (P>0.32. The clinical effect of oral l-histidine in AD was similar to that of mid-potency topical corticosteroids

  3. The Female Athlete Triad: A Metabolic Phenomenon

    Directory of Open Access Journals (Sweden)

    Anne B. Loucks

    2014-06-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE The Female Athlete Triad (Triad is a syndrome in which low energy availability triggers a broad range of endocrine mechanisms that conserve energy expenditure, and thereby impairs reproductive and skeletal health.  Energy availability is the amount of dietary energy remaining after exercise training for all other physiological functions each day.  The specific kind of reproductive dysfunctions caused by low energy availability are functional hypothalamic menstrual disorders.  To ensure that affected athletes receive appropriate care, endocrine tests are required to diagnose these disorders by the exclusion of other types of menstrual disorders unrelated to the Triad.  In addition, low energy availability impairs skeletal health by uncoupling bone turnover, in which the rate of bone resorption increases while the rate of bone formation declines.  The result is a progressive loss or failure to accrue bone mass, which increases the risks of stress fractures and osteoporosis.  Low energy availability originates in one or more of three sources:  restrictive eating disorders, especially anorexia nervosa; intentional efforts to lose body weight or body fat to improve athletic performance or appearance; and the inadvertent suppression of appetite by exercise and diets containing a high percentage of carbohydrates.  It is necessary to know the origin of low energy availability in a particular athlete in order to intervene effectively with her.  The key behavior modification for preventing and treating the Triad is to increase energy availability, either by increasing dietary energy intake, reducing exercise energy expenditure, or both.  Guidelines for doing so are provided. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5

  4. Histidine Metabolism and IGPD Play a Key Role in Cefquinome Inhibiting Biofilm Formation of Staphylococcus xylosus

    Directory of Open Access Journals (Sweden)

    Yong-hui Zhou

    2018-04-01

    Full Text Available Staphylococcus xylosus (S. xylosus is an AT-rich and coagulase-negative Staphylococcus (CNS. It is normally regarded as non-pathogenic, however, recent studies have demonstrated that it is related to human opportunistic infections and bovine mastitis. In addition, S. xylosus strains have the ability to form biofilm. Biofilms are also involved in chronic infections and antibiotic resistance, there are only a few reports about cefquinome inhibiting S. xylosus biofilm formation and the protein targets of cefquinome. In our study, we found that sub-MICs of cefquinome were sufficient to inhibit biofilm formation. To investigate the potential protein targets of cefquinome, we used iTRAQ for the analyses of cells at two different conditions: 1/2-MIC (0.125 μg/mL cefquinome treatment and no treatment. Using iTRAQ technique and KEGG database analysis, we found that proteins differently expression in histidine metabolism pathway may play a role in the process by which 1/2-MIC (0.125 μg/mL cefquinome inhibits S. xylosus biofilm formation. Interestingly, we found a sharply down-regulated enzyme [A0A068E9J3 imidazoleglycerol-phosphate dehydratase (IGPD] involved in histidine metabolism pathway in cefquinome-treated cells. We demonstrated the important role of IGPD in sub-MICs cefquinome inhibiting biofilm formation of S. xylosus by gene (hisB knockout, IGPD enzyme activity and histidine content assays. Thus, our data sheds light on important role of histidine metabolism in S. xylosus biofilm formation; especially, IGPD involved in histidine metabolism might play a crucial role in sub-MICs cefquinome inhibition of biofilm formation of S. xylosus, and we propose IGPD as an attractive protein target of cefquinome.

  5. Dark Triad of Croatian Management Students

    Directory of Open Access Journals (Sweden)

    Mario Bogdanovic

    2015-12-01

    Full Text Available This paper researches the so-called “dark triad” personality traits of management student populations, because of their potential to generate dysfunctional organizational behavior and processes. Namely, the dark triad with characteristics such as lack of empathy, willingness to manipulate others (for self-betterment, antagonism, and belief in one’s own superiority can represent a real organizational threat. The goal of this paper is to stimulate thinking and discussion around this issue. The paper is based on questionnaire measurement that adopts the standardized short dark triad measurement instrument of Jones and Paulhus (2012 who measure the scales of Machiavellianism (9 items, narcissism (9 items and psychopathy (9 items. The sample included 150 students of professional management studies at the Faculty of Economics, University of Split in Croatia. Results of the Croatian students are compared with the results of 387 students in Canada. The results suggest significant statistical differences in the “dark triad” variables between the Canadian and Croatian samples. The practical implications of this paper are in raising awareness and stimulating the thinking of managers around the potential of the “dark triad” traits of engaged human resources to create organizational crisis, and to make preventive and responsive actions to manage the “toxic triad” threat.

  6. The Female Athlete Triad: Disordered Eating, Amenorrhea, and Osteoporosis.

    Science.gov (United States)

    Rust, Dawnella M.

    2002-01-01

    Describes the Female Athlete Triad, an interrelated combination of disorders that can occur in girls and women who are physically active. Presents nine resources for the Female Athlete Triad. Concludes that as more young females become physically active, school personnel need to be aware of the importance of promoting healthy eating and training…

  7. The triad of Iron deficiency anemia, hepatosplenomegaly and ...

    African Journals Online (AJOL)

    A triad of iron deficiency anemia, hepatosplenomegaly and growth retardation occurring in tandem with zinc deficiency has been reported in the past as components of either Prasad's syndrome or hypopituitarism. There are no documented cases of such triad occurring in the presence of normal serum zinc levels. We report ...

  8. Ubiquitylation of an internalized killer cell Ig-like receptor by Triad3A disrupts sustained NF-κB signaling.

    Science.gov (United States)

    Miah, S M Shahjahan; Purdy, Amanda K; Rodin, Nicholas B; MacFarlane, Alexander W; Oshinsky, Jennifer; Alvarez-Arias, Diana A; Campbell, Kerry S

    2011-03-01

    Killer cell Ig-like receptor (KIR) with two Ig-like domains and a long cytoplasmic domain 4 (2DL4; CD158d) is a unique KIR expressed on human NK cells, which stimulates cytokine production, but mechanisms regulating its expression and function are poorly understood. By yeast two-hybrid screening, we identified the E3 ubiquitin ligase, Triad3A, as an interaction partner for the 2DL4 cytoplasmic domain. The protein interaction was confirmed in vivo, and Triad3A expression induced polyubiquitylation and degradation of 2DL4. Overexpression of Triad3A selectively abrogated the cytokine-producing function of 2DL4, whereas Triad3A short hairpin RNA reversed ubiquitylation and restored cytokine production. Expression of Triad3A in an NK cell line did not affect receptor surface expression, internalization, or early signaling, but significantly reduced receptor turnover and suppressed sustained NF-κB activation. 2DL4 endocytosis was found to be vital to stimulate cytokine production, and Triad3A expression diminished localization of internalized receptor in early endosomes. Our results reveal a critical role for endocytosed 2DL4 receptor to generate sustained NF-κB signaling and drive cytokine production. We conclude that Triad3A is a key negative regulator of sustained 2DL4-mediated NF-κB signaling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes.

  9. Relationships of Dietary Histidine and Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study.

    Science.gov (United States)

    Li, Yan-Chuan; Li, Chun-Long; Qi, Jia-Yue; Huang, Li-Na; Shi, Dan; Du, Shan-Shan; Liu, Li-Yan; Feng, Ren-Nan; Sun, Chang-Hao

    2016-07-11

    Our previous studies have demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women and high-fat diet-induced obese rats. However, the effects of dietary histidine on general population are not known. The objective of this Internet-based cross-sectional study was to evaluate the associations between dietary histidine and prevalence of overweight/obesity and abdominal obesity in northern Chinese population. A total of 2376 participants were randomly recruited and asked to finish our Internet-based dietary questionnaire for the Chinese (IDQC). Afterwards, 88 overweight/obese participants were randomly selected to explore the possible mechanism. Compared with healthy controls, dietary histidine was significantly lower in overweight (p obese (p Dietary histidine was inversely associated with body mass index (BMI), waist circumference (WC) and blood pressure in overall population and stronger associations were observed in women and overweight/obese participants. Higher dietary histidine was associated with lower prevalence of overweight/obesity and abdominal obesity, especially in women. Further studies indicated that higher dietary histidine was associated with lower fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), 2-h postprandial glucose (2 h-PG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP), malonaldehyde (MDA) and vaspin and higher glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and adiponectin of overweight/obese individuals of both sexes. In conclusion, higher dietary histidine is inversely associated with energy intake, status of insulin resistance, inflammation and oxidative stress in overweight/obese participants and lower prevalence of overweight/obesity in northern Chinese adults.

  10. Relationships of Dietary Histidine and Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Yan-Chuan Li

    2016-07-01

    Full Text Available Our previous studies have demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women and high-fat diet-induced obese rats. However, the effects of dietary histidine on general population are not known. The objective of this Internet-based cross-sectional study was to evaluate the associations between dietary histidine and prevalence of overweight/obesity and abdominal obesity in northern Chinese population. A total of 2376 participants were randomly recruited and asked to finish our Internet-based dietary questionnaire for the Chinese (IDQC. Afterwards, 88 overweight/obese participants were randomly selected to explore the possible mechanism. Compared with healthy controls, dietary histidine was significantly lower in overweight (p < 0.05 and obese (p < 0.01 participants of both sexes. Dietary histidine was inversely associated with body mass index (BMI, waist circumference (WC and blood pressure in overall population and stronger associations were observed in women and overweight/obese participants. Higher dietary histidine was associated with lower prevalence of overweight/obesity and abdominal obesity, especially in women. Further studies indicated that higher dietary histidine was associated with lower fasting blood glucose (FBG, homeostasis model assessment of insulin resistance (HOMA-IR, 2-h postprandial glucose (2 h-PG, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, C-reactive protein (CRP, malonaldehyde (MDA and vaspin and higher glutathione peroxidase (GSH-Px, superoxide dismutase (SOD and adiponectin of overweight/obese individuals of both sexes. In conclusion, higher dietary histidine is inversely associated with energy intake, status of insulin resistance, inflammation and oxidative stress in overweight/obese participants and lower prevalence of overweight/obesity in northern Chinese adults.

  11. Generation of a proton motive force by histidine decarboxylation and electrogenic histidine/histamine antiport in Lactobacillus buchneri.

    Science.gov (United States)

    Molenaar, D; Bosscher, J S; ten Brink, B; Driessen, A J; Konings, W N

    1993-05-01

    Lactobacillus buchneri ST2A vigorously decarboxylates histidine to the biogenic amine histamine, which is excreted into the medium. Cells grown in the presence of histidine generate both a transmembrane pH gradient, inside alkaline, and an electrical potential (delta psi), inside negative, upon addition of histidine. Studies of the mechanism of histidine uptake and histamine excretion in membrane vesicles and proteoliposomes devoid of cytosolic histidine decarboxylase activity demonstrate that histidine uptake, histamine efflux, and histidine/histamine exchange are electrogenic processes. Histidine/histamine exchange is much faster than the unidirectional fluxes of these substrates, is inhibited by an inside-negative delta psi and is stimulated by an inside positive delta psi. These data suggest that the generation of metabolic energy from histidine decarboxylation results from an electrogenic histidine/histamine exchange and indirect proton extrusion due to the combined action of the decarboxylase and carrier-mediated exchange. The abundance of amino acid decarboxylation reactions among bacteria suggests that this mechanism of metabolic energy generation and/or pH regulation is widespread.

  12. l-Histidine Decarboxylase and Tourette's Syndrome

    Science.gov (United States)

    Ercan-Sencicek, A. Gulhan; Stillman, Althea A.; Ghosh, Ananda K.; Bilguvar, Kaya; O'Roak, Brian J.; Mason, Christopher E.; Abbott, Thomas; Gupta, Abha; King, Robert A.; Pauls, David L.; Tischfield, Jay A.; Heiman, Gary A.; Singer, Harvey S.; Gilbert, Donald L.; Hoekstra, Pieter J.; Morgan, Thomas M.; Loring, Erin; Yasuno, Katsuhito; Fernandez, Thomas; Sanders, Stephan; Louvi, Angeliki; Cho, Judy H.; Mane, Shrikant; Colangelo, Christopher M.; Biederer, Thomas; Lifton, Richard P.; Gunel, Murat; State, Matthew W.

    2010-01-01

    Summary Tourette's syndrome is a common developmental neuropsychiatric disorder characterized by chronic motor and vocal tics. Despite a strong genetic contribution, inheritance is complex, and risk alleles have proven difficult to identify. Here, we describe an analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding l-histidine decarboxylase, the rate-limiting enzyme in histamine biosynthesis. Our findings, together with previously published data from model systems, point to a role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics. PMID:20445167

  13. Anorexia, bulimia, and the female athlete triad: evaluation and management.

    Science.gov (United States)

    Mendelsohn, Felicia A; Warren, Michelle P

    2010-03-01

    The female athlete triad is an increasingly prevalent condition involving disordered eating, amenorrhea, and osteoporosis. An athlete can suffer from all 3 components of the triad, or just 1 or 2 of the individual conditions. The main element underlying all the aspects of the triad is an adaptation to a negative caloric balance. Screening for these disorders should be an important component of an athlete's care. Prevention and treatment should involve a team approach, including a physician, a nutritionist, and a mental health provider. Copyright 2010 Elsevier Inc. All rights reserved.

  14. The Female Athlete Triad: Prevalence in Military Women

    National Research Council Canada - National Science Library

    Lauder, Tamara

    1997-01-01

    The female athlete triad, otherwise known as the inter-relatedness of disordered eating, amenorrhea, and osteoporosis, is an area of increasing awareness in female athletes, which has not been explored in military women...

  15. The triad of Iron deficiency anemia, hepatosplenomegaly and ...

    African Journals Online (AJOL)

    2014-12-04

    Dec 4, 2014 ... In conclusion, iron deficiency anemia occurring in the triad without zinc deficiency as .... a negative zinc balance and mask existing zinc deficiency.[10] ... erythropoiesis‑stimulating agents in men with chronic kidney disease.

  16. Currarino triad associated with malrotation of the colon

    International Nuclear Information System (INIS)

    Daoud, Fajez S.; AbuRub, Mohammad A.; Hadidy, Azmy M.

    2007-01-01

    Currarino triad is a rare congenital condition characterized by a sacral bony defect, presacral mass, and anorectal malformations. We describe an unusual case of complete Currarino triad in a 22-year-old female with sacral bony defect, anal stenosis, recto-vaginal fistula, and dual pathology meningocele and teratoma in the pre sacral mass associated with malrotation of the colon. This combination has not been reported previously. The clinical presentation, surgical management and review of literature are discussed. (author)

  17. Currarino triad associated with malrotation of the colon

    Energy Technology Data Exchange (ETDEWEB)

    Daoud, Fajez S [Dept. of General Surgery, Jordan University Hospital, Amman (Jordan); AbuRub, Mohammad A [Dept. of Neurosurgery, Jordan University Hospital, Amman (Jordan); Hadidy, Azmy M [Dept. of Radiology (Hadidy), Jordan University Hospital, Amman (Jordan)

    2007-07-01

    Currarino triad is a rare congenital condition characterized by a sacral bony defect, presacral mass, and anorectal malformations. We describe an unusual case of complete Currarino triad in a 22-year-old female with sacral bony defect, anal stenosis, recto-vaginal fistula, and dual pathology meningocele and teratoma in the pre sacral mass associated with malrotation of the colon. This combination has not been reported previously. The clinical presentation, surgical management and review of literature are discussed. (author)

  18. Strong contributions from vertical triads to helix-partner preferences in parallel coiled coils.

    Science.gov (United States)

    Steinkruger, Jay D; Bartlett, Gail J; Woolfson, Derek N; Gellman, Samuel H

    2012-09-26

    Pairing preferences in heterodimeric coiled coils are determined by complementarities among side chains that pack against one another at the helix-helix interface. However, relationships between dimer stability and interfacial residue identity are not fully understood. In the context of the "knobs-into-holes" (KIH) packing pattern, one can identify two classes of interactions between side chains from different helices: "lateral", in which a line connecting the adjacent side chains is perpendicular to the helix axes, and "vertical", in which the connecting line is parallel to the helix axes. We have previously analyzed vertical interactions in antiparallel coiled coils and found that one type of triad constellation (a'-a-a') exerts a strong effect on pairing preferences, while the other type of triad (d'-d-d') has relatively little impact on pairing tendencies. Here, we ask whether vertical interactions (d'-a-d') influence pairing in parallel coiled-coil dimers. Our results indicate that vertical interactions can exert a substantial impact on pairing specificity, and that the influence of the d'-a-d' triad depends on the lateral a' contact within the local KIH motif. Structure-informed bioinformatic analyses of protein sequences reveal trends consistent with the thermodynamic data derived from our experimental model system in suggesting that heterotriads involving Leu and Ile are preferred over homotriads involving Leu and Ile.

  19. IRT analyses of the Swedish Dark Triad Dirty Dozen

    Directory of Open Access Journals (Sweden)

    Danilo Garcia

    2018-03-01

    Full Text Available Background: The Dark Triad (i.e., Machiavellianism, narcissism, and psychopathy can be captured quickly with 12 items using the Dark Triad Dirty Dozen (Jonason and Webster, 2010. Previous Item Response Theory (IRT analyses of the original English Dark Triad Dirty Dozen have shown that all three subscales adequately tap into the dark domains of personality. The aim of the present study was to analyze the Swedish version of the Dark Triad Dirty Dozen using IRT. Method: 570 individuals (nmales = 326, nfemales = 242, and 2 unreported, including university students and white-collar workers with an age range between 19 and 65 years, responded to the Swedish version of the Dark Triad Dirty Dozen (Garcia et al., 2017a,b. Results: Contrary to previous research, we found that the narcissism scale provided most information, followed by psychopathy, and finally Machiavellianism. Moreover, the psychopathy scale required a higher level of the latent trait for endorsement of its items than the narcissism and Machiavellianism scales. Overall, all items provided reasonable amounts of information and are thus effective for discriminating between individuals. The mean item discriminations (alphas were 1.92 for Machiavellianism, 2.31 for narcissism, and 1.99 for psychopathy. Conclusion: This is the first study to provide IRT analyses of the Swedish version of the Dark Triad Dirty Dozen. Our findings add to a growing literature on the Dark Triad Dirty Dozen scale in different cultures and highlight psychometric characteristics, which can be used for comparative studies. Items tapping into psychopathy showed higher thresholds for endorsement than the other two scales. Importantly, the narcissism scale seems to provide more information about a lack of narcissism, perhaps mirroring cultural conditions. Keywords: Psychology, Psychiatry, Clinical psychology

  20. Characterization of mu s-ms dynamics of proteins using a combined analysis of N-15 NMR relaxation and chemical shift: Conformational exchange in plastocyanin induced by histidine protonations

    DEFF Research Database (Denmark)

    Hass, M. A. S.; Thuesen, Marianne Hallberg; Christensen, Hans Erik Mølager

    2004-01-01

    of the exchanging species can be determined independently of the relaxation rates. The applicability of the approach is demonstrated by a detailed analysis of the conformational exchange processes previously observed in the reduced form of the blue copper protein, plastocyanin from the cyanobacteria Anabaena......An approach is presented that allows a detailed, quantitative characterization of conformational exchange processes in proteins on the mus-ms time scale. The approach relies on a combined analysis of NMR relaxation rates and chemical shift changes and requires that the chemical shift...... quantitatively by the correlation between the R-ex terms and the corresponding chemical shift differences of the exchanging species. By this approach, the R-ex terms of N-15 nuclei belonging to contiguous regions in the protein could be assigned to the same exchange process. Furthermore, the analysis...

  1. The currarino triad of anorectal, sacral, and presacral anomalies

    International Nuclear Information System (INIS)

    Kim, Jong Chul; Yeon, Kyung Mo

    1986-01-01

    The Currarino triad is a unique complex of congenital anomalies including anorectal including anorectal malformation, scral bony abnormality, and presacral mass. The usual symptomatology is constipation due to anorectal stenosis. Three patients with this triad confirmed by surgical operation during recent two years in Seoul National University Children's Hospital were presented with a brief review of clinical features, unique radiologic appearance and postulated pathophysiology. The presacral mass was a mature teratoma in the first patient, a lipomyelomeningocele-epidermoid inclusion cyst in the second patients, and myelomeningocele in the third patient. A correct diagnosis of the Currarino triad by radiologists is important, and may help the physicians to investigate detailed family history and associated anomalies and to establish adequate surgical plans.

  2. Borchardt Triade: A Symptom of Acute Gastric Volvulus

    Directory of Open Access Journals (Sweden)

    Salim Bilici

    2013-10-01

    Full Text Available Gastric volvulus, especially cases with an acute onset, may result in strangulation, perforation, peritonitis, shock and death. The disease is rarely seen in children, but early diagnosis and treatment is essential due to its life-threatening potential. In patients with acute gastric volvulus, the clinical Borchardt triade may be observed, which is characterized by acute severe pain and distension in the upper abdomen or lower thoracic region, retching and the inability to pass a nasogastric tube. In this article, We  aimed to emphasize the Borchardt’s triad by presenting a pediatric case who was diagnosed with Borchardt’s triad and who had acute mesenteric axial gastric volvulus which diaphragmatic hernia and mobile (wandering spleen were accompanied.

  3. Potassium sensing histidine kinase in Bacillus subtilis.

    Science.gov (United States)

    López, Daniel; Gontang, Erin A; Kolter, Roberto

    2010-01-01

    The soil-dwelling organism Bacillus subtilis is able to form multicellular aggregates known as biofilms. It was recently reported that the process of biofilm formation is activated in response to the presence of various, structurally diverse small-molecule natural products. All of these small-molecule natural products made pores in the membrane of the bacterium, causing the leakage of potassium cations from the cytoplasm of the cell. The potassium cation leakage was sensed by the membrane histidine kinase KinC, triggering the genetic pathway to the production of the extracellular matrix that holds cells within the biofilm. This chapter presents the methodology used to characterize the leakage of cytoplasmic potassium as the signal that induces biofilm formation in B. subtilis via activation of KinC. Development of novel techniques to monitor activation of gene expression in microbial populations led us to discover the differentiation of a subpopulation of cells specialized to produce the matrix that holds all cells together within the biofilm. This phenomenon of cell differentiation was previously missed by conventional techniques used to monitor transcriptional gene expression. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. 78 FR 70561 - Patient Safety Organizations: Delisting for Cause for Leadership Triad

    Science.gov (United States)

    2013-11-26

    ... Organizations: Delisting for Cause for Leadership Triad AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Notice of delisting. SUMMARY: AHRQ has delisted Leadership Triad due to its failure to...)(C), Leadership Triad stated that it did not meet the requirement that, within 24 months of initial...

  5. Complex vector triads in spinor theory in Minkowski space

    International Nuclear Information System (INIS)

    Zhelnorovich, V.A.

    1990-01-01

    It is shown that tensor equations corresponding to the spinor Dirac equations represent a three-dimensional part of four-dimensional vector equations. The equations are formulated in an evidently invariant form in antisymmetric tensor components and in the corresponding components of a complex vector triad. A complete system of relativistically invariant tensor equations is ascertained

  6. Resilience: Enhancing Well-Being through the Positive Cognitive Triad

    Science.gov (United States)

    Mak, Winnie W. S.; Ng, Ivy S. W.; Wong, Celia C. Y.

    2011-01-01

    The present study tested whether the relationships among resilience, life satisfaction, and depression could be explained by positive views toward the self, the world, and the future (positive cognitive triad). Structural equation modeling and mediation analyses were conducted based on 1,419 college students in Hong Kong. The model of positive…

  7. Dark triad traits and health outcomes: An exploratory study

    Directory of Open Access Journals (Sweden)

    Jasna Hudek-Knežević

    2016-04-01

    Full Text Available On the sample of 637 participants (358 women and 279 men we explored the relationshipbetween Dark Triad traits (psychopathy, Machiavellianism and Narcissism and various healthindicators including subjective (positive and negative mood and perceived physical symptoms,protective health behaviors as well as some more objective health indicators (number ofhospitalizations, number of diseases, having specific chronic diseases, injuries and addictions.Because of the moderate relations between Dark Triad and broad personality traits that also exerttheir influence on various health-related indices, we examined the unique effects of Dark Triad traitson health indicators above and beyond five-factor personality traits as well as sociodemographicvariables related to health (gender, age and education.When sociodemographic variables, as well as five-factor personality traits were controlled inhierarchical regression analyses, Dark Triad traits significantly improved the prediction of almostall subjective health indicators, protective health behaviors, number of hospitalizations and numberof diseases. The effect sizes obtained were relatively low, and psychopathy was the most consistentpredictor.Regarding chronic diseases, injuries and addictions, the results of hierarchical binary logisticregressions showed that when sociodemographic variables were controlled, psychopathy was apositive predictor of the risk of digestive diseases, tobacco use and injuries, Machiavellianismnegatively predicted the risk of injuries, while Narcissism negatively predicted the risk of skindiseases and tobacco use. When five-factor personality traits were controlled, psychopathy was alsoa positive predictor of digestive diseases, tobacco use and injuries. Machiavellianism was a positivepredictor of high blood pressure, and negative predictor of cancer, spine and back diseases andinjuries, while Narcissism was a negative predictor of skin diseases.The results obtained are discussed

  8. Integumentary L-histidine transport in a euryhaline polychaete worm: regulatory roles of calcium and cadmium in the transport event.

    Science.gov (United States)

    Ahearn, H R; Ahearn, G A; Gomme, J

    2000-09-01

    Integumentary uptake of L-[(3)H]histidine by polychaete worms (Nereis succinea) from estuarine waters of Oahu, Hawaii was measured in the presence and absence of calcium and cadmium using a physiological saline that approximated the ion composition of 60 % sea water. In this medium 1 micromol L(-1) cadmium significantly increased (Psystem carrier protein that is regulated by the external divalent cations calcium and cadmium.

  9. The IOC consensus statement: beyond the Female Athlete Triad--Relative Energy Deficiency in Sport (RED-S).

    Science.gov (United States)

    Mountjoy, Margo; Sundgot-Borgen, Jorunn; Burke, Louise; Carter, Susan; Constantini, Naama; Lebrun, Constance; Meyer, Nanna; Sherman, Roberta; Steffen, Kathrin; Budgett, Richard; Ljungqvist, Arne

    2014-04-01

    Protecting the health of the athlete is a goal of the International Olympic Committee (IOC). The IOC convened an expert panel to update the 2005 IOC Consensus Statement on the Female Athlete Triad. This Consensus Statement replaces the previous and provides guidelines to guide risk assessment, treatment and return-to-play decisions. The IOC expert working group introduces a broader, more comprehensive term for the condition previously known as 'Female Athlete Triad'. The term 'Relative Energy Deficiency in Sport' (RED-S), points to the complexity involved and the fact that male athletes are also affected. The syndrome of RED-S refers to impaired physiological function including, but not limited to, metabolic rate, menstrual function, bone health, immunity, protein synthesis, cardiovascular health caused by relative energy deficiency. The cause of this syndrome is energy deficiency relative to the balance between dietary energy intake and energy expenditure required for health and activities of daily living, growth and sporting activities. Psychological consequences can either precede RED-S or be the result of RED-S. The clinical phenomenon is not a 'triad' of the three entities of energy availability, menstrual function and bone health, but rather a syndrome that affects many aspects of physiological function, health and athletic performance. This Consensus Statement also recommends practical clinical models for the management of affected athletes. The 'Sport Risk Assessment and Return to Play Model' categorises the syndrome into three groups and translates these classifications into clinical recommendations.

  10. L-histidine enhances learning in stressed zebrafish

    Directory of Open Access Journals (Sweden)

    L.P.V. Cofiel

    2009-01-01

    Full Text Available The aim of the present study was to determine the effect of the histaminergic precursor L-histidine and the H3 receptor antagonist thioperamide on the learning process of zebrafish submitted or not to confinement stress. On each of the 5 consecutive days of experiment (D1, D2, D3, D4, D5, animals had to associate an interruption of the aquarium air supply with food offering. Non-stressed zebrafish received an intraperitoneal injection of 100 mg/kg L-histidine, 10 mg/kg thioperamide or saline after training. Stressed animals received drug treatment and then were submitted to confinement stress for 1 h before the learning procedure. Time to approach the feeder was measured (in seconds and was considered to be indicative of learning. A decrease in time to approach the feeder was observed in the saline-treated group (D1 = 141.92 ± 13.57; D3 = 55 ± 13.54, indicating learning. A delay in learning of stressed animals treated with saline was observed (D1 = 217.5 ± 25.66. L-histidine facilitated learning in stressed (D1 = 118.68 ± 13.9; D2 = 45.88 ± 8.2 and non-stressed (D1 = 151.11 ± 19.20; D5 = 62 ± 14.68 animals. Thioperamide inhibited learning in non-stressed (D1 = 110.38 ± 9.49; D4 = 58.79 ± 16.83 and stressed animals (D1 = 167.3 ± 26.39; D5 = 172.15 ± 27.35. L-histidine prevented the increase in blood glucose after one session of confinement (L-histidine = 65.88 ± 4.50; control = 53 ± 3.50 mg/dL. These results suggest that the histaminergic system enhances learning and modulates stress responses in zebrafish.

  11. Crystallization of a newly discovered histidine acid phosphatase from Francisella tularensis

    Energy Technology Data Exchange (ETDEWEB)

    Felts, Richard L. [Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211 (United States); Reilly, Thomas J. [Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri 65212 (United States); Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri 65212 (United States); Calcutt, Michael J. [Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri 65212 (United States); Tanner, John J., E-mail: tannerjj@missouri.edu [Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211 (United States); Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65211 (United States)

    2006-01-01

    A histidine acid phosphatase from the CDC Category A pathogen F. tularensis has been crystallized in space group P4{sub 1}2{sub 1}2, with unit-cell parameters a = 61.96, c = 210.78 Å. A 1.75 Å resolution data set was collected at Advanced Light Source beamline 4.2.2. Francisella tularensis is a highly infectious bacterial pathogen that is considered by the Centers for Disease Control and Prevention to be a potential bioterrorism weapon. Here, the crystallization of a 37.2 kDa phosphatase encoded by the genome of F. tularensis subsp. holarctica live vaccine strain is reported. This enzyme shares 41% amino-acid sequence identity with Legionella pneumophila major acid phosphatase and contains the RHGXRXP motif that is characteristic of the histidine acid phosphatase family. Large diffraction-quality crystals were grown in the presence of Tacsimate, HEPES and PEG 3350. The crystals belong to space group P4{sub 1}2{sub 1}2, with unit-cell parameters a = 61.96, c = 210.78 Å. The asymmetric unit is predicted to contain one protein molecule, with a solvent content of 53%. A 1.75 Å resolution native data set was recorded at beamline 4.2.2 of the Lawrence Berkeley National Laboratory Advanced Light Source. Molecular-replacement trials using the human prostatic acid phosphatase structure as the search model (28% amino-acid sequence identity) did not produce a satisfactory solution. Therefore, the structure of F. tularensis histidine acid phosphatase will be determined by multiwavelength anomalous dispersion phasing using a selenomethionyl derivative.

  12. Crystallization of a newly discovered histidine acid phosphatase from Francisella tularensis

    International Nuclear Information System (INIS)

    Felts, Richard L.; Reilly, Thomas J.; Calcutt, Michael J.; Tanner, John J.

    2005-01-01

    A histidine acid phosphatase from the CDC Category A pathogen F. tularensis has been crystallized in space group P4 1 2 1 2, with unit-cell parameters a = 61.96, c = 210.78 Å. A 1.75 Å resolution data set was collected at Advanced Light Source beamline 4.2.2. Francisella tularensis is a highly infectious bacterial pathogen that is considered by the Centers for Disease Control and Prevention to be a potential bioterrorism weapon. Here, the crystallization of a 37.2 kDa phosphatase encoded by the genome of F. tularensis subsp. holarctica live vaccine strain is reported. This enzyme shares 41% amino-acid sequence identity with Legionella pneumophila major acid phosphatase and contains the RHGXRXP motif that is characteristic of the histidine acid phosphatase family. Large diffraction-quality crystals were grown in the presence of Tacsimate, HEPES and PEG 3350. The crystals belong to space group P4 1 2 1 2, with unit-cell parameters a = 61.96, c = 210.78 Å. The asymmetric unit is predicted to contain one protein molecule, with a solvent content of 53%. A 1.75 Å resolution native data set was recorded at beamline 4.2.2 of the Lawrence Berkeley National Laboratory Advanced Light Source. Molecular-replacement trials using the human prostatic acid phosphatase structure as the search model (28% amino-acid sequence identity) did not produce a satisfactory solution. Therefore, the structure of F. tularensis histidine acid phosphatase will be determined by multiwavelength anomalous dispersion phasing using a selenomethionyl derivative

  13. Determination of Histidine pKa Values in the Propeptides of Furin and Proprotein Convertase 1/3 Using Histidine Hydrogen-Deuterium Exchange Mass Spectrometry.

    Science.gov (United States)

    Elferich, Johannes; Williamson, Danielle M; David, Larry L; Shinde, Ujwal

    2015-08-04

    Propeptides of proprotein convertases regulate activation of their protease domains by sensing the organellar pH within the secretory pathway. Earlier experimental work highlighted the importance of a conserved histidine residue within the propeptide of a widely studied member, furin. A subsequent evolutionary analysis found an increase in histidine content within propeptides of secreted eukaryotic proteases compared with their prokaryotic orthologs. However, furin activates in the trans-golgi network at a pH of 6.5 while a paralog, proprotein convertase 1/3, activates in secretory vesicles at a pH of 5.5. It is unclear how a conserved histidine can mediate activation at two different pH values. In this manuscript, we measured the pKa values of histidines within the propeptides of furin and proprotein convertase 1/3 using a histidine hydrogen-deuterium exchange mass spectrometry approach. The high density of histidine residues combined with an abundance of basic residues provided challenges for generation of peptide ions with unique histidine residues, which were overcome by employing ETD fragmentation. During this analysis, we found slow hydrogen-deuterium exchange in residues other than histidine at basic pH. Finally, we demonstrate that the pKa of the conserved histidine in proprotein convertase 1/3 is acid-shifted compared with furin and is consistent with its lower pH of activation.

  14. Exogenous addition of histidine reduces copper availability in the yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Daisuke Watanabe

    2014-07-01

    Full Text Available The basic amino acid histidine inhibited yeast cell growth more severely than lysine and arginine. Overexpression of CTR1, which encodes a high-affinity copper transporter on the plasma membrane, or addition of copper to the medium alleviated this cytotoxicity. However, the intracellular level of copper ions was not decreased in the presence of excess histidine. These results indicate that histidine cytotoxicity is associated with low copper availability inside cells, not with impaired copper uptake. Furthermore, histidine did not affect cell growth under limited respiration conditions, suggesting that histidine cytotoxicity is involved in deficiency of mitochondrial copper.

  15. Exogenous addition of histidine reduces copper availability in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Watanabe, Daisuke; Kikushima, Rie; Aitoku, Miho; Nishimura, Akira; Ohtsu, Iwao; Nasuno, Ryo; Takagi, Hiroshi

    2014-07-07

    The basic amino acid histidine inhibited yeast cell growth more severely than lysine and arginine. Overexpression of CTR1 , which encodes a high-affinity copper transporter on the plasma membrane, or addition of copper to the medium alleviated this cytotoxicity. However, the intracellular level of copper ions was not decreased in the presence of excess histidine. These results indicate that histidine cytotoxicity is associated with low copper availability inside cells, not with impaired copper uptake. Furthermore, histidine did not affect cell growth under limited respiration conditions, suggesting that histidine cytotoxicity is involved in deficiency of mitochondrial copper.

  16. Not the Sum of Its Parts: A Critical Review of the MacDonald Triad.

    Science.gov (United States)

    Parfitt, Charlotte Hannah; Alleyne, Emma

    2018-01-01

    The MacDonald triad posits that animal cruelty, fire setting, and bed wetting in childhood is indicative of later aggressive and violent behavior in adults. Researchers refer to this phenomenon as a precursor to later antisocial behaviors including serial and sexual murder; while practitioners cite the triad in clinical formulations and risk assessments. However, there is yet to be a critical review and consolidation of the literature that establishes whether there is empirical support. This article explores the validity of the triad. We conducted a narrative review of the relevant studies examining the MacDonald triad and its individual constituents. There is evidence that any one of the triad behaviors could predict future violent offending, but it is very rare to find all three behaviors together as predictors. Thus, the empirical research on the MacDonald triad does not fully substantiate its premise. Rather, it would appear that the triad, or its individual constituents, is better used as an indicator of dysfunctional home environments, or poor coping skills in children. Future research is needed with robust and rigorous methodologies (e.g., adequate control groups, longitudinal designs) to fully establish the MacDonald triad's validity. Finally, further consideration is needed as to whether the triad behaviors are more indicative of other problematic outcomes (e.g., maladaptive coping to life stressors).

  17. Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

    OpenAIRE

    Alkan , Manal; Machavoine , François; Rignault , Rachel; Dam , Julie; Dy , Michel; Thieblemont , Nathalie

    2015-01-01

    International audience; Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC −/− m...

  18. Influence of histidine on zinc transport into rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto [Shizuoka Univ. (Japan). School of Pharmaceutical Sciences

    2000-06-01

    The brain of rats injected intravenously with {sup 65}Zn-His or {sup 65}ZnCl{sub 2} was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from {sup 65}Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from {sup 65}Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of {sup 65}Zn-His in the brain was similar to that of {sup 65}ZnCl{sub 2} group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the {sup 65}Zn-His group from the blood was higher than that of the {sup 65}ZnCl{sub 2} group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

  19. Influence of histidine on zinc transport into rat brain

    International Nuclear Information System (INIS)

    Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto

    2000-01-01

    The brain of rats injected intravenously with 65 Zn-His or 65 ZnCl 2 was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from 65 Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from 65 Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of 65 Zn-His in the brain was similar to that of 65 ZnCl 2 group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the 65 Zn-His group from the blood was higher than that of the 65 ZnCl 2 group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

  20. Subgroup conflicts? Try the psychodramatic "double triad method".

    Science.gov (United States)

    Verhofstadt-Denève, Leni M F

    2012-04-01

    The present article suggests the application of a psychodramatic action method for tackling subgroup conflicts in which the direct dialogue between representatives of two opposing subgroups is prepared step by step through an indirect dialogue strategy within two triads, a strategy known as the Double Triad Method (DTM). In order to achieve integration in the group as a whole, it is important that all the members of both subgroups participate actively during the entire process. The first part of the article briefly explores the theoretical background, with a special emphasis on the Phenomenological-Dialectical Personality Model (Phe-Di PModel). In the second part, the DTM procedure is systematically described through its five action stages, each accompanied with 1) a spatial representation of the consecutive actions, 2) some illustrative statements for each stage, and 3) a theoretical interpretation of the dialectically involved personality dimensions in both protagonists. The article concludes with a discussion and suggestions for more extensive applications of the DTM method, including the question of its relationships to Agazarian's functional subgrouping, psychodrama, and sociodrama.

  1. THE INTELLIGIBLE TRIAD IN NEO-PLATONISM AND PATRISTICS

    Directory of Open Access Journals (Sweden)

    A. FOKIN

    2011-10-01

    Full Text Available The author attempts to better defi ne the concept of the so-called «intelligible Triad» (esse, vivere, intellegere in Neo-Platonism and the Fathers of the Church. In the fi rst section, he explores the origins of this doctrine in Plato’s dialogue «Sophistes» as well as in the twelfth book of Aristotle’s «Metaphysics». This idea is also apparent in the doctrine concerning the distinct levels of being and the faculties of the human soul, a concept common to various Greek philosophical schools. The larger section of the article provides a reconstruction of the basic features and the elements of this theory of the «intelligible Triad» in the Neo-Platonic philosophy of Plotinus, Porphyry, Iamblichus, Syrianus, and Proclus, as well as in the diff erent Gnostic schools. Finally, the author raises the question of how this concept was employed and transformed by the Church Fathers. This will be the topic of the section of the article to follow.

  2. Dusting off the epidemiological triad: could it work with obesity?

    Science.gov (United States)

    Egger, G; Swinburn, B; Rossner, S

    2003-05-01

    The search for effective ways of dealing with obesity has centred on biological research and clinical management. However, obesity needs to be conceptualized more broadly if the modern pandemic is to be arrested. The epidemiological triad (hosts, agent/vectors and environments) has served us well in dealing with epidemics in the past, and may be worth re-evaluating to this end. Education, behaviour change and clinical practices deal predominantly with the host, although multidisciplinary practices such as shared-care might also be expected to impact on other corners of the triad. Technology deals best with the agent of obesity (energy imbalance) and it's vectors (excessive energy intake and/or inadequate energy expenditure), and policy and social change are needed to cope with the environment. The value of a broad model like this, rather than specific isolated approaches, is that the key players such as legislators, health professionals, governments and industry can see their roles in attenuating and eventually reversing the epidemic. It also highlights the need to intervene at all levels in obesity control and reduces the relevance of arguments about nature vs. nurture.

  3. Applying a Modified Triad Approach to Investigate Wastewater lines

    International Nuclear Information System (INIS)

    Pawlowicz, R.; Urizar, L.; Blanchard, S.; Jacobsen, K.; Scholfield, J.

    2006-01-01

    Approximately 20 miles of wastewater lines are below grade at an active military Base. This piping network feeds or fed domestic or industrial wastewater treatment plants on the Base. Past wastewater line investigations indicated potential contaminant releases to soil and groundwater. Further environmental assessment was recommended to characterize the lines because of possible releases. A Remedial Investigation (RI) using random sampling or use of sampling points spaced at predetermined distances along the entire length of the wastewater lines, however, would be inefficient and cost prohibitive. To accomplish RI goals efficiently and within budget, a modified Triad approach was used to design a defensible sampling and analysis plan and perform the investigation. The RI task was successfully executed and resulted in a reduced fieldwork schedule, and sampling and analytical costs. Results indicated that no major releases occurred at the biased sampling points. It was reasonably extrapolated that since releases did not occur at the most likely locations, then the entire length of a particular wastewater line segment was unlikely to have contaminated soil or groundwater and was recommended for no further action. A determination of no further action was recommended for the majority of the waste lines after completing the investigation. The modified Triad approach was successful and a similar approach could be applied to investigate wastewater lines on other United States Department of Defense or Department of Energy facilities. (authors)

  4. Alkali metals in addition to acidic pH activate the EvgS histidine kinase sensor in Escherichia coli.

    Science.gov (United States)

    Eguchi, Yoko; Utsumi, Ryutaro

    2014-09-01

    Two-component signal transduction systems (TCSs) in bacteria perceive environmental stress and transmit the information via phosphorelay to adjust multiple cellular functions for adaptation. The EvgS/EvgA system is a TCS that confers acid resistance to Escherichia coli cells. Activation of the EvgS sensor initiates a cascade of transcription factors, EvgA, YdeO, and GadE, which induce the expression of a large group of acid resistance genes. We searched for signals activating EvgS and found that a high concentration of alkali metals (Na(+), K(+)) in addition to low pH was essential for the activation. EvgS is a histidine kinase, with a large periplasmic sensor region consisting of two tandem PBPb (bacterial periplasmic solute-binding protein) domains at its N terminus. The periplasmic sensor region of EvgS was necessary for EvgS activation, and Leu152, located within the first PBPb domain, was involved in the activation. Furthermore, chimeras of EvgS and PhoQ histidine kinases suggested that alkali metals were perceived at the periplasmic sensor region, whereas the cytoplasmic linker domain, connecting the transmembrane region and the histidine kinase domain, was required for low-pH perception. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  5. The role of proline-containing peptide triads in β-sheet formation: A kinetic study.

    Science.gov (United States)

    Takor, Gaius A; Higashiya, Seiichiro; Sikirzhytski, Vitali K; Seeley, Jason P; Lednev, Igor K; Welch, John T

    2015-06-01

    The design of biomimetic materials through molecular self-assembly is a growing area of modern nanotechnology. With problems of protein folding, self-assembly, and sequence-structure relationships as essential in nanotechnology as in biology, the effect of the nucleation of β-hairpin formation by proline on the folding process has been investigated in model studies. Previously such studies were limited to investigations of the influence of proline on the formation of turns in short peptide sequences. The effect of proline-based triads on the folding of an 11-kDa amyloidogenic peptide GH6[(GA)3GY(GA)3GE]8 GAH6 (YE8) was investigated by selective substitution of the proline-substituted triads at the γ-turn sites. The folding and fibrillation of the singly proline-substituted polypeptides, e.g., GH6-[(GA)3GY(GA)3GE]7(GA)3GY(GA)3PD-GAH6 (8PD), and doubly proline-substituted polypeptides, e.g., GH6-[(GA)3GY(GA)3GE]3(GA)3GY(GA)3PD[(GA)3GY(GA)3GE]3(GA)3GY(GA)3PD-GAH6 (4,8PD), were directly monitored by circular dichroism and deep UV resonance Raman and fluorescence spectroscopies. These findings were used to identify the essential folding domains, i.e., the minimum number of β-strands necessary for stable folding. These experimental findings may be especially useful in the design and construction of peptidic materials for a wide range of applications as well as in understanding the mechanisms of folding critical to fibril formation. © 2015 Wiley Periodicals, Inc.

  6. Structural and Functional Analysis of the Escherichia coli Acid-Sensing Histidine Kinase EvgS.

    Science.gov (United States)

    Sen, Hrishiraj; Aggarwal, Nikhil; Ishionwu, Chibueze; Hussain, Nosheen; Parmar, Chandni; Jamshad, Mohammed; Bavro, Vassiliy N; Lund, Peter A

    2017-09-15

    The EvgS/EvgA two-component system of Escherichia coli is activated in response to low pH and alkali metals and regulates many genes, including those for the glutamate-dependent acid resistance system and a number of efflux pumps. EvgS, the sensor kinase, is one of five unconventional histidine kinases (HKs) in E. coli and has a large periplasmic domain and a cytoplasmic PAS domain in addition to phospho-acceptor, HK and dimerization, internal receiver, and phosphotransfer domains. Mutations that constitutively activate the protein at pH 7 map to the PAS domain. Here, we built a homology model of the periplasmic region of EvgS, based on the structure of the equivalent region of the BvgS homologue, to guide mutagenesis of potential key residues in this region. We show that histidine 226 is required for induction and that it is structurally colocated with a proline residue (P522) at the top of the predicted transmembrane helix that is expected to play a key role in passing information to the cytoplasmic domains. We also show that the constitutive mutations in the PAS domain can be further activated by low external pH. Expression of the cytoplasmic part of the protein alone also gives constitutive activation, which is lost if the constitutive PAS mutations are present. These findings are consistent with a model in which EvgS senses both external and internal pH and is activated by a shift from a tight inactive to a weak active dimer, and we present an analysis of the purified cytoplasmic portion of EvgS that supports this. IMPORTANCE One of the ways bacteria sense their environment is through two-component systems, which have one membrane-bound protein to do the sensing and another inside the cell to turn genes on or off in response to what the membrane-bound protein has detected. The membrane-bound protein must thus be able to detect the stress and signal this detection event to the protein inside the cell. To understand this process, we studied a protein that helps

  7. Groundwater quality assessment of one former industrial site in Belgium using a TRIAD-like approach

    International Nuclear Information System (INIS)

    Crevecoeur, Sophie; Debacker, Virginie; Joaquim-Justo, Celia; Gobert, Sylvie; Scippo, Marie-Louise; Dejonghe, Winnie; Martin, Patrick; Thome, Jean-Pierre

    2011-01-01

    Contaminated industrial sites are important sources of pollution and may result in ecotoxicological effects on terrestrial, aquatic and groundwater ecosystems. An effect-based approach to evaluate and assess pollution-induced degradation due to contaminated groundwater was carried out in this study. The new concept, referred to as 'Groundwater Quality TRIAD-like' (GwQT) approach, is adapted from classical TRIAD approaches. GwQT is based on measurements of chemical concentrations, laboratory toxicity tests and physico-chemical analyses. These components are combined in the GwQT using qualitative and quantitative (using zero to one subindices) integration approaches. The TRIAD approach is applied for the first time on groundwater from one former industrial site located in Belgium. This approach will allow the classification of sites into categories according to the degree of contaminant-induced degradation. This new concept is a starting point for groundwater characterization and is open for improvement and adjustment. - Highlights: → This study presents the first application of the TRIAD approach on groundwater system. → Groundwater Quality TRIAD-like approach is based on measurements of chemical concentrations, laboratory toxicity tests and physico-chemical analyses. → None of the three TRIAD components could reliably predict the other one. - This study presents the first application of the TRIAD approach on groundwater system. None of the TRIAD components (chemistry, physico-chemistry and ecotoxicity) could reliably predict the other one.

  8. Disciplinary Politics and the Institutionalization of the Generic Triad in Classical Rhetoric.

    Science.gov (United States)

    Liu, Yameng

    1995-01-01

    Discusses the concepts of rhetoric in general and specifically the generic triad in classical rhetoric. Outlines contemporary versions of the function and realm of rhetoric. Discusses the clash between Aristotle and Quintilian regarding the triad and its relationship to contemporary debates. (HB)

  9. Dark Triad, Perceptions of Organizational Politics and Counterproductive Work Behaviors: The Moderating Effect of Political Skills

    Directory of Open Access Journals (Sweden)

    Muhammad A. Baloch

    2017-11-01

    Full Text Available The aim of this work focuses on the relationship among the Dark Triad (psychopathy, narcissism, and Machiavellianism, perceptions of organizational politics, political skills, and counterproductive work behavior. This study empirically tests the mediating role of perceptions of organizational politics in the relationship between the Dark Triad and counterproductive work behavior. Furthermore, the study investigates the moderating role of political skills in strengthening the link between the Dark Triad and the perceptions of organizational politics. A sample of 149 participants was randomly selected. To analyze the data of the present work, we employed a structural equation model using partial least square and PROCESS. From empirical findings, we imply an inference that perception of organizational politics partially mediates the Dark Triad's influence on the counterproductive work behavior. Moreover, the results identify the moderating role of political skills in strengthening the link between the Dark Triad and the perceptions of organizational politics. Empirical findings suggest important policy implications for the hospitality industry.

  10. Dark Triad, Perceptions of Organizational Politics and Counterproductive Work Behaviors: The Moderating Effect of Political Skills.

    Science.gov (United States)

    Baloch, Muhammad A; Meng, Fanchen; Xu, Zefeng; Cepeda-Carrion, Ignacio; Danish; Bari, Muhammad W

    2017-01-01

    The aim of this work focuses on the relationship among the Dark Triad (psychopathy, narcissism, and Machiavellianism), perceptions of organizational politics, political skills, and counterproductive work behavior. This study empirically tests the mediating role of perceptions of organizational politics in the relationship between the Dark Triad and counterproductive work behavior. Furthermore, the study investigates the moderating role of political skills in strengthening the link between the Dark Triad and the perceptions of organizational politics. A sample of 149 participants was randomly selected. To analyze the data of the present work, we employed a structural equation model using partial least square and PROCESS. From empirical findings, we imply an inference that perception of organizational politics partially mediates the Dark Triad's influence on the counterproductive work behavior. Moreover, the results identify the moderating role of political skills in strengthening the link between the Dark Triad and the perceptions of organizational politics. Empirical findings suggest important policy implications for the hospitality industry.

  11. Dark Triad, Perceptions of Organizational Politics and Counterproductive Work Behaviors: The Moderating Effect of Political Skills

    Science.gov (United States)

    Baloch, Muhammad A.; Meng, Fanchen; Xu, Zefeng; Cepeda-Carrion, Ignacio; Danish; Bari, Muhammad W.

    2017-01-01

    The aim of this work focuses on the relationship among the Dark Triad (psychopathy, narcissism, and Machiavellianism), perceptions of organizational politics, political skills, and counterproductive work behavior. This study empirically tests the mediating role of perceptions of organizational politics in the relationship between the Dark Triad and counterproductive work behavior. Furthermore, the study investigates the moderating role of political skills in strengthening the link between the Dark Triad and the perceptions of organizational politics. A sample of 149 participants was randomly selected. To analyze the data of the present work, we employed a structural equation model using partial least square and PROCESS. From empirical findings, we imply an inference that perception of organizational politics partially mediates the Dark Triad's influence on the counterproductive work behavior. Moreover, the results identify the moderating role of political skills in strengthening the link between the Dark Triad and the perceptions of organizational politics. Empirical findings suggest important policy implications for the hospitality industry. PMID:29167654

  12. Mechanisms of High Temperature Resistance of Synechocystis sp. PCC 6803: An Impact of Histidine Kinase 34

    Directory of Open Access Journals (Sweden)

    Jan Červený

    2015-03-01

    Full Text Available Synechocystis sp. PCC 6803 is a widely used model cyanobacterium for studying responses and acclimation to different abiotic stresses. Changes in transcriptome, proteome, lipidome, and photosynthesis in response to short term heat stress are well studied in this organism, and histidine kinase 34 (Hik34 is shown to play an important role in mediating such response. Corresponding data on long term responses, however, are fragmentary and vary depending on parameters of experiments and methods of data collection, and thus are hard to compare. In order to elucidate how the early stress responses help cells to sustain long-term heat stress, as well as the role of Hik34 in prolonged acclimation, we examined the resistance to long-term heat stress of wild-type and ΔHik34 mutant of Synechocystis. In this work, we were able to precisely control the long term experimental conditions by cultivating Synechocystis in automated photobioreactors, measuring selected physiological parameters within a time range of minutes. In addition, morphological and ultrastructural changes in cells were analyzed and western blotting of individual proteins was used to study the heat stress-affected protein expression. We have shown that the majority of wild type cell population was able to recover after 24 h of cultivation at 44 °C. In contrast, while ΔHik34 mutant cells were resistant to heat stress within its first hours, they could not recover after 24 h long high temperature treatment. We demonstrated that the early induction of HspA expression and maintenance of high amount of other HSPs throughout the heat incubation is critical for successful adaptation to long-term stress. In addition, it appears that histidine kinase Hik34 is an essential component for the long term high temperature resistance.

  13. Mechanisms of High Temperature Resistance of Synechocystis sp. PCC 6803: An Impact of Histidine Kinase 34.

    Science.gov (United States)

    Červený, Jan; Sinetova, Maria A; Zavřel, Tomáš; Los, Dmitry A

    2015-03-02

    Synechocystis sp. PCC 6803 is a widely used model cyanobacterium for studying responses and acclimation to different abiotic stresses. Changes in transcriptome, proteome, lipidome, and photosynthesis in response to short term heat stress are well studied in this organism, and histidine kinase 34 (Hik34) is shown to play an important role in mediating such response. Corresponding data on long term responses, however, are fragmentary and vary depending on parameters of experiments and methods of data collection, and thus are hard to compare. In order to elucidate how the early stress responses help cells to sustain long-term heat stress, as well as the role of Hik34 in prolonged acclimation, we examined the resistance to long-term heat stress of wild-type and ΔHik34 mutant of Synechocystis. In this work, we were able to precisely control the long term experimental conditions by cultivating Synechocystis in automated photobioreactors, measuring selected physiological parameters within a time range of minutes. In addition, morphological and ultrastructural changes in cells were analyzed and western blotting of individual proteins was used to study the heat stress-affected protein expression. We have shown that the majority of wild type cell population was able to recover after 24 h of cultivation at 44 °C. In contrast, while ΔHik34 mutant cells were resistant to heat stress within its first hours, they could not recover after 24 h long high temperature treatment. We demonstrated that the early induction of HspA expression and maintenance of high amount of other HSPs throughout the heat incubation is critical for successful adaptation to long-term stress. In addition, it appears that histidine kinase Hik34 is an essential component for the long term high temperature resistance.

  14. Unusual chemical properties of N-terminal histidine residues of glucagon and vasoactive intestinal peptide

    International Nuclear Information System (INIS)

    Hefford, M.A.; Evans, R.M.; Oda, G.; Kaplan, H.

