WorldWideScience

Sample records for binding suggests cross-species

  1. Leveraging cross-species transcription factor binding site patterns

    DEFF Research Database (Denmark)

    Claussnitzer, Melina; Dankel, Simon N; Klocke, Bernward

    2014-01-01

    Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to...... that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms....

  2. Cross-species correlation between queen mating numbers and worker ovary sizes suggests kin conflict may influence ovary size evolution in honeybees

    Science.gov (United States)

    Rueppell, Olav; Phaincharoen, Mananya; Kuster, Ryan; Tingek, Salim

    2011-09-01

    During social evolution, the ovary size of reproductively specialized honey bee queens has dramatically increased while their workers have evolved much smaller ovaries. However, worker division of labor and reproductive competition under queenless conditions are influenced by worker ovary size. Little comparative information on ovary size exists in the different honey bee species. Here, we report ovariole numbers of freshly dissected workers from six Apis species from two locations in Southeast Asia. The average number of worker ovarioles differs significantly among species. It is strongly correlated with the average mating number of queens, irrespective of body size. Apis dorsata, in particular, is characterized by numerous matings and very large worker ovaries. The relation between queen mating number and ovary size across the six species suggests that individual selection via reproductive competition plays a role in worker ovary size evolution. This indicates that genetic diversity, generated by multiple mating, may bear a fitness cost at the colony level.

  3. Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

    Science.gov (United States)

    Zhang, Ji-Long; Zheng, Qing-Chuan; Li, Zheng-Qiang; Zhang, Hong-Xing

    2012-01-01

    The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

  4. Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

    Directory of Open Access Journals (Sweden)

    Ji-Long Zhang

    Full Text Available The research on the binding process of ligand to pyrazinamidase (PncA is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD simulation methods were performed to investigate the unbinding process of nicotinamide (NAM from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF based on the steered molecular dynamics (SMD simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

  5. In silico docking of forchlorfenuron (FCF to septins suggests that FCF interferes with GTP binding.

    Directory of Open Access Journals (Sweden)

    Dimitrios Angelis

    Full Text Available Septins are GTP-binding proteins that form cytoskeleton-like filaments, which are essential for many functions in eukaryotic organisms. Small molecule compounds that disrupt septin filament assembly are valuable tools for dissecting septin functions with high temporal control. To date, forchlorfenuron (FCF is the only compound known to affect septin assembly and functions. FCF dampens the dynamics of septin assembly inducing the formation of enlarged stable polymers, but the underlying mechanism of action is unknown. To investigate how FCF binds and affects septins, we performed in silico simulations of FCF docking to all available crystal structures of septins. Docking of FCF with SEPT2 and SEPT3 indicated that FCF interacts preferentially with the nucleotide-binding pockets of septins. Strikingly, FCF is predicted to form hydrogen bonds with residues involved in GDP-binding, mimicking nucleotide binding. FCF docking with the structure of SEPT2-GppNHp, a nonhydrolyzable GTP analog, and SEPT7 showed that FCF may assume two alternative non-overlapping conformations deeply into and on the outer side of the nucleotide-binding pocket. Surprisingly, FCF was predicted to interact with the P-loop Walker A motif GxxxxGKS/T, which binds the phosphates of GTP, and the GTP specificity motif AKAD, which interacts with the guanine base of GTP, and highly conserved amino acids including a threonine, which is critical for GTP hydrolysis. Thus, in silico FCF exhibits a conserved mechanism of binding, interacting with septin signature motifs and residues involved in GTP binding and hydrolysis. Taken together, our results suggest that FCF stabilizes septins by locking them into a conformation that mimics a nucleotide-bound state, preventing further GTP binding and hydrolysis. Overall, this study provides the first insight into how FCF may bind and stabilize septins, and offers a blueprint for the rational design of FCF derivatives that could target septins with

  6. Molecular dynamics simulations suggest that electrostatic funnel directs binding of Tamiflu to influenza N1 neuraminidases.

    Directory of Open Access Journals (Sweden)

    Ly Le

    2010-09-01

    Full Text Available Oseltamivir (Tamiflu is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD and steered molecular dynamics (SMD simulations, as well as graphics processing unit (GPU-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 "avian" and H1N1pdm "swine" flu N1-subtype neuraminidases. The simulations reveal an electrostatic binding funnel that plays a key role in directing oseltamivir into and out of its binding site on N1 neuraminidase. The binding pathway for oseltamivir suggests how mutations disrupt drug binding and how new drugs may circumvent the resistance mechanisms.

  7. A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.

    Directory of Open Access Journals (Sweden)

    Emanuela Leonardi

    Full Text Available Mutations of human leucine-rich glioma inactivated (LGI1 gene encoding the epitempin protein cause autosomal dominant temporal lateral epilepsy (ADTLE, a rare familial partial epileptic syndrome. The LGI1 gene seems to have a role on the transmission of neuronal messages but the exact molecular mechanism remains unclear. In contrast to other genes involved in epileptic disorders, epitempin shows no homology with known ion channel genes but contains two domains, composed of repeated structural units, known to mediate protein-protein interactions.A three dimensional in silico model of the two epitempin domains was built to predict the structure-function relationship and propose a functional model integrating previous experimental findings. Conserved and electrostatic charged regions of the model surface suggest a possible arrangement between the two domains and identifies a possible ADAM protein binding site in the β-propeller domain and another protein binding site in the leucine-rich repeat domain. The functional model indicates that epitempin could mediate the interaction between proteins localized to different synaptic sides in a static way, by forming a dimer, or in a dynamic way, by binding proteins at different times.The model was also used to predict effects of known disease-causing missense mutations. Most of the variants are predicted to alter protein folding while several other map to functional surface regions. In agreement with experimental evidence, this suggests that non-secreted LGI1 mutants could be retained within the cell by quality control mechanisms or by altering interactions required for the secretion process.

  8. Molecular Dynamics Simulations Suggest Ligand’s Binding to Nicotinamidase/Pyrazinamidase

    Science.gov (United States)

    Zhang, Ji-Long; Zheng, Qing-Chuan; Li, Zheng-Qiang; Zhang, Hong-Xing

    2012-01-01

    The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA’s activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM’s unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand’s binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs. PMID:22761821

  9. A cross-species alignment tool (CAT)

    DEFF Research Database (Denmark)

    Li, Heng; Guan, Liang; Liu, Tao

    2007-01-01

    BACKGROUND: The main two sorts of automatic gene annotation frameworks are ab initio and alignment-based, the latter splitting into two sub-groups. The first group is used for intra-species alignments, among which are successful ones with high specificity and speed. The other group contains more...... sensitive methods which are usually applied in aligning inter-species sequences. RESULTS: Here we present a new algorithm called CAT (for Cross-species Alignment Tool). It is designed to align mRNA sequences to mammalian-sized genomes. CAT is implemented using C scripts and is freely available on the web...... at http://xat.sourceforge.net/. CONCLUSIONS: Examined from different angles, CAT outperforms other extant alignment tools. Tested against all available mouse-human and zebrafish-human orthologs, we demonstrate that CAT combines the specificity and speed of the best intra-species algorithms, like BLAT...

  10. Structures of the Streptococcus sanguinis SrpA Binding Region with Human Sialoglycans Suggest Features of the Physiological Ligand.

    Science.gov (United States)

    Loukachevitch, Lioudmila V; Bensing, Barbara A; Yu, Hai; Zeng, Jie; Chen, Xi; Sullam, Paul M; Iverson, T M

    2016-10-11

    Streptococcus sanguinis is a leading cause of bacterial infective endocarditis, a life-threatening infection of heart valves. S. sanguinis binds to human platelets with high avidity, and this adherence is likely to enhance virulence. Previous studies suggest that a serine-rich repeat adhesin termed SrpA mediates the binding of S. sanguinis to human platelets via its interaction with sialoglycans on the receptor GPIbα. However, in vitro binding assays with SrpA and defined sialoglycans failed to identify specific high-affinity ligands. To improve our understanding of the interaction between SrpA and human platelets, we determined cocrystal structures of the SrpA sialoglycan binding region (SrpA BR ) with five low-affinity ligands: three sialylated trisaccharides (sialyl-T antigen, 3'-sialyllactose, and 3'-sialyl-N-acetyllactosamine), a sialylated tetrasaccharide (sialyl-Lewis X ), and a sialyl galactose disaccharide component common to these sialoglyans. We then combined structural analysis with mutagenesis to further determine whether our observed interactions between SrpA BR and glycans are important for binding to platelets and to better map the binding site for the physiological receptor. We found that the sialoglycan binding site of SrpA BR is significantly larger than the sialoglycans cocrystallized in this study, which suggests that binding of SrpA to platelets either is multivalent or occurs via a larger, disialylated glycan.

  11. Role of multiple hosts in the cross-species transmission and emergence of a pandemic parvovirus.

    Science.gov (United States)

    Allison, Andrew B; Harbison, Carole E; Pagan, Israel; Stucker, Karla M; Kaelber, Jason T; Brown, Justin D; Ruder, Mark G; Keel, M Kevin; Dubovi, Edward J; Holmes, Edward C; Parrish, Colin R

    2012-01-01

    Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV-2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence.

  12. Role of Multiple Hosts in the Cross-Species Transmission and Emergence of a Pandemic Parvovirus

    Science.gov (United States)

    Allison, Andrew B.; Harbison, Carole E.; Pagan, Israel; Stucker, Karla M.; Kaelber, Jason T.; Brown, Justin D.; Ruder, Mark G.; Keel, M. Kevin; Dubovi, Edward J.; Holmes, Edward C.

    2012-01-01

    Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV-2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence. PMID:22072763

  13. Different roles suggested by sex-biased expression and pheromone binding affinity among three pheromone binding proteins in the pink rice borer, Sesamia inferens (Walker) (Lepidoptera: Noctuidae).

    Science.gov (United States)

    Jin, Jun-Yan; Li, Zhao-Qun; Zhang, Ya-Nan; Liu, Nai-Yong; Dong, Shuang-Lin

    2014-07-01

    Pheromone binding proteins (PBPs) are thought to bind and transport hydrophobic sex pheromone molecules across the aqueous sensillar lymph to specific pheromone receptors on the dendritic membrane of olfactory neurons. A maximum of 3 PBP genes have been consistently identified in noctuid species, and each of them shares high identity with its counterparts in other species within the family. The functionality differences of the 3 proteins are poorly understood. In the present study, 3 PBP cDNAs (SinfPBP1, 2, 3) were identified from the pink rice borer, Sesamia inferens, for the first time. The quantitative real-time PCR indicated that the 3 PBPs displayed similar temporal but very different sex related expression profiles. Expression of SinfPBP1 and SinfPBP2 were highly and moderately male biased, respectively, while SinfPBP3 was slightly female biased, as SinfPBPs were expressed at very different levels (PBP1>PBP2≫PBP3) in male antennae, but at similar levels in female antennae. Furthermore, the 3 SinfPBPs displayed different ligand binding profiles in fluorescence competitive binding assays. SinfPBP1 exhibited high and similar binding affinities to all 3 sex pheromone components (Ki=0.72-1.60 μM), while SinfPBP2 showed selective binding to the alcohol and aldehyde components (Ki=0.78-1.71 μM), and SinfPBP3 showed no obvious binding to the 3 sex pheromone components. The results suggest that SinfPBP1 plays a major role in the reception of female sex pheromones in S. inferens, while SinfPBP3 plays a least role (if any) and SinfPBP2 functions as a recognizer of alcohol and aldehyde components. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Structural analysis of dihydrofolate reductases enables rationalization of antifolate binding affinities and suggests repurposing possibilities.

    Science.gov (United States)

    Bhosle, Amrisha; Chandra, Nagasuma

    2016-03-01

    Antifolates are competitive inhibitors of dihydrofolate reductase (DHFR), a conserved enzyme that is central to metabolism and widely targeted in pathogenic diseases, cancer and autoimmune disorders. Although most clinically used antifolates are known to be target specific, some display a fair degree of cross-reactivity with DHFRs from other species. A method that enables identification of determinants of affinity and specificity in target DHFRs from different species and provides guidelines for the design of antifolates is currently lacking. To address this, we first captured the potential druggable space of a DHFR in a substructure called the 'supersite' and classified supersites of DHFRs from 56 species into 16 'site-types' based on pairwise structural similarity. Analysis of supersites across these site-types revealed that DHFRs exhibit varying extents of dissimilarity at structurally equivalent positions in and around the binding site. We were able to explain the pattern of affinities towards chemically diverse antifolates exhibited by DHFRs of different site-types based on these structural differences. We then generated an antifolate-DHFR network by mapping known high-affinity antifolates to their respective supersites and used this to identify antifolates that can be repurposed based on similarity between supersites or antifolates. Thus, we identified 177 human-specific and 458 pathogen-specific antifolates, a large number of which are supported by available experimental data. Thus, in the light of the clinical importance of DHFR, we present a novel approach to identifying differences in the druggable space of DHFRs that can be utilized for rational design of antifolates. © 2016 Federation of European Biochemical Societies.

  15. Two-stage DNA compaction induced by silver ions suggests a cooperative binding mechanism

    Science.gov (United States)

    Jiang, Wen-Yan; Ran, Shi-Yong

    2018-05-01

    The interaction between silver ions and DNA plays an important role in the therapeutic use of silver ions and in related technologies such as DNA sensors. However, the underlying mechanism has not been fully understood. In this study, the dynamics of Ag+-DNA interaction at a single-molecule level was studied using magnetic tweezers. AgNO3 solutions with concentrations ranging from 1 μM to 20 μM led to a 1.4-1.8 μm decrease in length of a single λ-DNA molecule, indicating that Ag+ has a strong binding with DNA, causing the DNA conformational change. The compaction process comprises one linear declining stage and another sigmoid-shaped stage, which can be attributed to the interaction mechanism. Considering the cooperative effect, the sigmoid trend was well explained using a phenomenological model. By contrast, addition of silver nanoparticle solution induced no detectable transition of DNA. The dependence of the interaction on ionic strength and DNA concentration was examined via morphology characterization and particle size distribution measurement. The size of the Ag+-DNA complex decreased with an increase in Ag+ ionic strength ranging from 1 μM to 1 mM. Morphology characterization confirmed that silver ions induced DNA to adopt a compacted globular conformation. At a fixed [AgNO3]:[DNA base pairs] ratio, increasing DNA concentration led to increased sizes of the complexes. Intermolecular interaction is believed to affect the Ag+-DNA complex formation to a large extent.

  16. Pitfalls of DNA Quantification Using DNA-Binding Fluorescent Dyes and Suggested Solutions.

    Science.gov (United States)

    Nakayama, Yuki; Yamaguchi, Hiromi; Einaga, Naoki; Esumi, Mariko

    2016-01-01

    The Qubit fluorometer is a DNA quantification device based on the fluorescence intensity of fluorescent dye binding to double-stranded DNA (dsDNA). Qubit is generally considered useful for checking DNA quality before next-generation sequencing because it measures intact dsDNA. To examine the most accurate and suitable methods for quantifying DNA for quality assessment, we compared three quantification methods: NanoDrop, which measures UV absorbance; Qubit; and quantitative PCR (qPCR), which measures the abundance of a target gene. For the comparison, we used three types of DNA: 1) DNA extracted from fresh frozen liver tissues (Frozen-DNA); 2) DNA extracted from formalin-fixed, paraffin-embedded liver tissues comparable to those used for Frozen-DNA (FFPE-DNA); and 3) DNA extracted from the remaining fractions after RNA extraction with Trizol reagent (Trizol-DNA). These DNAs were serially diluted with distilled water and measured using three quantification methods. For Frozen-DNA, the Qubit values were not proportional to the dilution ratio, in contrast with the NanoDrop and qPCR values. This non-proportional decrease in Qubit values was dependent on a lower salt concentration, and over 1 mM NaCl in the DNA solution was required for the Qubit measurement. For FFPE-DNA, the Qubit values were proportional to the dilution ratio and were lower than the NanoDrop values. However, electrophoresis revealed that qPCR reflected the degree of DNA fragmentation more accurately than Qubit. Thus, qPCR is superior to Qubit for checking the quality of FFPE-DNA. For Trizol-DNA, the Qubit values were proportional to the dilution ratio and were consistently lower than the NanoDrop values, similar to FFPE-DNA. However, the qPCR values were higher than the NanoDrop values. Electrophoresis with SYBR Green I and single-stranded DNA (ssDNA) quantification demonstrated that Trizol-DNA consisted mostly of non-fragmented ssDNA. Therefore, Qubit is not always the most accurate method for

  17. The structure of Plasmodium vivax phosphatidylethanolamine-binding protein suggests a functional motif containing a left-handed helix

    International Nuclear Information System (INIS)

    Arakaki, Tracy; Neely, Helen; Boni, Erica; Mueller, Natasha; Buckner, Frederick S.; Van Voorhis, Wesley C.; Lauricella, Angela; DeTitta, George; Luft, Joseph; Hol, Wim G. J.; Merritt, Ethan A.

    2007-01-01

    The crystal structure of a phosphatidylethanolamine-binding protein from P. vivax, a homolog of Raf-kinase inhibitor protein (RKIP), has been solved to a resolution of 1.3 Å. The inferred interaction surface near the anion-binding site is found to include a distinctive left-handed α-helix. The structure of a putative Raf kinase inhibitor protein (RKIP) homolog from the eukaryotic parasite Plasmodium vivax has been studied to a resolution of 1.3 Å using multiple-wavelength anomalous diffraction at the Se K edge. This protozoan protein is topologically similar to previously studied members of the phosphatidylethanolamine-binding protein (PEBP) sequence family, but exhibits a distinctive left-handed α-helical region at one side of the canonical phospholipid-binding site. Re-examination of previously determined PEBP structures suggests that the P. vivax protein and yeast carboxypeptidase Y inhibitor may represent a structurally distinct subfamily of the diverse PEBP-sequence family

  18. Diversifying selection and functional analysis of interleukin-4 suggests antagonism-driven evolution at receptor-binding interfaces

    Directory of Open Access Journals (Sweden)

    Brown Scott

    2010-07-01

    Full Text Available Abstract Background Interleukin-4 (IL4 is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths 1. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution. Results This analysis revealed evidence of diversifying selection at 15 residues, clustered in epitopes responsible for IL4 binding to its Type I and Type II receptors. Such a striking signature of selective pressure suggested either recurrent episodes of pathogen antagonism or ligand/receptor co-evolution. To test the latter possibility, we performed detailed functional analysis of IL4 allotypes expressed by Mus musculus musculus and Mus musculus castaneus, which happen to differ at 5 residues (including three at positively selected sites in and adjacent to the site 1 epitope that binds the IL4Rα subunit shared by the Type I and Type II IL4 receptors. We show that this intra-species variation affects the ability of IL4 neither to bind IL4 receptor alpha (IL4Rα nor to signal biological responses through its Type I receptor. Conclusions Our results -- reminiscent of clustered positively selected sites revealing functionally important residues at host-virus interaction interfaces -- are consistent with IL4 having evolved to avoid recurrent pathogen antagonism, while maintaining the capacity to bind and signal through its cognate receptor. This work exposes what may be a general feature of evolutionary conflicts fought by pathogen antagonists at host protein-protein interaction interfaces involved in immune signaling: the emergence of receptor-binding ligand epitopes capable of buffering amino acid variation.

  19. Deciphering chemotaxis pathways using cross species comparisons

    Directory of Open Access Journals (Sweden)

    Armitage Judith P

    2010-01-01

    Full Text Available Abstract Background Chemotaxis is the process by which motile bacteria sense their chemical environment and move towards more favourable conditions. Escherichia coli utilises a single sensory pathway, but little is known about signalling pathways in species with more complex systems. Results To investigate whether chemotaxis pathways in other bacteria follow the E. coli paradigm, we analysed 206 species encoding at least 1 homologue of each of the 5 core chemotaxis proteins (CheA, CheB, CheR, CheW and CheY. 61 species encode more than one of all of these 5 proteins, suggesting they have multiple chemotaxis pathways. Operon information is not available for most bacteria, so we developed a novel statistical approach to cluster che genes into putative operons. Using operon-based models, we reconstructed putative chemotaxis pathways for all 206 species. We show that cheA-cheW and cheR-cheB have strong preferences to occur in the same operon as two-gene blocks, which may reflect a functional requirement for co-transcription. However, other che genes, most notably cheY, are more dispersed on the genome. Comparison of our operons with shuffled equivalents demonstrates that specific patterns of genomic location may be a determining factor for the observed in vivo chemotaxis pathways. We then examined the chemotaxis pathways of Rhodobacter sphaeroides. Here, the PpfA protein is known to be critical for correct partitioning of proteins in the cytoplasmically-localised pathway. We found ppfA in che operons of many species, suggesting that partitioning of cytoplasmic Che protein clusters is common. We also examined the apparently non-typical chemotaxis components, CheA3, CheA4 and CheY6. We found that though variants of CheA proteins are rare, the CheY6 variant may be a common type of CheY, with a significantly disordered C-terminal region which may be functionally significant. Conclusions We find that many bacterial species potentially have multiple

  20. Dissociation and metal-binding characteristics of yellow lichen substances suggest a relationship with site preferences of lichens.

    Science.gov (United States)

    Hauck, Markus; Jürgens, Sascha-René; Willenbruch, Karen; Huneck, Siegfried; Leuschner, Christoph

    2009-01-01

    Many species of lichen-forming fungi contain yellow or orange extracellular pigments belonging to the dibenzofurans (usnic acid), anthraquinones (e.g. parietin) or pulvinic acid group. These pigments are all equally efficient light screens, leading us to question the potential ecological and evolutionary significance of diversity in yellow and orange lichen substances. Here the hypothesis is tested that the different pigments differ in metal-binding characteristics, which suggest that they may contribute to adaptation to sites differing in pH and metal availability. UV spectroscopy was used to study the dissociation and the pH dependence of the metal-binding behaviour of seven isolated lichen substances in methanol. Metals applied were selected macro- and micro-nutrients (Cu(2+), Fe(2+), Fe(3+), Mg(2+), Mn(2+) and Zn(2+)). All the pigments studied are strong to moderate acids with pK(a1) values between 2.8 and 4.5. Metal complexation is common in the lichen substances studied. Complexation takes place under acidic conditions with usnic acid, but under alkaline conditions with parietin and most compounds of the pulvinic acid group. The pulvinic acid derivative rhizocarpic acid forms metal complexes both in the acidic and the alkaline range. Metal complexation by lichen substances could be a prerequisite for lichen substance-mediated control of metal uptake. Assuming such an effect at pH values where the affinity of the metal for the lichen substance is intermediate would explain the strong preference of lichens with usnic or rhizocarpic acids to acidic substrata. Moreover, it would explain the preference of lichens with parietin and some lichens with compounds of the pulvinic acid group either for nutrient-rich substrata at low pH or for calcareous substrata.

  1. Alkylation sensitivity screens reveal a conserved cross-species functionome

    Science.gov (United States)

    Svilar, David; Dyavaiah, Madhu; Brown, Ashley R.; Tang, Jiang-bo; Li, Jianfeng; McDonald, Peter R.; Shun, Tong Ying; Braganza, Andrea; Wang, Xiao-hong; Maniar, Salony; St Croix, Claudette M.; Lazo, John S.; Pollack, Ian F.; Begley, Thomas J.; Sobol, Robert W.

    2013-01-01

    To identify genes that contribute to chemotherapy resistance in glioblastoma, we conducted a synthetic lethal screen in a chemotherapy-resistant glioblastoma derived cell line with the clinical alkylator temozolomide (TMZ) and an siRNA library tailored towards “druggable” targets. Select DNA repair genes in the screen were validated independently, confirming the DNA glycosylases UNG and MYH as well as MPG to be involved in the response to high dose TMZ. The involvement of UNG and MYH is likely the result of a TMZ-induced burst of reactive oxygen species. We then compared the human TMZ sensitizing genes identified in our screen with those previously identified from alkylator screens conducted in E. coli and S. cerevisiae. The conserved biological processes across all three species composes an Alkylation Functionome that includes many novel proteins not previously thought to impact alkylator resistance. This high-throughput screen, validation and cross-species analysis was then followed by a mechanistic analysis of two essential nodes: base excision repair (BER) DNA glycosylases (UNG, human and mag1, S. cerevisiae) and protein modification systems, including UBE3B and ICMT in human cells or pby1, lip22, stp22 and aim22 in S. cerevisiae. The conserved processes of BER and protein modification were dual targeted and yielded additive sensitization to alkylators in S. cerevisiae. In contrast, dual targeting of BER and protein modification genes in human cells did not increase sensitivity, suggesting an epistatic relationship. Importantly, these studies provide potential new targets to overcome alkylating agent resistance. PMID:23038810

  2. Structure of an odorant-binding protein from the mosquito Aedes aegypti suggests a binding pocket covered by a pH-sensitive "Lid".

    Directory of Open Access Journals (Sweden)

    Ney Ribeiro Leite

    Full Text Available BACKGROUND: The yellow fever mosquito, Aedes aegypti, is the primary vector for the viruses that cause yellow fever, mostly in tropical regions of Africa and in parts of South America, and human dengue, which infects 100 million people yearly in the tropics and subtropics. A better understanding of the structural biology of olfactory proteins may pave the way for the development of environmentally-friendly mosquito attractants and repellents, which may ultimately contribute to reduction of mosquito biting and disease transmission. METHODOLOGY: Previously, we isolated and cloned a major, female-enriched odorant-binding protein (OBP from the yellow fever mosquito, AaegOBP1, which was later inadvertently renamed AaegOBP39. We prepared recombinant samples of AaegOBP1 by using an expression system that allows proper formation of disulfide bridges and generates functional OBPs, which are indistinguishable from native OBPs. We crystallized AaegOBP1 and determined its three-dimensional structure at 1.85 A resolution by molecular replacement based on the structure of the malaria mosquito OBP, AgamOBP1, the only mosquito OBP structure known to date. CONCLUSION: The structure of AaegOBP1 ( = AaegOBP39 shares the common fold of insect OBPs with six alpha-helices knitted by three disulfide bonds. A long molecule of polyethylene glycol (PEG was built into the electron-density maps identified in a long tunnel formed by a crystallographic dimer of AaegOBP1. Circular dichroism analysis indicated that delipidated AaegOBP1 undergoes a pH-dependent conformational change, which may lead to release of odorant at low pH (as in the environment in the vicinity of odorant receptors. A C-terminal loop covers the binding cavity and this "lid" may be opened by disruption of an array of acid-labile hydrogen bonds thus explaining reduced or no binding affinity at low pH.

  3. A Semantic Cross-Species Derived Data Management Application

    Directory of Open Access Journals (Sweden)

    David B. Keator

    2017-09-01

    Full Text Available Managing dynamic information in large multi-site, multi-species, and multi-discipline consortia is a challenging task for data management applications. Often in academic research studies the goals for informatics teams are to build applications that provide extract-transform-load (ETL functionality to archive and catalog source data that has been collected by the research teams. In consortia that cross species and methodological or scientific domains, building interfaces which supply data in a usable fashion and make intuitive sense to scientists from dramatically different backgrounds increases the complexity for developers. Further, reusing source data from outside one’s scientific domain is fraught with ambiguities in understanding the data types, analysis methodologies, and how to combine the data with those from other research teams. We report on the design, implementation, and performance of a semantic data management application to support the NIMH funded Conte Center at the University of California, Irvine. The Center is testing a theory of the consequences of “fragmented” (unpredictable, high entropy early-life experiences on adolescent cognitive and emotional outcomes in both humans and rodents. It employs cross-species neuroimaging, epigenomic, molecular, and neuroanatomical approaches in humans and rodents to assess the potential consequences of fragmented unpredictable experience on brain structure and circuitry. To address this multi-technology, multi-species approach, the system uses semantic web techniques based on the Neuroimaging Data Model (NIDM to facilitate data ETL functionality. We find this approach enables a low-cost, easy to maintain, and semantically meaningful information management system, enabling the diverse research teams to access and use the data.

  4. A cross-species socio-emotional behaviour development revealed by a multivariate analysis.

    Science.gov (United States)

    Koshiba, Mamiko; Senoo, Aya; Mimura, Koki; Shirakawa, Yuka; Karino, Genta; Obara, Saya; Ozawa, Shinpei; Sekihara, Hitomi; Fukushima, Yuta; Ueda, Toyotoshi; Kishino, Hirohisa; Tanaka, Toshihisa; Ishibashi, Hidetoshi; Yamanouchi, Hideo; Yui, Kunio; Nakamura, Shun

    2013-01-01

    Recent progress in affective neuroscience and social neurobiology has been propelled by neuro-imaging technology and epigenetic approach in neurobiology of animal behaviour. However, quantitative measurements of socio-emotional development remains lacking, though sensory-motor development has been extensively studied in terms of digitised imaging analysis. Here, we developed a method for socio-emotional behaviour measurement that is based on the video recordings under well-defined social context using animal models with variously social sensory interaction during development. The behaviour features digitized from the video recordings were visualised in a multivariate statistic space using principal component analysis. The clustering of the behaviour parameters suggested the existence of species- and stage-specific as well as cross-species behaviour modules. These modules were used to characterise the behaviour of children with or without autism spectrum disorders (ASDs). We found that socio-emotional behaviour is highly dependent on social context and the cross-species behaviour modules may predict neurobiological basis of ASDs.

  5. A Plea for Cross-species Social Neuroscience.

    Science.gov (United States)

    Keysers, Christian; Gazzola, Valeria

    2017-01-01

    Over the past two decades, the question of how our brain makes us sensitive to the state of conspecifics and how that affects our behaviour has undergone a profound change. Twenty years ago what would now be called social neuroscience was focused on the visual processing of facial expressions and body movements in temporal lobe structures of primates (Puce and Perrett 2003). With the discovery of mirror neurons, this changed rapidly towards the modern field of social neuroscience, in which high-level vision is but one of many focuses of interest. In this essay, we will argue that for the further progress of the field, the integration of animal neuroscience and human neuroscience is paramount. We will do so, by focusing on the field of embodied social cognition. We will first show how the combination of animal and human neuroscience was critical in how the discovery of mirror neurons placed the motor system on the map of social cognition. We will then argue why an integrated cross-species approach will be pivotal to our understanding of the neural basis of emotional empathy and its link to prosocial behaviour.

  6. An online conserved SSR discovery through cross-species comparison

    Directory of Open Access Journals (Sweden)

    Tun-Wen Pai

    2009-02-01

    Full Text Available Tun-Wen Pai1, Chien-Ming Chen1, Meng-Chang Hsiao1, Ronshan Cheng2, Wen-Shyong Tzou3, Chin-Hua Hu31Department of Computer Science and Engineering; 2Department of Aquaculture, 3Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, Republic of ChinaAbstract: Simple sequence repeats (SSRs play important roles in gene regulation and genome evolution. Although there exist several online resources for SSR mining, most of them only extract general SSR patterns without providing functional information. Here, an online search tool, CG-SSR (Comparative Genomics SSR discovery, has been developed for discovering potential functional SSRs from vertebrate genomes through cross-species comparison. In addition to revealing SSR candidates in conserved regions among various species, it also combines accurate coordinate and functional genomics information. CG-SSR is the first comprehensive and efficient online tool for conserved SSR discovery.Keywords: microsatellites, genome, comparative genomics, functional SSR, gene ontology, conserved region

  7. Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, Marina E.; Fletcher, Georgina C.; O’Reilly, Nicola; Purkiss, Andrew G.; Thompson, Barry J. [Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3LY (United Kingdom); McDonald, Neil Q., E-mail: neil.mcdonald@cancer.org.uk [Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3LY (United Kingdom); Birkbeck College, University of London, Malet Street, London WC1E 7HX (United Kingdom)

    2015-03-01

    This study characterizes the interaction between the carboxy-terminal (ERLI) motif of the essential polarity protein Crb and the Pals1/Stardust PDZ-domain protein. Structures of human Pals1 PDZ with and without a Crb peptide are described, explaining the highly conserved nature of the ERLI motif and revealing a sterically blocked peptide-binding groove in the absence of ligand. Many components of epithelial polarity protein complexes possess PDZ domains that are required for protein interaction and recruitment to the apical plasma membrane. Apical localization of the Crumbs (Crb) transmembrane protein requires a PDZ-mediated interaction with Pals1 (protein-associated with Lin7, Stardust, MPP5), a member of the p55 family of membrane-associated guanylate kinases (MAGUKs). This study describes the molecular interaction between the Crb carboxy-terminal motif (ERLI), which is required for Drosophila cell polarity, and the Pals1 PDZ domain using crystallography and fluorescence polarization. Only the last four Crb residues contribute to Pals1 PDZ-domain binding affinity, with specificity contributed by conserved charged interactions. Comparison of the Crb-bound Pals1 PDZ structure with an apo Pals1 structure reveals a key Phe side chain that gates access to the PDZ peptide-binding groove. Removal of this side chain enhances the binding affinity by more than fivefold, suggesting that access of Crb to Pals1 may be regulated by intradomain contacts or by protein–protein interaction.

  8. Binding of influenza A virus NS1 protein to the inter-SH2 domain of p85 suggests a novel mechanism for phosphoinositide 3-kinase activation.

    Science.gov (United States)

    Hale, Benjamin G; Batty, Ian H; Downes, C Peter; Randall, Richard E

    2008-01-18

    Influenza A virus NS1 protein stimulates host-cell phosphoinositide 3-kinase (PI3K) signaling by binding to the p85beta regulatory subunit of PI3K. Here, in an attempt to establish a mechanism for this activation, we report further on the functional interaction between NS1 and p85beta. Complex formation was found to be independent of NS1 RNA binding activity and is mediated by the C-terminal effector domain of NS1. Intriguingly, the primary direct binding site for NS1 on p85beta is the inter-SH2 domain, a coiled-coil structure that acts as a scaffold for the p110 catalytic subunit of PI3K. In vitro kinase activity assays, together with protein binding competition studies, reveal that NS1 does not displace p110 from the inter-SH2 domain, and indicate that NS1 can form an active heterotrimeric complex with PI3K. In addition, it was established that residues at the C terminus of the inter-SH2 domain are essential for mediating the interaction between p85beta and NS1. Equivalent residues in p85alpha have previously been implicated in the basal inhibition of p110. However, such p85alpha residues were unable to substitute for those in p85beta with regards NS1 binding. Overall, these data suggest a model by which NS1 activates PI3K catalytic activity by masking a normal regulatory element specific to the p85beta inter-SH2 domain.

  9. Cross-species functionality of pararetroviral elements driving ribosome shunting.

    Directory of Open Access Journals (Sweden)

    Mikhail M Pooggin

    Full Text Available BACKGROUND: Cauliflower mosaic virus (CaMV and Rice tungro bacilliform virus (RTBV belong to distinct genera of pararetroviruses infecting dicot and monocot plants, respectively. In both viruses, polycistronic translation of pregenomic (pg RNA is initiated by shunting ribosomes that bypass a large region of the pgRNA leader with several short (sORFs and a stable stem-loop structure. The shunt requires translation of a 5'-proximal sORF terminating near the stem. In CaMV, mutations knocking out this sORF nearly abolish shunting and virus viability. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that two distant regions of the CaMV leader that form a minimal shunt configuration comprising the sORF, a bottom part of the stem, and a shunt landing sequence can be replaced by heterologous sequences that form a structurally similar configuration in RTBV without any dramatic effect on shunt-mediated translation and CaMV infectivity. The CaMV-RTBV chimeric leader sequence was largely stable over five viral passages in turnip plants: a few alterations that did eventually occur in the virus progenies are indicative of fine tuning of the chimeric sequence during adaptation to a new host. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate cross-species functionality of pararetroviral cis-elements driving ribosome shunting and evolutionary conservation of the shunt mechanism. We are grateful to Matthias Müller and Sandra Pauli for technical assistance. This work was initiated at Friedrich Miescher Institute (Basel, Switzerland. We thank Prof. Thomas Boller for hosting the group at the Institute of Botany.

  10. Refined repetitive sequence searches utilizing a fast hash function and cross species information retrievals

    Directory of Open Access Journals (Sweden)

    Reneker Jeff

    2005-05-01

    Full Text Available Abstract Background Searching for small tandem/disperse repetitive DNA sequences streamlines many biomedical research processes. For instance, whole genomic array analysis in yeast has revealed 22 PHO-regulated genes. The promoter regions of all but one of them contain at least one of the two core Pho4p binding sites, CACGTG and CACGTT. In humans, microsatellites play a role in a number of rare neurodegenerative diseases such as spinocerebellar ataxia type 1 (SCA1. SCA1 is a hereditary neurodegenerative disease caused by an expanded CAG repeat in the coding sequence of the gene. In bacterial pathogens, microsatellites are proposed to regulate expression of some virulence factors. For example, bacteria commonly generate intra-strain diversity through phase variation which is strongly associated with virulence determinants. A recent analysis of the complete sequences of the Helicobacter pylori strains 26695 and J99 has identified 46 putative phase-variable genes among the two genomes through their association with homopolymeric tracts and dinucleotide repeats. Life scientists are increasingly interested in studying the function of small sequences of DNA. However, current search algorithms often generate thousands of matches – most of which are irrelevant to the researcher. Results We present our hash function as well as our search algorithm to locate small sequences of DNA within multiple genomes. Our system applies information retrieval algorithms to discover knowledge of cross-species conservation of repeat sequences. We discuss our incorporation of the Gene Ontology (GO database into these algorithms. We conduct an exhaustive time analysis of our system for various repetitive sequence lengths. For instance, a search for eight bases of sequence within 3.224 GBases on 49 different chromosomes takes 1.147 seconds on average. To illustrate the relevance of the search results, we conduct a search with and without added annotation terms for the

  11. Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

    Science.gov (United States)

    Cauli, Alberto; Mathieu, Alessandro; Tedeschi, Valentina; Caristi, Silvana; Sorrentino, Rosa; Böckmann, Rainer A.; Fiorillo, Maria Teresa

    2012-01-01

    The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype. PMID:22403718

  12. Role of plant MicroRNA in cross-species regulatory networks of humans.

    Science.gov (United States)

    Zhang, Hao; Li, Yanpu; Liu, Yuanning; Liu, Haiming; Wang, Hongyu; Jin, Wen; Zhang, Yanmei; Zhang, Chao; Xu, Dong

    2016-08-08

    It has been found that microRNAs (miRNAs) can function as a regulatory factor across species. For example, food-derived plant miRNAs may pass through the gastrointestinal (GI) tract, enter into the plasma and serum of mammals, and interact with endogenous RNAs to regulate their expression. Although this new type of regulatory mechanism is not well understood, it provides a fresh look at the relationship between food consumption and physiology. To investigate this new type of mechanism, we conducted a systematic computational study to analyze the potential functions of these dietary miRNAs in the human body. In this paper, we predicted human and plant target genes using RNAhybrid and set some criteria to further filter them. Then we built the cross-species regulatory network according to the filtered targets, extracted central nodes by PageRank algorithm and built core modules. We summarized the functions of these modules to three major categories: ion transport, metabolic process and stress response, and especially some target genes are highly related to ion transport, polysaccharides and the lipid metabolic process. Through functional analysis, we found that human and plants have similar functions such as ion transport and stress response, so our study also indicates the existence of a close link between exogenous plant miRNA targets and digestive/urinary organs. According to our analysis results, we suggest that the ingestion of these plant miRNAs may have a functional impact on consuming organisms in a cross-kingdom way, and the dietary habit may affect the physiological condition at a genetic level. Our findings may be useful for discovering cross-species regulatory mechanism in further study.