    1985-01-01

    An N-terminal histidine residue of a protein or peptide has two functional groups, viz., an alpha-amino group and an imidazole group. A new procedure, based on the competitive labeling approach described by Duggleby and Kaplan has been developed by which the chemical reactivity of each functional group in such a residue can be determined as a function of pH. Only very small amounts of material are required, which makes it possible to determine the chemical properties in dilute solution or in proteins and polypeptides that can be obtained in only minute quantities. With this approach, the reactivity of the alpha-amino group of histidylglycine toward 1-fluoro-2,4-dinitrobenzene gave an apparent pK /sub a/ value of 7.64 +/- 0.07 at 37 degrees C, in good agreement with a value of 7.69 +/- 0.02 obtained by acid-base titration. However, the reactivity of the imidazole function gave an apparent pK /sub a/ value of 7.16 +/- 0.07 as compared to the pK /sub a/ value of 5.85 +/- 0.01 obtained by acid-base titration. Similarly, in glucagon and vasoactive intestinal peptide (VIP), apparent pKa values of 7.60 +/- 0.04 and 7.88 +/- 0.18, respectively, were obtained for the alpha-amino of their N-terminal histidine, and pKa values of 7.43 +/- 0.09 and 7.59 +/- 0.18 were obtained for the imidazole function

  15. Characterization of bud emergence 46 (BEM46) protein: Sequence, structural, phylogenetic and subcellular localization analyses

    International Nuclear Information System (INIS)

    Kumar, Abhishek; Kollath-Leiß, Krisztina; Kempken, Frank

    2013-01-01

    Highlights: •All eukaryotes have at least a single copy of a bem46 ortholog. •The catalytic triad of BEM46 is illustrated using sequence and structural analysis. •We identified indels in the conserved domain of BEM46 protein. •Localization studies of BEM46 protein were carried out using GFP-fusion tagging. -- Abstract: The bud emergence 46 (BEM46) protein from Neurospora crassa belongs to the α/β-hydrolase superfamily. Recently, we have reported that the BEM46 protein is localized in the perinuclear ER and also forms spots close by the plasma membrane. The protein appears to be required for cell type-specific polarity formation in N. crassa. Furthermore, initial studies suggested that the BEM46 amino acid sequence is conserved in eukaryotes and is considered to be one of the widespread conserved “known unknown” eukaryotic genes. This warrants for a comprehensive phylogenetic analysis of this superfamily to unravel origin and molecular evolution of these genes in different eukaryotes. Herein, we observe that all eukaryotes have at least a single copy of a bem46 ortholog. Upon scanning of these proteins in various genomes, we find that there are expansions leading into several paralogs in vertebrates. Usingcomparative genomic analyses, we identified insertion/deletions (indels) in the conserved domain of BEM46 protein, which allow to differentiate fungal classes such as ascomycetes from basidiomycetes. We also find that exonic indels are able to differentiate BEM46 homologs of different eukaryotic lineage. Furthermore, we unravel that BEM46 protein from N. crassa possess a novel endoplasmic-retention signal (PEKK) using GFP-fusion tagging experiments. We propose that three residues namely a serine 188S, a histidine 292H and an aspartic acid 262D are most critical residues, forming a catalytic triad in BEM46 protein from N. crassa. We carried out a comprehensive study on bem46 genes from a molecular evolution perspective with combination of functional

  16. Characterization of bud emergence 46 (BEM46) protein: Sequence, structural, phylogenetic and subcellular localization analyses

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Abhishek; Kollath-Leiß, Krisztina; Kempken, Frank, E-mail: fkempken@bot.uni-kiel.de

    2013-08-30

    Highlights: •All eukaryotes have at least a single copy of a bem46 ortholog. •The catalytic triad of BEM46 is illustrated using sequence and structural analysis. •We identified indels in the conserved domain of BEM46 protein. •Localization studies of BEM46 protein were carried out using GFP-fusion tagging. -- Abstract: The bud emergence 46 (BEM46) protein from Neurospora crassa belongs to the α/β-hydrolase superfamily. Recently, we have reported that the BEM46 protein is localized in the perinuclear ER and also forms spots close by the plasma membrane. The protein appears to be required for cell type-specific polarity formation in N. crassa. Furthermore, initial studies suggested that the BEM46 amino acid sequence is conserved in eukaryotes and is considered to be one of the widespread conserved “known unknown” eukaryotic genes. This warrants for a comprehensive phylogenetic analysis of this superfamily to unravel origin and molecular evolution of these genes in different eukaryotes. Herein, we observe that all eukaryotes have at least a single copy of a bem46 ortholog. Upon scanning of these proteins in various genomes, we find that there are expansions leading into several paralogs in vertebrates. Usingcomparative genomic analyses, we identified insertion/deletions (indels) in the conserved domain of BEM46 protein, which allow to differentiate fungal classes such as ascomycetes from basidiomycetes. We also find that exonic indels are able to differentiate BEM46 homologs of different eukaryotic lineage. Furthermore, we unravel that BEM46 protein from N. crassa possess a novel endoplasmic-retention signal (PEKK) using GFP-fusion tagging experiments. We propose that three residues namely a serine 188S, a histidine 292H and an aspartic acid 262D are most critical residues, forming a catalytic triad in BEM46 protein from N. crassa. We carried out a comprehensive study on bem46 genes from a molecular evolution perspective with combination of functional

  17. Contributions of the Histidine Side Chain and the N-terminal α-Amino Group to the Binding Thermodynamics of Oligopeptides to Nucleic Acids as a Function of pH

    Science.gov (United States)

    Ballin, Jeff D.; Prevas, James P.; Ross, Christina R.; Toth, Eric A.; Wilson, Gerald M.; Record, M. Thomas

    2010-01-01

    Interactions of histidine with nucleic acid phosphates and histidine pKa shifts make important contributions to many protein-nucleic acid binding processes. To characterize these phenomena in simplified systems, we quantified binding of a histidine-containing model peptide HWKK (+NH3-His-Trp-Lys-Lys-NH2) and its lysine analog KWKK (+NH3-Lys-Trp-Lys-Lys-NH2) to a single-stranded RNA model, polyuridylate (polyU), by changes in tryptophan fluorescence as a function of salt concentration and pH. For both HWKK and KWKK, equilibrium binding constants, Kobs, and magnitudes of log-log salt derivatives SKobs ≡ (∂logKobs/∂log[Na+]), decreased with increasing pH in the manner expected for a titration curve model in which deprotonation of the histidine and α-amino groups weakens binding and reduces its salt-dependence. Fully protonated HWKK and KWKK exhibit the same Kobs and SKobs within uncertainty, and these SKobs values are consistent with limiting-law polyelectrolyte theory for +4 cationic oligopeptides binding to single-stranded nucleic acids. The pH-dependence of HWKK binding to polyU provides no evidence for pKa shifts nor any requirement for histidine protonation, in stark contrast to the thermodynamics of coupled protonation often seen for these cationic residues in the context of native protein structure where histidine protonation satisfies specific interactions (e.g., salt-bridge formation) within highly complementary binding interfaces. The absence of pKa shifts in our studies indicates that additional Coulombic interactions across the nonspecific-binding interface between RNA and protonated histidine or the α-amino group are not sufficient to promote proton uptake for these oligopeptides. We present our findings in the context of hydration models for specific versus nonspecific nucleic acid binding. PMID:20108951

  18. Current perspectives on the etiology and manifestation of the "silent" component of the Female Athlete Triad

    Directory of Open Access Journals (Sweden)

    Mallinson RJ

    2014-05-01

    Full Text Available Rebecca J Mallinson, Mary Jane De SouzaDepartment of Kinesiology, Women's Health and Exercise Laboratory in Noll Laboratory, Pennsylvania State University, University Park, PA, USAAbstract: The Female Athlete Triad (Triad represents a syndrome of three interrelated conditions that originate from chronically inadequate energy intake to compensate for energy expenditure; this environment results in insufficient stored energy to maintain physiological processes, a condition known as low energy availability. The physiological adaptations associated with low energy availability, in turn, contribute to menstrual cycle disturbances. The downstream effects of both low energy availability and suppressed estrogen concentrations synergistically impair bone health, leading to low bone mineral density, compromised bone structure and microarchitecture, and ultimately, a decrease in bone strength. Unlike the other components of the Triad, poor bone health often does not have overt symptoms, and therefore develops silently, unbeknownst to the athlete. Compromised bone health among female athletes increases the risk of fracture throughout the lifespan, highlighting the long-term health consequences of the Triad. The purpose of this review is to examine the current state of Triad research related to the third component of the Triad, ie, poor bone health, in an effort to summarize what we know, what we are learning, and what remains unknown.Keywords: female athlete Triad, bone health, treatment

  19. Crystallization and preliminary X-ray crystallographic analysis of SMU.412c protein from the caries pathogen Streptococcus mutans

    International Nuclear Information System (INIS)

    Ye, Zhao-Yang; Hou, Qiao-Ming; Li, Lan-Fen; Su, Xiao-Dong

    2009-01-01

    Crystallization of SMU.412c protein from the caries pathogen Streptococcus mutans can easily appear in the condition 2.8 M sodium acetate pH 7.0 and its crystal belongs to space group P4 1 2 1 2. The smu.412c gene encodes a putative histidine triad-like protein (SMU.412c) with 139 residues that is involved in cell-cycle regulation in Streptococcus mutans. The gene was cloned into the expression vector pET28a and subsequently expressed in Escherichia coli strain BL21 (DE3) to give a substantially soluble form of SMU.412c with a His 6 tag at its N-terminus. The recombinant protein was purified to homogeneity in a two-step procedure involving Ni 2+ -chelating and size-exclusion chromatography. Crystals suitable for X-ray diffraction were obtained using the sitting-drop vapour-diffusion method and diffracted to 1.8 Å resolution on beamline BL6A at Photon Factory, Tsukuba, Japan. The crystal belonged to space group P4 1 2 1 2, with unit-cell parameters a = b = 53.5, c = 141.1 Å

  20. Mutations in the NOT Genes or in the Translation Machinery Similarly Display Increased Resistance to Histidine Starvation

    Directory of Open Access Journals (Sweden)

    Martine A. Collart

    2017-05-01

    Full Text Available The NOT genes encode subunits of the conserved Ccr4-Not complex, a global regulator of gene expression, and in particular of mRNA metabolism. They were originally identified in a selection for increased resistance to histidine starvation in the yeast S. cerevisiae. Recent work indicated that the Not5 subunit, ortholog of mammalian CNOT3, determines global translation levels by defining binding of the Ccr4-Not scaffold protein Not1 to ribosomal mRNAs during transcription. This is needed for optimal translation of ribosomal proteins. In this work we searched for mutations in budding yeast that were resistant to histidine starvation using the same selection that originally led to the isolation of the NOT genes. We thereby isolated mutations in ribosome-related genes. This common phenotype of ribosome mutants and not mutants is in good agreement with the positive role of the Not proteins for translation. In this regard, it is interesting that frequent mutations in RPL5 and RPL10 or in CNOT3 have been observed to accumulate in adult T-cell acute lymphoblastic leukemia (T-ALL. This suggests that in metazoans a common function implicating ribosome subunits and CNOT3 plays a role in the development of cancer. In this perspective we suggest that the Ccr4-Not complex, according to translation levels and fidelity, could itself be involved in the regulation of amino acid biosynthesis levels. We discuss how this could explain why mutations have been identified in many cancers.

  1. Histidine at Position 195 is Essential for Association of Heme- b in Lcp1VH2

    Science.gov (United States)

    Oetermann, Sylvia; Vivod, Robin; Hiessl, Sebastian; Hogeback, Jens; Holtkamp, Michael; Karst, Uwe; Steinbüchel, Alexander

    2018-05-01

    The latex clearing protein (Lcp) is the key enzyme of polyisoprene degradation in actinomycetes (Yikmis and Steinbüchel in Appl Environ Microbiol 78:4543-4551, https://doi.org/10.1128/AEM.00001-12 , 2012). In this study it was shown that Lcp from Gordonia polyisoprenivorans VH2 (Lcp1VH2) harbors a non-covalently bound heme b as cofactor, which was identified by pyridine hemochrome spectra and confirmed by LC/ESI-ToF-MS. It contains iron, most likely in the Fe3+ state. We focused on the characterization of the heme-cofactor, its accessibility with respect to the conformation of Lcp1VH2, and the identification of putative histidine residues involved in the coordination of heme. A change was detectable in UV/Vis-spectra of reduced Lcp1VH2 when imidazole was added, showing that Lcp1VH2 "as isolated" occurs in an open state, directly being accessible for external ligands. In addition, three highly conserved histidines (H195, H200 and H228), presumably acting as ligands coordinating the heme within the heme pocket, were replaced with alanines by site-directed mutagenesis. The effect of these changes on in vivo rubber-mineralization was investigated. The lcp- deletion mutant complemented with the H195A variant of lcp1 VH2 was unable to mineralize poly( cis-1,4-isoprene). In vitro analyses of purified, recombinant Lcp1VH2H195A confirmed the loss of enzyme activity, which could be ascribed to the loss of heme. Hence, H195 is essential for the association of heme- b in the central region of Lcp1VH2.

  2. PsHint1, associated with the G-protein α subunit PsGPA1, is required for the chemotaxis and pathogenicity of Phytophthora sojae.

    Science.gov (United States)

    Zhang, Xin; Zhai, Chunhua; Hua, Chenlei; Qiu, Min; Hao, Yujuan; Nie, Pingping; Ye, Wenwu; Wang, Yuanchao

    2016-02-01

    Zoospore chemotaxis to soybean isoflavones is essential in the early stages of infection by the oomycete pathogen Phytophthora sojae. Previously, we have identified a G-protein α subunit encoded by PsGPA1 which regulates the chemotaxis and pathogenicity of P. sojae. In the present study, we used affinity purification to identify PsGPA1-interacting proteins, including PsHint1, a histidine triad (HIT) domain-containing protein orthologous to human HIT nucleotide-binding protein 1 (HINT1). PsHint1 interacted with both the guanosine triphosphate (GTP)- and guanosine diphosphate (GDP)-bound forms of PsGPA1. An analysis of the gene-silenced transformants revealed that PsHint1 was involved in the chemotropic response of zoospores to the isoflavone daidzein. During interaction with a susceptible soybean cultivar, PsHint1-silenced transformants displayed significantly reduced infectious hyphal extension and caused a strong cell death in plants. In addition, the transformants displayed defective cyst germination, forming abnormal germ tubes that were highly branched and exhibited apical swelling. These results suggest that PsHint1 not only regulates chemotaxis by interacting with PsGPA1, but also participates in a Gα-independent pathway involved in the pathogenicity of P. sojae. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  3. The Essential WalK Histidine Kinase and WalR Regulator Differentially Mediate Autolysis of Staphylococcus aureus RN4220.

    Science.gov (United States)

    Zheng, Li; Yan, Meiying; Fan, Frank; Ji, Yinduo

    2015-06-01

    The two-component regulatory system, WalR/WalK is necessary for growth of different gram-positive bacteria, including Staphylococcus aureus . In present study, we confirmed the essentiality of both the histidine kinase protein WalK and the response regulator WalR for growth using S. aureus RN4220 strain and demonstrated that the histidine kinase protein WalK and the response regulator WalR function differently in regulation of staphylococcal autolysis. The down-regulation of walR expression effectively inhibited Triton X-100-induced lysis and had a weak impact on bacterial tolerance to penicillin induced cell lysis. In contrast, the down-regulation of walK expression had no influence on either Triton X-100- or penicillin-caused autolysis. Moreover, we determined the effect of WalR and WalK on bacterial hydrolase activity using a zymogram analysis. The results showed that the cell lysate of down-regulated walR expression mutant displayed several bands of decreased cell wall hydrolytic activities; however, the down-regulation of WalK had no dramatic impact on the hydrolytic activities. Furthermore, we examined the impact of WalR on the transcription of cidA associated with staphylococcal autolysis, and the results showed that the down-regulation of WalR led to decreased transcription of cidA in the log phase of growth. Taken together, the above results suggest that the essential WalR response regulator and the essential WalK histidine kinase might differently control bacterial lysis in RN4220 strain.

  4. ATP forms a stable complex with the essential histidine kinase WalK (YycG) domain

    Energy Technology Data Exchange (ETDEWEB)

    Celikel, Reha; Veldore, Vidya Harini [University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Mathews, Irimpan [Stanford Synchrotron Radiation Lightsource, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Devine, Kevin M., E-mail: kdevine@tcd.ie [Trinity College Dublin, Dublin 2 (Ireland); Varughese, Kottayil I., E-mail: kdevine@tcd.ie [University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2012-07-01

    The histidine WalK (YycG) plays a crucial role in coordinating murein synthesis with cell division and the crystal structure of its ATP binding domain has been determined. Interestingly the bound ATP was not hydrolyzed during crystallization and remains intact in the crystal lattice. In Bacillus subtilis, the WalRK (YycFG) two-component system coordinates murein synthesis with cell division. It regulates the expression of autolysins that function in cell-wall remodeling and of proteins that modulate autolysin activity. The transcription factor WalR is activated upon phosphorylation by the histidine kinase WalK, a multi-domain homodimer. It autophosphorylates one of its histidine residues by transferring the γ-phosphate from ATP bound to its ATP-binding domain. Here, the high-resolution crystal structure of the ATP-binding domain of WalK in complex with ATP is presented at 1.61 Å resolution. The bound ATP remains intact in the crystal lattice. It appears that the strong binding interactions and the nature of the binding pocket contribute to its stability. The triphosphate moiety of ATP wraps around an Mg{sup 2+} ion, providing three O atoms for coordination in a near-ideal octahedral geometry. The ATP molecule also makes strong interactions with the protein. In addition, there is a short contact between the exocyclic O3′ of the sugar ring and O2B of the β-phosphate, implying an internal hydrogen bond. The stability of the WalK–ATP complex in the crystal lattice suggests that such a complex may exist in vivo poised for initiation of signal transmission. This feature may therefore be part of the sensing mechanism by which the WalRK two-component system is so rapidly activated when cells encounter conditions conducive for growth.

  5. Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

    Science.gov (United States)

    Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto

    2016-03-27

    In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Allisonella histaminiformans gen. nov., sp. nov. A novel bacterium that produces histamine, utilizes histidine as its sole energy source, and could play a role in bovine and equine laminitis.

    Science.gov (United States)

    Garner, Matthew R; Flint, Joseph F; Russell, James B

    2002-12-01

    When cattle and horses are fed large amounts of grain, histamine can accumulate in the gastrointestinal tract, and this accumulation can cause an acute inflammation of the hooves (laminitis). When ruminal fluid from dairy cattle fed grain supplements was serially diluted in anaerobic MRS medium containing histidine (50 mM), histamine was detected at dilutions as high as 10(-7). The histidine enrichments were then transferred successively in an anaerobic, carbonate-based medium (50 mM histidine) without glucose. The histamine producing bacteria could not be isolated from the rumens of cattle fed hay; however, histamine producing bacteria could be isolated the feces of cattle fed grain and the cecum of a horse. All of the histamine producing isolates had the same ovoid morphology. The cells stained Gram-negative and were resistant to the ionophore, monensin (25 microM). The doubling time was 110 min, and the yield was 1.5 mg cell protein per mmol histidine. The G+C content was 46.8%. Lysine was the only other amino acid used, but lysine did not allow growth if histidine was absent. Because carbohydrate and organic acid utilization was not detected, it appeared that the isolates used histidine decarboxylation as their sole mechanism of energy derivation. 16s rRNA gene sequencing indicated that the isolates were most closely related to low G+C Gram-positive bacteria (firmicutes), but similarities were < or = 94%. Because the most closely related bacteria (Dialister pneumonsintes, Megasphaera elsdenii and Selenomonas ruminantium) did not produce histamine from histidine, we propose that these histamine producing bacteria be assigned to a new genus, Allisonella, as Allisonella histaminiformans gen. nov., sp. nov. The type strain is MR2 (ATCC BAA610, DSM 15230).

  7. Monitoring in service triads consisting of buyers, subcontractors and end customers

    NARCIS (Netherlands)

    Valk, van der W.; Iwaarden, van J.

    2011-01-01

    Organisations increasingly outsource service delivery to specialist subcontractors. These buyers, their subcontractors and their end customers operate in a triadic service relationship. In these triads, the buyer lacks direct control over service delivery and completely depends on the subcontractor

  8. Radiological findings of Currarino's triad - a case report and review of the literature

    International Nuclear Information System (INIS)

    Machado Junior, Marcos Alberto; Barbosa, Veronica Aline de Oliveira; Rocha, Josilton Antonio; Ferreira, Eliane Fiuza; Maximo, Marcia Andrade; Castro, Luiz Eduardo; Vieira, Lauro Conceicao

    1998-01-01

    The authors report a child case with congenital malformation Currarino triad characterized by a rare complex of a congenital sacral bony abnormality, anorectal malformation and a presacral mass. A bibliographic review was done, focusing the radiological and tomographic findings. (author)

  9. Joint en Environmental Promotion from the Triad: School, Family, Community

    Directory of Open Access Journals (Sweden)

    Adriana Del Rosario Mejías Vetancourt

    2016-08-01

    Full Text Available The present research has as main objective to generate a theoretical approach of the Joint Environmental Promotion from the Triad: School, Family, Community Primary School "Cinqueña III" town Barinas state of Barinas. The nature of this research is supported by the phenomenological qualitative approach critical partner paradigm. Key informants were considered five (05, which were chosen at the discretion of the investigator, according to the actors who are considered binding: a manager, a teacher, a representative, a member of the school board, a member of the community council. Among the techniques of information collection are: participant observation and qualitative depth interview. As techniques for analyzing information categorization, coding and triangulation, accompanied by descriptive and interpretative phase it is contemplated. Then, a comparative matrix is made to analyze the information collected and shall determine the findings as a result of addressing the issue of research in the Basic School Cinqueña III, municipality of Barinas Barinas state.

  10. O Wave Interactions: Explosive Resonant Triads and Critical Layers.

    Science.gov (United States)

    Mahoney, Daniel J.

    This thesis considers the phenomenon of explosive resonant triads in weakly nonlinear, dispersive wave systems. These are nearly linear waves with slowly varying amplitudes which become unbounded in finite time. It is shown that such interactions are much stronger than previously thought. These waves can be thought of as a nonlinear instability, in the sense that a weakly nonlinear perturbation to some system grows to such magnitudes that the behavior of the system is governed by strongly nonlinear effects. This may occur for systems which are linearly or neutrally stable. This is contrasted with previous resolutions of this problem, which treated such perturbations as being large amplitude, nearly linear waves. Analytical and numerical evidence is presented to support these claims. These waves represent a potentially important effect in a variety of physical systems, most notably plasma physics. Attention here is turned to their occurrence in fluid mechanics. Here previous work is extended to include flow systems with continuously varying basic velocities and densities. Many of the problems encountered here will be found to be of a singular nature themselves, and the techniques for analyzing these difficulties will be developed. This will involve the concept of a critical layer in a fluid, a level at which a wave phase speed equals the unperturbed fluid velocity in the direction of propagation. Examples of such waves in this context will be presented. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253 -1690.).

  11. O'Donoghue's triad: magnetic resonance imaging evidence

    International Nuclear Information System (INIS)

    Staron, R.B.; Haramati, N.; Feldman, F.; Kiernan, H.A.; Pfaff, H.C.; Rubin, S.J.; Zwass, A.

    1994-01-01

    The objective was to search for magnetic resonance imaging evidence of medial collateral ligament (MCL) injury in knees with proven tears of the anterior cruciate ligament (ACL) and medial meniscus; the three abnormalities that make up O'Donoghue's triad. Although the MCL injury can be unapparent clinically, knee joint stability may be compromised. The superficial portion of the MCL was evaluated on 19 MR studies of 16 knees with arthroscopically proven ACL and medial meniscal tears. MCL thicknesses were compared to those on MR images of 19 normal knees. The injured knees were of 13 men and 3 women, ranging in age from 19 to 56 years; the normal knees were of 10 men and 9 women, ranging in age from 19 to 55 years. The medial collateral ligaments of all injured knees were abnormal, and, as a group, they had greater thicknesses and more intraligamentous thickness variability than normal knees. The MR appearance of both ACL and medial meniscal tears served as indirect evidence of MCL injury, with irregular MCL thickening indicative of prior injury. (orig.)

  12. Currarino triad with dual pathology in the presacral mass: report of a case.

    Science.gov (United States)

    Thambidorai, C R; Muin, I; Razman, J; Zulfiqar, A

    2003-07-01

    Currarino triad, which comprises anorectal stenosis, anterior sacral defect, and a presacral mass, is an uncommon cause of constipation in children and adults. The presacral mass in this triad is most often caused by an anterior sacral meningocele, a teratoma, or an enterogenous cyst, but rarely may be caused by dual pathology. A neonate with Currarino triad and dual pathology in the presacral mass is described in this report. A male Chinese neonate, who presented with abdominal distention and constipation on the second day of life, was found to have features of Currarino triad. Colostomy was done in the neonatal period, and the presacral mass was excised by posterior sagittal perineal approach at the age of six months. The excised presacral mass consisted of an anterior meningocele and a teratoma. The patient continued to have constipation during follow-up and required anorectoplasty to correct residual anorectal stenosis. At the time of this report the patient was three years old and growing normally with normal anorectal function. Of a total of about 200 cases of complete Currarino triad found in the literature, in only 22 patients did the presacral mass contain both meningocele and teratoma. The features of these 22 patients and the current views on the surgical management of Currarino triad are discussed.

  13. Beyond the big five: the Dark Triad and the supernumerary personality inventory.

    Science.gov (United States)

    Veselka, Livia; Schermer, Julie Aitken; Vernon, Philip A

    2011-04-01

    The Dark Triad of personality, comprising Machiavellianism, narcissism, and psychopathy, was investigated in relation to the Supernumerary Personality Inventory (SPI) traits, because both sets of variables are predominantly distinct from the Big Five model of personality. Correlational and principal factor analyses were conducted to assess the relations between the Dark Triad and SPI traits. Multivariate behavioral genetic model-fitting analyses were also conducted to determine the correlated genetic and/or environmental underpinnings of the observed phenotypic correlations. Participants were 358 monozygotic and 98 same-sex dizygotic adult twin pairs from North America. As predicted, results revealed significant correlations between the Dark Triad and most SPI traits, and these correlations were primarily attributable to common genetic and non-shared environmental factors, except in the case of Machiavellianism, where shared environmental effects emerged. Three correlated factors were extracted during joint factor analysis of the Dark Triad and SPI traits, as well as a heritable general factor of personality - results that clarified the structure of the Dark Triad construct. It is concluded that the Dark Triad represents an exploitative and antisocial construct that extends beyond the Big Five model and shares a theoretical space with the SPI traits.

  14. Electrochemical and spectroscopic investigations of immobilized de novo designed heme proteins on metal electrodes

    DEFF Research Database (Denmark)

    Albrecht, Tim; Li, WW; Ulstrup, Jens

    2005-01-01

    On the basis of rational design principles, template-assisted four-helix-bundle proteins that include two histidines for coordinative binding of a heme were synthesized. Spectroscopic and thermodynamic characterization of the proteins in solution reveals the expected bis-histidine coordinated heme...

  15. Formation of RNA phosphodiester bond by histidine-containing dipeptides

    DEFF Research Database (Denmark)

    Wieczorek, Rafal; Dörr, Mark; Chotera, Agata

    2013-01-01

    A new scenario for prebiotic formation of nucleic acid oligomers is presented. Peptide catalysis is applied to achieve condensation of activated RNA monomers into short RNA chains. As catalysts, L-dipeptides containing a histidine residue, primarily Ser-His, were used. Reactions were carried out...... in self-organised environment, a water-ice eutectic phase, with low concentrations of reactants. Incubation periods up to 30 days resulted in the formation of short oligomers of RNA. During the oligomerisation, an active intermediate (dipeptide-mononucleotide) is produced, which is the reactive species...... by a transamination mechanism. Because peptides are much more likely products of spontaneous condensation than nucleotide chains, their potential as catalysts for the formation of RNA is interesting from the origin-of-life perspective. Finally, the formation of the dipeptide-mononucleotide intermediate and its...

  16. Roles of the redox-active disulfide and histidine residues forming a catalytic dyad in reactions catalyzed by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

    Science.gov (United States)

    Kofoed, Melissa A; Wampler, David A; Pandey, Arti S; Peters, John W; Ensign, Scott A

    2011-09-01

    NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC), an atypical member of the disulfide oxidoreductase (DSOR) family of enzymes, catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate; 2-KPC] to form acetoacetate and coenzyme M (CoM) in the bacterial pathway of propylene metabolism. Structural studies of 2-KPCC from Xanthobacter autotrophicus strain Py2 have revealed a distinctive active-site architecture that includes a putative catalytic triad consisting of two histidine residues that are hydrogen bonded to an ordered water molecule proposed to stabilize enolacetone formed from dithiol-mediated 2-KPC thioether bond cleavage. Site-directed mutants of 2-KPCC were constructed to test the tenets of the mechanism proposed from studies of the native enzyme. Mutagenesis of the interchange thiol of 2-KPCC (C82A) abolished all redox-dependent reactions of 2-KPCC (2-KPC carboxylation or protonation). The air-oxidized C82A mutant, as well as wild-type 2-KPCC, exhibited the characteristic charge transfer absorbance seen in site-directed variants of other DSOR enzymes but with a pK(a) value for C87 (8.8) four units higher (i.e., four orders of magnitude less acidic) than that for the flavin thiol of canonical DSOR enzymes. The same higher pK(a) value was observed in native 2-KPCC when the interchange thiol was alkylated by the CoM analog 2-bromoethanesulfonate. Mutagenesis of the flavin thiol (C87A) also resulted in an inactive enzyme for steady-state redox-dependent reactions, but this variant catalyzed a single-turnover reaction producing a 0.8:1 ratio of product to enzyme. Mutagenesis of the histidine proximal to the ordered water (H137A) led to nearly complete loss of redox-dependent 2-KPCC reactions, while mutagenesis of the distal histidine (H84A) reduced these activities by 58 to 76%. A redox-independent reaction of 2-KPCC (acetoacetate decarboxylation) was not decreased for any of the

  17. Partial alanine scan of mast cell degranulating peptide (MCD): importance of the histidine- and arginine residues.

    Science.gov (United States)

    Buku, Angeliki; Mendlowitz, Milton; Condie, Barry A; Price, Joseph A

    2004-06-01

    The influence of the two histidine and two arginine residues of mast cell degranulating peptide (MCD) in activity and binding was studied by replacing these amino acids in the MCD sequence with L-alanine. Their histamine releasing activity was determined on rat peritoneal mast cells. Their binding affinity to the FcepsilonRIalpha binding subunit of the human mast cell receptor protein, was carried out using fluorescence polarization. The histamine assay showed that replacement of His13 by Ala o ccurred without loss of activity compared with the activity of MCD. Alanine substitutions for Arg7 and His8 resulted in an approximately 40 fold increase, and for Arg16 in a 14-fold increase in histamine-releasing activity of MCD. The binding affinities of the analogs were tested by competitive displacement of bound fluorescent MCD peptide from the FcepsilonRIalpha binding protein of the mast cell receptor by the Ala analogs using fluorescence polarization. The analogs Ala8 (for His) and Ala16 (for Arg) showed the same binding affinities as MCD, whereas analog Ala7 (for Arg) and analog Ala13 (for His) showed slightly better binding affinity than the parent compound. This study showed that the introduction of alanine residues in these positions resulted in MCD agonists of diverse potency. These findings will be useful in further MCD structure-activity studies.

  18. L-histidine inhibits biofilm formation and FLO11-associated phenotypes in Saccharomyces cerevisiae flor yeasts.

    Science.gov (United States)

    Bou Zeidan, Marc; Zara, Giacomo; Viti, Carlo; Decorosi, Francesca; Mannazzu, Ilaria; Budroni, Marilena; Giovannetti, Luciana; Zara, Severino

    2014-01-01

    Flor yeasts of Saccharomyces cerevisiae have an innate diversity of Flo11p which codes for a highly hydrophobic and anionic cell-wall glycoprotein with a fundamental role in biofilm formation. In this study, 380 nitrogen compounds were administered to three S. cerevisiae flor strains handling Flo11p alleles with different expression levels. S. cerevisiae strain S288c was used as the reference strain as it cannot produce Flo11p. The flor strains generally metabolized amino acids and dipeptides as the sole nitrogen source, although with some exceptions regarding L-histidine and histidine containing dipeptides. L-histidine completely inhibited growth and its effect on viability was inversely related to Flo11p expression. Accordingly, L-histidine did not affect the viability of the Δflo11 and S288c strains. Also, L-histidine dramatically decreased air-liquid biofilm formation and adhesion to polystyrene of the flor yeasts with no effect on the transcription level of the Flo11p gene. Moreover, L-histidine modified the chitin and glycans content on the cell-wall of flor yeasts. These findings reveal a novel biological activity of L-histidine in controlling the multicellular behavior of yeasts [corrected].

  19. Wastewater Triad Project: Solid-Liquid Separator FY 2000 Deployment

    International Nuclear Information System (INIS)

    Walker, J.F.

    2001-01-01

    The Wastewater Triad Project (WTP) consists of three operational units: the cesium removal (CsR) system, the out-of-tank evaporator (OTE) system, and the solid/liquid separation (SLS) system. These systems were designed to reduce the volume and radioactivity of low-level liquid waste (LLLW) stored in the Melton Valley Storage Tanks (MVSTs) and are operated independently or in series in order to accomplish the treatment goals. Each is a modular, skid-mounted system that is self-contained, individually shielded, and designed to be decontaminated and removed once the project has been completed. The CsR and OTE systems are installed inside Building 7877; the SLS system is installed adjacent to the east side of the MVST 7830 vault cover. The CsR, which consists of ion-exchange equipment for removing 137 Cs from LLLW, was demonstrated in 1997. During the Cesium Removal Demonstration, 30,853 gal of radioactive supernate was processed and 1142 Ci of 137 Cs was removed from the supernate and loaded onto 70 gal of a crystalline silicotitanate sorbent manufactured by UOP, Inc. The OTE system is a subatmospheric single-stage evaporator system designed to concentrate LLLW to smaller volumes. It was previously demonstrated in 1996 and was operated in 1998 to process about 80,000 gal of LLLW. The SLS system was designed to filter and remove suspended solids from LLLW in order to minimize further accumulation of sludge in new storage tanks or to prevent fouling of CsR and OTE systems. The SLS was installed and demonstrated in 1999; ∼45,000 gal of radioactive supernate was processed during the demonstration

  20. Specific chemical and structural damage to proteins produced by synchrotron radiation.

    Science.gov (United States)

    Weik, M; Ravelli, R B; Kryger, G; McSweeney, S; Raves, M L; Harel, M; Gros, P; Silman, I; Kroon, J; Sussman, J L

    2000-01-18

    Radiation damage is an inherent problem in x-ray crystallography. It usually is presumed to be nonspecific and manifested as a gradual decay in the overall quality of data obtained for a given crystal as data collection proceeds. Based on third-generation synchrotron x-ray data, collected at cryogenic temperatures, we show for the enzymes Torpedo californica acetylcholinesterase and hen egg white lysozyme that synchrotron radiation also can cause highly specific damage. Disulfide bridges break, and carboxyl groups of acidic residues lose their definition. Highly exposed carboxyls, and those in the active site of both enzymes, appear particularly susceptible. The catalytic triad residue, His-440, in acetylcholinesterase, also appears to be much more sensitive to radiation damage than other histidine residues. Our findings have direct practical implications for routine x-ray data collection at high-energy synchrotron sources. Furthermore, they provide a direct approach for studying the radiation chemistry of proteins and nucleic acids at a detailed, structural level and also may yield information concerning putative "weak links" in a given biological macromolecule, which may be of structural and functional significance.

  1. Treatment strategies for the female athlete triad in the adolescent athlete: current perspectives

    Directory of Open Access Journals (Sweden)

    Thein-Nissenbaum J

    2017-04-01

    Full Text Available Jill Thein-Nissenbaum,1 Erin Hammer2 1Department of Family Medicine, University of Wisconsin-Madison, Madison, WI, USA; 2Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA Abstract: Since the passage of Title IX in 1972, female sports participation has dramatically increased. The benefits of physical activity, including decreased risk for heart disease and diabetes as well as improved body image and self-esteem, far outweigh the risks. However, a select population of adolescent and young adult females may experience symptoms related to the female athlete triad (Triad, which refers to the interrelatedness of energy availability, menstrual function, and bone mineral density (BMD. These conditions often manifest clinically as disordered eating behaviors, menstrual irregularity, and stress fractures; an individual may suffer from 1 or all of the Triad components simultaneously. Because of the complex nature of the Triad, treatment is challenging and requires a multidisciplinary approach. Team members often include a physician, psychologist or psychiatrist, nutritionist or dietitian, physical therapist, athletic trainer, coach, family members, and most importantly, the patient. A thorough physical examination by a primary care physician is essential to identify all organs/systems that may be impacted by Triad-related conditions. Laboratory tests, assessment of bone density, nutritional assessment, and behavior health evaluation guide the management of the female athlete with Triad-related conditions. Treatment of the Triad includes adequate caloric consumption to restore a positive energy balance; this is often the first step in successful management of the Triad. In addition, determining the cause of menstrual dysfunction (MD and resumption of menses is very important. Nonpharmacologic interventions are the first choice; pharmacologic treatment for MD is reserved only for those patients with symptoms of

  2. The Dark Triad Traits from a Life History Perspective in Six Countries

    Directory of Open Access Journals (Sweden)

    Peter K. Jonason

    2017-08-01

    Full Text Available Work on the Dark Triad traits has benefited from the use of a life history framework but it has been limited to primarily Western samples and indirect assessments of life history strategies. Here, we examine how the Dark Triad traits (i.e., psychopathy, Machiavellianism, and narcissism relate to two measures of individual differences in life history strategies. In Study 1 (N = 937, we replicated prior observed links between life history strategies, as measured by the Mini-K, and the Dark Triad traits using samples recruited from three countries. In Study 2 (N = 1032, we measured life history strategies using the Consideration of Future Consequences Scale and correlated it with the Dark Triad traits in samples recruited from three additional countries. While there was some variability across participants’ sex and country, the results were generally consistent in that psychopathy and (to a lesser extent Machiavellianism were related to faster life history strategies and narcissism was related to slower life history strategies. These results add cross-cultural data and the use of two measures of life history speed to understand the Dark Triad traits from a life history perspective.

  3. Characterization and evolutionary implications of the triad Asp-Xxx-Glu in group II phosphopantetheinyl transferases.

    Science.gov (United States)

    Wang, Yue-Yue; Li, Yu-Dong; Liu, Jian-Bo; Ran, Xin-Xin; Guo, Yuan-Yang; Ren, Ni-Ni; Chen, Xin; Jiang, Hui; Li, Yong-Quan

    2014-01-01

    Phosphopantetheinyl transferases (PPTases), which play an essential role in both primary and secondary metabolism, are magnesium binding enzymes. In this study, we characterized the magnesium binding residues of all known group II PPTases by biochemical and evolutionary analysis. Our results suggested that group II PPTases could be classified into two subgroups, two-magnesium-binding-residue-PPTases containing the triad Asp-Xxx-Glu and three-magnesium-binding-residue-PPTases containing the triad Asp-Glu-Glu. Mutations of two three-magnesium-binding-residue-PPTases and one two-magnesium-binding-residue-PPTase indicate that the first and the third residues in the triads are essential to activities; the second residues in the triads are non-essential. Although variations of the second residues in the triad Asp-Xxx-Glu exist throughout the whole phylogenetic tree, the second residues are conserved in animals, plants, algae, and most prokaryotes, respectively. Evolutionary analysis suggests that: the animal group II PPTases may originate from one common ancestor; the plant two-magnesium-binding-residue-PPTases may originate from one common ancestor; the plant three-magnesium-binding-residue-PPTases may derive from horizontal gene transfer from prokaryotes.

  4. HinT proteins and their putative interaction partners in Mollicutes and Chlamydiaceae

    Directory of Open Access Journals (Sweden)

    Hegemann Johannes H

    2005-05-01

    Full Text Available Background HinT proteins are found in prokaryotes and eukaryotes and belong to the superfamily of HIT proteins, which are characterized by an histidine-triad sequence motif. While the eukaryotic variants hydrolyze AMP derivates and modulate transcription, the function of prokaryotic HinT proteins is less clearly defined. In Mycoplasma hominis, HinT is concomitantly expressed with the proteins P60 and P80, two domains of a surface exposed membrane complex, and in addition interacts with the P80 moiety. Results An cluster of hitABL genes, similar to that of M. hominis was found in M. pulmonis, M. mycoides subspecies mycoides SC, M. mobile and Mesoplasma florum. RT-PCR analyses provided evidence that the P80, P60 and HinT homologues of M. pulmonis were polycistronically organized, suggesting a genetic and physical interaction between the proteins encoded by these genes in these species. While the hit loci of M. pneumoniae and M. genitalium encoded, in addition to HinT, a protein with several transmembrane segments, the hit locus of Ureaplasma parvum encoded a pore-forming protein, UU270, a P60 homologue, UU271, HinT, UU272, and a membrane protein of unknown function, UU273. Although a full-length mRNA spanning the four genes was not detected, amplification of all intergenic regions from the center of UU270 to the end of UU273 by RT-PCR may be indicative of a common, but unstable mRNA. In Chlamydiaceae the hit gene is flanked upstream by a gene predicted to encode a metal dependent hydrolase and downstream by a gene putatively encoding a protein with ARM-repeats, which are known to be involved in protein-protein interactions. In RT-PCR analyses of C. pneumoniae, regions comprising only two genes, Cp265/Cp266 and Cp266/Cp267 were able to be amplified. In contrast to this in vivo interaction analysis using the yeast two-hybrid system and in vitro immune co-precipitation revealed an interaction between Cp267, which contains the ARM repeats, Cp265, the

  5. Monodispersed Zinc Oxide Nanoparticle-Dye Dyads and Triads

    Energy Technology Data Exchange (ETDEWEB)

    Gladfelter, Wayne L. [Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Chemistry; Blank, David A. [Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Chemistry; Mann, Kent R. [Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Chemistry

    2017-06-22

    The overall energy conversion efficiency of photovoltaic cells depends on the combined efficiencies of light absorption, charge separation and charge transport. Dye-sensitized solar cells are photovoltaic devices in which a molecular dye absorbs light and uses this energy to initiate charge separation. The most efficient dye-sensitized solar cells (DSSCs) use nanocrystal titanium dioxide films to which are attached ruthenium complexes. Numerous studies have provided valuable insight into the dynamics of these and analogous photosystems, but the lack of site homogeneity in binding dye molecules to metal oxide films and nanocrystals (NCs) is a significant impediment to extracting fundamental details about the electron transfer across the interface. Although zinc oxide is emerging as a potential semiconducting component in DSSCs, there is less known about the factors controlling charge separation across the dye/ZnO interface. Zinc oxide crystallizes in the wurtzite lattice and has a band gap of 3.37 eV. One of the features that makes ZnO especially attractive is the remarkable ability to control the morphology of the films. Using solution deposition processes, one can prepare NCs, nanorods and nanowires having a variety of shapes and dimensions. This project solved problems associated with film heterogeneity through the use of dispersible sensitizer/ZnO NC ensembles. The overarching goal of this research was to study the relationship between structure, energetics and dynamics in a set of synthetically controlled donor-acceptor dyads and triads. These studies provided access to unprecedented understanding of the light absorption and charge transfer steps that lie at the heart of DSSCs, thus enabling significant future advances in cell efficiencies. The approach began with the construction of well-defined dye-NC dyads that were sufficiently dispersible to allow the use of state of the art pulsed laser spectroscopic and kinetic methods to understand the charge transfer

  6. Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

    Directory of Open Access Journals (Sweden)

    Manal Alkan

    2015-01-01

    Full Text Available Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD mouse model. To this end, we used mice (inactivated knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC−/− mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC−/− mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC−/− mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response.

  7. Role of histidine-related compounds to intracellular buffering in fish skeletal muscle.

    Science.gov (United States)

    Abe, H; Dobson, G P; Hoeger, U; Parkhouse, W S

    1985-10-01

    Histidine-related compounds (HRC) were analyzed in fish skeletal muscle as a means of identifying their precise role in intracellular buffering. Fish muscle was used because it contains two functionally and spatially distinct fiber types, red and white. Two fish species, rainbow trout (Salmo gairdneri) and the Pacific blue marlin (Makaira nigricans), were studied because these species demonstrate widely different activity patterns. Marlin red and white muscle buffer capacity was two times higher than trout with white muscle, buffering being two times greater than red in both species. Buffer capacity was highest in the 6.5-7.5 pH range for all tissues, which corresponded to their high anserine levels. The titrated HRC buffering was greater than the observed HRC buffering, which suggested that not all HRC were available to absorb protons. The HRC contribution to total cellular buffering varied from a high of 62% for marlin white to a low of 7% for trout red. The other principal buffers were found to be phosphate and protein with taurine contributing within red muscle in the 7.0-8.0 pH range. HRC were found to be dominant in skeletal muscle buffering by principally accounting for the buffering capacity differences found between the species and fiber types.

  8. Histidine-rich glycoprotein can prevent development of mouse experimental glioblastoma.

    Directory of Open Access Journals (Sweden)

    Maria Kärrlander

    Full Text Available Extensive angiogenesis, formation of new capillaries from pre-existing blood vessels, is an important feature of malignant glioma. Several antiangiogenic drugs targeting vascular endothelial growth factor (VEGF or its receptors are currently in clinical trials as therapy for high-grade glioma and bevacizumab was recently approved by the FDA for treatment of recurrent glioblastoma. However, the modest efficacy of these drugs and emerging problems with anti-VEGF treatment resistance welcome the development of alternative antiangiogenic therapies. One potential candidate is histidine-rich glycoprotein (HRG, a plasma protein with antiangiogenic properties that can inhibit endothelial cell adhesion and migration. We have used the RCAS/TV-A mouse model for gliomas to investigate the effect of HRG on brain tumor development. Tumors were induced with platelet-derived growth factor-B (PDGF-B, in the presence or absence of HRG. We found that HRG had little effect on tumor incidence but could significantly inhibit the development of malignant glioma and completely prevent the occurrence of grade IV tumors (glioblastoma.

  9. Zinc ion coordination as a modulating factor of the ZnuA histidine-rich loop flexibility: A molecular modeling and fluorescence spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Castelli, Silvia [Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome (Italy); Stella, Lorenzo [Department of Chemical Sciences and Technologies, University of Roma Tor Vergata, Via della Ricerca Scientifica, 00133 Rome (Italy); Neuromed, IRCCS, Pozzilli 86077 (Italy); Petrarca, Patrizia [Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome (Italy); Battistoni, Andrea [Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome (Italy); Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), Viale delle Medaglie D' Oro 305, 00136 Rome (Italy); Desideri, Alessandro [Department of Biology, University of Rome Tor Vergata and CIBB, Center of Biostatistics and Bioinformatics, Via della Ricerca Scientifica, 00133 Rome (Italy); Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), Viale delle Medaglie D' Oro 305, 00136 Rome (Italy); Falconi, Mattia, E-mail: falconi@uniroma2.it [Department of Biology, University of Rome Tor Vergata and CIBB, Center of Biostatistics and Bioinformatics, Via della Ricerca Scientifica, 00133 Rome (Italy); Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), Viale delle Medaglie D' Oro 305, 00136 Rome (Italy)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Fluorescence data indicate that the His-loop of ZnuA interacts with Zn{sup +2} ions. Black-Right-Pointing-Pointer The ZnuA structural model proposed validates these spectroscopic findings. Black-Right-Pointing-Pointer It is proposed that a zinc loaded His-loop may facilitate the ZnuA-ZnuB recognition. -- Abstract: ZnuA is the soluble component of the high-affinity ZnuABC zinc transporter belonging to the ATP-binding cassette-type periplasmic Zn-binding proteins. The zinc transporter ZnuABC is composed by three proteins: ZnuB, the membrane permease, ZnuC, the ATPase component and ZnuA, the soluble periplasmic metal-binding protein which captures Zn and delivers it to ZnuB. The ZnuA protein contains a charged flexible loop, rich in histidines and acidic residues, showing significant species-specific differences. Various studies have established that this loop contributes to the formation of a secondary zinc binding site, which has been proposed to be important in the acquisition of periplasmic Zn for its delivery to ZnuB or for regulation of zinc uptake. Due to its high mobility the structure of the histidine-rich loop has never been solved by X-ray diffraction studies. In this paper, through a combined use of molecular modeling, mutagenesis and fluorescence spectroscopy, we confirm the presence of two zinc binding sites characterized by different affinities for the metal ion and show that the flexibility of the loop is modulated by the binding of the zinc ions to the protein. The data obtained by fluorescence spectroscopy have then be used to validate a 3D model including the unsolved histidine-rich loop.

  10. Computational analysis of histidine mutations on the structural stability of human tyrosinases leading to albinism insurgence.

    Science.gov (United States)

    Hassan, Mubashir; Abbas, Qamar; Raza, Hussain; Moustafa, Ahmed A; Seo, Sung-Yum

    2017-07-25

    Misfolding and structural alteration in proteins lead to serious malfunctions and cause various diseases in humans. Mutations at the active binding site in tyrosinase impair structural stability and cause lethal albinism by abolishing copper binding. To evaluate the histidine mutational effect, all mutated structures were built using homology modelling. The protein sequence was retrieved from the UniProt database, and 3D models of original and mutated human tyrosinase sequences were predicted by changing the residual positions within the target sequence separately. Structural and mutational analyses were performed to interpret the significance of mutated residues (N 180 , R 202 , Q 202 , R 211 , Y 363 , R 367 , Y 367 and D 390 ) at the active binding site of tyrosinases. CSpritz analysis depicted that 23.25% residues actively participate in the instability of tyrosinase. The accuracy of predicted models was confirmed through online servers ProSA-web, ERRAT score and VERIFY 3D values. The theoretical pI and GRAVY generated results also showed the accuracy of the predicted models. The CCA negative correlation results depicted that the replacement of mutated residues at His within the active binding site disturbs the structural stability of tyrosinases. The predicted CCA scores of Tyr 367 (-0.079) and Q/R 202 (0.032) revealed that both mutations have more potential to disturb the structural stability. MD simulation analyses of all predicted models justified that Gln 202 , Arg 202 , Tyr 367 and D 390 replacement made the protein structures more susceptible to destabilization. Mutational results showed that the replacement of His with Q/R 202 and Y/R 363 has a lethal effect and may cause melanin associated diseases such as OCA1. Taken together, our computational analysis depicts that the mutated residues such as Q/R 202 and Y/R 363 actively participate in instability and misfolding of tyrosinases, which may govern OCA1 through disturbing the melanin biosynthetic pathway.

  11. Relationship between the dark triad personality and cyber bullying in student internet users

    Directory of Open Access Journals (Sweden)

    Nader Hajlo

    2015-04-01

    Full Text Available Background: Cyber bullying is defined as a series of deliberate and repeated sadistic behaviors which occur through such tools as computer, phone and other electronic devices. The current study was aimed to determine to what extent the dark triad personality predicts the phenomenon of cyber bullying among the youth. Methods: For this investigation, 200 internet users were selected through snowball sampling and data were obtained by the questionnaires sent via e-mail. Results: The results of investigation indicated that all dark triad personality traits (Machiavellianism, Psychopath and Narcissism had a significantly positive relationship with cyber bullying. Also, Machiavellianism and Psychopath personality traits were respectively the strongest variables in predicting cyber bullying. Conclusion: all dark triad personality traits have the ability to predict cyber bullying phenomenon.

  12. Mediating the Maltreatment-Delinquency Relationship: The Role of Triad Gang Membership.

    Science.gov (United States)

    Chui, Wing Hong; Khiatani, Paul Vinod

    2018-02-01

    The primary aim of this article is to examine the role of triad affiliation in mediating the relationship between child maltreatment (neglect, punishment, emotional abuse, and sexual abuse) and delinquency among active young gang members in Hong Kong. A sample of 177 gang members aged 12 to 24 was recruited to complete a questionnaire with the assistance of a youth outreach social work team. Neglect was identified as the most common form of maltreatment, followed by emotional abuse, punishment, and sexual abuse. Mediation analyses confirmed that triad affiliation acts as a mediating variable in the child maltreatment-delinquency relationship, except in cases of sexual abuse. Only the relationship between punishment and delinquency was found to be fully mediated by triad affiliation; partial mediation effects were found for neglect and emotional abuse. Recommendations for child protection and youth workers are provided.

  13. The occurrence of technological triad: descriptive concept of today’s totality of reality

    Directory of Open Access Journals (Sweden)

    Milijana Mičunović

    2016-07-01

    Full Text Available Scientific discourse refers to triads as conceptual structures whose purpose is to emphasize the connection between concepts included in the description of a certain phenomenon. The famous Popper’s triad is comprised of the world of physical objects and processes (World 1, the world of mental objects, i.e. subjective human experience (World 2 and the world of objective knowledge (World 3, which can be thought of as all the products of thought – the world of information, knowledge, scientific theories, literature, etc. During the past half-century, Information and Communication Technology (ICT and new media began to change our reality on all three levels. Using a comparative analysis, this paper will examine the impact ICT and new media have on the Popper’s World 1, 2 and 3.As it will be shown, the modern age offers a new conceptual triad the aim of which is not to stand against the Popper’s triad but to introduce new integral elements that intersect and interact with it. In this new triad the world of physical objects is being replaced by the world of virtual reality (i.e. the Virtual World, the world of mental objects is replaced by transmental objects (i.e. the Transmental World and the world of objective knowledge is being replaced by the world of digitized data/information/ knowledge in the context of developing AI (i.e. the Digital World. These new architectonic elements build new conceptual structure the aim of which is to define, describe and represent new interrelated concepts essential for better understanding of today’s totality of reality. They form new ontology of the world which describes reality as inseparable from the concepts of information and technology.Keywords: Popper’s triad, ICT, totality of reality, virtual realities, human-technology interaction, artificial intelligence

  14. Currarino triad: characteristic appearances on magnetic resonance imaging and plain radiography

    International Nuclear Information System (INIS)

    Low, G.; Irwin, G.J; Maroo, S.V.; Haddock, G.

    2006-01-01

    The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings Copyright (2006) Blackwell Publishing Asia Pty Ltd

  15. The triad enters its fourth decade: The next steps in U.S. strategic forces

    International Nuclear Information System (INIS)

    Nolan, J.

    1990-01-01

    There is a distinct correlation between development and deployment of US deterrent systems - our strategic triad- and the incentive for potential adversaries to engagin in meaningful arms control discussions. The USSR has, and will retain, enormous strategic strength and conventional forces with attendant moderization programs under way. If the threat diminishes, it will do so slowly. While the strategic forces on which the US relies for deterrence account for only a small percentage of the DOD budget, they but a great deal of deterrence. Continued modernization of the strategic triad is essential as restructuring goes on in the wake of impending arms control agreements

  16. Pulse radiolytic and electrochemical investigations of intramolecular electron transfer in carotenoporphyrins and carotenoporphyrin-quinone triads

    International Nuclear Information System (INIS)

    Land, E.J.; Lexa, D.; Bensasson, R.V.; Gust, D.; Moore, T.A.; Moore, A.L.; Liddell, P.A.; Nemeth, G.A.

    1987-01-01

    Thermodynamic and kinetic aspects of intramolecular electron-transfer reactions in carotenoporphyrin dyads and carotenoid-porphyrin-quinone triads have been studied by using pulse radiolysis and cyclic voltammetry. Rapid (<1 μs) electron transfer from carotenoid radical anions to attached porphyrins has been inferred. Carotenoid cations, on the other hand, do not readily accept electrons from attached porphyrins or pyropheophorbides. Electrochemical studies provide the thermodynamic basis for these observations and also allow estimation of the energetics of photoinitiated two-step electron transfer and two-step charge recombination in triad models for photosynthetic charge separation

  17. 78 FR 45181 - Foreign-Trade Zone 230-Piedmont Triad Area, North Carolina, Authorization of Production Activity...

    Science.gov (United States)

    2013-07-26

    ... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-31-2013] Foreign-Trade Zone 230--Piedmont Triad Area, North Carolina, Authorization of Production Activity, Oracle Flexible Packaging, Inc., (Foil-Backed Paperboard), Winston-Salem, North Carolina On March 25, 2013, the Piedmont Triad Partnership...

  18. Signal Sensing and Transduction by Histidine Kinases as Unveiled through Studies on a Temperature Sensor.

    Science.gov (United States)

    Abriata, Luciano A; Albanesi, Daniela; Dal Peraro, Matteo; de Mendoza, Diego

    2017-06-20

    Histidine kinases (HK) are the sensory proteins of two-component systems, responsible for a large fraction of bacterial responses to stimuli and environmental changes. Prototypical HKs are membrane-bound proteins that phosphorylate cognate response regulator proteins in the cytoplasm upon signal detection in the membrane or periplasm. HKs stand as potential drug targets but also constitute fascinating systems for studying proteins at work, specifically regarding the chemistry and mechanics of signal detection, transduction through the membrane, and regulation of catalytic outputs. In this Account, we focus on Bacillus subtilis DesK, a membrane-bound HK part of a two-component system that maintains appropriate membrane fluidity at low growth temperatures. Unlike most HKs, DesK has no extracytoplasmic signal-sensing domains; instead, sensing is carried out by 10 transmembrane helices (coming from two protomers) arranged in an unknown structure. The fifth transmembrane helix from each protomer connects, without any of the intermediate domains found in other HKs, into the dimerization and histidine phosphotransfer (DHp) domain located in the cytoplasm, which is followed by the ATP-binding domains (ABD). Throughout the years, genetic, biochemical, structural, and computational studies on wild-type, mutant, and truncated versions of DesK allowed us to dissect several aspects of DesK's functioning, pushing forward a more general understanding of its own structure/function relationships as well as those of other HKs. We have shown that the sensing mechanism is rooted in temperature-dependent membrane properties, most likely a combination of thickness, fluidity, and water permeability, and we have proposed possible mechanisms by which DesK senses these properties and transduces the signals. X-ray structures and computational models have revealed structural features of TM and cytoplasmic regions in DesK's kinase- and phosphatase-competent states. Biochemical and genetic

  19. Role of individual histidines in the pH-dependent global stability of human chloride intracellular channel 1.

    Science.gov (United States)

    Achilonu, Ikechukwu; Fanucchi, Sylvia; Cross, Megan; Fernandes, Manuel; Dirr, Heini W

    2012-02-07

    Chloride intracellular channel proteins exist in both a soluble cytosolic form and a membrane-bound form. The mechanism of conversion between the two forms is not properly understood, although one of the contributing factors is believed to be the variation in pH between the cytosol (~7.4) and the membrane (~5.5). We systematically mutated each of the three histidine residues in CLIC1 to an alanine at position 74 and a phenylalanine at positions 185 and 207. We examined the effect of the histidine-mediated pH dependence on the structure and global stability of CLIC1. None of the mutations were found to alter the global structure of the protein. However, the stability of H74A-CLIC1 and H185F-CLIC1, as calculated from the equilibrium unfolding data, is no longer dependent on pH because similar trends are observed at pH 7.0 and 5.5. The crystal structures show that the mutations result in changes in the local hydrogen bond coordination. Because the mutant total free energy change upon unfolding is not different from that of the wild type at pH 7.0, despite the presence of intermediates that are not seen in the wild type, we propose that it may be the stability of the intermediate state rather than the native state that is dependent on pH. On the basis of the lower stability of the intermediate in the H74A and H185F mutants compared to that of the wild type, we conclude that both His74 and His185 are involved in triggering the pH changes to the conformational stability of wild-type CLIC1 via their protonation, which stabilizes the intermediate state.

  20. Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.

    Science.gov (United States)

    Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg; Kretzschmar, Hans; Westaway, David

    2017-01-01

    Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain.

  1. Photoinduced energy and electron transfer in fullerene- oligothiophene-fullerene triads

    NARCIS (Netherlands)

    Hal, Paul A. van; Knol, Joop; Langeveld-Voss, Bea M.W.; Meskers, Stefan C.J.; Hummelen, J.C.; Janssen, René A.J.

    2000-01-01

    A series of fullerene-oligothiophene-fullerene (C60-nT-C60) triads with n = 3, 6, or 9 thiophene units has been synthesized, and their photophysical properties have been studied using photoinduced absorption and fluorescence spectroscopy in solution and in the solid state as thin films. The results

  2. GRAND PLAZA SITE INVESTIGATION USING THE TRIAD APPROACH AND EVALUATION OF VAPOR INTRUSION - (ITER)

    Science.gov (United States)

    This document provides a detailed report about a field study conducted by EQM/URS on behalf of EPA/NRMRL to characterize the subsurface contamination of volatile organic compounds (VOCs) at a Brownfield commercial site. The TRIAD approach was implemented to characterize the exten...

  3. USING THE SEDIMENT QUALITY TRIAD (SQT) APPROACH TO ASSESS SEDIMENTARY CONTAMINATION IN THE ANACOSTIA RIVER, WASHINGTON

    Science.gov (United States)

    Using the Sediment Quality Triad (SQT) Approach to Assess Sedimentary Contamination in the Anacostia River, Washington, D.C. Velinsky, DJ*1, Ashley, JTF1,2, Pinkney, F.3, McGee, BL3 and Norberg-King, TJ.4 1Academy of Natural Sciences-PCER, Philadelphia, PA. 2Philadelphia Universi...

  4. Low bone density risk is higher in exercising women with multiple triad risk factors.

    Science.gov (United States)

    Gibbs, Jenna C; Nattiv, Aurelia; Barrack, Michelle T; Williams, Nancy I; Rauh, Mitchell J; Nichols, Jeanne F; De Souza, Mary Jane

    2014-01-01

    The cumulative effect of the female athlete triad (Triad) risk factors on the likelihood of low bone mineral density (BMD) in exercising women is unclear. This study aimed to determine the risk of low BMD in exercising women with multiple Triad risk factors. We retrospectively examined cross-sectional data from 437 exercising women (mean ± SD age of 18.0 ± 3.5 yr, weighed 57.5 ± 7.1 kg with 24.5% ± 6.1% body fat) obtained at baseline from 4 prospective cohort studies examining Triad risk factors. Questionnaires were completed to obtain information on demographic characteristics, self-reported eating attitudes/behaviors, menstrual function, sport/activity participation, and medication use. Height and body weight were measured. BMD was measured using dual energy x-ray absorptiometry. Low BMD was defined as z-scores of exercising women. Further research should be conducted to develop a user-friendly algorithm integrating these indicators of risk for low BMD in exercising women (particularly factors associated with low BMI/body weight, menstrual dysfunction, lean sport/activity participation, and elevated dietary restraint).

  5. The AGI-ASU-NASA Triad Program for K-12 Earth and Space Science Education

    Science.gov (United States)

    Pacheco, H. A.; Semken, S. C.; Taylor, W.; Benbow, A. E.

    2011-12-01

    The NASA Triad program of the American Geological Institute (AGI) and Arizona State University School of Earth and Space Exploration (ASU SESE) is a three-part effort to promote Earth and space science literacy and STEM education at the national level, funded by NASA through a cooperative agreement starting in 2010. NASA Triad comprises (1) infusion of NASA STEM content into AGI's secondary Earth science curricula; (2) national lead teacher professional development workshops; and (3) an online professional development guide for teachers running NASA STEM workshops. The Triad collaboration draws on AGI's inquiry-based curriculum and teacher professional-development resources and workforce-building programs; ASU SESE's spectrum of research in Mars and Moon exploration, astrobiology, meteoritics, Earth systems, and cyberlearning; and direct access to NASA facilities and dynamic education resources. Triad milestones to date include integration of NASA resources into AGI's print and online curricula and two week-long, national-scale, teacher-leader professional development academies in Earth and space sciences presented at ASU Dietz Museum in Tempe and NASA Johnson Space Flight Center in Houston. Robust front-end and formative assessments of these program components, including content gains, teacher-perceived classroom relevance, teacher-cohort lesson development, and teacher workshop design, have been conducted. Quantitative and qualitative findings from these assessment activities have been applied to identify best and most effective practices, which will be disseminated nationally and globally through AGI and NASA channels.

  6. A Rare Triad of Giant Occipital Encephalocele with Lipomyelomeningocele, Tetralogy of Fallot, and Situs Inversus

    Science.gov (United States)

    Franco, Arie; Jo, Stephanie Y; Mehta, Amar S; Pandya, Dave J; Yang, Carina W

    2016-01-01

    Giant encephalocele is an uncommon congenital anomaly with very few published reports available in the English literature. Tetralogy of Fallot associated with situs inversus is also infrequently reported. To our knowledge there are no published reports of an association between giant encephalocele and Tetralogy of Fallot. The additional finding of situs inversus results in a rare pathologic triad, not heretofore described. PMID:27200165

  7. Collegiate coaches' knowledge of the female athlete triad in relation to sport type.

    Science.gov (United States)

    Frideres, Jillian E; Mottinger, Sue G; Palao, José M

    2016-03-01

    The purpose of this study was to determine what coaches of female athletes know about the three components of the female athlete triad with regard to type of sport coached and the characteristics of the coach. The sample consisted of 309 NCAA Division I coaches of female athletes in the sports of: sports with subjective scoring of performance (gymnastics and diving), low body weight sports (cross country and rowing), revealing or fitted clothing (volleyball and swimming), and other (soccer and basketball). An original, self-report questionnaire, and a 4-point Likert scale to measure confidence in answer was used. The variables were: knowledge, confidence, and coach's characteristics (coach's gender, degree held, years of experience in coaching females, continuing education participation specific to the triad and triad components, and type of sport coached). Coaches of low body weight sports scored significantly higher than both coaches of sports requiring fitted clothing and "other" sports in the overall score. They further had significantly more confidence in their answers than coaches of "other" sports. No significant differences in the overall score in any of the types of sport or total values were found regarding gender, experience, and degree. Coaches who had received training about the triad or its components scored significantly higher than coaches who did not receive training. The results demonstrated a lack of information among coaches and that participating in formative training can help to reduce this problem. The results found can help in the design of continuing education for coaches.

  8. A Rare Triad of Giant Occipital Encephalocele with Lipomyelomeningocele, Tetralogy of Fallot, and Situs Inversus.

    Science.gov (United States)

    Franco, Arie; Jo, Stephanie Y; Mehta, Amar S; Pandya, Dave J; Yang, Carina W

    2016-03-01

    Giant encephalocele is an uncommon congenital anomaly with very few published reports available in the English literature. Tetralogy of Fallot associated with situs inversus is also infrequently reported. To our knowledge there are no published reports of an association between giant encephalocele and Tetralogy of Fallot. The additional finding of situs inversus results in a rare pathologic triad, not heretofore described.

  9. The Triad Research University or a Post 20th Century Research University Model

    Science.gov (United States)

    Tadmor, Zehev

    2006-01-01

    In this paper, a model for the future research university is proposed, which answers some of the key challenges facing universities. It consists of three independent yet closely knitted entities: a research institute, a university teaching college and a business unit creating a "triad" structure. The possible inevitability, the advantages and…

  10. A global energy network? The expansion and integration of non-triad national oil companies

    NARCIS (Netherlands)

    de Graaff, N.A.

    2011-01-01

    It is widely perceived that the rising influence of state-owned energy companies from outside the traditional triad (USA, EU, Japan) is transforming the structure of the global energy market and generating a new wave of resource-nationalism. There is, however, little empirical analysis of how this

  11. Ecological risks of an old wood impregnation mill: application of the triad approach.

    NARCIS (Netherlands)

    Karjalainen, A.-M.; Kilpi-Koski, J.; Väisänen, A.O.; Penttinen, S.; van Gestel, C.A.M.; Penttinen, O.-P.

    2009-01-01

    Although many studies deal with the distribution and mobility of chromated copper arsenate (CCA) metals in soil, the ecotoxicity of CCA-contaminated soils is rarely studied. The Triad approach was applied to determine the ecological risks posed by a CCA mixture at a decommissioned wood impregnation

  12. The Role of New Information Technologies in Facilitating Professional Reflective Practice across the Supervisory Triad.

    Science.gov (United States)

    Hodder, Jacqueline; Carter, David

    This study investigated the role of new information management technologies in facilitating student teacher supervision across the supervisory triad of student teacher, cooperating teacher, and university supervisor. The study investigated how data routinely generated by teachers and stored within an Instructional Information Management System…

  13. Triads in Equine-Assisted Social Work Enhance Therapeutic Relationships with Self-Harming Adolescents.

    Science.gov (United States)

    Carlsson, Catharina

    2017-01-01

    Despite an increasing number of studies, there is still a lack of knowledge about the unique features that underlie the process in equine assisted social work (EASW). This study aimed to reveal, through qualitative methods, the dyads within the triad that become stronger during the process of EASW, as well as the effect of the participation of the horse on the relationship between the counselor and client. Data were collected through in-depth interviews with nine female self-harming clients aged 15-21 years and eight staff members. The interviews, together with video-recorded human-horse interactions with three staff members and four clients were analyzed, resulting in additional issues answered by these three staff members and four clients in a second interview. Critical dialogues between patterns and fragmentations in the narratives and video-recordings, as well as a dialogue with the participants while they were viewing videos of their own EASW sessions, led to the conclusion that adding a horse qualitatively changes therapeutic relationships in EASW. The different triads consist of different liaisons between actors in the triad, giving rise to unique combinations. The quality of the relationships depends on both the staff and the clients' attachment orientations. Further research is needed to investigate how the degree of emotional connection to the horse affects the impact that horses have on triads in EASW.

  14. Charge Separation and Recombination in Small Band Gap Oligomer-Fullerene Triads

    NARCIS (Netherlands)

    Karsten, Bram P.; Bouwer, Ricardo K. M.; Hummelen, Jan C.; Williams, Rene M.; Janssen, Rene A. J.

    2010-01-01

    Synthesis and photophysics of a series of thiophene-thienopyrazine small band gap oligomers end-capped at both ends with C(60) are presented In these triads a photoinduced electron transfer reaction occurs between the oligomer as a donor and the fullerene as an acceptor Femtosecond photoinduced

  15. Coalitions in Primary Triads: Reexamining the Theoretical Constructs From A Feminist Perspective.

    Science.gov (United States)

    Milstein, Kaylene; Baldwin, Cynthia

    1997-01-01

    Examines the theoretical constructs about the effects of coalitions in the father-mother-child triad from a family systems perspective. How this triadic view interacts with the historical patriarchal structure and with issues of power is addressed from a feminist perspective. (Author/MKA)

  16. Complete classification of discrete resonant Rossby/drift wave triads on periodic domains

    Science.gov (United States)

    Bustamante, Miguel D.; Hayat, Umar

    2013-09-01

    We consider the set of Diophantine equations that arise in the context of the partial differential equation called "barotropic vorticity equation" on periodic domains, when nonlinear wave interactions are studied to leading order in the amplitudes. The solutions to this set of Diophantine equations are of interest in atmosphere (Rossby waves) and Tokamak plasmas (drift waves), because they provide the values of the spectral wavevectors that interact resonantly via three-wave interactions. These wavenumbers come in "triads", i.e., groups of three wavevectors. We provide the full solution to the Diophantine equations in the physically sensible limit when the Rossby deformation radius is infinite. The method is completely new, and relies on mapping the unknown variables via rational transformations, first to rational points on elliptic curves and surfaces, and from there to rational points on quadratic forms of "Minkowski" type (such as the familiar space-time in special relativity). Classical methods invented centuries ago by Fermat, Euler, Lagrange, Minkowski, are used to classify all solutions to our original Diophantine equations, thus providing a computational method to generate numerically all the resonant triads in the system. Computationally speaking, our method has a clear advantage over brute-force numerical search: on a 10,0002 grid, the brute-force search would take 15 years using optimised C codes on a cluster, whereas our method takes about 40 min using a laptop. Moreover, the method is extended to generate so-called quasi-resonant triads, which are defined by relaxing the resonant condition on the frequencies, allowing for a small mismatch. Quasi-resonant triads' distribution in wavevector space is robust with respect to physical perturbations, unlike resonant triads' distribution. Therefore, the extended method is really valuable in practical terms. We show that the set of quasi-resonant triads form an intricate network of connected triads, forming

  17. The active transport of histidine and its role in ATP production in Trypanosoma cruzi.

    Science.gov (United States)

    Barisón, M J; Damasceno, F S; Mantilla, B S; Silber, A M

    2016-08-01

    Trypanosoma cruzi, the aetiological agent of Chagas's disease, metabolizes glucose, and after its exhaustion, degrades amino acids as energy source. Here, we investigate histidine uptake and its participation in energy metabolism. No putative genes for the histidine biosynthetic pathway have been identified in genome databases of T. cruzi, suggesting that its uptake from extracellular medium is a requirement for the viability of the parasite. From this assumption, we characterized the uptake of histidine in T. cruzi, showing that this amino acid is incorporated through a single and saturable active system. We also show that histidine can be completely oxidised to CO2. This finding, together with the fact that genes encoding the putative enzymes for the histidine - glutamate degradation pathway were annotated, led us to infer its participation in the energy metabolism of the parasite. Here, we show that His is capable of restoring cell viability after long-term starvation. We confirm that as an energy source, His provides electrons to the electron transport chain, maintaining mitochondrial inner membrane potential and O2 consumption in a very efficient manner. Additionally, ATP biosynthesis from oxidative phosphorylation was found when His was the only oxidisable metabolite present, showing that this amino acid is involved in bioenergetics and parasite persistence within its invertebrate host.

  18. Mussel-inspired histidine-based transient network metal coordination hydrogels

    Science.gov (United States)

    Fullenkamp, Dominic E.; He, Lihong; Barrett, Devin G.; Burghardt, Wesley R.; Messersmith, Phillip B.

    2013-01-01

    Transient network hydrogels cross-linked through histidine-divalent cation coordination bonds were studied by conventional rheologic methods using histidine-modified star poly(ethylene glycol) (PEG) polymers. These materials were inspired by the mussel, which is thought to use histidine-metal coordination bonds to impart self-healing properties in the mussel byssal thread. Hydrogel viscoelastic mechanical properties were studied as a function of metal, pH, concentration, and ionic strength. The equilibrium metal-binding constants were determined by dilute solution potentiometric titration of monofunctional histidine-modified methoxy-PEG and were found to be consistent with binding constants of small molecule analogs previously studied. pH-dependent speciation curves were then calculated using the equilibrium constants determined by potentiometric titration, providing insight into the pH dependence of histidine-metal ion coordination and guiding the design of metal coordination hydrogels. Gel relaxation dynamics were found to be uncorrelated with the equilibrium constants measured, but were correlated to the expected coordination bond dissociation rate constants. PMID:23441102

  19. Hydrogen-deuterium exchange in imidazole as a tool for studying histidine phosphorylation.

    Science.gov (United States)

    Cebo, Małgorzata; Kielmas, Martyna; Adamczyk, Justyna; Cebrat, Marek; Szewczuk, Zbigniew; Stefanowicz, Piotr

    2014-12-01

    Isotope exchange at the histidine C2 atom of imidazole in D2O solution is well known to occur at a significantly slower rate than the exchange of amide protons. Analysis of the kinetics of this isotope-exchange reaction is proposed herein as a method of detecting histidine phosphorylation. This modification of His-containing peptides is challenging to pinpoint because of its instability under acidic conditions as well as during CID-MS analysis. In this work, we investigated the effect of phosphorylation of the histidine side chain in peptides on deuterium-hydrogen exchange (DHX) in the imidazole. The results demonstrate that phosphorylation dramatically slows the rate of the DHX reaction. This phenomenon can be applied to detect phosphorylation of peptides at the histidine residue (e.g., in enzymatic digests). We also found that the influence of the peptide sequence on the exchange kinetics is relatively small. A CID fragmentation experiment revealed that there was no detectable hydrogen scrambling in peptides deuterated at C2 of the imidazole ring. Therefore, MS/MS can be used to directly identify the locations of deuterium ions incorporated into peptides containing multiple histidine moieties.

  20. The female athlete triad in student track and field athletes

    African Journals Online (AJOL)

    2012-08-22

    Aug 22, 2012 ... that is available for other metabolic processes in the body after the energy cost of ... availability, and 12.5% reported stress fractures during the past two years. .... fat high-carbohydrate diets, high-protein low-carbohydrate diets.

  1. Photo-oxidation of histidine peptides yields high concentrations of unstable peroxides

    International Nuclear Information System (INIS)

    Policarpio, V.V.; Hawkins, C.L.; Davies, M.J.

    2003-01-01

    Oxidation of proteins by UV, and visible light in the presence of sensitizers, results in side chain modification as well as aggregation and fragmentation. In particular, singlet oxygen has been reported to oxidize Met, Trp, Tyr, Cys and His side chains in a selective manner. In this study the oxidation of histidine and its derivatives, and His-containing peptides is examined using a range of sensitizers, to determine whether peroxides are major intermediates, and the mechanism of formation of these species. Visible light-sensitised oxidation of Gly-His-Gly in the presence of oxygen and rose bengal gives unstable substrate-derived peroxides with the peroxide yield increasing with increasing photolysis time. Similar behaviour was detected with other photosensitizers, though the peroxide yields varied with the sensitizer at identical concentrations with rose bengal > aluminium phthalocyanine > hematoporphyrin IX > zinc phthalocyanine > tetrakisporphine. The peroxide yield was decreased in the presence of azide and enhanced when deuterium oxide was employed as the solvent, consistent with peroxide formation being singlet oxygen mediated. Experiments using anoxic conditions gave low yields of peroxides confirming the oxygen-dependence of these reactions. HPLC analysis showed rapid loss of the parent peptide, with subsequent formation of both stable and unstable products; these are currently being characterized by MS and NMR. Similar behavior has been observed with other His derivatives. The yield of singlet oxygen formed in these reactions has been estimated using a bleaching assay (N, N-dimethyl-4-nitrosoaniline). Quantification of singlet oxygen formation and Gly-His-Gly derived peroxide during rose bengal-mediated photooxidation indicated a conversion efficiency of the initial singlet oxygen into substrate-derived peroxides of ca. 75% indicating that peroxide formation is a highly efficient and major reaction pathway

  2. Histidine at Position 195 is Essential for Association of Heme-b in Lcp1VH2

    Science.gov (United States)

    Oetermann, Sylvia; Vivod, Robin; Hiessl, Sebastian; Hogeback, Jens; Holtkamp, Michael; Karst, Uwe; Steinbüchel, Alexander

    2018-03-01

    The latex clearing protein (Lcp) is the key enzyme of polyisoprene degradation in actinomycetes (Yikmis and Steinbüchel in Appl Environ Microbiol 78:4543-4551, https://doi.org/10.1128/AEM.00001-12, 2012). In this study it was shown that Lcp from Gordonia polyisoprenivorans VH2 (Lcp1VH2) harbors a non-covalently bound heme b as cofactor, which was identified by pyridine hemochrome spectra and confirmed by LC/ESI-ToF-MS. It contains iron, most likely in the Fe3+ state. We focused on the characterization of the heme-cofactor, its accessibility with respect to the conformation of Lcp1VH2, and the identification of putative histidine residues involved in the coordination of heme. A change was detectable in UV/Vis-spectra of reduced Lcp1VH2 when imidazole was added, showing that Lcp1VH2 "as isolated" occurs in an open state, directly being accessible for external ligands. In addition, three highly conserved histidines (H195, H200 and H228), presumably acting as ligands coordinating the heme within the heme pocket, were replaced with alanines by site-directed mutagenesis. The effect of these changes on in vivo rubber-mineralization was investigated. The lcp- deletion mutant complemented with the H195A variant of lcp1 VH2 was unable to mineralize poly(cis-1,4-isoprene). In vitro analyses of purified, recombinant Lcp1VH2H195A confirmed the loss of enzyme activity, which could be ascribed to the loss of heme. Hence, H195 is essential for the association of heme-b in the central region of Lcp1VH2.

  3. Histidine side-chain dynamics and protonation monitored by C-13 CPMG NMR relaxation dispersion

    DEFF Research Database (Denmark)

    Hass, M. A. S.; Yilmaz, A.; Christensen, Hans Erik Mølager

    2009-01-01

    the chemical shift titration experiments, and the CPMG derived exchange rates agree with those obtained previously from N-15 backbone relaxation measurements. Compared to measurements of backbone nuclei, C-13(epsilon 1) dispersion provides a more direct method to monitor interchanging protonation states...... or other kinds of conformational changes of histidine side chains or their environment. Advantages and shortcomings of using the C-13(epsilon 1) dispersion experiments in combination with chemical shift titration experiments to obtain information on exchange dynamics of the histidine side chains...

  4. Neighbor-directed histidine N(τ) alkylation. A route to imidazolium-containing phosphopeptide macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Wen-Jian [National Cancer Inst., Frederick, MD (United States); Park, Jung-Eun [National Cancer Inst., Bethesda, MD (United States); Grant, Robert [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lai, Christopher C. [National Cancer Inst., Frederick, MD (United States); Kelley, James A. [National Cancer Inst., Frederick, MD (United States); Yaffe, Michael B. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lee, Kyung S. [National Cancer Inst., Bethesda, MD (United States); Burke, Terrence R. [National Cancer Inst., Frederick, MD (United States)

    2015-07-07

    Our recently discovered, selective, on-resin route to N(τ)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. These cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Furthermore, neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.

  5. The translation research in a dental setting (TRiaDS programme protocol

    Directory of Open Access Journals (Sweden)

    McKee Lorna

    2010-07-01

    Full Text Available Abstract Background It is well documented that the translation of knowledge into clinical practice is a slow and haphazard process. This is no less true for dental healthcare than other types of healthcare. One common policy strategy to help promote knowledge translation is the production of clinical guidance, but it has been demonstrated that the simple publication of guidance is unlikely to optimise practice. Additional knowledge translation interventions have been shown to be effective, but effectiveness varies and much of this variation is unexplained. The need for researchers to move beyond single studies to develop a generalisable, theory based, knowledge translation framework has been identified. For dentistry in Scotland, the production of clinical guidance is the responsibility of the Scottish Dental Clinical Effectiveness Programme (SDCEP. TRiaDS (Translation Research in a Dental Setting is a multidisciplinary research collaboration, embedded within the SDCEP guidance development process, which aims to establish a practical evaluative framework for the translation of guidance and to conduct and evaluate a programme of integrated, multi-disciplinary research to enhance the science of knowledge translation. Methods Set in General Dental Practice the TRiaDS programmatic evaluation employs a standardised process using optimal methods and theory. For each SDCEP guidance document a diagnostic analysis is undertaken alongside the guidance development process. Information is gathered about current dental care activities. Key recommendations and their required behaviours are identified and prioritised. Stakeholder questionnaires and interviews are used to identify and elicit salient beliefs regarding potential barriers and enablers towards the key recommendations and behaviours. Where possible routinely collected data are used to measure compliance with the guidance and to inform decisions about whether a knowledge translation intervention is

  6. Ergothioneine, histidine, and two naturally occurring histidine dipeptides as radioprotectors against gamma-irradiation inactivation of bacteriophages T4 and P22

    International Nuclear Information System (INIS)

    Hartman, P.E.; Hartman, Z.; Citardi, M.J.

    1988-01-01

    Bacteriophages P22, T4+, and T4os (osmotic shock-resistant mutant with altered capsids) were diluted in 0.85% NaCl and exposed to gamma irradiation (2.79 Gy/min) at room temperature (24 degrees C). T4+ was more sensitive to inactivation than was P22, and the T4os mutant was even more sensitive than T4+. Catalase exhibited a strong protective effect and superoxide dismutase a weaker protection, indicating that H 2 O 2 or some product derived therefrom was predominant in causing inactivation of plaque formation. Low but significant (0.1-0.3 mM) reduced glutathione (GSH) enhanced phage inactivation, but a higher (1 mM) GSH concentration protected. A similar effect was found for the polyamine, spermidine. In contrast, 0.1 mM L-ergothioneine (2-thiol-L-histidine betaine) exhibited strong protection and 1 mM afforded essentially complete protection. L-Ergothioneine is present in millimolar concentrations in some fungi and is conserved up to millimolar concentrations in critical tissues when consumed by man. L-Histidine and two histidine-containing dipeptides, carnosine and anserine, protected at a concentration of 1 mM, a level at which they are present in striated muscles of various animals

  7. Structure of the sporulation histidine kinase inhibitor Sda from Bacillus subtilis and insights into its solution state

    Energy Technology Data Exchange (ETDEWEB)

    Jacques, David A.; Streamer, Margaret [School of Molecular and Microbial Biosciences, University of Sydney (Australia); Rowland, Susan L.; King, Glenn F. [Institute of Molecular Biology, University of Queensland (Australia); Guss, J. Mitchell; Trewhella, Jill; Langley, David B., E-mail: d.langley@usyd.edu.au [School of Molecular and Microbial Biosciences, University of Sydney (Australia)

    2009-06-01

    The crystal structure of Sda, a DNA-replication/damage checkpoint inhibitor of sporulation in B. subtilis, has been solved via the MAD method. The subunit arrangement in the crystal has enabled a reappraisal of previous biophysical data, resulting in a new model for the behaviour of the protein in solution. The crystal structure of the DNA-damage checkpoint inhibitor of sporulation, Sda, from Bacillus subtilis, has been solved by the MAD technique using selenomethionine-substituted protein. The structure closely resembles that previously solved by NMR, as well as the structure of a homologue from Geobacillus stearothermophilus solved in complex with the histidine kinase KinB. The structure contains three molecules in the asymmetric unit. The unusual trimeric arrangement, which lacks simple internal symmetry, appears to be preserved in solution based on an essentially ideal fit to previously acquired scattering data for Sda in solution. This interpretation contradicts previous findings that Sda was monomeric or dimeric in solution. This study demonstrates the difficulties that can be associated with the characterization of small proteins and the value of combining multiple biophysical techniques. It also emphasizes the importance of understanding the physical principles behind these techniques and therefore their limitations.

  8. Can you put too much on your plate? Uncertainty exposure in servitized triads

    DEFF Research Database (Denmark)

    Kreye, Melanie E.

    2017-01-01

    -national servitized triad in a European-North African set-up which was collected through 29 semi-structured interviews and secondary data. Findings: The empirical study identified the existence of the three uncertainty types and directional knock-on effects between them. Specifically, environmental uncertainty...... relational governance reduced relational uncertainty. The knock-on effects were reduced through organisational and relational responses. Originality: This paper makes two contributions. First, a structured analysis of the uncertainty exposure in servitized triads is presented which shows the existence...... of three individual uncertainty types and the knock-on effects between them. Second, organisational responses to reduce the three uncertainty types individually and the knock-on effects between them are presented....

  9. Design, validation, and reliability of survey to measure female athlete triad knowledge among coaches

    Directory of Open Access Journals (Sweden)

    Jillian E. Frideres

    2015-06-01

    Full Text Available The purpose of this study was to design and to test the validity and reliability of an instrument to evaluate coaches' knowledge about the female athlete triad syndrome and their confidence in this knowledge. The instrument collects information regarding: knowledge of the syndrome, components, prevention and intervention; confidence of the coaches in their answers; and coach's characteristics (gender, degree held, years of experience in coaching females, continuing education participation specific to the syndrome and its components, and sport coached. The process of designing the questionnaire and testing the validity and reliability of it was done in four phases: a design and development of the instrument, b content validity, c instrument reliability, and d concurrent validity. The results show that the instrument is suitable for measuring coaches' female athlete triad knowledge. The instrument can contribute to assessing the coaches' knowledge level in relation to this topic.

  10. The Future of the Ballistic Missile Submarine Force in the Russian Nuclear Triad

    Science.gov (United States)

    2008-09-01

    based forces are the more economical leg of the triad.61 An estimate made in 1995 by B.I. Pustovit , then the expert for the Committee for Military...Theodore Gerber, a professor of sociology at the University of Wisconsin–Madison, and Sarah Mendelson, a senior fellow in the Russia and Eurasia... Sarah Mendelson, “Strong Public Support for Military Reform in Russia” Program on New Approaches to Russian Security, Policy memo 288 (2003), 3. 45 In

  11. Family Triad Systemic Scale: An Instrument for Assessment of Relationships between Couple and Families of Origin

    OpenAIRE

    مونا چراغی; محمدعلی مظاهری; فرشته موتابی; لیلی پناغی; منصوره السادات صادقی; خدیجه سلمانی

    2017-01-01

    Because of noticeable role of relationships with in-laws in prediction of marital adjustment and satisfaction in Iran, it is necessary to provide an instrument based on Family Triad Systemic Model (FTSM) to assess the relationships between couple and two original families. The objective of present study was providing the instrument and checking the psychometric properties of it. An item pool (107 items) was created by using other related tools, interviews by experts and married people. Then 4...

  12. Sex and dark times' strategy: The Dark Triad and time perspective.

    Science.gov (United States)

    Moraga, Fernando R G; Nima, Ali A; Garcia, Danilo

    2017-03-01

    We investigated the effect of sex on associations between dark traits and time perspective dimensions. Responses by participants (N = 338) to the Short Dark Triad Inventory and the Zimbardo Time Perspective Inventory showed that while sex was involved in different time perspective associations of Machiavellianism, psychopathy, and narcissism, it did not moderate the dark times' strategy. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  13. Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity.

    Directory of Open Access Journals (Sweden)

    Shotaro Sasaki

    Full Text Available Monocarboxylate transporter 4 (MCT4 is a pH-dependent bi-directional lactate transporter. Transport of lactate via MCT4 is increased by extracellular acidification. We investigated the critical histidine residue involved in pH regulation of MCT4 function. Transport of lactate via MCT4 was measured by using a Xenopus laevis oocyte expression system. MCT4-mediated lactate transport was inhibited by Zn2+ in a pH physiological condition but not in an acidic condition. The histidine modifier DEPC (diethyl pyrocarbonate reduced MCT4 activity but did not completely inactivate MCT4. After treatment with DEPC, pH regulation of MCT4 function was completely knocked out. Inhibitory effects of DEPC were reversed by hydroxylamine and suppressed in the presence of excess lactate and Zn2+. Therefore, we performed an experiment in which the extracellular histidine residue was replaced with alanine. Consequently, the pH regulation of MCT4-H382A function was also knocked out. Our findings demonstrate that the histidine residue His382 in the extracellular loop of the transporter is essential for pH regulation of MCT4-mediated substrate transport activity.

  14. Highly Efficient Photocatalytic Hydrogen Production of Flower-like Cadmium Sulfide Decorated by Histidine

    Science.gov (United States)

    Wang, Qizhao; Lian, Juhong; Li, Jiajia; Wang, Rongfang; Huang, Haohao; Su, Bitao; Lei, Ziqiang

    2015-09-01

    Morphology-controlled synthesis of CdS can significantly enhance the efficiency of its photocatalytic hydrogen production. In this study, a novel three-dimensional (3D) flower-like CdS is synthesized via a facile template-free hydrothermal process using Cd(NO3)2•4H2O and thiourea as precursors and L-Histidine as a chelating agent. The morphology, crystal phase, and photoelectrochemical performance of the flower-like CdS and pure CdS nanocrystals are carefully investigated via various characterizations. Superior photocatalytic activity relative to that of pure CdS is observed on the flower-like CdS photocatalyst under visible light irradiation, which is nearly 13 times of pure CdS. On the basis of the results from SEM studies and our analysis, a growth mechanism of flower-like CdS is proposed by capturing the shape evolution. The imidazole ring of L-Histidine captures the Cd ions from the solution, and prevents the growth of the CdS nanoparticles. Furthermore, the photocatalytic contrast experiments illustrate that the as-synthesized flower-like CdS with L-Histidine is more stable than CdS without L-Histidine in the hydrogen generation.

  15. Structure-based discovery of inhibitors of the YycG histidine kinase

    DEFF Research Database (Denmark)

    Qin, X.; Zhang, J.; Xu, B.

    2006-01-01

    inhibitors of YycG histidine kinase thus are of potential value as leads for developing new antibiotics against infecting staphylococci. The structure-based virtual screening (SBVS) technology can be widely used in screening potential inhibitors of other bacterial TCSs, since it is more rapid and efficacious...... than traditional screening technology....

  16. C@Fe 3 O 4 /NTA-Ni magnetic nanospheres purify histidine-tagged ...

    African Journals Online (AJOL)

    This study reports synthesis of Ni-nitrilotriacetic acid (Ni-NTA) modified carbon nanospheres containing magnetic Fe3O4 particles (C@Fe3O4), which can act as a general tool to separate and purify histidine-tagged fetidin. In this experiment, C nanospheres are prepared from glucose using the hydrothermal process, ...

  17. Geometry and Framework Interactions of Zeolite-Encapsulated Copper(II)-Histidine Complexes

    NARCIS (Netherlands)

    Weckhuysen, B.M.; Grommen, R.; Manikandan, P.; Gao, Y.; Shane, T.; Shane, J.J.; Schoonheydt, R.A.; Goldfarb, D.

    2000-01-01

    The coordination geometry of zeolite-encapsulated copper(II)-histidine (CuHis) complexes, prepared by ion exchange of the complexes from aqueous solutions into zeolite NaY, was determined by a combination of UV-vis-NIR diffuse reflectance spectroscopy (DRS), X-band EPR, electron-spin-echo envelope

  18. Structural and Functional Aspects of the Sensor Histidine Kinase PrrB from Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Nowak, E.; Panjikar, S.; Morth, J.P.

    2006-01-01

    We describe the solution structures of two- and three-domain constructs of the sensor histidine kinase PrrB from Mycobacterium tuberculosis, which allow us to locate the HAMP linker relative to the ATP binding and dimerization domains. We show that the three-domain construct is active both...

  19. Dark Triad Personality and Wisdom in Prediction of Students' Academic Self-Efficacy

    Directory of Open Access Journals (Sweden)

    Sajjad Saadat

    2018-01-01

    Full Text Available Introduction: A number of studies have argued that students' academic self-efficacy is affected by various factors. This study investigates the role of the dark triad personality and wisdom on the Iranian students' academic self-efficacy. Methods: In this correlational study, 177 (84 female and 93 male students of the University of Isfahan aged 18-54 years old (M = 23.1, SD = 4.9 were selected. Total academic mean range of the participants was 10 to 20 (M = 16.4, SD = 1.6. Participants completed the College Academic Self-Efficacy Scale, The Dark Triad Dirty Dozen, and Three-dimensional wisdom scales. Results: Results showed that there was a negative relationship between the variables of Machiavellianism and psychopathy and academic self-efficacy; inversely, there was a positive relationship between variables of cognitive and reflective wisdom and academic self-efficacy. Reflective wisdom, narcissism, and Machiavellianism predicted 0.17% of the self-efficacy. Conclusion: The results of the present study supported the importance of the dark triad personality and wisdom, as the variables, which were able to predict the academic self-efficacy of the students.

  20. Comparing the Measured and Latent Dark Triad: Are Three Measures Better than One?

    Directory of Open Access Journals (Sweden)

    Peter K. Jonason

    2011-10-01

    Full Text Available Could measurement level be a factor worth considering when studying the Dark Triad (i.e., narcissism, psychopathy, and Machiavellianism? In two studies (N  = 465, we compared the relative fit of two Dark Triad models: one that treats the three measures as separate-yet-related personality traits and another that treats the measures as tapping a single, latent construct. Mid-level personality traits, such as mate-retention strategies (Study 1 were best explained by a three-measure model, whereas the higher-order trait of sociosexuality (Study 2, were best explained by a single, latent-factor model. When considering mid-level measurement in personality, the three traits may provide independent effects for interpersonal relationships, whereas at the higher-order level, the three traits may function as a single entity relating to other higher-order traits. We suggest one should consider level of measurement between the predictor and criterion variables to better predict correlations among variables such as the Dark Triad. DOI: 10.2458/azu_jmmss.v2i1.12363

  1. Effect of bottom slope on the nonlinear triad interactions in shallow water

    Science.gov (United States)

    Chen, Hongzhou; Tang, Xiaocheng; Zhang, Ri; Gao, Junliang

    2018-05-01

    This paper aims at investigating the effect of bottom slope to the nonlinear triad interactions for irregular waves propagating in shallow water. The physical experiments are conducted in a wave flume with respect to the transformation of waves propagating on three bottom slopes ( β = 1/15, 1/30, and 1/45). Irregular waves with different type of breaking that are mechanically generated based on JONSWAP spectra are used for the test. The obviously different variations of spectra measured on each bottom reveal a crucial role of slope effect in the energy transfer between harmonics. The wavelet-based bispectrum were used to examine the bottom slope effect on the nonlinear triad interactions. Results show that the different bottom slopes which waves are propagated on will cause a significant discrepancy of triad interactions. Then, the discussions on the summed bicoherence which denote the distribution of phase coupling on each frequency further clarify the effect of bottom slope. Furthermore, the summed of the real and imaginary parts of bispectrum which could reflect the intensity of frequency components participating in the wave skewness and asymmetry were also investigated. Results indicate that the value of these parameters will increase as the bottom slope gets steeper.

  2. Internal wave mode resonant triads in an arbitrarly stratified finite-depth ocean with background rotation

    Science.gov (United States)

    Varma, Dheeraj; Mathur, Manikandan

    2017-11-01

    Internal tides generated by barotropic tides on bottom topography or the spatially compact near-inertial mixed layer currents excited by surface winds can be conveniently represented in the linear regime as a superposition of vertical modes at a given frequency in an arbitrarily stratified ocean of finite depth. Considering modes (m , n) at a frequency ω in the primary wave field, we derive the weakly nonlinear solution, which contains a secondary wave at 2 ω that diverges when it forms a resonant triad with the primary waves. In nonuniform stratifications, resonant triads are shown to occur when the horizontal component of the classical RTI criterion k->1 +k->2 +k->3 = 0 is satisfied along with a non-orthogonality criterion. In nonuniform stratifications with a pycnocline, infinitely more pairs of primary wave modes (m , n) result in RTI when compared to a uniform stratification. Further, two nearby high modes at around the near-inertial frequency often form a resonant triad with a low mode at 2 ω , reminiscent of the features of PSI near the critical latitude. The theoretical framework is then adapted to investigate RTI in two different scenarios: low-mode internal tide scattering over topography, and internal wave beams incident on a pycnocline. The authors thank the Ministry of Earth Sciences, Government of India for financial support under the Monsoon Mission Grant MM/2014/IND-002.

  3. Ion pairs in non-redundant protein structures

    Indian Academy of Sciences (India)

    Ion pairs contribute to several functions including the activity of catalytic triads, fusion of viral membranes, stability in thermophilic proteins and solvent–protein interactions. Furthermore, they have the ability to affect the stability of protein structures and are also a part of the forces that act to hold monomers together.

  4. Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.

    Science.gov (United States)

    Shinagawa-Kobayashi, Yoko; Kamimura, Kenya; Goto, Ryo; Ogawa, Kohei; Inoue, Ryosuke; Yokoo, Takeshi; Sakai, Norihiro; Nagoya, Takuro; Sakamaki, Akira; Abe, Satoshi; Sugitani, Soichi; Yanagi, Masahiko; Fujisawa, Koichi; Nozawa, Yoshizu; Koyama, Naoto; Nishina, Hiroshi; Furutani-Seiki, Makoto; Sakaida, Isao; Terai, Shuji

    2018-02-05

    Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation

    Directory of Open Access Journals (Sweden)

    Shahida A. Khan

    2014-01-01

    Full Text Available Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs and G protein coupled receptors (GPCRs. In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.

  6. Photochemical coupling of 5-bromouracil to tryptophan, tyrosine and histidine, peptide-like derivatives in aqueous fluid solution

    International Nuclear Information System (INIS)

    Dietz, T.M.; Koch, T.H.

    1987-01-01

    Direct irradiation of 5-bromouracil (BU) in aqueous fluid solution in the presence of tryptophan (trp), tyrosine (tyr) or histidine (his) derivatives using a XeCl excimer laser at 308 nm yielded photocoupling of BU to the aromatic ring of each amino acid. Irradiation of BU at 308 nm most likely results in excitation of the n-π* transition, intersystem crossing to the triplet manifold, and coupling via electron transfer from the aromatic amino acid. The coupling observed was regiospecific between the 5-position of uracil (U) and the 2-position of the indole and phenol rings and the 5-position of the imidazole ring of the respective amino acids. Quantum yields of photocoupling to BU ranged from 1 x 10 -3 to 7 x 10 -3 and paralleled known rates of electron transfer and ionization potentials of the aromatic rings. The photocoupling between BU and some of the aromatic amino acid peptide-like derivatives possibly mimics photocrosslinking of BU-DNA to associated proteins, a potentially useful photoreaction for studying nucleic acid-protein interactions. Formation of crosslinks of the type proposed here might be detected by the characteristic fluorescence emission of the uracil amino acid adducts. (author)

  7. Assignment of histidine resonances in the 1H NMR (500 MHz) spectrum of subtilisin BPN' using site-directed mutagenesis

    International Nuclear Information System (INIS)

    Bycroft, M.; Fersht, A.R.

    1988-01-01

    A spin-echo pulse sequence has been used to resolve the six histidine C-2H protons in the 500-MHz NMR spectrum of subtilisin BPN'. Five of these residues have been substituted by site-directed mutagenesis, and this has enabled a complete assignment of these protons to be obtained. Analysis of the pH titration curves of these signals has provided microscopic pK a 's for the six histidines in this enzyme. The pK a 's of the histidine residues in subtilisin BPN' have been compared with the values obtained for the histidines in the homologous enzyme from Bacillus licheniformis (subtilisin Carlsberg). Four of the five conserved histidines titrate with essentially identical pK a 's in the two enzymes. It therefore appears that the assignments made for these residues in subtilisin BPN' can be transferred to subtilisin Carlsberg. On the basis of these assignments, the one histidine that titrates with a substantially different pK a in the two enzymes can be assigned to histidine-238. This difference in pK a has been attributed to a Trp to Lys substitution at position 241 in subtilisin Carlsberg

  8. Biological functions of histidine-dipeptides and metabolic syndrome

    OpenAIRE

    Song, Byeng Chun; Joo, Nam-Seok; Aldini, Giancarlo; Yeum, Kyung-Jin

    2014-01-01

    The rapid increase in the prevalence of metabolic syndrome, which is associated with a state of elevated systemic oxidative stress and inflammation, is expected to cause future increases in the prevalence of diabetes and cardiovascular diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive carbonyl species, which, due to their electrophilic nature, react with the nucleophilic sites of certain amino acids. This leads to formation of protein adducts such as advanced gly...

  9. Complete Familial Currarino Triad in Association with Hirschsprung's Disease: Magnetic Resonance Imaging Features and the Spectrum of Anorectal Malformations

    Energy Technology Data Exchange (ETDEWEB)

    Kilickesmez, O.; Hakki Gol, I.; Uzun, M.; Oruk, C. [Diyarbakir Military Hospital (Turkey). Dept. of Radiology

    2006-07-15

    Currarino syndrome, a rare hereditary condition, is defined as a partial sacral agenesis associated with a presacral mass and anorectal malformation. The authors present two siblings with complete Currarino triad and their mother with incomplete triad. The complete Currarino triad in the older sibling was associated with Hirschsprung's disease as the second reported case in the literature. Anorectal malformations, whether suspected of Currarino syndrome or not, should be examined with lumbosacral magnetic resonance imaging.

  10. Lyophilized histidine investigated using X-ray photoelectron spectroscopy and cryogenics: Deprotonation in vacuum

    International Nuclear Information System (INIS)

    Cardenas, Juan F.; Groebner, Gerhard

    2005-01-01

    Lyophilized histidine samples were investigated using X-ray photoelectron spectroscopy (XPS). Lyophilized samples were prepared from aqueous solutions at a pH in the range between ∼1.5 and ∼10, and with no further addition of electrolyte. The use of cryogenics allowed the determination of protonated to unprotonated molar ratios of sites in L-histidine, which correlates well with the dissociation constants of the residual amino acid sites. When cryogenics was not used deprotonation of the lyophilized samples occurred, where the degree and the total concentration of deprotonated sites correlates well with the formation constants and the decrease in Cl concentration, respectively. This later relation clearly indicates a correlation between deprotonation and the desorption of HCl from lyophilized samples

  11. Lyophilized histidine investigated using X-ray photoelectron spectroscopy and cryogenics: Deprotonation in vacuum

    Energy Technology Data Exchange (ETDEWEB)

    Cardenas, Juan F. [Inorganic Chemistry, Umeaa University, 90187 Umeaa (Sweden)]. E-mail: juan.cardenas@chem.umu.se; Groebner, Gerhard [Biophysical Chemistry, Umeaa University, 90187 Umeaa (Sweden)

    2005-08-15

    Lyophilized histidine samples were investigated using X-ray photoelectron spectroscopy (XPS). Lyophilized samples were prepared from aqueous solutions at a pH in the range between {approx}1.5 and {approx}10, and with no further addition of electrolyte. The use of cryogenics allowed the determination of protonated to unprotonated molar ratios of sites in L-histidine, which correlates well with the dissociation constants of the residual amino acid sites. When cryogenics was not used deprotonation of the lyophilized samples occurred, where the degree and the total concentration of deprotonated sites correlates well with the formation constants and the decrease in Cl concentration, respectively. This later relation clearly indicates a correlation between deprotonation and the desorption of HCl from lyophilized samples.

  12. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads

    International Nuclear Information System (INIS)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-01-01

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes

  13. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads.

    Science.gov (United States)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-05-21

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes.

  14. Structural Failure Sites in Anterior Vaginal Wall Prolapse: Identification of a Collinear Triad.

    Science.gov (United States)

    Chen, Luyun; Lisse, Sean; Larson, Kindra; Berger, Mitchell B; Ashton-Miller, James A; DeLancey, John O L

    2016-10-01

    To test the null hypothesis that six factors representing potential fascial and muscular failure sites contribute equally to the presence and size of a cystocele: two vaginal attachment factors (apical support and paravaginal defects), two vaginal wall factors (vaginal length and width), and two levator ani factors (hiatus size and levator ani defects). Thirty women with anterior-predominant prolapse (women in a case group) and 30 women in a control group underwent three-dimensional stress magnetic resonance imaging. The location of the anterior vaginal wall at maximal Valsalva was identified with the modified Pelvic Inclination Coordinate System and the six factors measured. Analysis included repeated-measure analysis of variance, logistic regression, and stepwise linear regression. We identified a collinear triad consisting of apical location, paravaginal location, and hiatus size that were not only the strongest predictors of cystocele size, but were also highly correlated with one another (r=0.84-0.89, P<.001) for the presence and size of the prolapse. Together they explain up to 83% of the variation in cystocele size. Among the less significant vaginal factors, vaginal length explained 19% of the variation in cystocele size, but no significant difference in vaginal width existed. Women in the case group were more likely to have abnormalities in collinear triad factors (up to 80%) than vaginal wall factors (up to 23.3%). Combining the strongest collinear triad with the vaginal factors, the model explained 92.5% of the variation in cystocele size. Apical location, paravaginal location, and hiatus size are highly correlated and are strong predictors of cystocele presence and size.

  15. Association Between the Female Athlete Triad and Endothelial Dysfunction in Dancers

    Science.gov (United States)

    Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Schimke, Jane E.; Gutterman, David D.

    2013-01-01

    Objective To determine the prevalence of the 3 components of the female athlete triad [disordered eating, menstrual dysfunction, low bone mineral density (BMD)] and their relationships with brachial artery flow-mediated dilation in professional dancers. Design Prospective study. Setting Academic institution in the Midwest. Participants Twenty-two professional ballet dancers volunteered for this study. Interventions The prevalence of the female athlete triad and its relationship to endothelial dysfunction. Main Outcome Measures Subjects completed questionnaires to assess disordered eating and menstrual status/history. They also completed a 3-day food record and wore an accelerometer for 3 days to determine energy availability. Serum baseline thyrotropin, prolactin, and hormonal concentrations were obtained. Bone mineral density and body composition were measured with a GE Lunar Prodigy dual-energy X-ray absorptiometry. Endothelial function was determined as flow-mediated vasodilation measured by high-frequency ultrasound in the brachial artery. An increase in brachial diameter <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Results Seventeen dancers (77%) had evidence of low/negative energy availability. Thirty-two percent had disordered eating (EDE-Q score). Thirty-six percent had menstrual dysfunction and 14% were currently using hormone contraception. Twenty-three percent had evidence of low bone density (Z-score < −1.0). Sixty-four percent had abnormal brachial artery flow-mediated dilation (<5%). Flow-mediated dilation values were significantly correlated with serum estrogen and whole-body and lumbar BMD. All the 3 components of the triad plus endothelial dysfunction were present in 14% of the subjects. Conclusions Endothelial dysfunction was correlated with reduced BMD, menstrual dysfunction, and low serum estrogen. These findings may have profound implications for cardiovascular and bone health in professional women dancers

  16. The predictive ability of triglycerides and waist (hypertriglyceridemic waist) in assessing metabolic triad change in obese children and adolescents.

    Science.gov (United States)

    Hobkirk, James P; King, Roderick F; Gately, Paul; Pemberton, Philip; Smith, Alexander; Barth, Julian H; Harman, Nicola; Davies, Ian; Carroll, Sean

    2013-10-01

    The metabolic triad [fasting insulin, apolipoprotein B, and low-density lipoporotein (LDL) peak particle density] is characteristic of increased intra-abdominal adipose tissue and insulin resistance and can be predicted by the simple and adoptable screening tool, the hypertriglyceridemic waist. The associations between hypertriglyceridemic waist components [fasting triglycerides (TG) and waist circumference cut-points derived from a child-specific metabolic syndrome definition] with the metabolic triad were examined in obese youth before and after weight loss. A continuous metabolic triad score (MTS) was calculated as a cumulative and standardized residual score of fasting insulin, apolipoprotein B, and LDL peak particle density (z-scores of the metabolic triad variables regressed onto age and sex). The predictive ability of TG and waist in assessing metabolic triad change was undertaken in 75 clinically obese boys and girls, aged 8-18, body mass index (BMI) 34.2±6.4 kg/m(2) before and after weight loss. Fasting TG concentrations (r(2)=0.216, PFasting TG change was the only significant predictor of the MTS change (r(2)=0.177, Pfasting TG concentration (but not waist circumference) was the only significant predictor of MTS change. Fasting TG may be the most important metabolic syndrome component to best characterize the metabolic heterogeneity in obese cohorts and the changes in metabolic risk in clinically obese youth.

  17. The LEAF questionnaire: a screening tool for the identification of female athletes at risk for the female athlete triad.

    Science.gov (United States)

    Melin, Anna; Tornberg, Asa B; Skouby, Sven; Faber, Jens; Ritz, Christian; Sjödin, Anders; Sundgot-Borgen, Jorunn

    2014-04-01

    Low energy availability (EA) in female athletes with or without an eating disorder (ED) increases the risk of oligomenorrhoea/functional hypothalamic amenorrhoea and impaired bone health, a syndrome called the female athlete triad (Triad). There are validated psychometric instruments developed to detect disordered eating behaviour (DE), but no validated screening tool to detect persistent low EA and Triad conditions, with or without DE/ED, is available. The aim of this observational study was to develop and test a screening tool designed to identify female athletes at risk for the Triad. Female athletes (n=84) with 18-39 years of age and training ≥5 times/week filled out the Low Energy Availability in Females Questionnaire (LEAF-Q), which comprised questions regarding injuries and gastrointestinal and reproductive function. Reliability and internal consistency were evaluated in a subsample of female dancers and endurance athletes (n=37). Discriminant as well as concurrent validity was evaluated by testing self-reported data against measured current EA, menstrual function and bone health in endurance athletes from sports such as long distance running and triathlon (n=45). The 25-item LEAF-Q produced an acceptable sensitivity (78%) and specificity (90%) in order to correctly classify current EA and/or reproductive function and/or bone health. The LEAF-Q is brief and easy to administer, and relevant as a complement to existing validated DE screening instruments, when screening female athletes at risk for the Triad, in order to enable early detection and intervention.