  13. Identification, validation and cross-species transferability of novel Lavandula EST-SSRs.

    Science.gov (United States)

    Adal, Ayelign M; Demissie, Zerihun A; Mahmoud, Soheil S

    2015-04-01

    We identified and characterized EST-SSRs with strong discrimination power against Lavandula angustifolia and Lavandula x intermedia . The markers also showed considerable cross-species transferability rate into six related Lavandula species. Lavenders (Lavandula) are important economical crops grown around the globe for essential oil production. In an attempt to develop genetic markers for these plants, we analyzed over 13,000 unigenes developed from L. angustifolia and L. x intermedia EST databases, and identified 3,459 simple sequence repeats (SSR), which were dominated by trinucleotides (41.2 %) and dinucleotides (31.45 %). Approximately, 19 % of the unigenes contained at least one SSR marker, over 60 % of which were localized in the UTRs. Only 252 EST-SSRs were 18 bp or longer from which 31 loci were validated, and 24 amplified discrete fragments with 85 % polymorphism in L. x intermedia and L. angustifolia. The average number of alleles in L. x intermedia and L. angustifolia were 3.42 and 3.71 per marker with average PIC values of 0.47 and 0.52, respectively. These values suggest a moderate to strong level of informativeness for the markers, with some loci producing unique fingerprints. The cross-species transferability rate of the markers ranges 50-100 % across eight species. The utility of these markers was assessed in eight Lavandula species and 15 L. angustifolia and L. x intermedia cultivars, and the dendrogram deduced from their similarity indexes successfully delineated the species into their respective sections and the cultivars into their respective species. These markers have potential for application in fingerprinting, diversity studies and marker-assisted breeding of Lavandula.

  14. The relationship between impulsive choice and impulsive action: a cross-species translational study.

    Directory of Open Access Journals (Sweden)

    Nienke Broos

    Full Text Available Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task and impulsive action (five-choice serial reaction time task paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT and impulsive action (immediate and delayed memory task, IMT/DMT. Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action and filled out the Barratt impulsiveness scale (BIS-11. Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1 self-reported impulsivity (BIS-11; (2 impulsive action (IMT/DMT and SST; (3 impulsive choice (DDT. This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology.

  15. Application of cross-species PET imaging to assess neurotransmitter release in brain.

    Science.gov (United States)

    Finnema, Sjoerd J; Scheinin, Mika; Shahid, Mohammed; Lehto, Jussi; Borroni, Edilio; Bang-Andersen, Benny; Sallinen, Jukka; Wong, Erik; Farde, Lars; Halldin, Christer; Grimwood, Sarah

    2015-11-01

    This review attempts to summarize the current status in relation to the use of positron emission tomography (PET) imaging in the assessment of synaptic concentrations of endogenous mediators in the living brain. Although PET radioligands are now available for more than 40 CNS targets, at the initiation of the Innovative Medicines Initiative (IMI) "Novel Methods leading to New Medications in Depression and Schizophrenia" (NEWMEDS) in 2009, PET radioligands sensitive to an endogenous neurotransmitter were only validated for dopamine. NEWMEDS work-package 5, "Cross-species and neurochemical imaging (PET) methods for drug discovery", commenced with a focus on developing methods enabling assessment of changes in extracellular concentrations of serotonin and noradrenaline in the brain. Sharing the workload across institutions, we utilized in vitro techniques with cells and tissues, in vivo receptor binding and microdialysis techniques in rodents, and in vivo PET imaging in non-human primates and humans. Here, we discuss these efforts and review other recently published reports on the use of radioligands to assess changes in endogenous levels of dopamine, serotonin, noradrenaline, γ-aminobutyric acid, glutamate, acetylcholine, and opioid peptides. The emphasis is on assessment of the availability of appropriate translational tools (PET radioligands, pharmacological challenge agents) and on studies in non-human primates and human subjects, as well as current challenges and future directions. PET imaging directed at investigating changes in endogenous neurochemicals, including the work done in NEWMEDS, have highlighted an opportunity to further extend the capability and application of this technology in drug development.

  16. Leveraging Cross- Species Transcription Factor Binding Site Patterns : From Diabetes Risk Loci to Disease Mechanisms

    NARCIS (Netherlands)

    Claussnitzer, Melina; Dankel, Simon N.; Klocke, Bernward; Grallert, Harald; Glunk, Viktoria; Berulava, Tea; Lee, Heekyoung; Oskolkov, Nikolay; Fadista, Joao; Ehlers, Kerstin; Wahl, Simone; Hoffmann, Christoph; Qian, Kun; Ronn, Tina; Riess, Helene; Mueller-Nurasyid, Martina; Bretschneider, Nancy; Schroeder, Timm; Skurk, Thomas; Horsthemke, Bernhard; Spieler, Derek; Klingenspor, Martin; Seifert, Martin; Kern, Michael J.; Mejhert, Niklas; Dahlman, Ingrid; Hansson, Ola; Hauck, Stefanie M.; Blueher, Matthias; Arner, Peter; Groop, Leif; Illig, Thomas; Suhre, Karsten; Hsu, Yi-Hsiang; Mellgren, Gunnar; Hauner, Hans; Laumen, Helmut; Wijmenga, Tjitske N.; van Vliet-Ostaptchouk, Jana V.

    2014-01-01

    Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to

  17. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

    Science.gov (United States)

    Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

    2016-02-01

    Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  18. Cross species amplification ability of novel microsatellites isolated from Jatropha curcas and genetic relationship with sister taxa : Cross species amplification and genetic relationship of Jatropha using novel microsatellites

    KAUST Repository

    Pamidimarri, D. V N N Sudheer; Mastan, Shaik G.; Rahman, Hifzur; Ravi Prakash, Ch; Singh, Sweta V.; Reddy, Muppala P.

    2010-01-01

    -21 amplified in J. curcas. However, these markers did not show any cross species amplification. Overall percentage of polymorphism (PP) among the species studied was 38% and the mean genetic similarity (GS) was found to be 0.86. The highest PP (24

  19. In vivo immunotherapy of lung cancer using cross-species reactive vascular endothelial growth factor nanobodies

    Directory of Open Access Journals (Sweden)

    vFatemeh Kazemi-Lomedasht v

    2017-05-01

    Full Text Available Objective(s: Lung cancer is the main leading cause of cancer death worldwide. Angiogenesis is the main step in proliferation and spreading of tumor cells. Targeting vascular endothelial growth factor (VEGF is an effective approach for inhibition of cancer angiogenesis. Nanobodies (NBs are a novel class of antibodies derived from the camel. Unique characteristics of Nbs like their small size and good penetration to tumor tissues makes them promising tools in drug development.  Development of NBs targeting both human and mouse VEGF is required for understanding their in vivo functions.  Therefore, development of cross-species reactive anti-VEGF Nbs for immunotherapy of lung cancer was the main aim of the current study. Materials and Methods: Here we developed NBs from Camelus dromedarius library with high specificity and binding affinity to both human and mouse VEGF. In vitro and In vivo function of developed NB was evaluated on human endothelial cells and lung epithelial tumor cells (TC-1. Results: A nanobody showed the highest affinity to human and mouse VEGF and potently inhibited VEGF in the ELISA experiment. Anti-VEGF NBs significantly inhibited in vitro human endothelial cell migration through blockade of VEGF (P=0.045. Anti-VEGF NBs also significantly inhibited in vivo TC-1 growth in a dose-dependent manner (P=0.001 and resulted in higher survival rate in the nanobody treated group Conclusion: These findings demonstrate the potential of anti-VEGF NBsin tumor growth inhibition and are promising as novel cancer therapeutic candidate.

  20. Modeling of arylamide helix mimetics in the p53 peptide binding site of hDM2 suggests parallel and anti-parallel conformations are both stable.

    Directory of Open Access Journals (Sweden)

    Jonathan C Fuller

    Full Text Available The design of novel α-helix mimetic inhibitors of protein-protein interactions is of interest to pharmaceuticals and chemical genetics researchers as these inhibitors provide a chemical scaffold presenting side chains in the same geometry as an α-helix. This conformational arrangement allows the design of high affinity inhibitors mimicking known peptide sequences binding specific protein substrates. We show that GAFF and AutoDock potentials do not properly capture the conformational preferences of α-helix mimetics based on arylamide oligomers and identify alternate parameters matching solution NMR data and suitable for molecular dynamics simulation of arylamide compounds. Results from both docking and molecular dynamics simulations are consistent with the arylamides binding in the p53 peptide binding pocket. Simulations of arylamides in the p53 binding pocket of hDM2 are consistent with binding, exhibiting similar structural dynamics in the pocket as simulations of known hDM2 binders Nutlin-2 and a benzodiazepinedione compound. Arylamide conformations converge towards the same region of the binding pocket on the 20 ns time scale, and most, though not all dihedrals in the binding pocket are well sampled on this timescale. We show that there are two putative classes of binding modes for arylamide compounds supported equally by the modeling evidence. In the first, the arylamide compound lies parallel to the observed p53 helix. In the second class, not previously identified or proposed, the arylamide compound lies anti-parallel to the p53 helix.

  1. Cross species amplification ability of novel microsatellites isolated from Jatropha curcas and genetic relationship with sister taxa : Cross species amplification and genetic relationship of Jatropha using novel microsatellites

    KAUST Repository

    Pamidimarri, D. V N N Sudheer

    2010-07-30

    The present investigation was undertaken with an aim to check the ability of cross species amplification of microsatellite markers isolated from Jatropha curcas-a renewable source of biodiesel to deduce the generic relationship with its six sister taxa (J. glandulifera, J. gossypifolia, J. integerrima, J. multifida, J. podagrica, and J. tanjorensis). Out of the 49 markers checked 31 markers showed cross species amplification in all the species studied. JCDS-30, JCDS-69, JCDS-26, JCMS-13 and JCMS-21 amplified in J. curcas. However, these markers did not show any cross species amplification. Overall percentage of polymorphism (PP) among the species studied was 38% and the mean genetic similarity (GS) was found to be 0.86. The highest PP (24) and least GS (0.76) was found between J. curcas/J. podagrica and J. curcas/J. multifida and least PP (4.44) and highest GS (0.96) was found between J. integerrima/J. tanjorensis. Dendrogram analysis showed good congruence to RAPD and AFLP than nrDNA ITS data reported earlier. The characterized microsatellites will pave way for intraspecies molecular characterization which can be further utilized in species differentiation, molecular identification, characterization of interspecific hybrids, exploitation of genetic resource management and genetic improvement of the species through marker assisted breeding for economically important traits. © 2010 Springer Science+Business Media B.V.

  2. Residues essential for Panton-Valentine leukocidin S component binding to its cell receptor suggest both plasticity and adaptability in its interaction surface.

    Directory of Open Access Journals (Sweden)

    Benoit-Joseph Laventie

    Full Text Available Panton-Valentine leukocidin (PVL, a bicomponent staphylococcal leukotoxin, is involved in the poor prognosis of necrotizing pneumonia. The present study aimed to elucidate the binding mechanism of PVL and in particular its cell-binding domain. The class S component of PVL, LukS-PV, is known to ensure cell targeting and exhibits the highest affinity for the neutrophil membrane (Kd∼10(-10 M compared to the class F component of PVL, LukF-PV (Kd∼10(-9 M. Alanine scanning mutagenesis was used to identify the residues involved in LukS-PV binding to the neutrophil surface. Nineteen single alanine mutations were performed in the rim domain previously described as implicated in cell membrane interactions. Positions were chosen in order to replace polar or exposed charged residues and according to conservation between leukotoxin class S components. Characterization studies enabled to identify a cluster of residues essential for LukS-PV binding, localized on two loops of the rim domain. The mutations R73A, Y184A, T244A, H245A and Y250A led to dramatically reduced binding affinities for both human leukocytes and undifferentiated U937 cells expressing the C5a receptor. The three-dimensional structure of five of the mutants was determined using X-ray crystallography. Structure analysis identified residues Y184 and Y250 as crucial in providing structural flexibility in the receptor-binding domain of LukS-PV.

  3. Cloning of cDNA sequences encoding cowpea (Vigna unguiculata) vicilins: Computational simulations suggest a binding mode of cowpea vicilins to chitin oligomers.

    Science.gov (United States)

    Rocha, Antônio J; Sousa, Bruno L; Girão, Matheus S; Barroso-Neto, Ito L; Monteiro-Júnior, José E; Oliveira, José T A; Nagano, Celso S; Carneiro, Rômulo F; Monteiro-Moreira, Ana C O; Rocha, Bruno A M; Freire, Valder N; Grangeiro, Thalles B

    2018-05-27

    Vicilins are 7S globulins which constitute the major seed storage proteins in leguminous species. Variant vicilins showing differential binding affinities for chitin have been implicated in the resistance and susceptibility of cowpea to the bruchid Callosobruchus maculatus. These proteins are members of the cupin superfamily, which includes a wide variety of enzymes and non-catalytic seed storage proteins. The cupin fold does not share similarity with any known chitin-biding domain. Therefore, it is poorly understood how these storage proteins bind to chitin. In this work, partial cDNA sequences encoding β-vignin, the major component of cowpea vicilins, were obtained from developing seeds. Three-dimensional molecular models of β-vignin showed the characteristic cupin fold and computational simulations revealed that each vicilin trimer contained 3 chitin-binding sites. Interaction models showed that chito-oligosaccharides bound to β-vignin were stabilized mainly by hydrogen bonds, a common structural feature of typical carbohydrate-binding proteins. Furthermore, many of the residues involved in the chitin-binding sites of β-vignin are conserved in other 7S globulins. These results support previous experimental evidences on the ability of vicilin-like proteins from cowpea and other leguminous species to bind in vitro to chitin as well as in vivo to chitinous structures of larval C. maculatus midgut. Copyright © 2018. Published by Elsevier B.V.

  4. Ultra-deep sequencing of intra-host rabies virus populations during cross-species transmission.

    Directory of Open Access Journals (Sweden)

    Monica K Borucki

    2013-11-01

    Full Text Available One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350 in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009 and geographic location (northern vs. southern. A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change.

  5. A critical look at the calculation of the binding characteristics and concentration of iron complexing ligands in seawater with suggested improvements

    NARCIS (Netherlands)

    Gerringa, L.J.A.; Rijkenberg, M.J.A.; Thuróczy, C.-E.; Maas, L.R.M.

    2014-01-01

    Environmental context
    The low concentration of iron in the oceans limits growth of phytoplankton. Dissolved organic molecules, called ligands, naturally present in seawater, bind iron thereby increasing its solubility and, consequently, its availability for biological uptake by phytoplankton. The

  6. In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function.

    Science.gov (United States)

    Follin, Elna; Karlsson, Maria; Lundegaard, Claus; Nielsen, Morten; Wallin, Stefan; Paulsson, Kajsa; Westerdahl, Helena

    2013-04-01

    The major histocompatibility complex (MHC) genes are the most polymorphic genes found in the vertebrate genome, and they encode proteins that play an essential role in the adaptive immune response. Many songbirds (passerines) have been shown to have a large number of transcribed MHC class I genes compared to most mammals. To elucidate the reason for this large number of genes, we compared 14 MHC class I alleles (α1-α3 domains), from great reed warbler, house sparrow and tree sparrow, via phylogenetic analysis, homology modelling and in silico peptide-binding predictions to investigate their functional and genetic relationships. We found more pronounced clustering of the MHC class I allomorphs (allele specific proteins) in regards to their function (peptide-binding specificities) compared to their genetic relationships (amino acid sequences), indicating that the high number of alleles is of functional significance. The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged 10 million years ago (MYA), had overlapping peptide-binding specificities, and these similarities across species were also confirmed in phylogenetic analyses based on amino acid sequences. Notably, there were also overlapping peptide-binding specificities in the allomorphs from house sparrow and great reed warbler, although these species diverged 30 MYA. This overlap was not found in a tree based on amino acid sequences. Our interpretation is that convergent evolution on the level of the protein function, possibly driven by selection from shared pathogens, has resulted in allomorphs with similar peptide-binding repertoires, although trans-species evolution in combination with gene conversion cannot be ruled out.

  7. The structure of lactoferrin-binding protein B from Neisseria meningitidis suggests roles in iron acquisition and neutralization of host defences

    Science.gov (United States)

    Brooks, Cory L.; Arutyunova, Elena; Lemieux, M. Joanne

    2014-01-01

    Pathogens have evolved a range of mechanisms to acquire iron from the host during infection. Several Gram-negative pathogens including members of the genera Neisseria and Moraxella have evolved two-component systems that can extract iron from the host glycoproteins lactoferrin and transferrin. The homologous iron-transport systems consist of a membrane-bound transporter and an accessory lipoprotein. While the mechanism behind iron acquisition from transferrin is well understood, relatively little is known regarding how iron is extracted from lactoferrin. Here, the crystal structure of the N-terminal domain (N-lobe) of the accessory lipoprotein lactoferrin-binding protein B (LbpB) from the pathogen Neisseria meningitidis is reported. The structure is highly homologous to the previously determined structures of the accessory lipoprotein transferrin-binding protein B (TbpB) and LbpB from the bovine pathogen Moraxella bovis. Docking the LbpB structure with lactoferrin reveals extensive binding interactions with the N1 subdomain of lactoferrin. The nature of the interaction precludes apolactoferrin from binding LbpB, ensuring the specificity of iron-loaded lactoferrin. The specificity of LbpB safeguards proper delivery of iron-bound lactoferrin to the transporter lactoferrin-binding protein A (LbpA). The structure also reveals a possible secondary role for LbpB in protecting the bacteria from host defences. Following proteolytic digestion of lactoferrin, a cationic peptide derived from the N-terminus is released. This peptide, called lactoferricin, exhibits potent antimicrobial effects. The docked model of LbpB with lactoferrin reveals that LbpB interacts extensively with the N-terminal lactoferricin region. This may provide a venue for preventing the production of the peptide by proteolysis, or directly sequestering the peptide, protecting the bacteria from the toxic effects of lactoferricin. PMID:25286931

  8. Structural models of zebrafish (Danio rerio NOD1 and NOD2 NACHT domains suggest differential ATP binding orientations: insights from computational modeling, docking and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Jitendra Maharana

    Full Text Available Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds and Aspartic acid (Walker B formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2 interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

  9. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  10. Polymorphic microsatellites developed by cross-species amplifications in common pheasant breeds

    NARCIS (Netherlands)

    Baratti, M.; Alberti, A.; Groenen, M.A.M.; Veenendaal, T.; Fulgheri, F.D.

    2001-01-01

    Genetic variability was analysed in two common breeds of pheasant (Phasianus colchicus L. 1758) by means of cross-species amplifications of microsatellite loci: 154 chicken, Gallus gallus and 32 turkey, Meleagris gallopavo, primers were tested for amplification of pheasant DNA. Thirty-six primers

  11. CROPPER: a metagene creator resource for cross-platform and cross-species compendium studies.

    Science.gov (United States)

    Paananen, Jussi; Storvik, Markus; Wong, Garry

    2006-09-22

    Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.

  12. PNA binding to the non-template DNA strand interferes with transcription, suggesting a blockage mechanism mediated by R-loop formation.

    Science.gov (United States)

    Belotserkovskii, Boris P; Hanawalt, Philip C

    2015-11-01

    Peptide Nucleic Acids (PNAs) are artificial DNA mimics with superior nucleic acid binding capabilities. T7 RNA polymerase (T7 RNAP) transcription upon encountering PNA bound to the non-template DNA strand was studied in vitro. A characteristic pattern of blockage signals was observed, extending downstream from the PNA binding site, similar to that produced by G-rich homopurine-homopyrimidine (hPu-hPy) sequences and likely caused by R-loop formation. Since blocked transcription complexes in association with stable R-loops may interfere with replication and in some cases trigger apoptosis, targeted R-loop formation might be employed to inactivate selected cells, such as those in tumors, based upon their unique complement of expressed genes. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

  13. Elucidation of cross-species proteomic effects in human and hominin bone proteome identification through a bioinformatics experiment.

    Science.gov (United States)

    Welker, F

    2018-02-20

    The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein identifications at increased evolutionary distances due to a larger number of protein sequence differences between the database sequence and the analyzed organism. Error-tolerant proteomic search algorithms should theoretically overcome this problem at both the peptide and protein level; however, this has not been demonstrated. If error-tolerant searches do not overcome the cross-species proteomic issue then there might be inherent biases in the identified proteomes. Here, a bioinformatics experiment is performed to test this using a set of modern human bone proteomes and three independent searches against sequence databases at increasing evolutionary distances: the human (0 Ma), chimpanzee (6-8 Ma) and orangutan (16-17 Ma) reference proteomes, respectively. Incorrectly suggested amino acid substitutions are absent when employing adequate filtering criteria for mutable Peptide Spectrum Matches (PSMs), but roughly half of the mutable PSMs were not recovered. As a result, peptide and protein identification rates are higher in error-tolerant mode compared to non-error-tolerant searches but did not recover protein identifications completely. Data indicates that peptide length and the number of mutations between the target and database sequences are the main factors influencing mutable PSM identification. The error-tolerant results suggest that the cross-species proteomics problem is not overcome at increasing evolutionary distances, even at the protein level. Peptide and protein loss has the potential to significantly impact divergence dating and proteome comparisons when using ancient samples as there is a bias towards the identification of conserved sequences and proteins. Effects are minimized

  14. Feline Immunodeficiency Virus Cross-Species Transmission: Implications for Emergence of New Lentiviral Infections.

    Science.gov (United States)

    Lee, Justin; Malmberg, Jennifer L; Wood, Britta A; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin; Serieys, Laurel; Riley, Seth; Crooks, Kevin; VandeWoude, Sue

    2017-03-01

    Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats ( Lynx rufus ) and mountain lions ( Puma concolor ) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers ( Puma concolor coryi ) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates. IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which

  15. Heterochrony and cross-species intersensory matching by infant vervet monkeys.

    Directory of Open Access Journals (Sweden)

    Shahin Zangenehpour

    Full Text Available Understanding the evolutionary origins of a phenotype requires understanding the relationship between ontogenetic and phylogenetic processes. Human infants have been shown to undergo a process of perceptual narrowing during their first year of life, whereby their intersensory ability to match the faces and voices of another species declines as they get older. We investigated the evolutionary origins of this behavioral phenotype by examining whether or not this developmental process occurs in non-human primates as well.We tested the ability of infant vervet monkeys (Cercopithecus aethiops, ranging in age from 23 to 65 weeks, to match the faces and voices of another non-human primate species (the rhesus monkey, Macaca mulatta. Even though the vervets had no prior exposure to rhesus monkey faces and vocalizations, our findings show that infant vervets can, in fact, recognize the correspondence between rhesus monkey faces and voices (but indicate that they do so by looking at the non-matching face for a greater proportion of overall looking time, and can do so well beyond the age of perceptual narrowing in human infants. Our results further suggest that the pattern of matching by vervet monkeys is influenced by the emotional saliency of the Face+Voice combination. That is, although they looked at the non-matching screen for Face+Voice combinations, they switched to looking at the matching screen when the Voice was replaced with a complex tone of equal duration. Furthermore, an analysis of pupillary responses revealed that their pupils showed greater dilation when looking at the matching natural face/voice combination versus the face/tone combination.Because the infant vervets in the current study exhibited cross-species intersensory matching far later in development than do human infants, our findings suggest either that intersensory perceptual narrowing does not occur in Old World monkeys or that it occurs later in development. We argue that these

  16. GeMprospector--online design of cross-species genetic marker candidates in legumes and grasses.

    Science.gov (United States)

    Fredslund, Jakob; Madsen, Lene H; Hougaard, Birgit K; Sandal, Niels; Stougaard, Jens; Bertioli, David; Schauser, Leif

    2006-07-01

    The web program GeMprospector (URL: http://cgi-www.daimi.au.dk/cgi-chili/GeMprospector/main) allows users to automatically design large sets of cross-species genetic marker candidates targeting either legumes or grasses. The user uploads a collection of ESTs from one or more legume or grass species, and they are compared with a database of clusters of homologous EST and genomic sequences from other legumes or grasses, respectively. Multiple sequence alignments between submitted ESTs and their homologues in the appropriate database form the basis of automated PCR primer design in conserved exons such that each primer set amplifies an intron. The only user input is a collection of ESTs, not necessarily from more than one species, and GeMprospector can boost the potential of such an EST collection by combining it with a large database to produce cross-species genetic marker candidates for legumes or grasses.

  17. Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

    Energy Technology Data Exchange (ETDEWEB)

    Ovacik, Meric A. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Androulakis, Ioannis P., E-mail: yannis@rci.rutgers.edu [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Biomedical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States)

    2013-09-15

    Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.

  18. Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

    International Nuclear Information System (INIS)

    Ovacik, Meric A.; Androulakis, Ioannis P.

    2013-01-01

    Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy

  19. Spontaneous cross-species imitation in interactions between chimpanzees and zoo visitors.

    Science.gov (United States)

    Persson, Tomas; Sauciuc, Gabriela-Alina; Madsen, Elainie Alenkær

    2018-01-01

    Imitation is a cornerstone of human development, serving both a cognitive function (e.g. in the acquisition and transmission of skills and knowledge) and a social-communicative function, whereby the imitation of familiar actions serves to maintain social interaction and promote prosociality. In nonhuman primates, this latter function is poorly understood, or even claimed to be absent. In this observational study, we documented interactions between chimpanzees and zoo visitors and found that the two species imitated each other at a similar rate, corresponding to almost 10% of all produced actions. Imitation appeared to accomplish a social-communicative function, as cross-species interactions that contained imitative actions lasted significantly longer than interactions without imitation. In both species, physical proximity promoted cross-species imitation. Overall, imitative precision was higher among visitors than among chimpanzees, but this difference vanished in proximity contexts, i.e. in the indoor environment. Four of five chimpanzees produced imitations; three of them exhibited comparable imitation rates, despite large individual differences in level of cross-species interactivity. We also found that chimpanzees evidenced imitation recognition, yet only when visitors imitated their actions (as opposed to postures). Imitation recognition was expressed by returned imitation in 36% of the cases, and all four imitating chimpanzees engaged in so-called imitative games. Previously regarded as unique to early human socialization, such games serve to maintain social engagement. The results presented here indicate that nonhuman apes exhibit spontaneous imitation that can accomplish a communicative function. The study raises a number of novel questions for imitation research and highlights the imitation of familiar behaviours as a relevant-yet thus far understudied-research topic.

  20. Experimental cross-species infection of common marmosets by titi monkey adenovirus.

    Directory of Open Access Journals (Sweden)

    Guixia Yu

    Full Text Available Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV, as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus. Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.

  1. Cross-Species Virus-Host Protein-Protein Interactions Inhibiting Innate Immunity

    Science.gov (United States)

    2016-07-01

    diseases are a regular occurrence globally (Figure 1). The Zika virus is the latest example gaining widespread attention. Many of the (re-)emerging...for establishing infection and/or modulating pathogenesis (Figures 2 and 3). 3 Figure 2. Schematic of several virus -host protein interactions within...8725 John J. Kingman Road, MS 6201 Fort Belvoir, VA 22060-6201 T E C H N IC A L R E P O R T DTRA-TR-16-79 Cross-species virus -host

  2. Frequent cross-species transmission of parvoviruses among diverse carnivore hosts

    Science.gov (United States)

    Allison, Andrew B.; Kohler, Dennis J.; Fox, Karen A.; Brown, Justin D.; Gerhold, Richard W.; Shearn-Bochsler, Valerie I.; Dubovi, Edward J.; Parrish, Colin R.; Holmes, Edward C.

    2013-01-01

    Although parvoviruses are commonly described in domestic carnivores, little is known about their biodiversity in nondomestic species. A phylogenetic analysis of VP2 gene sequences from puma, coyote, gray wolf, bobcat, raccoon, and striped skunk revealed two major groups related to either feline panleukopenia virus (“FPV-like”) or canine parvovirus (“CPV-like”). Cross-species transmission was commonplace, with multiple introductions into each host species but, with the exception of raccoons, relatively little evidence for onward transmission in nondomestic species.

  3. Three-dimensional models of Mycobacterium tuberculosis proteins Rv1555, Rv1554 and their docking analyses with sildenafil, tadalafil, vardenafil drugs, suggest interference with quinol binding likely to affect protein's function.

    Science.gov (United States)

    Dash, Pallabini; Bala Divya, M; Guruprasad, Lalitha; Guruprasad, Kunchur

    2018-04-18

    Earlier based on bioinformatics analyses, we had predicted the Mycobacterium tuberculosis (M.tb) proteins; Rv1555 and Rv1554, among the potential new tuberculosis drug targets. According to the 'TB-drugome' the Rv1555 protein is 'druggable' with sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra) drugs. In the present work, we intended to understand via computer modeling studies, how the above drugs are likely to inhibit the M.tb protein's function. The three-dimensional computer models for M.tb proteins; Rv1555 and Rv1554 constructed on the template of equivalent membrane anchor subunits of the homologous E.coli quinol fumarate reductase respiratory protein complex, followed by drug docking analyses, suggested that the binding of above drugs interferes with quinol binding sites. Also, we experimentally observed the in-vitro growth inhibition of E.coli bacteria containing the homologous M.tb protein sequences with sildenafil and tadalafil drugs. The predicted binding sites of the drugs is likely to affect the above M.tb proteins function as quinol binding is known to be essential for electron transfer function during anaerobic respiration in the homologous E.coli protein complex. Therefore, sildenafil and related drugs currently used in the treatment of male erectile dysfunction targeting the human phosphodiesterase 5 enzyme may be evaluated for their plausible role as repurposed drugs to treat human tuberculosis.

  4. “Controlled, cross-species dataset for exploring biases in genome annotation and modification profiles”

    Directory of Open Access Journals (Sweden)

    Alison McAfee

    2015-12-01

    Full Text Available Since the sequencing of the honey bee genome, proteomics by mass spectrometry has become increasingly popular for biological analyses of this insect; but we have observed that the number of honey bee protein identifications is consistently low compared to other organisms [1]. In this dataset, we use nanoelectrospray ionization-coupled liquid chromatography–tandem mass spectrometry (nLC–MS/MS to systematically investigate the root cause of low honey bee proteome coverage. To this end, we present here data from three key experiments: a controlled, cross-species analyses of samples from Apis mellifera, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Mus musculus and Homo sapiens; a proteomic analysis of an individual honey bee whose genome was also sequenced; and a cross-tissue honey bee proteome comparison. The cross-species dataset was interrogated to determine relative proteome coverages between species, and the other two datasets were used to search for polymorphic sequences and to compare protein cleavage profiles, respectively.

  5. Reranking candidate gene models with cross-species comparison for improved gene prediction

    Directory of Open Access Journals (Sweden)

    Pereira Fernando CN

    2008-10-01

    Full Text Available Abstract Background Most gene finders score candidate gene models with state-based methods, typically HMMs, by combining local properties (coding potential, splice donor and acceptor patterns, etc. Competing models with similar state-based scores may be distinguishable with additional information. In particular, functional and comparative genomics datasets may help to select among competing models of comparable probability by exploiting features likely to be associated with the correct gene models, such as conserved exon/intron structure or protein sequence features. Results We have investigated the utility of a simple post-processing step for selecting among a set of alternative gene models, using global scoring rules to rerank competing models for more accurate prediction. For each gene locus, we first generate the K best candidate gene models using the gene finder Evigan, and then rerank these models using comparisons with putative orthologous genes from closely-related species. Candidate gene models with lower scores in the original gene finder may be selected if they exhibit strong similarity to probable orthologs in coding sequence, splice site location, or signal peptide occurrence. Experiments on Drosophila melanogaster demonstrate that reranking based on cross-species comparison outperforms the best gene models identified by Evigan alone, and also outperforms the comparative gene finders GeneWise and Augustus+. Conclusion Reranking gene models with cross-species comparison improves gene prediction accuracy. This straightforward method can be readily adapted to incorporate additional lines of evidence, as it requires only a ranked source of candidate gene models.

  6. Cross-species genetic exchange between visceral and cutaneous strains of Leishmania in the sand fly vector.

    Science.gov (United States)

    Romano, Audrey; Inbar, Ehud; Debrabant, Alain; Charmoy, Melanie; Lawyer, Phillip; Ribeiro-Gomes, Flavia; Barhoumi, Mourad; Grigg, Michael; Shaik, Jahangheer; Dobson, Deborah; Beverley, Stephen M; Sacks, David L

    2014-11-25

    Genetic exchange between Leishmania major strains during their development in the sand fly vector has been experimentally shown. To investigate the possibility of genetic exchange between different Leishmania species, a cutaneous strain of L. major and a visceral strain of Leishmania infantum, each bearing a different drug-resistant marker, were used to coinfect Lutzomyia longipalpis sand flies. Eleven double-drug-resistant progeny clones, each the product of an independent mating event, were generated and submitted to genotype and phenotype analyses. The analysis of multiple allelic markers across the genome suggested that each progeny clone inherited at least one full set of chromosomes from each parent, with loss of heterozygosity at some loci, and uniparental retention of maxicircle kinetoplast DNA. Hybrids with DNA contents of approximately 2n, 3n, and 4n were observed. In vivo studies revealed clear differences in the ability of the hybrids to produce pathology in the skin or to disseminate to and grow in the viscera, suggesting polymorphisms and differential inheritance of the gene(s) controlling these traits. The studies, to our knowledge, represent the first experimental confirmation of cross-species mating in Leishmania, opening the way toward genetic linkage analysis of important traits and providing strong evidence that genetic exchange is responsible for the generation of the mixed-species genotypes observed in natural populations.

  7. Cross species association examination of UCN3 and CRHR2 as potential pharmacological targets for antiobesity drugs.

    Directory of Open Access Journals (Sweden)

    Zhihua Jiang

    Full Text Available BACKGROUND: Obesity now constitutes a leading global public health problem. Studies have shown that insulin resistance affiliated with obesity is associated with intramyocellular lipid (IMCL accumulation. Therefore, identification of genes associated with the phenotype would provide a clear target for pharmaceutical intervention and care for the condition. We hypothesized that urocortin 3 (UCN3 and corticotropin-releasing hormone receptor 2 (CRHR2 are associated with IMCL and subcutaneous fat depth (SFD, because the corticotropin-releasing hormone family of peptides are capable of strong anorectic and thermogenic effects. METHODOLOGY/PRINCIPAL FINDINGS: We annotated both bovine UCN3 and CRHR2 genes and identified 12 genetic mutations in the former gene and 5 genetic markers in the promoter region of the latter gene. Genotyping of these 17 markers on Wagyu times Limousin F(2 progeny revealed significant associations between promoter polymorphisms and SFD (P = 0.0203-0.0685 and between missense mutations of exon 2 and IMCL (P = 0.0055-0.0369 in the bovine UCN3 gene. The SFD associated promoter SNPs caused a gain/loss of 12 potential transcription regulatory binding sites, while the IMCL associated coding SNPs affected the secondary structure of UCN3 mRNA. However, none of five polymorphisms in CRHR2 gene clearly co-segregated with either trait in the population (P>0.6000. CONCLUSIONS/SIGNIFICANCE: Because UCN3 is located on human chromosome 10p15.1 where quantitative trait loci for obesity have been reported, our cross species study provides further evidence that it could be proposed as a potential target for developing antiobesity drugs. None of the markers in CRHR2 was associated with obesity-type traits in cattle, which is consistent with findings in human. Therefore, CRHR2 does not lend itself to the development of antiobesity drugs.

  8. Soaking suggests "alternative facts": Only co-crystallization discloses major ligand-induced interface rearrangements of a homodimeric tRNA-binding protein indicating a novel mode-of-inhibition.