  18. Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications

    OpenAIRE

    Xie, Zhengzhi; Baba, Shahid P.; Sweeney, Brooke R.; Barski, Oleg A.

    2013-01-01

    Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. In most tissues, aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines, such as glutathione and histidine dipeptid...

  19. Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications

    Science.gov (United States)

    Xie, Zhengzhi; Baba, Shahid P.; Sweeney, Brooke R.; Barski, Oleg A.

    2015-01-01

    Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. In most tissues, aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines, such as glutathione and histidine dipeptides. Histidine dipeptides are present in micromolar to millimolar range in the tissues of vertebrates, where they are involved in a variety of physiological functions such as pH buffering, metal chelation, oxidant and aldehyde scavenging. Histidine dipeptides such as carnosine form Michael adducts with lipid-derived unsaturated aldehydes, and react with carbohydrate-derived oxo- and hydroxy- aldehydes forming products of unknown structure. Although these peptides react with electrophilic molecules at lower rate than glutathione, they can protect glutathione from modification by oxidant and they may be important for aldehyde quenching in glutathione-depleted cells or extracellular space where glutathione is scarce. Consistent with in vitro findings, treatment with carnosine has been shown to diminish ischemic injury, improve glucose control, ameliorate the development of complications in animal models of diabetes and obesity, promote wound healing and decrease atherosclerosis. The protective effects of carnosine have been linked to its anti-oxidant properties, it ability to promote glycolysis, detoxify reactive aldehydes and enhance histamine levels. Thus, treatment with carnosine and related histidine dipeptides may be a promising strategy for the prevention and treatment of diseases associated with high carbonyl load. PMID:23313711

  20. The putative sensor histidine kinase CKI1 is involved in female gametophyte development in Arabidopsis

    Czech Academy of Sciences Publication Activity Database

    Hejátko, Jan; Pernisová, M.; Eneva, T.; Palme, K.; Brzobohatý, Břetislav

    2003-01-01

    Roč. 269, č. 4 (2003), s. 443-453 ISSN 1617-4615 R&D Projects: GA MŠk VS96096; GA MŠk LN00A081 Grant - others:INCO-Copernicus(XE) ERB3512-PL966135; QLRT(XE) 2000-0020 Institutional research plan: CEZ:AV0Z5004920 Keywords : female gametophyte development * two-component signaling * sensor histidine kinase Subject RIV: BO - Biophysics Impact factor: 2.240, year: 2003

  1. Digging in the Dark Triad: A Replication of ``Machiavellianism and Dating: Deception and Intimacy''

    Directory of Open Access Journals (Sweden)

    Durand, Guillaume

    2016-10-01

    Full Text Available The present study is a replication and an extension of Dussault, Hojjat, and Boone (2013. Machiavellianism and dating: Deception and intimacy. Social Behavior and Personality: an international journal, 41(2, 283-294. The results support the positive association between Machiavellianism and the use of deceptive dating strategies, but fail to detect a correlation between Machiavellianism and perceived intimacy. The extension to the Dark Triad reveals that psychopathy is a stronger predictor than Machiavellianism to assess deceptive dating strategies, and supports a relationship between higher degrees of narcissism and history of intimate behaviors.

  2. The (mismeasurement of the Dark Triad Dirty Dozen: exploitation at the core of the scale

    Directory of Open Access Journals (Sweden)

    Petri J. Kajonius

    2016-03-01

    Full Text Available Background. The dark side of human character has been conceptualized in the Dark Triad Model: Machiavellianism, psychopathy, and narcissism. These three dark traits are often measured using single long instruments for each one of the traits. Nevertheless, there is a necessity of short and valid personality measures in psychological research. As an independent research group, we replicated the factor structure, convergent validity and item response for one of the most recent and widely used short measures to operationalize these malevolent traits, namely, Jonason’s Dark Triad Dirty Dozen. We aimed to expand the understanding of what the Dirty Dozen really captures because the mixed results on construct validity in previous research. Method. We used the largest sample to date to respond to the Dirty Dozen (N = 3,698. We firstly investigated the factor structure using Confirmatory Factor Analysis and an exploratory distribution analysis of the items in the Dirty Dozen. Secondly, using a sub-sample (n = 500 and correlation analyses, we investigated the Dirty Dozen dark traits convergent validity to Machiavellianism measured by the Mach-IV, psychopathy measured by Eysenck’s Personality Questionnaire Revised, narcissism using the Narcissism Personality Inventory, and both neuroticism and extraversion from the Eysenck’s questionnaire. Finally, besides these Classic Test Theory analyses, we analyzed the responses for each Dirty Dozen item using Item Response Theory (IRT. Results. The results confirmed previous findings of a bi-factor model fit: one latent core dark trait and three dark traits. All three Dirty Dozen traits had a striking bi-modal distribution, which might indicate unconcealed social undesirability with the items. The three Dirty Dozen traits did converge too, although not strongly, with the contiguous single Dark Triad scales (r between .41 and .49. The probabilities of filling out steps on the Dirty Dozen narcissism-items were

  3. Identification and Expression Profiles of Six Transcripts Encoding Carboxylesterase Protein in Vitis flexuosa Infected with Pathogens

    Directory of Open Access Journals (Sweden)

    Md. Zaherul Islam

    2016-08-01

    Full Text Available Plants protect themselves from pathogen attacks via several mechanisms, including hypersensitive cell death. Recognition of pathogen attack by the plant resistance gene triggers expression of carboxylesterase genes associated with hypersensitive response. We identified six transcripts of carboxylesterase genes, Vitis flexuosa carboxylesterase 5585 (VfCXE5585, VfCXE12827, VfCXE13132, VfCXE17159, VfCXE18231, and VfCXE47674, which showed different expression patterns upon transcriptome analysis of V. flexuosa inoculated with Elsinoe ampelina. The lengths of genes ranged from 1,098 to 1,629 bp, and their encoded proteins consisted of 309 to 335 amino acids. The predicted amino acid sequences showed hydrolase like domains in all six transcripts and contained two conserved motifs, GXSXG of serine hydrolase characteristics and HGGGF related to the carboxylesterase family. The deduced amino acid sequence also contained a potential catalytic triad consisted of serine, aspartic acid and histidine. Of the six transcripts, VfCXE12827 showed upregulated expression against E. ampelina at all time points. Three genes (VfCXE5585, VfCXE12827, and VfCXE13132 showed upregulation, while others (VfCXE17159, VfCXE18231, and VfCXE47674 were down regulated in grapevines infected with Botrytis cinerea. All transcripts showed upregulated expression against Rhizobium vitis at early and later time points except VfCXE12827, and were downregulated for up to 48 hours post inoculation (hpi after upregulation at 1 hpi in response to R. vitis infection. All tested genes showed high and differential expression in response to pathogens, indicating that they all may play a role in defense pathways during pathogen infection in grapevines.

  4. Association of Rare Loss-Of-Function Alleles in HAL, Serum Histidine: Levels and Incident Coronary Heart Disease.

    Science.gov (United States)

    Yu, Bing; Li, Alexander H; Muzny, Donna; Veeraraghavan, Narayanan; de Vries, Paul S; Bis, Joshua C; Musani, Solomon K; Alexander, Danny; Morrison, Alanna C; Franco, Oscar H; Uitterlinden, André; Hofman, Albert; Dehghan, Abbas; Wilson, James G; Psaty, Bruce M; Gibbs, Richard; Wei, Peng; Boerwinkle, Eric

    2015-04-01

    Histidine is a semiessential amino acid with antioxidant and anti-inflammatory properties. Few data are available on the associations between genetic variants, histidine levels, and incident coronary heart disease (CHD) in a population-based sample. By conducting whole exome sequencing on 1152 African Americans in the Atherosclerosis Risk in Communities (ARIC) study and focusing on loss-of-function (LoF) variants, we identified 3 novel rare LoF variants in HAL, a gene that encodes histidine ammonia-lyase in the first step of histidine catabolism. These LoF variants had large effects on blood histidine levels (β=0.26; P=1.2×10(-13)). The positive association with histidine levels was replicated by genotyping an independent sample of 718 ARIC African Americans (minor allele frequency=1%; P=1.2×10(-4)). In addition, high blood histidine levels were associated with reduced risk of developing incident CHD with an average of 21.5 years of follow-up among African Americans (hazard ratio=0.18; P=1.9×10(-4)). This finding was validated in an independent sample of European Americans from the Framingham Heart Study (FHS) Offspring Cohort. However, LoF variants in HAL were not directly significantly associated with incident CHD after meta-analyzing results from the CHARGE Consortium. Three LoF mutations in HAL were associated with increased histidine levels, which in turn were shown to be inversely related to the risk of CHD among both African Americans and European Americans. Future investigations on the association between HAL gene variation and CHD are warranted. © 2015 American Heart Association, Inc.

  5. Doped zinc sulfide quantum dots based phosphorescence turn-off/on probe for detecting histidine in biological fluid

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Wei [School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); School of Basic Medical Science, Shanxi Medical University, Taiyuan 030001 (China); Wang, Fang [School of Basic Medical Science, Shanxi Medical University, Taiyuan 030001 (China); Wei, Yanli; Wang, Li; Liu, Qiaoling; Dong, Wenjuan [School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Shuang, Shaomin, E-mail: smshuang@sxu.edu.cn [School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Choi, Martin M.F., E-mail: mmfchoi@gmail.com [Partner State Key Laboratory of Environmental and Biological Analysis, and Department of Chemistry, Hong Kong Baptist University, 224 Waterloo Road, Kowloon Tong, Hong Kong SAR (China)

    2015-01-26

    Highlights: • A turn-on phosphorescence quantum dots probe for histidine is fabricated. • High sensitivity, good selectivity and low interference are achieved. • Histidine in urine samples can be easily detected by the phosphorescence probe. - Abstract: We report a turn-on phosphorescence probe for detection of histidine based on Co{sup 2+}-adsorbed N-acetyl-L-cysteine (NAC) capped Mn: ZnS quantum dots (QDs) which is directly synthesized by the hydrothermal method. The phosphorescence of NAC-Mn: ZnS QDs is effectively quenched by Co{sup 2+} attributing to the adsorption of Co{sup 2+} onto the surface of QDs with a concomitant in suppressing the recombination process of hole and electron of QDs. The phosphorescence of Co{sup 2+}-adsorbed NAC-Mn: ZnS QDs can be recovered by binding of Co{sup 2+} with histidine. The quenching and regeneration of the phosphorescence of NAC-Mn: ZnS QDs have been studied in detail. The as-prepared QDs-based probe is applied to determine histidine with a linear range of 1.25–30 μM and a detection limit of 0.74 μM. The relative standard deviation for eleven repeat detections of 20 μM histidine is 0.65%. Co{sup 2+}-adsorbed NAC-Mn: ZnS QDs show high sensitivity and good selectivity to histidine over other amino acids, metal ions and co-existing substances. The proposed QDs probe has been successfully applied to determination of histidine in human urine samples with good recoveries of 98.5–103%.

  6. Molecular characterization and expression study of a histidine auxotrophic mutant (his1-) of Nicotiana plumbaginifolia.

    Science.gov (United States)

    El Malki, F; Jacobs, M

    2001-01-01

    The histidine auxotroph mutant his 1(-) isolated from Nicotiana plumbaginifolia haploid protoplasts was first characterized to be deficient for the enzyme histidinol phosphate aminotransferase that is responsible for one of the last steps of histidine biosynthesis. Expression of the mutated gene at the RNA level was assessed by northern analysis of various tissues. Transcriptional activity was unimpaired by the mutation and, in contrast, a higher level of expression was obtained when compared to the wild-type. The cDNA sequence encoding the mutated gene was isolated by RT-PCR and compared to the wild-type gene. A single point mutation corresponding to the substitution of a G nucleotide by A was identified at position 1212 starting from the translation site. The alignment of the deduced amino acid sequences from the mutated and wild-type gene showed that this mutation resulted in the substitution of an Arg by a His residue at position 381. This Arg residue is a conserved amino acid for histidinol phosphate aminotransferase of many species. These results indicate that the identified mutation results in an altered histidinol phosphate aminotransferase enzyme that is unable to convert the substrate imidazole acetol phosphate to histidinol phosphate and thereby leads to the blockage of histidine biosynthesis. Possible consequences of this blockage on the expression of other amino acid biosynthesis genes were evaluated by analysing the expression of the dhdps gene encoding dihydrodipicolinate synthase, the first key enzyme of the lysine pathway.

  7. Validation of a microfluorimetric method for quantitation of L-Histidine in peripheral blood

    International Nuclear Information System (INIS)

    Contreras Roura, Jiovanna; Hernandez Cuervo, Orietta; Alonso Jimenez, Elsa

    2008-01-01

    Histidinemia is a rare inherited metabolic disorder characterized by deficient histidase enzyme, which results in elevated histidine levels in blood, urine and cerebrospinal fluid and, sometimes, hyperalaninemia. Histidinemia clinical picture varies from mental retardation and speech disorders to absence of any symptoms. This disease can be diagnosed by histidine-level-in-blood-quantitating tests using different analytical methods such as spectrofluorimetry and High Pressure Liquid Chromatography. An analytical method using SUMA Technology was developed and validated at our laboratory to determine L-Histidine in blood: serum and dried blood spot (adult and neonatal) so as to use it in Histidinemia screening in children with speech disorders. This paper presents selectivity, linearity, accuracy and precision data. The calibration curve showed linearity ranging 1-12 mg/dL or 64.5-774 μM, and correlation coefficient (r) and determination coefficient (r2) higher than 0.99 for each biological matrix studied were obtained. Accuracy (repeatability and intermediate accuracy assays) was demonstrated, variation coefficients lower than 20 % being obtained. Accuracy was assessed by determining absolute recovery percentage. Assay recoveries were 97.83 -105.50 % (serum), 93-121.50 % (adult spot dried blood) and 86.50-104.50 % (neonatal spot dried blood)

  8. A conserved histidine in human DNLZ/HEP is required for stimulation of HSPA9 ATPase activity.

    Science.gov (United States)

    Zhai, Peng; Vu, Michael T; Hoff, Kevin G; Silberg, Jonathan J

    2011-05-20

    The DNL-type zinc-finger protein DNLZ regulates the activity and solubility of the human mitochondrial chaperone HSPA9. To identify DNLZ residues that are critical for chaperone regulation, we carried out an alanine mutagenesis scan of charged residues in a W115I mutant of human DNLZ and assessed the effect of each mutation on interactions with HSPA9. All mutants analyzed promote the solubility of HSPA9 upon expression in Escherichia coli. However, binding studies examining the effect of DNLZ mutants on chaperone tryptophan fluorescence identified three mutations (R81A, H107A, and D111A) that decrease DNLZ binding affinity for nucleotide-free chaperone. In addition, ATPase measurements revealed that DNLZ-R81A and DNLZ-D111A both stimulate the catalytic activity HSPA9, whereas DNLZ-H107A does not elicit an increase in activity even when present at a concentration that is 10-fold higher than the level required for half-maximal stimulation by DNLZ. These findings implicate a conserved histidine as critical for DNLZ regulation of mitochondrial HSPA9 catalytic activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity.

    Science.gov (United States)

    Hammerstrom, Troy G; Horton, Lori B; Swick, Michelle C; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M

    2015-02-01

    The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO(2)/bicarbonate, and there is a positive correlation between the CO(2)/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His→Asp) and phosphoablative (His→Ala) amino acid changes for activity in B. anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism. © 2014 John Wiley & Sons Ltd.

  10. Specific and reversible immobilization of histidine-tagged proteins on functionalized silicon nanowires

    DEFF Research Database (Denmark)

    Liu, Yi-Chi; Rieben, Nathalie Ines; Iversen, Lars

    2010-01-01

    Silicon nanowire (Si NW)-based field effect transistors (FETs) have shown great potential as biosensors (bioFETs) for ultra-sensitive and label-free detection of biomolecular interactions. Their sensitivity depends not only on the device properties, but also on the function of the biological reco...

  11. The Cu2+-nitrilotriacetic acid complex improves loading of α-helical double histidine site for precise distance measurements by pulsed ESR

    Science.gov (United States)

    Ghosh, Shreya; Lawless, Matthew J.; Rule, Gordon S.; Saxena, Sunil

    2018-01-01

    Site-directed spin labeling using two strategically placed natural histidine residues allows for the rigid attachment of paramagnetic Cu2+. This double histidine (dHis) motif enables extremely precise, narrow distance distributions resolved by Cu2+-based pulsed ESR. Furthermore, the distance measurements are easily relatable to the protein backbone-structure. The Cu2+ ion has, till now, been introduced as a complex with the chelating agent iminodiacetic acid (IDA) to prevent unspecific binding. Recently, this method was found to have two limiting concerns that include poor selectivity towards α-helices and incomplete Cu2+-IDA complexation. Herein, we introduce an alternative method of dHis-Cu2+ loading using the nitrilotriacetic acid (NTA)-Cu2+ complex. We find that the Cu2+-NTA complex shows a four-fold increase in selectivity toward α-helical dHis sites. Furthermore, we show that 100% Cu2+-NTA complexation is achievable, enabling precise dHis loading and resulting in no free Cu2+ in solution. We analyze the optimum dHis loading conditions using both continuous wave and pulsed ESR. We implement these findings to show increased sensitivity of the Double Electron-Electron Resonance (DEER) experiment in two different protein systems. The DEER signal is increased within the immunoglobulin binding domain of protein G (called GB1). We measure distances between a dHis site on an α-helix and dHis site either on a mid-strand or a non-hydrogen bonded edge-strand β-sheet. Finally, the DEER signal is increased twofold within two α-helix dHis sites in the enzymatic dimer glutathione S-transferase exemplifying the enhanced α-helical selectivity of Cu2+-NTA.

  12. Delinquency Among Members of Hong Kong Youth Street Gangs: The Role of the Organizational Structures of Gangs and Triad Affiliations.

    Science.gov (United States)

    Chui, Wing Hong; Khiatani, Paul Vinod

    2018-07-01

    This study explores the importance of organizational structures and formal affiliations with the Hong Kong triads to delinquency among youth street gang members in Hong Kong. More specifically, this study examines the relative importance of the number of organizational structures and triad affiliation to patterns of delinquency in a sample of active members of youth street gangs ( N = 201). With the aid of outreach social workers, a convenience sampling method was used to recruit a gender-balanced sample of at-risk youths. Logistic regression analysis of the survey data that was gathered indicated that formal affiliation to Hong Kong triads and the presence of organizational structures significantly increased the odds of delinquency (independently of each other). Suggestions for future research on gang membership and delinquency, with particular reference to the Asian context, are provided.

  13. Is focusing on the triad in suspected child abuse cases really irrelevant and of no practical use?

    Science.gov (United States)

    Lynøe, Niels; Eriksson, Anders

    2018-06-11

    Since its publication in 2016, the report by the Swedish Agency for Health Technology Assessment and Assessment of Social Services on the diagnostic accuracy of the triad for determining traumatic shaking (1) has been criticised, mainly by paediatricians. One repeated criticism has been that the report focused on the triad of symptoms, namely subdural haematoma, retinal haemorrhages and encephalopathy, in cases without signs of impact. This focus has been described by some critics as one that has been created by lawyers to use in court cases and the triad itself has been dismissed as irrelevant and of no practical or clinical use (2-3) This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Evolutionary convergence in the biosyntheses of the imidazole moieties of histidine and purines.

    Directory of Open Access Journals (Sweden)

    Alberto Vázquez-Salazar

    Full Text Available The imidazole group is an ubiquitous chemical motif present in several key types of biomolecules. It is a structural moiety of purines, and plays a central role in biological catalysis as part of the side-chain of histidine, the amino acid most frequently found in the catalytic site of enzymes. Histidine biosynthesis starts with both ATP and the pentose phosphoribosyl pyrophosphate (PRPP, which is also the precursor for the de novo synthesis of purines. These two anabolic pathways are also connected by the imidazole intermediate 5-aminoimidazole-4-carboxamide ribotide (AICAR, which is synthesized in both routes but used only in purine biosynthesis. Rather surprisingly, the imidazole moieties of histidine and purines are synthesized by different, non-homologous enzymes. As discussed here, this phenomenon can be understood as a case of functional molecular convergence.In this work, we analyze these polyphyletic processes and argue that the independent origin of the corresponding enzymes is best explained by the differences in the function of each of the molecules to which the imidazole moiety is attached. Since the imidazole present in histidine is a catalytic moiety, its chemical arrangement allows it to act as an acid or a base. On the contrary, the de novo biosynthesis of purines starts with an activated ribose and all the successive intermediates are ribotides, with the key β-glycosidic bondage joining the ribose and the imidazole moiety. This prevents purine ribonucleotides to exhibit any imidazole-dependent catalytic activity, and may have been the critical trait for the evolution of two separate imidazole-synthesizing-enzymes. We also suggest that, in evolutionary terms, the biosynthesis of purines predated that of histidine.As reviewed here, other biosynthetic routes for imidazole molecules are also found in extant metabolism, including the autocatalytic cyclization that occurs during the formation of creatinine from creatine phosphate

  15. Thinking Towards Peace: On Triades and New Cosmology of the Mesocosm

    Directory of Open Access Journals (Sweden)

    Lenart Škof

    2016-06-01

    Full Text Available This paper has three parts. In the first part, we bring to the fore an ancient Vedic concept of mesocosm and discuss its religious and cosmic significance within Indian religion. This part also brings an initial approach towards philosophy of spirituality by focusing on the role of breath within the very concept of mesocosm. In the second part, based on our preliminary analysis, we present an original account on triades and Trinitarian thinking in some of the religious traditions by discussing the following questions: (1 What does the triade as a concept bring to theology and religious studies? (2 How could it be understood as a form, representing the most perfect model for the sacred correlation between divine and for the human Being? (3 How is it related to the idea of the “Third Presence,” the relational link between One and Two as primeval ontological realms? In the third and concluding part, we return to the ancient Indoeuropean religion by discussing the mediatory role of the Indo-Iranian Mit(hra.

  16. Distortion of the Actin A-Triad Results in Contractile Disinhibition and Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Meera C. Viswanathan

    2017-09-01

    Full Text Available Striated muscle contraction is regulated by the movement of tropomyosin over the thin filament surface, which blocks or exposes myosin binding sites on actin. Findings suggest that electrostatic contacts, particularly those between K326, K328, and R147 on actin and tropomyosin, establish an energetically favorable F-actin-tropomyosin configuration, with tropomyosin positioned in a location that impedes actomyosin associations and promotes relaxation. Here, we provide data that directly support a vital role for these actin residues, termed the A-triad, in tropomyosin positioning in intact functioning muscle. By examining the effects of an A295S α-cardiac actin hypertrophic cardiomyopathy-causing mutation, over a range of increasingly complex in silico, in vitro, and in vivo Drosophila muscle models, we propose that subtle A-triad-tropomyosin perturbation can destabilize thin filament regulation, which leads to hypercontractility and triggers disease. Our efforts increase understanding of basic thin filament biology and help unravel the mechanistic basis of a complex cardiac disorder.

  17. Female Athlete Triad/Relative Energy Deficiency in Sport: A Perspective Interview With Professor Barbara Drinkwater.

    Science.gov (United States)

    Carter, Susan

    2018-06-07

    Barbara Drinkwater has been a lifelong champion of equality for women in many areas of life well before it was widely accepted. Her "walking the walk" of women breaking barriers in traditional male roles in administration and leadership is exemplified by her election as the first woman president of the American College of Sports Medicine in 1988. Some of the controversial areas in which Barbara was vocal in the arena of women in sport, besides triad/relative energy deficiency in sport, include increased opportunity and participation, total equality, acceptance of diversity, intolerance of harassment and abuse, and fairness with transgender athletes. She co-founded the evidence-based advocacy group on the international stage known as Women Sport International. As a physiologist, Barbara has had a major influence on attention to the health of the female athlete, and she produced the original pioneering work in the field. Her impactful study, "Bone mineral density after resumption of menses in amenorrheic athletes," was published in the Journal of the American Medical Association in 1986. Since that time, the female athlete triad has set the stage for research and treatment to enhance women in physical activity at all levels.

  18. Observations of Traveling Crossflow Resonant Triad Interactions on a Swept Wing

    Science.gov (United States)

    Eppink, Jenna L.; Wlezien, Richard

    2012-01-01

    Experimental evidence indicates the presence of a triad resonance interaction between traveling crossflow modes in a swept wing flow. Results indicate that this interaction occurs when the stationary and traveling crossflow modes have similar and relatively low amplitudes (approx.1% to 6% of the total freestream velocity). The resonant interaction occurs at instability amplitudes well below those typically known to cause transition, yet transition is observed to occur just downstream of the resonance. In each case, two primary linearly unstable traveling crossflow modes are nonlinearly coupled to a higher frequency linearly stable mode at the sum of their frequencies. The higher-frequency mode is linearly stable and presumed to exist as a consequence of the interaction of the two primary modes. Autoand cross-bicoherence are used to determine the extent of phase-matching between the modes, and wavenumber matching confirms the triad resonant nature of the interaction. The bicoherence results indicate a spectral broadening mechanism and the potential path to early transition. The implications for laminar flow control in swept wing flows are significant. Even if stationary crossflow modes remain subcritical, traveling crossflow interactions can lead to early transition.

  19. Role of endocrine-genotoxic switchings in cancer and other human diseases: basic triad.

    Science.gov (United States)

    Berstein, Lev M

    2008-01-01

    Cancer is one of the leading causes of human death and belongs to the group of main chronic noncommunicable diseases (NCD). Certain specific features ofNCD have raised the concept of 'normal' and 'successful' aging. The apparent paradox of simultaneous increase with aging of the diseases connected with estrogen deficiency as well as with estrogenic excess can be explained by the existence of the phenomenon of the switching of estrogen effects. An isolated or combined with the weakening of hormonal effect increase in genotoxic action of estrogens can modify the course ofage-associated pathology. In particular, such changes in estrogen effect may alter the biology of tumors to make them less favorable/more aggressive. Two other endocrine-genotoxic switchings (EGS) involving phenomena ofJanus (dual) function of glucose and adipogenotoxicosis may produce similar influences on tumor and other NCD biology. These three phenomena form a'basic triad' and can act independently of each other or in concert. EGS and their inductors may serve as targets for prevention and, probably, treatment of main noncommunicable diseases. The measures to correct components of the 'triad' can be divided into several groups aimed to optimally orchestrate the balance between endocrine and DNA-damagingeffects of estrogens, glucose and adipose tissue-related factors.

  20. Development of Triad approach based system for ecological risk assessment for contaminated areas of Kyrgyzstan

    Science.gov (United States)

    Kydralieva, Kamilia; Uzbekov, Beksultan; Khudaibergenova, Bermet; Terekhova, Vera; Jorobekova, Sharipa

    2014-05-01

    This research is aimed to develop a high-effective system of an ecological risk assessment and risk-based decision making for anthropogenic ecosystems, with particular focus on the soils of the Kyrgyz Republic. The study is focused on the integration of Triad data including chemical, biological and ecotoxicological soil markers to estimate the potential risk from soils of highly anthropized areas impacted by deposition of different pollutants from mining operation. We focus on technogenic areas of Kyrgyzstan, the former uranium-producing province. Triad-based ecological risk assessment for technogenic sites are not currently used in Kyrgyzstan. However, the vitality of such research is self-evident. There are about 50 tailing dumps and more than 80 tips of radioactive waste which are formed as a result of uranium and complex ores (mercury, antimony, lead, cadmium and etc) mining around the unfavorable aforementioned places. According to the Mining Wastes' Tailings and Fills Rehabilitation Centre established in 1999 by a special Government's Resolution, one of the most ecologically dangerous uranium tailings resides in Kadzhi-Say. Although uranium processing is no longer practiced in Kadzhi-Say, a large number of open landfills and uranium ore storages still remain abandoned at the vicinity of this settlement. These neglected sites have enormous problems associated with soil erosion known as "technogenic deserts". The upper soil horizons are deprived of humus and vegetation, which favor the formation of low-buffer landscapes in the zones of maximum contamination. As a result, most of these areas are not re-cultivated and remain in critical environmental condition (Bykovchenko, et al., 2005; Tukhvatshin, 2005; Suranova, 2006). Triad data for assessing environmental risk and biological vulnerability at contaminated sites will be integrated. The following Triad-based parameters will be employed: 1) chemical soil analyses (revealing the presence of potentially dangerous

  1. Single histidine residue in head-group region is sufficient to impart remarkable gene transfection properties to cationic lipids: evidence for histidine-mediated membrane fusion at acidic pH.

    Science.gov (United States)

    Kumar, V V; Pichon, C; Refregiers, M; Guerin, B; Midoux, P; Chaudhuri, A

    2003-08-01

    Presence of endosome-disrupting multiple histidine functionalities in the molecular architecture of cationic polymers, such as polylysine, has previously been demonstrated to significantly enhance their in vitro gene delivery efficiencies. Towards harnessing improved transfection property through covalent grafting of endosome-disrupting single histidine functionality in the molecular structure of cationic lipids, herein, we report on the design, the synthesis and the transfection efficiency of two novel nonglycerol-based histidylated cationic amphiphiles. We found that L-histidine-(N,N-di-n-hexadecylamine)ethylamide (lipid 1) and L-histidine-(N,N-di-n-hexadecylamine,-N-methyl)ethylamide (lipid 2) in combination with cholesterol gave efficient transfections into various cell lines. The transfection efficiency of Chol/lipid 1 lipoplexes into HepG2 cells was two order of magnitude higher than that of FuGENE(TM)6 and DC-Chol lipoplexes, whereas it was similar into A549, 293T7 and HeLa cells. A better efficiency was obtained with Chol/lipid 2 lipoplexes when using the cytosolic luciferase expression vector (pT7Luc) under the control of the bacterial T7 promoter. Membrane fusion activity measurements using fluorescence resonance energy transfer (FRET) technique showed that the histidine head-groups of Chol/lipid 1 liposomes mediated membrane fusion in the pH range 5-7. In addition, the transgene expression results using the T7Luc expression vector convincingly support the endosome-disrupting role of the presently described mono-histidylated cationic transfection lipids and the release of DNA into the cytosol. We conclude that covalent grafting of a single histidine amino acid residue to suitable twin-chain hydrophobic compounds is able to impart remarkable transfection properties on the resulting mono-histidylated cationic amphiphile, presumably via the endosome-disrupting characteristics of the histidine functionalities.

  2. A Social Capital Perspective on the Mentoring of Undergraduate Life Science Researchers: An Empirical Study of Undergraduate-Postgraduate-Faculty Triads

    Science.gov (United States)

    Aikens, Melissa L.; Sadselia, Sona; Watkins, Keiana; Evans, Mara; Eby, Lillian T.; Dolan, Erin L.

    2016-01-01

    Undergraduate researchers at research universities are often mentored by graduate students or postdoctoral researchers (referred to collectively as "postgraduates") and faculty, creating a mentoring triad structure. Triads differ based on whether the undergraduate, postgraduate, and faculty member interact with one another about the…

  3. Structural investigations of the active-site mutant Asn156Ala of outer membrane phospholipase A: Function of the Asn-His interaction in the catalytic triad

    NARCIS (Netherlands)

    Snijder, H.J.; van Eerde, J.H.; Kalk, K.H.; Dekker, N.; Egmond, M.R.; Dijkstra, B.W.

    2010-01-01

    Outer membrane phospholipase A (OMPLA) from Escherichia coli is an integral-membrane enzyme with a unique His-Ser-Asn catalytic triad. In serine proteases and serine esterases usually an Asp occurs in the catalytic triad; its role has been the subject of much debate. Here the role of the uncharged

  4. The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues.

    Directory of Open Access Journals (Sweden)

    Helene J Bustad

    Full Text Available Mammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for membranes, which might contribute to modulate the subcellular localization of the partners and substantiate the importance of investigating molecular mechanisms of membrane interaction. By applying surface plasmon resonance we here show that the binding to phospholipid bilayers is stimulated when 14-3-3γ is complexed with its partner, a peptide corresponding to the Ser19-phosphorylated N-terminal region of tyrosine hydroxylase. Moreover, membrane interaction is dependent on salts of kosmotropic ions, which also stabilize 14-3-3γ. Electrostatic analysis of available crystal structures of γ and of the non-membrane-binding ζ-isoform, complemented with molecular dynamics simulations, indicate that the electrostatic potential distribution of phosphopeptide-bound 14-3-3γ is optimal for interaction with the membrane through amphipathic helices at the N-terminal dimerization region. In addition, His158, and especially His195, both specific to 14-3-3γ and located at the convex lateral side, appeared to be pivotal for the ligand induced membrane interaction, as corroborated by site-directed mutagenesis. The participation of these histidine residues might be associated to their increased protonation upon membrane binding. Overall, these results reveal membrane-targeting motifs and give insights on mechanisms that furnish the 14-3-3γ scaffold with the capacity for tuned shuffling from soluble to membrane-bound states.

  5. Advanced drug delivery of N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine), carcinine (beta-alanylhistamine) and L-carnosine (beta-alanyl-L-histidine) in targeting peptide compounds as pharmacological chaperones for use in tissue engineering, human disease management and therapy: from in vitro to the clinic.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2010-11-01

    A pharmacological chaperone is a relatively new concept in the treatment of certain chronic disabling diseases. Cells maintain a complete set of functionally competent proteins normally and in the face of injury or environmental stress with the use of various mechanisms, including systems of proteins called molecular chaperones. Proteins that are denatured by any form of proteotoxic stress are cooperatively recognized by heat shock proteins (HSP) and directed for refolding or degradation. Under non-denaturing conditions HSP have important functions in cell physiology such as in transmembrane protein transport and in enabling assembly and folding of newly synthesized polypeptides. Besides cellular molecular chaperones, which are stress-induced proteins, there have been recently reported chemical, or so-called pharmacological chaperones with demonstrated ability to be effective in preventing misfolding of different disease causing proteins, specifically in the therapeutic management of sight-threatening eye diseases, essentially reducing the severity of several neurodegenerative disorders (such as age-related macular degeneration), cataract and many other protein-misfolding diseases. This work reviews the biological and therapeutic activities protected with the patents of the family of imidazole-containing peptidomimetics Carcinine (β-alanylhistamine), N-acetylcarnosine (N-acetyl-β-alanylhistidine) and Carnosine (β-alanyl-L-histidine) which are essential constituents possessing diverse biological and pharmacological chaperone properties in human tissues.

  6. Currarino triad: surgical management and follow-up results of four [correction of three] cases.

    Science.gov (United States)

    Isik, Nejat; Elmaci, Ilhan; Gokben, Bekir; Balak, Naci; Tosyali, Nadir

    2010-08-01

    The Currarino syndrome is a rare triad that is a combination of a presacral mass, a congenital sacral bony abnormality and an anorectal malformation. We present 4 children with complete Currarino triad who were diagnosed using MRI. Our aim was to report the neurosurgical management of Currarino syndrome in children. All of the patients had chronic constipation and pain in the lumbosacral region. In the plain radiograph, 3 patients had a sacral scimitar-shaped bony abnormality, and 1 patient had total sacral agenesis. There was a narrow anal canal or narrow ventrally displaced anus in all patients. Their anorectal malformations were characterized as anal stenoses (4 patients), associated with Hirschsprung's disease in 2 cases. In 3 patients, MRI showed tethered cord syndrome in addition to the presacral mass. There was hydrocephalus in 1 patient. Anal stenosis was treated by anal dilatation. In 2 patients, rectal biopsy and temporary colostomy (2 patients) had been performed previously due to Hirschsprung's disease. We performed a posterior procedure via lumbar and sacral partial laminectomy-laminoplasty and transdural ligation of the neck of the meningocele for anterior sacral meningoceles, or alternatively, tumor excision for other types of presacral lesions. Histopathologically, 3 were cases of anterior sacral meningoceles and 1 was a teratoma. One of them also had a spinal abscess. He required reoperation (twice) and appeared at the time to have improved with medical therapy. All patients improved and stabilized. There were no additional neurological deficits and no recurrence of the presacral mass over the follow-up period (6 years, on average). The family pedigree did not reveal any familial transmission pattern. In cases of Currarino triad, MRI can allow the characterization of the presacral masses. If it is an anterior sacral meningocele or a solid tumor without severe anorectal malformation, it can be managed with posterior lumbar and sacral procedures

  7. Menkes disease and response to copper histidine: An Indian case series

    Directory of Open Access Journals (Sweden)

    Sangeetha Yoganathan

    2017-01-01

    Full Text Available Background: Menkes disease (MD is an X-linked recessive neurodegenerative disorder caused by mutations in ATP7A gene. Depending on the residual ATP7A activity, manifestation may be classical MD, occipital horn syndrome, or distal motor neuropathy. Neurological sparing is expected in female carriers. However, on rare occasions, females may manifest with classical clinical phenotype due to skewed X-chromosome inactivation, X-autosome translocation, and XO genotype. Here, we describe a small series of probands with MD and their response to copper histidine therapy. This series also includes a female with X-13 translocation manifesting neurological symptoms. Methods: The clinical profile, laboratory and radiological data, and follow-up of four children with MD were collected from the hospital database and are being presented. Results: All the four children in our series had developmental delay, recurrent respiratory tract infections, hair and skeletal changes, axial hypotonia, tortuous vessels on imaging, low serum copper, ceruloplasmin, and elevated lactate. Fetal hypokinesia and fetal growth retardation were present in two cases. Failure to thrive was present in three children and only one child had epilepsy. Subcutaneous copper histidine was administered to all children. The average time lapse in the initiation of treatment was 20.3 months, and average duration of follow-up was 14.3 months. Conclusion: We conclude that copper histidine therapy is beneficial in reversing the skin and hair changes, improving appendicular tone, socio-cognitive milestones, and improving weight gain, and immunity. Early diagnosis and management of MD are essential to have a better clinical outcome. More research is needed to explore and devise new strategies in the management of patients with MD.

  8. Studies on L-histidine capped Ag and Au nanoparticles for dopamine detection

    Energy Technology Data Exchange (ETDEWEB)

    Nivedhini Iswarya, Chandrasekaran; Kiruba Daniel, S.C.G. [Division of Nanoscience and Technology, Anna University-BIT Campus, Tiruchirappalli 620024 (India); Sivakumar, Muthusamy, E-mail: muthusiva@gmail.com [Division of Nanoscience and Technology, Anna University-BIT Campus, Tiruchirappalli 620024 (India); Department of Chemistry, Anna University-BIT Campus, Tiruchirappalli 620024 (India)

    2017-06-01

    This work demonstrates the effective surface functionalization of Ag, Au and bimetallic Ag-Au nanoparticles using L-histidine for colorimetric detection of dopamine (DA) which plays majorly in recognizing the neurological disorder. L-Histidine (L-His) capped Ag, Au, and bimetallic Ag-Au nanoparticles are characterized using physico-chemical techniques. The optical behaviour of nanoparticles has been analysed at various time intervals using UV–Vis absorption spectroscopy. FT-IR results provide the evidence of chemical bonding between L-histidine and metal nanoparticles. Its structure with the capping of L-His was clearly shown in HR-TEM images. The average size of nanoparticles has calculated from TEM image fringes are 11 nm, 5 nm and 6.5 nm respectively, matches with crystals size calculated from X-ray diffraction pattern. Enhanced optical nature of nanoparticles provides the best platform to develop a colorimetric-based biosensor for DA detection. After addition of DA, a rapid colour change has been noted in colloids of nanoparticles. The substantial changes in absorbance and λ{sub max} in metal nanoparticles respect to DA concentration have been observed and formulated. This is one of the successive methods for trace level determination of DA and will be going to a significant material for designing biosensor to determine DA in real extracellular body fluids. - Highlights: • L-His functionalized Ag, Au and bimetallic Ag-Au nanoparticles were prepared and its properties were studied. • L-His based Ag, Au, Ag-Au nanoparticles have characterized by spectroscopy, XRD and microscopic studies. • Enhanced optical nature of nanoparticles delivers the best platform to develop a biosensor for DA detection. • For qualitative determination of dopamine, SPR of metal nanoparticles plays a major role in dopamine determination. • This basic finding can be utilized for further identification of imbalanced DA concentration in body fluids.

  9. Assessing the Awareness and Behaviors of U.S. High School Nurses with Respect to the Female Athlete Triad

    Science.gov (United States)

    Kroshus, Emily; Fischer, Anastasia N.; Nichols, Jeanne F.

    2015-01-01

    Female high school athletes are an at-risk population for the Female Athlete Triad--a syndrome including low energy availability (with or without disordered eating), menstrual dysfunction, and low bone mineral density. School nurses can play an important role in reducing the health burden of this syndrome, by educating coaches and athletes, and by…

  10. The Dark Triad and the PID-5 Maladaptive Personality Traits: Accuracy, Confidence and Response Bias in Judgments of Veracity

    Directory of Open Access Journals (Sweden)

    Benno G. Wissing

    2017-09-01

    Full Text Available The Dark Triad traits—narcissism, Machiavellianism and psychopathy—have been found to be associated with intra- or interpersonal deception production frequency. This cross-sectional study (N = 207 investigated if the Dark Triad traits are also associated with deception detection accuracy, as implicated by the recent conception of a deception-general ability. To investigate associations between maladaptive personality space and deception, the PID-5 maladaptive personality traits were included to investigate if besides Machiavellianism, Detachment is negatively associated with response bias. Finally, associations between the Dark Triad traits, Antagonism, Negative Affectivity and confidence judgments were investigated. Participants watched videos of lying vs. truth-telling senders and judged the truthfulness of the statements. None of the Dark Triad traits was found to be associated with the ability to detect deception. Detachment was negatively associated with response bias. Psychopathy was associated with global confidence judgments. The results provide additional support that dark and maladaptive personality traits are associated with judgmental biases but not with accuracy in deception detection. The internal consistencies of 4 of the 8 subscales of the used personality short scales were only low and nearly sufficient (αs =0.65–0.69.

  11. The dynamics of triads in aggregated journal-journal citation relations: specialty developments at the above-journal level

    NARCIS (Netherlands)

    de Nooy, W.; Leydesdorff, L.

    2015-01-01

    Dyads of journals—related by citations—can agglomerate into specialties through the mechanism of triadic closure. Using the Journal Citation Reports 2011, 2012, and 2013, we analyze triad formation as indicators of integration (specialty growth) and disintegration (restructuring). The strongest

  12. The Dark Triad and three types of jealousy : Its’ relations among heterosexuals and homosexuals involved in a romantic relationship

    NARCIS (Netherlands)

    Barelds, Dick P.H.; Dijkstra, Pieternel; Groothof, Hinke A.K.; Pastoor, Charlotte D.

    2017-01-01

    The current study examined the relations between the three Dark Triad (DT) traits and three types of jealousy, among both heterosexual and homosexual men and women involved in a romantic relationship (n = 439). It was hypothesized that the three DT traits would be related positively to those types

  13. Autism and the cognitive processing triad: a case for revising the criteria in the diagnostic and statistical manual.

    Science.gov (United States)

    Cashin, Andrew; Gallagher, Hilary; Newman, Claire; Hughes, Mark

    2012-08-01

    The next iteration of the Diagnostic and Statistical Manual of Mental Disorders is due for release in May 2013. The current diagnostic criteria for autism are based on a behavioral triad of impairment, which has been helpful for diagnosis and identifying the need for intervention, but is not useful with regard to developing interventions. Revised diagnostic criteria are needed to better inform research and therapeutic intervention. This article examines the research underpinning the behavioral triad of impairment to consider alternative explanations and a more useful framing for diagnosis and intervention. Contemporary research and literature on autism were used in this study. It is proposed that the cognitive processing triad of impaired abstraction, impaired theory of mind, and impaired linguistic processing become the triad of impairment for autism in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. These are investigable at the diagnostic level and can usefully inform intervention. Further, in addressing the debate on whether restrictive and repetitive behavior should remain central to diagnosis or be replaced by a deficit in imagination, the authors argue that both behavioral manifestations are underpinned by impaired abstraction. © 2012 Wiley Periodicals, Inc.

  14. Homo- or Hetero- Triplet-Triplet Annihilation? A Case Study with Perylene-Bodipy Dyads/Triads

    KAUST Repository

    Cui, Xiaoneng; El-Zohry, Ahmed M.; Wang, Zhijia; Zhao, Jianzhang; Mohammed, Omar F.

    2017-01-01

    The photophysical processes of intramolecular ‘ping-pong’ energy transfers in the iodinated reference dyad BDP-I2-Py, as well as the uniodinated dyad BDP-Py and triad BDP-2Py, were studied. For BDP-I2-Py, a forward Förster resonance energy transfer

  15. 78 FR 23220 - Foreign-Trade Zone (FTZ) 230-Piedmont Triad Area, North Carolina; Notification of Proposed...

    Science.gov (United States)

    2013-04-18

    ...-backed paperboard and to laminate plastic film (the laminating activity is not ``production'' activity...--Piedmont Triad Area, North Carolina; Notification of Proposed Production Activity; Oracle Flexible..., grantee of FTZ 230, submitted a notification of proposed production activity on behalf of Oracle Flexible...

  16. Highly Efficient Photocatalytic Hydrogen Production of Flower-like Cadmium Sulfide Decorated by Histidine

    OpenAIRE

    Wang, Qizhao; Lian, Juhong; Li, Jiajia; Wang, Rongfang; Huang, Haohao; Su, Bitao; Lei, Ziqiang

    2015-01-01

    Morphology-controlled synthesis of CdS can significantly enhance the efficiency of its photocatalytic hydrogen production. In this study, a novel three-dimensional (3D) flower-like CdS is synthesized via a facile template-free hydrothermal process using Cd(NO3)2•4H2O and thiourea as precursors and L-Histidine as a chelating agent. The morphology, crystal phase, and photoelectrochemical performance of the flower-like CdS and pure CdS nanocrystals are carefully investigated via various characte...

  17. Identification of novel bacterial histidine biosynthesis inhibitors using docking, ensemble rescoring, and whole-cell assays

    DEFF Research Database (Denmark)

    Henriksen, Signe Teuber; Liu, J.; Estiu, G.

    2010-01-01

    histidine biosynthesis pathway, which is predicted to be essential for bacterial biomass productions. Virtual screening of a library of similar to 10(6) compounds identified 49 potential inhibitors of three enzymes of this pathway. Eighteen representative compounds were directly tested on three S. aureus......-and two Escherichia coli strains in standard disk inhibition assays. Thirteen compounds are inhibitors of some or all of the S. aureus strains, while 14 compounds weakly inhibit growth in one or both E. coli strains. The high hit rate obtained from a fast virtual screen demonstrates the applicability...

  18. Proton affinity of the histidine-tryptophan cluster motif from the influenza A virus from ab initio molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Bankura, Arindam; Klein, Michael L.; Carnevale, Vincenzo, E-mail: vincenzo.carnevale@temple.edu

    2013-08-30

    Highlights: • The estimated pK{sub a} is in agreement with the experimental one. • The affinity for protons is similar to that of a histidine residue in aqueous solution. • The electrostatic environment is responsible for the stabilization of the charged imidazolium moiety. - Abstract: Ab initio molecular dynamics calculations have been used to compare and contrast the deprotonation reaction of a histidine residue in aqueous solution with the situation arising in a histidine-tryptophan cluster. The latter is used as a model of the proton storage unit present in the pore of the M2 proton conducting ion channel. We compute potentials of mean force for the dissociation of a proton from the Nδ and N∊ positions of the imidazole group to estimate the pK{sub a}s. Anticipating our results, we will see that the estimated pK{sub a} for the first protonation event of the M2 channel is in good agreement with experimental estimates. Surprisingly, despite the fact that the histidine is partially desolvated in the M2 channel, the affinity for protons is similar to that of a histidine in aqueous solution. Importantly, the electrostatic environment provided by the indoles is responsible for the stabilization of the charged imidazolium.

  19. Strengthening the dementia care triad: identifying knowledge gaps and linking to resources.

    Science.gov (United States)

    Jensen, Christine J; Inker, Jennifer

    2015-05-01

    This article describes a project to identify the needs of family caregivers and health care providers caring for persons with dementia. Participants included 128 caregivers, who completed a survey, and 27 health care providers, who participated in a focus group and completed a survey. Caregivers reported their primary source of information about the disease was the doctor; however, the majority also reported they were primarily informed of medications and not about needed resources. Health care providers identified limited time with patients and families, and lack of awareness of community services, as their main challenges. Recommendations include strengthening the partnership between physicians, patients, and caregivers (the dementia care triad) through additional support and training for physicians and caregivers, increasing awareness of the Alzheimer's Association, and utilization of technology for families and professionals to track the needs of persons with dementia. © The Author(s) 2014.

  20. Practicing the triad teaching-research- extension in supervised internship of licentiateship in biological sciences

    Directory of Open Access Journals (Sweden)

    Lilliane Miranda Freitas

    2012-06-01

    Full Text Available In this paper we report an educational experience based on the triad teaching-research-extension occurred in the supervised internship in licentiateship in Biological Sciences. In this experiment, the students made a transposition of the scientific knowledge produced in their course conclusion work to the knowledge of basic education curriculum. We analyze in this article the impressions of undergraduates after completion of pedagogical actions. We discuss, based on the reports, how the knowledge that is constructed and reconstructed in academic research can contribute directly to the improvement of the science education quality through science literacy and also in teacher training of undergraduates, through the reflection on their own practice. Therefore, we consider that, with the practice of the inseparability of teaching-research-extension, there will be more return for academic research and also for the school community, generating significant changes in educational practices in schools

  1. Age-related Hearing Impairment and the Triad of Acquired Hearing Loss

    Directory of Open Access Journals (Sweden)

    Chao-Hui eYang

    2015-07-01

    Full Text Available Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss ¬¬displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI in human and animal models and address selected aspects of the commonality (or lack thereof of cellular responses in ARHI to drugs and noise.

  2. Quantum chemical study of TiO2/dopamine-DNA triads

    International Nuclear Information System (INIS)

    Vega-Arroyo, Manuel; LeBreton, Pierre R.; Zapol, Peter; Curtiss, Larry A.; Rajh, Tijana

    2007-01-01

    Photoinduced charge separation in triads of DNA covalently linked to an anatase nanoparticle via a dopamine bridge was studied by ab initio calculations of the oxidation potentials of carboxyl-DNA trimers and the TiO 2 /dopamine complex. Conjugation of dopamine to the TiO 2 surface results in a lower oxidation potential of the complex relative to the surface and in localization of photogenerated holes on dopamine, while photogenerated electrons are excited into the conduction band of TiO 2 . Linking dopamine to the DNA trimers at the 5' end of the oligonucleotide may lead to further hole migration to the DNA. Calculations show that for several different sequences hole migration is favorable in double stranded DNA and unfavorable in single-stranded DNA. This extended charge separation was shown to follow from the redox properties of DNA sequence rather than from the modification of DNA's electron donating properties by the dopamine linker, which explains experimental observations

  3. Validation of a food frequency questionnaire to determine vitamin D intakes using the method of triads.

    Science.gov (United States)

    Weir, R R; Carson, E L; Mulhern, M S; Laird, E; Healy, M; Pourshahidi, L K

    2016-04-01

    Dietary sources of vitamin D (both natural and fortified) are increasingly contributing to consumers' vitamin D intake and status. Therefore, the present study aimed to validate a vitamin D food frequency questionnaire (FFQ) for the assessment of habitual vitamin D intake. A total of 49 apparently healthy consenting adults (aged 18-64 years) from the local community were sampled at the end of winter. Dietary intakes were recorded using a 4-day weighed food record (4d-WFR) and a 17-item FFQ based on foods known to contribute to dietary vitamin D intake. Fasting vitamin D status was quantified by serum 25-hydroxyvitamin D [25(OH)D] using liquid chromatography tandem mass spectrometry. The method of triads was applied using these three measurements to determine the overall validity of the FFQ. Vitamin D intakes from 4d-WFR ranged between 0.42 and 31.65 μg day(-1), whereas intakes determined from the FFQ ranged from 1.03 to 36.08 μg day(-1). Serum 25(OH)D concentrations ranged between 12.89 and 279.00 nmol L(-1). The mean (SD) difference between the FFQ and 4d-WFR was +1.62 ( 3.86). There were strong correlations between the vitamin D intake estimated by the FFQ and that from the 4d-WFR (r = 0.562) and also with serum 25(OH)D concentrations (r = 0.567). Vitamin D intake estimated from the 4d-WFR was also strongly correlated with serum 25(OH)D concentrations (r = 0.411). The overall validity coefficient calculated using the method of triads was high (0.881). The vitamin D FFQ has been validated for use in future studies aiming to assess habitual vitamin D intake. © 2015 The British Dietetic Association Ltd.

  4. The Goal Triad in Games. A Conceptual Map and Case Studies

    Directory of Open Access Journals (Sweden)

    Filip Kobiela

    2016-04-01

    Full Text Available Although the very existence and need for an exact definition of sport is still debatable, there is common agreement that competitive sport events on elite level are, among others, goal directed, rule-governed and institutionalized activities. These three facts will guide us in an analysis of the complex issue concerning the idea of goal in games. The first of these facts - that games are goal-oriented activities – is reflected in the very basic notion of prelusory goal. The fact that achieving the prelusory goal in games is rule-governed is reflected in the notion of a lusory goal. Finally, the institutionalized aspect of games is reflected in the notion of, nomen omen, an institutional goal.            The paper is thus devoted to detailed analysis of the notion of goal in games. It is argued that Suits' analysis which provides a distinction between prelusory goal and lusory goal is insufficient, and thus introduction of a third kind of goal is necessary. I suggest to call this third kind of goal institutional goal.The paper discusses the definition of this kind of goal as well as its relations to other kinds of goals in games and other elements of game-playing. These three goals create the goal triad, a conceptual map of all possible goal-related situations. Both Venn diagrams and Euler diagrams are used to represent this triad.            Various fields of these diagrams, which represent a spectrum of specific situations that occur in games, are illustrated by case-studies, taken mainly (although not exclusively from the history of association football (soccer. These examples are meant to test the usefulness of distinctions provided in the analytical part of the paper.

  5. Assessment of nutritional knowledge in female athletes susceptible to the Female Athlete Triad syndrome

    Directory of Open Access Journals (Sweden)

    Petroczi Andrea

    2007-09-01

    Full Text Available Abstract Background The study aimed to i assess nutritional knowledge in female athletes susceptible to the Female Athlete Triad (FAT syndrome and to compare with controls; and ii to compare nutritional knowledge of those who were classified as being 'at risk' for developing FAT syndrome and those who are 'not at risk'. Methods In this study, participants completed General Nutritional Knowledge Questionnaire (GNKQ, the Eating Attitude Test (EAT-26 and survey measures of training/physical activity, menstrual and skeletal injury history. The sample consisted of 48 regional endurance athletes, 11 trampoline gymnasts and 32 untrained controls. Based on proxy measures for the FAT components, participants were classified being 'at risk' or 'not at risk' and nutrition knowledge scores were compared for the two groups. Formal education related to nutrition was considered. Results A considerably higher percentage of athletes were classified 'at risk' of menstrual dysfunction than controls (28.8% and 9.4%, respectively and a higher percentage scored at or above the cutoff value of 20 on the EAT-26 test among athletes than controls (10.2% and 3.1%, respectively. 8.5% of athletes were classified 'at risk' for bone mineral density in contrast to none from the control group. Nutrition knowledge and eating attitude appeared to be independent for both athletes and controls. GNKQ scores of athletes were higher than controls but the differences between the knowledge of 'at risk' and 'not at risk' athletes and controls were inconsequential. Formal education in nutrition or closely related subjects does not have an influence on nutrition knowledge or on being classified as 'at risk' or 'not at risk'. Conclusion The lack of difference in nutrition knowledge between 'at risk' and 'not at risk' athletes suggests that lack of information is not accountable for restricted eating associated with the Female Athlete Triad.

  6. Examining Dark Triad traits in relation to mental toughness and physical activity in young adults

    Directory of Open Access Journals (Sweden)

    Sabouri S

    2016-01-01

    Full Text Available Sarah Sabouri,1 Markus Gerber,2 Dena Sadeghi Bahmani,3 Sakari Lemola,4 Peter J Clough,5 Nadeem Kalak,3 Mahin Shamsi,1 Edith Holsboer-Trachsler,3 Serge Brand2,3 1Faculty of Educational Sciences and Psychology, AllamehTabataba’i University, Tehran, Iran; 2Department of Sport, Exercise and Health, Sport Science Section, University of Basel, 3Center for Affective, Stress and Sleep Disorders, Psychiatric Clinics of the University of Basel, 4Faculty of Psychology, University of Basel, Basel, Switzerland; 5Department of Psychology, Manchester Metropolitan University, Manchester, UK Objective: The Dark Triad (DT describes a set of three closely related personality traits: Machiavellianism, narcissism, and psychopathy. Mental toughness (MT refers to a psychological construct combining confidence, commitment, control, and challenge. High MT is related to greater physical activity (PA and, relative to men, women have lower MT scores. The aims of the present study were 1 to investigate the association between DT, MT, and PA, and 2 to compare the DT, MT, and PA scores of men and women.Methods: A total of 341 adults (M=29 years; 51.6% women; range: 18–37 years took part in the study. Participants completed a series of questionnaires assessing DT, MT, and PA.Results: Machiavellianism, narcissism, and psychopathy were all significantly associated with higher MT scores (rs =0.45, 0.50, and 0.20, respectively. DT traits and MT were associated with more vigorous PA. Compared to men, women participants had lower scores for DT traits (overall score and psychopathy, while no differences were found for MT or PA in both sexes.Conclusion: DT traits, high MT, and vigorous PA are interrelated. This pattern of results might explain why, for instance, successful professional athletes can at the same time be tough and ruthless. Keywords: dark triad, mental toughness, physical activity, young adults, sex

  7. Random mutagenesis in Corynebacterium glutamicum ATCC 13032 using an IS6100-based transposon vector identified the last unknown gene in the histidine biosynthesis pathway

    Directory of Open Access Journals (Sweden)

    Gaigalat Lars

    2006-08-01

    Full Text Available Abstract Background Corynebacterium glutamicum, a Gram-positive bacterium of the class Actinobacteria, is an industrially relevant producer of amino acids. Several methods for the targeted genetic manipulation of this organism and rational strain improvement have been developed. An efficient transposon mutagenesis system for the completely sequenced type strain ATCC 13032 would significantly advance functional genome analysis in this bacterium. Results A comprehensive transposon mutant library comprising 10,080 independent clones was constructed by electrotransformation of the restriction-deficient derivative of strain ATCC 13032, C. glutamicum RES167, with an IS6100-containing non-replicative plasmid. Transposon mutants had stable cointegrates between the transposon vector and the chromosome. Altogether 172 transposon integration sites have been determined by sequencing of the chromosomal inserts, revealing that each integration occurred at a different locus. Statistical target site analyses revealed an apparent absence of a target site preference. From the library, auxotrophic mutants were obtained with a frequency of 2.9%. By auxanography analyses nearly two thirds of the auxotrophs were further characterized, including mutants with single, double and alternative nutritional requirements. In most cases the nutritional requirement observed could be correlated to the annotation of the mutated gene involved in the biosynthesis of an amino acid, a nucleotide or a vitamin. One notable exception was a clone mutagenized by transposition into the gene cg0910, which exhibited an auxotrophy for histidine. The protein sequence deduced from cg0910 showed high sequence similarities to inositol-1(or 4-monophosphatases (EC 3.1.3.25. Subsequent genetic deletion of cg0910 delivered the same histidine-auxotrophic phenotype. Genetic complementation of the mutants as well as supplementation by histidinol suggests that cg0910 encodes the hitherto unknown

  8. Does the Dark Triad of personality predict corrupt intention? The mediating role of belief in good luck

    Directory of Open Access Journals (Sweden)

    Huanhuan eZhao

    2016-04-01

    Full Text Available The current study is the first attempt to examine the association between the Dark Triad of personality (i.e., Machiavellianism, narcissism, and psychopathy and corruption through a mediator – belief in good luck. Based on Ajzen’s theory of planned behavior, we assumed that individuals with Dark Triad would be more likely to engage in corruption as a result of belief in good luck. In Study 1, a set of hypothetical scenarios was used to assess the bribe-offering intention and the corresponding belief in good luck. Results indicated that while the Dark Triad of personality positively predicted bribe-offering intention, it was mediated by the belief in good luck in bribe-offering. In Study 2, we presented participants with some hypothetical scenarios of bribe-taking and the corresponding belief in good luck. Findings revealed that the Dark Triad of personality was positively related to bribe-taking intention; the relationship between narcissism and bribe-taking intention, and that between psychopathy and bribe-taking intention was mediated by the belief in good luck in penalty-avoidance. However, this belief in good luck did not mediate the relationship between Machiavellianism and bribe-taking intention. These results hold while controlling for demographic variables, dispositional optimism, and self-efficacy. Taken together, this study extended previous research by providing evidence that belief in good luck may be one of the reasons explaining why people with Dark Triad are more likely to engage in corruption regardless of the potential outcomes. Theoretical and practical implications were discussed.

  9. Does the Dark Triad of Personality Predict Corrupt Intention? The Mediating Role of Belief in Good Luck.

    Science.gov (United States)

    Zhao, Huanhuan; Zhang, Heyun; Xu, Yan

    2016-01-01

    The current study is the first attempt to examine the association between the Dark Triad of personality (i.e., Machiavellianism, narcissism, and psychopathy) and corruption through a mediator-belief in good luck. Based on Ajzen's theory of planned behavior, we assumed that individuals with Dark Triad would be more likely to engage in corruption as a result of belief in good luck. In Study 1, a set of hypothetical scenarios was used to assess the bribe-offering intention and the corresponding belief in good luck. Results indicated that while the Dark Triad of personality positively predicted bribe-offering intention, it was mediated by the belief in good luck in gain-seeking. In Study 2, we presented participants with some hypothetical scenarios of bribe-taking and the corresponding belief in good luck. Findings revealed that the Dark Triad of personality was positively related to bribe-taking intention; the relationship between narcissism and bribe-taking intention, and that between psychopathy and bribe-taking intention was mediated by the belief in good luck in penalty-avoidance. However, this belief in good luck did not mediate the relationship between Machiavellianism and bribe-taking intention. These results hold while controlling for demographic variables, dispositional optimism, and self-efficacy. Taken together, this study extended previous research by providing evidence that belief in good luck may be one of the reasons explaining why people with Dark Triad are more likely to engage in corruption regardless of the potential outcomes. Theoretical and practical implications were discussed.

  10. Does the Dark Triad of Personality Predict Corrupt Intention? The Mediating Role of Belief in Good Luck

    Science.gov (United States)

    Zhao, Huanhuan; Zhang, Heyun; Xu, Yan

    2016-01-01

    The current study is the first attempt to examine the association between the Dark Triad of personality (i.e., Machiavellianism, narcissism, and psychopathy) and corruption through a mediator—belief in good luck. Based on Ajzen's theory of planned behavior, we assumed that individuals with Dark Triad would be more likely to engage in corruption as a result of belief in good luck. In Study 1, a set of hypothetical scenarios was used to assess the bribe-offering intention and the corresponding belief in good luck. Results indicated that while the Dark Triad of personality positively predicted bribe-offering intention, it was mediated by the belief in good luck in gain-seeking. In Study 2, we presented participants with some hypothetical scenarios of bribe-taking and the corresponding belief in good luck. Findings revealed that the Dark Triad of personality was positively related to bribe-taking intention; the relationship between narcissism and bribe-taking intention, and that between psychopathy and bribe-taking intention was mediated by the belief in good luck in penalty-avoidance. However, this belief in good luck did not mediate the relationship between Machiavellianism and bribe-taking intention. These results hold while controlling for demographic variables, dispositional optimism, and self-efficacy. Taken together, this study extended previous research by providing evidence that belief in good luck may be one of the reasons explaining why people with Dark Triad are more likely to engage in corruption regardless of the potential outcomes. Theoretical and practical implications were discussed. PMID:27199841

  11. Mutations in Cancer Cause Gain of Cysteine, Histidine, and Tryptophan at the Expense of a Net Loss of Arginine on the Proteome Level

    Directory of Open Access Journals (Sweden)

    Viktoriia Tsuber

    2017-07-01

    Full Text Available Accumulation of somatic mutations is critical for the transition of a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties of proteins. However, it has not been studied as to what extent the composition and accordingly chemical properties of the cell proteome is altered as a result of the increased mutation load in cancer. Here, we analyzed data on amino acid substitutions caused by mutations in about 2000 protein coding genes from the Cancer Cell Line Encyclopedia that contains information on nucleotide and amino acid alterations in 782 cancer cell lines, and validated the analysis with information on amino acid substitutions for the same set of proteins in the Catalogue of Somatic Mutations in Cancer (COSMIC; v78 in circa 18,000 tumor samples. We found that nonsynonymous single nucleotide substitutions in the analyzed proteome subset ultimately result in a net gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine. The extraordinary loss of arginine may be attributed to some extent to composition of its codons as well as to the importance of arginine in the functioning of prominent tumor suppressor proteins like p53.

  12. The identification of four histidine kinases that influence sporulation in Clostridium thermocellum.

    Science.gov (United States)

    Mearls, Elizabeth B; Lynd, Lee R

    2014-08-01

    In this study, we sought to identify genes involved in the onset of spore formation in Clostridium thermocellum via targeted gene deletions, gene over-expression, and transcriptional analysis. We determined that three putative histidine kinases, clo1313_0286, clo1313_2735 and clo1313_1942 were positive regulators of sporulation, while a fourth kinase, clo1313_1973, acted as a negative regulator. Unlike Bacillus or other Clostridium species, the deletion of a single positively regulating kinase was sufficient to abolish sporulation in this organism. Sporulation could be restored in these asporogenous strains via overexpression of any one of the positive regulators, indicating a high level of redundancy between these kinases. In addition to having a sporulation defect, deletion of clo1313_2735 produced L-forms. Thus, this kinase may play an additional role in repressing L-form formation. This work suggests that C. thermocellum enters non-growth states based on the sensory input from multiple histidine kinases. The ability to control the development of non-growth states at the genetic level has the potential to inform strategies for improved strain development, as well as provide valuable insight into C. thermocellum biology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Structural, evolutionary and genetic analysis of the histidine biosynthetic "core" in the genus Burkholderia.

    Science.gov (United States)

    Papaleo, Maria Cristiana; Russo, Edda; Fondi, Marco; Emiliani, Giovanni; Frandi, Antonio; Brilli, Matteo; Pastorelli, Roberta; Fani, Renato

    2009-12-01

    In this work a detailed analysis of the structure, the expression and the organization of his genes belonging to the core of histidine biosynthesis (hisBHAF) in 40 newly determined and 13 available sequences of Burkholderia strains was carried out. Data obtained revealed a strong conservation of the structure and organization of these genes through the entire genus. The phylogenetic analysis showed the monophyletic origin of this gene cluster and indicated that it did not undergo horizontal gene transfer events. The analysis of the intergenic regions, based on the substitution rate, entropy plot and bendability suggested the existence of a putative transcription promoter upstream of hisB, that was supported by the genetic analysis that showed that this cluster was able to complement Escherichia colihisA, hisB, and hisF mutations. Moreover, a preliminary transcriptional analysis and the analysis of microarray data revealed that the expression of the his core was constitutive. These findings are in agreement with the fact that the entire Burkholderiahis operon is heterogeneous, in that it contains "alien" genes apparently not involved in histidine biosynthesis. Besides, they also support the idea that the proteobacterial his operon was piece-wisely assembled, i.e. through accretion of smaller units containing only some of the genes (eventually together with their own promoters) involved in this biosynthetic route. The correlation existing between the structure, organization and regulation of his "core" genes and the function(s) they perform in cellular metabolism is discussed.

  14. Novel Organotin(IV) Schiff Base Complexes with Histidine Derivatives: Synthesis, Characterization, and Biological Activity

    Science.gov (United States)

    Garza-Ortiz, Ariadna; Camacho-Camacho, Carlos; Sainz-Espuñes, Teresita; Rojas-Oviedo, Irma; Gutiérrez-Lucas, Luis Raúl; Gutierrez Carrillo, Atilano; Vera Ramirez, Marco A.

    2013-01-01

    Five novel tin Schiff base complexes with histidine analogues (derived from the condensation reaction between L-histidine and 3,5-di-tert-butyl-2-hydroxybenzaldehyde) have been synthesized and characterized. Characterization has been completed by IR and high-resolution mass spectroscopy, 1D and 2D solution NMR (1H, 13C  and 119Sn), as well as solid state 119Sn NMR. The spectroscopic evidence shows two types of structures: a trigonal bipyramidal stereochemistry with the tin atom coordinated to five donating atoms (two oxygen atoms, one nitrogen atom, and two carbon atoms belonging to the alkyl moieties), where one molecule of ligand is coordinated in a three dentate fashion. The second structure is spectroscopically described as a tetrahedral tin complex with four donating atoms (one oxygen atom coordinated to the metal and three carbon atoms belonging to the alkyl or aryl substituents), with one molecule of ligand attached. The antimicrobial activity of the tin compounds has been tested against the growth of bacteria in vitro to assess their bactericidal properties. While pentacoordinated compounds 1, 2, and 3 are described as moderate effective to noneffective drugs against both Gram-positive and Gram-negative bacteria, tetracoordinated tin(IV) compounds 4 and 5 are considered as moderate effective and most effective compounds, respectively, against the methicillin-resistant Staphylococcus aureus strains (Gram-positive). PMID:23864839

  15. Immobilized poly-L-histidine for chelation of metal cations and metal oxyanions

    International Nuclear Information System (INIS)

    Malachowski, Lisa; Holcombe, James A.

    2003-01-01

    The biohomopolymer poly-L-histidine (PLHis) was immobilized onto controlled pore glass (CPG) and its metal binding capabilities evaluated through the use of a flow injection-flame atomic absorption system. The metal binding capability of PLHis-CPG was determined through the analysis of the generated breakthrough curves. The polymer likely coordinates cationic metals through the imidazole side chain (pK a ∼6) present on each histidine residue with both strong and weak binding sites for Cu 2+ , Cd 2+ , Co 2+ , and Ni 2+ . Weak to minimal binding was observed for Mn 2+ , Ca 2+ , Mg 2+ , Na + , and Cr 3+ . The bound metals are quantitatively released from the column with an acid strip. It has also been shown that the protonated imidazole side chain present in acidic solutions is capable of binding metal oxyanions such as chromates, arsenates, and selenites; although oxyanion binding currently exhibits interferences from competing anions in solution, such as sulfate and nitrate. The interference in oxyanion binding is less severe in the presence of chloride, phosphate, and acetate. PLHis-CPG exhibits a capacity of ∼30 μmol Cu 2+ /g CPG in neutral to basic conditions, and a capacity of ∼70 μmol Cr(VI)/g CPG, ∼4 μmol As(V)/g CPG, and ∼4 μmol Se(IV)/g CPG in acidic conditions

  16. Kinetic alteration of a human dihydrodiol/3alpha-hydroxysteroid dehydrogenase isoenzyme, AKR1C4, by replacement of histidine-216 with tyrosine or phenylalanine.

    Science.gov (United States)

    Ohta, T; Ishikura, S; Shintani, S; Usami, N; Hara, A

    2000-01-01

    Human dihydrodiol dehydrogenase with 3alpha-hydroxysteroid dehydrogenase activity exists in four forms (AKR1C1-1C4) that belong to the aldo-keto reductase (AKR) family. Recent crystallographic studies on the other proteins in this family have indicated a role for a tyrosine residue (corresponding to position 216 in these isoenzymes) in stacking the nicotinamide ring of the coenzyme. This tyrosine residue is conserved in most AKR family members including AKR1C1-1C3, but is replaced with histidine in AKR1C4 and phenylalanine in some AKR members. In the present study we prepared mutant enzymes of AKR1C4 in which His-216 was replaced with tyrosine or phenylalanine. The two mutations decreased 3-fold the K(m) for NADP(+) and differently influenced the K(m) and k(cat) for substrates depending on their structures. The kinetic constants for bile acids with a 12alpha-hydroxy group were decreased 1.5-7-fold and those for the other substrates were increased 1.3-9-fold. The mutation also yielded different changes in sensitivity to competitive inhibitors such as hexoestrol analogues, 17beta-oestradiol, phenolphthalein and flufenamic acid and 3,5,3', 5'-tetraiodothyropropionic acid analogues. Furthermore, the mutation decreased the stimulatory effects of the enzyme activity by sulphobromophthalein, clofibric acid and thyroxine, which increased the K(m) for the coenzyme and substrate of the mutant enzymes more highly than those of the wild-type enzyme. These results indicate the importance of this histidine residue in creating the cavity of the substrate-binding site of AKR1C4 through the orientation of the nicotinamide ring of the coenzyme, as well as its involvement in the conformational change by binding non-essential activators. PMID:11104674

  17. Identification of five B-type response regulators as members of a multistep phosphorelay system interacting with histidine-containing phosphotransfer partners of Populus osmosensor

    Directory of Open Access Journals (Sweden)

    Bertheau Lucie

    2012-12-01

    Full Text Available Abstract Background In plants, the multistep phosphorelay signaling pathway mediates responses to environmental factors and plant hormones. This system is composed of three successive partners: hybrid Histidine-aspartate Kinases (HKs, Histidine-containing Phosphotransfer proteins (HPts, and Response Regulators (RRs. Among the third partners, B-type RR family members are the final output elements of the pathway; they act as transcription factors and clearly play a pivotal role in the early response to cytokinin in Arabidopsis. While interactions studies between partners belonging to the multistep phosphorelay system are mainly focused on protagonists involved in cytokinin or ethylene pathways, very few reports are available concerning partners of osmotic stress signaling pathway. Results In Populus, we identified eight B-type RR proteins, RR12-16, 19, 21 and 22 in the Dorskamp genotype. To assess HPt/B-type RR interactions and consequently determine potential third partners in the osmosensing multistep phosphorelay system, we performed global yeast two-hybrid (Y2H assays in combination with Bimolecular Fluorescence Complementation (BiFC assays in plant cells. We found that all B-type RRs are able to interact with HPt predominant partners (HPt2, 7 and 9 of HK1, which is putatively involved in the osmosensing pathway. However, different profiles of interaction are observed depending on the studied HPt. HPt/RR interactions displayed a nuclear localization, while the nuclear and cytosolic localization of HPt and nuclear localization of RR proteins were validated. Although the nuclear localization of HPt/RR interaction was expected, this work constitutes the first evidence of such an interaction in plants. Furthermore, the pertinence of this partnership is reinforced by highlighting a co-expression of B-type RR transcripts and the other partners (HK1 and HPts belonging to a potential osmosensing pathway. Conclusion Based on the interaction studies

  18. Protein modification by acrolein: Formation and stability of cysteine adducts

    OpenAIRE

    Cai, Jian; Bhatnagar, Aruni; Pierce, William M.

    2009-01-01

    The toxicity of the ubiquitous pollutant and endogenous metabolite, acrolein, is due in part to covalent protein modifications. Acrolein reacts readily with protein nucleophiles via Michael addition and Schiff base formation. Potential acrolein targets in protein include the nucleophilic side chains of cysteine, histidine, and lysine residues as well as the free amino terminus of proteins. Although cysteine is the most acrolein-reactive residue, cysteine-acrolein adducts are difficult to iden...

  19. Future Naval Concepts -- Crew Reductions through Improved Damage Control Communications (FNC-CRIDCC), Triad Test 2 Report (18-22 Sep 2006)

    National Research Council Canada - National Science Library

    Street, Thomas T; Williams, Frederick W; Cooper, L. S; Halloway, III, Kenneth E; Rininger, Michael; Miller, Charles; Shirley, Bradley; Genovese, Samuel; Perry, Rendell; McCombs, Kenney

    2007-01-01

    The object of Triad Test 2 was to conduct and document an RF coverage survey of the installed WLAN aboard ex-USS Shadwell in a benign environment, obtain RF WLA data during fire events, and evaluate...

  20. The CAD triad hypothesis: a mapping between three moral emotions (contempt, anger, disgust) and three moral codes (community, autonomy, divinity).

    Science.gov (United States)

    Rozin, P; Lowery, L; Imada, S; Haidt, J

    1999-04-01

    It is proposed that 3 emotions--contempt, anger, and disgust--are typically elicited, across cultures, by violations of 3 moral codes proposed by R. A. Shweder and his colleagues (R. A. Shweder, N. C. Much, M. Mahapatra, & L. Park, 1997). The proposed alignment links anger to autonomy (individual rights violations), contempt to community (violation of communal codes including hierarchy), and disgust to divinity (violations of purity-sanctity). This is the CAD triad hypothesis. Students in the United States and Japan were presented with descriptions of situations that involve 1 of the types of moral violations and asked to assign either an appropriate facial expression (from a set of 6) or an appropriate word (contempt, anger, disgust, or their translations). Results generally supported the CAD triad hypothesis. Results were further confirmed by analysis of facial expressions actually made by Americans to the descriptions of these situations.

  1. Shelbourne's update of the O'Donoghue knee triad in a 17-year-old male Rugby player.

    Science.gov (United States)

    Dacombe, Peter Jonathan

    2013-01-23

    Acute athletic knee injuries are often caused by a combination of valgus impact with external rotation of the tibia leading to a triad of injuries involving medial collateral and anterior cruciate ligament disruption with associated meniscal damage. This injury pattern has been greatly discussed in the literature with conflicts of opinion and evidence as to whether medial or lateral meniscal pathology has a higher incidence. This case report introduces a 17-year-old male athlete with this unhappy triad It will evaluate the clinical assessment which suggested a medial meniscal lesion follow the patient through arthroscopy revealing a lateral meniscal tear in addition to complete anterior cruciate ligament rupture and grade 2 medial collateral ligament tear. It will go on to look at the evidence base for the relative incidence of lateral and medial meniscal injuries and will evaluate the role of MRI in assessing acute athletic knee injuries.

  2. Chromium III histidinate exposure modulates antioxidant gene expression in HaCaT human keratinocytes exposed to oxidative stress

    Science.gov (United States)

    While the toxicity of hexavalent chromium is well established, trivalent Cr (Cr(III)) is an essential nutrient involved in insulin and glucose homeostasis. Recently, antioxidant effects of chromium (III) histidinate (Cr(III)His) were reported in HaCaT human keratinocytes exposed to oxidative stress...

  3. Platinum(II) complexes with steroidal esters of L-methionine and L-histidine: Synthesis, characterization and cytotoxic activity

    Czech Academy of Sciences Publication Activity Database

    Kvasnica, Miroslav; Buděšínský, Miloš; Swaczynová, Jana; Pouzar, Vladimír; Kohout, Ladislav

    2008-01-01

    Roč. 16, č. 7 (2008), s. 3704-3713 ISSN 0968-0896 R&D Projects: GA AV ČR KAN200200651 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50380511 Keywords : steroids * platinum * L-histidin * L-methionin Subject RIV: CC - Organic Chemistry Impact factor: 3.075, year: 2008

  4. Triazacyclophane (TAC)-scaffolded histidine and aspartic acid residues as mimics of non-heme metalloenzyme active sites

    NARCIS (Netherlands)

    Albada, H.B.; Soulimani, F.; Jacobs, H.J.F.; Versluis, C.; Weckhuysen, B.M.; Liskamp, R.M.J.

    2012-01-01

    We describe the synthesis and coordination behaviour to copper(II) of two close structural triazacyclophane-based mimics of two often encountered aspartic acid and histidine containing metalloenzyme active sites. Coordination of these mimics to copper(I) and their reaction with molecular oxygen

  5. Tritium labeling of gonadotropin releasing hormone in its proline and histidine residues

    International Nuclear Information System (INIS)

    Klauschenz, E.; Bienert, M.; Egler, H.; Pleiss, U.; Niedrich, H.; Nikolics, K.

    1981-01-01

    3,4-dehydroproline9-GnRH prepared by solid phase peptide synthesis was tritiated catalytically under various conditions yielding 3H-GnRH with specific radioactivities in the range from 35-60 Ci/mmol and full LH releasing activity in vitro. Using palladium/alumina catalyst, the tritiation of the double bond occurs within ten minutes. Investigation of the tritium distribution between the amino acid residues showed a remarkably high incorporation of tritium into the histidine residue (11 to 37%). On the basis of this observation, the tritium labeling of GnRH and angiotensin I by direct catalytic hydrogen-tritium exchange was found to be useful for the labeling of these peptides at remarkably high specific radioactivity

  6. Using Poly-L-Histidine Modified Glassy Carbon Electrode to Trace Hydroquinone in the Sewage Water

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2014-01-01

    Full Text Available A sensitive voltammetric method for trace measurements of hydroquinone in the sewage water is described. The poly-L-histidine is prepared to modify the glassy carbon electrode in order to improve the electrochemical catalysis of interesting substances such as hydroquinone. The influence of the base solution, pH value, and scanning speed on the tracing of hydroquinone is discussed, and the experimental procedures and conditions are optimized. The laboratory results show that it is possible to construct a linear calibration curve between the peak current of hydroquinone on modified electrode and its concentration at the level of 0.00001 mol/L. The potential limitation of the method is suggested by a linear peaking shift model as well. The method was successfully applied to the determination of hydroquinone in the actual sample of industrial waste water.

  7. Final Verification Success Story Using the Triad Approach at the Oak Ridge National Laboratory's Melton Valley Soils and Sediment Project

    International Nuclear Information System (INIS)

    King, D.A.; Haas, D.A.; Cange, J.B.

    2006-01-01

    The United States Environmental Protection Agency recently published guidance on the Triad approach, which supports the use of smarter, faster, and better technologies and work strategies during environmental site assessment, characterization, and cleanup. The Melton Valley Soils and Sediment Project (Project) at the Oak Ridge National Laboratory embraced this three-pronged approach to characterize contaminants in soil/sediment across the 1000-acre Melton Valley Watershed. Systematic Project Planning is the first of three prongs in the Triad approach. Management initiated Project activities by identifying key technical personnel, included regulators early in the planning phase, researched technologies, and identified available resources necessary to meet Project objectives. Dynamic Work Strategies is the second prong of the Triad approach. Core Team members, including State and Federal regulators, helped develop a Sampling and Analysis Plan that allowed experienced field managers to make real-time, in-the-field decisions and, thus, to adjust to conditions unanticipated during the planning phase. Real-time Measurement Technologies is the third and last prong of the Triad approach. To expedite decision-making, the Project incorporated multiple in-field technologies, including global positioning system equipment integrated with field screening instrumentation, magnetometers for utility clearance, and an on-site gamma spectrometer (spec) for rapid contaminant speciation and quantification. As a result of a relatively complex but highly efficient program, a Project field staff of eight collected approximately 1900 soil samples for on-site gamma spec analysis (twenty percent were also shipped for off-site analyses), 4.7 million gamma radiation measurements, 1000 systematic beta radiation measurements, and 3600 systematic dose rate measurements between July 1, 2004, and October 31, 2005. The site database previously contained results for less than 500 soil samples dating

  8. A "weight of evidence" approach for the integration of environmental "triad" data to assess ecological risk and biological vulnerability.

    Science.gov (United States)

    Dagnino, Alessandro; Sforzini, Susanna; Dondero, Francesco; Fenoglio, Stefano; Bona, Elisa; Jensen, John; Viarengo, Aldo

    2008-07-01

    A new Expert Decision Support System (EDSS) that can integrate Triad data for assessing environmental risk and biological vulnerability at contaminated sites has been developed. Starting with ecosystem relevance, the EDSS assigns different weights to the results obtained from Triad disciplines. The following parameters have been employed: 1) chemical soil analyses (revealing the presence of potentially dangerous substances), 2) ecotoxicological bioassays (utilizing classical endpoints such as survival and reproduction rates), 3) biomarkers (showing sublethal pollutant effects), and 4) ecological parameters (assessing changes in community structure and functions). For each Triad discipline, the EDSS compares the data obtained at the studied field sites with reference values and calculates different 0-1 indexes (e.g., Chemical Risk Index, Ecotoxicological Risk Index, and Ecological Risk Index). The EDSS output consists of 3 indexes: 1) Environmental Risk index (EnvRI), quantifying the levels of biological damage at population-community level, 2) Biological Vulnerability Index (BVI), assessing the potential threats to biological equilibriums, and 3) Genotoxicity Index (GTI), screening genotoxicity effects. The EDSS has been applied in the integration of a battery of Triad data obtained during the European Union-funded Life Intervention in the Fraschetta Area (LINFA) project, which has been carried out in order to estimate the potential risk from soils of a highly anthropized area (Alessandria, Italy) mainly impacted by deposition of atmospheric pollutants. Results obtained during 4 seasonal sampling campaigns (2004-2005) show maximum values of EnvRI in sites A and B (characterized by industrial releases) and lower levels in site D (affected by vehicular traffic emissions). All 3 potentially polluted sites have shown high levels of BVI and GTI, suggesting a general change from reference conditions (site C).

  9. Histidine-tryptophan-ketoglutarate solution with added ebselen augments myocardial protection in neonatal porcine hearts undergoing ischemia/reperfusion.

    Science.gov (United States)

    Chen, Yan; Liu, Jinping; Li, Shoujun; Yan, Fuxia; Xue, Qinghua; Wang, Huiying; Sun, Peng; Long, Cun

    2015-02-01

    Whether modified histidine-tryptophan-ketoglutarate (HTK) solution offers myocardial protection to newborn heart has not been documented. The purpose of this study was to compare myocardial protection using HTK added by ebselen with HTK in a piglet model of cardiopulmonary bypass (CPB). Fifteen piglets were randomly assigned to three groups: the control group (C group, n = 5), HTK solution group (HTK group, n = 5), and HTK added by 10 nM ebselen group (HTK+E group, n = 5). Animals in the two experimental groups were placed on hypothermic CPB, after which the ascending aorta had been clamped for 2 h. The control animals underwent normothermic CPB without cardiac arrest. Myocardial antioxidant activities, myocytes apoptosis and mitochondrial structures, as well as the release of cytochrome c and the expression of Bax, Bcl-2, and HSP72 protein in myocardium were measured. Increased myocardial superoxide dismutase (SOD) and Mn-SOD activities, decreased TUNEL-positive cells, and reduced release of cytochrome c were noted in the HTK+E group compared with those in the HTK group (P = 0.021, P = 0.020, P = 0.045, and P = 0.010, respectively). The Bax/Bcl-2 ratio in the HTK group was significantly higher than that in the C group (P = 0.024). The expression of HSP72 protein and mRNA in the HTK+E group was higher than that in the HTK group (P = 0.039 and P = 0.035, respectively). Mitochondrial score under electron microscope in the HTK+E group was lower than that in the HTK group (P = 0.047). Improved antioxidant defense, reduced myocytes apoptosis, and better preserved mitochondrial structure were observed in the HTK+E group. Ebselen added to HTK provides better myocardioprotection to HTK solution for the neonatal heart. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  10. The dark side of social media: Associations between the Dark Triad of personality, self-disclosure online and selfie-related behaviours

    OpenAIRE

    Elżbieta Sanecka

    2017-01-01

    The present study investigated the relations between the Dark Triad personality traits (i.e., Machiavellianism, narcissism, and psychopathy), distinct dimensions of self-disclosure online (i.e., honesty, amount, positive valence, and intent) and selfie related-behaviours (taking, posting and editing selfies). The results indicated, that all three Dark Triad components were positively correlated with posting and editing selfies on social networking sites (SNSs). However, multiple regression an...

  11. Affinity labeling and characterization of the active site histidine of glucosephosphate isomerase

    International Nuclear Information System (INIS)

    Gibson, D.R.; Gracy, R.W.; Hartman, F.C.

    1980-01-01

    N-bromoacetylethanolamine phosphate was found to act as a specific affinity label for the active center of glucosephosphate isomerase. The inactivation process followed pseudo-first order kinetics, was irreversible, and exhibited rate saturation kinetics with minimal half-lives of inactivation of 4.5 and 6.3 min for the enzyme isolated from human placenta and rabbit muscle, respectively. The pH dependence of the inactivation process closely paralleled the pH dependence of the overall catalytic process with pK/sub a/ values at pH 6.4 and 9.0. The stoichiometry of labeling of either enzyme, as determined with N-bromo[ 14 C 2 ]acetylethanolamine phosphate, was 1 eq of the affinity label/subunit of enzyme. After acid hydrolysis and amino acid analysis of the radioactive affinity-labeled human enzyme, only radioactive 3-carboxymethyl histidine was found. In the case of the rabbit enzyme, the only radioactive derivative obtained was 1-carboxymethyl histidine. Active site tryptic peptides were isolated by solvent extraction, thin layer peptide fingerprinting, and ion exchange chromatography before and after removal of the phosphate from the active site peptide. Amino acid analysis of the labeled peptides from the two species were very similar. Using high sensitivity methods for sequence analysis, the primary structure of the active site was established as Val-Leu-His-Ala-Glu-Asn-Val-Asp (Gly,Thr,Ser) Glu-Ile (Thr-Gly-His-Lys-Glx)-Tyr-Phe. Apparent sequence homology between the catalytic center of glucosephosphate isomerase and triosephosphate isomerase suggest that the two enzymes may have evolved from a common ancestral gene

  12. Homo- or Hetero- Triplet-Triplet Annihilation? A Case Study with Perylene-Bodipy Dyads/Triads

    KAUST Repository

    Cui, Xiaoneng

    2017-07-06

    The photophysical processes of intramolecular ‘ping-pong’ energy transfers in the iodinated reference dyad BDP-I2-Py, as well as the uniodinated dyad BDP-Py and triad BDP-2Py, were studied. For BDP-I2-Py, a forward Förster resonance energy transfer (FRET) from the perylene (Py) unit to the diiodoBDP unit (7 ps) and a backward triplet energy transfer (TTET, 3 ns) from the diiodoBDP unit to the Py unit were observed. For the BDP-Py and BDP-2Py systems, a FRET (5 ~ 8 ps) and a photo-induced electron transfer (PET) (1-1.5 ns) were observed in acetonitrile. The uniodinated dyad and triad were used as the triplet energy acceptor and emitter for a TTA upconversion with palladium tetraphenyltetrabenzoporphyrin as the triplet photosensitizer. A maximum upconversion quantum yield of 12.6 % was measured. Given that the dyad (BDP-Py) contains one BDP unit and one Py unit, while the triad (BDP-2Py) contains two Py units and one BDP unit, and based on the results from steady-state femtosecond and nanosecond transient optical spectroscopies, it is concluded that neither intramolecular homo- triplet-triplet annihilation (TTA) nor intramolecular hetero-TTA is possible during a TTA upconversion for those upconversion systems.

  13. Educational processes in the family: Linkage between the quality of dyad and triad relations

    Directory of Open Access Journals (Sweden)

    Mihić Ivana

    2009-01-01

    Full Text Available The goal of the research presented in this paper is to describe the relations between educational styles as dyad and co-parenting relations, as well as triad relations in the family which include processes of upbringing and taking care of the child. The sample comprised families with an adolescent. Data were obtained from 200 respondents, of the average age of 18. Respondents evaluated educational styles of their parents (separately father's, separately mother's in the Questionnaire for evaluating parenting style, and then also the quality of co-parenting cooperation in their families in the questionnaire Co-parenting relations in the family. The results indicate a significant correlation between the dimensions of parental styles and co-parenting relation. In that process, more prominent is the contribution of affective dimensions of parenting style, and what was also perceived and described are the differences in mutual relations of educational styles and co-parenting cooperation regarding parent's gender. The effects of the evaluated co-parental cooperation on educational behavior of the father are more evident.

  14. Sustainability Through Technology Licensing and Commercialization: Lessons Learned from the TRIAD Project.

    Science.gov (United States)

    Payne, Philip R O

    2014-01-01

    Ongoing transformation relative to the funding climate for healthcare research programs housed in academic and non-profit research organizations has led to a new (or renewed) emphasis on the pursuit of non-traditional sustainability models. This need is often particularly acute in the context of data management and sharing infrastructure that is developed under the auspices of such research initiatives. One option for achieving sustainability of such data management and sharing infrastructure is the pursuit of technology licensing and commercialization, in an effort to establish public-private or equivalent partnerships that sustain and even expand upon the development and dissemination of research-oriented data management and sharing technologies. However, the critical success factors for technology licensing and commercialization efforts are often unknown to individuals outside of the private sector, thus making this type of endeavor challenging to investigators in academic and non-profit settings. In response to such a gap in knowledge, this article will review a number of generalizable lessons learned from an effort undertaken at The Ohio State University to commercialize a prototypical research-oriented data management and sharing infrastructure, known as the Translational Research Informatics and Data Management (TRIAD) Grid. It is important to note that the specific emphasis of these lessons learned is on the early stages of moving a technology from the research setting into a private-sector entity and as such are particularly relevant to academic investigators interested in pursuing such activities.

  15. The Effect of Relation-Specific Investments in the Supply Chain Triad on Innovation Performance

    Directory of Open Access Journals (Sweden)

    Andrea Gelei

    2016-06-01

    Full Text Available Using a comprehensive survey, this paper analyzes the effect of committed and heavy supply chain relationships characterized by high levels of relation-specific investments in innovation performance in Hungary, an emerging economy in Central and Eastern Europe. For this research, we carry out a two-step analysis. First, we investigate the effect of Relation Specific Investments (RSI on four different innovation-related performance dimensions of a focal firm. In contrast to previous research, we did not limit our analysis to the dyadic relationship level, but rather, we analyzed the triadic supply chain relationships. Uniquely, this paper conceptualizes and measures innovation performance in a complex way, both product and process, but also analyzes incremental and radical innovations. As a second step, the effect of internationalization on the focal firm is tested. Triad level RSI has a positive effect on all innovation related performance dimensions. A test of the moderation effect produced mixed results, indicating the need to treat innovation in a complex, sophisticated way in future research.

  16. From social talk to social action: shaping the social triad with emotion sharing.

    Science.gov (United States)

    Peters, Kim; Kashima, Yoshihisa

    2007-11-01

    Seemingly trivial social talk provides fertile ground for emotion sharing (a narrator and audience's realization that they experience the same emotional response toward a target), which in turn creates a coalition between the narrator and the audience, configures the narrator and audience's relationship with the target, and coordinates their target-directed action. In this article, the authors use 4 studies to investigate this thesis. In Studies 1 and 2--where participants rated scenarios in which narrators told them anecdotes--the authors found that when there was emotion sharing (a) participants were more bonded with narrators, (b) the narrator and audience's relationship with the target (as reflected in action tendencies) was determined by the emotionality of the anecdotes, and (c) they coordinated their target-directed actions. Study 3 demonstrated that this effect was indeed due to emotion sharing. Study 4 provided behavioral evidence for the effects of emotion sharing using a 2-person trust game. Together, these studies reveal that the everyday act of social talk is a powerful act that is able to shape the social triad of the narrator, the audience, and the social target, with powerful consequences for social structure and group action. (c) 2007 APA, all rights reserved.

  17. Physical and subjective evaluation of a three-detector (TRIAD 88) SPECT system

    International Nuclear Information System (INIS)

    D'Souza, M.F.; Mumma, C.G.; Allen, E.W.; Phal, J.J.; Prince, J.R.

    1995-01-01

    The three-detector TRIAD 88 is a variable cylindrical FOV whole-body SPECT system designed for both brain as well as body organ imaging. The system performance was assessed in terms of physical indices and clinical quality. Measures of low contrast resolution using contrast-detail curves, high contrast resolution using LSFs and associated frequency descriptors, display characteristics, system sensitivity, energy resolution and uniformity analysis were utilized. In addition, images of Carlson phantom, Hoffman brain phantom and clinical brain images were used to compare two collimators subjectively. Measurements and calculations were obtained for two sets of parallel hole collimators, i.e., LEUR P AR and LEHR P AR. Of special interest is the consistency among the three detectors. The planar and volume sensitivities for the LEUR P AR collimator were about 58% of those of the LEHR P AR collimator. The planar spatial resolution of the two collimators differed by about 14%. The display was characterized by a logistic model H and D curve. The planar contrast-detail curves demonstrated no statistical difference in lesion detectability between the two collimator types, however SPECT phantom and clinical images demonstrated improved performance with the LEUR P AR collimator. Images of Hoffman single slice brain and Carlson phantoms and Tc-99m (HMPAO) brain images demonstrated excellent image quality. There was similarity in performance parameters of the three detector heads. 49 refs., 6 tabs., 8 figs

  18. A triad of evidence for care of women with genital piercings.

    Science.gov (United States)

    Young, Cathy; Armstrong, Myrna L; Roberts, Alden E; Mello, Inola; Angel, Elayne

    2010-02-01

    To add three further dimensions of evidence for the care of women with genital piercings (GPs). Following a literature review, a cross-sectional study replicated previous work, using a web-based survey. This triad of evidence provides (a) descriptive quantitative data (N = 240) about women with GPs, (b) qualitative data about women with GPs, as well as (c) clinical observations from 60 healthcare providers (HCPs) who have cared for women with GPs. Three important findings about women with GPs were validated: (a) GPs were deliberate actions, sought for personal and sexual expression; (b) women with GPs treat piercings as a normal, meaningful part of their lives which produce sexual enhancement and expression; and (c) they continue to seek information about GP care from nonhealth providers. New data indicate that they have experienced depression (47%), abuse (physical 18%; emotional, 27%; sexual, 14%), and forced sexual activity (35%) in their lives. Several unsubstantiated assumptions about women with GPs are challenged with these data. GPs should not delay important health care. Health-protective, as well as health promotion, behaviors are important to reduce risks. Nurse practitioners (NPs) can become effective and resourceful advocates in three specific areas of care: (a) responsiveness to women with GPs, (b) collaborative decision making for the removal of jewelry, and (c) promotion of applicable patient education.

  19. Working With Chinese Triad Youth Gangs: Correct Diagnosis and Strategic Intervention.

    Science.gov (United States)

    Lo, T Wing; Tam, H L

    2018-02-01

    Across the world, youth workers have been active in helping vulnerable youth groups. In Hong Kong, government-funded youth services are conducted by professional social workers to help vulnerable youths. This article adopted a case study approach to investigate a youth group who committed a murder. Nine murderers and two social workers were interviewed. It aims to uncover the structure and activities of the group and analyse the gang intervention prior to the murder to find out what had gone wrong and identify the lessons that social workers can learn from the murder. Four misconceptions in gang intervention have been identified. First, because of the Triad (Chinese-organised crime) affiliation, this is not just a group of deviant youths but a youth gang. Second, because it is a gang, the social workers should not group them but should instead degroup them to avoid contamination. Third, diagnosis is different from labelling. With the right diagnosis, services can be tailor-made to delabel them. Fourth, when the youths are diagnosed as a gang, outreach work instead of centre work should be provided-social workers should reach out to the gangland to uncover the youths' gang participation and crime involvement.

  20. Photoluminescence in Carborane-Stilbene Triads: A Structural, Spectroscopic, and Computational Study.

    Science.gov (United States)

    Cabrera-González, Justo; Viñas, Clara; Haukka, Matti; Bhattacharyya, Santanu; Gierschner, Johannes; Núñez, Rosario

    2016-09-12

    A set of triads in which o- and m-carborane clusters are bonded to two stilbene units through Ccluster -CH2 bonds was synthesized, and their structures were confirmed by X-ray diffraction. A study on the influence of the o- and m- isomers on the absorption and photoluminescence properties of the stilbene units in solution revealed no charge-transfer contributions in the lowest excited state, as confirmed by (TD)DFT calculations. The presence of one or two B-I groups in m-carborane derivatives does not affect the emission properties of the stilbenes in solution, probably due to the rather large distance between the iodo substituents and the fluorophore. Nevertheless, a significant redshift of the photoluminescence (PL) emission maximum in the solid state (thin films and powder samples) compared to solution was observed; this can be traced back to PL sensitization, most probably due to more densely packed stilbene moieties. Remarkably, the PL absolute quantum yields of powder samples are significantly higher than those in solution, and this was attributed to the restricted environment and the aforementioned sensitization. Thus, the bonding of the carborane clusters to two stilbene units preserves their PL behavior in solution, but produces significant changes in the solid state. Furthermore, iodinated species can be considered to be promising precursors for theranostic agents in which both imaging and therapeutic functions could possibly be combined. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Examining Dark Triad traits in relation to mental toughness and physical activity in young adults.

    Science.gov (United States)

    Sabouri, Sarah; Gerber, Markus; Sadeghi Bahmani, Dena; Lemola, Sakari; Clough, Peter J; Kalak, Nadeem; Shamsi, Mahin; Holsboer-Trachsler, Edith; Brand, Serge

    2016-01-01

    The Dark Triad (DT) describes a set of three closely related personality traits: Machiavellianism, narcissism, and psychopathy. Mental toughness (MT) refers to a psychological construct combining confidence, commitment, control, and challenge. High MT is related to greater physical activity (PA) and, relative to men, women have lower MT scores. The aims of the present study were 1) to investigate the association between DT, MT, and PA, and 2) to compare the DT, MT, and PA scores of men and women. A total of 341 adults (M=29 years; 51.6% women; range: 18-37 years) took part in the study. Participants completed a series of questionnaires assessing DT, MT, and PA. Machiavellianism, narcissism, and psychopathy were all significantly associated with higher MT scores (rs =0.45, 0.50, and 0.20, respectively). DT traits and MT were associated with more vigorous PA. Compared to men, women participants had lower scores for DT traits (overall score and psychopathy), while no differences were found for MT or PA in both sexes. DT traits, high MT, and vigorous PA are interrelated. This pattern of results might explain why, for instance, successful professional athletes can at the same time be tough and ruthless.

  2. TITANIUM DIOXIDE TRIADS FOR IMPROVED CHARGE-SEPARATION USING CONDUCTIVE POLYMERS

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, T.M.; Gaylor, T.N.; de la Garza, L.; Rajh, T.

    2009-01-01

    Dye-sensitized solar cells are potentially one of the best solutions to solar energy conversion because of the low cost of required materials and production processes. Titanium dioxide (TiO2) nanoparticulate fi lms are the basis for one of these types of cells, providing large surface area for dye-sensitizer adsorption. Because TiO2 nanoparticulate fi lms develop defects caused by oxygen defi ciency, deep reactive electron traps are formed. With the addition of an enediol ligand, these electron traps are deliberately removed, enhancing the conduction of electrons within the fi lm. In this project, TiO2 nanoparticulate fi lms made by a layer-by-layer dip coating method were modifi ed with 3,4-dihydroxyphenylacetic acid (DOPAC). DOPAC binds to the titanium atoms on the surface of the nanoparticles, restoring their octahedral geometry. This restructuring of the surface shifts the spectral properties of the TiO2 to the visible spectrum and improves the separation of charges which is observed using photoelectrochemistry. Furthermore, DOPAC enables the electronic attachment of other molecules to the surface of TiO2 fi lms, such as the conductive polymer polyaniline base. This conductive polymer provides an extended separation of charges which increases photocurrent production by forming a triad with the TiO2 semiconductor through the 3,4-dihydroxyphenylacetic acid linker. The photocurrent increases due to the donor properties of the conductive polymer thereby decreasing charge pair recombination.

  3. Conformational flexibility in the catalytic triad revealed by the high-resolution crystal structure of Streptomyces erythraeus trypsin in an unliganded state

    Energy Technology Data Exchange (ETDEWEB)

    Blankenship, Elise; Vukoti, Krishna [Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Miyagi, Masaru, E-mail: mxm356@cwru.edu [Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Lodowski, David T., E-mail: mxm356@cwru.edu [Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States)

    2014-03-01

    This work reports the first sub-angstrom resolution structure of S. erythraeus trypsin. The detailed model of a prototypical serine protease at a catalytically relevant pH with an unoccupied active site is presented and is compared with other high-resolution serine protease structures. With more than 500 crystal structures determined, serine proteases make up greater than one-third of all proteases structurally examined to date, making them among the best biochemically and structurally characterized enzymes. Despite the numerous crystallographic and biochemical studies of trypsin and related serine proteases, there are still considerable shortcomings in the understanding of their catalytic mechanism. Streptomyces erythraeus trypsin (SET) does not exhibit autolysis and crystallizes readily at physiological pH; hence, it is well suited for structural studies aimed at extending the understanding of the catalytic mechanism of serine proteases. While X-ray crystallographic structures of this enzyme have been reported, no coordinates have ever been made available in the Protein Data Bank. Based on this, and observations on the extreme stability and unique properties of this particular trypsin, it was decided to crystallize it and determine its structure. Here, the first sub-angstrom resolution structure of an unmodified, unliganded trypsin crystallized at physiological pH is reported. Detailed structural analysis reveals the geometry and structural rigidity of the catalytic triad in the unoccupied active site and comparison to related serine proteases provides a context for interpretation of biochemical studies of catalytic mechanism and activity.

  4. Conformational flexibility in the catalytic triad revealed by the high-resolution crystal structure of Streptomyces erythraeus trypsin in an unliganded state

    International Nuclear Information System (INIS)

    Blankenship, Elise; Vukoti, Krishna; Miyagi, Masaru; Lodowski, David T.

    2014-01-01

    This work reports the first sub-angstrom resolution structure of S. erythraeus trypsin. The detailed model of a prototypical serine protease at a catalytically relevant pH with an unoccupied active site is presented and is compared with other high-resolution serine protease structures. With more than 500 crystal structures determined, serine proteases make up greater than one-third of all proteases structurally examined to date, making them among the best biochemically and structurally characterized enzymes. Despite the numerous crystallographic and biochemical studies of trypsin and related serine proteases, there are still considerable shortcomings in the understanding of their catalytic mechanism. Streptomyces erythraeus trypsin (SET) does not exhibit autolysis and crystallizes readily at physiological pH; hence, it is well suited for structural studies aimed at extending the understanding of the catalytic mechanism of serine proteases. While X-ray crystallographic structures of this enzyme have been reported, no coordinates have ever been made available in the Protein Data Bank. Based on this, and observations on the extreme stability and unique properties of this particular trypsin, it was decided to crystallize it and determine its structure. Here, the first sub-angstrom resolution structure of an unmodified, unliganded trypsin crystallized at physiological pH is reported. Detailed structural analysis reveals the geometry and structural rigidity of the catalytic triad in the unoccupied active site and comparison to related serine proteases provides a context for interpretation of biochemical studies of catalytic mechanism and activity

  5. Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis.

    Science.gov (United States)

    Xu, Qingfu; Surendran, Naveen; Verhoeven, David; Klapa, Jessica; Ochs, Martina; Pichichero, Michael E

    2015-02-18

    Due to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model. C57BL/6J infant mice were intramuscularly vaccinated at age 1-3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3-4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48h after challenge. PPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6-24h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden. Trivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation

  6. Spontaneous nisin-resistant Listeria monocytogenes mutants with increased expression of a putative penicillin-binding protein and their sensitivity to various antibiotics

    DEFF Research Database (Denmark)

    Gravesen, Anne; Sorensen, K.; Aarestrup, Frank Møller

    2001-01-01

    -molecular-weight penicillin-binding proteins (PBPs), a histidine protein kinase, a protein of unknown function, and ClpB (putative functions from homology), The three former proteins had increased expression in a total of six out of 10 independent mutants originating from five different wildtype strains, indicating...

  7. Group X hybrid histidine kinase Chk1 is dispensable for stress adaptation, host-pathogen interactions and virulence in the opportunistic yeast Candida guilliermondii.

    Science.gov (United States)

    Navarro-Arias, María J; Dementhon, Karine; Defosse, Tatiana A; Foureau, Emilien; Courdavault, Vincent; Clastre, Marc; Le Gal, Solène; Nevez, Gilles; Le Govic, Yohann; Bouchara, Jean-Philippe; Giglioli-Guivarc'h, Nathalie; Noël, Thierry; Mora-Montes, Hector M; Papon, Nicolas

    2017-09-01

    Hybrid histidine kinases (HHKs) progressively emerge as prominent sensing proteins in the fungal kingdom and as ideal targets for future therapeutics. The group X HHK is of major interest, since it was demonstrated to play an important role in stress adaptation, host-pathogen interactions and virulence in some yeast and mold models, and particularly Chk1, that corresponds to the sole group X HHK in Candida albicans. In the present work, we investigated the role of Chk1 in the low-virulence species Candida guilliermondii, in order to gain insight into putative conservation of the role of group X HHK in opportunistic yeasts. We demonstrated that disruption of the corresponding gene CHK1 does not influence growth, stress tolerance, drug susceptibility, protein glycosylation or cell wall composition in C. guilliermondii. In addition, we showed that loss of CHK1 does not affect C. guilliermondii ability to interact with macrophages and to stimulate cytokine production by human peripheral blood mononuclear cells. Finally, the C. guilliermondii chk1 null mutant was found to be as virulent as the wild-type strain in the experimental model Galleria mellonella. Taken together, our results demonstrate that group X HHK function is not conserved in Candida species. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. Protein immobilization on Ni(II) ion patterns prepared by microcontact printing and dip-pen nanolithography

    NARCIS (Netherlands)

    Wu, Chien-Ching; Reinhoudt, David N; Otto, Cees; Velders, Aldrik H; Subramaniam, Vinod

    2010-01-01

    An indirect method of protein patterning by using Ni(II) ion templates for immobilization via a specific metal-protein interaction is described. A nitrilotriacetic acid (NTA)-terminated self-assembled monolayer (SAM) allows oriented binding of histidine-tagged proteins via complexation with late

  9. Production of polyclonal antiserum specific to the 27.5 kDa envelope protein of white spot syndrome virus

    NARCIS (Netherlands)

    You, Z.O.; Nadala, E.C.B.; Yang, J.S.; Hulten, van M.C.W.; Loh, P.C.

    2002-01-01

    A truncated version of the white spot syndrome virus (WSSV) 27.5 kDa envelope protein was expressed as a histidine tag fusion protein in Escherichia coli. The bacterial expression system allowed the production of up to 10 mg of purified recombinant protein per liter of bacterial culture. Antiserum

  10. TRIAD OF SENSORY FINDINGS LOCALISES TO CORTEX- ANALYSIS OF 5 CASES

    Directory of Open Access Journals (Sweden)

    Beena Vasanthy Vijayan

    2018-02-01

    Full Text Available BACKGROUND A fifty-two-year-old man presented with acute onset right lower facial and ear numbness and facial weakness, after two weeks of the onset of symptoms. Examination revealed right central facial palsy, depressed corneal reflex and hemifacial sensory loss (mild over forehead, severe over lower cheek, jaw & pinna Localization was proposed in brainstem Vs Cerebellopontine angle. MRI Brain revealed infarct in peri Rolandic area; four more patients had similar presentation over next few years. 1 Core findings were ipsilateral graded facial sensory impairment with central facial palsy, ear involvement & impaired corneal reflex. Four had spastic hand. Hypothesis- Cortical lesions can have LMN- like presentation; impairment of facial and external ear (pinna sensations, and attenuated corneal reflex. MATERIALS AND METHODS Settings and Design- Patients presenting to the Neurology OPD with facial weakness and isolated sensory loss of face were admitted and evaluated with detailed neurological examination, including facial & ear sensations and corneal reflex; Stroke work up & MRI Brain with MRA was done. They were treated and kept under follow up. RESULTS Patients with post central gyrus infarct had uniformity in presentation, graded sensory loss over face, depressed corneal reflex & ear involvement, had uniformity in presentations and medical help seeking usually were delayed. Two had lower face (mandibular region severely affected; while three had maxillary involvement. Spastic hand weakness was found in four. CONCLUSION Cortical lesions can produce LMN-like sensory phenomena, of face. Corneal reflex abnormality & ear involvement occur in cortical lesions. Ear representation is closer to lower face in sensory cortex. Four out of five patients had spastic hand in this series. Hence in spastic hand due to cortical lesions, triad of sensory findings should be specifically elicited.