    Directory of Open Access Journals (Sweden)

    Frederik Rainer Ehrmann

    Full Text Available For the efficient pathogenesis of Shigella, the causative agent of bacillary dysentery, full functionality of tRNA-guanine transglycosylase (TGT is mandatory. TGT performs post-transcriptional modifications of tRNAs in the anticodon loop taking impact on virulence development. This suggests TGT as a putative target for selective anti-shigellosis drug therapy. Since bacterial TGT is only functional as homodimer, its activity can be inhibited either by blocking its active site or by preventing dimerization. Recently, we discovered that in some crystal structures obtained by soaking the full conformational adaptation most likely induced in solution upon ligand binding is not displayed. Thus, soaked structures may be misleading and suggest irrelevant binding modes. Accordingly, we re-investigated these complexes by co-crystallization. The obtained structures revealed large conformational rearrangements not visible in the soaked complexes. They result from spatial perturbations in the ribose-34/phosphate-35 recognition pocket and, consequently, an extended loop-helix motif required to prevent access of water molecules into the dimer interface loses its geometric integrity. Thermodynamic profiles of ligand binding in solution indicate favorable entropic contributions to complex formation when large conformational adaptations in the dimer interface are involved. Native MS titration experiments reveal the extent to which the homodimer is destabilized in the presence of each inhibitor. Unexpectedly, one ligand causes a complete rearrangement of subunit packing within the homodimer, never observed in any other TGT crystal structure before. Likely, this novel twisted dimer is catalytically inactive and, therefore, suggests that stabilizing this non-productive subunit arrangement may be used as a further strategy for TGT inhibition.

  9. A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

    Science.gov (United States)

    Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

    2016-01-01

    Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

  10. Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

    Directory of Open Access Journals (Sweden)

    Zeli Zhang

    2018-04-01

    Full Text Available The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV was found to be sensitive to several feline cellular restriction factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3 and tetherin, but FIV evolved to counteract them. Here, we describe the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV replication and discuss the molecular interaction of APOBEC3 proteins with the viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could explain some of the observed FIV cross-species transmissions described in wild Felids.

  11. Cross-species transmission and emergence of novel viruses from birds.

    Science.gov (United States)

    Chan, Jasper Fuk-Woo; To, Kelvin Kai-Wang; Chen, Honglin; Yuen, Kwok-Yung

    2015-02-01

    Birds, the only living member of the Dinosauria clade, are flying warm-blooded vertebrates displaying high species biodiversity, roosting and migratory behavior, and a unique adaptive immune system. Birds provide the natural reservoir for numerous viral species and therefore gene source for evolution, emergence and dissemination of novel viruses. The intrusions of human into natural habitats of wild birds, the domestication of wild birds as pets or racing birds, and the increasing poultry consumption by human have facilitated avian viruses to cross species barriers to cause zoonosis. Recently, a novel adenovirus was exclusively found in birds causing an outbreak of Chlamydophila psittaci infection among birds and humans. Instead of being the primary cause of an outbreak by jumping directly from bird to human, a novel avian virus can be an augmenter of another zoonotic agent causing the outbreak. A comprehensive avian virome will improve our understanding of birds' evolutionary dynamics. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Developing a Genetically Encoded, Cross-Species Biosensor for Detecting Ammonium and Regulating Biosynthesis of Cyanophycin.

    Science.gov (United States)

    Xiao, Yi; Jiang, Wen; Zhang, Fuzhong

    2017-10-20

    Responding to nitrogen status is essential for all living organisms. Bacteria have evolved various complex and exquisite regulatory systems to control nitrogen metabolism. However, natural nitrogen regulatory systems, owing to their complexity, often function only in their original hosts and do not respond properly when transferred to another species. By harnessing the Lactococcus GlnRA system, we developed a genetically encoded, cross-species ammonium biosensor that displays a dynamic range up to 9-fold upon detection of ammonium ion. We demonstrated applications of this ammonium biosensor in three different species (Escherichia coli, Pseudomonas putida, and Synechocystis sp.) to detect different nitrogen sources. This ammonium sensor was further used to regulate the biosynthesis of a nitrogen-rich polymer, cyanophycin, based on ammonium concentration. Given the importance of nitrogen responses, the developed biosensor should be broadly applicable to synthetic biology and bioengineering.

  13. Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

    Science.gov (United States)

    Zhang, Zeli; Gu, Qinyong; Marino, Daniela; Lee, Kyeong-Lim; Kong, Il-Keun; Häussinger, Dieter; Münk, Carsten

    2018-01-01

    The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV) was found to be sensitive to several feline cellular restriction factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) and tetherin, but FIV evolved to counteract them. Here, we describe the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV replication and discuss the molecular interaction of APOBEC3 proteins with the viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could explain some of the observed FIV cross-species transmissions described in wild Felids. PMID:29642583

  14. Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain.

    Science.gov (United States)

    Ou, Wu; Delisle, Josie; Jacques, Jerome; Shih, Joanna; Price, Graeme; Kuhn, Jens H; Wang, Vivian; Verthelyi, Daniela; Kaplan, Gerardo; Wilson, Carolyn A

    2012-01-25

    The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD) would induce cross-species immunity by making more conserved regions accessible to the immune system. To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs) bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP) that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs. Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced. Our findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system.

  15. Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain

    Directory of Open Access Journals (Sweden)

    Ou Wu

    2012-01-01

    Full Text Available Abstract Background The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2 is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD. We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD would induce cross-species immunity by making more conserved regions accessible to the immune system. Methods To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs. Results Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced. Conclusion Our findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system.

  16. Cross-Species Extrapolation of Models for Predicting Lead Transfer from Soil to Wheat Grain.

    Directory of Open Access Journals (Sweden)

    Ke Liu

    Full Text Available The transfer of Pb from the soil to crops is a serious food hygiene security problem in China because of industrial, agricultural, and historical contamination. In this study, the characteristics of exogenous Pb transfer from 17 Chinese soils to a popular wheat variety (Xiaoyan 22 were investigated. In addition, bioaccumulation prediction models of Pb in grain were obtained based on soil properties. The results of the analysis showed that pH and OC were the most important factors contributing to Pb uptake by wheat grain. Using a cross-species extrapolation approach, the Pb uptake prediction models for cultivar Xiaoyan 22 in different soil Pb levels were satisfactorily applied to six additional non-modeled wheat varieties to develop a prediction model for each variety. Normalization of the bioaccumulation factor (BAF to specific soil physico-chemistry is essential, because doing so could significantly reduce the intra-species variation of different wheat cultivars in predicted Pb transfer and eliminate the influence of soil properties on ecotoxicity parameters for organisms of interest. Finally, the prediction models were successfully verified against published data (including other wheat varieties and crops and used to evaluate the ecological risk of Pb for wheat in contaminated agricultural soils.

  17. Cross-species microarray hybridization to identify developmentally regulated genes in the filamentous fungus Sordaria macrospora.

    Science.gov (United States)

    Nowrousian, Minou; Ringelberg, Carol; Dunlap, Jay C; Loros, Jennifer J; Kück, Ulrich

    2005-04-01

    The filamentous fungus Sordaria macrospora forms complex three-dimensional fruiting bodies that protect the developing ascospores and ensure their proper discharge. Several regulatory genes essential for fruiting body development were previously isolated by complementation of the sterile mutants pro1, pro11 and pro22. To establish the genetic relationships between these genes and to identify downstream targets, we have conducted cross-species microarray hybridizations using cDNA arrays derived from the closely related fungus Neurospora crassa and RNA probes prepared from wild-type S. macrospora and the three developmental mutants. Of the 1,420 genes which gave a signal with the probes from all the strains used, 172 (12%) were regulated differently in at least one of the three mutants compared to the wild type, and 17 (1.2%) were regulated differently in all three mutant strains. Microarray data were verified by Northern analysis or quantitative real time PCR. Among the genes that are up- or down-regulated in the mutant strains are genes encoding the pheromone precursors, enzymes involved in melanin biosynthesis and a lectin-like protein. Analysis of gene expression in double mutants revealed a complex network of interaction between the pro gene products.

  18. Cross-species transferability of SSR loci developed from transciptome sequencing in lodgepole pine.

    Science.gov (United States)

    Lesser, Mark R; Parchman, Thomas L; Buerkle, C Alex

    2012-05-01

    With the advent of next generation sequencing technologies, transcriptome level sequence collections are arising as prominent resources for the discovery of gene-based molecular markers. In a previous study more than 15,000 simple sequence repeats (SSRs) in expressed sequence tag (EST) sequences resulting from 454 pyrosequencing of Pinus contorta cDNA were identified. From these we developed PCR primers for approximately 4000 candidate SSRs. Here, we tested 184 of these SSRs for successful amplification across P. contorta and eight other pine species and examined patterns of polymorphism and allelic variability for a subset of these SSRs. Cross-species transferability was high, with high percentages of loci producing PCR products in all species tested. In addition, 50% of the loci we screened across panels of individuals from three of these species were polymorphic and allelically diverse. We examined levels of diversity in a subset of these SSRs by collecting genotypic data across several populations of Pinus ponderosa in northern Wyoming. Our results indicate the utility of mining pyrosequenced EST collections for gene-based SSRs and provide a source of molecular markers that should bolster evolutionary genetic investigations across the genus Pinus. © 2011 Blackwell Publishing Ltd.

  19. Cross-species transmission of canine distemper virus—an update

    Directory of Open Access Journals (Sweden)

    Andreas Beineke

    2015-12-01

    Full Text Available Canine distemper virus (CDV is a pantropic morbillivirus with a worldwide distribution, which causes fatal disease in dogs. Affected animals develop dyspnea, diarrhea, neurological signs and profound immunosuppression. Systemic CDV infection, resembling distemper in domestic dogs, can be found also in wild canids (e.g. wolves, foxes, procyonids (e.g. raccoons, kinkajous, ailurids (e.g. red pandas, ursids (e.g. black bears, giant pandas, mustelids (e.g. ferrets, minks, viverrids (e.g. civets, genets, hyaenids (e.g. spotted hyenas, and large felids (e.g. lions, tigers. Furthermore, besides infection with the closely related phocine distemper virus, seals can become infected by CDV. In some CDV outbreaks including the mass mortalities among Baikal and Caspian seals and large felids in the Serengeti Park, terrestrial carnivores including dogs and wolves have been suspected as vectors for the infectious agent. In addition, lethal infections have been described in non-carnivore species such as peccaries and non-human primates demonstrating the remarkable ability of the pathogen to cross species barriers. Mutations affecting the CDV H protein required for virus attachment to host-cell receptors are associated with virulence and disease emergence in novel host species. The broad and expanding host range of CDV and its maintenance within wildlife reservoir hosts considerably hampers disease eradication.

  20. Cross-species transmission of canine distemper virus-an update.

    Science.gov (United States)

    Beineke, Andreas; Baumgärtner, Wolfgang; Wohlsein, Peter

    2015-12-01

    Canine distemper virus (CDV) is a pantropic morbillivirus with a worldwide distribution, which causes fatal disease in dogs. Affected animals develop dyspnea, diarrhea, neurological signs and profound immunosuppression. Systemic CDV infection, resembling distemper in domestic dogs, can be found also in wild canids (e.g. wolves, foxes), procyonids (e.g. raccoons, kinkajous), ailurids (e.g. red pandas), ursids (e.g. black bears, giant pandas), mustelids (e.g. ferrets, minks), viverrids (e.g. civets, genets), hyaenids (e.g. spotted hyenas), and large felids (e.g. lions, tigers). Furthermore, besides infection with the closely related phocine distemper virus, seals can become infected by CDV. In some CDV outbreaks including the mass mortalities among Baikal and Caspian seals and large felids in the Serengeti Park, terrestrial carnivores including dogs and wolves have been suspected as vectors for the infectious agent. In addition, lethal infections have been described in non-carnivore species such as peccaries and non-human primates demonstrating the remarkable ability of the pathogen to cross species barriers. Mutations affecting the CDV H protein required for virus attachment to host-cell receptors are associated with virulence and disease emergence in novel host species. The broad and expanding host range of CDV and its maintenance within wildlife reservoir hosts considerably hampers disease eradication.

  1. Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt.

    Science.gov (United States)

    Weljie, Aalim M; Meerlo, Peter; Goel, Namni; Sengupta, Arjun; Kayser, Matthew S; Abel, Ted; Birnbaum, Morris J; Dinges, David F; Sehgal, Amita

    2015-02-24

    Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the molecular mechanisms underlying effects of sleep loss is only in its nascent stages. In this study we used rat and human models to simulate modern-day conditions of restricted sleep and addressed cross-species consequences via comprehensive metabolite profiling. Serum from sleep-restricted rats was analyzed using polar and nonpolar methods in two independent datasets (n = 10 per study, 3,380 measured features, 407 identified). A total of 38 features were changed across independent experiments, with the majority classified as lipids (18 from 28 identified). In a parallel human study, 92 metabolites were identified as potentially significant, with the majority also classified as lipids (32 of 37 identified). Intriguingly, two metabolites, oxalic acid and diacylglycerol 36:3, were robustly and quantitatively reduced in both species following sleep restriction, and recovered to near baseline levels after sleep restriction (P discovery rate neurotransmitters, vitamin B3, and gut metabolism were elevated in sleep-restricted humans. These results are consistent with induction of peroxisome proliferator-activated receptors and disruptions of the circadian clock. The findings provide a potential link between known pathologies of reduced sleep duration and metabolic dysfunction, and potential biomarkers for sleep loss.

  2. Multidirectional cross-species painting illuminates the history of karyotypic evolution in Perissodactyla.

    Science.gov (United States)

    Trifonov, Vladimir A; Stanyon, Roscoe; Nesterenko, Anastasia I; Fu, Beiyuan; Perelman, Polina L; O'Brien, Patricia C M; Stone, Gary; Rubtsova, Nadezhda V; Houck, Marlys L; Robinson, Terence J; Ferguson-Smith, Malcolm A; Dobigny, Gauthier; Graphodatsky, Alexander S; Yang, Fengtang

    2008-01-01

    The order Perissodactyla, the group of odd-toed ungulates, includes three extant families: Equidae, Tapiridae, and Rhinocerotidae. The extremely rapid karyotypic diversification in perissodactyls has so far prevented the establishment of genome-wide homology maps between these three families by traditional cytogenetic approaches. Here we report the first genome-wide comparative chromosome maps of African rhinoceroses, four tapir species, four equine species, and humans. These maps were established by multidirectional chromosome painting, with paint probes derived from flow-sorted chromosomes of Equus grevyi, Tapirus indicus, and Ceratotherium simum as well as painting probes from horse and human. The Malayan tapir (Tapirus indicus), Baird's tapir (T. bairdii), mountain tapir (T. pinchaque), lowland tapir (T. terrestris), and onager (E. hemionus onager), were studied by cross-species chromosome painting for the first time. Our results, when integrated with previously published comparative chromosome maps of the other perissodactyl species, have enabled the reconstruction of perissodactyl, ceratomorph, and equid ancestral karyotypes, and the identification of the defining evolutionary chromosomal rearrangements along each lineage. Our results allow a more reliable estimate of the mode and tempo of evolutionary chromosomal rearrangements, revealing a striking switch between the slowly evolving ceratomorphs and extremely rapidly evolving equids.

  3. Microsatellite loci in Japanese quail and cross-species amplification in chicken and guinea fowl

    Directory of Open Access Journals (Sweden)

    Mizutani Makoto

    2002-03-01

    Full Text Available Abstract In line with the Gifu University's initiative to map the Japanese quail genome, a total of 100 Japanese quail microsatellite markers isolated in our laboratory were evaluated in a population of 20 unrelated quails randomly sampled from a colony of wild quail origin. Ninety-eight markers were polymorphic with an average of 3.7 alleles per locus and a mean heterozygosity of 0.423. To determine the utility of these markers for comparative genome mapping in Phasianidae, cross-species amplification of all the markers was tested with chicken and guinea fowl DNA. Amplification products similar in size to the orthologous loci in quail were observed in 42 loci in chicken and 20 loci in guinea fowl. Of the cross-reactive markers, 57.1% in chicken and 55.0% in guinea fowl were polymorphic when tested in 20 birds from their respective populations. Five of 15 markers that could cross-amplify Japanese quail, chicken, and guinea fowl DNA were polymorphic in all three species. Amplification of orthologous loci was confirmed by sequencing 10 loci each from chicken and guinea fowl and comparing with them the corresponding quail sequence. The microsatellite markers reported would serve as a useful resource base for genetic mapping in quail and comparative mapping in Phasianidae.

  4. Novel and highly informative Capsicum SSR markers and their cross-species transferability.

    Science.gov (United States)

    Buso, G S C; Reis, A M M; Amaral, Z P S; Ferreira, M E

    2016-09-23

    This study was undertaken primarily to develop new simple sequence repeat (SSR) markers for Capsicum. As part of this project aimed at broadening the use of molecular tools in Capsicum breeding, two genomic libraries enriched for AG/TC repeat sequences were constructed for Capsicum annuum. A total of 475 DNA clones were sequenced from both libraries and 144 SSR markers were tested on cultivated and wild species of Capsicum. Forty-five SSR markers were randomly selected to genotype a panel of 48 accessions of the Capsicum germplasm bank. The number of alleles per locus ranged from 2 to 11, with an average of 6 alleles. The polymorphism information content was on average 0.60, ranging from 0.20 to 0.83. The cross-species transferability to seven cultivated and wild Capsicum species was tested with a set of 91 SSR markers. We found that a high proportion of the loci produced amplicons in all species tested. C. frutescens had the highest number of transferable markers, whereas the wild species had the lowest. Our results indicate that the new markers can be readily used in genetic analyses of Capsicum.

  5. Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium

    Directory of Open Access Journals (Sweden)

    Dhir Rajiv

    2004-08-01

    Full Text Available Abstract Background Gene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations. Results Using gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using

  6. Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

    Directory of Open Access Journals (Sweden)

    Forgacs Agnes L

    2009-04-01

    Full Text Available Abstract Background Tamoxifen (TAM is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level in vivo.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge. Results A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns. Conclusion Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.

  7. Co-infection and cross-species transmission of divergent Hepatocystis lineages in a wild African primate community★

    Science.gov (United States)

    Thurber, Mary I.; Ghai, Ria R.; Hyeroba, Hyeroba; Weny, Geoffrey; Tumukunde, Alex; Chapman, Colin A.; Wiseman, Roger W.; Dinis, Jorge; Steeil, James; Greiner, Ellis C.; Friedrich, Thomas C.; O’Connor, David H.; Goldberg, Tony L.

    2013-01-01

    Hemoparasites of the apicomplexan family Plasmodiidae include the etiological agents of malaria, as well as a suite of non-human primate parasites from which the human malaria agents evolved. Despite the significance of these parasites for global health, little information is available about their ecology in multi-host communities. Primates were investigated in Kibale National Park, Uganda, where ecological relationships among host species are well characterized. Blood samples were examined for parasites of the genera Plasmodium and Hepatocystis using microscopy and PCR targeting the parasite mitochondrial cytochrome b gene, followed by Sanger sequencing. To assess co-infection, “deep sequencing” of a variable region within cytochrome b was performed. Out of nine black-and-white colobus (Colobus guereza), one blue guenon (Cercopithecus mitis), five grey-cheeked mangabeys (Lophocebus albigena), 23 olive baboons (Papio anubis), 52 red colobus (Procolobus rufomitratus) and 12 red-tailed guenons (Cercopithecus ascanius), 79 infections (77.5%) were found, all of which were Hepatocystis spp. Sanger sequencing revealed 25 different parasite haplotypes that sorted phylogenetically into six species-specific but morphologically similar lineages. “Deep sequencing” revealed mixed-lineage co-infections in baboons and red colobus (41.7% and 64.7% of individuals, respectively) but not in other host species. One lineage infecting red colobus also infected baboons, but always as the minor variant, suggesting directional cross-species transmission. Hepatocystis parasites in this primate community are a diverse assemblage of cryptic lineages, some of which co-infect hosts and at least one of which can cross primate species barriers. PMID:23603520

  8. Large-scale cross-species chemogenomic platform proposes a new drug discovery strategy of veterinary drug from herbal medicines.

    Directory of Open Access Journals (Sweden)

    Chao Huang

    Full Text Available Veterinary Herbal Medicine (VHM is a comprehensive, current, and informative discipline on the utilization of herbs in veterinary practice. Driven by chemistry but progressively directed by pharmacology and the clinical sciences, drug research has contributed more to address the needs for innovative veterinary medicine for curing animal diseases. However, research into veterinary medicine of vegetal origin in the pharmaceutical industry has reduced, owing to questions such as the short of compatibility of traditional natural-product extract libraries with high-throughput screening. Here, we present a cross-species chemogenomic screening platform to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future veterinary medicines, thereby increasing the number of treatment options. First, based on critically examined pharmacology and text mining, we build a cross-species drug-likeness evaluation approach to screen the lead compounds in veterinary medicines. Second, a specific cross-species target prediction model is developed to infer drug-target connections, with the purpose of understanding how drugs work on the specific targets. Third, we focus on exploring the multiple targets interference effects of veterinary medicines by heterogeneous network convergence and modularization analysis. Finally, we manually integrate a disease pathway to test whether the cross-species chemogenomic platform could uncover the active mechanism of veterinary medicine, which is exemplified by a specific network module. We believe the proposed cross-species chemogenomic platform allows for the systematization of current and traditional knowledge of veterinary medicine and, importantly, for the application of this emerging body of knowledge to the development of new drugs for animal diseases.

  9. Cross-species transcriptomic approach reveals genes in hamster implantation sites.

    Science.gov (United States)

    Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

    2014-12-01

    The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS. © 2014 Society for Reproduction and Fertility.

  10. XenDB: Full length cDNA prediction and cross species mapping in Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Giegerich Robert

    2005-09-01

    Full Text Available Abstract Background Research using the model system Xenopus laevis has provided critical insights into the mechanisms of early vertebrate development and cell biology. Large scale sequencing efforts have provided an increasingly important resource for researchers. To provide full advantage of the available sequence, we have analyzed 350,468 Xenopus laevis Expressed Sequence Tags (ESTs both to identify full length protein encoding sequences and to develop a unique database system to support comparative approaches between X. laevis and other model systems. Description Using a suffix array based clustering approach, we have identified 25,971 clusters and 40,877 singleton sequences. Generation of a consensus sequence for each cluster resulted in 31,353 tentative contig and 4,801 singleton sequences. Using both BLASTX and FASTY comparison to five model organisms and the NR protein database, more than 15,000 sequences are predicted to encode full length proteins and these have been matched to publicly available IMAGE clones when available. Each sequence has been compared to the KOG database and ~67% of the sequences have been assigned a putative functional category. Based on sequence homology to mouse and human, putative GO annotations have been determined. Conclusion The results of the analysis have been stored in a publicly available database XenDB http://bibiserv.techfak.uni-bielefeld.de/xendb/. A unique capability of the database is the ability to batch upload cross species queries to identify potential Xenopus homologues and their associated full length clones. Examples are provided including mapping of microarray results and application of 'in silico' analysis. The ability to quickly translate the results of various species into 'Xenopus-centric' information should greatly enhance comparative embryological approaches. Supplementary material can be found at http://bibiserv.techfak.uni-bielefeld.de/xendb/.

  11. Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

    Science.gov (United States)

    2009-01-01

    Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8) and solute carrier family 1 (glial high affinity glutamate transporter), member 3 (SLC1A3), which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively). Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies. PMID:20028558

  12. Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

    Directory of Open Access Journals (Sweden)

    Triche Timothy

    2009-12-01

    Full Text Available Abstract Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8 and solute carrier family 1 (glial high affinity glutamate transporter, member 3 (SLC1A3, which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively. Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.

  13. Identifying human disease genes through cross-species gene mapping of evolutionary conserved processes.

    Directory of Open Access Journals (Sweden)

    Martin Poot

    2011-05-01

    Full Text Available Understanding complex networks that modulate development in humans is hampered by genetic and phenotypic heterogeneity within and between populations. Here we present a method that exploits natural variation in highly diverse mouse genetic reference panels in which genetic and environmental factors can be tightly controlled. The aim of our study is to test a cross-species genetic mapping strategy, which compares data of gene mapping in human patients with functional data obtained by QTL mapping in recombinant inbred mouse strains in order to prioritize human disease candidate genes.We exploit evolutionary conservation of developmental phenotypes to discover gene variants that influence brain development in humans. We studied corpus callosum volume in a recombinant inbred mouse panel (C57BL/6J×DBA/2J, BXD strains using high-field strength MRI technology. We aligned mouse mapping results for this neuro-anatomical phenotype with genetic data from patients with abnormal corpus callosum (ACC development.From the 61 syndromes which involve an ACC, 51 human candidate genes have been identified. Through interval mapping, we identified a single significant QTL on mouse chromosome 7 for corpus callosum volume with a QTL peak located between 25.5 and 26.7 Mb. Comparing the genes in this mouse QTL region with those associated with human syndromes (involving ACC and those covered by copy number variations (CNV yielded a single overlap, namely HNRPU in humans and Hnrpul1 in mice. Further analysis of corpus callosum volume in BXD strains revealed that the corpus callosum was significantly larger in BXD mice with a B genotype at the Hnrpul1 locus than in BXD mice with a D genotype at Hnrpul1 (F = 22.48, p<9.87*10(-5.This approach that exploits highly diverse mouse strains provides an efficient and effective translational bridge to study the etiology of human developmental disorders, such as autism and schizophrenia.

  14. Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance.

    Science.gov (United States)

    Lindsey, J C; Kawauchi, D; Schwalbe, E C; Solecki, D J; Selby, M P; McKinnon, P J; Olson, J M; Hayden, J T; Grundy, R G; Ellison, D W; Williamson, D; Bailey, S; Roussel, M F; Clifford, S C

    2015-09-03

    The identification of key tumorigenic events in Sonic Hedgehog (SHH) subgroup medulloblastomas (MBSHH) will be essential for the development of individualized therapies and improved outcomes. However, beyond confirmation of characteristic SHH pathway mutations, recent genome-wide sequencing studies have not revealed commonly mutated genes with widespread relevance as potential therapeutic targets. We therefore examined any role for epigenetic DNA methylation events in MBSHH using a cross-species approach to candidate identification, prioritization and validation. MBSHH-associated DNA methylation events were first identified in 216 subgrouped human medulloblastomas (50 MBSHH, 28 Wnt/Wingless, 44 Group 3 and 94 Group 4) and their conservation then assessed in tumors arising from four independent murine models of Shh medulloblastoma, alongside any role in tumorigenesis using functional assessments in mouse and human models. This strategy identified widespread regional CpG hypo-methylation of VAV1, leading to its elevated expression, as a conserved aberrant epigenetic event, which characterizes the majority of MBSHH tumors in both species, and is associated with a poor outcome in MBSHH patients. Moreover, direct modulation of VAV1 in mouse and human models revealed a critical role in tumor maintenance, and its abrogation markedly reduced medulloblastoma growth. Further, Vav1 activity regulated granule neuron precursor germinal zone exit and migration initiation in an ex vivo model of early postnatal cerebellar development. These findings establish VAV1 as a critical epigenetically regulated oncogene with a key role in MBSHH maintenance, and highlight its potential as a validated therapeutic target and prognostic biomarker for the improved therapy of medulloblastoma.

  15. Cross-species genomics matches driver mutations and cell compartments to model ependymoma

    Science.gov (United States)

    Johnson, Robert A.; Wright, Karen D.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; Finkelstein, David; Pounds, Stanley B.; Rand, Vikki; Leary, Sarah E.S.; White, Elsie; Eden, Christopher; Hogg, Twala; Northcott, Paul; Mack, Stephen; Neale, Geoffrey; Wang, Yong-Dong; Coyle, Beth; Atkinson, Jennifer; DeWire, Mariko; Kranenburg, Tanya A.; Gillespie, Yancey; Allen, Jeffrey C.; Merchant, Thomas; Boop, Fredrick A.; Sanford, Robert. A.; Gajjar, Amar; Ellison, David W.; Taylor, Michael D.; Grundy, Richard G.; Gilbertson, Richard J.

    2010-01-01

    Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult since their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown1–3. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumor that arises throughout the central nervous system (CNS). Subgroup specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumors to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus. The transcriptome of human cerebral ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf−/− NSCs. Remarkably, activation of Ephb2 signaling in these, but not other NSCs, generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human cerebral tumor. Further comparative analysis of matched mouse and human tumors revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup specific driver mutations with cellular compartments to model and interrogate cancer subgroups. PMID:20639864

  16. Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

    Science.gov (United States)

    Rinne, Teemu; Muers, Ross S; Salo, Emma; Slater, Heather; Petkov, Christopher I

    2017-06-01

    The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio-visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio-visual selective attention modulates the primate brain, identify sources for "lost" attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. © The Author 2017. Published by Oxford University Press.

  17. Functional Imaging of Audio–Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

    Science.gov (United States)

    Muers, Ross S.; Salo, Emma; Slater, Heather; Petkov, Christopher I.

    2017-01-01

    Abstract The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio–visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio–visual selective attention modulates the primate brain, identify sources for “lost” attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. PMID:28419201

  18. Identification of conserved drought-adaptive genes using a cross-species meta-analysis approach.

    Science.gov (United States)

    Shaar-Moshe, Lidor; Hübner, Sariel; Peleg, Zvi

    2015-05-03

    Drought is the major environmental stress threatening crop-plant productivity worldwide. Identification of new genes and metabolic pathways involved in plant adaptation to progressive drought stress at the reproductive stage is of great interest for agricultural research. We developed a novel Cross-Species meta-Analysis of progressive Drought stress at the reproductive stage (CSA:Drought) to identify key drought adaptive genes and mechanisms and to test their evolutionary conservation. Empirically defined filtering criteria were used to facilitate a robust integration of 17 deposited microarray experiments (148 arrays) of Arabidopsis, rice, wheat and barley. By prioritizing consistency over intensity, our approach was able to identify 225 differentially expressed genes shared across studies and taxa. Gene ontology enrichment and pathway analyses classified the shared genes into functional categories involved predominantly in metabolic processes (e.g. amino acid and carbohydrate metabolism), regulatory function (e.g. protein degradation and transcription) and response to stimulus. We further investigated drought related cis-acting elements in the shared gene promoters, and the evolutionary conservation of shared genes. The universal nature of the identified drought-adaptive genes was further validated in a fifth species, Brachypodium distachyon that was not included in the meta-analysis. qPCR analysis of 27, randomly selected, shared orthologs showed similar expression pattern as was found by the CSA:Drought.In accordance, morpho-physiological characterization of progressive drought stress, in B. distachyon, highlighted the key role of osmotic adjustment as evolutionary conserved drought-adaptive mechanism. Our CSA:Drought strategy highlights major drought-adaptive genes and metabolic pathways that were only partially, if at all, reported in the original studies included in the meta-analysis. These genes include a group of unclassified genes that could be involved

  19. Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer.

    Directory of Open Access Journals (Sweden)

    Michael H Matho

    2015-09-01

    Full Text Available Vaccinia virus A33 is an extracellular enveloped virus (EEV-specific type II membrane glycoprotein that is essential for efficient EEV formation and long-range viral spread within the host. A33 is a target for neutralizing antibody responses against EEV. In this study, we produced seven murine anti-A33 monoclonal antibodies (MAbs by immunizing mice with live VACV, followed by boosting with the soluble A33 homodimeric ectodomain. Five A33 specific MAbs were capable of neutralizing EEV in the presence of complement. All MAbs bind to conformational epitopes on A33 but not to linear peptides. To identify the epitopes, we have adetermined the crystal structures of three representative neutralizing MAbs in complex with A33. We have further determined the binding kinetics for each of the three antibodies to wild-type A33, as well as to engineered A33 that contained single alanine substitutions within the epitopes of the three crystallized antibodies. While the Fab of both MAbs A2C7 and A20G2 binds to a single A33 subunit, the Fab from MAb A27D7 binds to both A33 subunits simultaneously. A27D7 binding is resistant to single alanine substitutions within the A33 epitope. A27D7 also demonstrated high-affinity binding with recombinant A33 protein that mimics other orthopoxvirus strains in the A27D7 epitope, such as ectromelia, monkeypox, and cowpox virus, suggesting that A27D7 is a potent cross-neutralizer. Finally, we confirmed that A27D7 protects mice against a lethal challenge with ectromelia virus.

  20. Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens

    Directory of Open Access Journals (Sweden)

    Schirmacher Peter

    2008-09-01

    Full Text Available Abstract Background Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. Results This study examined the suitability of a murine model (CT26/Balb/C of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver, invasion (invasion front, and immune response (invasion front and liver. Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%. Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%. However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0% despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments. Conclusion In summary, cross-species

  1. Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families.

    Directory of Open Access Journals (Sweden)

    Jemma L Geoghegan

    2017-02-01

    Full Text Available The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections. However, it is unclear whether some virus families have a greater propensity to jump host species than others. If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies. By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families. Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses. Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here. At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching. Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping.

  2. Detection of Genotype 4 Swine Hepatitis E Virus in Systemic Tissues in Cross-Species Infected Rabbits

    OpenAIRE

    Wu, Qiaoxing; An, Junqing; She, Ruiping; Shi, Ruihan; Hao, Wenzhuo; Soomro, MajidHussain; Yuan, Xuerui; Yang, Jinling; Wang, Jingyuan

    2017-01-01

    Increasing evidence demonstrates that hepatitis E virus (HEV) can be transmitted across species. According to previous reports, swine HEV has two genotypes, genotype 3 and 4, and both can infect humans by the fecal-oral route. Thus, it is crucial for the control of HEV zoonotic transmission to evaluate the dynamics of viral shedding and distribution in different tissues during cross-species infection by HEV. In this study, rabbits were infected with genotype 4 swine HEV by the intraperitoneal...

  3. Eighteen microsatellite loci in Salix arbutifolia (Salicaceae) and cross-species amplification in Salix and Populus species.

    Science.gov (United States)

    Hoshikawa, Takeshi; Kikuchi, Satoshi; Nagamitsu, Teruyoshi; Tomaru, Nobuhiro

    2009-07-01

    Salix arbutifolia is a riparian dioecious tree species that is of conservation concern in Japan because of its highly restricted distribution. Eighteen polymorphic loci of dinucleotide microsatellites were isolated and characterized. Among these, estimates of the expected heterozygosity ranged from 0.350 to 0.879. Cross-species amplification was successful at 9-13 loci among six Salix species and at three loci in one Populus species. © 2009 Blackwell Publishing Ltd.

  4. Elucidation of cross-species proteomic effects in human and hominin bone proteome identification through a bioinformatics experiment

    DEFF Research Database (Denmark)

    Welker, F.

    2018-01-01

    Background: The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein identificati......Background: The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein...... not been demonstrated. If error-tolerant searches do not overcome the cross-species proteomic issue then there might be inherent biases in the identified proteomes. Here, a bioinformatics experiment is performed to test this using a set of modern human bone proteomes and three independent searches against......), but roughly half of the mutable PSMs were not recovered. As a result, peptide and protein identification rates are higher in error-tolerant mode compared to non-error-tolerant searches but did not recover protein identifications completely. Data indicates that peptide length and the number of mutations...

  5. Evidence for Cross-species Influenza A Virus Transmission Within Swine Farms, China: A One Health, Prospective Cohort Study.

    Science.gov (United States)

    Ma, Mai-Juan; Wang, Guo-Lin; Anderson, Benjamin D; Bi, Zhen-Qiang; Lu, Bing; Wang, Xian-Jun; Wang, Chuang-Xin; Chen, Shan-Hui; Qian, Yan-Hua; Song, Shao-Xia; Li, Min; Lednicky, John A; Zhao, Teng; Wu, Meng-Na; Cao, Wu-Chun; Gray, Gregory C

    2018-02-01

    Our understanding of influenza A virus transmission between humans and pigs is limited. Beginning in 2015, we used a One Health approach and serial sampling to prospectively study 299 swine workers and 100 controls, their 9000 pigs, and 6 pig farm environments in China for influenza A viruses (IAVs) using molecular, culture, and immunological techniques. Study participants were closely monitored for influenza-like illness (ILI) events. Upon enrollment, swine workers had higher serum neutralizing antibody titers against swine H1N1 and higher nasal wash total immunoglobulin A (IgA) and specific IgA titers against swine H1N1 and H3N2 viruses. Over a period of 12 months, IAVs were detected by quantitative reverse-transcription polymerase chain reaction in 46 of 396 (11.6%) environmental swabs, 235 of 3300 (7.1%) pig oral secretion, 23 of 396 (5.8%) water, 20 of 396 (5.1%) aerosol, and 19 of 396 (4.8%) fecal-slurry specimens. Five of 32 (15.6%) participants with ILI events had nasopharyngeal swab specimens that were positive for IAV, and 17 (53.1%) demonstrated 4-fold rises in neutralization titers against a swine virus. Reassorted Eurasian avian-lineage H1N1, A(H1N1)pdm09-like, and swine-lineage H3N2 viruses were identified in pig farms. The A(H1N1)pdm09-like H1N1 viruses identified in swine were nearly genetically identical to the human H1N1 viruses isolated from the participants with ILI. There was considerable evidence of A(H1N1)pdm09-like, swine-lineage H1N1, and swine-lineage H3N2 viruses circulating, likely reassorting, and likely crossing species within the pig farms. These data suggest that stronger surveillance for novel influenza virus emergence within swine farms is imperative. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  6. Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach

    Science.gov (United States)

    Rodríguez-Cruz, Maricela; Coral-Vázquez, Ramón M.; Hernández-Stengele, Gabriel; Sánchez, Raúl; Salazar, Emmanuel; Sanchez-Muñoz, Fausto; Encarnación-Guevara, Sergio; Ramírez-Salcedo, Jorge

    2013-01-01

    The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development. PMID:24288657

  7. PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modifications.

    Science.gov (United States)

    Chaudhuri, Rima; Sadrieh, Arash; Hoffman, Nolan J; Parker, Benjamin L; Humphrey, Sean J; Stöckli, Jacqueline; Hill, Adam P; James, David E; Yang, Jean Yee Hwa

    2015-08-19

    Most biological processes are influenced by protein post-translational modifications (PTMs). Identifying novel PTM sites in different organisms, including humans and model organisms, has expedited our understanding of key signal transduction mechanisms. However, with increasing availability of deep, quantitative datasets in diverse species, there is a growing need for tools to facilitate cross-species comparison of PTM data. This is particularly important because functionally important modification sites are more likely to be evolutionarily conserved; yet cross-species comparison of PTMs is difficult since they often lie in structurally disordered protein domains. Current tools that address this can only map known PTMs between species based on known orthologous phosphosites, and do not enable the cross-species mapping of newly identified modification sites. Here, we addressed this by developing a web-based software tool, PhosphOrtholog ( www.phosphortholog.com ) that accurately maps protein modification sites between different species. This facilitates the comparison of datasets derived from multiple species, and should be a valuable tool for the proteomics community. Here we describe PhosphOrtholog, a web-based application for mapping known and novel orthologous PTM sites from experimental data obtained from different species. PhosphOrtholog is the only generic and automated tool that enables cross-species comparison of large-scale PTM datasets without relying on existing PTM databases. This is achieved through pairwise sequence alignment of orthologous protein residues. To demonstrate its utility we apply it to two sets of human and rat muscle phosphoproteomes generated following insulin and exercise stimulation, respectively, and one publicly available mouse phosphoproteome following cellular stress revealing high mapping and coverage efficiency. Although coverage statistics are dataset dependent, PhosphOrtholog increased the number of cross-species mapped sites

  8. Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison.

    Science.gov (United States)

    Kazemian, Majid; Zhu, Qiyun; Halfon, Marc S; Sinha, Saurabh

    2011-12-01

    Despite recent advances in experimental approaches for identifying transcriptional cis-regulatory modules (CRMs, 'enhancers'), direct empirical discovery of CRMs for all genes in all cell types and environmental conditions is likely to remain an elusive goal. Effective methods for computational CRM discovery are thus a critically needed complement to empirical approaches. However, existing computational methods that search for clusters of putative binding sites are ineffective if the relevant TFs and/or their binding specificities are unknown. Here, we provide a significantly improved method for 'motif-blind' CRM discovery that does not depend on knowledge or accurate prediction of TF-binding motifs and is effective when limited knowledge of functional CRMs is available to 'supervise' the search. We propose a new statistical method, based on 'Interpolated Markov Models', for motif-blind, genome-wide CRM discovery. It captures the statistical profile of variable length words in known CRMs of a regulatory network and finds candidate CRMs that match this profile. The method also uses orthologs of the known CRMs from closely related genomes. We perform in silico evaluation of predicted CRMs by assessing whether their neighboring genes are enriched for the expected expression patterns. This assessment uses a novel statistical test that extends the widely used Hypergeometric test of gene set enrichment to account for variability in intergenic lengths. We find that the new CRM prediction method is superior to existing methods. Finally, we experimentally validate 12 new CRM predictions by examining their regulatory activity in vivo in Drosophila; 10 of the tested CRMs were found to be functional, while 6 of the top 7 predictions showed the expected activity patterns. We make our program available as downloadable source code, and as a plugin for a genome browser installed on our servers. © The Author(s) 2011. Published by Oxford University Press.

  9. RNA interference analyses suggest a transcript-specific regulatory role for mitochondrial RNA-binding proteins MRP1 and MRP2 in RNA editing and other RNA processing in Trypanosoma brucei

    NARCIS (Netherlands)

    Vondrusková, Eva; van den Burg, Janny; Zíková, Alena; Ernst, Nancy Lewis; Stuart, Kenneth; Benne, Rob; Lukes, Julius

    2005-01-01

    Mitochondrial RNA-binding proteins MRP1 and MRP2 occur in a heteromeric complex that appears to play a role in U-insertion/deletion editing in trypanosomes. Reduction in the levels of MRP1 (gBP21) and/or MRP2 (gBP25) mRNA by RNA interference in procyclic Trypanosoma brucei resulted in severe growth

  10. HTLV-3/4 and simian foamy retroviruses in humans: discovery, epidemiology, cross-species transmission and molecular virology.

    Science.gov (United States)

    Gessain, Antoine; Rua, Réjane; Betsem, Edouard; Turpin, Jocelyn; Mahieux, Renaud

    2013-01-05

    Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Hepatitis E virus infection in central China reveals no evidence of cross-species transmission between human and swine in this area.

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    Full Text Available Hepatitis E virus (HEV is a zoonotic pathogen of which several species of animal were reported as reservoirs. Swine stands out as the major reservoir for HEV infection in humans, as suggested by the close genetic relationship of swine and human virus. Since 2000, Genotype 4 HEV has become the dominant cause of hepatitis E disease in China. Recent reports showed that genotype 4 HEV is freely transmitted between humans and swine in eastern and southern China. However, the infection status of HEV in human and swine populations in central China is still unclear. This study was conducted in a rural area of central China, where there are many commercial swine farms. A total of 1476 serum and 554 fecal specimens were collected from the general human and swine populations in this area, respectively. The seroepidemiological study was conducted by enzyme-linked immunosorbent assay. Conserved genomic sequences of open reading frame 2 were detected using reverse transcription-PCR. The results indicated that the overall viral burden of the general human subjects was 0.95% (14/1476, while 7.0% (39/554 of the swine excreted HEV in stool. The positive rate of anti-HEV IgG and IgM in the serum samples was 7.9% (117/1476 and 1.6% (24/1476, respectively. Phylogenetic analysis based on the 150 nt partial sequence of the capsid protein gene showed that the 53 swine and human HEV isolates in the current study all belonged to genotype 4, clustering into three major groups. However, the HEV isolates prevalent in the human and swine populations were classified into known distinct subgenotypes, which suggested that no cross-species transmission between swine and humans had taken place in this area. This result was confirmed by cloning and phylogenetic analysis of the complete capsid protein gene sequence of three representative HEV strains in the three major groups. The cross reactivity between anti-HEV IgG from human sera and the two representative strains from swine in

  12. Cross-species induction of antimicrobial compounds, biosurfactants and quorum-sensing inhibitors in tropical marine epibiotic bacteria by pathogens and biofouling microorganisms.

    Science.gov (United States)

    Dusane, Devendra H; Matkar, Pratiek; Venugopalan, Valayam P; Kumar, Ameeta Ravi; Zinjarde, Smita S

    2011-03-01

    Enhancement or induction of antimicrobial, biosurfactant, and quorum-sensing inhibition property in marine bacteria due to cross-species and cross-genera interactions was investigated. Four marine epibiotic bacteria (Bacillus sp. S3, B. pumilus S8, B. licheniformis D1, and Serratia marcescens V1) displaying antimicrobial activity against pathogenic or biofouling fungi (Candida albicans CA and Yarrowia lipolytica YL), and bacteria (Pseudomonas aeruginosa PA and Bacillus pumilus BP) were chosen for this study. The marine epibiotic bacteria when co-cultivated with the aforementioned fungi or bacteria showed induction or enhancement in antimicrobial activity, biosurfactant production, and quorum-sensing inhibition. Antifungal activity against Y. lipolytica YL was induced by co-cultivation of the pathogens or biofouling strains with the marine Bacillus sp. S3, B. pumilus S8, or B. licheniformis D1. Antibacterial activity against Ps. aeruginosa PA or B. pumilus BP was enhanced in most of the marine isolates after co-cultivation. Biosurfactant activity was significantly increased when cells of B. pumilus BP were co-cultivated with S. marcescens V1, B. pumilus S8, or B. licheniformis D1. Pigment reduction in the quorum-sensing inhibition indicator strain Chromobacterium violaceum 12472 was evident when the marine strain of Bacillus sp. S3 was grown in the presence of the inducer strain Ps. aeruginosa PA, suggesting quorum-sensing inhibition. The study has important ecological and biotechnological implications in terms of microbial competition in natural environments and enhancement of secondary metabolite production.

  13. Rapid development of microsatellite markers for the endangered fish Schizothorax biddulphi (Günther) using next generation sequencing and cross-species amplification.

    Science.gov (United States)

    Luo, Wei; Nie, Zhulan; Zhan, Fanbin; Wei, Jie; Wang, Weimin; Gao, Zexia

    2012-11-14

    Tarim schizothoracin (Schizothorax biddulphi) is an endemic fish species native to the Tarim River system of Xinjiang and has been classified as an extremely endangered freshwater fish species in China. Here, we used a next generation sequencing platform (ion torrent PGM™) to obtain a large number of microsatellites for S. biddulphi, for the first time. A total of 40577 contigs were assembled, which contained 1379 SSRs. In these SSRs, the number of dinucleotide repeats were the most frequent (77.08%) and AC repeats were the most frequently occurring microsatellite, followed by AG, AAT and AT. Fifty loci were randomly selected for primer development; of these, 38 loci were successfully amplified and 29 loci were polymorphic across panels of 30 individuals. The H(o) ranged from 0.15 to 0.83, and H(e) ranged from 0.15 to 0.85, with 3.5 alleles per locus on average. Cross-species utility indicated that 20 of these markers were successfully amplified in a related, also an endangered fish species, S. irregularis. This study suggests that PGM™ sequencing is a rapid and cost-effective tool for developing microsatellite markers for non-model species and the developed microsatellite markers in this study would be useful in Schizothorax genetic analysis.

  14. Development, characterization and cross species amplification of polymorphic microsatellite markers from expressed sequence tags of turmeric (Curcuma longa L.).

    Science.gov (United States)

    Siju, S; Dhanya, K; Syamkumar, S; Sasikumar, B; Sheeja, T E; Bhat, A I; Parthasarathy, V A

    2010-02-01

    Expressed sequence tags (ESTs) from turmeric (Curcuma longa L.) were used for the screening of type and frequency of Class I (hypervariable) simple sequence repeats (SSRs). A total of 231 microsatellite repeats were detected from 12,593 EST sequences of turmeric after redundancy elimination. The average density of Class I SSRs accounts to one SSR per 17.96 kb of EST. Mononucleotides were the most abundant class of microsatellite repeat in turmeric ESTs followed by trinucleotides. A robust set of 17 polymorphic EST-SSRs were developed and used for evaluating 20 turmeric accessions. The number of alleles detected ranged from 3 to 8 per loci. The developed markers were also evaluated in 13 related species of C. longa confirming high rate (100%) of cross species transferability. The polymorphic microsatellite markers generated from this study could be used for genetic diversity analysis and resolving the taxonomic confusion prevailing in the genus.

  15. Cross-species transmission of honey bee viruses in associated arthropods.

    Science.gov (United States)

    Levitt, Abby L; Singh, Rajwinder; Cox-Foster, Diana L; Rajotte, Edwin; Hoover, Kelli; Ostiguy, Nancy; Holmes, Edward C

    2013-09-01

    There are a number of RNA virus pathogens that represent a serious threat to the health of managed honey bees (Apis mellifera). That some of these viruses are also found in the broader pollinator community suggests the wider environmental spread of these viruses, with the potential for a broader impact on ecosystems. Studies on the ecology and evolution of these viruses in the arthropod community as a whole may therefore provide important insights into these potential impacts. We examined managed A. mellifera colonies, nearby non-Apis hymenopteran pollinators, and other associated arthropods for the presence of five commonly occurring picorna-like RNA viruses of honey bees - black queen cell virus, deformed wing virus, Israeli acute paralysis virus, Kashmir bee virus and sacbrood virus. Notably, we observed their presence in several arthropod species. Additionally, detection of negative-strand RNA using strand-specific RT-PCR assays for deformed wing virus and Israeli acute paralysis virus suggests active replication of deformed wing virus in at least six non-Apis species and active replication of Israeli acute paralysis virus in one non-Apis species. Phylogenetic analysis of deformed wing virus also revealed that this virus is freely disseminating across the species sampled in this study. In sum, our study indicates that these viruses are not specific to the pollinator community and that other arthropod species have the potential to be involved in disease transmission in pollinator populations. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Quantitative Cross-Species Extrapolation between Humans and Fish: The Case of the Anti-Depressant Fluoxetine

    Science.gov (United States)

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Cumming, Rob I.; de Polo, Anna; Winter, Matthew J.; Panter, Grace H.; Rand-Weaver, Mariann; Sumpter, John P.

    2014-01-01

    Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 µg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the

  17. Harnessing cross-species alignment to discover SNPs and generate a draft genome sequence of a bighorn sheep (Ovis canadensis).

    Science.gov (United States)

    Miller, Joshua M; Moore, Stephen S; Stothard, Paul; Liao, Xiaoping; Coltman, David W

    2015-05-20

    Whole genome sequences (WGS) have proliferated as sequencing technology continues to improve and costs decline. While many WGS of model or domestic organisms have been produced, a growing number of non-model species are also being sequenced. In the absence of a reference, construction of a genome sequence necessitates de novo assembly which may be beyond the ability of many labs due to the large volumes of raw sequence data and extensive bioinformatics required. In contrast, the presence of a reference WGS allows for alignment which is more tractable than assembly. Recent work has highlighted that the reference need not come from the same species, potentially enabling a wide array of species WGS to be constructed using cross-species alignment. Here we report on the creation a draft WGS from a single bighorn sheep (Ovis canadensis) using alignment to the closely related domestic sheep (Ovis aries). Two sequencing libraries on SOLiD platforms yielded over 865 million reads, and combined alignment to the domestic sheep reference resulted in a nearly complete sequence (95% coverage of the reference) at an average of 12x read depth (104 SD). From this we discovered over 15 million variants and annotated them relative to the domestic sheep reference. We then conducted an enrichment analysis of those SNPs showing fixed differences between the reference and sequenced individual and found significant differences in a number of gene ontology (GO) terms, including those associated with reproduction, muscle properties, and bone deposition. Our results demonstrate that cross-species alignment enables the creation of novel WGS for non-model organisms. The bighorn sheep WGS will provide a resource for future resequencing studies or comparative genomics.

  18. The effect of cleft lip on adults' responses to faces: cross-species findings.

    Directory of Open Access Journals (Sweden)

    Christine E Parsons

    Full Text Available Cleft lip and palate is the most common of the congenital conditions affecting the face and cranial bones and is associated with a raised risk of difficulties in infant-caregiver interaction; the reasons for such difficulties are not fully understood. Here, we report two experiments designed to explore how adults respond to infant faces with and without cleft lip, using behavioural measures of attractiveness appraisal ('liking' and willingness to work to view or remove the images ('wanting'. We found that infants with cleft lip were rated as less attractive and were viewed for shorter durations than healthy infants, an effect that was particularly apparent where the cleft lip was severe. Women rated the infant faces as more attractive than men did, but there were no differences in men and women's viewing times of these faces. In a second experiment, we found that the presence of a cleft lip in domestic animals affected adults' 'liking' and 'wanting' responses in a comparable way to that seen for human infants. Adults' responses were also remarkably similar for images of infants and animals with cleft lip, although no gender difference in attractiveness ratings or viewing times emerged for animals. We suggest that the presence of a cleft lip can substantially change the way in which adults respond to human and animal faces. Furthermore, women may respond in different ways to men when asked to appraise infant attractiveness, despite the fact that men and women 'want' to view images of infants for similar durations.

  19. Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae

    Directory of Open Access Journals (Sweden)

    Rita S. Valente

    2017-05-01

    Full Text Available Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora, two signaling networks—the N-acyl homoserine lactone (AHL quorum-sensing system and the Gac/Rsm signal transduction pathway—control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources.

  20. Cross-species complementation of bacterial- and eukaryotic-type cardiolipin synthases

    Directory of Open Access Journals (Sweden)

    Petra Gottier

    2017-11-01

    Full Text Available The glycerophospholipid cardiolipin is a unique constituent of bacterial and mitochondrial membranes. It is involved in forming and stabilizing high molecular mass membrane protein complexes and in maintaining membrane architecture. Absence of cardiolipin leads to reduced efficiency of the electron transport chain, decreased membrane potential, and, ultimately, impaired respiratory metabolism. For the protozoan parasite Trypanosoma brucei cardiolipin synthesis is essential for survival, indicating that the enzymes involved in cardiolipin production represent potential drug targets. T. brucei cardiolipin synthase (TbCLS is unique as it belongs to the family of phospholipases D (PLD, harboring a prokaryotic-type cardiolipin synthase (CLS active site domain. In contrast, most other eukaryotic CLS, including the yeast ortholog ScCrd1, are members of the CDP-alcohol phosphatidyl­ transferase family. To study if these mechanistically distinct CLS enzymes are able to catalyze cardiolipin production in a cell that normally expresses a different type of CLS, we expressed TbCLS and ScCrd1 in CLS-deficient yeast and trypanosome strains, respectively. Our results show that TbCLS complemented cardiolipin production in CRD1 knockout yeast and partly restored wild-type colony forming capability under stress conditions. Remarkably, CL remodeling appeared to be impaired in the transgenic construct, suggesting that CL production and remodeling are tightly coupled processes that may require a clustering of the involved proteins into specific CL-synthesizing domains. In contrast, no complementation was observed by heterologous expression of ScCrd1 in conditional TbCLS knockout trypanosomes, despite proper mitochondrial targeting of the protein.

  1. Cross-species affective neuroscience decoding of the primal affective experiences of humans and related animals.

    Science.gov (United States)

    Panksepp, Jaak

    2011-01-01

    The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as 'rewards' and 'punishments' in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher brain regions. Such findings suggest

  2. Building and analyzing protein interactome networks by cross-species comparisons

    Directory of Open Access Journals (Sweden)

    Blackman Barron

    2010-03-01

    Full Text Available Abstract Background A genomic catalogue of protein-protein interactions is a rich source of information, particularly for exploring the relationships between proteins. Numerous systems-wide and small-scale experiments have been conducted to identify interactions; however, our knowledge of all interactions for any one species is incomplete, and alternative means to expand these network maps is needed. We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species. Results The connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced. Conclusions Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website http://www.interologfinder.org provides research biologists intuitive access to this data.

  3. Profiling conserved biological pathways in Autosomal Dominant Polycystic Kidney Disorder (ADPKD) to elucidate key transcriptomic alterations regulating cystogenesis: A cross-species meta-analysis approach.

    Science.gov (United States)

    Chatterjee, Shatakshee; Verma, Srikant Prasad; Pandey, Priyanka

    2017-09-05

    Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen. Intra-species combined analysis was performed after considering removal of batch effect. Significantly enriched GO biological processes and KEGG pathways were computed and their overlap was observed. For the conserved pathways, biological modules and gene regulatory networks were observed. Additionally, Gene Set Enrichment Analysis (GSEA) using Molecular Signature Database (MSigDB) was performed for genes found in conserved pathways. We obtained 28 modules of significantly enriched GO processes and 5 major functional categories from significantly enriched KEGG pathways conserved in human, mice and rats that in turn suggest a global transcriptomic perturbation affecting cyst - formation, growth and progression. Significantly enriched pathways obtained from up-regulated genes such as Genomic instability, Protein localization in ER and Insulin Resistance were found to regulate cyst formation and growth whereas cyst progression due to increased cell adhesion and inflammation was suggested by perturbations in Angiogenesis, TGF-beta, CAMs, and Infection related pathways. Additionally, networks revealed shared genes among pathways e.g. SMAD2 and SMAD7 in Endocytosis and TGF-beta. Our study suggests cyst formation and progression to be an outcome of interplay between a set of several key deregulated pathways. Thus, further translational research is warranted focusing on developing a combinatorial therapeutic

  4. Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae.

    Science.gov (United States)

    Valente, Rita S; Nadal-Jimenez, Pol; Carvalho, André F P; Vieira, Filipe J D; Xavier, Karina B

    2017-05-23

    Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora ), two signaling networks-the N-acyl homoserine lactone (AHL) quorum-sensing system and the Gac/Rsm signal transduction pathway-control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone

  5. Cross-species affective neuroscience decoding of the primal affective experiences of humans and related animals.

    Directory of Open Access Journals (Sweden)

    Jaak Panksepp

    higher brain regions. Such findings suggest nested-hierarchies of BrainMind affective processing, with primal emotional functions being foundational for secondary-process learning and memory mechanisms, which interface with tertiary-process cognitive-thoughtful functions of the BrainMind.

  6. Hypnosis, suggestion, and suggestibility: an integrative model.

    Science.gov (United States)

    Lynn, Steven Jay; Laurence, Jean-Roch; Kirsch, Irving

    2015-01-01

    This article elucidates an integrative model of hypnosis that integrates social, cultural, cognitive, and neurophysiological variables at play both in and out of hypnosis and considers their dynamic interaction as determinants of the multifaceted experience of hypnosis. The roles of these variables are examined in the induction and suggestion stages of hypnosis, including how they are related to the experience of involuntariness, one of the hallmarks of hypnosis. It is suggested that studies of the modification of hypnotic suggestibility; cognitive flexibility; response sets and expectancies; the default-mode network; and the search for the neurophysiological correlates of hypnosis, more broadly, in conjunction with research on social psychological variables, hold much promise to further understanding of hypnosis.

  7. Mining online genomic resources in Anolis carolinensis facilitates rapid and inexpensive development of cross-species microsatellite markers for the Anolis lizard genus.

    Science.gov (United States)

    Wordley, Claire; Slate, Jon; Stapley, Jessica

    2011-01-01

    Online sequence databases can provide valuable resources for the development of cross-species genetic markers. In particular, mining expressed tag sequences (EST) for microsatellites and developing conserved cross-species microsatellite markers can provide a rapid and relatively inexpensive method to develop new markers for a range of species. Here, we adopt this approach to develop cross-species microsatellite markers in Anolis lizards, which is a model genus in evolutionary biology and ecology. Using EST sequences from Anolis carolinensis, we identified 127 microsatellites that satisfied our criteria, and tested 49 of these in five species of Anolis (carolinensis, distichus, apletophallus, porcatus and sagrei). We identified between 8 and 25 new variable genetic markers for five Anolis species. These markers will be a valuable resource for studies of population genetics, comparative mapping, mating systems, behavioural ecology and adaptive radiations in this diverse lineage. © 2010 Blackwell Publishing Ltd.

  8. Quantitative cross-species extrapolation between humans and fish: the case of the anti-depressant fluoxetine.

    Directory of Open Access Journals (Sweden)

    Luigi Margiotta-Casaluci

    Full Text Available Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis. To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 µg/L to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (H(TPCs. Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the H(TPC range, whereas no effects were observed at plasma concentrations below the H(TPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool

  9. Cross-species ChIP-seq studies provide insights into regulatory strategies of PPAR¿ in adipocytes

    DEFF Research Database (Denmark)

    Schmidt, Søren Fisker; Jørgensen, Mette; Sandelin, Albin Gustav

    2012-01-01

    Three recent studies have investigated interspecies retention of binding sites of peroxisome proliferator-activated receptor ¿ (PPAR¿), the master regulator of adipocyte differention, between mouse and human adipocytes. Here we discuss the major findings and demonstrate that retention of binding ...

  10. Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development.

    Science.gov (United States)

    Brett, Zoë H; Humphreys, Kathryn L; Fleming, Alison S; Kraemer, Gary W; Drury, Stacy S

    2015-05-01

    Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic-pituitary-adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal-infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence.

  11. Development of novel microsatellite markers for the Northern Goshawk (Accipiter gentilis) and their utility in cross-species amplification

    Science.gov (United States)

    Haughey, Christy; Sage, George K.; Degange, Gabriel; Sonsthagen, Sarah A.; Talbot, Sandra L.

    2016-01-01

    The Northern Goshawk (Accipiter gentilis) is a large forest raptor with a Holarctic distribution and, in some portions of its range, a species of conservation concern. To augment previously reported genetic markers, 13 novel polymorphic microsatellite markers were developed to establish individual identification and familial relationships, to assess levels of genetic diversity, and to identify diagnostic markers. Of the 22 loci tested, 13 were polymorphic, seven were monomorphic, and two failed to amplify. This suite of microsatellite loci yielded a combined probability of parental exclusion of 98%; a single individual sampled from a North American population can be reliably identified using a combination of seven of the 13 polymorphic loci. Cross-species screening in Cooper's Hawks (A. cooperii) and Sharp-shinned Hawks (A. striatus) of the 20 loci that successfully amplified in Northern Goshawks identified 13 loci as polymorphic in each species. Six of these loci (Age1303, Age1308, Age1309, Age1312, and Age1314) appeared to be useful in distinguishing between Accipiter species. These markers will be useful to researchers investigating populations of North American accipiters.

  12. Exposure to early adversity: Points of cross-species translation that can lead to improved understanding of depression.

    Science.gov (United States)

    Andersen, Susan L

    2015-05-01

    The relationship between developmental exposure to adversity and affective disorders is reviewed. Adversity discussed herein includes physical and sexual abuse, neglect, or loss of a caregiver in humans. While these stressors can occur at any point during development, the unique temporal relationship to specific depressive symptoms was the focus of discussion. Further influences of stress exposure during sensitive periods can vary by gender and duration of abuse as well. Data from animal studies are presented to provide greater translational and causal understanding of how sensitive periods, different types of psychosocial stressors, and sex interact to produce depressive-like behaviors. Findings from maternal separation, isolation rearing, chronic variable stress, and peer-peer rearing paradigms clarify interpretation about how various depressive behaviors are influenced by age of exposure. Depressive behaviors are broken down into the following categories: mood and affect, anhedonia, energy, working memory, sleep-wake, appetite changes, suicide, and general malaise. Cross-species evidence from humans, nonhuman primates, rats, and mice within each of these categories is discussed. In conclusion, sensitive periods for affective-related behaviors (anxiety, mood, and controllability) occur earlier in life, while other aspects of depression are associated with adversity later during adolescence.

  13. Cross-species comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei quorum-sensing regulons.

    Science.gov (United States)

    Majerczyk, Charlotte D; Brittnacher, Mitchell J; Jacobs, Michael A; Armour, Christopher D; Radey, Matthew C; Bunt, Richard; Hayden, Hillary S; Bydalek, Ryland; Greenberg, E Peter

    2014-11-01

    Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei (the Bptm group) are close relatives with very different lifestyles: B. pseudomallei is an opportunistic pathogen, B. thailandensis is a nonpathogenic saprophyte, and B. mallei is a host-restricted pathogen. The acyl-homoserine lactone quorum-sensing (QS) systems of these three species show a high level of conservation. We used transcriptome sequencing (RNA-seq) to define the quorum-sensing regulon in each species, and we performed a cross-species analysis of the QS-controlled orthologs. Our analysis revealed a core set of QS-regulated genes in all three species, as well as QS-controlled factors shared by only two species or unique to a given species. This global survey of the QS regulons of B. pseudomallei, B. thailandensis, and B. mallei serves as a platform for predicting which QS-controlled processes might be important in different bacterial niches and contribute to the pathogenesis of B. pseudomallei and B. mallei. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. Cross-Species Comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei Quorum-Sensing Regulons

    Science.gov (United States)

    Majerczyk, Charlotte D.; Brittnacher, Mitchell J.; Jacobs, Michael A.; Armour, Christopher D.; Radey, Matthew C.; Bunt, Richard; Hayden, Hillary S.; Bydalek, Ryland

    2014-01-01

    Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei (the Bptm group) are close relatives with very different lifestyles: B. pseudomallei is an opportunistic pathogen, B. thailandensis is a nonpathogenic saprophyte, and B. mallei is a host-restricted pathogen. The acyl-homoserine lactone quorum-sensing (QS) systems of these three species show a high level of conservation. We used transcriptome sequencing (RNA-seq) to define the quorum-sensing regulon in each species, and we performed a cross-species analysis of the QS-controlled orthologs. Our analysis revealed a core set of QS-regulated genes in all three species, as well as QS-controlled factors shared by only two species or unique to a given species. This global survey of the QS regulons of B. pseudomallei, B. thailandensis, and B. mallei serves as a platform for predicting which QS-controlled processes might be important in different bacterial niches and contribute to the pathogenesis of B. pseudomallei and B. mallei. PMID:25182491

  15. Open to Suggestion.

    Science.gov (United States)

    Journal of Reading, 1987

    1987-01-01

    Offers (1) suggestions for improving college students' study skills; (2) a system for keeping track of parent, teacher, and community contacts; (3) suggestions for motivating students using tic tac toe; (4) suggestions for using etymology to improve word retention; (5) a word search grid; and (6) suggestions for using postcards in remedial reading…

  16. Suicidality and interrogative suggestibility.

    Science.gov (United States)

    Pritchard-Boone, Lea; Range, Lillian M

    2005-01-01

    All people are subject to memory suggestibility, but suicidal individuals may be especially so. The link between suicidality and suggestibility is unclear given mixed findings and methodological weaknesses of past research. To test the link between suicidality and interrogative suggestibility, 149 undergraduates answered questions about suicidal thoughts and reasons for living, and participated in a direct suggestibility procedure. As expected, suggestibility correlated with suicidality but accounted for little overall variance (4%). Mental health professionals might be able to take advantage of client suggestibility by directly telling suicidal persons to refrain from suicidal thoughts or actions.

  17. Cross-species chromosome painting in bats from Madagascar: the contribution of Myzopodidae to revealing ancestral syntenies in Chiroptera.

    Science.gov (United States)

    Richards, Leigh R; Rambau, Ramugondo V; Lamb, Jennifer M; Taylor, Peter J; Yang, Fengtang; Schoeman, M Corrie; Goodman, Steven M

    2010-09-01

    The chiropteran fauna of Madagascar comprises eight of the 19 recognized families of bats, including the endemic Myzopodidae. While recent systematic studies of Malagasy bats have contributed to our understanding of the morphological and genetic diversity of the island's fauna, little is known about their cytosystematics. Here we investigate karyotypic relationships among four species, representing four families of Chiroptera endemic to the Malagasy region using cross-species chromosome painting with painting probes of Myotis myotis: Myzopodidae (Myzopoda aurita, 2n = 26), Molossidae (Mormopterus jugularis, 2n = 48), Miniopteridae (Miniopterus griveaudi, 2n = 46), and Vespertilionidae (Myotis goudoti, 2n = 44). This study represents the first time a member of the family Myzopodidae has been investigated using chromosome painting. Painting probes of M. myotis were used to delimit 29, 24, 23, and 22 homologous chromosomal segments in the genomes of M. aurita, M. jugularis, M. griveaudi, and M. goudoti, respectively. Comparison of GTG-banded homologous chromosomes/chromosomal segments among the four species revealed the genome of M. aurita has been structured through 14 fusions of chromosomes and chromosomal segments of M. myotis chromosomes leading to a karyotype consisting solely of bi-armed chromosomes. In addition, chromosome painting revealed a novel X-autosome translocation in M. aurita. Comparison of our results with published chromosome maps provided further evidence for karyotypic conservatism within the genera Mormopterus, Miniopterus, and Myotis. Mapping of chromosomal rearrangements onto a molecular consensus phylogeny revealed ancestral syntenies shared between Myzopoda and other bat species of the infraorders Pteropodiformes and Vespertilioniformes. Our study provides further evidence for the involvement of Robertsonian (Rb) translocations and fusions/fissions in chromosomal evolution within Chiroptera.

  18. Characterisation of the zebrafish serotonin transporter functionally links TM10 to the ligand binding site

    DEFF Research Database (Denmark)

    Severinsen, Kasper; Müller, Heidi Kaastrup; Wiborg, Ove

    2008-01-01

    and [(3)H]-escitalopram binding in transiently transfected human embryonic kidney cells; HEK-293-MSR. Residues responsible for altered affinities inhibitors were pinpointed by generating cross-species chimeras and subsequent point mutations by site directed mutagenesis. drSERT has a higher affinity...

  19. Distinguishing between cancer driver and passenger gene alteration candidates via cross-species comparison: a pilot study

    International Nuclear Information System (INIS)

    Ji, Xinglai; Tang, Jie; Halberg, Richard; Busam, Dana; Ferriera, Steve; Peña, Maria Marjorette O; Venkataramu, Chinnambally; Yeatman, Timothy J; Zhao, Shaying

    2010-01-01

    We are developing a cross-species comparison strategy to distinguish between cancer driver- and passenger gene alteration candidates, by utilizing the difference in genomic location of orthologous genes between the human and other mammals. As an initial test of this strategy, we conducted a pilot study with human colorectal cancer (CRC) and its mouse model C57BL/6J Apc Min/+ , focusing on human 5q22.2 and 18q21.1-q21.2. We first performed bioinformatics analysis on the evolution of 5q22.2 and 18q21.1-q21.2 regions. Then, we performed exon-targeted sequencing, real time quantitative polymerase chain reaction (qPCR), and real time quantitative reverse transcriptase PCR (qRT-PCR) analyses on a number of genes of both regions with both human and mouse colon tumors. These two regions (5q22.2 and 18q21.1-q21.2) are frequently deleted in human CRCs and encode genuine colorectal tumor suppressors APC and SMAD4. They also encode genes such as MCC (mutated in colorectal cancer) with their role in CRC etiology unknown. We have discovered that both regions are evolutionarily unstable, resulting in genes that are clustered in each human region being found scattered at several distinct loci in the genome of many other species. For instance, APC and MCC are within 200 kb apart in human 5q22.2 but are 10 Mb apart in the mouse genome. Importantly, our analyses revealed that, while known CRC driver genes APC and SMAD4 were disrupted in both human colorectal tumors and tumors from Apc Min/+ mice, the questionable MCC gene was disrupted in human tumors but appeared to be intact in mouse tumors. These results indicate that MCC may not actually play any causative role in early colorectal tumorigenesis. We also hypothesize that its disruption in human CRCs is likely a mere result of its close proximity to APC in the human genome. Expanding this pilot study to the entire genome may identify more questionable genes like MCC, facilitating the discovery of new CRC driver gene candidates

  20. Expression profiling and cross-species RNA interference (RNAi of desiccation-induced transcripts in the anhydrobiotic nematode Aphelenchus avenae

    Directory of Open Access Journals (Sweden)

    Culleton Bridget A

    2010-01-01

    Full Text Available Abstract Background Some organisms can survive extreme desiccation by entering a state of suspended animation known as anhydrobiosis. The free-living mycophagous nematode Aphelenchus avenae can be induced to enter anhydrobiosis by pre-exposure to moderate reductions in relative humidity (RH prior to extreme desiccation. This preconditioning phase is thought to allow modification of the transcriptome by activation of genes required for desiccation tolerance. Results To identify such genes, a panel of expressed sequence tags (ESTs enriched for sequences upregulated in A. avenae during preconditioning was created. A subset of 30 genes with significant matches in databases, together with a number of apparently novel sequences, were chosen for further study. Several of the recognisable genes are associated with water stress, encoding, for example, two new hydrophilic proteins related to the late embryogenesis abundant (LEA protein family. Expression studies confirmed EST panel members to be upregulated by evaporative water loss, and the majority of genes was also induced by osmotic stress and cold, but rather fewer by heat. We attempted to use RNA interference (RNAi to demonstrate the importance of this gene set for anhydrobiosis, but found A. avenae to be recalcitrant with the techniques used. Instead, therefore, we developed a cross-species RNAi procedure using A. avenae sequences in another anhydrobiotic nematode, Panagrolaimus superbus, which is amenable to gene silencing. Of 20 A. avenae ESTs screened, a significant reduction in survival of desiccation in treated P. superbus populations was observed with two sequences, one of which was novel, while the other encoded a glutathione peroxidase. To confirm a role for glutathione peroxidases in anhydrobiosis, RNAi with cognate sequences from P. superbus was performed and was also shown to reduce desiccation tolerance in this species. Conclusions This study has identified and characterised the

  1. Distinguishing between cancer driver and passenger gene alteration candidates via cross-species comparison: a pilot study.

    Science.gov (United States)

    Ji, Xinglai; Tang, Jie; Halberg, Richard; Busam, Dana; Ferriera, Steve; Peña, Maria Marjorette O; Venkataramu, Chinnambally; Yeatman, Timothy J; Zhao, Shaying

    2010-08-13

    We are developing a cross-species comparison strategy to distinguish between cancer driver- and passenger gene alteration candidates, by utilizing the difference in genomic location of orthologous genes between the human and other mammals. As an initial test of this strategy, we conducted a pilot study with human colorectal cancer (CRC) and its mouse model C57BL/6J ApcMin/+, focusing on human 5q22.2 and 18q21.1-q21.2. We first performed bioinformatics analysis on the evolution of 5q22.2 and 18q21.1-q21.2 regions. Then, we performed exon-targeted sequencing, real time quantitative polymerase chain reaction (qPCR), and real time quantitative reverse transcriptase PCR (qRT-PCR) analyses on a number of genes of both regions with both human and mouse colon tumors. These two regions (5q22.2 and 18q21.1-q21.2) are frequently deleted in human CRCs and encode genuine colorectal tumor suppressors APC and SMAD4. They also encode genes such as MCC (mutated in colorectal cancer) with their role in CRC etiology unknown. We have discovered that both regions are evolutionarily unstable, resulting in genes that are clustered in each human region being found scattered at several distinct loci in the genome of many other species. For instance, APC and MCC are within 200 kb apart in human 5q22.2 but are 10 Mb apart in the mouse genome. Importantly, our analyses revealed that, while known CRC driver genes APC and SMAD4 were disrupted in both human colorectal tumors and tumors from ApcMin/+ mice, the questionable MCC gene was disrupted in human tumors but appeared to be intact in mouse tumors. These results indicate that MCC may not actually play any causative role in early colorectal tumorigenesis. We also hypothesize that its disruption in human CRCs is likely a mere result of its close proximity to APC in the human genome. Expanding this pilot study to the entire genome may identify more questionable genes like MCC, facilitating the discovery of new CRC driver gene candidates.