  11. Complications of treating terrible triad injury of the elbow: a systematic review.

    Directory of Open Access Journals (Sweden)

    Hong-wei Chen

    Full Text Available Terrible triad injury of the elbow (TTIE, comprising elbow dislocation with radial head and coronoid process fracture, is notoriously challenging to treat and has typically been associated with complications and poor outcomes. The objective of this systematic review was to summarize the most recent available evidence regarding functional outcomes and complications following surgical management of TTIE.Medline, EMBASE, Cochrane Library, and Google Scholar were searched to identify relevant studies, which were included if they were retrospective or prospective in design, involved participants who had TTIE, and were published in English. Outcomes of interest were functional outcomes and complications.Sixteen studies, involving 312 patients, were included in the systematic review. Mean follow up after surgery was typically 25 to 30 months. Mean Mayo elbow performance scores ranged from 78 to 95. Mean Broberg-Morrey scores ranged from 76 to 90. Mean DASH scores ranged from 9 to 31. The proportion of patients who required reoperation due to complications ranged from 0 to 54.5% (overall  = 70/312 [22.4%]. Most of these complications were related to hardware fixation problems, joint stiffness, joint instability, and ulnar neuropathy. The most common complications that did not require reoperation were heterotopic ossification (39/312 [12.5%] patients and arthrosis (35/312 [11.2%] patients.The results of this systematic review indicate that functional outcomes after surgery for TTIE are generally satisfactory and that complications are common. Further research is warranted to determine which surgical techniques optimize functional outcomes and reduce the risk of complications.

  12. A SYNTHESIS METHOD OF BASIC TERNARY BENT-SQUARES BASED ON THE TRIAD SHIFT OPERATOR

    Directory of Open Access Journals (Sweden)

    O. N. Zhdanov

    2017-01-01

    Full Text Available Practical application of advanced algebraic constructions in modern communication systems based on MC-CDMA (Multi Code Code Division Multiple Access technology and in cryptography necessitates their further research. One of the most commonly used advanced algebraic construction is the binary bent-function having a uniform amplitude spectrum of the Walsh-Hadamard transform and, accordingly, having the maximal distance from the codewords of affine code. In addition to the binary bent-functions researchers are currently focuses on the development of synthesis methods of their many-valued analogues. In particular, one of the most effective methods for the synthesis of many-valued bent-functions is the method based on the Agievich bent-squares. In this paper, we developed a regular synthesis method of the ternary bent-squares on the basis of an arbitrary spectral vector and the regular operator of the triad shift. The classification of spectral vectors of lengths N = 3 and N = 9 is performed. On the basis of spectral classification more precise definition of many-valued bent-sequences is given, taking into account the existence of the phenomenon of many-valued bent-sequences for the length, determined by odd power of base. The paper results are valuable for practical use: the development of new constant amplitude codes for MC-CDMA technology, cryptographic primitives, data compression algorithms, signal structures, algorithms of block and stream encryption, based on advanced principles of many-valued logic. The developed bent-squares design method is also a basis for further theoretical research: development of methods of the permutation of rows and columns of basic bent-squares and their sign coding, synthesis of composite bent-squares. In addition, the data on the spectral classification of vectors give the task of constructing the synthesis methods of bent-functions of lengths N = 32k+1, k Є ℕ.

  13. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    Directory of Open Access Journals (Sweden)

    Samman S

    2014-06-01

    Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

  14. Requirement of histidine 217 for ubiquinone reductase activity (Qi site) in the cytochrome bc1 complex.

    Science.gov (United States)

    Gray, K A; Dutton, P L; Daldal, F

    1994-01-25

    Folding models suggest that the highly conserved histidine 217 of the cytochrome b subunit from the cytochrome bc1 complex is close to the quinone reductase (Qi) site. This histidine (bH217) in the cytochrome b polypeptide of the photosynthetic bacterium Rhodobacter capsulatus has been replaced with three other residues, aspartate (D), arginine (R), and leucine (L). bH217D and bH217R are able to grow photoheterotrophically and contain active cytochrome bc1 complexes (60% of wild-type activity), whereas the bH217L mutant is photosynthetically incompetent and contains a cytochrome bc1 complex that has only 10% of the wild-type activity. Single-turnover flash-activated electron transfer experiments show that cytochrome bH is reduced via the Qo site with near native rates in the mutant strains but that electron transfer between cytochrome bH and quinone bound at the Qi site is greatly slowed. These results are consistent with redox midpoint potential (Em) measurements of the cytochrome b subunit hemes and the Qi site quinone. The Em values of cyt bL and bH are approximately the same in the mutants and wild type, although the mutant strains have a larger relative concentration of what may be the high-potential form of cytochrome bH, called cytochrome b150. However, the redox properties of the semiquinone at the Qi site are altered significantly. The Qi site semiquinone stability constant of bH217R is 10 times higher than in the wild type, while in the other two strains (bH217D and bH217L) the stability constant is much lower than in the wild type. Thus H217 appears to have major effects on the redox properties of the quinone bound at the Qi site. These data are incorporated into a suggestion that H217 forms part of the binding pocket of the Qi site in a manner reminiscent of the interaction between quinone bound at the Qb site and H190 of the L subunit of the bacterial photosynthetic reaction center.

  15. A method for investigating protein-protein interactions related to Salmonella typhimurium pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, Saiful M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Shi, Liang [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Yoon, Hyunjin [Dartmouth College, Hanover, NH (United States); Ansong, Charles [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rommereim, Leah M. [Dartmouth College, Hanover, NH (United States); Norbeck, Angela D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Auberry, Kenneth J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moore, R. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Adkins, Joshua N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Heffron, Fred [Oregon Health and Science Univ., Portland, OR (United States); Smith, Richard D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-02-10

    We successfully modified an existing method to investigate protein-protein interactions in the pathogenic bacterium Salmonella typhimurium (STM). This method includes i) addition of a histidine-biotin-histidine tag to the bait proteins via recombinant DNA techniques; ii) in vivo cross-linking with formaldehyde; iii) tandem affinity purification of bait proteins under fully denaturing conditions; and iv) identification of the proteins cross-linked to the bait proteins by liquid-chromatography in conjunction with tandem mass-spectrometry. In vivo cross-linking stabilized protein interactions permitted the subsequent two-step purification step conducted under denaturing conditions. The two-step purification greatly reduced nonspecific binding of non-cross-linked proteins to bait proteins. Two different negative controls were employed to reduce false-positive identification. In an initial demonstration of this approach, we tagged three selected STM proteins- HimD, PduB and PhoP- with known binding partners that ranged from stable (e.g., HimD) to transient (i.e., PhoP). Distinct sets of interacting proteins were identified with each bait protein, including the known binding partners such as HimA for HimD, as well as anticipated and unexpected binding partners. Our results suggest that novel protein-protein interactions may be critical to pathogenesis by Salmonella typhimurium. .

  16. Hydrothermal synthesis of histidine-functionalized single-crystalline gold nanoparticles and their pH-dependent UV absorption characteristic.

    Science.gov (United States)

    Liu, Zhiguo; Zu, Yuangang; Fu, Yujie; Meng, Ronghua; Guo, Songling; Xing, Zhimin; Tan, Shengnan

    2010-03-01

    L-Histidine capped single-crystalline gold nanoparticles have been synthesized by a hydrothermal process under a basic condition at temperature between 65 and 150 degrees C. The produced gold nanoparticles were spherical with average diameter of 11.5+/-2.9nm. The synthesized gold colloidal solution was very stable and can be stored at room temperature for more than 6 months. The color of the colloidal solution can change from wine red to mauve, purple and blue during the acidifying process. This color changing phenomenon is attributed to the aggregation of gold nanoparticles resulted from hydrogen bond formation between the histidines adsorbed on the gold nanoparticles surfaces. This hydrothermal synthetic method is expected to be used for synthesizing some other amino acid functionalized gold nanomaterials.

  17. Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

    NARCIS (Netherlands)

    Velikova, Nadya; Mas, Nuria; Miguel-Romero, Laura; Polo, Lorena; Stolte, Ellen; Zaccaria, Edoardo; Cao, Rui; Taverne, Nico; Murguía, José Ramón; Martinez-Manez, Ramon; Marina, Alberto; Wells, Jerry

    2017-01-01

    Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation

  18. Supramolecular Self-Assembly of Histidine-Capped-Dialkoxy-Anthracene: A Visible Light Triggered Platform for facile siRNA Delivery

    KAUST Repository

    Patil, Sachin; Moosa, Basem; Alsaiari, Shahad; Alamoudi, Kholod; Alshamsan, Aws; Almailk, Abdulaziz; Adil, Karim; Eddaoudi, Mohamed; Khashab, Niveen M.

    2016-01-01

    Supramolecular self-assembly of histidine-capped-dialkoxy-anthracene (HDA) results in the formation of light responsive nanostructures.Single-crystal X-ray diffraction analysis of HDA shows two types of hydrogen bonding. The first hydrogen bond

  19. Targeted in vivo inhibition of specific protein-protein interactions using recombinant antibodies.

    Directory of Open Access Journals (Sweden)

    Matej Zábrady

    Full Text Available With the growing availability of genomic sequence information, there is an increasing need for gene function analysis. Antibody-mediated "silencing" represents an intriguing alternative for the precise inhibition of a particular function of biomolecules. Here, we describe a method for selecting recombinant antibodies with a specific purpose in mind, which is to inhibit intrinsic protein-protein interactions in the cytosol of plant cells. Experimental procedures were designed for conveniently evaluating desired properties of recombinant antibodies in consecutive steps. Our selection method was successfully used to develop a recombinant antibody inhibiting the interaction of ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 3 with such of its upstream interaction partners as the receiver domain of CYTOKININ INDEPENDENT HISTIDINE KINASE 1. The specific down-regulation of the cytokinin signaling pathway in vivo demonstrates the validity of our approach. This selection method can serve as a prototype for developing unique recombinant antibodies able to interfere with virtually any biomolecule in the living cell.

  20. Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity

    OpenAIRE

    Hammerstrom, Troy G.; Horton, Lori B.; Swick, Michelle C.; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M.

    2014-01-01

    The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthesis operon. AtxA activity is elevated during growth in media containing glucose and CO2/bicarbonate, and there is a positive correlation between the CO2/bicarbonate signal, AtxA activity, and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-bin...

  1. Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes

    DEFF Research Database (Denmark)

    Wisniewska, Magdalena; Happonen, Lotta; Kahn, Fredrik

    2014-01-01

    strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG......), and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody...

  2. Molecular-wire behavior of OLED materials: exciton dynamics in multichromophoric Alq3-oligofluorene-Pt(II)porphyrin triads.

    Science.gov (United States)

    Montes, Victor A; Pérez-Bolívar, César; Agarwal, Neeraj; Shinar, Joseph; Anzenbacher, Pavel

    2006-09-27

    Donor-bridge-acceptor triads consisting of the Alq3 complex, oligofluorene bridge, and PtII tetraphenylporphyrin (PtTPP) were synthesized. The triads were designed to study the energy level/distance-dependence in energy transfer both in a solution and in solid state. The materials show effective singlet transfer from the Alq3-fluorene fluorophore to the porphyrin, while the triplet energy transfer, owing to the shorter delocalization of triplet excitons, appears to take place via a triplet energy cascade. Using femtosecond transient spectroscopy, the rate of the singlet-singlet energy transfer was determined. The exponential dependence of the donor-acceptor distance and the respective energy transfer rates of 7.1 x 1010 to 1.0 x 109 s-1 with the attenuation factor â of 0.21 +/- 0.02 A-1 suggest that the energy transfer proceeds via a mixed incohererent wire/superexchange mechanism. In the OLEDs fabricated using the Alq3-oligofluorene-PtTPP triads with better triplet level alignment, the order of a magnitude increase in efficacy appears to be due to facile triplet energy transfer. The devices, where the triplet-triplet energy transfer is of paramount importance, showed high color purity emission (CIE X,Y: 0.706, 0.277), which is almost identical to the emission from thin films. Most importantly, we believe that the design principles demonstrated above are general and may be used to prepare OLED materials with enhanced quantum efficacy at lowered operational potentials, being crucial for improved lifespan of OLEDs.

  3. Acute hyponatremia after cardioplegia by histidine-tryptophane-ketoglutarate – a retrospective study

    Directory of Open Access Journals (Sweden)

    Lindner Gregor

    2012-06-01

    Full Text Available Abstract Background Hyponatremia is the most common electrolyte disorder in hospitalized patients and is known to be associated with increased mortality. The administration of antegrade single-shot, up to two liters, histidine-tryptophane-ketoglutarate (HTK solution for adequate electromechanical cardiac arrest and myocardial preservation during minimally invasive aortic valve replacement (MIAVR is a standard procedure. We aimed to determine the impact of HTK infusion on electrolyte and acid–base balance. Methods In this retrospective analysis we reviewed data on patient characteristics, type of surgery, arterial blood gas analysis during surgery and intra-/postoperative laboratory results of patients receiving surgery for MIAVR at a large tertiary care university hospital. Results A total of 25 patients were included in the study. All patients were normonatremic at start of surgery. All patients developed hyponatremia after administration of HTK solution with a significant drop of serum sodium of 15 mmol/L (p  Conclusions Acute hyponatremia during cardioplegia with HTK solution is isotonic and should probably not be corrected without presence of hypotonicity as confirmed by measurement of serum osmolality.

  4. Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

    Directory of Open Access Journals (Sweden)

    Gloria E Hoffman

    Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

  5. Molecular dissection of the role of histidine in nickel hyperaccumulation in Thalspi goesingense (Halacsy)

    Energy Technology Data Exchange (ETDEWEB)

    Persans, M.W.; Yan, X.; Patnoe, J.M.M.L.; Kraemer, U.; Salt, D.E.

    1999-12-01

    To understand the role of free histidine (His) in Ni hyperaccumulation in Thlaspi goesingense, the authors investigated the regulation of His biosynthesis at both the molecular and biochemical levels. Three T. goesingense cDNAs encoding the following His biosynthetic enzymes, ATP phosphoribosyltransferase, imidazoleglycerol phosphate dehydratase, and histidinol dehydrogenase, were isolated by functional complementation of Escherichia coli His autotrophs. Northern analysis of THJG1, THD1, and THB1 gene expression revealed that each gene is expressed in both roots and shoots, but at the concentrations and dosage times of Ni treatment used in this study, these genes failed to show any regulation by Ni. The authors were also unable to observe any increases in the concentration of free His in root, shoot, or xylem sap of T. goesingense in response to Ni exposure. X-ray absorption spectroscopy of root and shoot tissue from T. goesingense and the non-accumulator species Thlaspi reverse revealed no major differences in the coordination of Ni by His in these tissues. They therefore conclude that the Ni hyperaccumulation phenotype in T. goesingense is not determined by the overproduction of His in response to Ni.

  6. A non-catalytic histidine residue influences the function of the metalloprotease of Listeria monocytogenes.

    Science.gov (United States)

    Forster, Brian M; Bitar, Alan Pavinski; Marquis, Hélène

    2014-01-01

    Mpl, a thermolysin-like metalloprotease, and PC-PLC, a phospholipase C, are synthesized as proenzymes by the intracellular bacterial pathogen Listeria monocytogenes. During intracellular growth, L. monocytogenes is temporarily confined in a membrane-bound vacuole whose acidification leads to Mpl autolysis and Mpl-mediated cleavage of the PC-PLC N-terminal propeptide. Mpl maturation also leads to the secretion of both Mpl and PC-PLC across the bacterial cell wall. Previously, we identified negatively charged and uncharged amino acid residues within the N terminus of the PC-PLC propeptide that influence the ability of Mpl to mediate the maturation of PC-PLC, suggesting that these residues promote the interaction of the PC-PLC propeptide with Mpl. In the present study, we identified a non-catalytic histidine residue (H226) that influences Mpl secretion across the cell wall and its ability to process PC-PLC. Our results suggest that a positive charge at position 226 is required for Mpl functions other than autolysis. Based on the charge requirement at this position, we hypothesize that this residue contributes to the interaction of Mpl with the PC-PLC propeptide.

  7. Visual detection of arginine, histidine and lysine using quercetin-functionalized gold nanoparticles

    International Nuclear Information System (INIS)

    Rawat, Karuna A.; Kailasa, Suresh Kumar

    2014-01-01

    We report on the use of quercetin-functionalized gold nanoparticles (QC-AuNPs) as a colorimetric probe for the amino acids arginine (Arg), histidine (His) and lysine (Lys). The method is based on the aggregation of the QC-AuNPs that is caused by these amino acids and leads to a visually detectable color change from red to blue. The absorption maxima shift from 525 nm to 702, 693, and 745 nm, respectively. Aggregations are confirmed by dynamic light scattering (DLS) and transmission electron microscopic techniques (TEM). The effects of the QC concentration, temperature and reaction time for the preparation of QC-Au NPs were tested. Other amino acids do not interfere. Under the optimal conditions, linear relationships exist between the absorption ratios at 702/525 nm (for Arg), 693/525 nm (for His), and 745/525 nm (for Lys) over the concentrations ranges from 2.5–1,250 μM (Arg) and 1–1,000 μM (His and Lys), respectively. The respective limits of detection are 0.04, 0.03, and 0.02 μM. The method provides a useful tool for the rapid visual and instrumental determination of the three amino acids. (author)

  8. Histidine Decarboxylase Knockout Mice as a Model of the Pathophysiology of Tourette Syndrome and Related Conditions.

    Science.gov (United States)

    Pittenger, Christopher

    2017-01-01

    While the normal functions of histamine (HA) in the central nervous system have gradually come into focus over the past 30 years, the relationship of abnormalities in neurotransmitter HA to human disease has been slower to emerge. New insight came with the 2010 description of a rare nonsense mutation in the biosynthetic enzyme histidine decarboxylase (Hdc) that was associated with Tourette syndrome (TS) and related conditions in a single family pedigree. Subsequent genetic work has provided further support for abnormalities of HA signaling in sporadic TS. As a result of this genetic work, Hdc knockout mice, which were generated more than 15 years ago, have been reexamined as a model of the pathophysiology of TS and related conditions. Parallel work in these KO mice and in human carriers of the Hdc mutation has revealed abnormalities in the basal ganglia system and its modulation by dopamine (DA) and has confirmed the etiologic, face, and predictive validity of the model. The Hdc-KO model thus serves as a unique platform to probe the pathophysiology of TS and related conditions, and to generate specific hypotheses for subsequent testing in humans. This chapter summarizes the development and validation of this model and recent and ongoing work using it to further investigate pathophysiological changes that may contribute to these disorders.

  9. Enhanced Indirect Photochemical Transformation of Histidine and Histamine through Association with Chromophoric Dissolved Organic Matter.

    Science.gov (United States)

    Chu, Chiheng; Lundeen, Rachel A; Remucal, Christina K; Sander, Michael; McNeill, Kristopher

    2015-05-05

    Photochemical transformations greatly affect the stability and fate of amino acids (AAs) in sunlit aquatic ecosystems. Whereas the direct phototransformation of dissolved AAs is well investigated, their indirect photolysis in the presence of chromophoric dissolved organic matter (CDOM) is poorly understood. In aquatic systems, CDOM may act both as sorbent for AAs and as photosensitizer, creating microenvironments with high concentrations of photochemically produced reactive intermediates, such as singlet oxygen (1O2). This study provides a systematic investigation of the indirect photochemical transformation of histidine (His) and histamine by 1O2 in solutions containing CDOM as a function of solution pH. Both His and histamine showed pH-dependent enhanced phototransformation in the CDOM systems as compared to systems in which model, low-molecular-weight 1O2 sensitizers were used. Enhanced reactivity resulted from sorption of His and histamine to CDOM and thus exposure to elevated 1O2 concentrations in the CDOM microenvironment. The extent of reactivity enhancement depended on solution pH via its effects on the protonation state of His, histamine, and CDOM. Sorption-enhanced reactivity was independently supported by depressed rate enhancements in the presence of a cosorbate that competitively displaced His and histamine from CDOM. Incorporating sorption and photochemical transformation processes into a reaction rate prediction model improved the description of the abiotic photochemical transformation rates of His in the presence of CDOM.

  10. The two parallel photocycles of the Chlamydomonas sensory photoreceptor histidine kinase rhodopsin 1.

    Science.gov (United States)

    Luck, Meike; Hegemann, Peter

    2017-10-01

    Histidine kinase rhodopsins (HKRs) belong to a class of unexplored sensory photoreceptors that share a similar modular architecture. The light sensing rhodopsin domain is covalently linked to signal-transducing modules and in some cases to a C-terminal guanylyl-cyclase effector. In spite of their wide distribution in unicellular organisms, very little is known about their physiological role and mechanistic functioning. We investigated the photochemical properties of the recombinant rhodopsin-fragment of Cr-HKR1 originating from Chlamydomonas reinhardtii. Our spectroscopic studies revealed an unusual thermal stability of the photoproducts with the deprotonated retinal Schiff base (RSB). Upon UV-irradiation these Rh-UV states with maximal absorbance in the UVA-region (Rh-UV) photochemically convert to stable blue light absorbing rhodopsin (Rh-Bl) with protonated chromophore. The heterogeneity of the sample is based on two parallel photocycles with the chromophore in C 15 =N-syn- or -anti-configuration. This report represents an attempt to decipher the underlying reaction schemes and interconversions of the two coexisting photocycles. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.

    Science.gov (United States)

    Xu, Meiyu; Li, Lina; Ohtsu, Hiroshi; Pittenger, Christopher

    2015-05-19

    Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Does aluminium bind to histidine? An NMR investigation of amyloid β12 and amyloid β16 fragments.

    Science.gov (United States)

    Narayan, Priya; Krishnarjuna, Bankala; Vishwanathan, Vinaya; Jagadeesh Kumar, Dasappa; Babu, Sudhir; Ramanathan, Krishna Venkatachala; Easwaran, Kalpathy Ramaier Katchap; Nagendra, Holenarasipur Gundurao; Raghothama, Srinivasarao

    2013-07-01

    Aluminium and zinc are known to be the major triggering agents for aggregation of amyloid peptides leading to plaque formation in Alzheimer's disease. While zinc binding to histidine in Aβ (amyloid β) fragments has been implicated as responsible for aggregation, not much information is available on the interaction of aluminium with histidine. In the NMR study of the N-terminal Aβ fragments, DAEFRHDSGYEV (Aβ12) and DAEFRHDSGYEVHHQK (Aβ16) presented here, the interactions of the fragments with aluminium have been investigated. Significant chemical shifts were observed for few residues near the C-terminus when aluminium chloride was titrated with Aβ12 and Aβ16 peptides. Surprisingly, it is nonhistidine residues which seem to be involved in aluminium binding. Based on NMR constrained structure obtained by molecular modelling, aluminium-binding pockets in Aβ12 were around charged residues such as Asp, Glu. The results are discussed in terms of native structure propagation, and the relevance of histidine residues in the sequences for metal-binding interactions. We expect that the study of such short amyloid peptide fragments will not only provide clues for plaque formation in aggregated conditions but also facilitate design of potential drugs for these targets. © 2013 John Wiley & Sons A/S.

  13. A Social Capital Perspective on the Mentoring of Undergraduate Life Science Researchers: An Empirical Study of Undergraduate–Postgraduate–Faculty Triads

    Science.gov (United States)

    Aikens, Melissa L.; Sadselia, Sona; Watkins, Keiana; Evans, Mara; Eby, Lillian T.; Dolan, Erin L.

    2016-01-01

    Undergraduate researchers at research universities are often mentored by graduate students or postdoctoral researchers (referred to collectively as “postgraduates”) and faculty, creating a mentoring triad structure. Triads differ based on whether the undergraduate, postgraduate, and faculty member interact with one another about the undergraduate’s research. Using a social capital theory framework, we hypothesized that different triad structures provide undergraduates with varying resources (e.g., information, advice, psychosocial support) from the postgraduates and/or faculty, which would affect the undergraduates’ research outcomes. To test this, we collected data from a national sample of undergraduate life science researchers about their mentoring triad structure and a range of outcomes associated with research experiences, such as perceived gains in their abilities to think and work like scientists, science identity, and intentions to enroll in a PhD program. Undergraduates mentored by postgraduates alone reported positive outcomes, indicating that postgraduates can be effective mentors. However, undergraduates who interacted directly with faculty realized greater outcomes, suggesting that faculty interaction is important for undergraduates to realize the full benefits of research. The “closed triad,” in which undergraduates, postgraduates, and faculty all interact directly, appeared to be uniquely beneficial; these undergraduates reported the highest gains in thinking and working like a scientist. PMID:27174583

  14. The (mis)measurement of the Dark Triad Dirty Dozen: exploitation at the core of the scale.

    Science.gov (United States)

    Kajonius, Petri J; Persson, Björn N; Rosenberg, Patricia; Garcia, Danilo

    2016-01-01

    Background. The dark side of human character has been conceptualized in the Dark Triad Model: Machiavellianism, psychopathy, and narcissism. These three dark traits are often measured using single long instruments for each one of the traits. Nevertheless, there is a necessity of short and valid personality measures in psychological research. As an independent research group, we replicated the factor structure, convergent validity and item response for one of the most recent and widely used short measures to operationalize these malevolent traits, namely, Jonason's Dark Triad Dirty Dozen. We aimed to expand the understanding of what the Dirty Dozen really captures because the mixed results on construct validity in previous research. Method. We used the largest sample to date to respond to the Dirty Dozen (N = 3,698). We firstly investigated the factor structure using Confirmatory Factor Analysis and an exploratory distribution analysis of the items in the Dirty Dozen. Secondly, using a sub-sample (n = 500) and correlation analyses, we investigated the Dirty Dozen dark traits convergent validity to Machiavellianism measured by the Mach-IV, psychopathy measured by Eysenck's Personality Questionnaire Revised, narcissism using the Narcissism Personality Inventory, and both neuroticism and extraversion from the Eysenck's questionnaire. Finally, besides these Classic Test Theory analyses, we analyzed the responses for each Dirty Dozen item using Item Response Theory (IRT). Results. The results confirmed previous findings of a bi-factor model fit: one latent core dark trait and three dark traits. All three Dirty Dozen traits had a striking bi-modal distribution, which might indicate unconcealed social undesirability with the items. The three Dirty Dozen traits did converge too, although not strongly, with the contiguous single Dark Triad scales (r between .41 and .49). The probabilities of filling out steps on the Dirty Dozen narcissism-items were much higher than on the

  15. Baroclinic flows, transports, and kinematic properties in a cyclonic-anticyclonic-cyclonic ring triad in the Gulf of Mexico

    Science.gov (United States)

    Vidal, VíCtor M. V.; Vidal, Francisco V.; HernáNdez, Abel F.; Meza, Eustorgio; PéRez-Molero, José M.

    1994-04-01

    During October-November 1986 the baroclinic circulation of the central and western Gulf of Mexico was dominated by an anticyclonic ring that was being bisected by two north and south flanking cyclonic rings. The baroclinic circulation revealed a well-defined cyclonic-anticyclonic-cyclonic triad system. The anticyclone's collision against the western gulf continental slope at 22.5°N, 97°W originated the north and south flanking cyclonic rings. The weakening of the anticyclone's relative vorticity, during the collision, was compensated by along-shelf north (26 cm s-1) and south (58 cm s-1) jet currents and by the anticyclone's flanking water mass's gain of cyclonic vorticity from lateral shear contributed by east (56 cm s-1) and west (42 cm s-1) current jets with individual mass transports of ˜18 Sv. Within the 0-1000 and 0-500 dbar layers and across 96°W the magnitudes of the colliding westward transports were 17.80 and 8.59 Sv, respectively. These corresponding transports were 85 and 94% balanced by along-shelf jet currents north and south of the anticyclone's collision zone. This indicates that only minor amounts (energy from the upper to the deeper water layers. Our vertical transport estimates through the 1000-m-depth surface revealed a net vertical descending transport of 0.4 Sv for the ring triad system. This mass flux occurred primordially within the south central gulf region and most likely constituted a principal mechanism that propelled the gulf's deep horizontal circulation. The volume renewal time is ˜5 years for the ring triad system within 0-1000 dbar. The volume renewal time for the gulf's deep water layer (2000-3000 dbar), estimated as a function of its horizontal outflowing mass flux (1.96 Sv), is of the same order of magnitude and reveals that the deeper layer of the Gulf of Mexico is as well ventilated as its upper layer (0-1000 dbar). The ring triad's surface kinematic properties were derived from the sea surface baroclinic circulation field

  16. Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

    Science.gov (United States)

    Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

    2016-01-01

    Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

  17. What Have You Done for Me Lately? Friendship-Selection in the Shadow of the Dark Triad Traits

    Directory of Open Access Journals (Sweden)

    Peter K. Jonason

    2012-07-01

    Full Text Available The current studies examined how the Dark Triad personality traits (i.e., Machiavellianism, narcissism, and psychopathy facilitate the strategic structuring of an individual's social environment in terms of same- and opposite-sex friends. In one study using normative questions (N = 267 and another using a budget-allocation task (N = 114, we found that the Dark Triad traits were associated with choosing friends for strategic purposes and to create a volatile environment. Narcissistic individuals reported relatively more reasons to form friendships, such as shared interests, makes me feel good, and intelligence. Women high in narcissism chose same-sex friends who were attractive and women high on Machiavellianism chose same-sex friends who have social status. Men high on psychopathy devalued traits associated with good social relationships in favor of friends who could facilitate their mating efforts and to offset risks incurred in their life history strategy. Results are discussed using the selection-manipulation-evocation framework for explaining how personality traits interact with social environments and integrated with findings from evolutionary biology.

  18. Identifying Motor, Emotional-Behavioral, and Cognitive Deficits that Comprise the Triad of HD Symptoms from Patient, Caregiver, and Provider Perspectives

    Directory of Open Access Journals (Sweden)

    David Victorson

    2014-04-01

    Full Text Available Background: The objective of this study was to identify important attributes associated with the triad of symptoms (cognition, emotional–behavioral, and motor of Huntington's disease (HD from patient, caregiver, and medical provider perspectives to facilitate development of a new disease‐specific, health‐related quality of life (HRQOL instrument. Methods: We conducted a targeted literature review of HD and HRQOL instruments, expert surveys, and patient and caregiver phone‐based interviews to extract information on the symptoms and issues most relevant to the HD symptom triad (HD triad. The data collected from these sources were used to generate themes and subdomains and to develop an integrated schema that highlights the key dimensions of the triad. Results: The search identified the following areas: emotional functioning/behavioral changes (e.g., positive emotions, sadness/depression; cognitive functioning (e.g., memory/learning, attention/comprehension; physical functioning (e.g., motor functioning, medication; social functioning (e.g., leisure, interpersonal relationships; end‐of‐life concerns/planning; and gene testing. Fifteen individuals diagnosed with HD and 16 HD caregivers, recruited from several Huntington's Disease Society of America support group networks, completed phone interviews. Nineteen US medical providers who specialize in HD completed the online survey. Twenty‐six subdomains of the HD symptom triad (seven cognition, 12 emotional–behavioral, and seven motor emerged relatively consistently across patient, caregiver, and provider samples. These included movements/chorea, memory impairment, depression, and anxiety. Discussion: Based on an integrated, mixed‐methods approach, important HD triad symptom were identified and organized into a guiding schema. These patient‐, caregiver‐, and provider‐triangulated data served as the basis for development of a HD‐specific HRQOL instrument, the HD‐PRO‐TRIAD™.

  19. The effect of structural changes on charge transfer states in a light-harvesting carotenoid-diaryl-porphyrin-C{sub 60} molecular triad

    Energy Technology Data Exchange (ETDEWEB)

    Olguin, Marco [Computational Science Program, University of Texas at El Paso, El Paso, Texas 79968 (United States); Basurto, Luis; Zope, Rajendra R. [Department of Physics, The University of Texas at El Paso, El Paso, Texas 79968 (United States); Baruah, Tunna, E-mail: tbaruah@utep.edu [Computational Science Program, University of Texas at El Paso, El Paso, Texas 79968 (United States); Department of Physics, The University of Texas at El Paso, El Paso, Texas 79968 (United States)

    2014-05-28

    We present a detailed study of charge transfer (CT) excited states for a large number of configurations in a light-harvesting Carotenoid-diaryl-Porphyrin-C{sub 60} (CPC{sub 60}) molecular triad. The chain-like molecular triad undergoes photoinduced charge transfer process exhibiting a large excited state dipole moment, making it suitable for application to molecular-scale opto-electronic devices. An important consideration is that the structural flexibility of the CPC{sub 60} triad impacts its dynamics in solvents. Since experimentally measured dipole moments for the triad of ∼110 D and ∼160 D strongly indicate a range in structural variability in the excited state, studying the effect of structural changes on the CT excited state energetics furthers the understanding of its charge transfer states. We have calculated the variation in the lowest CT excited state energies by performing a scan of possible variation in the structure of the triad. Some of these configurations were generated by incrementally scanning a 360° torsional (dihedral) twist at the C{sub 60}-porhyrin linkage and the porphyrin-carotenoid linkage. Additionally, five different CPC{sub 60} conformations were studied to determine the effect of pi-conjugation and particle-hole Coulombic attraction on the CT excitation energies. Our calculations show that configurational changes in the triad induces a variation of ∼0.6 eV in CT excited state energies in the gas-phase. The corresponding calculated excited state dipoles show a range of 47 D–188 D. The absorption spectra and density of states of these structures show little variation except for the structures where the porphyrin and aryl conjugation is changed.

  20. A Duo of Potassium-Responsive Histidine Kinases Govern the Multicellular Destiny of Bacillus subtilis

    Science.gov (United States)

    de Oña, Paula; Kunert, Maritta; Leñini, Cecilia; Gallegos-Monterrosa, Ramses; Mhatre, Eisha; Vileta, Darío; Hölscher, Theresa; Kuipers, Oscar P.

    2015-01-01

    ABSTRACT Multicellular biofilm formation and surface motility are bacterial behaviors considered mutually exclusive. However, the basic decision to move over or stay attached to a surface is poorly understood. Here, we discover that in Bacillus subtilis, the key root biofilm-controlling transcription factor Spo0A~Pi (phosphorylated Spo0A) governs the flagellum-independent mechanism of social sliding motility. A Spo0A-deficient strain was totally unable to slide and colonize plant roots, evidencing the important role that sliding might play in natural settings. Microarray experiments plus subsequent genetic characterization showed that the machineries of sliding and biofilm formation share the same main components (i.e., surfactin, the hydrophobin BslA, exopolysaccharide, and de novo-formed fatty acids). Sliding proficiency was transduced by the Spo0A-phosphorelay histidine kinases KinB and KinC. We discovered that potassium, a previously known inhibitor of KinC-dependent biofilm formation, is the specific sliding-activating signal through a thus-far-unnoticed cytosolic domain of KinB, which resembles the selectivity filter sequence of potassium channels. The differential expression of the Spo0A~Pi reporter abrB gene and the different levels of the constitutively active form of Spo0A, Sad67, in Δspo0A cells grown in optimized media that simultaneously stimulate motile and sessile behaviors uncover the spatiotemporal response of KinB and KinC to potassium and the gradual increase in Spo0A~Pi that orchestrates the sequential activation of sliding, followed by sessile biofilm formation and finally sporulation in the same population. Overall, these results provide insights into how multicellular behaviors formerly believed to be antagonistic are coordinately activated in benefit of the bacterium and its interaction with the host. PMID:26152584

  1. Virulence Effects and Signaling Partners Modulated by Brucella melitensis Light-sensing Histidine Kinase

    Science.gov (United States)

    Gourley, Christopher R.

    The facultative intracellular pathogen Brucella melitensis utilizes diverse virulence factors. A Brucella light sensing histidine kinase can influence in vitro virulence of the bacteria during intracellular infection. First, we demonstrated that the B. melitensis light sensing kinase (BM-LOV-HK) affects virulence in an IRF-1-/- mouse model of infection. Infection with a Δ BM-LOV-HK strain resulted in less bacterial colonization of IRF-1-/- spleens and extended survivorship compared to mice infected with wild type B. melitensis 16M. Second, using PCR arrays, we observed less expression of innate and adaptive immune system activation markers in ΔBM-LOV-HK infected mouse spleens than wild type B. melitensis 16M infected mouse spleens 6 days after infection. Third, we demonstrated by microarray analysis of B. melitensis that deletion of BM-LOV-HK alters bacterial gene expression. Downregulation of genes involved in control of the general stress response system included the alternative sigma factor RpoE1 and its anti-anti sigma factor PhyR. Conversely, genes involved in flagella production, quorum sensing, and the type IV secretion system (VirB operon) were upregulated in the Δ BM-LOV-HK strain compared to the wild type B. melitensis 16M. Analysis of genes differentially regulated in Δ BM-LOV-HK versus the wild type strain indicated an overlap of 110 genes with data from previous quorum sensing regulator studies of Δ vjbR and/ΔblxR(babR) strains. Also, several predicted RpoE1 binding sites located upstream of genes were differentially regulated in the ΔBM-LOV-HK strain. Our results suggest BM-LOV-HK is important for in vivo Brucella virulence, and reveals that BM-LOV-HK directly or indirect regulates members of the Brucella quorum sensing, type IV secretion, and general stress systems.

  2. A displaced stress fracture of the femoral neck in an adolescent female distance runner with female athlete triad: A case report

    Directory of Open Access Journals (Sweden)

    Okamoto Shinichi

    2010-03-01

    Full Text Available Abstract This report presents a case of a displaced stress fracture of the femoral neck in an adolescent female distance runner with amenorrhea. Both reduction and internal fixation were performed early after the injury. At 24 months postoperatively, magnetic resonance imaging and bone scintigraphy showed no positive signs of femoral head necrosis and bone union was confirmed on plain X-ray. A medical examination for the presence of the signs of the female athlete triad by checking weight, calorie intake and menstrual cycles is most important to prevent such stress fractures. Athletes as well as their coaches or parents therefore need to understand female athlete triad.

  3. pH-induced conformational change of IscU at low pH correlates with protonation/deprotonation of two conserved histidine residues.

    Science.gov (United States)

    Dai, Ziqi; Kim, Jin Hae; Tonelli, Marco; Ali, Ibrahim K; Markley, John L

    2014-08-19

    IscU, the scaffold protein for the major iron-sulfur cluster biosynthesis pathway in microorganisms and mitochondria (ISC pathway), plays important roles in the formation of [2Fe-2S] and [4Fe-4S] clusters and their delivery to acceptor apo-proteins. Our laboratory has shown that IscU populates two distinct, functionally relevant conformational states, a more structured state (S) and a more dynamic state (D), that differ by cis/trans isomerizations about two peptidyl-prolyl peptide bonds [Kim, J. H., Tonelli, M., and Markley, J. L. (2012) Proc. Natl. Acad. Sci. U.S.A., 109, 454-459. Dai Z., Tonelli, M., and Markley, J. L. (2012) Biochemistry, 51, 9595-9602. Cai, K., Frederick, R. O., Kim, J. H., Reinen, N. M., Tonelli, M., and Markley, J. L. (2013) J. Biol. Chem., 288, 28755-28770]. Here, we report our findings on the pH dependence of the D ⇄ S equilibrium for Escherichia coli IscU in which the D-state is stabilized at low and high pH values. We show that the lower limb of the pH dependence curve results from differences in the pKa values of two conserved histidine residues (His10 and His105) in the two states. The net proton affinity of His10 is about 50 times higher and that of His105 is 13 times higher in the D-state than in the S-state. The origin of the high limb of the D ⇄ S pH dependence remains to be determined. These results show that changes in proton inventory need to be taken into account in the steps in iron-sulfur cluster assembly and transfer that involve transitions of IscU between its S- and D-states.

  4. Chemical-modification studies of a unique sialic acid-binding lectin from the snail Achatina fulica. Involvement of tryptophan and histidine residues in biological activity.

    Science.gov (United States)

    Basu, S; Mandal, C; Allen, A K

    1988-01-01

    A unique sialic acid-binding lectin, achatininH (ATNH) was purified in single step from the haemolymph of the snail Achatina fulica by affinity chromatography on sheep submaxillary-gland mucin coupled to Sepharose 4B. The homogeneity was checked by alkaline gel electrophoresis, immunodiffusion and immunoelectrophoresis. Amino acid analysis showed that the lectin has a fairly high content of acidic amino acid residues (22% of the total). About 1.3% of the residues are half-cystine. The glycoprotein contains 21% carbohydrate. The unusually high content of xylose (6%) and fucose (2.7%) in this snail lectin is quite interesting. The protein was subjected to various chemical modifications in order to detect the amino acid residues and carbohydrate residues present in its binding sites. Modification of tyrosine and arginine residues did not affect the binding activity of ATNH; however, modification of tryptophan and histidine residues led to a complete loss of its biological activity. A marked decrease in the fluorescence emission was found as the tryptophan residues of ATNH were modified. The c.d. data showed the presence of an identical type of conformation in the native and modified agglutinin. The modification of lysine and carboxy residues partially diminished the biological activity. The activity was completely lost after a beta-elimination reaction, indicating that the sugars are O-glycosidically linked to the glycoprotein's protein moiety. This result confirms that the carbohydrate moiety also plays an important role in the agglutination property of this lectin. Images Fig. 3. PMID:3140796

  5. Identification and characterization of histidine-rich peptides from hard ticks Ixodes ricinus and Ixodes scapularis.

    OpenAIRE

    DORŇÁKOVÁ, Veronika

    2011-01-01

    Antimicrobial (cationic) proteins play an important role in innate imunity. Such proteins can possess antibacterial, antiendotoxic or fungicidal abilities. The rising resistence of microbes to common antibiotics evokes acute need of studying more endogenous proteins to reveal new potential antibiotics. Ticks, the blood-feeding ectoparasites with effectual defense system, present an endless source of newly described and unknown antimicrobial peptides/proteins with significant theurapeutic pote...

  6. Sensor histidine kinase is a β-lactam receptor and induces resistance to β-lactam antibiotics

    OpenAIRE

    Li, Lu; Wang, Qiyao; Zhang, Hui; Yang, Minjun; Khan, Mazhar I.; Zhou, Xiaohui

    2016-01-01

    Bacteria can produce β-lactamases, enzymes that destroy β-lactam antibiotics and thereby resist these potent antibiotics that target cell wall synthesis. Production of β-lactamases is often controlled by β-lactam-induced perturbations in the cell wall. Here, we have identified a new mechanism controlling β-lactamase production. We found a signaling system in which a membrane-associated histidine kinase directly binds β-lactams, triggering the expression of a β-lactamase and resistance to β-la...

  7. Binding of the human "electron transferring flavoprotein" (ETF) to the medium chain acyl-CoA dehydrogenase (MCAD) involves an arginine and histidine residue.

    Science.gov (United States)

    Parker, Antony R

    2003-10-01

    The interaction between the "electron transferring flavoprotein" (ETF) and medium chain acyl-CoA dehydrogenase (MCAD) enables successful flavin to flavin electron transfer, crucial for the beta-oxidation of fatty acids. The exact biochemical determinants for ETF binding to MCAD are unknown. Here we show that binding of human ETF, to MCAD, was inhibited by 2,3-butanedione and diethylpyrocarbonate (DEPC) and reversed by incubation with free arginine and hydroxylamine respectively. Spectral analyses of native ETF vs modified ETF suggested that flavin binding was not affected and that the loss of ETF activity with MCAD involved modification of one ETF arginine residue and one ETF histidine residue respectively. MCAD and octanoyl-CoA protected ETF against inactivation by both 2,3-butanedione and DEPC indicating that the arginine and histidine residues are present in or around the MCAD binding site. Comparison of exposed arginine and histidine residues among different ETF species, however, indicates that arginine residues are highly conserved but that histidine residues are not. These results lead us to conclude that this single arginine residue is essential for the binding of ETF to MCAD, but that the single histidine residue, although involved, is not.

  8. Phytoremediation of mixed-contaminated soil using the hyperaccumulator plant Alyssum lesbiacum: Evidence of histidine as a measure of phytoextractable nickel

    International Nuclear Information System (INIS)

    Singer, Andrew C.; Bell, Thomas; Heywood, Chloe A.; Smith, J.A.C.; Thompson, Ian P.

    2007-01-01

    In this study we examine the effects of polycyclic aromatic hydrocarbons (PAHs) on the ability of the hyperaccumulator plant Alyssum lesbiacum to phytoextract nickel from co-contaminated soil. Planted and unplanted mesocosms containing the contaminated soils were repeatedly amended with sorbitan trioleate, salicylic acid and histidine in various combinations to enhance the degradation of two PAHs (phenanthrene and chrysene) and increase nickel phytoextraction. Plant growth was negatively affected by PAHs; however, there was no significant effect on the phytoextraction of Ni per unit biomass of shoot. Exogenous histidine did not increase nickel phytoextraction, but the histidine-extractable fraction of soil nickel showed a high correlation with phytoextractable nickel. These results indicate that Alyssum lesbiacum might be effective in phytoextracting nickel from marginally PAH-contaminated soils. In addition, we provide evidence for the broader applicability of histidine for quantifying and predicting Ni phytoavailability in soils. - Alyssum lesbiacum was shown to phytoextract nickel from PAH-contaminated soils from which the pool of nickel accessed for phytoextraction is closely modelled by a histidine-soil extract

  9. Phytoremediation of mixed-contaminated soil using the hyperaccumulator plant Alyssum lesbiacum: Evidence of histidine as a measure of phytoextractable nickel

    Energy Technology Data Exchange (ETDEWEB)

    Singer, Andrew C. [Centre for Ecology and Hydrology-Oxford, Mansfield Road, Oxford OX1 3SR (United Kingdom)]. E-mail: acsi@ceh.ac.uk; Bell, Thomas [Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS (United Kingdom); Heywood, Chloe A. [Centre for Ecology and Hydrology-Oxford, Mansfield Road, Oxford OX1 3SR (United Kingdom); Smith, J.A.C. [Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB (United Kingdom); Thompson, Ian P. [Centre for Ecology and Hydrology-Oxford, Mansfield Road, Oxford OX1 3SR (United Kingdom)

    2007-05-15

    In this study we examine the effects of polycyclic aromatic hydrocarbons (PAHs) on the ability of the hyperaccumulator plant Alyssum lesbiacum to phytoextract nickel from co-contaminated soil. Planted and unplanted mesocosms containing the contaminated soils were repeatedly amended with sorbitan trioleate, salicylic acid and histidine in various combinations to enhance the degradation of two PAHs (phenanthrene and chrysene) and increase nickel phytoextraction. Plant growth was negatively affected by PAHs; however, there was no significant effect on the phytoextraction of Ni per unit biomass of shoot. Exogenous histidine did not increase nickel phytoextraction, but the histidine-extractable fraction of soil nickel showed a high correlation with phytoextractable nickel. These results indicate that Alyssum lesbiacum might be effective in phytoextracting nickel from marginally PAH-contaminated soils. In addition, we provide evidence for the broader applicability of histidine for quantifying and predicting Ni phytoavailability in soils. - Alyssum lesbiacum was shown to phytoextract nickel from PAH-contaminated soils from which the pool of nickel accessed for phytoextraction is closely modelled by a histidine-soil extract.

  10. Structural and Functional Models of Non-Heme Iron Enzymes : A Study of the 2-His-1-Carboxylate Facial Triad Structural Motif

    NARCIS (Netherlands)

    Bruijnincx, P.C.A.

    2007-01-01

    The structural and functional modeling of a specific group of non-heme iron enzymes by the synthesis of small synthetic analogues is the topic of this thesis. The group of non-heme iron enzymes with the 2-His-1-carboxylate facial triad has recently been established as a common platform for the

  11. Broadband Light-Harvesting Molecular Triads with High FRET Efficiency Based on the Coumarin-Rhodamine-BODIPY Platform.

    Science.gov (United States)

    He, Longwei; Zhu, Sasa; Liu, Yong; Xie, Yinan; Xu, Qiuyan; Wei, Haipeng; Lin, Weiying

    2015-08-17

    Broadband capturing and FRET-based light-harvesting molecular triads, CRBs, based on the coumarin-rhodamine-BODIPY platform were rationally designed and synthesized. The absorption band of CRBs starts from blue-green to yellow-orange regions (330-610 nm), covering the strong radiation scope of sunlight. The peripheral coumarin and BODIPY chromophore energy could transfer to the central acceptor rhodamine by a one-step direct way. The energy of the coumarin moiety could also transfer to the BODIPY unit, subsequently transferring to the rhodamine core by two-step sequential ways. Both the efficiencies of the coumarin moiety and the BODIPY unit to the rhodamine core in CRBs, determined by two different ways, are very high. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Examining Dark Triad traits in relation to sleep disturbances, anxiety sensitivity and intolerance of uncertainty in young adults.

    Science.gov (United States)

    Sabouri, Sarah; Gerber, Markus; Lemola, Sakari; Becker, Stephen P; Shamsi, Mahin; Shakouri, Zeinab; Sadeghi Bahmani, Dena; Kalak, Nadeem; Holsboer-Trachsler, Edith; Brand, Serge

    2016-07-01

    The Dark Triad (DT) describes a set of three closely related personality traits, Machiavellianism, narcissism, and psychopathy. The aim of this study was to examine the associations between DT traits, sleep disturbances, anxiety sensitivity and intolerance of uncertainty. A total of 341 adults (M=29years) completed a series of questionnaires related to the DT traits, sleep disturbances, anxiety sensitivity, and intolerance of uncertainty. A higher DT total score was associated with increased sleep disturbances, and higher scores for anxiety sensitivity and intolerance of uncertainty. In regression analyses Machiavellianism and psychopathy were predictors of sleep disturbances, anxiety sensitivity, and intolerance of uncertainty. Results indicate that specific DT traits, namely Machiavellianism and psychopathy, are associated with sleep disturbances, anxiety sensitivity and intolerance of uncertainty in young adults. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The false equivalent of terrible triad of elbow combined with neurovascular damage in a rugby player - A new case report.

    Directory of Open Access Journals (Sweden)

    Hassan BOUSSAKRI

    2014-12-01

    Full Text Available  Terrible triad is a severe traumatic injury of the elbow. We report a new variety of this clinical entity originating from a rare combination of injuries, namely the fracture-dislocation of the right elbow. The symptoms are acute ischemia of the hand with neurological damage following a sport accident suffered by a professional rugby player. We treated him surgically after immediate reduction of the dislocation. The short-term monitoring was clinical, while in the medium-term it was radiological and electrophysiological. On the whole, our (clinical, electrophysiological and radiological results obtained initially, and medium-term during the last consultation, were satisfactory. The objective of this study is to draw attention to this clinical and radiological variety, as well as to its neurovascular complications and to discuss its therapeutic treatment. During the vascular and neurologic exam we should pay attention to and systematically look for neurovascular complications when treating a similar clinical case.

  14. A Social Capital Perspective on the Mentoring of Undergraduate Life Science Researchers: An Empirical Study of Undergraduate-Postgraduate-Faculty Triads.

    Science.gov (United States)

    Aikens, Melissa L; Sadselia, Sona; Watkins, Keiana; Evans, Mara; Eby, Lillian T; Dolan, Erin L

    2016-01-01

    Undergraduate researchers at research universities are often mentored by graduate students or postdoctoral researchers (referred to collectively as "postgraduates") and faculty, creating a mentoring triad structure. Triads differ based on whether the undergraduate, postgraduate, and faculty member interact with one another about the undergraduate's research. Using a social capital theory framework, we hypothesized that different triad structures provide undergraduates with varying resources (e.g., information, advice, psychosocial support) from the postgraduates and/or faculty, which would affect the undergraduates' research outcomes. To test this, we collected data from a national sample of undergraduate life science researchers about their mentoring triad structure and a range of outcomes associated with research experiences, such as perceived gains in their abilities to think and work like scientists, science identity, and intentions to enroll in a PhD program. Undergraduates mentored by postgraduates alone reported positive outcomes, indicating that postgraduates can be effective mentors. However, undergraduates who interacted directly with faculty realized greater outcomes, suggesting that faculty interaction is important for undergraduates to realize the full benefits of research. The "closed triad," in which undergraduates, postgraduates, and faculty all interact directly, appeared to be uniquely beneficial; these undergraduates reported the highest gains in thinking and working like a scientist. © 2016 M. L. Aikens et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  15. Carbohydrate-protein interaction studies by laser photo CIDNP NMR methods

    NARCIS (Netherlands)

    Siebert, HC; Kaptein, R; Beintema, JJ; Soedjanaatmadja, UM; Wright, CS; Rice, A; Kleineidam, RG; Kruse, S; Schauer, R; Pouwels, PJW; Kamerling, JP; Gabius, HJ; Vliegenthart, JFG

    The side chains of tyrosine, tryptophan and histidine are able to produce CIDNP (Chemically Induced Dynamic Nuclear Polarization) signals after laser irradiation in the presence of a suitable radical pair-generating dye. Elicitation of such a response in proteins implies surface accessibility of the

  16. Dynamic factors affecting gaseous ligand binding in an artificial oxygen transport protein.

    Science.gov (United States)

    Zhang, Lei; Andersen, Eskil M E; Khajo, Abdelahad; Magliozzo, Richard S; Koder, Ronald L

    2013-01-22

    We report the functional analysis of an artificial hexacoordinate oxygen transport protein, HP7, which operates via a mechanism similar to that of human neuroglobin and cytoglobin: the destabilization of one of two heme-ligating histidine residues. In the case of HP7, this is the result of the coupling of histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Here we compare gaseous ligand binding, including rates, affinities, and oxyferrous state lifetimes, of both heme binding sites in HP7. We find that despite the identical sequence of helices in both binding sites, there are differences in oxygen affinity and oxyferrous state lifetime that may be the result of differences in the freedom of motion imposed by the candelabra fold on the two sites of the protein. We further examine the effect of mutational removal of the buried glutamates on function. Heme iron in the ferrous state of this mutant is rapidly oxidized when exposed to oxygen. Compared to that of HP7, the distal histidine affinity is increased by a 22-fold decrease in the histidine ligand off rate. Electron paramagnetic resonance comparison of these ferric hemoproteins demonstrates that the mutation increases the level of disorder at the heme binding site. Nuclear magnetic resonance-detected deuterium exchange demonstrates that the mutation greatly increases the degree of penetration of water into the protein core. The inability of the mutant protein to bind oxygen may be due to an increased level of water penetration, the large decrease in binding rate caused by the increase in distal histidine affinity, or a combination of the two factors. Together, these data underline the importance of the control of protein dynamics in the design of functional artificial proteins.

  17. Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

    Science.gov (United States)

    Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

    2009-05-01

    Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

  18. Role of the VirA histidine autokinase of Agrobacterium tumefaciens in the initial steps of pathogenesis

    Directory of Open Access Journals (Sweden)

    Yi-Han eLin

    2014-05-01

    Full Text Available Histidine kinases serve as critical environmental sensing modules, and despite their designation as simple two-component modules, their functional roles are remarkably diverse. In Agrobacterium tumefaciens pathogenesis, VirA serves with VirG as the initiating sensor/transcriptional activator for inter-kingdom gene transfer and transformation of higher plants. Through responses to three separate signal inputs, low pH, sugars, and phenols, A. tumefaciens commits to pathogenesis in virtually all flowering plants. However, how these three signals are integrated to regulate the response and why these signals might be diagnostic for susceptible cells across such a broad host-range remains poorly understood. Using a homology model of the VirA linker region, we provide evidence for coordinated long-range transmission of inputs perceived both outside and inside the cell through the creation of targeted VirA truncations. Further, our evidence is consistent with signal inputs weakening associations between VirA domains to position the active site histidine for phosphate transfer. This mechanism requires long-range regulation of inter-domain stability and the transmission of input signals through a common integrating domain for VirA signal transduction.