  2. Unlocking Barriers to DNA Vaccine Immunogenicity: A Cross-Species Analysis of Cytosolic DNA Sensing in Skeletal Muscle Myocytes

    Science.gov (United States)

    2017-10-01

    ELISA or... ELISA or quantitative immunofluorescence microscopy Ø Planned activity duration in SOW: 2017 Q1 – 2017 Q3 Ø Proportion of subtask completed: 0% Ø...Subtask 3A: i) validate mouse cell findings using chemiluminescent electrophoretic mobility shift assays (or DNA-binding ELISA technique in

  3. Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei

    Science.gov (United States)

    2010-08-01

    or the early liver-stages of the mammalian life cycle . One of these antigens is the cell-traversal protein for ookinetes and sporozoites (CelTOS...Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with... Plasmodium berghei Elke S. Bergmann-Leitner1*, Ryan M. Mease1, Patricia De La Vega1, Tatyana Savranskaya2, Mark Polhemus1, Christian Ockenhouse1, Evelina

  4. Right place, wrong species: a 20-year review of rabies virus cross species transmission among terrestrial mammals in the United States.

    Directory of Open Access Journals (Sweden)

    Ryan M Wallace

    Full Text Available In the continental US, four terrestrial mammalian species are reservoirs for seven antigenic rabies virus variants. Cross species transmission (CST occurs when a rabies virus variant causes disease in non-reservoir species.This study analyzed national surveillance data for rabies in terrestrial mammals. The CST rate was defined as: number of rabid non-reservoir animals/number of rabid reservoir animals. CST rates were analyzed for trend. Clusters of high CST rate counties were evaluated using space-time scanning statistics.The number of counties reporting a raccoon variant CST rate >1.0 increased from 75 in 1992 to 187 in 2011; counties with skunk variant CST rates >1.0 remained unchanged during the same period. As of 2011, for every rabid raccoon reported within the raccoon variant region, there were 0.73 cases of this variant reported in non-reservoir animals. Skunks were the most common non-reservoir animal reported with the raccoon rabies variant. Domestic animals were the most common non-reservoir animal diagnosed with a skunk rabies virus variant (n = 1,601. Cross species transmission rates increased fastest among domestic animals.Cross species transmission of rabies virus variants into non-reservoir animals increases the risk of human exposures and threatens current advances toward rabies control. Cross species transmission in raccoon rabies enzootic regions increased dramatically during the study period. Pet owners should vaccinate their dogs and cats to ensure against CST, particularly in regions with active foci of rabies circulation. Clusters of high CST activity represent areas for further study to better understand interspecies disease transmission dynamics. Each CST event has the potential to result in a rabies virus adapted for sustained transmission in a new species; therefore further understanding of the dynamics of CST may help in early detection or prevention of the emergence of new terrestrial rabies virus variants.

  5. Transcript profiling of two alfalfa genotypes with contrasting cell wall composition in stems using a cross-species platform: optimizing analysis by masking biased probes

    Directory of Open Access Journals (Sweden)

    Jung Hans-Joachim G

    2010-05-01

    Full Text Available Abstract Background The GeneChip® Medicago Genome Array, developed for Medicago truncatula, is a suitable platform for transcript profiling in tetraploid alfalfa [Medicago sativa (L. subsp. sativa]. However, previous research involving cross-species hybridization (CSH has shown that sequence variation between two species can bias transcript profiling by decreasing sensitivity (number of expressed genes detected and the accuracy of measuring fold-differences in gene expression. Results Transcript profiling using the Medicago GeneChip® was conducted with elongating stem (ES and post-elongation stem (PES internodes from alfalfa genotypes 252 and 1283 that differ in stem cell wall concentrations of cellulose and lignin. A protocol was developed that masked probes targeting inter-species variable (ISV regions of alfalfa transcripts. A probe signal intensity threshold was selected that optimized both sensitivity and accuracy. After masking for both ISV regions and previously identified single-feature polymorphisms (SFPs, the number of differentially expressed genes between the two genotypes in both ES and PES internodes was approximately 2-fold greater than the number detected prior to masking. Regulatory genes, including transcription factor and receptor kinase genes that may play a role in development of secondary xylem, were significantly over-represented among genes up-regulated in 252 PES internodes compared to 1283 PES internodes. Several cell wall-related genes were also up-regulated in genotype 252 PES internodes. Real-time quantitative RT-PCR of differentially expressed regulatory and cell wall-related genes demonstrated increased sensitivity and accuracy after masking for both ISV regions and SFPs. Over 1,000 genes that were differentially expressed in ES and PES internodes of genotypes 252 and 1283 were mapped onto putative orthologous loci on M. truncatula chromosomes. Clustering simulation analysis of the differentially expressed genes

  6. Suggestive Objects at Work

    DEFF Research Database (Denmark)

    Ratner, Helene Gad

    2009-01-01

    In Western secular societies, spiritual life is no longer limited to classical religious institutions but can also be found at workplace organizations. While spirituality is conventionally understood as a subjective and internal process, this paper proposes the concept of ‘suggestive objects......’, constructed by combining insights from Gabriel Tarde's sociology with Bruno Latour's actor-network theory, to theorize the material dimension of organizational spirituality. The sacred in organizations arises not from the internalization of collective values but through the establishment of material...... scaffolding. This has deep implications for our understanding of the sacred, including a better appreciation of the way that suggestive objects make the sacred durable, the way they organize it....

  7. TRIM5 suppresses cross-species transmission of a primate immunodeficiency virus and selects for emergence of resistant variants in the new species.

    Directory of Open Access Journals (Sweden)

    Andrea Kirmaier

    2010-08-01

    Full Text Available Simian immunodeficiency viruses of sooty mangabeys (SIVsm are the source of multiple, successful cross-species transmissions, having given rise to HIV-2 in humans, SIVmac in rhesus macaques, and SIVstm in stump-tailed macaques. Cellular assays and phylogenetic comparisons indirectly support a role for TRIM5alpha, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature. Here, we investigate the in vivo role of TRIM5 directly, focusing on transmission of primate immunodeficiency viruses between outbred primate hosts. Specifically, we retrospectively analyzed experimental cross-species transmission of SIVsm in two cohorts of rhesus macaques and found a significant effect of TRIM5 genotype on viral replication levels. The effect was especially pronounced in a cohort of animals infected with SIVsmE543-3, where TRIM5 genotype correlated with approximately 100-fold to 1,000-fold differences in viral replication levels. Surprisingly, transmission occurred even in individuals bearing restrictive TRIM5 genotypes, resulting in attenuation of replication rather than an outright block to infection. In cell-culture assays, the same TRIM5 alleles associated with viral suppression in vivo blocked infectivity of two SIVsm strains, but not the macaque-adapted strain SIVmac239. Adaptations appeared in the viral capsid in animals with restrictive TRIM5 genotypes, and similar adaptations coincide with emergence of SIVmac in captive macaques in the 1970s. Thus, host TRIM5 can suppress viral replication in vivo, exerting selective pressure during the initial stages of cross-species transmission.

  8. Characterization of highly informative cross-species microsatellite panels for the Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) including five novel primers.

    Science.gov (United States)

    Hunter, Margaret Kellogg; Broderick, Damien; Ovenden, Jennifer R; Tucker, Kimberly Pause; Bonde, Robert K; McGuire, Peter M; Lanyon, Janet M

    2010-03-01

    The Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) are threatened species of aquatic mammals in the order Sirenia. Sirenian conservation and management actions would benefit from a more complete understanding of genetic diversity and population structure. Generally, species-specific microsatellite markers are employed in conservation genetic studies; however, robust markers can be difficult and costly to isolate. To increase the number of available markers, dugong and manatee microsatellite primers were evaluated for cross-species amplification. Furthermore, one manatee and four dugong novel primers are reported. After polymerase chain reaction optimization, 23 (92%) manatee primers successfully amplified dugong DNA, of which 11 (48%) were polymorphic. Of the 32 dugong primers tested, 27 (84%) yielded product in the manatee, of which 17 (63%) were polymorphic. Dugong and manatee primers were compared and the most informative markers were selected to create robust and informative marker-panels for each species. These cross-species microsatellite marker-panels can be employed to assess other sirenian populations and can provide beneficial information for the protection and management of these unique mammals. Published 2009. This article is a US Government work and is in the public domain in the USA.

  9. Chromosome evolution in kangaroos (Marsupialia: Macropodidae): cross species chromosome painting between the tammar wallaby and rock wallaby spp. with the 2n = 22 ancestral macropodid karyotype.

    Science.gov (United States)

    O'Neill, R J; Eldridge, M D; Toder, R; Ferguson-Smith, M A; O'Brien, P C; Graves, J A

    1999-06-01

    Marsupial mammals show extraordinary karyotype stability, with 2n = 14 considered ancestral. However, macropodid marsupials (kangaroos and wallabies) exhibit a considerable variety of karyotypes, with a hypothesised ancestral karyotype of 2n = 22. Speciation and karyotypic diversity in rock wallabies (Petrogale) is exceptional. We used cross species chromosome painting to examine the chromosome evolution between the tammar wallaby (2n = 16) and three 2n = 22 rock wallaby species groups with the putative ancestral karyotype. Hybridization of chromosome paints prepared from flow sorted chromosomes of the tammar wallaby to Petrogale spp., showed that this ancestral karyotype is largely conserved among 2n = 22 rock wallaby species, and confirmed the identity of ancestral chromosomes which fused to produce the bi-armed chromosomes of the 2n = 16 tammar wallaby. These results illustrate the fission-fusion process of karyotype evolution characteristic of the kangaroo group.

  10. Development of New Microsatellite DNA Markers from Apostichopus japonicus and Their Cross-Species Application in Parastichopus parvimensis and Pathallus mollis

    Directory of Open Access Journals (Sweden)

    Guiping Chen

    2011-09-01

    Full Text Available Twenty microsatellite DNA markers were developed for sea cucumber and used to investigate polymorphisms of 60 wild Apostichopus japonicus individuals collected from China. It revealed that all the markers were polymorphic. A total of 164 alleles were detected at 20 loci. The number of alleles per locus varied from 3 to 17 with an average of 8.2, and the expected heterozygosities of each locus ranged from 0.03 to 0.89 with an average of 0.64. Cross-species amplification was also conducted in Parastichopus parvimensis collected from the United States and Pathallus mollis collected from Peru. The result showed that 17 loci amplified Parastichopus parvimensis DNAs while only 4 loci could amplify Pathallus mollis DNAs. All of the polymorphic markers would be useful for future genetic breeding and the assessment of genetic variation within sea cucumbers.

  11. Development of nine new microsatellite loci for the American beaver, Castor canadensis (Rodentia: Castoridae), and cross-species amplification in the European beaver, Castor fiber.

    Science.gov (United States)

    Pelz-Serrano, Karla; Munguia-Vega, Adrian; Piaggio, Antoinette J; Neubaum, Melissa; Munclinger, Pavel; Pártl, Adam; VAN Riper Iii, Charles; Culver, Melanie

    2009-03-01

    We developed nine new nuclear dinucleotide microsatellite loci for Castor canadensis. All loci were polymorphic, except for one. The number of alleles ranged from two to four and from five to 12 in populations from Arizona and Wisconsin, respectively. Average heterozygosity ranged from 0.13 to 0.86 per locus. Since cross-species amplification in Castor fiber was successful only in four loci, we tested also nine recently published C. canadensis loci in the Eurasian species. Eight of the published loci amplified; however, three were monomorphic. The number of alleles was lower in C. fiber than in C. canadensis at all loci tested. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd.

  12. Karyotype evolution in Rhinolophus bats (Rhinolophidae, Chiroptera) illuminated by cross-species chromosome painting and G-banding comparison.

    Science.gov (United States)

    Mao, Xiuguang; Nie, Wenhui; Wang, Jinhuan; Su, Weiting; Ao, Lei; Feng, Qing; Wang, Yingxiang; Volleth, Marianne; Yang, Fengtang

    2007-01-01

    Rhinolophus (Rhinolophidae) is the second most speciose genus in Chiroptera and has extensively diversified diploid chromosome numbers (from 2n = 28 to 62). In spite of many attempts to explore the karyotypic evolution of this genus, most studies have been based on conventional Giemsa staining rather than G-banding. Here we have made a whole set of chromosome-specific painting probes from flow-sorted chromosomes of Aselliscus stoliczkanus (Hipposideridae). These probes have been utilized to establish the first genome-wide homology maps among six Rhinolophus species with four different diploid chromosome numbers (2n = 36, 44, 58, and 62) and three species from other families: Rousettus leschenaulti (2n = 36, Pteropodidae), Hipposideros larvatus (2n = 32, Hipposideridae), and Myotis altarium (2n = 44, Vespertilionidae) by fluorescence in situ hybridization. To facilitate integration with published maps, human paints were also hybridized to A. stoliczkanus chromosomes. Our painting results substantiate the wide occurrence of whole-chromosome arm conservation in Rhinolophus bats and suggest that Robertsonian translocations of different combinations account for their karyotype differences. Parsimony analysis using chromosomal characters has provided some new insights into the Rhinolophus ancestral karyotype and phylogenetic relationships among these Rhinolophus species so far studied. In addition to Robertsonian translocations, our results suggest that whole-arm (reciprocal) translocations involving multiple non-homologous chromosomes as well could have been involved in the karyotypic evolution within Rhinolophus, in particular those bats with low and medium diploid numbers.

  13. Cross-species infection trials reveal cryptic parasite varieties and a putative polymorphism shared among host species.

    Science.gov (United States)

    Luijckx, Pepijn; Duneau, David; Andras, Jason P; Ebert, Dieter

    2014-02-01

    A parasite's host range can have important consequences for ecological and evolutionary processes but can be difficult to infer. Successful infection depends on the outcome of multiple steps and only some steps of the infection process may be critical in determining a parasites host range. To test this hypothesis, we investigated the host range of the bacterium Pasteuria ramosa, a Daphnia parasite, and determined the parasites success in different stages of the infection process. Multiple genotypes of Daphnia pulex, Daphnia longispina and Daphnia magna were tested with four Pasteuria genotypes using infection trials and an assay that determines the ability of the parasite to attach to the hosts esophagus. We find that attachment is not specific to host species but is specific to host genotype. This may suggest that alleles on the locus controlling attachment are shared among different host species that diverged 100 million year. However, in our trials, Pasteuria was never able to reproduce in nonnative host species, suggesting that Pasteuria infecting different host species are different varieties, each with a narrow host range. Our approach highlights the explanatory power of dissecting the steps of the infection process and resolves potentially conflicting reports on parasite host ranges. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  14. Rapid Development of Microsatellite Markers for Plantago ovata Forsk.: Using Next Generation Sequencing and Their Cross-Species Transferability

    Directory of Open Access Journals (Sweden)

    Ranbir Singh Fougat

    2014-06-01

    Full Text Available Isabgol (Plantago ovata Forsk. is an important medicinal plant having high pharmacological activity in its seed husk, which is substantially used in the food, beverages and packaging industries. Nevertheless, isabgol lags behind in research, particularly for genomic resources, like molecular markers, genetic maps, etc. Presently, molecular markers can be easily developed through next generation sequencing technologies, more efficiently, cost effectively and in less time than ever before. This study was framed keeping in view the need to develop molecular markers for this economically important crop by employing a microsatellite enrichment protocol using a next generation sequencing platform (ion torrent PGM™ to obtain simple sequence repeats (SSRs for Plantago ovata for the very first time. A total of 3447 contigs were assembled, which contained 249 SSRs. Thirty seven loci were randomly selected for primer development; of which, 30 loci were successfully amplified. The developed microsatellite markers showed the amplification of the expected size and cross-amplification in another six species of Plantago. The SSR markers were unable to show polymorphism within P. ovata, suggesting that low variability exists within genotypes of P. ovata. This study suggests that PGM™ sequencing is a rapid and cost-effective tool for developing SSR markers for non-model species, and the markers so-observed could be useful in the molecular breeding of P. ovata.

  15. Genetic diversity and differentiation in reef-building Millepora species, as revealed by cross-species amplification of fifteen novel microsatellite loci

    Directory of Open Access Journals (Sweden)

    Caroline E. Dubé

    2017-02-01

    Full Text Available Quantifying the genetic diversity in natural populations is crucial to address ecological and evolutionary questions. Despite recent advances in whole-genome sequencing, microsatellite markers have remained one of the most powerful tools for a myriad of population genetic approaches. Here, we used the 454 sequencing technique to develop microsatellite loci in the fire coral Millepora platyphylla, an important reef-builder of Indo-Pacific reefs. We tested the cross-species amplification of these loci in five other species of the genus Millepora and analysed its success in correlation with the genetic distances between species using mitochondrial 16S sequences. We succeeded in discovering fifteen microsatellite loci in our target species M. platyphylla, among which twelve were polymorphic with 2–13 alleles and a mean observed heterozygosity of 0.411. Cross-species amplification in the five other Millepora species revealed a high probability of amplification success (71% and polymorphism (59% of the loci. Our results show no evidence of decreased heterozygosity with increasing genetic distance. However, only one locus enabled measures of genetic diversity in the Caribbean species M. complanata due to high proportions of null alleles for most of the microsatellites. This result indicates that our novel markers may only be useful for the Indo-Pacific species of Millepora. Measures of genetic diversity revealed significant linkage disequilibrium, moderate levels of observed heterozygosity (0.323–0.496 and heterozygote deficiencies for the Indo-Pacific species. The accessibility to new polymorphic microsatellite markers for hydrozoan Millepora species creates new opportunities for future research on processes driving the complexity of their colonisation success on many Indo-Pacific reefs.

  16. Mechanisms of placebo analgesia: A dual-process model informed by insights from cross-species comparisons.

    Science.gov (United States)

    Schafer, Scott M; Geuter, Stephan; Wager, Tor D

    2018-01-01

    Placebo treatments are pharmacologically inert, but are known to alleviate symptoms across a variety of clinical conditions. Associative learning and cognitive expectations both play important roles in placebo responses, however we are just beginning to understand how interactions between these processes lead to powerful effects. Here, we review the psychological principles underlying placebo effects and our current understanding of their brain bases, focusing on studies demonstrating both the importance of cognitive expectations and those that demonstrate expectancy-independent associative learning. To account for both forms of placebo analgesia, we propose a dual-process model in which flexible, contextually driven cognitive schemas and attributions guide associative learning processes that produce stable, long-term placebo effects. According to this model, the placebo-induction paradigms with the most powerful effects are those that combine reinforcement (e.g., the experience of reduced pain after placebo treatment) with suggestions and context cues that disambiguate learning by attributing perceived benefit to the placebo. Using this model as a conceptual scaffold, we review and compare neurobiological systems identified in both human studies of placebo analgesia and behavioral pain modulation in rodents. We identify substantial overlap between the circuits involved in human placebo analgesia and those that mediate multiple forms of context-based modulation of pain behavior in rodents, including forebrain-brainstem pathways and opioid and cannabinoid systems in particular. This overlap suggests that placebo effects are part of a set of adaptive mechanisms for shaping nociceptive signaling based on its information value and anticipated optimal response in a given behavioral context. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks.

    Science.gov (United States)

    Eagle, Dawn M; Bari, Andrea; Robbins, Trevor W

    2008-08-01

    The term 'action inhibition' encapsulates the ability to prevent any form of planned physical response. Growing evidence suggests that different 'stages' or even subtypes of action inhibition activate subtly different neuropharmacological and neuroanatomical processes. In this review, we present evidence from two commonly used and apparently similar behavioural tests, the stop-signal task and the go/no-go task, to determine if these have similar neuroanatomical and neurochemical modulation. Whilst performance of the stop-signal and go/no-go tasks is modulated across only subtly different anatomical networks, serotonin (5-HT) is strongly implicated in inhibitory control on the go/no-go but not the stop-signal task, whereas the stop-signal reaction time appears more sensitive to the action of noradrenaline. There is clear neuropharmacological and neuroanatomical evidence that stop-signal and go/no-go tasks represent different forms of action inhibition. This evidence translates with remarkable consistency across species. We discuss the possible implications of this evidence with respect to the development of novel therapeutic treatments for disorders in which inhibitory deficits are prominent and debilitating.

  18. B cell recognition of the conserved HIV-1 co-receptor binding site is altered by endogenous primate CD4.

    Directory of Open Access Journals (Sweden)

    Mattias N E Forsell

    2008-10-01

    Full Text Available The surface HIV-1 exterior envelope glycoprotein, gp120, binds to CD4 on the target cell surface to induce the co-receptor binding site on gp120 as the initial step in the entry process. The binding site is comprised of a highly conserved region on the gp120 core, as well as elements of the third variable region (V3. Antibodies against the co-receptor binding site are abundantly elicited during natural infection of humans, but the mechanism of elicitation has remained undefined. In this study, we investigate the requirements for elicitation of co-receptor binding site antibodies by inoculating rabbits, monkeys and human-CD4 transgenic (huCD4 rabbits with envelope glycoprotein (Env trimers possessing high affinity for primate CD4. A cross-species comparison of the antibody responses showed that similar HIV-1 neutralization breadth was elicited by Env trimers in monkeys relative to wild-type (WT rabbits. In contrast, antibodies against the co-receptor site on gp120 were elicited only in monkeys and huCD4 rabbits, but not in the WT rabbits. This was supported by the detection of high-titer co-receptor antibodies in all sera from a set derived from human volunteers inoculated with recombinant gp120. These findings strongly suggest that complexes between Env and (high-affinity primate CD4 formed in vivo are responsible for the elicitation of the co-receptor-site-directed antibodies. They also imply that the naïve B cell receptor repertoire does not recognize the gp120 co-receptor site in the absence of CD4 and illustrate that conformational stabilization, imparted by primary receptor interaction, can alter the immunogenicity of a type 1 viral membrane protein.

  19. B cell recognition of the conserved HIV-1 co-receptor binding site is altered by endogenous primate CD4.

    Science.gov (United States)

    Forsell, Mattias N E; Dey, Barna; Mörner, Andreas; Svehla, Krisha; O'dell, Sijy; Högerkorp, Carl-Magnus; Voss, Gerald; Thorstensson, Rigmor; Shaw, George M; Mascola, John R; Karlsson Hedestam, Gunilla B; Wyatt, Richard T

    2008-10-03

    The surface HIV-1 exterior envelope glycoprotein, gp120, binds to CD4 on the target cell surface to induce the co-receptor binding site on gp120 as the initial step in the entry process. The binding site is comprised of a highly conserved region on the gp120 core, as well as elements of the third variable region (V3). Antibodies against the co-receptor binding site are abundantly elicited during natural infection of humans, but the mechanism of elicitation has remained undefined. In this study, we investigate the requirements for elicitation of co-receptor binding site antibodies by inoculating rabbits, monkeys and human-CD4 transgenic (huCD4) rabbits with envelope glycoprotein (Env) trimers possessing high affinity for primate CD4. A cross-species comparison of the antibody responses showed that similar HIV-1 neutralization breadth was elicited by Env trimers in monkeys relative to wild-type (WT) rabbits. In contrast, antibodies against the co-receptor site on gp120 were elicited only in monkeys and huCD4 rabbits, but not in the WT rabbits. This was supported by the detection of high-titer co-receptor antibodies in all sera from a set derived from human volunteers inoculated with recombinant gp120. These findings strongly suggest that complexes between Env and (high-affinity) primate CD4 formed in vivo are responsible for the elicitation of the co-receptor-site-directed antibodies. They also imply that the naïve B cell receptor repertoire does not recognize the gp120 co-receptor site in the absence of CD4 and illustrate that conformational stabilization, imparted by primary receptor interaction, can alter the immunogenicity of a type 1 viral membrane protein.

  20. A novel cross-species inhibitor to study the function of CatSper Ca2+ channels in sperm.

    Science.gov (United States)

    Rennhack, Andreas; Schiffer, Christian; Brenker, Christoph; Fridman, Dmitry; Nitao, Elis T; Cheng, Yi-Min; Tamburrino, Lara; Balbach, Melanie; Stölting, Gabriel; Berger, Thomas K; Kierzek, Michelina; Alvarez, Luis; Wachten, Dagmar; Zeng, Xu-Hui; Baldi, Elisabetta; Publicover, Stephen; Kaupp, U Benjamin; Strünker, Timo

    2018-05-03

    Sperm from many species share the sperm-specific Ca 2+ channel CatSper (cation channel of sperm) that controls the intracellular Ca 2+ concentration and, thereby, the swimming behaviour. A growing body of evidence suggests that the mechanisms controlling CatSper activity and the role of the channel during fertilization differ among species. However, a lack of suitable pharmacological tools has hampered the elucidation of the function of CatSper. Known CatSper inhibitors exhibit considerable side effects and inhibit also Slo3, the K + channel in mammalian sperm. The drug RU1968 was reported to suppress Ca 2+ signaling in human sperm by an unknown mechanism. We resynthesized the drug and revisited its mechanism of action in sperm form humans, mice, and sea urchins. We show by Ca 2+ fluorimetry, single-cell Ca 2+ imaging, electrophysiology, opto-chemistry, and motility analysis that RU1968 inhibits CatSper in sperm from invertebrates and mammals. The drug lacks toxic side effects in human sperm, does not affect mouse Slo3, and inhibits human Slo3 with about 15-fold lower potency than CatSper. Moreover, in human sperm, the inhibitor mimics CatSper dysfunction and suppresses motility responses evoked by progesterone, an oviductal steroid that activates CatSper. Finally, we show that the drug abolishes CatSper-mediated chemotactic navigation in sea urchin sperm. We propose RU1968 as a novel tool to elucidate the function of CatSper in sperm across species. This article is protected by copyright. All rights reserved.

  1. Combining Human Epigenetics and Sleep Studies in Caenorhabditis elegans: A Cross-Species Approach for Finding Conserved Genes Regulating Sleep.

    Science.gov (United States)

    Huang, Huiyan; Zhu, Yong; Eliot, Melissa N; Knopik, Valerie S; McGeary, John E; Carskadon, Mary A; Hart, Anne C

    2017-06-01

    We aimed to test a combined approach to identify conserved genes regulating sleep and to explore the association between DNA methylation and sleep length. We identified candidate genes associated with shorter versus longer sleep duration in college students based on DNA methylation using Illumina Infinium HumanMethylation450 BeadChip arrays. Orthologous genes in Caenorhabditis elegans were identified, and we examined whether their loss of function affected C. elegans sleep. For genes whose perturbation affected C. elegans sleep, we subsequently undertook a small pilot study to re-examine DNA methylation in an independent set of human participants with shorter versus longer sleep durations. Eighty-seven out of 485,577 CpG sites had significant differential methylation in young adults with shorter versus longer sleep duration, corresponding to 52 candidate genes. We identified 34 C. elegans orthologs, including NPY/flp-18 and flp-21, which are known to affect sleep. Loss of five additional genes alters developmentally timed C. elegans sleep (B4GALT6/bre-4, DOCK180/ced-5, GNB2L1/rack-1, PTPRN2/ida-1, ZFYVE28/lst-2). For one of these genes, ZFYVE28 (also known as hLst2), the pilot replication study again found decreased DNA methylation associated with shorter sleep duration at the same two CpG sites in the first intron of ZFYVE28. Using an approach that combines human epigenetics and C. elegans sleep studies, we identified five genes that play previously unidentified roles in C. elegans sleep. We suggest sleep duration in humans may be associated with differential DNA methylation at specific sites and that the conserved genes identified here likely play roles in C. elegans sleep and in other species. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  2. Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets.

    Science.gov (United States)

    Koshiba, Mamiko; Karino, Genta; Mimura, Koki; Nakamura, Shun; Yui, Kunio; Kunikata, Tetsuya; Yamanouchi, Hideo

    2016-01-01

    Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.

  3. Types of suggestibility: Relationships among compliance, indirect, and direct suggestibility.

    Science.gov (United States)

    Polczyk, Romuald; Pasek, Tomasz

    2006-10-01

    It is commonly believed that direct suggestibility, referring to overt influence, and indirect suggestibility, in which the intention to influence is hidden, correlate poorly. This study demonstrates that they are substantially related, provided that they tap similar areas of influence. Test results from 103 students, 55 women and 48 men, were entered into regression analyses. Indirect suggestibility, as measured by the Sensory Suggestibility Scale for Groups, and compliance, measured by the Gudjonsson Compliance Scale, were predictors of direct suggestibility, assessed with the Barber Suggestibility Scale. Spectral analyses showed that indirect suggestibility is more related to difficult tasks on the BSS, but compliance is more related to easy tasks on this scale.

  4. Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers

    International Nuclear Information System (INIS)

    Holstege, Henne; Wessels, Lodewyk FA; Nederlof, Petra M; Jonkers, Jos; Beers, Erik van; Velds, Arno; Liu, Xiaoling; Joosse, Simon A; Klarenbeek, Sjoerd; Schut, Eva; Kerkhoven, Ron; Klijn, Christiaan N

    2010-01-01

    Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development. To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1 Δ/Δ ;p53 Δ/Δ , Brca2 Δ/Δ ;p53 Δ/Δ and p53 Δ/Δ mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers. Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYC-associated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2 Δ/Δ ;p53 Δ/Δ tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species. The selection of the oncogenome during

  5. Suggestibility and suggestive modulation of the Stroop effect.

    Science.gov (United States)

    Kirsch, Irving

    2011-06-01

    Although the induction of a hypnotic state does not seem necessary for suggestive modulation of the Stroop effect, this important phenomenon has seemed to be dependent on the subject's level of hypnotic suggestibility. Raz and Campbell's (2011) study indicates that suggestion can modulate the Stroop effect substantially in very low suggestible subjects, as well as in those who are highly suggestible. This finding casts doubt on the presumed mechanism by which suggestive modulation is brought about. Research aimed at uncovering the means by which low suggestible individuals are able to modulate the Stroop effect would be welcome, as would assessment of this effect in moderately suggestible people. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Development of novel microsatellite markers for Holothurian scabra (Holothuriidae), Apostichopus japonicas (Stichopodidae) and cross-species testing in other sea cucumbers

    Science.gov (United States)

    Shangguan, Jingbo; Li, Zhongbao

    2018-03-01

    Thirty-five new microsatellite loci from the sea cucumbers Holothurian scabra (Jaeger, 1833) and Apostichopus japonicas (Selenka, 1867) were screened and characterized using the method of magnetic bead enrichment. Of the twenty-four polymorphic loci tested, eighteen were consistent with Hardy-Weinberg equilibrium after a modified false discovery rate (B-Y FDR) correction, whereas six showed statistically significant deviations (CHS2 and CHS11: Psea cucumbers ( Holothurian scabra, Holothuria leucospilota, Stichopus horrens and Apostichopus japonicas) were tested for mutual cross-amplification using a total of ninety microsatellite loci. Although transferability and universality of all loci were generally low, the results of the cross-species study showed that the markers can be applied to identify individuals to species according to the presence or absence of specific microsatellite alleles. The microsatellite markers reported here will contribute to the study of genetic diversity, assisted breeding, and population conservation in sea cucumbers, as well as allow for the identification of individuals to closely related species.

  7. Characterization of highly informative cross-species microsatellite panels for the Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) including five novel primers

    Science.gov (United States)

    Hunter, Margaret Kellogg; Broderick, Damien; Ovenden, Jennifer R.; Tucker, Kimberly Pause; Bonde, Robert K.; McGuire, Peter M.; Lanyon, Janet M.

    2010-01-01

    The Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) are threatened species of aquatic mammals in the order Sirenia. Sirenian conservation and management actions would benefit from a more complete understanding of genetic diversity and population structure. Generally, species-specific microsatellite markers are employed in conservation genetic studies; however, robust markers can be difficult and costly to isolate. To increase the number of available markers, dugong and manatee microsatellite primers were evaluated for cross-species amplification. Furthermore, one manatee and four dugong novel primers are reported. After polymerase chain reaction optimization, 23 (92%) manatee primers successfully amplified dugong DNA, of which 11 (48%) were polymorphic. Of the 32 dugong primers tested, 27 (84%) yielded product in the manatee, of which 17 (63%) were polymorphic. Dugong and manatee primers were compared and the most informative markers were selected to create robust and informative marker-panels for each species. These crossspecies microsatellite marker-panels can be employed to assess other sirenian populations and can provide beneficial information for the protection and management of these unique mammals.

  8. Deepening Sleep by Hypnotic Suggestion

    Science.gov (United States)

    Cordi, Maren J.; Schlarb, Angelika A.; Rasch, Björn

    2014-01-01

    Study Objectives: Slow wave sleep (SWS) plays a critical role in body restoration and promotes brain plasticity; however, it markedly declines across the lifespan. Despite its importance, effective tools to increase SWS are rare. Here we tested whether a hypnotic suggestion to “sleep deeper” extends the amount of SWS. Design: Within-subject, placebo-controlled crossover design. Setting: Sleep laboratory at the University of Zurich, Switzerland. Participants: Seventy healthy females 23.27 ± 3.17 y. Intervention: Participants listened to an auditory text with hypnotic suggestions or a control tape before napping for 90 min while high-density electroencephalography was recorded. Measurements and Results: After participants listened to the hypnotic suggestion to “sleep deeper” subsequent SWS was increased by 81% and time spent awake was reduced by 67% (with the amount of SWS or wake in the control condition set to 100%). Other sleep stages remained unaffected. Additionally, slow wave activity was significantly enhanced after hypnotic suggestions. During the hypnotic tape, parietal theta power increases predicted the hypnosis-induced extension of SWS. Additional experiments confirmed that the beneficial effect of hypnotic suggestions on SWS was specific to the hypnotic suggestion and did not occur in low suggestible participants. Conclusions: Our results demonstrate the effectiveness of hypnotic suggestions to specifically increase the amount and duration of slow wave sleep (SWS) in a midday nap using objective measures of sleep in young, healthy, suggestible females. Hypnotic suggestions might be a successful tool with a lower risk of adverse side effects than pharmacological treatments to extend SWS also in clinical and elderly populations. Citation: Cordi MJ, Schlarb AA, Rasch B. Deepening sleep by hypnotic suggestion. SLEEP 2014;37(6):1143-1152. PMID:24882909

  9. Representational constraints on children's suggestibility.

    Science.gov (United States)

    Ceci, Stephen J; Papierno, Paul B; Kulkofsky, Sarah

    2007-06-01

    In a multistage experiment, twelve 4- and 9-year-old children participated in a triad rating task. Their ratings were mapped with multidimensional scaling, from which euclidean distances were computed to operationalize semantic distance between items in target pairs. These children and age-mates then participated in an experiment that employed these target pairs in a story, which was followed by a misinformation manipulation. Analyses linked individual and developmental differences in suggestibility to children's representations of the target items. Semantic proximity was a strong predictor of differences in suggestibility: The closer a suggested distractor was to the original item's representation, the greater was the distractor's suggestive influence. The triad participants' semantic proximity subsequently served as the basis for correctly predicting memory performance in the larger group. Semantic proximity enabled a priori counterintuitive predictions of reverse age-related trends to be confirmed whenever the distance between representations of items in a target pair was greater for younger than for older children.

  10. Classification of hadith into positive suggestion, negative suggestion, and information

    Science.gov (United States)

    Faraby, Said Al; Riviera Rachmawati Jasin, Eliza; Kusumaningrum, Andina; Adiwijaya

    2018-03-01

    As one of the Muslim life guidelines, based on the meaning of its sentence(s), a hadith can be viewed as a suggestion for doing something, or a suggestion for not doing something, or just information without any suggestion. In this paper, we tried to classify the Bahasa translation of hadith into the three categories using machine learning approach. We tried stemming and stopword removal in preprocessing, and TF-IDF of unigram, bigram, and trigram as the extracted features. As the classifier, we compared between SVM and Neural Network. Since the categories are new, so in order to compare the results of the previous pipelines, we created a baseline classifier using simple rule-based string matching technique. The rule-based algorithm conditions on the occurrence of words such as “janganlah, sholatlah, and so on” to determine the category. The baseline method achieved F1-Score of 0.69, while the best F1-Score from the machine learning approach was 0.88, and it was produced by SVM model with the linear kernel.

  11. Interrogative suggestibility in opiate users.

    Science.gov (United States)

    Murakami, A; Edelmann, R J; Davis, P E

    1996-09-01

    The present study investigated interrogative suggestibility in opiate users. A group of patients undergoing a methadone detoxification programme in an in-patient drug treatment unit (Detox group, n = 21), and a group of residents who had come off drugs and were no longer suffering from withdrawal syndrome (Rehab group, n = 19) were compared on interrogative suggestibility and various other psychological factors. Significant differences were found between the two groups, with the Detox group having more physical and psychological problems, and a higher total suggestibility score in comparison with the Rehab group. These findings are discussed in relation to the context of police interrogations and the reliability of confessions made by suspects and witnesses dependent on opiates.

  12. Genetic characterization of 11 microsatellite loci in Egyptian pigeons (Columba livia domestica) and their cross-species amplification in other Columbidae populations.

    Science.gov (United States)

    Ramadan, Sherif; Dawod, Ahmed; El-Garhy, Osama; Nowier, Amira M; Eltanany, Marwa; Inoue-Murayama, Miho

    2018-04-01

    the CliµD17, CliµT17, CliµD16, CliµD32, CliµT13 , CliµD01 , PG1, PG2, PG4, PG6 , and PG7 microsatellite markers among Egyptian domestic pigeons and across other pigeon species using cross-species amplification method. The information from this study should be useful for genetic characterization and for developing conservation programs of this important species.