  19. Comparative analysis of LytS/LytTR-type histidine kinase/response regulator systems in γ-proteobacteria.

    Directory of Open Access Journals (Sweden)

    Stefan Behr

    Full Text Available Bacterial histidine kinase/response regulator systems operate at the interface between environmental cues and physiological states. Escherichia coli contains two LytS/LytTR-type histidine kinase/response regulator systems, BtsS/BtsR (formerly YehU/YehT and YpdA/YpdB, which have been identified as pyruvate-responsive two-component systems. Since they exhibit remarkable similarity, we analyzed their phylogenetic distribution within the γ-proteobacteria, and experimentally characterized them in a set of representative species. We found that BtsS/BtsR is the predominant LytS/LytTR-type two-component system among γ-proteobacteria, whereas YpdA/YpdB primarily appears in a supplementary role. Based on our observations in E. coli, we used the highly conserved DNA-binding motifs to test the in vivo functionality of both systems in various genera, including Salmonella, Enterobacter, Citrobacter, Xenorhabdus, Yersinia, Aeromonas and Vibrio. The results suggest that, in all cases tested, BtsS/BtsR and YpdA/YpdB respond to different levels of pyruvate in the environment.

  20. Inhibition by etomoxir of rat liver carnitine octanoyltransferase is produced through the co-ordinate interaction with two histidine residues.

    Science.gov (United States)

    Morillas, M; Clotet, J; Rubí, B; Serra, D; Ariño, J; Hegardt, F G; Asins, G

    2000-10-15

    Rat peroxisomal carnitine octanoyltransferase (COT), which facilitates the transport of medium-chain fatty acids through the peroxisomal membrane, is irreversibly inhibited by the hypoglycaemia-inducing drug etomoxir. To identify the molecular basis of this inhibition, cDNAs encoding full-length wild-type COT, two different variant point mutants and one variant double mutant from rat peroxisomal COT were expressed in Saccharomyces cerevisiae, an organism devoid of endogenous COT activity. The recombinant mutated enzymes showed activity towards both carnitine and decanoyl-CoA in the same range as the wild type. Whereas the wild-type version expressed in yeast was inhibited by etomoxir in an identical manner to COT from rat liver peroxisomes, the activity of the enzyme containing the double mutation H131A/H340A was completely insensitive to etomoxir. Individual point mutations H131A and H340A also drastically reduced sensitivity to etomoxir. Taken together, these results indicate that the two histidine residues, H131 and H340, are the sites responsible for inhibition by etomoxir and that the full inhibitory properties of the drug will be shown only if both histidines are intact at the same time. Our data demonstrate that both etomoxir and malonyl-CoA inhibit COT by interacting with the same sites.

  1. Construction of a catalytically inactive cholesterol oxidase mutant: investigation of the interplay between active site-residues glutamate 361 and histidine 447.

    Science.gov (United States)

    Yin, Ye; Liu, Pingsheng; Anderson, Richard G W; Sampson, Nicole S

    2002-06-15

    Cholesterol oxidase catalyzes the oxidation of cholesterol to cholest-5-en-3-one and its subsequent isomerization into cholest-4-en-3-one. Two active-site residues, His447 and Glu361, are important for catalyzing the oxidation and isomerization reactions, respectively. Double-mutants were constructed to test the interplay between these residues in catalysis. We observed that the k(cat) of oxidation for the H447Q/E361Q mutant was 3-fold less than that for H447Q and that the k(cat) of oxidation for the H447E/E361Q mutant was 10-fold slower than that for H447E. Because both doubles-mutants do not have a carboxylate at position 361, they do not catalyze isomerization of the reaction intermediate cholest-5-en-3-one to cholest-4-en-3-one. These results suggest that Glu361 can compensate for the loss of histidine at position 447 by acting as a general base catalyst for oxidation of cholesterol. Importantly, the construction of the double-mutant H447E/E361Q yields an enzyme that is 31,000-fold slower than wild type in k(cat) for oxidation. The H447E/E361Q mutant is folded like native enzyme and still associates with model membranes. Thus, this mutant may be used to study the effects of membrane binding in the absence of catalytic activity. It is demonstrated that in assays with caveolae membrane fractions, the wild-type enzyme uncouples platelet-derived growth factor receptor beta (PDGFRbeta) autophosphorylation from tyrosine phosphorylation of neighboring proteins, and the H447E/E361Q mutant does not. Thus maintenance of membrane structure by cholesterol is important for PDGFRbeta-mediated signaling. The cholesterol oxidase mutant probe described will be generally useful for investigating the role of membrane structure in signal transduction pathways in addition to the PDGFRbeta-dependent pathway tested.

  2. Investigation of Unanticipated Alkylation at the N(π) Position of a Histidyl Residue Under Mitsunobu Conditions and Synthesis of Orthogonally Protected Histidine Analogues

    Science.gov (United States)

    Qian, Wenjian; Liu, Fa; Burke, Terrence R.

    2011-01-01

    We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(π)-position of a key histidine residue in phosphothreonine-containing peptides can impart high binding affinity against the polo box domain of polo like kinase 1. Our current paper investigates the mechanism leading to this N(π)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(π)-modified peptides. These agents represent new and potentially important tools for biological studies. PMID:21950469

  3. A Duo of Potassium-Responsive Histidine Kinases Govern the Multicellular Destiny of Bacillus subtilis.

    Science.gov (United States)

    Grau, Roberto R; de Oña, Paula; Kunert, Maritta; Leñini, Cecilia; Gallegos-Monterrosa, Ramses; Mhatre, Eisha; Vileta, Darío; Donato, Verónica; Hölscher, Theresa; Boland, Wilhelm; Kuipers, Oscar P; Kovács, Ákos T

    2015-07-07

    Multicellular biofilm formation and surface motility are bacterial behaviors considered mutually exclusive. However, the basic decision to move over or stay attached to a surface is poorly understood. Here, we discover that in Bacillus subtilis, the key root biofilm-controlling transcription factor Spo0A~Pi (phosphorylated Spo0A) governs the flagellum-independent mechanism of social sliding motility. A Spo0A-deficient strain was totally unable to slide and colonize plant roots, evidencing the important role that sliding might play in natural settings. Microarray experiments plus subsequent genetic characterization showed that the machineries of sliding and biofilm formation share the same main components (i.e., surfactin, the hydrophobin BslA, exopolysaccharide, and de novo-formed fatty acids). Sliding proficiency was transduced by the Spo0A-phosphorelay histidine kinases KinB and KinC. We discovered that potassium, a previously known inhibitor of KinC-dependent biofilm formation, is the specific sliding-activating signal through a thus-far-unnoticed cytosolic domain of KinB, which resembles the selectivity filter sequence of potassium channels. The differential expression of the Spo0A~Pi reporter abrB gene and the different levels of the constitutively active form of Spo0A, Sad67, in Δspo0A cells grown in optimized media that simultaneously stimulate motile and sessile behaviors uncover the spatiotemporal response of KinB and KinC to potassium and the gradual increase in Spo0A~Pi that orchestrates the sequential activation of sliding, followed by sessile biofilm formation and finally sporulation in the same population. Overall, these results provide insights into how multicellular behaviors formerly believed to be antagonistic are coordinately activated in benefit of the bacterium and its interaction with the host. Alternation between motile and sessile behaviors is central to bacterial adaptation, survival, and colonization. However, how is the collective

  4. Early Clinical Outcomes of Tricuspid Valve Repair with a Tri-Ad Annuloplasty Ring in Comparison with the Outcomes Using an MC³ Ring

    Directory of Open Access Journals (Sweden)

    Woohyun Jung

    2018-04-01

    Full Text Available Background: We evaluated the early clinical outcomes of tricuspid valve annuloplasty (TAP with the Tri-Ad annuloplasty ring for functional tricuspid regurgitation (TR. Methods: From January 2015 to March 2017, 36 patients underwent TAP with a Tri-Ad ring for functional TR. To evaluate the early clinical outcomes of TAP with the Tri-Ad ring, we conducted a propensity score-matched analysis comparing the Tri-Ad and MC³ tri-cuspid annuloplasty rings (n=34 in each group. The follow-up duration was 11.0±7.07 months. Results: There was 1 case of operative mortality (2.8% and no cases of late mortality. Postoperative complications occurred in 15 patients (41%, including acute kidney injury in 6 patients (16%, bleeding requiring reoperation in 4 patients (11%, and low cardiac output syndrome in 4 patients (11%. There were no ring-related complications, such as atrioventricular block or ring dehiscence. The TR grade decreased significantly (from 2.03±1.06 to 1.18±0.92, p<0.01, as did the systolic pulmonary artery pressure (from 43.53±13.84 to 38.00±9.72 mm Hg, p=0.03. There were no cases of severe residual TR, but moderate TR was observed in 3 patients, all of whom had severe TR preoperatively. Severe preoperative TR was also associated with moderate in the univariate analysis (p<0.01. In the propensity score-matched analysis comparing the Tri-Ad and MC³ rings, there was no significant difference in early clinical outcomes. Conclusion: TAP with the Tri-Ad ring corrected functional TR effectively and provided good early clinical and echocardiographic results without ring-related complications. However, severe preoperative TR was associated with moderate or severe residual TR in the immediate postoperative period. A follow-up study is necessary to confirm the stability of this procedure.

  5. L’inscrutabile voce della triade. I tintinnabuli di Arvo Pärt tra filosofia e liturgia

    Directory of Open Access Journals (Sweden)

    Marcello La Matina

    2011-01-01

    Full Text Available Può il brusio di una voce essere anche il luogo di una lingua? E vale questa topica anche nel caso in cui la voce sia quella di uno strumento musicale? Queste domande sono alla base della indagine sulla tecnica compositiva della tintinnabulatio, inventata e sperimentata dal musicista estone Arvo Pärt (Paide, 1935. I tintinnabuli consistono di due elementi apparentemente contraddittori: la sonorità pastosa dello zvod (le campane della liturgia ortodossa russa e l’armonia della triade perfetta. Muovendo da un disco ricevuto in dono e dalla interpretazione in parte inedita di un passo di san Paolo, l’autore cerca di individuare il punto di articolazione dei tintinnabuli,  quella “grana” dove – come disse una volta Roland Barthes – una lingua incontra una voce. Il problema musicale sottende le interminabili discussioni trinitarie dell’Oriente cristiano  – qui per sfortuna solo accennate – e si manifesta nella figura dell’iconografo medievale Andrej Rublëv, cui il regista russo Tarkovskij ha dedicato, nel 1966, un denso e ispiratissimo film.   Could the rustling of a voice be also the place of a language?  And does it happen all the same, when the voice at issue is that of an instrumental body? Such questions are the basic ones for any inquiry into Arvo Pärt’s tintinnabuli—the technique invented and experienced by the famous Esthonian composer ( born in Paide, the 1935. It consists of  two seemingly conflicting elements: the doughy resonance of the zvot (i.e. the Russian liturgical set of bells; and the harmony of the perfect triad. The present paper moves from the personal memory of listening Pärt’s elegy Silouans Song. The delicate instrumental piece is said to conceal a prosodical calque of the voice of the famous staretz Silouan the Athonite (1866-1938. Silouan’s song —to use Barthes’ words—is the very place where “a language does meet a voice”.  Some interpretive consequences lead off such a

  6. Reprodaetion of an animal model of multiple intestinal injuries mimicking "lethal triad" caused by severe penetrating abdominal trauma

    Directory of Open Access Journals (Sweden)

    Peng-fei WANG

    2011-03-01

    Full Text Available Objective To reproduce an animal model of multi-intestinal injuries with "lethal triad" characterized by low body temperature,acidosis and coagulopathy.Methods Six female domestic outbred pigs were anesthetized,and the carotid artery and jugular vein were cannulated for monitoring the blood pressure and heart rate and for infusion of fluid.The animals were shot with a gun to create a severe penetrating abdominal trauma.Immediately after the shooting,50% of total blood volume(35ml/kg hemorrhage was drawn from the carotid artery in 20min.After a 40min shock period,4h of pre-hospital phase was mimicked by normal saline(NS resuscitation to maintain systolic blood pressure(SBP > 80mmHg or mean arterial pressure(MAP > 60mmHg.When SBP > 80mmHg or MAP > 60mmHg,no fluid infusion or additional bleeding was given.Hemodynamic parameters were recorded,and pathology of myocardium,lung,small intestine and liver was observed.Results There were multiple intestinal perforations(8-10 site injuries/pig leading to intra-abdominal contamination,mesenteric injury(1-2 site injuries/pig resulted in partial intestinal ischemia and intra-abdominal hemorrhage,and no large colon and mesenteric vascular injury.One pig died before the completion of the model establishment(at the end of pre-hospital resuscitation.The typical symptoms of trauma-induced hemorrhagic shock were observed in survival animals.Low temperature(33.3±0.5℃,acidosis(pH=7.242±0.064,and coagulopathy(protrombin time and activated partial thromboplasting time prolonged were observed after pre-hospital resuscitation.Pathology showed that myocardium,lung,small intestine and liver were severely injured.Conclusions A new model,simulating three stages of "traumatic hemorrhagic shock,pre-hospital recovery and hospital treatment" and inducing the "lethal triad" accompanied with abdominal pollution,has been successfully established.This model has good stability and high reproducibility.The survival animals can be

  7. Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells

    DEFF Research Database (Denmark)

    Gräs, S; Ovesen, Per Glud; Andersen, A N

    1994-01-01

    Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicula...

  8. Contribution of Histidine and Lysine to the Generation of Volatile Compounds in Jinhua Ham Exposed to Ripening Conditions Via Maillard Reaction.

    Science.gov (United States)

    Zhu, Chao-Zhi; Zhao, Jing-Li; Tian, Wei; Liu, Yan-Xia; Li, Miao-Yun; Zhao, Gai-Ming

    2018-01-01

    To evaluate the role of Maillard reactions in the generation of flavor compounds in Jinhua ham, the reactions of glucose and ethanal with histidine and lysine, respectively, were studied by simulating the ripening conditions of Jinhua ham. The volatile products produced were analyzed using solid phase microextraction-gas chromatography/mass spectrometry. The results showed that 8 volatile compounds were generated by the reaction of glucose and histidine and 10 volatile compounds were generated by the reaction of glucose and lysine. Reactions of ethanal with lysine and with histidine both generated 31 volatile compounds that contributed to the flavor of Jinhua ham. This indicates that histidine and lysine related to Maillard reactions possibly play important roles in the generation of the unique flavor compounds in Jinhua ham. This research demonstrates that free amino acids participate in the generation of volatile compounds from Jinhua ham via the Maillard reaction and provides a basic mechanism to explain flavor formation in Jinhua ham. Jinhua ham is a well-known traditional Chinese dry-cured meat product. However, the formation of the compounds comprising its special flavor is not well understood. Our results indicate that Maillard reactions occur in Jinhua ham under ripening conditions. This work illustrates the contribution of Maillard reactions to the flavor of Jinhua ham. © 2017 Institute of Food Technologists®.

  9. Detection of Cu2+ in Water Based on Histidine-Gold Labeled Multiwalled Carbon Nanotube Electrochemical Sensor

    Directory of Open Access Journals (Sweden)

    Rilong Zhu

    2017-01-01

    Full Text Available Based on the strong interaction between histidine and copper ions and the signal enhancement effect of gold-labeling carbon nanotubes, an electrochemical sensor is established and used to measure copper ions in river water. In this study the results show that the concentrations of copper ion have well linear relationship with the peak current in the range of 10−11–10−7 mol/L, and the limit of detection is 10−12 mol/L. When using this method to detect copper ions in the Xiangjiang River, the test results are consistent with the atomic absorption method. This study shows that the sensor is convenient to be used in daily monitoring of copper ions in river water.

  10. Mitsunobu mischief: Neighbor-directed histidine N(π)–alkylation provides access to peptides containing selectively functionalized imidazolium heterocycles

    Science.gov (United States)

    Qian, Wen-Jian

    2015-01-01

    There are few methodologies that yield peptides containing His residues with selective N(π), N(π)-bis-alkylated imidazole rings. We have found that, under certain conditions, on-resin Mitsunobu coupling of alcohols with peptides having a N(π)-alkylated His residue results in selective and high-yield alkylation of the imidazole N(π) nitrogen. The reaction requires the presence of a proximal phosphoric, carboxylic or sulfonic acid, and proceeds through an apparent intramolecular mechanism involving Mitsunobu intermediates. These transformations have particular application to phosphopeptides, where “charge masking” of one phosphoryl anionic charge by the cationic histidine imidazolium ion is now possible. This chemistry opens selective access to peptides containing differentially functionalized imidazolium heterocycles, which provide access to new classes of peptides and peptide mimetics. PMID:25739367

  11. Hg-coordination studies of oligopeptides containing cysteine, histidine and tyrosine by $^{199m}$Hg-TDPAC

    CERN Document Server

    Ctortecka, B; Mallion, S; Butz, T; Hoffmann, R

    1999-01-01

    In order to study the interaction of histidine- and tyrosine- containing peptide chains with Hg(II), the nuclear quadrupole interaction (NQI) of /sup 199m/Hg in the Hg complexes of the oligopeptides alanyl-alanyl-histidyl-alanyl-alanine-amid (AAHAA-NH /sub 2/) and alanyl-alanyl-tyrosyl-alanyl-alanine-amid (AAYAA-NH/sub 2/) was determined by time differential perturbed angular correlation and is compared with previous data on alanyl-alanyl-cysteyl-alanyl- alanyl (AACAA-OH). The /sup 199m/Hg-NQIs depend on the oligopeptide to Hg(II) stoichiometry and indicate that two-fold and four-fold coordinations occur for the bound Hg(II). (12 refs).

  12. Evolutionary Profiling of Group II Pyridoxal-Phosphate-Dependent Decarboxylases Suggests Expansion and Functional Diversification of Histidine Decarboxylases in Tomato

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    Rahul Kumar

    2016-03-01

    Full Text Available Pyridoxal phosphate (PLP-dependent enzymes are one of the most important enzymes involved in plant N metabolism. Here, we explored the evolution of group II PLP-dependent decarboxylases (PLP_deC, including aromatic L-amino acid decarboxylase, glutamate decarboxylase, and histidine decarboxylase in the plant lineage. Gene identification analysis revealed a higher number of genes encoding PLP_deC in higher plants than in lower plants. Expression profiling of PLP_deC orthologs and syntelogs in (L. Heynh., pepper ( L., and tomato ( L. pointed toward conserved as well as distinct roles in developmental processes such as fruit maturation and ripening and abiotic stress responses. We further characterized a putative promoter of tomato ripening-associated gene ( operating in a complex regulatory circuit. Our analysis provides a firm basis for further in-depth exploration of the PLP_deC gene family, particularly in the economically important Solanaceae family.

  13. Moessbauer spectroscopic evidence on the heme binding to the proximal histidine in unfolded carbonmonoxy myoglobin by guanidine hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Harami, Taikan, E-mail: harami.taikan@jaea.go.jp [Japan Atomic Energy Agency (Japan); Kitao, Shinji; Kobayashi, Yasuhiro [Kyoto University, Research Reactor Institute (Japan); Mitsui, Takaya [Japan Atomic Energy Agency (Japan)

    2008-01-15

    The unfolded heme structure in myoglobin is controversial because of no chance of direct X-ray structure analyses. The unfolding of carbonmonoxy myoglobin (MbCO) by guanidine hydrochloride (GdnHCl) was studied by the Moessbauer spectroscopy. The spectra show the presence of a sort of spectrum in the unfolded MbCO, independent on the concentration of GdnHCl from 1 to 6 M and the increase of the fraction of unfolded MbCO, depending on the GdnHCl concentration. The isomer shift of the iron of heme in the unfolded MbCO was identified to be different from that of the native MbCO as the globin structure in Mb collapses under the unfolded conditions. This result and the existing related Moessbauer data proved that the heme in the unfolded MbCO may remain coordinated to the proximal histidine.

  14. Crystal Structures of Trypanosoma cruzi UDP-Galactopyranose Mutase Implicate Flexibility of the Histidine Loop in Enzyme Activation

    Energy Technology Data Exchange (ETDEWEB)

    Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle; Sobrado, Pablo; Tanner, John J. (Virginia Tech); (UMC)

    2012-11-01

    Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitor design. Activation of the enzyme via reduction of the FAD induces profound conformational changes, including a 2.3 {angstrom} movement of the histidine loop (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and cooperative movement of residues located on the si face of the FAD. Interestingly, these changes are substantially different from those described for Aspergillus fumigatus UGM, which is 45% identical to T. cruzi UGM. The importance of Gly61 and His62 for enzymatic activity was studied with the site-directed mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic efficiency by factors of 10-50, primarily by decreasing k{sub cat}. Considered together, the structural, kinetic, and sequence data suggest that the middle Gly of the histidine loop imparts flexibility that is essential for activation of eukaryotic UGMs. Our results provide new information about UGM biochemistry and suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic pathogens.

  15. Crystal structures of Trypanosoma cruzi UDP-galactopyranose mutase implicate flexibility of the histidine loop in enzyme activation.

    Science.gov (United States)

    Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle; Sobrado, Pablo; Tanner, John J

    2012-06-19

    Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitor design. Activation of the enzyme via reduction of the FAD induces profound conformational changes, including a 2.3 Å movement of the histidine loop (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and cooperative movement of residues located on the si face of the FAD. Interestingly, these changes are substantially different from those described for Aspergillus fumigatus UGM, which is 45% identical to T. cruzi UGM. The importance of Gly61 and His62 for enzymatic activity was studied with the site-directed mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic efficiency by factors of 10-50, primarily by decreasing k(cat). Considered together, the structural, kinetic, and sequence data suggest that the middle Gly of the histidine loop imparts flexibility that is essential for activation of eukaryotic UGMs. Our results provide new information about UGM biochemistry and suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic pathogens.

  16. Circumvention of P-gp and MRP2 mediated efflux of lopinavir by a histidine based dipeptide prodrug.

    Science.gov (United States)

    Mandal, Abhirup; Pal, Dhananjay; Mitra, Ashim K

    2016-10-15

    This study was aimed to develop a novel Histidine-Leucine-Lopinavir (His-Leu-LPV) dipeptide prodrug and evaluate its potential for circumvention of P-gp and MRP2-mediated efflux of lopinavir (LPV) indicated for HIV-1 infection. His-Leu-LPV was synthesized following esterification of hydroxyl group of LPV and was identified by (1)H NMR and LCMS/MS techniques. Aqueous solubility, stability and cell cytotoxicity of prodrug was determined. Uptake and permeability studies were carried out using P-gp (MDCK-MDR1) and MRP2 (MDCK-MRP2) transfected cell lines. To further delineate prodrug uptake, prodrug interaction with influx transporters (PepT1 and PHT1) was determined. Enzymatic hydrolysis and reconversion of His-Leu-LPV to LPV was examined using Caco-2 cell homogenates. Aqueous solubility generated by the prodrug was markedly higher relative to unmodified LPV. Importantly, His-Leu-LPV displayed significantly lower affinity towards P-gp and MRP2 as evident from higher uptake and transport rates. [3H]-GlySar and [3H]-l-His uptake receded to approximately 30% in the presence of His-Leu-LPV supporting the PepT1/PHT1 mediated uptake process. A steady regeneration of LPV and Leu-LPV in Caco-2 cell homogenates indicated His-Leu-LPV undergoes both esterase and peptidase-mediated hydrolysis. Histidine based dipeptide prodrug approach can be an alternative strategy to improve LPV absorption across poorly permeable intestinal barrier. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Sensor histidine kinase is a β-lactam receptor and induces resistance to β-lactam antibiotics.

    Science.gov (United States)

    Li, Lu; Wang, Qiyao; Zhang, Hui; Yang, Minjun; Khan, Mazhar I; Zhou, Xiaohui

    2016-02-09

    β-Lactams disrupt bacterial cell wall synthesis, and these agents are the most widely used antibiotics. One of the principle mechanisms by which bacteria resist the action of β-lactams is by producing β-lactamases, enzymes that degrade β-lactams. In Gram-negative bacteria, production of β-lactamases is often induced in response to the antibiotic-associated damage to the cell wall. Here, we have identified a previously unidentified mechanism that governs β-lactamase production. In the Gram-negative enteric pathogen Vibrio parahaemolyticus, we found a histidine kinase/response regulator pair (VbrK/VbrR) that controls expression of a β-lactamase. Mutants lacking either VbrK or VbrR do not produce the β-lactamase and are no longer resistant to β-lactam antibiotics. Notably, VbrK autophosphorylation is activated by β-lactam antibiotics, but not by other lactams. However, single amino acid substitutions in the putative periplasmic binding pocket of VbrK leads its phosphorylation in response to both β-lactam and other lactams, suggesting that this kinase is a β-lactam receptor that can directly detect β-lactam antibiotics instead of detecting the damage to cell wall resulting from β-lactams. In strong support of this idea, we found that purified periplasmic sensor domain of VbrK binds penicillin, and that such binding is critical for VbrK autophosphorylation and β-lactamase production. Direct recognition of β-lactam antibiotics by a histidine kinase receptor may represent an evolutionarily favorable mechanism to defend against β-lactam antibiotics.

  18. An active site aromatic triad in Escherichia coli DNA Pol IV coordinates cell survival and mutagenesis in different DNA damaging agents.

    Directory of Open Access Journals (Sweden)

    Ryan W Benson

    Full Text Available DinB (DNA Pol IV is a translesion (TLS DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N(2-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ, a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site "aromatic triad", namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS. Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent.

  19. CD and MCD of CytC3 and taurine dioxygenase: role of the facial triad in alpha-KG-dependent oxygenases.

    Science.gov (United States)

    Neidig, Michael L; Brown, Christina D; Light, Kenneth M; Fujimori, Danica Galonić; Nolan, Elizabeth M; Price, John C; Barr, Eric W; Bollinger, J Martin; Krebs, Carsten; Walsh, Christopher T; Solomon, Edward I

    2007-11-21

    The alpha-ketoglutarate (alpha-KG)-dependent oxygenases are a large and diverse class of mononuclear non-heme iron enzymes that require FeII, alpha-KG, and dioxygen for catalysis with the alpha-KG cosubstrate supplying the additional reducing equivalents for oxygen activation. While these systems exhibit a diverse array of reactivities (i.e., hydroxylation, desaturation, ring closure, etc.), they all share a common structural motif at the FeII active site, termed the 2-His-1-carboxylate facial triad. Recently, a new subclass of alpha-KG-dependent oxygenases has been identified that exhibits novel reactivity, the oxidative halogenation of unactivated carbon centers. These enzymes are also structurally unique in that they do not contain the standard facial triad, as a Cl- ligand is coordinated in place of the carboxylate. An FeII methodology involving CD, MCD, and VTVH MCD spectroscopies was applied to CytC3 to elucidate the active-site structural effects of this perturbation of the coordination sphere. A significant decrease in the affinity of FeII for apo-CytC3 was observed, supporting the necessity of the facial triad for iron coordination to form the resting site. In addition, interesting differences observed in the FeII/alpha-KG complex relative to the cognate complex in other alpha-KG-dependent oxygenases indicate the presence of a distorted 6C site with a weak water ligand. Combined with parallel studies of taurine dioxygenase and past studies of clavaminate synthase, these results define a role of the carboxylate ligand of the facial triad in stabilizing water coordination via a H-bonding interaction between the noncoordinating oxygen of the carboxylate and the coordinated water. These studies provide initial insight into the active-site features that favor chlorination by CytC3 over the hydroxylation reactions occurring in related enzymes.

  20. Evaluation of the U.S. strategic nuclear triad. Hearing before the Committee on Governmental Affairs, United States Senate, One Hundred Third Congress, First Session, June 10, 1993

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    These hearings address the issue of the US nuclear deterrent bassed on a triad of land-based, air-based, and sea-based ability to deliver nuclear weapons and how the decisions about such a policy were made. The goal is to apply this information to consideration about new weapons systems. Testimony is from the following: Chelimsky, General Accounting Office; Perry, Deputy Secretary of Defense. Written testimony and documents comprise a large part of the hearing

  1. A sulfhydryl-reactive ruthenium (II complex and its conjugation to protein G as a universal reagent for fluorescent immunoassays.

    Directory of Open Access Journals (Sweden)

    Jing-Tang Lin

    Full Text Available To develop a fluorescent ruthenium complex for biosensing, we synthesized a novel sulfhydryl-reactive compound, 4-bromophenanthroline bis-2,2'-dipyridine Ruthenium bis (hexafluorophosphate. The synthesized Ru(II complex was crosslinked with thiol-modified protein G to form a universal reagent for fluorescent immunoassays. The resulting Ru(II-protein G conjugates were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. The emission peak wavelength of the Ru(II-protein G conjugate was 602 nm at the excitation of 452 nm which is similar to the spectra of the Ru(II complex, indicating that Ru(II-protein G conjugates still remain the same fluorescence after conjugation. To test the usefulness of the conjugate for biosensing, immunoglobulin G (IgG binding assay was conducted. The result showed that Ru(II-protein G conjugates were capable of binding IgG and the more cross-linkers to modify protein G, the higher conjugation efficiency. To demonstrate the feasibility of Ru(II-protein G conjugates for fluorescent immunoassays, the detection of recombinant histidine-tagged protein using the conjugates and anti-histidine antibody was developed. The results showed that the histidine-tagged protein was successfully detected with dose-response, indicating that Ru(II-protein G conjugate is a useful universal fluorescent reagent for quantitative immunoassays.

  2. Examination of correlation between histidine and nickel absorption by Morus L., Robinia pseudoacacia L. and Populus nigra L. using HPLC-MS and ICP-MS.

    Science.gov (United States)

    Ozen, Sukran Akkus; Yaman, Mehmet

    2016-08-02

    In this study, HPLC-MS and ICP-MS methods were used for the determination of histidine and nickel in Morus L., Robinia pseudoacacia L., and Populus nigra L. leaves taken from industrial areas including Gaziantep and Bursa cities. In the determination of histidine by HPLC-MS, all of the system parameters such as flow rate of mobile phase, fragmentor potential, injection volume and column temperature were optimized and found to be 0.2 mL min(-1), 70 V, 15 µL, and 20°C, respectively. Under the optimum conditions, histidine was extracted from plant sample by distilled water at 90°C for 30 min. Concentrations of histidine as mg kg(-1) were found to be between 2-9 for Morus L., 6-13 for Robinia pseudoacacia L., and 2-10 for Populus nigra L. Concentrations of nickel were in the ranges of 5-10 mg kg(-1) for Morus L., 3-10 mg kg(-1) for Robinia pseudoacacia L., and 0.6-4 mg kg(-1) for Populus nigra L. A significant linear correlation (r = 0.78) between histidine and Ni was observed for Populus nigra L., whereas insignificant linear correlation for Robinia pseudoacacia L. (r = 0.22) were seen. Limits of detection (LOD) and quantitation (LOQ) were found to be 0.025 mg Ni L(-1) and 0.075 mg Ni L(-1), respectively.

  3. Real-Time Remediation Utilizing The Backpack Sodium Iodide System And The U.S. EPA Triad Approach

    International Nuclear Information System (INIS)

    John R. Giles; Michael V. Carpenter; Lyle G. Roybal; C. P. Oertel; J. J. Jacobson; D. L. Eaton; G. L. Schwendiman

    2006-01-01

    Real-time characterization during remediation activities is being accomplished at the Idaho National Laboratory (INL) with the use of the backpack sodium iodide system (BaSIS). The BaSIS is comprised of a 3-in. by 5-in. sodium iodide (NaI) detector, differential corrected global positioning system (GPS), and portable computer, integrated into a lightweight backpack deployment platform. The system is operated with specialized software that allows the operator and/or remediation field manager to view data as they are collected. Upon completion of planned excavation stages, the area is surveyed for residual radiological contamination. After data collection is complete, data is available to the remediation field manager as a contour map showing the area(s) that require further excavation. The use of real-time measurement systems, rapid turn-around time of data, and dynamic work strategy support the U.S. Environmental Protection Agency's (EPA) Triad approach. Decisions are made in real-time as to the need for further remediation. This paper describes the BaSIS system calibration, testing and use, and outlines negotiations with the appropriate CERCLA regulatory agencies (U.S. Environmental Protection Agency, Idaho Department of Environmental Quality, and U.S. Department of Energy Idaho Operations Office) to allow the use of real-time instrumentation during the remediation process, and for confirmation surveys. By using the BaSIS in such a manner, the INL seeks to demonstrate compliance with remediation objectives

  4. The triad Zeus, Herakles and Dionysos a contribution to the study of ancient cults in upper Moesia

    Directory of Open Access Journals (Sweden)

    Pilipović Sanja

    2008-01-01

    Full Text Available The triad Zeus, Herakles and Dionysos has been attested in Upper Moesia by the relief from the village of Bukovo near Negotin, eastern Serbia. The Roman supreme god was frequently shown in association with other deities but the presence of Bacchus and Hercules in such associations is Greek rather than Roman in origin. The association of Liber and Hercules was promoted by the emperor Septimius Severus, a native of the city of Leptis Magna whose patron gods were concurrently Liber and Hercules. Septimius even granted the dii patrii a sort of official recognition as patrons of the dynasty he founded. The village of Bukovo where the relief was found had not been known as an archaeological site. There is no specific evidence for the worship of Jupiter in that area, while the worship of Herakles is attested on the sites of Rovine and Tamnič near Negotin. The relief is close to north-Macedonian reliefs in style, and reflects Hellenistic and Thracian influence in associating the cults of Dionysos and Herakles. The depicted deities are compatible and close to Septimius Severus’ official religion. The central position of the supreme god indicates his importance as well as the fact that the other two deities are associated to him, as his children patrons of nature and fertility in the underground and aboveground worlds. It is also important to note that the relief confirms Hellenistic religious influences in the area of the Upper Moesian limes.

  5. Design and synthesis of bipyridine platinum(II) bisalkynyl fullerene donor-chromophore-acceptor triads with ultrafast charge separation.

    Science.gov (United States)

    Lee, Sai-Ho; Chan, Chris Tsz-Leung; Wong, Keith Man-Chung; Lam, Wai Han; Kwok, Wai-Ming; Yam, Vivian Wing-Wah

    2014-07-16

    Donor-chromophore-acceptor triads, (PTZ)2-Pt(bpy)-C60 and ((t)BuPTZ)2-Pt(bpy)-C60, along with their model compound, (Ph)2-Pt(bpy)-C60, have been synthesized and characterized; their photophysical and electrochemical properties have been studied, and the origin of the absorption and emission properties has been supported by computational studies. The photoinduced electron transfer reactions have been investigated using the femtosecond and nanosecond transient absorption spectroscopy. In dichloromethane, (Ph)2-Pt(bpy)-C60 shows ultrafast triplet-triplet energy transfer from the (3)MLCT/LLCT excited state within 4 ps to give the (3)C60* state, while in (PTZ)2-Pt(bpy)-C60 and ((t)BuPTZ)2-Pt(bpy)-C60, charge-separated state forms within 400 fs from the (3)MLCT/LLCT excited state with efficiency of over 0.90, and the total efficiency with the contribution of (3)C60* is estimated to be 0.99. Although the forward electron transfer reactions are very rapid, the charge-separated state recombines to the singlet ground state at a time of hundreds of nanoseconds because of the difference in spin multiplicity between the charge-separated state and the ground state.

  6. The Membrane Topology of ALMT1, an Aluminum-Activated Malate Transport Protein in Wheat (Triticum aestivum)

    OpenAIRE

    Motoda, Hirotoshi; Sasaki, Takayuki; Kano, Yoshio; Ryan, Peter R; Delhaize, Emmanuel; Matsumoto, Hideaki; Yamamoto, Yoko

    2007-01-01

    The wheat ALMT1 gene encodes an aluminum (Al)-activated malate transport protein which confers Al-resistance. We investigated the membrane topology of this plasma-membrane localized protein with immunocytochemical techniques. Several green fluorescent protein (GFP)-fused and histidine (His)-tagged chimeras of ALMT1 were prepared based on a computer-predicted secondary structure and transiently expressed in cultured mammalian cells. Antibodies raised to polypeptide epitopes of ALMT1 were used ...

  7. Effects of rumen-protected methionine, lysine, and histidine on lactation performance of dairy cows.

    Science.gov (United States)

    Giallongo, F; Harper, M T; Oh, J; Lopes, J C; Lapierre, H; Patton, R A; Parys, C; Shinzato, I; Hristov, A N

    2016-06-01

    The objective of this study was to evaluate the effects of supplementing a metabolizable protein (MP)-deficient diet with rumen-protected (RP) Met, Lys, and His, individually or combined, on the performance of lactating dairy cows. The experiment was a 9-wk randomized complete block design with 72 Holstein cows. Following a 2-wk covariate period, cows were blocked by days in milk, milk yield, and parity, and randomly assigned to 1 of the following 6 treatments: (1) MP-adequate diet [MPA; +243g/d MP balance, according to the National Research Council (2001) requirements]; (2) MP-deficient diet (MPD; -54g/d MP balance); (3) MPD supplemented with RPMet (MPDM); (4) MPD supplemented with RPLys (MPDL); (5) MPD supplemented with RPHis (MPDH); and (6) MPD supplemented with RPMet, RPLys, and RPHis (MPDMLH). Dry matter intake (DMI), yields of milk and milk components (fat, protein, lactose) and energy-corrected milk (ECM), feed and ECM feed efficiencies, and milk and plasma urea N were decreased by MPD, compared with MPA. Supplementation of the MPD diet with RPLys increased milk protein content and plasma glucose concentration and tended to increase milk urea N. Addition of RPHis tended to increase DMI, increased milk protein concentration, and numerically increased yields of milk fat, protein, and ECM. In addition to the trends for increased DMI and milk fat content, and higher milk protein concentration, supplementation of the 3 RP AA also increased yields of milk fat, protein, and ECM and ECM feed efficiency. Relative to MPA, milk N efficiency tended to be increased by MPD. Concentrations of plasma essential AA (except Met and Thr) were decreased by MPD compared with MPA. Supplementation of RPMet, RPLys, and RPHis increased plasma Met (except for MPDM), Lys, and His concentrations, respectively. Cows fed MPD had lower blood hemoglobin concentration and numerically higher plasma ghrelin than cows fed MPA. Concentration of total saturated fatty acids in milk fat were or

  8. Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Kurt A. Jellinger

    2011-01-01

    Full Text Available Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious.

  9. Heteronuclear 2D (1H-13C) MAS NMR Resolves the Electronic Structure of Coordinated Histidines in Light-Harvesting Complex II: Assessment of Charge Transfer and Electronic Delocalization Effect

    International Nuclear Information System (INIS)

    Matysik, Joerg; Boer, Ido de; Gast, Peter; Gorkom, Hans J. van; Groot, Huub J.M. de

    2004-01-01

    In a recent MAS NMR study, two types of histidine residues in the light-harvesting complex II (LH2) of Rhodopseudomonas acidophila were resolved: Type 1 (neutral) and Type 2 (positively charged) (Alia et al. J. Am. Chem. Soc.). The isotropic 13 C shifts of histidines coordinating to B850 BChl a are similar to fully positively charged histidine, while the 15 N shift anisotropy shows a predominantly neutral character. In addition the possibility that the ring currents are quenched by overlap in the superstructure of the complete ring of 18 B850 molecules in the LH2 complex could not be excluded. In the present work, by using two-dimensional heteronuclear ( 1 H- 13 C) dipolar correlation spectroscopy with phase-modulated Lee-Goldburg homonuclear 1 H decoupling applied during the t 1 period, a clear and unambiguous assignment of the protons of histidine interacting with the magnesium of a BChl a molecule is obtained and a significant ring current effect from B850 on the coordinating histidine is resolved. Using the ring current shift on 1 H, we refine the 13 C chemical shift assignment of the coordinating histidine and clearly distinguish the electronic structure of coordinating histidines from that of fully positively charged histidine. The DFT calculations corroborate that the coordinating histidines carry ∼0.2 electronic equivalent of positive charge in LH2. In addition, the data indicate that the ground state electronic structures of individual BChl a/His complexes is largely independent of supermolecular π interactions in the assembly of 18 B850 ring in LH2

  10. Mechanisms of High Temperature Resistance of Synechocystis sp. PCC 6803: An Impact of Histidine Kinase 34

    Czech Academy of Sciences Publication Activity Database

    Červený, Jan; Sinětova, M. A.; Zavřel, Tomáš; Los, D. A.

    2015-01-01

    Roč. 5, č. 1 (2015), s. 676-699 ISSN 2075-1729 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MŠk(CZ) EE2.3.20.0256; GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : photosynthesis * pigments * ultrastructure * heat stress proteins * photobioreactor * cyanobacteria Subject RIV: EH - Ecology, Behaviour

  11. Specific association of growth-associated protein 43 with calcium release units in skeletal muscles of lower vertebrates

    Directory of Open Access Journals (Sweden)

    G.A. Caprara

    2014-10-01

    Full Text Available Growth-associated protein 43 (GAP43, is a strictly conserved protein among vertebrates implicated in neuronal development and neurite branching. Since GAP43 structure contains a calmodulin-binding domain, this protein is able to bind calmodulin and gather it nearby membrane network, thus regulating cytosolic calcium and consequently calcium-dependent intracellular events. Even if for many years GAP43 has been considered a neuronal-specific protein, evidence from different laboratories described its presence in myoblasts, myotubes and adult skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized between calcium release units (CRUs and mitochondria in mammalian skeletal muscle suggesting that, also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis. However, the previous studies could not clearly distinguish between a mitochondrion- or a triad-related positioning of GAP43. To solve this question, the expression and localization of GAP43 was studied in skeletal muscle of Xenopus and Zebrafish known to have triads located at the level of the Z-lines and mitochondria not closely associated with them. Western blotting and immunostaining experiments revealed the expression of GAP43 also in skeletal muscle of lower vertebrates (like amphibians and fishes, and that the protein is localized closely to the triad junction. Once more, these results and GAP43 structural features, support an involvement of the protein in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species.

  12. UVA photolysis using the protein-bound sensitizers present in human lens

    International Nuclear Information System (INIS)

    Ortwerth, B.J.; Olesen, P.R.

    1994-01-01

    This research was undertaken to demonstrate that the protein-bound chromophores in aged human lens can act as sensitizers for protein damage by UVA light. The water-insoluble (WI) proteins from pooled human and bovine lenses were solubilized by sonication in water and illuminated with UV light similar in output to that transmitted by the cornea. Analysis of the irradiated proteins showed a linear decrease in sulfhydryl groups with a 30% loss after 2 h. No loss was seen when native α-crystallin was irradiated under the same conditions. A 25% loss of histidine residues was also observed with the human lens WI fraction, and sodium dodecyl sulfate polyacrylamide gels indicated considerable protein cross-linking. Similar photodamage was seen with a WI fraction from old bovine lenses. While the data show the presence of UVA sensitizers, some histidine destruction and protein cross-linking were also obtained with α-crystallin and with lysozyme which argue that part of the histidine loss in the human WISS was likely due to tryptophan acting as a sensitizer. (Author)

  13. Role of allosteric switch residue histidine 195 in maintaining active-site asymmetry in presynaptic filaments of bacteriophage T4 UvsX recombinase.

    Science.gov (United States)

    Farb, Joshua N; Morrical, Scott W

    2009-01-16

    Recombinases of the highly conserved RecA/Rad51 family play central roles in homologous recombination and DNA double-stranded break repair. RecA/Rad51 enzymes form presynaptic filaments on single-stranded DNA (ssDNA) that are allosterically activated to catalyze ATPase and DNA strand-exchange reactions. Information is conveyed between DNA- and ATP-binding sites, in part, by a highly conserved glutamine residue (Gln194 in Escherichia coli RecA) that acts as an allosteric switch. The T4 UvsX protein is a divergent RecA ortholog and contains histidine (His195) in place of glutamine at the allosteric switch position. UvsX and RecA catalyze similar strand-exchange reactions, but differ in other properties. UvsX produces both ADP and AMP as products of its ssDNA-dependent ATPase activity--a property that is unique among characterized recombinases. Details of the kinetics of ssDNA-dependent ATP hydrolysis reactions indicate that UvsX-ssDNA presynaptic filaments are asymmetric and contain two classes of ATPase active sites: one that generates ADP, and another that generates AMP. Active-site asymmetry is reduced by mutations at the His195 position, since UvsX-H195Q and UvsX-H195A mutants both exhibit stronger ssDNA-dependent ATPase activity, with lower cooperativity and markedly higher ADP/AMP product ratios, than wild-type UvsX. Reduced active-site asymmetry correlates strongly with reduced ssDNA-binding affinity and DNA strand-exchange activity in both H195Q and H195A mutants. These and other results support a model in which allosteric switch residue His195 controls the formation of an asymmetric conformation of UvsX-ssDNA filaments that is active in DNA strand exchange. The implications of our findings for UvsX recombination functions, and for RecA functions in general, are discussed.

  14. Anthropogenic pollutants affect ecosystem services of freshwater sediments. The need for a 'triad plus x' approach

    Energy Technology Data Exchange (ETDEWEB)

    Gerbersdorf, Sabine Ulrike; Wieprecht, Silke [Stuttgart Univ. (Germany). Dept. of Hydraulic Engineering and Water Resources Management; Hollert, Henner; Brinkmann, Markus [RWTH Aachen Univ. (Germany). Dept. of Ecosystem Analysis; Schuettrumpf, Holger [RWTH Aachen Univ. (Germany). Inst. of Hydraulic Engineering and Water Resources Management; Manz, Werner [Koblenz-Landau Univ., Koblenz (Germany). Inst. for Integrated Natural Sciences

    2011-09-15

    Purpose: Freshwater sediments and their attached microbial communities (biofilms) are essential features of rivers and lakes, providing valuable ecosystem services such as nutrient recycling or self-purification which extend beyond the aquatic environment. Anthropogenic pollutants, whether from the industrial era or as a result of our contemporary lifestyles, can negatively affect these functions with hitherto unknown consequences on ecology, the economy and human health. Thus far, the singular view of the involved disciplines such as ecotoxicology, environmental microbiology, hydrology and geomorphology has prevented a deeper understanding of this emerging issue. Main features: This paper discusses briefly the progressions and the state-of-the-art methods within the disciplines of concern related to contaminated sediments, ranging from ecotoxicological test systems, microbiological/molecular approaches to unravel changes of microbial ecosystems, up to the modelling of sediment transport and sorption/desorption of associated pollutants. The first bilateral research efforts on contaminated sediments include efforts to assess ecotoxicological sediment risk including sediment mobility (i.e. ecotoxicology and engineering), enhance bioremediation potential (i.e. microbiology and ecotoxicology) or to understand biostabilisation processes of sediments by microbial assemblages (i.e. microbiology and engineering). Conclusions and perspectives: In freshwater habitats, acute, chronic and mechanism-specific toxic effects on organisms, shifts in composition, structure and functionality of benthic microbial communities, as well as the obstruction of important ecosystem services by continuously discharged and long-deposited pollutants, should be related to the in situ sediment dynamics. To achieve an improved understanding of the ecology of freshwater sediments and the impairment of their important ecosystem functions by human-derived pollutants, we suggest a 'triad plus x

  15. The employee retention triad in health care: Exploring relationships amongst organisational justice, affective commitment and turnover intention.

    Science.gov (United States)

    Perreira, Tyrone A; Berta, Whitney; Herbert, Monique

    2018-04-01

    To increase understanding of the relationships between organisational justice, affective commitment and turnover intention in health care. Turnover in health care is a serious concern, as it contributes to the global nursing shortage and is associated with declines in quality of care, patient safety and patient outcomes. Turnover also impacts care teams and is associated with decreased staff cohesion and morale. A survey was developed and administered to frontline nurses working in the Province of Ontario, Canada. The data were used to test a hypothetical model developed from a review of the literature. The relationships amongst the three constructs were evaluated using structural equation modelling and mediation analysis. The hypothesised model was generally supported, although we were limited to considerations of interpersonal justice, affective commitment to one's organisation and turnover intention. Interpersonal justice is associated with affective commitment to one's organisation, which is negatively associated with turnover intention. Interpersonal justice was also found to be directly and negatively associated with turnover intention. Affective commitment to one's organisation was also found to mediate the relationship between interpersonal justice and turnover intention. The examination of relationships within the "employee retention triad" in a single, comprehensive model is novel and provides new information regarding relational complexity and insights into what healthcare leaders can do to retain employees. Reducing turnover may help to decrease some of the stressors related to turnover for clinical staff remaining at the organisation such as constant onboarding and orientation of new hires, working with less experienced staff and increased workload due to decreased staffing. © 2018 John Wiley & Sons Ltd.

  16. ANOTHER "LETHAL TRIAD"-RISK FACTORS FOR VIOLENT INJURY AND LONG-TERM MORTALITY AMONG ADULT VICTIMS OF VIOLENT INJURY.

    Science.gov (United States)

    Laytin, Adam D; Shumway, Martha; Boccellari, Alicia; Juillard, Catherine J; Dicker, Rochelle A

    2018-04-14

    Mental illness, substance abuse, and poverty are risk factors for violent injury, and violent injury is a risk factor for early mortality that can be attenuated through hospital-based violence intervention programs. Most of these programs focus on victims under the age of 30 years. Little is known about risk factors or long-term mortality among older victims of violent injury. To explore the prevalence of risk factors for violent injury among younger (age < 30 years) and older (age 30 ≥ years) victims of violent injury, to determine the long-term mortality rates in these age groups, and to explore the association between risk factors for violent injury and long-term mortality. Adults with violent injuries were enrolled between 2001 and 2004. Demographic and injury data were recorded on enrollment. Ten-year mortality rates were measured. Descriptive analysis and logistic regression were used to compare older and younger subjects. Among 541 subjects, 70% were over age 30. The overall 10-year mortality rate was 15%, and was much higher than in the age-matched general population in both age groups. Risk factors for violent injury including mental illness, substance abuse, and poverty were prevalent, especially among older subjects, and were each independently associated with increased risk of long-term mortality. Mental illness, substance abuse, and poverty constitute a "lethal triad" that is associated with an increased risk of long-term mortality among victims of violent injury, including both younger adults and those over age 30 years. Both groups may benefit from targeted risk-reduction efforts. Emergency department visits offer an invaluable opportunity to engage these vulnerable patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Integrating the fish embryo toxicity test as triad element for sediment toxicity assessment based on the water framework directive approach

    Energy Technology Data Exchange (ETDEWEB)

    Bartzke, Mariana [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany); Gobio GmbH, Aarbergen/Kettenbach (Germany); Dept. Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research, UFZ, Leipzig (Germany); Delov, Vera [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany); Gobio GmbH, Aarbergen/Kettenbach (Germany); Ecotoxicology, Fraunhofer Inst. for Molecular Biology and Applied Ecology IME, Aachen (Germany); Stahlschmidt-Allner, Petra; Allner, Bernhard [Gobio GmbH, Aarbergen/Kettenbach (Germany); Oehlmann, Joerg [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany)

    2010-04-15

    Purpose: The objective of this study was to complement analyses according to the European Union Water Framework Directive (WFD) with a sediment toxicity analysis as part of an integrated river assessment. To this end, Hessian water courses were analyzed using the sediment quality triad concept according to Chapman with chemical analyses, in situ effect evaluations, and ecotoxicological assessments. For the ecotoxicological assessment (fish embryo toxicity test with Danio rerio), a new evaluation scheme was developed, the fish teratogenicity index (FTI), that allows for a classification of sediments into ecological quality classes compliant to the WFD. Materials and methods sediment and macrozoobenthos samples were taken from tributaries of the rivers Fulda and Lahn. Sediments were characterized regarding particle size, carbon, heavy metals, and polyaromatic hydrocarbon content. Macroinvertebrate samples were taken via multi-habitat sampling. The fish embryo toxicity test with D. rerio was conducted as a contact assay on the basis of DIN 38415-6. Results and discussion The integrated assessment indicated a significant influence of heavy metals and carbon content on macroinvertebrate communities. The bioaccessibility of sediment pollutants were clearly demonstrated by the FTI, which showed a wide range of adverse effects. A significant linear relationship between metals and the FTI was detected. However, there was no statistically significant evidence that macroinvertebrate communities were affected by the hydromorphological quality clements at the sampling sites. Conclusions The new scheme for the assessment of fish embryo toxicity test was successfully applied. The results suggest that sediment compounds impact macroinvertebrate communities and early development of fish. It demonstrates that the quality of sediments should be evaluated on a routine basis as part of an integrated river assessment. (orig.)

  18. Reaction of protein chloramines with DNA and nucleosides

    DEFF Research Database (Denmark)

    Hawkins, Clare Louise; Pattison, David I; Davies, Michael Jonathan

    2002-01-01

    Stimulated phagocyte cells produce the oxidant HOCl, via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is important in bacterial cell killing, but excessive or misplaced generation can damage the host tissue and may lead to the development of certain diseases such as cance......, 50-80% of the HOCl is predicted to react with histone lysine and histidine residues to yield chloramines. The yield and stability of such chloramines predicted by these modelling studies agrees well with experimental data. Decomposition of these species gives protein-derived, nitrogen......-centred radicals, probably on the lysine side chains, as characterized by the EPR and spin-trapping experiments. It is shown that isolated lysine, histidine, peptide and protein chloramines can react with plasmid DNA to cause strand breaks. The protection against such damage afforded by the radical scavengers...... to give nucleobase radicals. Further evidence for the formation of such covalent cross-links has been obtained from experiments performed using (3)H-lysine and (14)C-histidine chloramines. These results are consistent with the predictions of the kinetic model and suggest that histones are major targets...

  19. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of AHP2, a signal transmitter protein from Arabidopsis thaliana

    Czech Academy of Sciences Publication Activity Database

    Degtjarik, O.; Dopitová, R.; Puehringer, S.; Nejedlá, E.; Kutý, Michal; Weiss, M.S.; Hejatko, J.; Janda, L.; Kutá-Smatanová, Ivana

    2013-01-01

    Roč. 69, FEB 2013 (2013), s. 158-161 ISSN 1744-3091 Institutional support: RVO:67179843 Keywords : AHP2 * Arabidopsis thaliana * histidine phosphotransfer proteins * multi-step phosphorelay Subject RIV: CE - Biochemistry Impact factor: 0.568, year: 2013

  20. High quality protein microarray using in situ protein purification

    Directory of Open Access Journals (Sweden)

    Fleischmann Robert D

    2009-08-01

    Full Text Available Abstract Background In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC. This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. Results Two slide surfaces were examined, chelated Cu2+ slides suspended on a polyethylene glycol (PEG coating and chelated Ni2+ slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu2+ slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents

  1. Neighbor-Directed Histidine N (s)–Alkylation: A Route to Imidazolium-Containing Phosphopeptide Macrocycles-Biopolymers | Center for Cancer Research

    Science.gov (United States)

    Our recently discovered, selective, on-resin route to N(s)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation.

  2. Combustion energies and standard molar enthalpies of formation for the complexes of the first-row transitional metal chlorides with L-α-histidine

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Seven novel solid complexes of the first-row transitional metal with L-α-histidine were synthesized, and their compositions were determined. The constant-volume combustion energies of the complexes were measured by a precision rotation bomb calorimeter. The standard molar enthalpies of combustion and the standard molar enthalpies of formation were calculated. The results indicated thatthe plots of the standard enthalpies of formation against the atomic number of the metal show a regularity of zigzag.

  3. EPR and optical investigation of Mn2+ doped L-histidine-4-nitrophenolate 4-nitrophenol single crystal

    Science.gov (United States)

    Prabakaran, R.; Subramanian, P.