  13. Bioinformatics resource manager v2.3: an integrated software environment for systems biology with microRNA and cross-species analysis tools

    Directory of Open Access Journals (Sweden)

    Tilton Susan C

    2012-11-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are noncoding RNAs that direct post-transcriptional regulation of protein coding genes. Recent studies have shown miRNAs are important for controlling many biological processes, including nervous system development, and are highly conserved across species. Given their importance, computational tools are necessary for analysis, interpretation and integration of high-throughput (HTP miRNA data in an increasing number of model species. The Bioinformatics Resource Manager (BRM v2.3 is a software environment for data management, mining, integration and functional annotation of HTP biological data. In this study, we report recent updates to BRM for miRNA data analysis and cross-species comparisons across datasets. Results BRM v2.3 has the capability to query predicted miRNA targets from multiple databases, retrieve potential regulatory miRNAs for known genes, integrate experimentally derived miRNA and mRNA datasets, perform ortholog mapping across species, and retrieve annotation and cross-reference identifiers for an expanded number of species. Here we use BRM to show that developmental exposure of zebrafish to 30 uM nicotine from 6–48 hours post fertilization (hpf results in behavioral hyperactivity in larval zebrafish and alteration of putative miRNA gene targets in whole embryos at developmental stages that encompass early neurogenesis. We show typical workflows for using BRM to integrate experimental zebrafish miRNA and mRNA microarray datasets with example retrievals for zebrafish, including pathway annotation and mapping to human ortholog. Functional analysis of differentially regulated (p Conclusions BRM provides the ability to mine complex data for identification of candidate miRNAs or pathways that drive phenotypic outcome and, therefore, is a useful hypothesis generation tool for systems biology. The miRNA workflow in BRM allows for efficient processing of multiple miRNA and mRNA datasets in a single

  14. Genetic characterization of 11 microsatellite loci in Egyptian pigeons (Columba livia domestica) and their cross-species amplification in other Columbidae populations

    Science.gov (United States)

    Ramadan, Sherif; Dawod, Ahmed; El-Garhy, Osama; Nowier, Amira M.; Eltanany, Marwa; Inoue-Murayama, Miho

    2018-01-01

    We confirm the applicability of the CliµD17, CliµT17, CliµD16, CliµD32, CliµT13, CliµD01, PG1, PG2, PG4, PG6, and PG7 microsatellite markers among Egyptian domestic pigeons and across other pigeon species using cross-species amplification method. The information from this study should be useful for genetic characterization and for developing conservation programs of this important species. PMID:29805216

  15. Cross-species multiple environmental stress responses: An integrated approach to identify candidate genes for multiple stress tolerance in sorghum (Sorghum bicolor (L. Moench and related model species.

    Directory of Open Access Journals (Sweden)

    Adugna Abdi Woldesemayat

    associated with different traits that are responsive to multiple stresses. Ontology mapping was used to validate the identified genes, while reconstruction of the phylogenetic tree was instrumental to infer the evolutionary relationship of the sorghum orthologs. The results also show specific genes responsible for various interrelated components of drought response mechanism such as drought tolerance, drought avoidance and drought escape.We submit that this approach is novel and to our knowledge, has not been used previously in any other research; it enables us to perform cross-species queries for genes that are likely to be associated with multiple stress tolerance, as a means to identify novel targets for engineering stress resistance in sorghum and possibly, in other crop species.

  16. Bioinformatics resource manager v2.3: an integrated software environment for systems biology with microRNA and cross-species analysis tools

    Science.gov (United States)

    2012-01-01

    Background MicroRNAs (miRNAs) are noncoding RNAs that direct post-transcriptional regulation of protein coding genes. Recent studies have shown miRNAs are important for controlling many biological processes, including nervous system development, and are highly conserved across species. Given their importance, computational tools are necessary for analysis, interpretation and integration of high-throughput (HTP) miRNA data in an increasing number of model species. The Bioinformatics Resource Manager (BRM) v2.3 is a software environment for data management, mining, integration and functional annotation of HTP biological data. In this study, we report recent updates to BRM for miRNA data analysis and cross-species comparisons across datasets. Results BRM v2.3 has the capability to query predicted miRNA targets from multiple databases, retrieve potential regulatory miRNAs for known genes, integrate experimentally derived miRNA and mRNA datasets, perform ortholog mapping across species, and retrieve annotation and cross-reference identifiers for an expanded number of species. Here we use BRM to show that developmental exposure of zebrafish to 30 uM nicotine from 6–48 hours post fertilization (hpf) results in behavioral hyperactivity in larval zebrafish and alteration of putative miRNA gene targets in whole embryos at developmental stages that encompass early neurogenesis. We show typical workflows for using BRM to integrate experimental zebrafish miRNA and mRNA microarray datasets with example retrievals for zebrafish, including pathway annotation and mapping to human ortholog. Functional analysis of differentially regulated (p<0.05) gene targets in BRM indicates that nicotine exposure disrupts genes involved in neurogenesis, possibly through misregulation of nicotine-sensitive miRNAs. Conclusions BRM provides the ability to mine complex data for identification of candidate miRNAs or pathways that drive phenotypic outcome and, therefore, is a useful hypothesis

  17. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    Kendall, D.A.; Taylor, D.P.; Enna, S.J.

    1983-01-01

    High (17 nM) and low (603 nM) affinity binding sites for [ 3 ]tetrahydrotrazodone ([ 3 ] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [ 3 ]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [ 3 ] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [ 3 ]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  18. Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Guiqing; Sun, Dawei; Rajashankar, Kanagalaghatta R.; Qian, Zhaohui; Holmes, Kathryn V.; Li, Fang (Cornell); (UMM-MED); (Colorado)

    2011-09-28

    Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same {beta}-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusive protein-protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the {beta}-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.

  19. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G.

    1990-01-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  20. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  1. A cross-species study of gesture and its role in symbolic development: Implications for the gestural theory of language evolution

    Directory of Open Access Journals (Sweden)

    Kristen eGillespie-Lynch

    2013-06-01

    Full Text Available Using a naturalistic video database, we examined whether gestures scaffolded the symbolic development of a language-enculturated chimpanzee, a language-enculturated bonobo, and a human child during the second year of life. These three species constitute a complete clade: species possessing a common immediate ancestor. A basic finding was the functional and formal similarity of many gestures between chimpanzee, bonobo, and human child. The child’s symbols were spoken words; the apes’ symbols were lexigrams, noniconic visual signifiers. A developmental pattern in which gestural representation of a referent preceded symbolic representation of the same referent appeared in all three species (but was statistically significant only for the child. Nonetheless, across species, the ratio of symbol to gesture increased significantly with age. But even though their symbol production increased, the apes continued to communicate more frequently by gesture than by symbol. In contrast, by15-18 months of age, the child used symbols more frequently than gestures. This ontogenetic sequence from gesture to symbol, present across the clade but more pronounced in child than ape, provides support for the role of gesture in language evolution. In all three species, the overwhelming majority of gestures were communicative (paired with eye-contact, vocalization, and/or persistence. However, vocalization was rare for the apes, but accompanied the majority of the child’s communicative gestures. This finding suggests the co-evolution of speech and gesture after the evolutionary divergence of the hominid line. Multimodal expressions of communicative intent (e.g., vocalization plus persistence were normative for the child, but less common for the apes. This finding suggests that multimodal expression of communicative intent was also strengthened after hominids diverged from apes.

  2. Viruses of managed alfalfa leafcutting bees (Megachille rotundata Fabricus) and honey bees (Apis mellifera L.) in Western Canada: Incidence, impacts, and prospects of cross-species viral transmission.

    Science.gov (United States)

    Melathopoulos, Andony; Ovinge, Lynae; Veiga, Patricia Wolf; Castillo, Carlos; Ostermann, David; Hoover, Shelley

    2017-06-01

    We examined whether alfalfa leafcutting bees (ALCB, Megachille rotundata) experienced a higher incidence of seven viruses commonly found honey bees (Apis mellifera) when placed alongside honey bees for hybrid canola seed pollination. Although two viruses - sacbrood virus (SBV) and deformed wing virus (DWV) - were detected in ALCB adults, their presence appeared independent of whether honey bees were present in the same field or not. A further survey of viruses among ALCB adults in three different alfalfa seed growing regions in Western Canada confirmed the ubiquity of sacbrood virus (SBV) as well as the infrequent presence of acute bee paralysis virus (ABPV), both of which had not been previously reported on ALCB. Moreover, SBV and ABPV were detected in the cocoon stage and only in one region. Co-infection among pools of ALCB adults with both of these viruses was more closely correlated with decreasing levels of cocoon viability than infection levels in cocoons themselves. This research suggests ongoing viral transmission between honey bees and ALCB in the same fields is likely low but that co-infection with these viruses may lower ALCB productivity. Copyright © 2017. Published by Elsevier Inc.

  3. Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease

    Directory of Open Access Journals (Sweden)

    Peter J. Belmont

    2014-06-01

    Full Text Available Effective treatment options for advanced colorectal cancer (CRC are limited, survival rates are poor and this disease continues to be a leading cause of cancer-related deaths worldwide. Despite being a highly heterogeneous disease, a large subset of individuals with sporadic CRC typically harbor relatively few established ‘driver’ lesions. Here, we describe a collection of genetically engineered mouse models (GEMMs of sporadic CRC that combine lesions frequently altered in human patients, including well-characterized tumor suppressors and activators of MAPK signaling. Primary tumors from these models were profiled, and individual GEMM tumors segregated into groups based on their genotypes. Unique allelic and genotypic expression signatures were generated from these GEMMs and applied to clinically annotated human CRC patient samples. We provide evidence that a Kras signature derived from these GEMMs is capable of distinguishing human tumors harboring KRAS mutation, and tracks with poor prognosis in two independent human patient cohorts. Furthermore, the analysis of a panel of human CRC cell lines suggests that high expression of the GEMM Kras signature correlates with sensitivity to targeted pathway inhibitors. Together, these findings implicate GEMMs as powerful preclinical tools with the capacity to recapitulate relevant human disease biology, and support the use of genetic signatures generated in these models to facilitate future drug discovery and validation efforts.

  4. A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core body temperature reduction by the TRPM8 blocker PF-05105679.

    Science.gov (United States)

    Gosset, James R; Beaumont, Kevin; Matsuura, Tomomi; Winchester, Wendy; Attkins, Neil; Glatt, Sophie; Lightbown, Ian; Ulrich, Kristina; Roberts, Sonia; Harris, Jolie; Mesic, Emir; van Steeg, Tamara; Hijdra, Diana; van der Graaf, Piet H

    2017-11-15

    PF-05105679 is a moderately potent TRPM8 blocker which has been evaluated for the treatment of cold pain sensitivity. The TRPM8 channel is responsible for the sensation of cold environmental temperatures and has been implicated in regulation of core body temperature. Consequently, blockade of TRPM8 has been suggested to result in lowering of core body temperature. As part of the progression to human studies, the effect of PF-05105679 on core body temperature has been investigated in animals. Safety pharmacology studies showed that PF-05105679 reduced core body temperature in a manner that was inversely related to body weight of the species tested (greater exposure to PF-05105679 was required to lower temperature by 1°C in higher species). Based on an allometric (body weight) relationship, it was hypothesized that PF-05105679 would not lower core body temperature in humans at exposures that could exhibit pharmacological effects on cold pain sensation. On administration to humans, PF-05105679 was indeed effective at reversing the cold pain sensation associated with the cold pressor test in the absence of effects on core body temperature. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    Energy Technology Data Exchange (ETDEWEB)

    Gangi Setty, Thanuja [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Cho, Christine [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Govindappa, Sowmya [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Apicella, Michael A. [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Ramaswamy, S., E-mail: ramas@instem.res.in [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India)

    2014-07-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

  6. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    International Nuclear Information System (INIS)

    Gangi Setty, Thanuja; Cho, Christine; Govindappa, Sowmya; Apicella, Michael A.; Ramaswamy, S.

    2014-01-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states

  7. Development, cross-species/genera transferability of novel EST-SSR markers and their utility in revealing population structure and genetic diversity in sugarcane

    KAUST Repository

    Singh, Ram K.

    2013-07-01

    Sugarcane (Saccharum spp. hybrid) with complex polyploid genome requires a large number of informative DNA markers for various applications in genetics and breeding. Despite the great advances in genomic technology, it is observed in several crop species, especially in sugarcane, the availability of molecular tools such as microsatellite markers are limited. Now-a-days EST-SSR markers are preferred to genomic SSR (gSSR) as they represent only the functional part of the genome, which can be easily associated with desired trait. The present study was taken up with a new set of 351 EST-SSRs developed from the 4085 non redundant EST sequences of two Indian sugarcane cultivars. Among these EST-SSRs, TNR containing motifs were predominant with a frequency of 51.6%. Thirty percent EST-SSRs showed homology with annotated protein. A high frequency of SSRs was found in the 5\\'UTR and in the ORF (about 27%) and a low frequency was observed in the 3\\'UTR (about 8%). Two hundred twenty-seven EST-SSRs were evaluated, in sugarcane, allied genera of sugarcane and cereals, and 134 of these have revealed polymorphism with a range of PIC value 0.12 to 0.99. The cross transferability rate ranged from 87.0% to 93.4% in Saccharum complex, 80.0% to 87.0% in allied genera, and 76.0% to 80.0% in cereals. Cloning and sequencing of EST-SSR size variant amplicons revealed that the variation in the number of repeat-units was the main source of EST-SSR fragment polymorphism. When 124 sugarcane accessions were analyzed for population structure using model-based approach, seven genetically distinct groups or admixtures thereof were observed in sugarcane. Results of principal coordinate analysis or UPGMA to evaluate genetic relationships delineated also the 124 accessions into seven groups. Thus, a high level of polymorphism adequate genetic diversity and population structure assayed with the EST-SSR markers not only suggested their utility in various applications in genetics and genomics in

  8. Feature Binding in Zebrafish

    Directory of Open Access Journals (Sweden)

    P Neri

    2012-07-01

    Full Text Available Binding operations are primarily ascribed to cortex or similarly complex avian structures. My experiments show that the zebrafish, a lower vertebrate lacking cortex, supports visual feature binding of form and motion for the purpose of social behavior. These results challenge the notion that feature binding may require highly evolved neural structures and demonstrate that the nervous system of lower vertebrates can afford unexpectedly complex computations.

  9. Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628.

    Science.gov (United States)

    Varnäs, Katarina; Finnema, Sjoerd J; Stepanov, Vladimir; Takano, Akihiro; Tóth, Miklós; Svedberg, Marie; Møller Nielsen, Søren; Khanzhin, Nikolay A; Juhl, Karsten; Bang-Andersen, Benny; Halldin, Christer; Farde, Lars

    2016-08-01

    Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. A novel neurokinin 3 receptor radioligand, [(18)F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[(18)F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  10. A systems biology approach to transcription factor binding site prediction.

    Directory of Open Access Journals (Sweden)

    Xiang Zhou

    2010-03-01

    Full Text Available The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates.We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data.Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct-interaction detection and TFBS-discovery accuracy. We estimated the accuracy

  11. Suggestibility and negative priming: two replication studies.

    Science.gov (United States)

    David, Daniel; Brown, Richard J

    2002-07-01

    Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

  12. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    Packer, S.; Fairchild, R.G.; Watts, K.P.; Greenberg, D.; Hannon, S.J.

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed

  13. Competitive protein binding assay

    International Nuclear Information System (INIS)

    Kaneko, Toshio; Oka, Hiroshi

    1975-01-01

    The measurement of cyclic GMP (cGMP) by competitive protein binding assay was described and discussed. The principle of binding assay was represented briefly. Procedures of our method by binding protein consisted of preparation of cGMP binding protein, selection of 3 H-cyclic GMP on market, and measurement procedures. In our method, binding protein was isolated from the chrysalis of silk worm. This method was discussed from the points of incubation medium, specificity of binding protein, the separation of bound cGMP from free cGMP, and treatment of tissue from which cGMP was extracted. cGMP existing in the tissue was only one tenth or one scores of cGMP, and in addition, cGMP competed with cGMP in binding with binding protein. Therefore, Murad's technique was applied to the isolation of cGMP. This method provided the measurement with sufficient accuracy; the contamination by cAMP was within several per cent. (Kanao, N.)

  14. Suggestibility and Expectancy in a Counseling Analogue

    Science.gov (United States)

    Kaul, Theodore J.; Parker, Clyde A.

    1971-01-01

    The data indicated that (a) subjectively experienced suggestibility was more closely related to attitude change than was objective suggestibility, and (b) the generalized expectancy treatments were ineffective in influencing different criterion scores. (Author)

  15. DEVELOPMENT AND CROSS-SPECIES AMPLIFICATION OF ...

    African Journals Online (AJOL)

    ACSS

    In this study, publicly available grass pea (Lathyrus sativus) EST sequences were used to develop 21 ... which are important food legumes, with whom it could share genes ... (Pisum saivum), faba bean (Vicia faba), chickpea. (Cicer arietinum) ...

  16. Evidentiality and Suggestibility: A New Research Venue

    Science.gov (United States)

    Aydin, Cagla; Ceci, Stephen J.

    2009-01-01

    Recent research suggests that acquisition of mental-state language may influence conceptual development. We examine this possibility by investigating the conceptual links between evidentiality in language and suggestibility. Young children are disproportionately suggestible and tend to change their reports or memories when questioned. The authors…

  17. The Effects of Suggestibility on Relaxation.

    Science.gov (United States)

    Rickard, Henry C.; And Others

    1985-01-01

    Selected undergraduates (N=32) on the basis of Creative Imagination Scale scores and randomly assigned high and low suggestibility subjects to progressive relaxation (PR) and suggestions of relaxation (SR) training modes. Results revealed a significant pre-post relaxation effect, and main efffects for both suggestibility and training mode. (NRB)

  18. Reinventing suggestion systems for continuous improvement

    NARCIS (Netherlands)

    Schuring, R.W.; Luijten, Harald

    2001-01-01

    This article reports an experiment to increase the effectiveness of a suggestion system by deliberately applying principles of the kaizen and performance management. Design rules for suggestion systems are derived from these theories. The suggestion system that resulted differs from traditional

  19. The influence of suggestibility on memory.

    Science.gov (United States)

    Nicolas, Serge; Collins, Thérèse; Gounden, Yannick; Roediger, Henry L

    2011-06-01

    We provide a translation of Binet and Henri's pioneering 1894 paper on the influence of suggestibility on memory. Alfred Binet (1857-1911) is famous as the author who created the IQ test that bears his name, but he is almost unknown as the psychological investigator who generated numerous original experiments and fascinating results in the study of memory. His experiments published in 1894 manipulated suggestibility in several ways to determine effects on remembering. Three particular modes of suggestion were employed to induce false recognitions: (1) indirect suggestion by a preconceived idea; (2) direct suggestion; and (3) collective suggestion. In the commentary we suggest that Binet and Henri's (1894) paper written over 115 years ago is still highly relevant even today. In particular, Binet's legacy lives on in modern research on misinformation effects in memory, in studies of conformity, and in experiments on the social contagion of memory. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. The relationships between suggestibility, influenceability, and relaxability.

    Science.gov (United States)

    Polczyk, Romuald; Frey, Olga; Szpitalak, Malwina

    2013-01-01

    This research explores the relationships between relaxability and various aspects of suggestibility and influenceability. The Jacobson Progressive Muscle Relaxation procedure was used to induce relaxation. Tests of direct suggestibility, relating to the susceptibility of overt suggestions, and indirect suggestibility, referring to indirect hidden influence, as well as self-description questionnaires on suggestibility and the tendency to comply were used. Thayer's Activation-Deactivation Adjective Check List, measuring various kinds of activation and used as a pre- and posttest, determined the efficacy of the relaxation procedure. Indirect, direct, and self-measured suggestibility proved to be positively related to the ability to relax, measured by Thayer's subscales relating to emotions. Compliance was not related to relaxability. The results are discussed in terms of the aspects of relaxation training connected with suggestibility.

  1. Effects of stereotypes and suggestion on memory.

    Science.gov (United States)

    Shechory, Mally; Nachson, Israel; Glicksohn, Joseph

    2010-02-01

    In this study, the interactive effect of stereotype and suggestion on accuracy of memory was examined by presenting 645 participants (native Israelis and immigrants from the former Soviet Union and Ethiopia) with three versions of a story about a worker who is waiting in a manager's office for a meeting. All versions were identical except for the worker's name, which implied a Russian or an Ethiopian immigrant or a person of no ethnic origin. Each participant was presented with one version of the story. After an hour delay, the participants' memories were tested via two questionnaires that differed in terms of level of suggestion. Data analyses show that (a) when a suggestion matched the participant's stereotypical perception, the suggestion was incorporated into memory but (b) when the suggestion contradicted the stereotype, it did not influence memory. The conclusion was that recall is influenced by stereotypes but can be enhanced by compatible suggestions.

  2. Behavioural Decision Making and Suggestional Processes

    OpenAIRE

    Molz, Günter

    2001-01-01

    Common features between the domains of behavioural decision making and suggestional processes are discussed. These features are allocated in two aspects. First, behavioural decision making and suggestional processes are traditionally considered to provoke inadequate human behaviour. In this article arguments are put forward against this interpretation: Actions induced by non-rational decisions and / or by suggestional processes often have adaptive functions. Second, two common themat...

  3. Interrogative suggestibility in patients with conversion disorders.

    Science.gov (United States)

    Foong, J; Lucas, P A; Ron, M A

    1997-09-01

    We tested the hypothesis that increased interrogative suggestibility may contribute to the shaping and maintaining of conversions symptoms. Interrogative suggestibility was measured in 12 patients with conversion disorder and 10 control patients with confirmed neurological disease matched for age, premorbid intelligence, and as closely as possible in terms of their neurological symptoms to the patients with conversion disorder. Our observations do not support the contention that individual differences in interrogative suggestibility are of importance in the etiology of conversion disorders.

  4. Personality Styles and Suggestibility: A Differential Approach

    OpenAIRE

    Pires, Rute; Silva, Danilo R.; Ferreira, Ana Sousa

    2013-01-01

    This study addresses the relationship between personality styles measured with the Portuguese adaptation of the Millon Index of Personality Styles Revised – MIPS-R and interrogative suggestibility assessed by the Portuguese adaptation of the Gudjonsson Suggestibility Scale – GSS1. Hypotheses predicted individual differences in suggestibility and that these differences correspond to differences in individuals’ personality styles. The study was conducted with a sample of 258 individuals (M age ...

  5. Interrogative suggestibility and perceptual motor performance.

    Science.gov (United States)

    Gudjonsson, G H

    1984-04-01

    This study investigates the relationship between interrogative suggestibility, as measured by the Gudjonsson Suggestibility Scale, and Arrow-Dot scores. The tendency of subjects (25 men and 25 women, mean age 30.2 yr.) to alter their answers once interpersonal pressure had been applied correlated significantly with poor Arrow-Dot Ego functioning.

  6. Maltreated Children's Memory: Accuracy, Suggestibility, and Psychopathology

    Science.gov (United States)

    Eisen, Mitchell L.; Goodman, Gail S.; Qin, Jianjian; Davis, Suzanne; Crayton, John

    2007-01-01

    Memory, suggestibility, stress arousal, and trauma-related psychopathology were examined in 328 3- to 16-year-olds involved in forensic investigations of abuse and neglect. Children's memory and suggestibility were assessed for a medical examination and venipuncture. Being older and scoring higher in cognitive functioning were related to fewer…

  7. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  8. Increased thyrotropin binding in hyperfunctioning thyroid nodules.

    Science.gov (United States)

    Müller-Gärtner, H W; Schneider, C; Bay, V; Tadt, A; Rehpenning, W; de Heer, K; Jessel, M

    1987-08-01

    The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

  9. LSD enhances suggestibility in healthy volunteers.

    Science.gov (United States)

    Carhart-Harris, R L; Kaelen, M; Whalley, M G; Bolstridge, M; Feilding, A; Nutt, D J

    2015-02-01

    Lysergic acid diethylamide (LSD) has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction, and it was also explored as an enhancer of mind control. The present study sought to test the effect of LSD on suggestibility in a modern research study. Ten healthy volunteers were administered with intravenous (i.v.) LSD (40-80 μg) in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale (CIS) and a mental imagery test (MIT). CIS and MIT items were split into two versions (A and B), balanced for 'efficacy' (i.e. A ≈ B) and counterbalanced across conditions (i.e. 50 % completed version 'A' under LSD). The MIT and CIS were issued 110 and 140 min, respectively, post-infusion, corresponding with the peak drug effects. Volunteers gave significantly higher ratings for the CIS (p = 0.018), but not the MIT (p = 0.11), after LSD than placebo. The magnitude of suggestibility enhancement under LSD was positively correlated with trait conscientiousness measured at baseline (p = 0.0005). These results imply that the influence of suggestion is enhanced by LSD. Enhanced suggestibility under LSD may have implications for its use as an adjunct to psychotherapy, where suggestibility plays a major role. That cued imagery was unaffected by LSD implies that suggestions must be of a sufficient duration and level of detail to be enhanced by the drug. The results also imply that individuals with high trait conscientiousness are especially sensitive to the suggestibility-enhancing effects of LSD.

  10. Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium.

    Science.gov (United States)

    Molehin, Adebayo J; Sennoune, Souad R; Zhang, Weidong; Rojo, Juan U; Siddiqui, Arif J; Herrera, Karlie A; Johnson, Laura; Sudduth, Justin; May, Jordan; Siddiqui, Afzal A

    2017-11-01

    Schistosomiasis remains a major global health problem. Despite large-scale schistosomiasis control efforts, clear limitations such as possible emergence of drug resistance and reinfection rates highlight the need for an effective schistosomiasis vaccine. Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine formulations have shown remarkable efficacy in protecting against S. mansoni challenge infections in mice and baboons. In this study, we evaluated the cross-species protective efficacy of Sm-p80 vaccine against S. japonicum and S. haematobium challenge infections in rodent models. We also elucidated the expression of Sm-p80 and Sm-p80 ortholog proteins in different developmental stages of S. mansoni, S. haematobium, and S. japonicum. Immunization with Sm-p80 vaccine reduced worm burden by 46.75% against S. japonicum challenge infection in mice. DNA prime/protein boost (1 + 1 dose administered on a single day) resulted in 26.95% reduction in worm burden in S. haematobium-hamster infection/challenge model. A balanced Th1 (IFN-γ, TNF-α, IL-2, and IL-12) and Th2 (IL-4, IgG1) type of responses were observed following vaccination in both S. japonicum and S. haematobium challenge trials and these are associated with the prophylactic efficacy of Sm-p80 vaccine. Immunohistochemistry demonstrated that Sm-p80/Sm-p80 ortholog proteins are expressed in different life cycle stages of the three major human species of schistosomes studied. The data presented in this study reinforce the potential of Sm-p80-based vaccine for both hepatic/intestinal and urogenital schistosomiasis occurring in different geographical areas of the world. Differential expression of Sm-p80/Sm-p80 protein orthologs in different life cycle makes this vaccine potentially useful in targeting different levels of infection, disease, and transmission.

  11. Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat

    Directory of Open Access Journals (Sweden)

    Juan Felipe Diaz Quiroz

    2014-06-01

    Full Text Available Most spinal cord injuries lead to permanent paralysis in mammals. By contrast, the remarkable regenerative abilities of salamanders enable full functional recovery even from complete spinal cord transections. The molecular differences underlying this evolutionary divergence between mammals and amphibians are poorly understood. We focused on upstream regulators of gene expression as primary entry points into this question. We identified a group of microRNAs (miRNAs that are conserved between the Mexican axolotl salamander (Ambystoma mexicanum and mammals but show marked cross-species differences in regulation patterns following spinal cord injury. We found that precise post-injury levels of one of these miRNAs (miR-125b is essential for functional recovery, and guides correct regeneration of axons through the lesion site in a process involving the direct downstream target Sema4D in axolotls. Translating these results to a mammalian model, we increased miR-125b levels in the rat through mimic treatments following spinal cord transection. These treatments downregulated Sema4D and other glial-scar-related genes, and enhanced the animal’s functional recovery. Our study identifies a key regulatory molecule conserved between salamander and mammal, and shows that the expression of miR-125b and Sema4D must be carefully controlled in the right cells at the correct level to promote regeneration. We also show that these molecular components of the salamander’s regeneration-permissive environment can be experimentally harnessed to improve treatment outcomes for mammalian spinal cord injuries.

  12. Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding.

    Science.gov (United States)

    Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R; Stevens, Raymond C

    2010-04-16

    Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent. Copyright (c) 2010. Published by Elsevier Ltd.

  13. Presence of a highly efficient binding to bacterial contamination can distort data from binding studies

    International Nuclear Information System (INIS)

    Balcar, V.J.

    1990-01-01

    3 HGABA at low concentrations (5-10 nM) was bound by what appeared to be a GABA receptor binding site in bacterial contamination originating from a batch of distilled water. Under experimental conditions similar to those usually employed in 3 HGABA binding studies, the apparent binding displayed a very high specific component and a high efficiency in terms of 3 HGABA bound per mg of protein. The binding was blocked by muscimol but not by isoguvacine, SR95531 and nipecotic acid. These characteristics suggest that the presence of such spurious binding in the experiments using 3H-labeled ligands in brain homogenates may not always be very obvious and, moreover, it can result in subtle, but serious, distortions of data from such studies, which may not be immediately recognized

  14. Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

    OpenAIRE

    Romuald Polczyk

    2016-01-01

    Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence ...

  15. CARBOHYDRATE-CONTAINING COMPOUNDS WHICH BIND TO CARBOHYDRATE BINDING RECEPTORS

    DEFF Research Database (Denmark)

    1995-01-01

    Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases.......Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases....

  16. Measuring Children's Suggestibility in Forensic Interviews.

    Science.gov (United States)

    Volpini, Laura; Melis, Manuela; Petralia, Stefania; Rosenberg, Melina D

    2016-01-01

    According to the scientific literature, childrens' cognitive development is not complete until adolescence. Therefore, the problems inherent in children serving as witnesses are crucial. In preschool-aged children, false memories may be identified because of misinformation and insight bias. Additionally, they are susceptible of suggestions. The aim of this study was to verify the levels of suggestibility in children between three and 5 years of age. Ninety-two children were examined (44 male, 48 female; M = 4.5 years, SD = 9.62). We used the correlation coefficient (Pearson's r) and the averages variance by SPSS statistical program. The results concluded that: younger children are almost always more susceptible to suggestibility. The dimension of immediate recall was negatively correlates with that of total suggestibility (r = -0.357 p suggestibility, because older children shift their answers more often (r = 0.394 p < 0.001). Younger children change their answers more times (r = -0.395 p < 0.001). © 2016 American Academy of Forensic Sciences.

  17. Impulsivity, self-control, and hypnotic suggestibility.

    Science.gov (United States)

    Ludwig, V U; Stelzel, C; Krutiak, H; Prunkl, C E; Steimke, R; Paschke, L M; Kathmann, N; Walter, H

    2013-06-01

    Hypnotic responding might be due to attenuated frontal lobe functioning after the hypnotic induction. Little is known about whether personality traits linked with frontal functioning are associated with responsiveness to hypnotic suggestions. We assessed whether hypnotic suggestibility is related to the traits of self-control and impulsivity in 154 participants who completed the Brief Self-Control Scale, the Self-Regulation Scale, the Barratt Impulsiveness Scale (BIS-11), and the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A). BIS-11 non-planning impulsivity correlated positively with HGSHS:A (Bonferroni-corrected). Furthermore, in the best model emerging from a stepwise multiple regression, both non-planning impulsivity and self-control positively predicted hypnotic suggestibility, and there was an interaction of BIS-11 motor impulsivity with gender. For men only, motor impulsivity tended to predict hypnotic suggestibility. Hypnotic suggestibility is associated with personality traits linked with frontal functioning, and hypnotic responding in men and women might differ. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Overview of the SBS 2016 Suggestion Track

    DEFF Research Database (Denmark)

    Koolen, Marijn; Bogers, Toine; Jaap, Kamps

    2016-01-01

    The goal of the SBS 2016 Suggestion Track is to evaluate approaches for supporting users in searching collections of books who express their information needs both in a query and through example books. The track investigates the complex nature of relevance in book search and the role of traditional...... and user-generated book metadata in retrieval. We consolidated last year’s investigation into the nature of book suggestions from the LibraryThing forums and how they compare to book relevance judgements. Participants were encouraged to incorporate rich user profiles of both topic creators and other...

  19. Leadership Theories--Managing Practices, Challenges, Suggestions

    Science.gov (United States)

    Hawkins, Cheryl

    2009-01-01

    A shortage of community college executives due to the number of retirements occurring among current leaders is predicted. An examination of three leadership theories--servant-leadership, business leadership and transformational leadership--suggests techniques for potential community college leaders. Servant-leaders focus on the needs of their…

  20. Seven Salutary Suggestions for Counselor Stamina

    Science.gov (United States)

    Osborn, Cynthia J.

    2004-01-01

    Counselor stamina is deemed essential in the midst of a consistently challenging, complex, and changing mental health care environment. Rather than perpetuating conversations about "burnout" and "burnout prevention," this article provides a salutary or health-promoting perspective. Seven suggestions for counselor stamina are presented and…

  1. Interrogative Suggestibility in an Adolescent Forensic Occupation.

    Science.gov (United States)

    Richardson, G.; And Others

    1995-01-01

    Sixty-five juvenile offenders in residential care completed the Gudjonsson Suggestibility Scale, and their scores were matched for IQ and memory with those of 60 adult offenders. The juveniles gave in significantly more to interrogative pressure through negative feedback but were no more yielding to leading questions than adults. (JPS)

  2. Evidence Suggesting Absence of Mitochondrial DNA Methylation

    DEFF Research Database (Denmark)

    Mechta, Mie; Ingerslev, Lars R; Fabre, Odile

    2017-01-01

    , 16S, ND5 and CYTB, suggesting that mtDNA supercoiled structure blocks the access to bisulfite conversion. Here, we identified an artifact of mtDNA bisulfite sequencing that can lead to an overestimation of mtDNA methylation levels. Our study supports that cytosine methylation is virtually absent...

  3. Didactic Experiments Suggest Enhanced Learning Outcomes

    DEFF Research Database (Denmark)

    Pals Svendsen, Lisbet

    2011-01-01

    and presenting material in the language studied, just as they were encouraged to systematically use evaluation processes to enhance learning outcomes. Eventually, increased grade point averages suggested that the experiment was successful. The article also mentions subsequent revisions to the original format...

  4. Do astrophysical measurements suggest massive neutrinos?

    International Nuclear Information System (INIS)

    Ali, M.; Fazal-e-Aleem; Rashid, H.

    1996-01-01

    We discuss the solar neutrino puzzle and suggest modification in the standard solar model. It has been observed that the discrepancy between experimental measurements and theoretically produced values can be removed by considering neutrinos to process non-zero mass. (author)

  5. The role of tag suggestions in folksonomies

    NARCIS (Netherlands)

    Bollen, D.G.F.M.; Halpin, H.

    2009-01-01

    Most tagging systems support the user in the tag selection process by providing tag suggestions, or recommendations, based on a popularity measurement of tags other users provided when tagging the same resource. The majority of theories and mathematical models of tagging found in the literature

  6. Cable Television Report and Suggested Ordinance.

    Science.gov (United States)

    League of California Cities, Sacramento.

    Guidelines and suggested ordinances for cable television regulation by local governments are comprehensively discussed in this report. The emphasis is placed on franchising the cable operator. Seventeen legal aspects of franchising are reviewed, and an exemplary ordinance is presented. In addition, current statistics about cable franchising in…

  7. Suggestions for Structuring a Research Article

    Science.gov (United States)

    Klein, James D.; Reiser, Robert A.

    2014-01-01

    Researchers often experience difficulty as they attempt to prepare journal articles that describe their work. The purpose of this article is to provide researchers in the field of education with a series of suggestions as to how to clearly structure each section of a research manuscript that they intend to submit for publication in a scholarly…

  8. Family Living: Suggestions for Effective Parenting.

    Science.gov (United States)

    Katz, Lilian G.; And Others

    Suggestions for effective parenting of preschool children are provided in 33 brief articles on children's feelings concerning self-esteem; fear; adopted children; the birth of a sibling; death; depression; and coping with stress, trauma, and divorce. Children's behavior is discussed in articles on toddlers' eating habits, punishment and…

  9. Overview of the SBS 2016 Suggestion Track

    DEFF Research Database (Denmark)

    Koolen, Marijn; Bogers, Toine; Jaap, Kamps

    2016-01-01

    and user-generated book metadata in retrieval. We consolidated last year’s investigation into the nature of book suggestions from the LibraryThing forums and how they compare to book relevance judgements. Participants were encouraged to incorporate rich user profiles of both topic creators and other...

  10. Accounting: Suggested Content for Postsecondary Tax Course

    Science.gov (United States)

    King, Patricia H.; Morgan, Samuel D.

    1978-01-01

    Surveys of community college graduates and of certified public accountants were made to determine employment relevance of the accounting curriculum. The article suggests topics from the study data which should be included in taxation courses, e.g., income tax accounting, corporate taxation accounting, and tax law. (MF)

  11. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    International Nuclear Information System (INIS)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-01-01

    Autoradiography using 125 I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat

  12. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-04-01

    Autoradiography using /sup 125/I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.

  13. Suggestion of a conventional Islamic calendar

    Directory of Open Access Journals (Sweden)

    M.G. Rashed

    2017-12-01

    Full Text Available There is a complexity of the problem concerning the first sighting of the new lunar crescent, which is attributed to various astronomical, astrophysical and geographical factors. Therefore, Astronomers adopted various criteria for the new crescent visibility. Muslims around the world differ in the beginning of the Hijric months. In fact the differences are not due to different methodology of astronomical calculations, which in turn the variations of the calendar at different countries gives. Farewell Hajj of Prophet Mohamed was on Friday, the ninth of Thul'hejja of the tenth year of immigration (Biography of the Prophet Mohamed. Therefor; the beginning of the month of Thul'hejja 10 A.H is on Thursday. Our suggested calendar takes Farewell Hajj of the Prophet Mohammad to be the base of this calendar. The advantage of our suggested calendar far away from any criteria; where the adoption of criteria for the new crescent visibility is often misleading.

  14. Suggestion of a conventional Islamic calendar

    Science.gov (United States)

    Rashed, M. G.; Moklof, M. G.

    2017-12-01

    There is a complexity of the problem concerning the first sighting of the new lunar crescent, which is attributed to various astronomical, astrophysical and geographical factors. Therefore, Astronomers adopted various criteria for the new crescent visibility. Muslims around the world differ in the beginning of the Hijric months. In fact the differences are not due to different methodology of astronomical calculations, which in turn the variations of the calendar at different countries gives. Farewell Hajj of Prophet Mohamed was on Friday, the ninth of Thul'hejja of the tenth year of immigration (Biography of the Prophet Mohamed). Therefor; the beginning of the month of Thul'hejja 10 A.H is on Thursday. Our suggested calendar takes Farewell Hajj of the Prophet Mohammad to be the base of this calendar. The advantage of our suggested calendar far away from any criteria; where the adoption of criteria for the new crescent visibility is often misleading.

  15. Hypnotic suggestibility, cognitive inhibition, and dissociation.

    Science.gov (United States)

    Dienes, Zoltán; Brown, Elizabeth; Hutton, Sam; Kirsch, Irving; Mazzoni, Giuliana; Wright, Daniel B

    2009-12-01

    We examined two potential correlates of hypnotic suggestibility: dissociation and cognitive inhibition. Dissociation is the foundation of two of the major theories of hypnosis and other theories commonly postulate that hypnotic responding is a result of attentional abilities (including inhibition). Participants were administered the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C. Under the guise of an unrelated study, 180 of these participants also completed: a version of the Dissociative Experiences Scale that is normally distributed in non-clinical populations; a latent inhibition task, a spatial negative priming task, and a memory task designed to measure negative priming. The data ruled out even moderate correlations between hypnotic suggestibility and all the measures of dissociation and cognitive inhibition overall, though they also indicated gender differences. The results are a challenge for existing theories of hypnosis.

  16. [Suggestions to improve dentist-endodontist collaboration].

    Science.gov (United States)

    Zabalegui, B; Zabalegui, I; Flores, L

    1989-01-01

    Referrals from the general dentist to the endodontist are in some occasions complicated with lack of proper communication among dentist-patient-specialist, resulting in the loss of confidence or even the patient. Suggestions to improve this communication are discussed, which will provide the patient a higher confidence in the indicated endodontic treatment and a better dental service. It will also enhance the prestige of the general dentists' and specialists' practice.

  17. Application for Suggesting Restaurants Using Clustering Algorithms

    Directory of Open Access Journals (Sweden)

    Iulia Alexandra IANCU

    2014-10-01

    Full Text Available The aim of this article is to present an application whose purpose is to make suggestions of restaurants to users. The application uses as input the descriptions of restaurants, reviews, user reviews available on the specialized Internet sites and blogs. In the application there are used processing techniques of natural language implemented using parsers, clustering algorithms and techniques for data collection from the Internet through web crawlers.

  18. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  19. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  20. Binding and Bulgarian

    NARCIS (Netherlands)

    Schürcks-Grozeva, Lilia Lubomirova

    2003-01-01

    In haar proefschrift analyseert Lilia Schürcks de anaforische verschijnselen in de Bulgaarse taal. Het gaat dan om wederkerende aspecten, uitgedrukt bij woorden als ‘zich’ en ‘elkaar’. De situatie in het Bulgaars blijkt moeilijk in te passen in de klassieke Binding Theory van Noam Chomsky. Bron: RUG

  1. Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

    Directory of Open Access Journals (Sweden)

    Romuald Polczyk

    2016-05-01

    Full Text Available Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence for the existence of the two factors has been scarce. In the present study, more sophisticated and reliable tools for measuring suggestibility were applied than in the previous research, in the hope that better measurement would reveal the factor structure of suggestibility. Two tests of direct suggestibility were used: the Harvard Group Scale of Hypnotic Susceptibility, Form A, measuring hypnotic susceptibility, and the Barber Suggestibility Scale, measuring non-hypnotic direct imaginative suggestibility. Three tests served to measure indirect suggestibility: the Sensory Suggestibility Scale, measuring indirect suggestibility relating to perception; the Gudjonsson Suggestibility Scale, measuring the tendency to yield to suggestive questions and changing answers after negative feedback; and the Emotional Dialogs Tests, measuring the tendency to perceive nonexistent aggression. Participants and procedure In sum, 115 participants were tested, 69 women, 49 men, mean age 22.20 years, SD = 2.20. Participants were tested in two sessions, lasting for a total of four hours. Results Confirmatory factor analyses confirmed the existence of two uncorrelated factors of suggestibility: direct and indirect. Conclusions Suggestibility may indeed involve two factors, direct and indirect, and failure to discover them in previous research may be due to methodological problems.

  2. New dynamic system suggested for earth expansion

    Energy Technology Data Exchange (ETDEWEB)

    Fitzpatrick, J [Asuncion Nacional Univ. (Paraguay). Inst. de Ciencias

    1972-01-01

    It is here suggested that there may have been much more radioactive materials in the deep interior of the earth than bitherto supposed. Trapped heat being generated in the interior would provide a mechanism for earth expansion. An assumption of heat generation in the deep interior of the earth of the order of 0,5 X 10-13 calories per second, per cubic centimeter, would provide sufficient thermal expansion to account for approximately 0.1 mm. change in the radius of the earth per year.

  3. Do experiments suggest a hierarchy problem?

    International Nuclear Information System (INIS)

    Vissani, F.

    1997-09-01

    The hierarchy problem of the scalar sector of the standard model is reformulated, emphasizing the role of experimental facts that may suggest the existence of a new physics large mass scale, for instance indications of the instability of the matter, or indications in favor of massive neutrinos. In the see-saw model for the neutrino masses a hierarchy problem arises if the mass of the right-handed neutrinos is larger than approximatively 10 7 GeV: this problem, and its possible solutions, are discussed. (author)

  4. Responding to hypnotic and nonhypnotic suggestions: performance standards, imaginative suggestibility, and response expectancies.

    Science.gov (United States)

    Meyer, Eric C; Lynn, Steven Jay

    2011-07-01

    This study examined the relative impact of hypnotic inductions and several other variables on hypnotic and nonhypnotic responsiveness to imaginative suggestions. The authors examined how imaginative suggestibility, response expectancies, motivation to respond to suggestions, and hypnotist-induced performance standards affected participants' responses to both hypnotic and nonhypnotic suggestions and their suggestion-related experiences. Suggestions were administered to 5 groups of participants using a test-retest design: (a) stringent performance standards; (b) lenient performance standards; (c) hypnosis test-retest; (d) no-hypnosis test-retest; and (e) no-hypnosis/hypnosis control. The authors found no support for the influence of a hypnotic induction or performance standards on responding to suggestions but found considerable support for the role of imaginative suggestibility and response expectancies in predicting responses to both hypnotic and nonhypnotic suggestions.

  5. The effect of posthypnotic suggestion, hypnotic suggestibility, and goal intentions on adherence to medical instructions.

    Science.gov (United States)

    Carvalho, Claudia; Mazzoni, Giuliana; Kirsch, Irving; Meo, Maria; Santandrea, Maura

    2008-04-01

    The effects of implementation intentions and posthypnotic suggestion were investigated in 2 studies. In Experiment 1, participants with high levels of hypnotic suggestibility were instructed to take placebo pills as part of an investigation of how to best enhance compliance with medical instruction. In Experiment 2, participants with high, medium, and low levels of hypnotic suggestibility were asked to run in place, take their pulse rate before, and send an e-mail report to the experimenter each day. Experiment 1 revealed enhanced adherence as a function of both implementation intentions and posthypnotic suggestion. Experiment 2 failed to find any significant main effects but found a significant interaction between suggestibility and the effects of posthypnotic suggestion. Posthypnotic suggestion enhanced adherence among high suggestible participants but lowered it among low suggestibles.

  6. Detection of secondary binding sites in proteins using fragment screening.

    Science.gov (United States)

    Ludlow, R Frederick; Verdonk, Marcel L; Saini, Harpreet K; Tickle, Ian J; Jhoti, Harren

    2015-12-29

    Proteins need to be tightly regulated as they control biological processes in most normal cellular functions. The precise mechanisms of regulation are rarely completely understood but can involve binding of endogenous ligands and/or partner proteins at specific locations on a protein that can modulate function. Often, these additional secondary binding sites appear separate to the primary binding site, which, for example for an enzyme, may bind a substrate. In previous work, we have uncovered several examples in which secondary binding sites were discovered on proteins using fragment screening approaches. In each case, we were able to establish that the newly identified secondary binding site was biologically relevant as it was able to modulate function by the binding of a small molecule. In this study, we investigate how often secondary binding sites are located on proteins by analyzing 24 protein targets for which we have performed a fragment screen using X-ray crystallography. Our analysis shows that, surprisingly, the majority of proteins contain secondary binding sites based on their ability to bind fragments. Furthermore, sequence analysis of these previously unknown sites indicate high conservation, which suggests that they may have a biological function, perhaps via an allosteric mechanism. Comparing the physicochemical properties of the secondary sites with known primary ligand binding sites also shows broad similarities indicating that many of the secondary sites may be druggable in nature with small molecules that could provide new opportunities to modulate potential therapeutic targets.

  7. Opioid binding sites in the guinea pig and rat kidney: Radioligand homogenate binding and autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Dissanayake, V.U.; Hughes, J.; Hunter, J.C. (Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge (England))

    1991-07-01

    The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE bound with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.

  8. FEM effective suggestion of guitar construction

    Directory of Open Access Journals (Sweden)

    Vladimír Dániel

    2006-01-01

    Full Text Available Modal analysis of the whole guitar construction was performed. The results of eigenfrequencies were obtained. Stress in strings affects not only static loading of material, but also shift of eigenfrequencies. From obtained natural frequencies for solved spectrum such frequencies were used which coincides with assumed ribs new positions of ribs were suggested. Other ribs which do not carry out the mechanical function were removed. Also static reaction was evaluated and new position of ribs was adjusted. For final model new eigenfrequencies were computed and compared with previous ones. Significant changes were revealed in low frequencies (bellow 400 Hz where fewer amounts of natural shapes were obtained. Approximately 50% were lost by adding of ribs. For chosen frequencies of equal temperament the harmonic analysis was performed. The analysis proved ability of oscillation for frequencies far of natural frequencies. The final model satisfies the requirement of minimization of static stress in material due to strings and allows very effective oscillation of top the guitar resonance board. In comparison with literature good agreement in amplitude size of front board and amount of modes in appropriate frequencies were achieved. Suggested model even offers higher amount of natural shapes in comparison with literature, namely in high frequencies. From additional comparison of eigenfrequencies and natural shapes the influence of ribs position on natural shapes was approved.

  9. Dinosaur peptides suggest mechanisms of protein survival.

    Science.gov (United States)

    San Antonio, James D; Schweitzer, Mary H; Jensen, Shane T; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P R O

    2011-01-01

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  10. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    Energy Technology Data Exchange (ETDEWEB)

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O. (Harvard-Med); (IIT); (NCSU); (UPENN); (Manchester); (Orthovita)

    2011-09-16

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  11. Imparting albumin-binding affinity to a human protein by mimicking the contact surface of a bacterial binding protein.

    Science.gov (United States)

    Oshiro, Satoshi; Honda, Shinya

    2014-04-18

    Attachment of a bacterial albumin-binding protein module is an attractive strategy for extending the plasma residence time of protein therapeutics. However, a protein fused with such a bacterial module could induce unfavorable immune reactions. To address this, we designed an alternative binding protein by imparting albumin-binding affinity to a human protein using molecular surface grafting. The result was a series of human-derived 6 helix-bundle proteins, one of which specifically binds to human serum albumin (HSA) with adequate affinity (KD = 100 nM). The proteins were designed by transferring key binding residues of a bacterial albumin-binding module, Finegoldia magna protein G-related albumin-binding domain (GA) module, onto the human protein scaffold. Despite 13-15 mutations, the designed proteins maintain the original secondary structure by virtue of careful grafting based on structural informatics. Competitive binding assays and thermodynamic analyses of the best binders show that the binding mode resembles that of the GA module, suggesting that the contacting surface of the GA module is mimicked well on the designed protein. These results indicate that the designed protein may act as an alternative low-risk binding module to HSA. Furthermore, molecular surface grafting in combination with structural informatics is an effective approach for avoiding deleterious mutations on a target protein and for imparting the binding function of one protein onto another.

  12. Chest magnetic resonance imaging: a protocol suggestion

    Directory of Open Access Journals (Sweden)

    Bruno Hochhegger

    2015-12-01

    Full Text Available Abstract In the recent years, with the development of ultrafast sequences, magnetic resonance imaging (MRI has been established as a valuable diagnostic modality in body imaging. Because of improvements in speed and image quality, MRI is now ready for routine clinical use also in the study of pulmonary diseases. The main advantage of MRI of the lungs is its unique combination of morphological and functional assessment in a single imaging session. In this article, the authors review most technical aspects and suggest a protocol for performing chest MRI. The authors also describe the three major clinical indications for MRI of the lungs: staging of lung tumors; evaluation of pulmonary vascular diseases; and investigation of pulmonary abnormalities in patients who should not be exposed to radiation.

  13. Ultrasonographic findings of early abortion: suggested predictors

    International Nuclear Information System (INIS)

    Jun, Soon Ae; Ahn, Myoung Ock; Cha, Kwang Yul; Lee, Young Doo

    1992-01-01

    To investigate predictable ultrasonographic findings of early abortion. To investigate objective rules for the screening of abortion. Ultrasonographic examination of 111 early pregnancies between the sixth and ninth week in women who had regular 28 day menstrual cycles was performed. Ultrasonographic measurements of the gestational sac, crown rump length and fetal heart rate were performed using a linear array real time transducer with doppler ultrasonogram. All measurements of 17 early abortions were compared to those of 94 normal pregnancies. Most of early aborted pregnancies were classified correctly by discriminant analysis with G-SAC and CRL (G-SAC=0.5 CRL + 15, sensitivity 76.5%, specificity 96.8%). With the addition of FHR, 94.1% of early abortions could be predicted. In conclusion, ultrasonographic findings of early intrauterine growth retardation, small gestational sac and bradycardia can be predictable signs suggestive of poor prognosis of early pregnancies

  14. Elastic wave scattering methods: assessments and suggestions

    International Nuclear Information System (INIS)

    Gubernatis, J.E.

    1985-01-01

    The author was asked by the meeting organizers to review and assess the developments over the past ten or so years in elastic wave scattering methods and to suggest areas of future research opportunities. He highlights the developments, focusing on what he feels were distinct steps forward in our theoretical understanding of how elastic waves interact with flaws. For references and illustrative figures, he decided to use as his principal source the proceedings of the various annual Reviews of Progress in Quantitative Nondestructive Evaluation (NDE). These meetings have been the main forum not only for presenting results of theoretical research but also for demonstrating the relevance of the theoretical research for the design and interpretation of experiment. In his opinion a quantitative NDE is possible only if this relevance exists, and his major objective is to discuss and illustrate the degree to which relevance has developed

  15. Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age.

    Science.gov (United States)

    van Geldorp, Bonnie; Parra, Mario A; Kessels, Roy P C

    2015-01-01

    The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding.

  16. Spectral characterization and DNA binding properties of lanthanide(III)

    African Journals Online (AJOL)

    Spectral data of complexes suggest that the ligand binds metal ion through pyridine- nitrogen, azomethine-nitrogen and amido-oxygen donor atoms. Electrochemical behaviour of metal complexes was investigated by using cyclic voltammetry. The complexes undergo quasi-reversible one electron reduction. The binding ...

  17. DNA minor groove binding of small molecules: Experimental and ...

    Indian Academy of Sciences (India)

    Administrator

    Abstract. Eight indole derivatives were studied for their DNA binding ability using fluorescence quenching and molecular docking methods. These indole compounds have structural moieties similar as in few indole alkaloids. Experimental and theoretical studies have suggested that indole derivatives bind in the minor ...

  18. Zinc ions bind to and inhibit activated protein C

    DEFF Research Database (Denmark)

    Zhu, Tianqing; Ubhayasekera, Wimal; Nickolaus, Noëlle

    2010-01-01

    fold enhanced, presumably due to the Ca2+-induced conformational change affecting the conformation of the Zn2+-binding site. The inhibition mechanism was non-competitive both in the absence and presence of Ca2+. Comparisons of sequences and structures suggested several possible sites for zinc binding...

  19. Maxillectomy defects: a suggested classification scheme.

    Science.gov (United States)

    Akinmoladun, V I; Dosumu, O O; Olusanya, A A; Ikusika, O F

    2013-06-01

    The term "maxillectomy" has been used to describe a variety of surgical procedures for a spectrum of diseases involving a diverse anatomical site. Hence, classifications of maxillectomy defects have often made communication difficult. This article highlights this problem, emphasises the need for a uniform system of classification and suggests a classification system which is simple and comprehensive. Articles related to this subject, especially those with specified classifications of maxillary surgical defects were sourced from the internet through Google, Scopus and PubMed using the search terms maxillectomy defects classification. A manual search through available literature was also done. The review of the materials revealed many classifications and modifications of classifications from the descriptive, reconstructive and prosthodontic perspectives. No globally acceptable classification exists among practitioners involved in the management of diseases in the mid-facial region. There were over 14 classifications of maxillary defects found in the English literature. Attempts made to address the inadequacies of previous classifications have tended to result in cumbersome and relatively complex classifications. A single classification that is based on both surgical and prosthetic considerations is most desirable and is hereby proposed.

  20. Suggestion on Information Sharing for AP implementation

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Hye Won; Kim, Min Su; Koh, Byung Marn [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2013-10-15

    Under the Additional Protocol, States should provide the IAEA with expanded declarations of activities related to the nuclear fuel cycle and other nuclear activities, and with expanded access to the relevant information and sites to allow the IAEA to verify the completeness of these declarations. The AP to the Safeguards Agreement (the Additional Protocol) was signed on June 21{sup st}, 1999 and entered into force on February 19{sup th}, 2004. ROK submitted initial declarations in August 2004. Since then, ROK has been submitting annual updated reports of initial declaration on every May 15{sup th}. To achieve successful implementation, it is necessary to collect the information for each individual article in Article 2 of the AP and verify the declared information provided by facility operators. Therefore, the cooperation among the ministries and offices concerned is a prerequisite for successful implementation of AP. Unfortunately, the formal procedure for inter-organizational information sharing and cooperation is not established. This paper will briefly outline the AP declarations and suggest the information sharing among the ministries, offices and organizations for effective and efficient implementation of AP. The State authority has responsibility for AP implementation and it should verify correctness and completeness of the information declared by facility operators before submitting the declarations. The close cooperation and information sharing among the ministries, offices and organizations are indispensable to effective and efficient implementation of AP.

  1. [Evidence that suggest the reality of reincarnation].

    Science.gov (United States)

    Bonilla, Ernesto

    2015-06-01

    Worldwide, children can be found who reported that they have memories of a previous life. More than 2,500 cases have been studied and their specifications have been published and preserved in the archives of the Division of Perceptual Studies at the University of Virginia (United States). Many of those children come from countries where the majority of the inhabitants believe in reincarnation, but others come from countries with different cultures and religions that reject it. In many cases, the revelations of the children have been verified and have corresponded to a particular individual, already dead. A good number of these children have marks and birth defects corresponding to wounds on the body of his previous personality. Many have behaviors related to their claims to their former life: phobias, philias, and attachments. Others seem to recognize people and places of his supposed previous life, and some of their assertions have been made under controlled conditions. The hypothesis of reincarnation is controversial. We can never say that it does not occur, or will obtain conclusive evidence that it happens. The cases that have been described so far, isolated or combined, do not provide irrefutable proof of reincarnation, but they supply evidence that suggest its reality.

  2. Effect of cobratoxin binding on the normal mode vibration within acetylcholine binding protein.

    Science.gov (United States)

    Bertaccini, Edward J; Lindahl, Erik; Sixma, Titia; Trudell, James R

    2008-04-01

    Recent crystal structures of the acetylcholine binding protein (AChBP) have revealed surprisingly small structural alterations upon ligand binding. Here we investigate the extent to which ligand binding may affect receptor dynamics. AChBP is a homologue of the extracellular component of ligand-gated ion channels (LGICs). We have previously used an elastic network normal-mode analysis to propose a gating mechanism for the LGICs and to suggest the effects of various ligands on such motions. However, the difficulties with elastic network methods lie in their inability to account for the modest effects of a small ligand or mutation on ion channel motion. Here, we report the successful application of an elastic network normal mode technique to measure the effects of large ligand binding on receptor dynamics. The present calculations demonstrate a clear alteration in the native symmetric motions of a protein due to the presence of large protein cobratoxin ligands. In particular, normal-mode analysis revealed that cobratoxin binding to this protein significantly dampened the axially symmetric motion of the AChBP that may be associated with channel gating in the full nAChR. The results suggest that alterations in receptor dynamics could be a general feature of ligand binding.

  3. Probing the binding of coumarins and cyclothialidines to DNA gyrase

    DEFF Research Database (Denmark)

    Kampranis, S C; Gormley, N A; Tranter, R

    1999-01-01

    B and coumarin and cyclothialidine drugs and made mutations by site-directed mutagenesis. We used proteolysis as a probe of drug binding to wild-type and mutant proteins. Limited proteolysis of gyrase revealed that binding of these antibiotics is associated with a characteristic proteolytic fingerprint......, suggesting a drug-induced conformational change. The ability of the mutants to bind the drugs was studied by testing their ability to induce the coumarin-associated proteolytic signature and to bind to a novobiocin-affinity column. To analyze further the interaction of the drugs with gyrase, we studied...

  4. Quantitative histological models suggest endothermy in plesiosaurs

    Directory of Open Access Journals (Sweden)

    Corinna V. Fleischle

    2018-06-01

    Full Text Available Background Plesiosaurs are marine reptiles that arose in the Late Triassic and survived to the Late Cretaceous. They have a unique and uniform bauplan and are known for their very long neck and hydrofoil-like flippers. Plesiosaurs are among the most successful vertebrate clades in Earth’s history. Based on bone mass decrease and cosmopolitan distribution, both of which affect lifestyle, indications of parental care, and oxygen isotope analyses, evidence for endothermy in plesiosaurs has accumulated. Recent bone histological investigations also provide evidence of fast growth and elevated metabolic rates. However, quantitative estimations of metabolic rates and bone growth rates in plesiosaurs have not been attempted before. Methods Phylogenetic eigenvector maps is a method for estimating trait values from a predictor variable while taking into account phylogenetic relationships. As predictor variable, this study employs vascular density, measured in bone histological sections of fossil eosauropterygians and extant comparative taxa. We quantified vascular density as primary osteon density, thus, the proportion of vascular area (including lamellar infillings of primary osteons to total bone area. Our response variables are bone growth rate (expressed as local bone apposition rate and resting metabolic rate (RMR. Results Our models reveal bone growth rates and RMRs for plesiosaurs that are in the range of birds, suggesting that plesiosaurs were endotherm. Even for basal eosauropterygians we estimate values in the range of mammals or higher. Discussion Our models are influenced by the availability of comparative data, which are lacking for large marine amniotes, potentially skewing our results. However, our statistically robust inference of fast growth and fast metabolism is in accordance with other evidence for plesiosaurian endothermy. Endothermy may explain the success of plesiosaurs consisting in their survival of the end-Triassic extinction

  5. Employee suggestion programs: the rewards of involvement.

    Science.gov (United States)

    Mishra, J M; McKendall, M

    1993-09-01

    Successful ESPs are the products of a great deal of effort by managers, administrators, teams, individuals, and reviewers, who are all striving to achieve the goals of increased profitability and enhanced employee involvement. A review of the literature indicates that there are several prescriptions that will increase the likelihood of a successful ESP (see the box). Today's American business prophets sound ceaseless calls to arms in the name of "world class performance," "global competitiveness," "total quality management," and a variety of other buzz terms. A burgeoning industry has evolved that promises, through speeches, teleconferences, seminars, and consulting contracts, to teach American organizations how to achieve excellence. In the face of a sputtering economy and unrelenting competitive pressure, today's managers must translate these laudatory ideals into hands-on reality without sacrificing the firm's profit margin to experimentation. If any idea can help an organization achieve improvement through a workable program, then that idea and that program deserve real consideration. An ESP represents an opportunity to tap the intelligence and resourcefulness of an organization's employees, and by doing so, reap significant cost savings. Those companies and managers that have an ESP program uniformly list economic advantages first when describing the benefits of their employee suggestion programs. But there is another deeper and longer term benefit inherent in an ESP. These programs allow employees to become involved in their organization; they drive deaccession to lower levels, they give employees more responsibility, they foster creative approaches to work, and they encourage creativity in pursuit of company goals.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Suggestions for an updated fusion power program

    International Nuclear Information System (INIS)

    Clarke, J.F.

    1976-02-01

    This document contains suggestions for a revised CTR Program strategy which should allow us to achieve equivalent goals while operating within the above constraints. The revised program is designed around three major facilities. The first is an upgrading of the present TFTR facility which will provide a demonstration of the generation of tens of megawatts electric equivalent originally envisioned for the 1985 EPR. The second device is the TTAP which will allow the integration and optimization of the plasma physics results obtained from the next generation of plasma physics experiments. The improvement in tokamak reactor operation resulting from this optimization of fusion plasma performance will enable an EPR to be designed which will produce several hundred megawatts of electric power by 1990. This will move the fusion program much closer to its goal of commercial fusion power by the turn of the century. In addition to this function the TTAP will serve as a prototype of the 1990 EPR system, thus making more certain the successful operation of this device. The third element of this revised program is an intense radiation damage facility which will provide the radiation damage information necessary for the EPR and subsequent fusion reactor facilities. The sum total of experience gained from reacting plasma experiments on TFTR, reactor grade plasma optimization and technological prototyping on TTAP, and end of life radiation damage results from the intense neutron facility will solve all of the presently foreseen problems associated with a tokamak fusion power reactor except those associated with the external nuclear systems. These external system problems such as tritium breeding and optimal power recovery can be developed in parallel on the 1990 EPR

  7. Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site.

    Science.gov (United States)

    Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J; Hogle, James M

    2016-01-13

    Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. The role of suggestibility in determinations of Miranda abilities: a study of the Gudjonsson Suggestibility Scales.

    Science.gov (United States)

    Rogers, Richard; Harrison, Kimberly S; Rogstad, Jill E; LaFortune, Kathryn A; Hazelwood, Lisa L

    2010-02-01

    Traditionally, high levels of suggestibility have been widely assumed to be linked with diminished Miranda abilities, especially in relationship to the voluntariness of waivers. The current investigation examined suggestibility on the Gudjonsson Suggestibility Scales in a multisite study of pretrial defendants. One important finding was the inapplicability of British norms to American jurisdictions. Moreover, suggestibility appeared unrelated to Miranda comprehension, reasoning, and detainees' perceptions of police coercion. In testing rival hypotheses, defendants with high compliance had significantly lower Miranda comprehension and ability to reason about exercising Miranda rights than their counterparts with low compliance. Implications of these findings to forensic practice are examined.

  9. Are Dysphoric Individuals More Suggestible or Less Suggestible Than Nondysphoric Individuals?

    Science.gov (United States)

    MacFarland, Wendy L.; Morris, Steven J.

    1998-01-01

    Dysphoric individuals are shown to be susceptible to interrogative suggestion, whether in the form of leading questions or interrogative pressure. The association of a clinically relevant condition of dysphoria (depression) with relatively high levels of suggestibility was investigated in a college student population (N=139). Applicability to…

  10. Suggestibility under Pressure: Theory of Mind, Executive Function, and Suggestibility in Preschoolers

    Science.gov (United States)

    Karpinski, Aryn C.; Scullin, Matthew H.

    2009-01-01

    Eighty preschoolers, ages 3 to 5 years old, completed a 4-phase study in which they experienced a live event and received a pressured, suggestive interview about the event a week later. Children were also administered batteries of theory of mind and executive function tasks, as well as the Video Suggestibility Scale for Children (VSSC), which…

  11. Testing increases suggestibility for narrative-based misinformation but reduces suggestibility for question-based misinformation.

    Science.gov (United States)

    LaPaglia, Jessica A; Chan, Jason C K

    2013-01-01

    A number of recent studies have found that recalling details of an event following its occurrence can increase people's suggestibility to later presented misinformation. However, several other studies have reported the opposite result, whereby earlier retrieval can reduce subsequent eyewitness suggestibility. In the present study, we investigated whether differences in the way misinformation is presented can modulate the effects of testing on suggestibility. Participants watched a video of a robbery and some were questioned about the event immediately afterwards. Later, participants were exposed to misinformation in a narrative (Experiment 1) or in questions (Experiment 2). Consistent with previous studies, we found that testing increased suggestibility when misinformation was presented via a narrative. Remarkably, when misinformation was presented in questions, testing decreased suggestibility. Copyright © 2013 John Wiley & Sons, Ltd.

  12. DNABP: Identification of DNA-Binding Proteins Based on Feature Selection Using a Random Forest and Predicting Binding Residues.

    Science.gov (United States)

    Ma, Xin; Guo, Jing; Sun, Xiao

    2016-01-01

    DNA-binding proteins are fundamentally important in cellular processes. Several computational-based methods have been developed to improve the prediction of DNA-binding proteins in previous years. However, insufficient work has been done on the prediction of DNA-binding proteins from protein sequence information. In this paper, a novel predictor, DNABP (DNA-binding proteins), was designed to predict DNA-binding proteins using the random forest (RF) classifier with a hybrid feature. The hybrid feature contains two types of novel sequence features, which reflect information about the conservation of physicochemical properties of the amino acids, and the binding propensity of DNA-binding residues and non-binding propensities of non-binding residues. The comparisons with each feature demonstrated that these two novel features contributed most to the improvement in predictive ability. Furthermore, to improve the prediction performance of the DNABP model, feature selection using the minimum redundancy maximum relevance (mRMR) method combined with incremental feature selection (IFS) was carried out during the model construction. The results showed that the DNABP model could achieve 86.90% accuracy, 83.76% sensitivity, 90.03% specificity and a Matthews correlation coefficient of 0.727. High prediction accuracy and performance comparisons with previous research suggested that DNABP could be a useful approach to identify DNA-binding proteins from sequence information. The DNABP web server system is freely available at http://www.cbi.seu.edu.cn/DNABP/.

  13. 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.

  14. Optical Binding of Nanowires

    Czech Academy of Sciences Publication Activity Database

    Simpson, Stephen Hugh; Zemánek, Pavel; Marago, O.M.; Jones, P.H.; Hanna, S.

    2017-01-01

    Roč. 17, č. 6 (2017), s. 3485-3492 ISSN 1530-6984 R&D Projects: GA ČR GB14-36681G Grant - others:AV ČR(CZ) CNR-16-12 Program:Bilaterální spolupráce Institutional support: RVO:68081731 Keywords : optical binding nanowires * Brownian motion * self-organization * non-equilibrium thermodynamics * non-equilibrium steady state * spin-orbit coupling * emergent phenomena Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 12.712, year: 2016

  15. IGF binding proteins.

    Science.gov (United States)

    Bach, Leon A

    2017-12-18

    Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF- and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

  16. Are You Suggesting That's My Hand? The Relation Between Hypnotic Suggestibility and the Rubber Hand Illusion.

    Science.gov (United States)

    Walsh, E; Guilmette, D N; Longo, M R; Moore, J W; Oakley, D A; Halligan, P W; Mehta, M A; Deeley, Q

    2015-01-01

    Hypnotic suggestibility (HS) is the ability to respond automatically to suggestions and to experience alterations in perception and behavior. Hypnotically suggestible participants are also better able to focus and sustain their attention on an experimental stimulus. The present study explores the relation between HS and susceptibility to the rubber hand illusion (RHI). Based on previous research with visual illusions, it was predicted that higher HS would lead to a stronger RHI. Two behavioral output measures of the RHI, an implicit (proprioceptive drift) and an explicit (RHI questionnaire) measure, were correlated against HS scores. Hypnotic suggestibility correlated positively with the implicit RHI measure contributing to 30% of the variation. However, there was no relation between HS and the explicit RHI questionnaire measure, or with compliance control items. High hypnotic suggestibility may facilitate, via attentional mechanisms, the multisensory integration of visuoproprioceptive inputs that leads to greater perceptual mislocalization of a participant's hand. These results may provide insight into the multisensory brain mechanisms involved in our sense of embodiment.

  17. Tritium NMR spectroscopy of ligand binding to maltose-binding protein

    International Nuclear Information System (INIS)

    Gehring, K.; Williams, P.G.; Pelton, J.G.; Morimoto, H.; Wemmer, D.E.

    1991-01-01

    Tritium-labeled α- and β-maltodextrins have been used to study their complexes with maltose-binding protein (MBP), a 40-kDa bacterial protein. Five substrates, from maltose to maltohexaose, were labeled at their reducing ends and their binding studied. Tritium NMR specctroscopy of the labeled sugars showed large upfield chamical shift changes upon binding and strong anomeric specficity. At 10 degrees C, MBP bound α-maltose with 2.7 ± 0.5-fold higher affinity than β-maltose, and, for longer maltodextrins, the ratio of affinities was even larger. The maximum chemical shift change was 2.2 ppm, suggesting that the reducing end of bound α-maltodextrin makes close contact with an aromatic residue in the MBP-binding site. Experiments with maltotriose (and longer maltodextrins) also revealed the presence of two bound β-maltotriose resonances in rapid exchange. The authors interpret these two resonances as arising from two distinct sugar-protein complexes. In one complex, the β-maltodextrin is bound by its reducing end, and, in the other complex, the β-maltodextrin is bound by the middle glucose residue(s). This interpretation also suggests how MBP is able to bind both linear and circular maltodextrins

  18. DNA Mismatch Binding and Antiproliferative Activity of Rhodium Metalloinsertors

    Science.gov (United States)

    Ernst, Russell J.; Song, Hang; Barton, Jacqueline K.

    2009-01-01

    Deficiencies in mismatch repair (MMR) are associated with carcinogenesis. Rhodium metalloinsertors bind to DNA base mismatches with high specificity and inhibit cellular proliferation preferentially in MMR-deficient cells versus MMR-proficient cells. A family of chrysenequinone diimine complexes of rhodium with varying ancillary ligands that serve as DNA metalloinsertors has been synthesized, and both DNA mismatch binding affinities and antiproliferative activities against the human colorectal carcinoma cell lines HCT116N and HCT116O, an isogenic model system for MMR deficiency, have been determined. DNA photocleavage experiments reveal that all complexes bind to the mismatch sites with high specificities; DNA binding affinities to oligonucleotides containing single base CA and CC mismatches, obtained through photocleavage titration or competition, vary from 104 to 108 M−1 for the series of complexes. Significantly, binding affinities are found to be inversely related to ancillary ligand size and directly related to differential inhibition of the HCT116 cell lines. The observed trend in binding affinity is consistent with the metalloinsertion mode where the complex binds from the minor groove with ejection of mismatched base pairs. The correlation between binding affinity and targeting of the MMR-deficient cell line suggests that rhodium metalloinsertors exert their selective biological effects on MMR-deficient cells through mismatch binding in vivo. PMID:19175313

  19. Binding of ATP by pertussis toxin and isolated toxin subunits

    International Nuclear Information System (INIS)

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L.

    1990-01-01

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of [ 3 H]ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of [ 3 H]ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of [ 3 H]ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site

  20. Binding of ATP by pertussis toxin and isolated toxin subunits

    Energy Technology Data Exchange (ETDEWEB)

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L. (Center for Biologics Evaluation and Research, Bethesda, MD (USA))

    1990-07-03

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of ({sup 3}H)ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of ({sup 3}H)ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of ({sup 3}H)ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.

  1. Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age

    NARCIS (Netherlands)

    Geldorp, B. van; Parra, M.A.; Kessels, R.P.C.

    2015-01-01

    The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven

  2. Children's Memory for Their Mother's Murder: Accuracy, Suggestibility, and Resistance to Suggestion.

    Science.gov (United States)

    McWilliams, Kelly; Narr, Rachel; Goodman, Gail S; Ruiz, Sandra; Mendoza, Macaria

    2013-01-31

    From its inception, child eyewitness memory research has been guided by dramatic legal cases that turn on the testimony of children. Decades of scientific research reveal that, under many conditions, children can provide veracious accounts of traumatic experiences. Scientific studies also document factors that lead children to make false statements. In this paper we describe a legal case in which children testified about their mother's murder. We discuss factors that may have influenced the accuracy of the children's eyewitness memory. Children's suggestibility and resistance to suggestion are illustrated. Expert testimony, based on scientific research, can aid the trier of fact when children provide crucial evidence in criminal investigations and courtroom trials about tragic events.

  3. Non-binding relationship between visual features

    Directory of Open Access Journals (Sweden)

    Dragan eRangelov

    2014-10-01

    Full Text Available The answer as to how visual attributes processed in different brain loci at different speeds are bound together to give us our unitary experience of the visual world remains unknown. In this study we investigated whether bound representations arise, as commonly assumed, through physiological interactions between cells in the visual areas. In a focal attentional task in which correct responses from either bound or unbound representations were possible, participants discriminated the colour or orientation of briefly presented single bars. On the assumption that representations of the two attributes are bound, the accuracy of reporting the colour and orientation should co-vary. By contrast, if the attributes are not mandatorily bound, the accuracy of reporting the two attributes should be independent. The results of our psychophysical studies reported here supported the latter, non-binding, relationship between visual features, suggesting that binding does not necessarily occur even under focal attention. We propose a task-contingent binding mechanism, postulating that binding occurs at late, post-perceptual, stages through the intervention of memory.