    2018-04-01

    Single crystals of L-histidine-4-nitrophenolate 4-nitrophenol[LHFNP] complex doped with Mn2+ were grown by the slow evaporation method at room temperature. The EPR spectrum reveals the entry of one Mn2+ ion in the lattice. The angular variation plot was drawn between the angles and the magnetic field position. The spin Hamiltonian parameters were obtained by EPR-NMR program. The D and E values show the rhombic field around the ion and is an interstitial one. The g value obtained here suggests that the Mn2+ ion experiences a strong field and there is a transfer of electron from the metal ion to the ligand atom. The optical absorption study shows various bands and are assigned to the transition from the ground state 6A1g(S). The Racah and crystal field parameters have also been evaluated and fitted to the experimental values. The Racah parameter shows the covalent bonding between the metal ion to the ligand.

  4. Oxygen-independent inactivation of Haemophilus influenzae transforming DNA by monochromatic radiation: action spectrum, effect of histidine and repair

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera-Juarez, E; Setlow, J K; Swenson, P A; Peak, M J

    1976-01-01

    The action spectrum for the oxygen-independent inactivation of native transforming DNA from Haemophilus influenzae with near-uv radiation revealed a shoulder beginning at 334 and extending to 460 nm. The presence of 0.2 M histidine during irradiation produced a small increase in inactivation at 254, 290 and 313 nm, a large increase at 334 nm and a decrease in inactivation at 365, 405, and 460 nm. Photoreactivation did not reverse the DNA damage produced at pH 7.0 at 334, 365, 405 and 460 nm, but did reactivate the DNA after irradiation at 254, 290 and 313 nm. The inactivation of DNA irradiated at 254, 290 and 313 nm was considerably greater when the transforming ability was assayed in an excision-defective mutant compared with the wild type, although DNA irradiated at 334, 365, 405 and 460 nm showed smaller differences. These results suggest that the oxygen-independent inactivation of H. influenzae DNA at pH 7 by irradiation at 334, 365, 405 and 460 nm is caused by lesions other than pyrimidine dimers.

  5. Screening for Methylated Poly(⌊-histidine with Various Dimethylimidazolium/Methylimidazole/Imidazole Contents as DNA Carrier

    Directory of Open Access Journals (Sweden)

    Shoichiro Asayama

    2015-08-01

    Full Text Available Methylated poly(l-histidine (PLH-Me, our original polypeptide, has controlled the contents of dimethylimidazolium, τ/π-methylimidazole and imidazole groups for efficient gene delivery. The screening for the PLH-Me as DNA carrier has been carried out by use of the PLH with 25 mol% (τ-methyl, 16 mol%; π-methyl, 17 mol%; deprotonated imidazole, 41 mol%, 68 mol% (τ-methyl, 16 mol%; π-methyl, 8 mol%; deprotonated imidazole, 8 mol% and 87 mol% (τ-methyl, 7 mol%; π-methyl, 4 mol%; deprotonated imidazole, 2 mol% dimethylimidazolium groups, that is, PLH-Me(25, PLH-Me(68 and PLH-Me(87, respectively. The screening of the chemical structure of PLH-Me has been carried out for DNA carrier properties, which are the stability of its DNA polyion complexes and gene expression. The DNA complexes with the 25 mol% and 68 mol% dimethylated PLH-Me possessed almost same ability to retain DNA, as compared with the 87 mol% dimethylated PLH-Me, which was examined by competitive exchange with dextran sulfate. From the gene transfection experiment against HepG2 cells, human hepatoma cell line, the PLH-Me(25/DNA complex was revealed to mediate highest gene expression. These results suggest that the dimethyl-imidazolium/methylimidazole/imidazole balance of the PLH-Me is important for DNA carrier design.

  6. The histidine transporter SLC15A4 coordinates mTOR-dependent inflammatory responses and pathogenic antibody production.

    Science.gov (United States)

    Kobayashi, Toshihiko; Shimabukuro-Demoto, Shiho; Yoshida-Sugitani, Reiko; Furuyama-Tanaka, Kaori; Karyu, Hitomi; Sugiura, Yuki; Shimizu, Yukiko; Hosaka, Toshiaki; Goto, Motohito; Kato, Norihiro; Okamura, Tadashi; Suematsu, Makoto; Yokoyama, Shigeyuki; Toyama-Sorimachi, Noriko

    2014-09-18

    SLC15A4 is a lysosome-resident, proton-coupled amino-acid transporter that moves histidine and oligopeptides from inside the lysosome to the cytosol of eukaryotic cells. SLC15A4 is required for Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon (IFN-I) productions in plasmacytoid dendritic cells (pDCs) and is involved in the pathogenesis of certain diseases including lupus-like autoimmunity. How SLC15A4 contributes to diseases is largely unknown. Here we have shown that B cell SLC15A4 was crucial for TLR7-triggered IFN-I and autoantibody productions in a mouse lupus model. SLC15A4 loss disturbed the endolysosomal pH regulation and probably the v-ATPase integrity, and these changes were associated with disruption of the mTOR pathway, leading to failure of the IFN regulatory factor 7 (IRF7)-IFN-I regulatory circuit. Importantly, SLC15A4's transporter activity was necessary for the TLR-triggered cytokine production. Our findings revealed that SLC15A4-mediated optimization of the endolysosomal state is integral to a TLR7-triggered, mTOR-dependent IRF7-IFN-I circuit that leads to autoantibody production. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Taxonomia da rede científica do Dark Triad: revelações no meio empresarial e contábil.

    Directory of Open Access Journals (Sweden)

    Márcia Figueredo D\\u2019Souza

    2017-01-01

    Full Text Available Objetivo: Caracterizar a pesquisa científica do Dark Triad, elucidando o direcionamento dessa temática, no contexto empresarial e contábil, no período de 2012 a 2014. Método: Para essa investigação, utilizou-se o levantamento sociobibliométrico como estratégia de pesquisa, com base na observação de conteúdos, em duas fontes: Portal Periódicos Capes e o Web Science Knowledge. A amostra do estudo totalizou 90 artigos e foram ilustrados por redes científicas. Ao final, foi elaborada a taxonomia dos 12 trabalhos que convergiram para a discussão do constructo Dark Triad. Resultados: Sobre o direcionamento dos artigos, o Narcisismo é o mais explorado e associado à liderança e tomada de decisão empresarial. A Psicopatia atrai atenção dos pesquisadores quanto ao comportamento aversivo do líder no meio corporativo. O Maquiavelismo tem maior ênfase em investigações relacionadas à manipulação. Especificamente à área contábil, a maioria associa os traços a comportamentos antiéticos com propensão a fraudes nos relatórios financeiros. Contribuições: Os resultados apontaram oportunidades de pesquisas com os traços do Dark Triad, especialmente pela interdisciplinaridade e relevância científica desta temática, ainda pouco explorado pelos pesquisadores da área contábil. Ademais, merecem a atenção de líderes, no sentido de refletirem suas atitudes e dos seus funcionários no ambiente empresarial.

  8. Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

    Science.gov (United States)

    Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L

    2014-07-04

    Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.

  9. Mechanism of the pH-induced conformational change in the sensor domain of the DraK Histidine kinase via the E83, E105, and E107 residues.

    Science.gov (United States)

    Yeo, Kwon Joo; Hong, Young-Soo; Jee, Jun-Goo; Lee, Jae Kyoung; Kim, Hyo Jeong; Park, Jin-Wan; Kim, Eun-Hee; Hwang, Eunha; Kim, Sang-Yoon; Lee, Eun-Gyeong; Kwon, Ohsuk; Cheong, Hae-Kap

    2014-01-01

    The DraR/DraK two-component system was found to be involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner; however, its function and signaling and sensing mechanisms remain unclear. Here, we describe the solution structure of the extracellular sensor domain of DraK and suggest a mechanism for the pH-dependent conformational change of the protein. The structure contains a mixed alpha-beta fold, adopting a fold similar to the ubiquitous sensor domain of histidine kinase. A biophysical study demonstrates that the E83, E105, and E107 residues have abnormally high pKa values and that they drive the pH-dependent conformational change for the extracellular sensor domain of DraK. We found that a triple mutant (E83L/E105L/E107A) is pH independent and mimics the low pH structure. An in vivo study showed that DraK is essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock. Our findings suggest that the DraR/DraK two-component system plays an important role in the pH regulation of S. coelicolor growth medium. This study provides a foundation for the regulation and the production of secondary metabolites in Streptomyces.

  10. Mechanism of the pH-induced conformational change in the sensor domain of the DraK Histidine kinase via the E83, E105, and E107 residues.

    Directory of Open Access Journals (Sweden)

    Kwon Joo Yeo

    Full Text Available The DraR/DraK two-component system was found to be involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner; however, its function and signaling and sensing mechanisms remain unclear. Here, we describe the solution structure of the extracellular sensor domain of DraK and suggest a mechanism for the pH-dependent conformational change of the protein. The structure contains a mixed alpha-beta fold, adopting a fold similar to the ubiquitous sensor domain of histidine kinase. A biophysical study demonstrates that the E83, E105, and E107 residues have abnormally high pKa values and that they drive the pH-dependent conformational change for the extracellular sensor domain of DraK. We found that a triple mutant (E83L/E105L/E107A is pH independent and mimics the low pH structure. An in vivo study showed that DraK is essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock. Our findings suggest that the DraR/DraK two-component system plays an important role in the pH regulation of S. coelicolor growth medium. This study provides a foundation for the regulation and the production of secondary metabolites in Streptomyces.

  11. Occurrence and formation of endogenous histidine hexa-coordination in cold-adapted hemoglobins.

    Science.gov (United States)

    Merlino, Antonello; Howes, Barry D; Prisco, Guido di; Verde, Cinzia; Smulevich, Giulietta; Mazzarella, Lelio; Vergara, Alessandro

    2011-05-01

    Spectroscopic and crystallographic evidence of endogenous (His) ligation at the sixth coordination site of the heme iron has been reported for monomeric, dimeric, and tetrameric hemoglobins (Hbs) in both ferrous (hemochrome) and ferric (hemichrome) oxidation states. In particular, the ferric bis- histidyl adduct represents a common accessible ordered state for the β chains of all tetrameric Hbs isolated from Antarctic and sub-Antarctic fish. Indeed, the crystal structures of known tetrameric Hbs in the bis-His state are characterized by a different binding state of the α and β chains. An overall analysis of the bis-histidyl adduct of globin structures deposited in the Protein Data Bank reveals a marked difference between hemichromes in tetrameric Hbs compared to monomeric/dimeric Hbs. Herein, we review the structural, spectroscopic and stability features of hemichromes in tetrameric Antarctic fish Hbs. The role of bis-histidyl adducts is also addressed in a more evolutionary context alongside the concept of its potential physiological role. Copyright © 2011 Wiley Periodicals, Inc.

  12. Histidine 114 Is Critical for ATP Hydrolysis by the Universally Conserved ATPase YchF.

    Science.gov (United States)

    Rosler, Kirsten S; Mercier, Evan; Andrews, Ian C; Wieden, Hans-Joachim

    2015-07-24

    GTPases perform a wide range of functions, ranging from protein synthesis to cell signaling. Of all known GTPases, only eight are conserved across all three domains of life. YchF is one of these eight universally conserved GTPases; however, its cellular function and enzymatic properties are poorly understood. YchF differs from the classical GTPases in that it has a higher affinity for ATP than for GTP and is a functional ATPase. As a hydrophobic amino acid-substituted ATPase, YchF does not possess the canonical catalytic Gln required for nucleotide hydrolysis. To elucidate the catalytic mechanism of ATP hydrolysis by YchF, we have taken a two-pronged approach combining classical biochemical and in silico techniques. The use of molecular dynamics simulations allowed us to complement our biochemical findings with information about the structural dynamics of YchF. We have thereby identified the highly conserved His-114 as critical for the ATPase activity of YchF from Escherichia coli. His-114 is located in a flexible loop of the G-domain, which undergoes nucleotide-dependent conformational changes. The use of a catalytic His is also observed in the hydrophobic amino acid-substituted GTPase RbgA and is an identifier of the translational GTPase family. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Substitution of arginine for histidine-47 in the coenzyme binding site of yeast alcohol dehydrogenase I

    International Nuclear Information System (INIS)

    Gould, R.M.; Plapp, B.V.

    1990-01-01

    Molecular modeling of alcohol dehydrogenases suggests that His-47 in the yeast enzyme (His-44 in the protein sequence, corresponding to Arg-47 in the horse liver enzyme) binds the pyrophosphate of the NAD coenzyme. His-47 in the Saccharomyces cerevisiae isoenzyme I was substituted with an arginine by a directed mutation. Steady-state kinetic results at pH 7.3 and 30 degree C of the mutant and wild-type enzymes were consistent with an ordered Bi-Bi mechanism. The substitution decreased dissociation constants by 4-fold for NAD + and 2-fold for NADH while turnover numbers were decreased by 4-fold for ethanol oxidation and 6-fold for acetaldehyde reduction. The magnitudes of these effects are smaller than those found for the same mutation in the human liver β enzyme, suggesting that other amino acid residues in the active site modulate the effects of the substitution. The pH dependencies of dissociation constants and other kinetic constants were similar in the two yeast enzymes. Thus, it appears that His-47 is not solely responsible for a pK value near 7 that controls activity and coenzyme binding rates in the wild-type enzyme. The small substrate deuterium isotope effect above pH 7 and the single exponential phase of NADH production during the transient oxidation of ethanol by the Arg-47 enzyme suggest that the mutation makes an isomerization of the enzyme-NAD + complex limiting for turnover with ethanol

  14. The 10 kDa domain of human erythrocyte protein 4.1 binds the Plasmodium falciparum EBA-181 protein

    Directory of Open Access Journals (Sweden)

    Coetzer Theresa L

    2006-11-01

    Full Text Available Abstract Background Erythrocyte invasion by Plasmodium falciparum parasites represents a key mechanism during malaria pathogenesis. Erythrocyte binding antigen-181 (EBA-181 is an important invasion protein, which mediates a unique host cell entry pathway. A novel interaction between EBA-181 and human erythrocyte membrane protein 4.1 (4.1R was recently demonstrated using phage display technology. In the current study, recombinant proteins were utilized to define and characterize the precise molecular interaction between the two proteins. Methods 4.1R structural domains (30, 16, 10 and 22 kDa domain and the 4.1R binding region in EBA-181 were synthesized in specific Escherichia coli strains as recombinant proteins and purified using magnetic bead technology. Recombinant proteins were subsequently used in blot-overlay and histidine pull-down assays to determine the binding domain in 4.1R. Results Blot overlay and histidine pull-down experiments revealed specific interaction between the 10 kDa domain of 4.1R and EBA-181. Binding was concentration dependent as well as saturable and was abolished by heat denaturation of 4.1R. Conclusion The interaction of EBA-181 with the highly conserved 10 kDa domain of 4.1R provides new insight into the molecular mechanisms utilized by P. falciparum during erythrocyte entry. The results highlight the potential multifunctional role of malaria invasion proteins, which may contribute to the success of the pathogenic stage of the parasite's life cycle.

  15. Crystal structure of B acillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity: AtxA multimerization, phosphorylation and activity

    Energy Technology Data Exchange (ETDEWEB)

    Hammerstrom, Troy G.; Lori, Horton B.; Swick, Michelle C.; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M.

    2014-12-30

    The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO2/bicarbonate, and there is a positive correlation between the CO2/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (HisAsp) and phosphoablative (HisAla) amino acid changes for activity in B.anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism.

  16. Learners´ treatment in the classroom according to their gender in the first and the second triad of the primary school

    OpenAIRE

    Sitar, Erika

    2016-01-01

    In this thesis, we focused on the learners´ treatment in the classroom according to their gender in the first and the second triad of the primary school by the teacher. We wanted to know whether teachers treated the learners´ in the classroom differently based on their gender. In the theoretical part of the master's thesis, we presented literature of Slovenian and foreign authors, which is related to the topic of gender and gender differentiation. Our focus was on different aspects of gender ...

  17. Eddy covariance fluxes of the NO-O3-NO2 triad above the forest canopy at the ATTO Site in the Amazon Basin

    Science.gov (United States)

    Tsokankunku, Anywhere; Wolff, Stefan; Sörgel, Matthias; Berger, Martina; Zelger, Michael; Dlugi, Ralf

    2017-04-01

    Nitrogen monoxide (NO) and nitrogen dioxide (NO2) (denoted together as NOx) determine the abundance of the tropospheric oxidants OH, O3 and NO3 that regulate atmospheric self-cleaning. The three reactive trace gases NO, NO2 and O3 undergo a series of interconnected photochemical reactions and are often referred to as the NO-O3-NO2 triad. Ozone deposition is mainly controlled by stomatal uptake, thus contributes to oxidative stress for the plants. Similarly, nitrogen dioxide from above or below the canopy is deposited to leaves through stomatal uptake. NO emissions from soils contribute to above canopy O3 formation and accelerate OH recycling. Therefore, quantification of the exchange fluxes of these species between the atmosphere and the biosphere are important for atmospheric chemistry and ecosystem research as well. The eddy covariance method is state of the art for direct measurements of ecosystem fluxes of trace gases. Eddy covariance measurements of NOx in pristine environments are rare because of lack of availability of instruments with the required precision to resolve concentrations characteristic of these environments. The Amazon Tall Tower Observatory (ATTO) is located in a pristine rainforest environment in the Amazon basin about 150 km northeast of the city of Manaus. It is the ideal site for studying the biosphere-atmosphere exchange of the NO-O3-NO2 triad, being largely undisturbed by anthropogenic sources. During an intensive measurement campaign in November 2015 at the ATTO site, measurements of NO, NO2 and O3 were carried out at 42 m above ground level on the 80 m walk-up tower with a fast (5 Hz) and sensitive (radiation. Vertical concentration profile measurements of NO, NO2 and O3 were available at 8 levels on the INSTANT tower from a reactive trace gas profile system which has been operational at the site since 2012. From these measurements, we present eddy covariance fluxes of the NO-O3-NO2 triad. We relate the fluxes to the canopy

  18. Eddy Covariance Fluxes of the NO-O3-NO2 Triad above the Forest Canopy at the ATTO Site in the Amazon Basin

    Science.gov (United States)

    Tsokankunku, A.; Wolff, S.; Berger, M.; Zelger, M.; Dlugi, R. J. W.; Andreae, M. O.; Sörgel, M.

    2017-12-01

    Nitrogen monoxide (NO) and nitrogen dioxide (NO2) (denoted together as NOx) determine the abundance of the tropospheric oxidants OH, O3 and NO3 that regulate atmospheric self-cleaning. The three reactive trace gases NO, NO2 and O3 undergo a series of interconnected photochemical reactions and are therefore often referred to as the NO-O3-NO2 triad. Ozone deposition is mainly controlled by stomatal uptake, therefore resulting in oxidative stress for the plants. Similarly, nitrogen dioxide from above or below the canopy is deposited to leaves through stomatal uptake. NO emissions from soils contribute to above canopy O3 formation and accelerate OH recycling. Therefore, quantification of the biosphere-atmosphere exchange fluxes of these species is important for atmospheric chemistry and ecosystem research. The eddy covariance method is state of the art for direct measurements of ecosystem fluxes of trace gases. Eddy covariance measurements of NOx in pristine environments are rare because of lack of availability of instruments with the required precision to resolve concentrations characteristic of these environments with the required high time resolution. The Amazon Tall Tower Observatory (ATTO) is located in a pristine rainforest environment in the Amazon basin about 150 km northeast of the city of Manaus. It is the ideal site for studying the biosphere-atmosphere exchange of the NO-O3-NO2 triad, because of the absence of nearby anthropogenic sources. During an intensive measurement campaign in November 2015 at the ATTO site, measurements of NO, NO2 and O3 were carried out at 42 m above ground level on the 80 m walk-up tower with a fast (5 Hz) and sensitive (< 30 ppt) instrument (CLD790SR2, Eco Physics) for NO and NO2 and with 10 Hz for O3 (Enviscope GmbH). Additionally, a suite of micrometeorological instruments was installed, including a profile of 3-dimensional sonic anemometers and meteorological sensors. Vertical concentration profile measurements of NO, NO2 and O

  19. PLASMA PROTEIN AND HEMOGLOBIN PRODUCTION

    Science.gov (United States)

    Robscheit-Robbins, F. S.; Miller, L. L.; Whipple, G. H.

    1947-01-01

    Given healthy dogs fed abundant iron and protein-free or low protein diets with sustained anemia and hypoproteinemia, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein. Reserve stores of blood protein-building materials are measurably depleted and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for weeks or months depending upon the intake of food proteins or amino acid mixtures. These dogs are very susceptible to infection and various poisons. Dogs tire of these diets and loss of appetite terminates many experiments. Under these conditions (double depletion) standard growth mixtures of essential amino acids are tested to show the response in blood protein output and urinary nitrogen balance. As a part of each tabulated experiment one of the essential amino acids is deleted from the complete growth mixture to compare such response with that of the whole mixture. Methionine, threonine, phenylalanine, and tryptophane when singly eliminated from the complete amino acid mixture do effect a sharp rise in urinary nitrogen. This loss of urinary nitrogen is corrected when the individual amino acid is replaced in the mixture. Histidine, lysine, and valine have a moderate influence upon urinary nitrogen balance toward nitrogen conservation. Leucine, isoleucine, and arginine have minimal or no effect upon urinary nitrogen balance when these individual amino acids are deleted from the complete growth mixture of amino acids during 3 to 4 week periods. Tryptophane and to a less extent phenylalanine and threonine when returned to the amino acid mixture are associated with a conspicuous preponderance of plasma protein output over the hemoglobin output (Table 4). Arginine, lysine, and histidine when returned to the amino acid mixture are associated with a large preponderance of hemoglobin output. Various amino acid mixtures under these conditions may give a positive

  20. Mechanism of phosphoryl transfer and protein-protein interaction in the PTS system-an NMR study

    Energy Technology Data Exchange (ETDEWEB)

    Rajagopal, P.; Klevit, R.E. [Univ. of Washington, Seattle, WA (United States)

    1994-12-01

    HPr and Enzyme IIA{sup Glc} are two of the components of the bacterial PTS (phosphoenolpyruvate: sugar phosphotranferase system) and are involved in the phosphorylation and concomitant translocation of sugars across the membrane. These PTS protein complexes also regulate sugar transport. HPr, phosphorylated at a histidine N1 site by Enzyme I and phosphoenol pyruvate, transfers the phosphoryl group to a histidine N3 position in Enzyme IIA{sup Glc}. HPrs from Gram-positive bacteria undergo regulatory phosphorylation at Ser{sup 46}, whereby phosphorylation of the histidine residue is inhibited. Conversely, histidine phosphorylation inhibits phosphorylation at Ser{sup 46}. HPrs from Gram-negative bacteria possess a serine residue at position 46, but do not undergo regulatory phosphorylation. HPr forms an open-faced sandwich structure with a four-strand S-sheet and 2 to 3 helices lying on top of the sheet. The active-site histidine and Ser{sup 46} occur in conformationally flexible regions. P-His-HPr from the Gram-positive bacterium Bacillus subtilus has been investigated by both homonuclear and heteronuclear two-dimensional and three-dimensional NMR experiments using an in-situ enzymatic regeneration system to maintain a constant level of P-His-HPr. The results show that localized conformational changes occur in the vicinity of the active-site histidine and also near Ser{sup 46}. HPr-Enzyme IIA{sup Glc} complexes from both Bacillus subtilis and Gram-negative Escherichia coli were also studied by a variety of {sup 15}N-edited two-dimensional NMR experiments, which were performed on uniformly {sup 15}N-labeled HPr complexed to unlabeled Enzyme IIA{sup Glc}. The complex is in fast exchange with a molecular weight of about 27 kDa. The focus of our work is to assess the changes undergone by HPr (the smaller of the two components), and so all the experiments were performed with excess Enzyme IIA present in the system.

  1. Role of folate-homocysteine pathway gene polymorphisms and nutritional cofactors in Down syndrome: A triad study.

    Science.gov (United States)

    Sukla, K K; Jaiswal, S K; Rai, A K; Mishra, O P; Gupta, V; Kumar, A; Raman, R

    2015-08-01

    Do gene-gene and gene-environment interactions in folate-homocysteine (Hcy) pathway have a predisposing role for Down syndrome (DS)? The study provides evidence that in addition to advanced age, maternal genotype, micronutrient deficiency and elevated Hcy levels, individually and in combination, are risk factors for Down syndrome. Polymorphisms in certain folate-Hcy-pathway genes (especially the T allele of MTHFR C677T), elevated Hcy and poor folate levels in mothers during pregnancy have been shown to be risk factors for Down syndrome in certain Asian populations (including the eastern region of India), while the same SNPs are not a risk factor in European populations. This conflicting situation alludes to differential gene-environment (nutrition) interactions in different populations which needs to be explored. Between 2008 and 2012, 151 Down syndrome triads and 200 age-matched controls (Control mothers n = 186) were included in the study. Seven polymorphisms in six genes of folate-Hcy metabolic pathway, along with Hcy, cysteine (Cys), vitamin B12 (vit-B12) and folate levels, were analysed and compared among the case and control groups. Genotyping was performed by the PCR-RFLP technique. Levels of homocysteine and cysteine were measured by HPLC while vitamin B12 and folate were estimated by chemiluminescence. We demonstrate that polymorphisms in the folate-Hcy pathway genes in mothers collectively constitute a genotypic risk for DS which is effectively modified by interactions among genes and by the environment affecting folate, Hcy and vitamin B12 levels. The study also supports the idea that these maternal risk factors provide an adaptive advantage during pregnancy supporting live birth of the DS child. Our inability to obtain genotype and nutritional assessments of unaffected siblings of the DS children was an important limitation of the study. Also, its confinement to a specific geographic region (the eastern part) of India, and relatively small sample size

  2. Light Controls Cytokinin Signaling via Transcriptional Regulation of Constitutively Active Sensor Histidine Kinase CKI1.

    Science.gov (United States)

    Dobisova, Tereza; Hrdinova, Vendula; Cuesta, Candela; Michlickova, Sarka; Urbankova, Ivana; Hejatkova, Romana; Zadnikova, Petra; Pernisova, Marketa; Benkova, Eva; Hejatko, Jan

    2017-05-01

    In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The cross talk between cytokinin response and light has been known for a long time. However, the molecular mechanism underlying the interaction between light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL ( LPH ) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT1 ( CKI1 ), encoding the constitutively active sensor His kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE1 ( HY1 ) that encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertible phytochromes. Our analysis confirmed the light-dependent regulation of the CKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors (TF) PHYTOCHROME INTERACTING FACTOR3 and CIRCADIAN CLOCK ASSOCIATED1. Changes in CKI1 expression observed in lph / hy1 - 7 and phy mutants correlate with misregulation of MSP signaling, changed cytokinin sensitivity, and developmental aberrations that were previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate a novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development. © 2017 American Society of Plant Biologists. All Rights Reserved.

  3. Female Athlete Triad

    Science.gov (United States)

    ... for some competitive female athletes, problems such as low self-esteem, a tendency toward perfectionism, and family stress place ... depression, pressure from coaches or family members, or low self-esteem and can help her find ways to deal ...

  4. Sensitive detection of biothiols and histidine based on the recovered fluorescence of the carbon quantum dots–Hg(II) system

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Juan; Zhang, Fengshuang; Yan, Xu; Wang, Long; Yan, Jin [College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012 (China); Ding, Hong [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Ding, Lan, E-mail: dinglan@jlu.edu.cn [College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012 (China)

    2015-02-15

    Highlights: • Carbon quantum dots-based probe was used for detection of GSH, Cys or His. • The fluorescence of CQDs was quenched by Hg(II) and then recovered by GSH, Cys or His. • No further surface modification or purification of CQDs was required. • This sensor exhibits superior accuracy and sensitivity. • The proposed method was simple in design, fast in operation. - Abstract: In this paper, we presented a novel, rapid and highly sensitive sensor for glutathione (GSH), cysteine (Cys) and histidine (His) based on the recovered fluorescence of the carbon quantum dots (CQDs)–Hg(II) system. The CQDs were synthesized by microwave-assisted approach in one pot according to our previous report. The fluorescence of CQDs could be quenched in the presence of Hg(II) due to the coordination occurring between Hg(II) and functional groups on the surface of CQDs. Subsequently, the fluorescence of the CQDs–Hg(II) system was recovered gradually with the addition of GSH, Cys or His due to their stronger affinity with Hg(II). A good linear relationship was obtained from 0.10 to 20 μmol L{sup −1} for GSH, from 0.20 to 45 μmol L{sup −1} for Cys and from 0.50 to 60 μmol L{sup −1} for His, respectively. This method has been successfully applied to the trace detection of GSH, Cys or His in human serum samples with satisfactory results. The proposed method was simple in design and fast in operation, which demonstrated great potential in bio-sensing fields.

  5. Sensitive detection of biothiols and histidine based on the recovered fluorescence of the carbon quantum dots–Hg(II) system

    International Nuclear Information System (INIS)

    Hou, Juan; Zhang, Fengshuang; Yan, Xu; Wang, Long; Yan, Jin; Ding, Hong; Ding, Lan

    2015-01-01

    Highlights: • Carbon quantum dots-based probe was used for detection of GSH, Cys or His. • The fluorescence of CQDs was quenched by Hg(II) and then recovered by GSH, Cys or His. • No further surface modification or purification of CQDs was required. • This sensor exhibits superior accuracy and sensitivity. • The proposed method was simple in design, fast in operation. - Abstract: In this paper, we presented a novel, rapid and highly sensitive sensor for glutathione (GSH), cysteine (Cys) and histidine (His) based on the recovered fluorescence of the carbon quantum dots (CQDs)–Hg(II) system. The CQDs were synthesized by microwave-assisted approach in one pot according to our previous report. The fluorescence of CQDs could be quenched in the presence of Hg(II) due to the coordination occurring between Hg(II) and functional groups on the surface of CQDs. Subsequently, the fluorescence of the CQDs–Hg(II) system was recovered gradually with the addition of GSH, Cys or His due to their stronger affinity with Hg(II). A good linear relationship was obtained from 0.10 to 20 μmol L −1 for GSH, from 0.20 to 45 μmol L −1 for Cys and from 0.50 to 60 μmol L −1 for His, respectively. This method has been successfully applied to the trace detection of GSH, Cys or His in human serum samples with satisfactory results. The proposed method was simple in design and fast in operation, which demonstrated great potential in bio-sensing fields

  6. Identification of a crucial histidine involved in metal transport activity in the Arabidopsis cation/H+ exchanger CAX1.

    Science.gov (United States)

    Shigaki, Toshiro; Barkla, Bronwyn J; Miranda-Vergara, Maria Cristina; Zhao, Jian; Pantoja, Omar; Hirschi, Kendal D

    2005-08-26

    In plants, yeast, and bacteria, cation/H+ exchangers (CAXs) have been shown to translocate Ca2+ and other metal ions utilizing the H+ gradient. The best characterized of these related transporters is the plant vacuolar localized CAX1. We have used site-directed mutagenesis to assess the impact of altering the seven histidine residues to alanine within Arabidopsis CAX1. The mutants were expressed in a Saccharomyces cerevisiae strain that is sensitive to Ca2+ and other metals. By utilizing a yeast growth assay, the H338A mutant was the only mutation that appeared to alter Ca2+ transport activity. The CAX1 His338 residue is conserved among various CAX transporters and may be located within a filter for cation selection. We proceeded to mutate His338 to every other amino acid residue and utilized yeast growth assays to estimate the transport properties of the 19 CAX mutants. Expression of 16 of these His338 mutants could not rescue any of the metal sensitivities. However, expression of H338N, H338Q, and H338K allowed for some growth on media containing Ca2+. Most interestingly, H338N exhibited increased tolerance to Cd2+ and Zn2+. Endomembrane fractions from yeast cells were used to measure directly the transport of H338N. Although the H338N mutant demonstrated 25% of the wild type Ca2+/H+ transport, it showed an increase in transport for both Cd2+ and Zn2+ reflected in a decrease in the Km for these substrates. This study provides insights into the CAX cation filter and novel mechanisms by which metals may be partitioned across membranes.

  7. Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions.

    Science.gov (United States)

    Nurul, Islam Mohammed; Mizuguchi, Hiroyuki; Shahriar, Masum; Venkatesh, Pichairajan; Maeyama, Kazutaka; Mukherjee, Pulok K; Hattori, Masashi; Choudhuri, Mohamed Sahabuddin Kabir; Takeda, Noriaki; Fukui, Hiroyuki

    2011-11-01

    Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations

    Science.gov (United States)

    2014-01-01

    Introduction Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. Methods An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). Results The original training cohort reached a statistically significant difference (p risk groups. Conclusions Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments. PMID:24996446

  9. The dark side of social media: Associations between the Dark Triad of personality, self-disclosure online and selfie-related behaviours

    Directory of Open Access Journals (Sweden)

    Elżbieta Sanecka

    2017-09-01

    Full Text Available The present study investigated the relations between the Dark Triad personality traits (i.e., Machiavellianism, narcissism, and psychopathy, distinct dimensions of self-disclosure online (i.e., honesty, amount, positive valence, and intent and selfie related-behaviours (taking, posting and editing selfies. The results indicated, that all three Dark Triad components were positively correlated with posting and editing selfies on social networking sites (SNSs. However, multiple regression analysis demonstrated that only narcissism predicted selfie-related behaviours. Narcissism and Machiavellianism were positively related to the amount of personal information disclosed online and the tendency to self-disclose intentionally in computer-mediated communication (CMC. Moreover, we found no significant correlations between the perceived controllability of Internet communication and two types of self-promotion in the Internet (self-disclosure online and selfie-related behaviours. Our findings demonstrate the importance of analysing the "dark" personality traits in the context of self-promotional behaviours in social media.

  10. Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies.

    Science.gov (United States)

    Bruijnincx, Pieter C A; van Koten, Gerard; Klein Gebbink, Robertus J M

    2008-12-01

    Iron-containing enzymes are one of Nature's main means of effecting key biological transformations. The mononuclear non-heme iron oxygenases and oxidases have received the most attention recently, primarily because of the recent availability of crystal structures of many different enzymes and the stunningly diverse oxidative transformations that these enzymes catalyze. The wealth of available structural data has furthermore established the so-called 2-His-1-carboxylate facial triad as a new common structural motif for the activation of dioxygen. This superfamily of mononuclear iron(ii) enzymes catalyzes a wide range of oxidative transformations, ranging from the cis-dihydroxylation of arenes to the biosynthesis of antibiotics such as isopenicillin and fosfomycin. The remarkable scope of oxidative transformations seems to be even broader than that associated with oxidative heme enzymes. Not only are many of these oxidative transformations of key biological importance, many of these selective oxidations are also unprecedented in synthetic organic chemistry. In this critical review, we wish to provide a concise background on the chemistry of the mononuclear non-heme iron enzymes characterized by the 2-His-1-carboxylate facial triad and to discuss the many recent developments in the field. New examples of enzymes with unique reactivities belonging to the superfamily have been reported. Furthermore, key insights into the intricate mechanistic details and reactive intermediates have been obtained from both enzyme and modeling studies. Sections of this review are devoted to each of these subjects, i.e. the enzymes, biomimetic models, and reactive intermediates (225 references).

  11. Heme environment in HmuY, the heme-binding protein of Porphyromonas gingivalis

    International Nuclear Information System (INIS)

    Wojtowicz, Halina; Wojaczynski, Jacek; Olczak, Mariusz; Kroliczewski, Jaroslaw; Latos-Grazynski, Lechoslaw; Olczak, Teresa

    2009-01-01

    Porphyromonas gingivalis, a Gram-negative anaerobic bacterium implicated in the development and progression of chronic periodontitis, acquires heme for growth by a novel mechanism composed of HmuY and HmuR proteins. The aim of this study was to characterize the nature of heme binding to HmuY. The protein was expressed, purified and detailed investigations using UV-vis absorption, CD, MCD, and 1 H NMR spectroscopy were carried out. Ferric heme bound to HmuY may be reduced by sodium dithionite and re-oxidized by potassium ferricyanide. Heme complexed to HmuY, with a midpoint potential of 136 mV, is in a low-spin Fe(III) hexa-coordinate environment. Analysis of heme binding to several single and double HmuY mutants with the methionine, histidine, cysteine, or tyrosine residues replaced by an alanine residue identified histidines 134 and 166 as potential heme ligands.

  12. A colloidal assembly approach to synthesize magnetic porous composite nanoclusters for efficient protein adsorption

    Science.gov (United States)

    Yang, Qi; Lan, Fang; Yi, Qiangying; Wu, Yao; Gu, Zhongwei

    2015-10-01

    A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation.A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c5nr05800g

  13. Heme environment in HmuY, the heme-binding protein of Porphyromonas gingivalis

    Energy Technology Data Exchange (ETDEWEB)

    Wojtowicz, Halina [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland); Wojaczynski, Jacek [Department of Chemistry, University of Wroclaw, 50-383 Wroclaw (Poland); Olczak, Mariusz [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland); Kroliczewski, Jaroslaw [Laboratory of Biophysics, Faculty of Biotechnology, University of Wroclaw, 50-148 Wroclaw (Poland); Latos-Grazynski, Lechoslaw [Department of Chemistry, University of Wroclaw, 50-383 Wroclaw (Poland); Olczak, Teresa [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland)

    2009-05-29

    Porphyromonas gingivalis, a Gram-negative anaerobic bacterium implicated in the development and progression of chronic periodontitis, acquires heme for growth by a novel mechanism composed of HmuY and HmuR proteins. The aim of this study was to characterize the nature of heme binding to HmuY. The protein was expressed, purified and detailed investigations using UV-vis absorption, CD, MCD, and {sup 1}H NMR spectroscopy were carried out. Ferric heme bound to HmuY may be reduced by sodium dithionite and re-oxidized by potassium ferricyanide. Heme complexed to HmuY, with a midpoint potential of 136 mV, is in a low-spin Fe(III) hexa-coordinate environment. Analysis of heme binding to several single and double HmuY mutants with the methionine, histidine, cysteine, or tyrosine residues replaced by an alanine residue identified histidines 134 and 166 as potential heme ligands.

  14. Specific protein-protein interactions of calsequestrin with junctional sarcoplasmic reticulum of skeletal muscle

    International Nuclear Information System (INIS)

    Damiani, E.; Margreth, A.

    1990-01-01

    Minor protein components of triads and of sarcoplasmic reticulum (SR) terminal cisternae (TC), i.e. 47 and 37 kDa peptides and 31-30 kDa and 26-25 kDa peptide doublets, were identified from their ability to bind 125 I calsequestrin (CS) in the presence of EGTA. The CS-binding peptides are specifically associated with the junctional membrane of TC, since they could not be detected in junctional transverse tubules and in longitudinal SR fragments. The 31-30 kDa peptide doublet, exclusively, did not bind CS in the presence of Ca 2+ . Thus, different types of protein-protein interactions appear to be involved in selective binding of CS to junctional TC

  15. Cholesterol Removal from Adult Skeletal Muscle impairs Excitation-Contraction Coupling and Aging reduces Caveolin-3 and alters the Expression of other Triadic Proteins

    Directory of Open Access Journals (Sweden)

    Genaro eBarrientos

    2015-04-01

    Full Text Available Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not sarcoplasmic reticulum membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX activity and protein content of NOX2 subunits (p47phox and gp91phox, implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs excitation-contraction coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged

  16. Differential metabolic effects of casein and soy protein meals on skeletal muscle in healthy volunteers.

    Science.gov (United States)

    Luiking, Yvette C; Engelen, Mariëlle P K J; Soeters, Peter B; Boirie, Yves; Deutz, Nicolaas E P

    2011-02-01

    Dietary protein intake is known to affect whole body and interorgan protein turnover. We examined if moderate-nitrogen and carbohydrate casein and soy meals have a different effect on skeletal muscle protein and amino acid kinetics in healthy young subjects. Muscle protein and amino acid kinetics were measured in the postabsorptive state and during 4-h enteral intake of isonitrogenous [0.21 g protein/(kg body weight. 4 h)] protein-based test meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2 separate groups. Stable isotope and muscle biopsy techniques were used to study metabolic effects. The net uptake of glutamate, serine, histidine, and lysine across the leg was larger during CAPM than during SOPM intake. Muscle concentrations of glutamate, serine, histidine, glutamine, isoleucine and BCAA changed differently after CAPM and SOPM (P CAPM and SOPM, but differences in their (net) breakdown rates were not significant. Muscle protein synthesis was not different between CAPM and SOPM. Moderate-nitrogen casein and soy protein meals differently alter leg amino acid uptake without a significant difference in influencing acute muscle protein metabolism. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Using porphyrin-amino acid pairs to model the electrochemistry of heme proteins: experimental and theoretical investigations.

    Science.gov (United States)

    Samajdar, Rudra N; Manogaran, Dhivya; Yashonath, S; Bhattacharyya, Aninda J

    2018-04-18

    Quasi reversibility in electrochemical cycling between different oxidation states of iron is an often seen characteristic of iron containing heme proteins that bind dioxygen. Surprisingly, the system becomes fully reversible in the bare iron-porphyrin complex: hemin. This leads to the speculation that the polypeptide bulk (globin) around the iron-porphyrin active site in these heme proteins is probably responsible for the electrochemical quasi reversibility. To understand the effect of such polypeptide bulk on iron-porphyrin, we study the interaction of specific amino acids with the hemin center in solution. We choose three representative amino acids-histidine (a well-known iron coordinator in bio-inorganic systems), tryptophan (a well-known fluoroprobe for proteins), and cysteine (a redox-active organic molecule). The interactions of these amino acids with hemin are studied using electrochemistry, spectroscopy, and density functional theory. The results indicate that among these three, the interaction of histidine with the iron center is strongest. Further, histidine maintains the electrochemical reversibility of iron. On the other hand, tryptophan and cysteine interact weakly with the iron center but disturb the electrochemical reversibility by contributing their own redox active processes to the system. Put together, this study attempts to understand the molecular interactions that can control electrochemical reversibility in heme proteins. The results obtained here from the three representative amino acids can be scaled up to build a heme-amino acid interaction database that may predict the electrochemical properties of any protein with a defined polypeptide sequence.

  18. Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells

    DEFF Research Database (Denmark)

    Gräs, S; Ovesen, P; Andersen, A N

    1994-01-01

    Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular....../l, respectively. VIP at a concentration of 10 nmol/l caused a significant increase in [3H]thymidine incorporation, and at 1000 nmol/l a significant increase in oestradiol secretion was observed. VIP had no effect on progesterone secretion. PHM at the concentrations tested did not influence any of the activities...

  19. catena-Poly[[bis(nitrato-κ2O,O′barium]-bis(μ-l-histidine-κ3O,O′:O

    Directory of Open Access Journals (Sweden)

    P. Arularasan

    2013-11-01

    Full Text Available In the polymeric title compound, [Ba(NO32(C6H9N3O22]n, the BaII atom is located on a crystallographic twofold axis and is coordinated by ten O atoms. Six are derived from two zwitterionic l-histidine molecules that simultaneously chelate one BaII atom and bridge to another. The remaining four O atoms are derived from two chelating nitrates. The molecules assemble to form a chain along [010]. In the crystal, chains are linked via N—H...O and N—H...N hydrogen bonds, generating a three-dimensional network.

  20. Supramolecular Self-Assembly of Histidine-Capped-Dialkoxy-Anthracene: A Visible Light Triggered Platform for facile siRNA Delivery

    KAUST Repository

    Patil, Sachin

    2016-06-29

    Supramolecular self-assembly of histidine-capped-dialkoxy-anthracene (HDA) results in the formation of light responsive nanostructures.Single-crystal X-ray diffraction analysis of HDA shows two types of hydrogen bonding. The first hydrogen bond is established between the imidazole moieties while the second involves the oxygen atom of one amide group and the hydrogen atom of a second amide group. When protonated in acidic aqueous media, HDA successfully complexes siRNA yielding spherical nanostructures. This biocompatible platform controllably delivers siRNA with high efficacy upon visible light irradiation leading up to 90% of gene silencing in live cells.

  1. DFT/TD-semiempirical study on the structural and electronic properties and absorption spectra of supramolecular fullerene-porphyrine-metalloporphyrine triads based dye-sensitized solar cells

    Science.gov (United States)

    Rezvani, M.; Darvish Ganji, M.; Jameh-Bozorghi, S.; Niazi, A.

    2018-04-01

    In the present work density functional theory (DFT) and time-dependent semiempirical ZNIDO/S (TD-ZNIDO/S) methods have been used to investigate the ground state geometries, electronic structures and excited state properties of triad systems. The influences of the type of metal in the porphyrin ring, change in bridge position and porphyrine-ZnP duplicate on the energies of frontier molecular orbital and UV-Vis spectra has been studied. Geometry optimization, the energy levels and electron density of the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO), chemical hardness (η), electrophilicity index (ω), electron accepting power (ω+) were calculated using ZINDO/S method to predict which molecule is the most efficient with a great capability to be used as a triad molecule in solar industry. Moreover the light harvesting efficiency (LHE) was calculated by means of the oscillator strengths which are obtained by TD-ZINDO/S calculation. Theoretical studies of the electronic spectra by ZINDO/S method were helpful in interpreting the observed electronic transitions. This aspect was systematically explored in a series of C60-Porphyrine-Metalloporphyrine (C60-P-Mp) triad system with M being Fe, Co, Ni, Ti, and Zn. Generally, transition metal coordination compounds are used as effective sensitizers, due to their intense charge-transfer absorption over the whole visible range and highly efficient metal-to-ligand charge transfer. We aim to optimize the performance of the title solar cells by altering the frontier orbital energy gaps. The results reveal that cell efficiency can be enhanced by metal functionalization of the free base porphyrin. Ti-porphyrin was found to be the most efficient dye sensitizer for dye sensitized solar cells (DSSCs) based on C60-P-Mptriad system due to C60-Por-TiP complex has lower chemical hardness, gap energy and chemical potential as well as higher electron accepting power among other complexes. In

  2. Peripheral Protein Unfolding Drives Membrane Bending.

    Science.gov (United States)

    Siaw, Hew Ming Helen; Raghunath, Gokul; Dyer, R Brian

    2018-06-20

    Dynamic modulation of lipid membrane curvature can be achieved by a number of peripheral protein binding mechanisms such as hy-drophobic insertion of amphipathic helices and membrane scaffolding. Recently, an alternative mechanism was proposed in which crowding of peripherally bound proteins induces membrane curvature through steric pressure generated by lateral collisions. This effect was enhanced using intrinsically disordered proteins that possess high hydrodynamic radii, prompting us to explore whether membrane bending can be triggered by the folding-unfolding transition of surface-bound proteins. We utilized histidine-tagged human serum albumin bound to Ni-NTA-DGS containing liposomes as our model system to test this hypothesis. We found that reduction of the disulfide bonds in the protein resulted in unfolding of HSA, which subsequently led to membrane tubule formation. The frequency of tubule formation was found to be significantly higher when the proteins were unfolded while being localized to a phase-separated domain as opposed to randomly distributed in fluid phase liposomes, indicating that the steric pressure generated from protein unfolding is directly responsible for membrane deformation. Our results are critical for the design of peripheral membrane protein-immobilization strategies and open new avenues for exploring mechanisms of membrane bending driven by conformational changes of peripheral membrane proteins.

  3. Incorporation of tritium into hair proteins of rat

    International Nuclear Information System (INIS)

    Rochalska, M.; Ardelt, W.; Szot, Z.

    1981-01-01

    A simple and relatively rapid procedure for the extraction and fractionation of hair proteins, was elaborated and used for an analysis of rat hair proteins, tritiated in vivo. The most radioactive protein, containing over 6% of the initial hair radioactivity, was isolated in a homogeneous state. The protein had a molecular weight of about 190,000 daltons, and showed high proportions of glutamic acid, cysteine, aspartic acid, serine, and glycine and a low content of methionine and histidine. More than 80% of total tritium radioactivity incorporated into this protein was distributed among indispensable phenylalanine (30.3%) and, isoleucine (17.2%), valine (17.6%), proline (10,5%) and tyrosine (8.4%). The highest values of specific radioactivity were recorded for phenylalanine, isoleucine, valine and methionine. The radioactivity recovered in the amino acids is due to the presence of firmly bound tritium. (author)

  4. Amylase-Binding Protein B of Streptococcus gordonii Is an Extracellular Dipeptidyl-Peptidase▿

    OpenAIRE

    Chaudhuri, Biswendu; Paju, Susanna; Haase, Elaine M.; Vickerman, M. Margaret; Tanzer, Jason M.; Scannapieco, Frank A.

    2008-01-01

    The oral commensal bacterium Streptococcus gordonii interacts with salivary amylase via two amylase-binding proteins, AbpA and AbpB. Based on sequence analysis, the 20-kDa AbpA protein is unique to S. gordonii, whereas the 82-kDa AbpB protein appears to share sequence homology with other bacterial dipeptidases. The aim of this study was to verify the peptidase activity of AbpB and further explore its potential functions. The abpB gene was cloned, and histidine-tagged AbpB (His-AbpB) was expre...

  5. Validity of the Food Frequency Questionnaire Assessing the Folate Intake in Women of Reproductive Age Living in a Country without Food Fortification: Application of the Method of Triads.

    Science.gov (United States)

    Zekovic, Milica; Djekic-Ivankovic, Marija; Nikolic, Marina; Gurinovic, Mirjana; Krajnovic, Dusanka; Glibetic, Marija

    2017-02-13

    The study aimed to examine the external validity of the Folate Food Frequency Questionnaire (F-FFQ) designed for assessing the folate intake in Serbian women of reproductive age. The F-FFQ was tested against repeated 24 h dietary recalls and correspondent nutritional biomarkers (red blood cells (RBC) and serum folate concentrations) using the method of triads. In a cross sectional study, 503 women aged 18-49 years completed dietary questionnaires and representative validation subsample ( n = 50) provided fasting blood samples for biomarker analyses. Correlation coefficients were calculated between each of the dietary methods and three pair-wise correlations were applied for the calculation of validity coefficients. Correlation coefficients observed between F-FFQ and three 24 h recalls were r = 0.56 ( p food fortification.

  6. [Study of hydrogen bonds in the "catalytic triad" of trypsin by NMR spectra at 1H, 13C, and 15N nuclei].

    Science.gov (United States)

    Golubeb, N S; Gindin, V A; Ligaĭ, S S; Smirnov, S N

    1994-05-01

    The 1H and 13C NMR of trypsin stabilized by chemical modification with a hydrophilic polymer have been obtained in a wide range of pH (1.0-11.0). The spectral features referred to some nuclei of the "catalytic triad" have been identified using different NMR techniques as well as chemical modification with selective reagents. It was found that the monoprotonation of this system results in a quasi-symmetrical hydrogen bond formed between the basic groups which provided explanation for the discrepancies between the experimental findings obtained by different authors concerning the protonation site in this catalytic system. Simulation of the catalytic triad by a 15N-labelled low molecular model suggests that an increase in the OH-group acidity is unaccompanied by a discrete double proton transfer; however, a smooth shift of the bridging protons from one basic atom to another occurs with quasi-symmetrical hydrogen bonds formed in intermediate cases. On the basis of experimental data a new concept has been proposed for the mechanism of acid-base catalysis performed by pains of weak basic groups, such as His-Im and Asp(Glu)-COO- (pKa = 3-7) which are not capable of proton abstraction from alcoholic or water OH-groups (pKa > 13). The catalysis may consist in changing the charge densities on the reacting groups due to strong H-bonding and, on the other hand, in facilitating the free movement of a proton in the field of several basic atoms when going along the reaction coordinate. The energy of very strong hydrogen bonds thus formed diminishes the activation energy of the reaction.

  7. Telegerontology as a Novel Approach to Address Health and Safety by Supporting Community-Based Rural Dementia Care Triads: Randomized Controlled Trial Protocol.

    Science.gov (United States)

    Wallack, Elizabeth M; Harris, Chelsea; Ploughman, Michelle; Butler, Roger

    2018-02-22

    Telegerontology is an approach using videoconferencing to connect an interdisciplinary team in a regional specialty center to patients in rural communities, which is becoming increasingly practical for addressing current limitations in rural community-based dementia care. Using the remotely-delivered expertise of the Telegerontology dementia care team, we aim to enhance the caregiver/patient/physician triad and thereby provide the necessary support for the person with dementia to "age in place." This is a cluster randomized feasibility trial with four rural regions in the province of Newfoundland and Labrador, Canada (2 regions randomly assigned to "intervention" and 2 to "control"). The study population includes 22 "dementia triads" that consist of a community-dwelling older Canadian with moderate to late dementia, their family caregivers, and their Primary Care Physician (PCP). Over the 6-month active study period, all participants will be provided an iPad. The intervention is intended as an adjunct to existing PCP care, consisting of weekly Skype-based videoconferencing calls with the Telegerontology physician, and other team members as needed (occupational therapist, physical therapist etc). Control participants receive usual community-based dementia care with their PCP. A baseline (pre-) assessment will be performed during a home visit with the study team. Post intervention, 6- and 12-month follow-up assessments will be collected remotely using specialized dementia monitoring applications and Skype calls. Primary outcomes include admission to long-term care, falls, emergency room visits, hospital stays, and caregiver burden. Results will be available in March of 2018. Results from this study will demonstrate a novel approach to dementia care that has the potential to impact both rural PCPs, family caregivers, and people with dementia, as well as provide evidence for the utility of Telegerontology in models of eHealth-based care. ©Elizabeth M. Wallack, Chelsea

  8. Validating polyphenol intake estimates from a food-frequency questionnaire by using repeated 24-h dietary recalls and a unique method-of-triads approach with 2 biomarkers.

    Science.gov (United States)

    Burkholder-Cooley, Nasira M; Rajaram, Sujatha S; Haddad, Ella H; Oda, Keiji; Fraser, Gary E; Jaceldo-Siegl, Karen

    2017-03-01

    Background: The assessment of polyphenol intake in free-living subjects is challenging, mostly because of the difficulty in accurately measuring phenolic content and the wide presence of phenolics in foods. Objective: The aims of this study were to evaluate the validity of polyphenol intake estimated from food-frequency questionnaires (FFQs) by using the mean of 6 measurements of a 24-h dietary recall (24-HR) as a reference and to apply a unique method-of-triads approach to assess validity coefficients (VCs) between latent "true" dietary estimates, total urinary polyphenol (TUP) excretion, and a surrogate biomarker (plasma carotenoids). Design: Dietary intake data from 899 adults of the Adventist Health Study 2 (AHS-2; 43% blacks and 67% women) were obtained. Pearson correlation coefficients ( r ), corrected for attenuation from within-person variation in the recalls, were calculated between 24-HRs and FFQs and between 24-HRs and TUPs. VCs and 95% CIs between true intake and polyphenol intakes from FFQs, 24-HRs, and the biomarkers TUPs and plasma carotenoids were calculated. Results: Mean ± SD polyphenol intakes were 717 ± 646 mg/d from FFQs and 402 ± 345 mg/d from 24-HRs. The total polyphenol intake from 24-HRs was correlated with FFQs in crude ( r = 0.51, P < 0.001) and deattenuated ( r = 0.63; 95% CI: 0.61, 0.69) models . In the triad model, the VC between the FFQs and theoretical true intake was 0.46 (95% CI: 0.20, 0.93) and between 24-HRs and true intake was 0.61 (95% CI: 0.38, 1.00). Conclusions: The AHS-2 FFQ is a reasonable indicator of total polyphenol intake in the AHS-2 cohort. Urinary polyphenol excretion is limited by genetic variance, metabolism, and bioavailability and should be used in addition to rather than as a replacement for dietary intake assessment. © 2017 American Society for Nutrition.

  9. Early detection and successful treatment of Wernicke's encephalopathy in outpatients without the complete classic triad of symptoms who attended a psycho-oncology clinic.

    Science.gov (United States)

    Onishi,