  4. PAK4 crystal structures suggest unusual kinase conformational movements.

    Science.gov (United States)

    Zhang, Eric Y; Ha, Byung Hak; Boggon, Titus J

    2018-02-01

    In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation. Protein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may

  5. Lil3 dimerization and chlorophyll binding in Arabidopsis thaliana.

    Science.gov (United States)

    Mork-Jansson, Astrid Elisabeth; Gargano, Daniela; Kmiec, Karol; Furnes, Clemens; Shevela, Dmitriy; Eichacker, Lutz Andreas

    2015-10-07

    The two-helix light harvesting like (Lil) protein Lil3 belongs to the family of chlorophyll binding light harvesting proteins of photosynthetic membranes. A function in tetrapyrrol synthesis and stabilization of geranylgeraniol reductase has been shown. Lil proteins contain the chlorophyll a/b-binding motif; however, binding of chlorophyll has not been demonstrated. We find that Lil3.2 from Arabidopsis thaliana forms heterodimers with Lil3.1 and binds chlorophyll. Lil3.2 heterodimerization (25±7.8 nM) is favored relative to homodimerization (431±59 nM). Interaction of Lil3.2 with chlorophyll a (231±49 nM) suggests that heterodimerization precedes binding of chlorophyll in Arabidopsis thaliana. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  6. Localization of gonadotropin binding sites in human ovarian neoplasms

    International Nuclear Information System (INIS)

    Nakano, R.; Kitayama, S.; Yamoto, M.; Shima, K.; Ooshima, A.

    1989-01-01

    The binding of human luteinizing hormone and human follicle-stimulating hormone to ovarian tumor biopsy specimens from 29 patients was analyzed. The binding sites for human luteinizing hormone were demonstrated in one tumor of epithelial origin (mucinous cystadenoma) and in one of sex cord-stromal origin (theca cell tumor). The binding sites for human follicle-stimulating hormone were found in three tumors of epithelial origin (serous cystadenoma and mucinous cystadenoma) and in two of sex cord-stromal origin (theca cell tumor and theca-granulosa cell tumor). The surface-binding autoradiographic study revealed that the binding sites for gonadotropins were localized in the stromal tissue. The results suggest that gonadotropic hormones may play a role in the growth and differentiation of a certain type of human ovarian neoplasms

  7. The effectiveness of ski bindings and their professional adjustment for preventing alpine skiing injuries.

    Science.gov (United States)

    Finch, C F; Kelsall, H L

    1998-06-01

    This article presents a critical review of the extent to which alpine ski bindings and their adjustment have been formally demonstrated to prevent injuries. It considers a range of evidence, from anecdotal evidence and informed opinion to biomechanical studies, testing of equipment, epidemiological studies and controlled field evaluations. A total of 15 published studies examining the effectiveness of bindings and their adjustment were identified. All of these included anecdotal or informed opinion, and all but one focused on equipment design. Seven studies involved the testing of bindings or binding prototypes, 2 studies presented biomechanical models of the forces involved in binding operation, 6 reported an epidemiological evaluation of ski bindings and 2 considered skiers' behaviours towards binding adjustment. Some of the reviewed articles relate to the study of the biomechanics of ski bindings and their release in response to various loads and loading patterns. Other studies examined the contribution of bindings and binding-release to lower extremity, equipment-related injuries, the effect of various methods of binding adjustment on injury risk and the determinants of skiers' behaviour relating to professional binding adjustment. Most of the evidence suggests that currently used bindings are insufficient for the multidirectional release required to reduce the risk of injury to the lower limb, especially at the knee. This evidence suggests that further technical developments and innovations are required. The standard of the manufacture of bindings and boots also needs to be considered. The optimal adjustment of bindings using a testing device has been shown to be associated with a reduced risk of lower extremity injury. Generally, however, the adjustment of bindings has been shown to be inadequate, especially for children's bindings. Recommendations for further research, development and implementation with respect to ski binding and their adjustment are given

  8. GABAA [gamma-aminobutyric acid] type binding sites on membranes of spermatozoa

    International Nuclear Information System (INIS)

    Erdoe, S.L.; Wekerle, L.

    1990-01-01

    The binding of [ 3 H] gamma-aminobutyric acid (GABA) to seminal membranes of swines and rams was examined. Specific, GABA binding was demonstrated in both species, which showed the features of GABA A type receptors. The affinity of binding was similar in both species, whereas the density of seminal GABA binding sites was 5 times higher in swine. Our findings suggest that GABA may have a direct effect on spermatozoa

  9. LHRH-pituitary plasma membrane binding: the presence of specific binding sites in other tissues.

    Science.gov (United States)

    Marshall, J C; Shakespear, R A; Odell, W D

    1976-11-01

    Two specific binding sites for LHRH are present on plasma membranes prepared from rat and bovine anterior pituitary glands. One site is of high affinity (K = 2X108 1/MOL) and the second is of lower affinity (8-5X105 1/mol) and much greater capacity. Studies on membrane fractions prepared from other tissues showed the presence of a single specific site for LHRH. The kinetics and specificity of this site were similar to those of the lower affinity pituitary receptor. These results indicate that only pituitary membranes possess the higher affinity binding site and suggest that the low affinity site is not of physiological importance in the regulation of gonadotrophin secretion. After dissociation from membranes of non-pituitary tissues 125I-LHRH rebound to pituitary membrane preparations. Thus receptor binding per se does not result in degradation of LHRH and the function of these peripheral receptors remains obscure.

  10. Thermodynamic Characterization of New Positive Allosteric Modulators Binding to the Glutamate Receptor A2 Ligand-Binding Domain

    DEFF Research Database (Denmark)

    Nørholm, Ann-Beth; Francotte, Pierre; Goffin, Eric

    2014-01-01

    , and 5a (5-F) and 5b (6-F) are entropy driven. For 5d (8-F), both quantities were equal in size. Thermodynamic integration (TI) and one-step perturbation (OSP) were used to calculate the relative binding affinity of the modulators. The OSP calculations had a higher predictive power than those from TI......,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides. Measurements of ligand binding by isothermal titration calorimetry (ITC) showed similar binding affinities for the modulator series at the GluA2 LBD but differences in the thermodynamic driving forces. Binding of 5c (7-F) and 6 (no-F) is enthalpy driven......, and combined with the shorter total simulation time, we found the OSP method to be more effective for this setup. Furthermore, from the molecular dynamics simulations, we extracted the enthalpies and entropies, and along with the ITC data, this suggested that the differences in binding free energies...

  11. Effect of benzimidazol-derivatives on the DNA-protein binding formation after UV-radiation of chromatin

    International Nuclear Information System (INIS)

    Mil', E.M.; Binyukov, V.I.; Zhil'tsova, V.M.; Stolyarova, L.G.; Kuznetsov, Yu.V.

    1991-01-01

    Effect of benzimidazol-derivatives on the DNA-protein binding formation was studied after UV-radiation of chromatin. These derivatives were shown to protect chromatin from UV-induced DNA-protein binding formation. Structural analog contained two aminomethyl residuals sensibilized additional binding formation in chromatin. Results suggested, that benzimidazol interacted with DNA, while aminomethyl groups interacted with protein and sensibilized binding of DNA, whilt aminomethyl groups interacted with protein and sensibilized binding of DNA with histone H1

  12. Pictorial binding: endeavor to classify

    Directory of Open Access Journals (Sweden)

    Zinchenko S.

    2015-01-01

    Full Text Available The article is devoted to the classification of bindings of the 1-19th centuries with a unique and untypical book binding decoration technique (encaustic, tempera and oil paintings. Analysis of design features, materials and techniques of art decoration made it possible to identify them as a separate type - pictorial bindings and divide them into four groups. The first group consists of Coptic bindings, decorated with icon-painting images in encaustic technique. The second group is made up of leather Western bindings of the 13-14th centuries, which have the decoration and technique of ornamentation close to iconography. The third group involves parchment bindings, ornamentation technique of which is closer to the miniature. The last group comprises bindings of East Slavic origin of the 15-19th centuries, decorated with icon-painting pictures made in the technique of tempera or oil painting. The proposed classification requires further basic research as several specific kinds of bindings have not yet been investigated

  13. UV-induced DNA-binding proteins in human cells

    International Nuclear Information System (INIS)

    Glazer, P.M.; Greggio, N.A.; Metherall, J.E.; Summers, W.C.

    1989-01-01

    To investigate the response of human cells to DNA-damaging agents such as UV irradiation, the authors examined nuclear protein extracts of UV-irradiated HeLa cells for the presence of DNA-binding proteins. Electrophoretically separated proteins were transferred to a nitrocellulose filter that was subsequently immersed in a binding solution containing radioactively labeled DNA probes. Several DNA-binding proteins were induced in HeLa cells after UV irradiation. These included proteins that bind predominantly double-stranded DNA and proteins that bind both double-stranded and single-stranded DNA. The binding proteins were induced in a dose-dependent manner by UV light. Following a dose of 12 J/m 2 , the binding proteins in the nuclear extracts increased over time to a peak in the range of 18 hr after irradiation. Experiments with metabolic inhibitors (cycloheximide and actinomycin D) revealed that de novo synthesis of these proteins is not required for induction of the binding activities, suggesting that the induction is mediated by protein modification

  14. Temperature-dependent binding of cyclosporine to an erythrocyte protein

    International Nuclear Information System (INIS)

    Agarwal, R.P.; Threatte, G.A.; McPherson, R.A.

    1987-01-01

    In this competitive binding assay to measure endogenous binding capacity for cyclosporine (CsA) in erythrocyte lysates, a fixed amount of [ 3 H]CsA plus various concentrations of unlabeled CsA is incubated with aliquots of a test hemolysate. Free CsA is then adsorbed onto charcoal and removed by centrifugation; CsA complexed with a cyclosporine-binding protein (CsBP) remains in the supernate. We confirmed the validity of this charcoal-separation mode of binding analysis by comparison with equilibrium dialysis. Scatchard plot analysis of the results at 4 degrees C yielded a straight line with slope corresponding to a binding constant of 1.9 X 10(7) L/mol and a saturation capacity of approximately 4 mumol per liter of packed erythrocytes. Similar analysis of binding data at 24 degrees C and 37 degrees C showed that the binding constant decreased with increasing temperature, but the saturation capacity did not change. CsBP was not membrane bound but appeared to be freely distributed within erythrocytes. 125 I-labeled CsA did not complex with the erythrocyte CsBP. Several antibiotics and other drugs did not inhibit binding between CsA and CsBP. These findings may explain the temperature-dependent uptake of CsA by erythrocytes in whole blood and suggest that measurement of CsBP in erythrocytes or lymphocytes may help predict therapeutic response or toxicity after administration of CsA

  15. Cation Binding to Xanthorhodopsin: Electron Paramagnetic Resonance and Magnetic Studies.

    Science.gov (United States)

    Smolensky Koganov, Elena; Leitus, Gregory; Rozin, Rinat; Weiner, Lev; Friedman, Noga; Sheves, Mordechai

    2017-05-04

    Xanthorhodopsin (xR) is a member of the retinal protein family and acts as a proton pump in the cell membranes of the extremely halophilic eubacterium Salinibacter ruber. In addition to the retinal chromophore, xR contains a carotenoid, which acts as a light-harvesting antenna as it transfers 40% of the quanta it absorbs to the retinal. Our previous studies have shown that the CD and absorption spectra of xR are dramatically affected due to the protonation of two different residues. It is still unclear whether xR can bind cations. Electron paramagnetic resonance (EPR) spectroscopy used in the present study revealed that xR can bind divalent cations, such as Mn 2+ and Ca 2+ , to deionized xR (DI-xR). We also demonstrate that xR can bind 1 equiv of Mn 2+ to a high-affinity binding site followed by binding of ∼40 equiv in cooperative manner and ∼100 equiv of Mn 2+ that are weakly bound. SQUID magnetic studies suggest that the high cooperative binding of Mn 2+ cations to xR is due to the formation of Mn 2+ clusters. Our data demonstrate that Ca 2+ cations bind to DI-xR with a lower affinity than Mn 2+ , supporting the assumption that binding of Mn 2+ occurs through cluster formation, because Ca 2+ cations cannot form clusters in contrast to Mn 2+ .

  16. Modification of opiate agonist binding by pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  17. Modification of opiate agonist binding by pertussis toxin

    International Nuclear Information System (INIS)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-01-01

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

  18. Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

    Directory of Open Access Journals (Sweden)

    Meyyammai Swaminathan

    2014-06-01

    Full Text Available Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM, comparable to that of acetylcholine (Ki = 59 µM. Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

  19. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  20. Analysis of leukocyte binding to depletion filters: role of passive binding, interaction with platelets, and plasma components.

    Science.gov (United States)

    Henschler, R; Rüster, B; Steimle, A; Hansmann, H L; Walker, W; Montag, T; Seifried, E

    2005-08-01

    Since limited knowledge exists on the mechanisms which regulate cell binding to leukocyte removal filter surfaces, we investigated the binding patterns of leukocytes to individual layers of leukocyte depletion filters. After passage of 1 unit of whole blood, blotting of isolated filter layers on glass slides or elution of cells from filter layers revealed that most leukocytes were located within the first 10 of a total of 28 filter layers, peaking at layers 6 to 8, with granulocytes binding on average to earlier filter layers than lymphocytes. Leukocytes preincubated with inhibitors of actin activation showed unchanged distribution between filter layers, suggesting that cytoskeletal activation does not significantly contribute to their binding. When leukocytes were directly incubated with single filter layers, binding of up to 30% of input cells was recorded in the absence of Ca(2+). Immunohistological analyses showed colocalization of platelets and leukocytes, with co-clustering of platelets and leukocytes. Monocytes and to some degree lymphocytes but not granulocytes competed with platelets for filter binding. Precoating of filter layers with individual plasma components showed that hyaluronic acid, plasma type fibronectin, and fibrinogen all increased the binding of leukocytes compared with albumin coating. In conclusion, leukocytes can bind passively to filters in a process which does not require Ca(2+), which is independent of cytoskeletal activation and which may depend on individual plasma components. These results are of importance when new selective cell enrichment or depletion strategies through specific filters are envisaged.

  1. Binding Preferences, Surface Attachment, Diffusivity, and Orientation of a Family 1 Carbohydrate-Binding Module on Cellulose

    Energy Technology Data Exchange (ETDEWEB)

    Nimlos, M. R.; Beckham, G. T.; Matthews, J. F.; Bu, L.; Himmel, M. E.; Crowley, M. F.

    2012-06-08

    Cellulase enzymes often contain carbohydrate-binding modules (CBMs) for binding to cellulose. The mechanisms by which CBMs recognize specific surfaces of cellulose and aid in deconstruction are essential to understand cellulase action. The Family 1 CBM from the Trichoderma reesei Family 7 cellobiohydrolase, Cel7A, is known to selectively bind to hydrophobic surfaces of native cellulose. It is most commonly suggested that three aromatic residues identify the planar binding face of this CBM, but several recent studies have challenged this hypothesis. Here, we use molecular simulation to study the CBM binding orientation and affinity on hydrophilic and hydrophobic cellulose surfaces. Roughly 43 {mu}s of molecular dynamics simulations were conducted, which enables statistically significant observations. We quantify the fractions of the CBMs that detach from crystal surfaces or diffuse to other surfaces, the diffusivity along the hydrophobic surface, and the overall orientation of the CBM on both hydrophobic and hydrophilic faces. The simulations demonstrate that there is a thermodynamic driving force for the Cel7A CBM to bind preferentially to the hydrophobic surface of cellulose relative to hydrophilic surfaces. In addition, the simulations demonstrate that the CBM can diffuse from hydrophilic surfaces to the hydrophobic surface, whereas the reverse transition is not observed. Lastly, our simulations suggest that the flat faces of Family 1 CBMs are the preferred binding surfaces. These results enhance our understanding of how Family 1 CBMs interact with and recognize specific cellulose surfaces and provide insights into the initial events of cellulase adsorption and diffusion on cellulose.

  2. Tetrodotoxin- and tributyltin-binding abilities of recombinant pufferfish saxitoxin and tetrodotoxin binding proteins of Takifugu rubripes.

    Science.gov (United States)

    Satone, Hina; Nonaka, Shohei; Lee, Jae Man; Shimasaki, Yohei; Kusakabe, Takahiro; Kawabata, Shun-Ichiro; Oshima, Yuji

    2017-01-01

    We investigated the ability of recombinant pufferfish saxitoxin and tetrodotoxin binding protein types 1 and 2 of Takifugu rubripes (rTrub.PSTBP1 and rTrub.PSTBP2) to bind to tetrodotoxin (TTX) and tributyltin. Both rTrub.PSTBPs bound to tributyltin in an ultrafiltration binding assay but lost this ability on heat denaturation. In contrast, only rTrub.PSTBP2 bound to TTX even heat denaturation. This result suggests that the amino acid sequence of PSTBP2 may be contributed for its affinity for TTX. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Mcm1p binding sites in ARG1 positively regulate Gcn4p binding and SWI/SNF recruitment

    OpenAIRE

    Yoon, Sungpil; Hinnebusch, Alan G.

    2009-01-01

    Transcription of the arginine biosynthetic gene ARG1 is activated by Gcn4p, a transcription factor induced by starvation for any amino acid. Previously we showed that Gcn4p binding stimulates the recruitment of Mcm1p and co-activator SWI/SNF to ARG1 in cells via Gcn4p induction through amino acid starvation. Here we report that Gcn4p binding is reduced by point mutations of the Mcm1p binding site and increased by overexpression of Mcm1p. This result suggests that Mcm1p plays a positive role i...

  4. Binding of kappa- and sigma-opiates in rat brain

    International Nuclear Information System (INIS)

    Wolozin, B.L.; Nishimura, S.; Pasternak, G.W.

    1982-01-01

    Detailed displacements of [ 3 H]dihydromorphine by ketocyclazocine and SKF 10,047, [ 3 H]ethylketocyclazocine by SKF 10,047, and [ 3 H]SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of 3 H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of [ 3 H]dihydromorphine (KD . 3 nM), [ 3 H]ethylketocyclazocine (KD . 4 nM), [ 3 H]SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-[ 3 H]enkephalin (KD . 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin

  5. Memory Binding in Early Childhood: Evidence for a Retrieval Deficit

    Science.gov (United States)

    Lloyd, Marianne E.; Doydum, Ayzit O.; Newcombe, Nora S.

    2009-01-01

    Previous research has suggested that performance for items requiring memory-binding processes improves between ages 4 and 6 (J. Sluzenski, N. Newcombe, & S. L. Kovacs, 2006). The present study suggests that much of this improvement is due to retrieval, as opposed to encoding, deficits for 4-year-olds. Four- and 6-year-old children (N = 48 per age)…

  6. The Structure of the ZMYND8/Drebrin Complex Suggests a Cytoplasmic Sequestering Mechanism of ZMYND8 by Drebrin.

    Science.gov (United States)

    Yao, Ningning; Li, Jianchao; Liu, Haiyang; Wan, Jun; Liu, Wei; Zhang, Mingjie

    2017-11-07

    Malfunctions of the actin binding protein Drebrin have been implicated in various human diseases such as Alzheimer's disease, cognitive impairments, cancer, and digestive disorders, though with poorly understood mechanisms. The ADF-H domain of Drebrin does not contain actin binding and depolymerizing activity. Instead, it binds to a histone marker reader, ZMYND8. Here we present the high-resolution crystal structure of Drebrin ADF-H in complex with the ZMYND8 PHD-BROMO-PWWP tandem, elucidating the mechanistic basis governing the highly specific interaction of the two proteins. The structure reveals that the ZMYND8 PHD-BROMO-PWWP tandem forms a structural supramodule that is necessary for binding to Drebrin ADF-H. Drebrin ADF-H competes with modified histone for binding to ZMYND8. Binding of Drebrin can shuttle ZMYND8 from nucleus to cytoplasm in living cells. Taken together, our study uncovers a non-actin target binding mode for ADF-H domains, and suggests that Drebrin may regulate activities of epigenetic reader ZMYND8 via its cytoplasmic sequestration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Structure of Epstein-Barr Virus Glycoprotein 42 Suggests a Mechanism for Triggering Receptor-Activated Virus Entry

    Energy Technology Data Exchange (ETDEWEB)

    Kirschner, Austin N.; Sorem, Jessica; Longnecker, Richard; Jardetzky, Theodore S.; (NWU); (Stanford-MED)

    2009-05-26

    Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B-cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLA complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor binding domain. Although the core of the lectin domain remains similar, significant shifts in two loops and an {alpha} helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.

  8. Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

    International Nuclear Information System (INIS)

    Lummis, S.C.R.; Johnston, G.A.R.; Nicoletti, G.; Holan, G.

    1991-01-01

    Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E. coli. The bacterial [ 3 H]diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli [ 3 H]diazepam binding are those that are active in displacing [ 3 H]benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligand spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed

  9. Binding of streptomycin with bovine serum albumin: Energetics and conformational aspects

    International Nuclear Information System (INIS)

    Jha, Niki S.; Kishore, Nand

    2009-01-01

    Thermodynamics of the binding of antibiotic streptomycin to bovine serum albumin have been studied using isothermal titration calorimetry in combination with fluorescence, UV-vis and circular dichroism spectroscopies. The values of van't Hoff enthalpy calculated from the temperature dependence of the binding constant do not agree with the calorimetric enthalpies indicating temperature dependent conformational changes in the protein upon binding. With increase in the ionic strength, reduction in the binding affinity of streptomycin to BSA is observed suggesting the predominance of electrostatic interactions in the binding. The contribution of hydrophobic interactions in the binding is also demonstrated by decrease in binding affinity in the presence of tetrabutylammonium bromide (TBAB). The value of binding affinity in the presence of sucrose indicates that hydrogen bonding is not a significant contribution in complexation. The results have permitted quantitative evaluation of the interaction of streptomycin with bovine serum albumin

  10. Protein binding of psychotropic agents

    International Nuclear Information System (INIS)

    Hassan, H.A.

    1990-01-01

    Based upon fluorescence measurements, protein binding of some psychotropic agents (chlorpromazine, promethazine, and trifluoperazine) to human IgG and HSA was studied in aqueous cacodylate buffer, PH7. The interaction parameters determined from emission quenching of the proteins. The interaction parameters determined include the equilibrium constant (K), calculated from equations derived by Borazan and coworkers, the number of binding sites (n) available to the monomer molecules on a single protein molecule. The results revealed a high level of affinity, as reflected by high values of K, and the existence of specific binding sites, since a limited number of n values are obtained. 39 tabs.; 37 figs.; 83 refs

  11. Protein-binding RNA aptamers affect molecular interactions distantly from their binding sites.

    Directory of Open Access Journals (Sweden)

    Daniel M Dupont

    Full Text Available Nucleic acid aptamer selection is a powerful strategy for the development of regulatory agents for molecular intervention. Accordingly, aptamers have proven their diligence in the intervention with serine protease activities, which play important roles in physiology and pathophysiology. Nonetheless, there are only a few studies on the molecular basis underlying aptamer-protease interactions and the associated mechanisms of inhibition. In the present study, we use site-directed mutagenesis to delineate the binding sites of two 2´-fluoropyrimidine RNA aptamers (upanap-12 and upanap-126 with therapeutic potential, both binding to the serine protease urokinase-type plasminogen activator (uPA. We determine the subsequent impact of aptamer binding on the well-established molecular interactions (plasmin, PAI-1, uPAR, and LRP-1A controlling uPA activities. One of the aptamers (upanap-126 binds to the area around the C-terminal α-helix in pro-uPA, while the other aptamer (upanap-12 binds to both the β-hairpin of the growth factor domain and the kringle domain of uPA. Based on the mapping studies, combined with data from small-angle X-ray scattering analysis, we construct a model for the upanap-12:pro-uPA complex. The results suggest and highlight that the size and shape of an aptamer as well as the domain organization of a multi-domain protein such as uPA, may provide the basis for extensive sterical interference with protein ligand interactions considered distant from the aptamer binding site.

  12. Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

    International Nuclear Information System (INIS)

    Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

    1988-01-01

    The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

  13. Characterization of (/sup 3/H)paroxetine binding in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Marcusson, J.O.; Bergstroem, M.E.; Eriksson, K.; Ross, S.B.

    1988-06-01

    The binding of the 5-hydroxytryptamine (5-HT, serotonin) uptake inhibitor (3H)paroxetine to rat cortical homogenates has been characterized. The effect of tissue concentration was examined and, with 0.75 mg wet weight tissue/ml in a total volume of 1,600 microliter, the binding was optimized with an apparent dissociation constant (KD) of 0.03-0.05 nM. Competition experiments with 5-HT, citalopram, norzimeldine, and desipramine revealed a high (90%) proportion of displaceable binding that fitted a single-site binding model. Fluoxetine and imipramine revealed, in addition to a high-affinity (nanomolar) site, also a low-affinity (micromolar) site representing approximately 10% of the displaceable binding. The specificity of the (3H)paroxetine binding was emphasized by the fact that 5-HT was the only active neurotransmitter bound and that the serotonin S1 and S2 antagonist methysergide was without effect on the binding. Both 5-HT- and fluoxetine-sensitive (3H)paroxetine binding was completely abolished after protease treatment, suggesting that the binding site is of protein nature. Saturation studies with 5-HT (100 microM) sensitive (3H)paroxetine binding were also consistent with a single-site binding model, and the binding was competitively inhibited by 5-HT and imipramine. The number of binding sites (Bmax) for 5-HT-sensitive (3H)paroxetine and (3H)imipramine binding was the same, indicating that the radioligands bind to the same sites. Lesion experiments with p-chloroamphetamine resulted in a binding in frontal and parietal cortices becoming undetectable and a greater than 60% reduction in the striatum and hypothalamus, indicating a selective localization on 5-HT terminals. Together these findings suggest that (3H)paroxetine specifically and selectively labels the substrate recognition site for 5-HT uptake in rat brain.

  14. Tannic acid and chromic chloride-induced binding of protein to red cells: a preliminary study of possible binding sites and reaction mechanisms.

    Science.gov (United States)

    Hunt, A F; Reed, M I

    1990-07-01

    The binding mechanisms and binding sites involved in the tannic acid and chromic chloride-induced binding of protein to red cells were investigated using the binding of IgA paraprotein to red cells as model systems. Inhibition studies of these model systems using amino acid homopolymers and compounds (common as red cell membrane constituents) suggest that the mechanisms involved are similar to those proposed for the conversion of hide or skin collagen to leather, as in commercial tanning. These studies also suggest that tannic acid-induced binding of IgA paraprotein to red cells involves the amino acid residues of L-arginine, L-lysine, L-histidine, and L-proline analogous to tanning with phenolic plant extracts. The amino acid residues of L-aspartate, L-glutamate and L-asparagine are involved in a similar manner in chronic chloride-induced binding of protein to red cells.

  15. Binding of acyl CoA by fatty acid binding protein and the effect on fatty acid activation

    International Nuclear Information System (INIS)

    Burrier, R.E.; Manson, C.R.; Brecher, P.

    1987-01-01

    The ability of purified rat liver and heart fatty acid binding proteins (FABPs) to bind oleoyl CoA and modulate acyl CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart FABP was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver FABP has a single binding site for acyl CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver FABP stimulated acyl CoA production whereas heart FABP did not stimulate production over control values. 14 C-Fatty acid-FABP complexes were prepared, incubated with membranes and acyl CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl CoA in the presence of liver FABP but in the presence of heart FABP, only 45% of the fatty acid was converted. The amount of product formed was not changed by additional membrane, enzyme cofactor, or incubation time. Liver but not heart FABP bound the acyl CoA formed and removed it from the membranes. These studies suggest that liver FABP can increase the amount of acyl CoA by binding this ligand thereby removing it from the membrane and possibly aiding transport within the cell

  16. Binding of acyl CoA by fatty acid binding protein and the effect on fatty acid activation

    Energy Technology Data Exchange (ETDEWEB)

    Burrier, R.E.; Manson, C.R.; Brecher, P.

    1987-05-01

    The ability of purified rat liver and heart fatty acid binding proteins (FABPs) to bind oleoyl CoA and modulate acyl CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart FABP was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver FABP has a single binding site for acyl CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver FABP stimulated acyl CoA production whereas heart FABP did not stimulate production over control values. /sup 14/C-Fatty acid-FABP complexes were prepared, incubated with membranes and acyl CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl CoA in the presence of liver FABP but in the presence of heart FABP, only 45% of the fatty acid was converted. The amount of product formed was not changed by additional membrane, enzyme cofactor, or incubation time. Liver but not heart FABP bound the acyl CoA formed and removed it from the membranes. These studies suggest that liver FABP can increase the amount of acyl CoA by binding this ligand thereby removing it from the membrane and possibly aiding transport within the cell.

  17. Superresolution microscopy with transient binding.

    Science.gov (United States)

    Molle, Julia; Raab, Mario; Holzmeister, Susanne; Schmitt-Monreal, Daniel; Grohmann, Dina; He, Zhike; Tinnefeld, Philip

    2016-06-01

    For single-molecule localization based superresolution, the concentration of fluorescent labels has to be thinned out. This is commonly achieved by photophysically or photochemically deactivating subsets of molecules. Alternatively, apparent switching of molecules can be achieved by transient binding of fluorescent labels. Here, a diffusing dye yields bright fluorescent spots when binding to the structure of interest. As the binding interaction is weak, the labeling is reversible and the dye ligand construct diffuses back into solution. This approach of achieving superresolution by transient binding (STB) is reviewed in this manuscript. Different realizations of STB are discussed and compared to other localization-based superresolution modalities. We propose the development of labeling strategies that will make STB a highly versatile tool for superresolution microscopy at highest resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. In vitro gibberellin A1 binding in Zea mays L

    International Nuclear Information System (INIS)

    Keith, B.; Rappaport, L.

    1987-01-01

    The first and second leaf sheaths of Zea mays L. cv Golden Jubilee were extracted and the extract centrifuged at 100,000g to yield a supernatant or cytosol fraction. Binding of [ 3 H]gibberellin A 1 (GA 1 ) to a soluble macromolecular component present in the cytosol was demonstrated at 4 0 C by Sephadex G-200 chromatography. The binding component was of high molecular weight (HMW) and greater than 500 kilodaltons. The HMW component was shown to be a protein and the 3 H-activity bound to this protein was largely [ 3 H]GA 1 and not a metabolite. Binding was pH sensitive but only a small percentage (20%) appeared to be exchangeable on addition of unlabeled GA 1 . Both biologically active and inactive GAs and non-GAs were able to inhibit GA 1 binding. [ 3 H]GA 1 binding to an intermediate molecular weight (IMW) fraction (40-100 kilodaltons) was also detected, provided cytosol was first desalted using Sephadex G-200 chromatography. Gel filtration studies suggest that the HMW binding component is an aggregate derived from the IMW fraction. The HMW binding fraction can be separated into two components using anion exchange chromatography

  19. Increased serum cortisol binding in chronic active hepatitis

    International Nuclear Information System (INIS)

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG

  20. (/sup 3/H)-beta-endorphin binding in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Houghten, R.A.; Johnson, N.; Pasternak, G.W.

    1984-10-01

    The binding of (/sup 3/H)-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the /sup 3/H-ligand is binding to more than one class of site. A portion of (/sup 3/H)-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of (/sup 3/H)-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers (/sup 3/H)-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of (/sup 3/H)-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo.

  1. Further biochemical characterization of Mycobacterium leprae laminin-binding proteins

    Directory of Open Access Journals (Sweden)

    M.A.M. Marques

    2001-04-01

    Full Text Available It has been demonstrated that the alpha2 chain of laminin-2 present on the surface of Schwann cells is involved in the process of attachment of Mycobacterium leprae to these cells. Searching for M. leprae laminin-binding molecules, in a previous study we isolated and characterized the cationic proteins histone-like protein (Hlp and ribosomal proteins S4 and S5 as potential adhesins involved in M. leprae-Schwann cell interaction. Hlp was shown to bind alpha2-laminins and to greatly enhance the attachment of mycobacteria to ST88-14 Schwann cells. In the present study, we investigated the laminin-binding capacity of the ribosomal proteins S4 and S5. The genes coding for these proteins were PCR amplified and their recombinant products were shown to bind alpha2-laminins in overlay assays. However, when tested in ELISA-based assays and in adhesion assays with ST88-14 cells, in contrast to Hlp, S4 and S5 failed to bind laminin and act as adhesins. The laminin-binding property and adhesin capacity of two basic host-derived proteins were also tested, and only histones, but not cytochrome c, were able to increase bacterial attachment to ST88-14 cells. Our data suggest that the alanine/lysine-rich sequences shared by Hlp and eukaryotic H1 histones might be involved in the binding of these cationic proteins to laminin.

  2. [3H]-beta-endorphin binding in rat brain

    International Nuclear Information System (INIS)

    Houghten, R.A.; Johnson, N.; Pasternak, G.W.

    1984-01-01

    The binding of [ 3 H]-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the 3 H-ligand is binding to more than one class of site. A portion of [ 3 H]-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of [ 3 H]-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers [ 3 H]-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of [ 3 H]-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo

  3. In vitro DNA binding studies of Aspartame, an artificial sweetener.

    Science.gov (United States)

    Kashanian, Soheila; Khodaei, Mohammad Mehdi; Kheirdoosh, Fahimeh

    2013-03-05

    A number of small molecules bind directly and selectively to DNA, by inhibiting replication, transcription or topoisomerase activity. In this work the interaction of native calf thymus DNA (CT-DNA) with Aspartame (APM), an artificial sweeteners was studied at physiological pH. DNA binding study of APM is useful to understand APM-DNA interaction mechanism and to provide guidance for the application and design of new and safer artificial sweeteners. The interaction was investigated using spectrophotometric, spectrofluorometric competition experiment and circular dichroism (CD). Hypochromism and red shift are shown in UV absorption band of APM. A strong fluorescence quenching reaction of DNA to APM was observed and the binding constants (Kf) of DNA with APM and corresponding number of binding sites (n) were calculated at different temperatures. Thermodynamic parameters, enthalpy changes (ΔH) and entropy changes (ΔS) were calculated to be +181kJmol(-1) and +681Jmol(-1)K(-1) according to Van't Hoff equation, which indicated that reaction is predominantly entropically driven. Moreover, spectrofluorometric competition experiment and circular dichroism (CD) results are indicative of non-intercalative DNA binding nature of APM. We suggest that APM interacts with calf thymus DNA via groove binding mode with an intrinsic binding constant of 5×10(+4)M(-1). Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Photoaffinity labeling of the oxysterol binding protein

    International Nuclear Information System (INIS)

    Taylor, F.R.; Kandutsch, A.A.; Anzalone, L.; Spencer, T.A.

    1986-01-01

    A cytosolic receptor protein for oxygenated sterols, that is thought to be involved in the regulation of HMG-CoA reductase and cholesterol biosynthesis, can be labeled covalently by the photoactivated affinity compound [5,6- 3 H]-7,7'-azocholestane-3β,25-diol (I). Several other compounds were tested including 25-hydroxycholesta-4,6-dien-3-one, 25-azido-27-norcholest-5-en-3β-ol,3β,25-dihydroxycholest-5-en-7-one and 3β-hydroxycholesta-8(14),9(11)-dien-15-one. However, these sterols either did not bind to the receptor with adequate affinity or did not react covalently with the receptor during photolysis. Compound I binds to the receptor with very high affinity (K/sub d/ = 30 nM). After activation with long wavelength UV, two tritium labeled proteins, M/sub r/ approximately 95K and 65K daltons, are found upon SDS gel electrophoresis. No labeling occurs when the binding reaction is carried out in the presence of a large excess of 25-hydroxycholesterol. It is possible that the smaller polypeptide is a degradation product. Under the reaction conditions investigated so far labeling is relatively inefficient (< 1% of bound sterol). These results are generally consistent with previous information suggesting that the M/sub r/ of the receptor subunit is 97,000. Covalent labeling of the receptor should greatly facilitate its further purification and characterization

  5. Competition increases binding errors in visual working memory.

    Science.gov (United States)

    Emrich, Stephen M; Ferber, Susanne

    2012-04-20

    When faced with maintaining multiple objects in visual working memory, item information must be bound to the correct object in order to be correctly recalled. Sometimes, however, binding errors occur, and participants report the feature (e.g., color) of an unprobed, non-target item. In the present study, we examine whether the configuration of sample stimuli affects the proportion of these binding errors. The results demonstrate that participants mistakenly report the identity of the unprobed item (i.e., they make a non-target response) when sample items are presented close together in space, suggesting that binding errors can increase independent of increases in memory load. Moreover, the proportion of these non-target responses is linearly related to the distance between sample items, suggesting that these errors are spatially specific. Finally, presenting sample items sequentially decreases non-target responses, suggesting that reducing competition between sample stimuli reduces the number of binding errors. Importantly, these effects all occurred without increases in the amount of error in the memory representation. These results suggest that competition during encoding can account for some of the binding errors made during VWM recall.

  6. Meta-analysis of crowdsourced data compendia suggests pan-disease transcriptional signatures of autoimmunity [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    William W. Lau

    2016-12-01

    Full Text Available Background: The proliferation of publicly accessible large-scale biological data together with increasing availability of bioinformatics tools have the potential to transform biomedical research. Here we report a crowdsourcing Jamboree that explored whether a team of volunteer biologists without formal bioinformatics training could use OMiCC, a crowdsourcing web platform that facilitates the reuse and (meta- analysis of public gene expression data, to compile and annotate gene expression data, and design comparisons between disease and control sample groups. Methods: The Jamboree focused on several common human autoimmune diseases, including systemic lupus erythematosus (SLE, multiple sclerosis (MS, type I diabetes (DM1, and rheumatoid arthritis (RA, and the corresponding mouse models. Meta-analyses were performed in OMiCC using comparisons constructed by the participants to identify 1 gene expression signatures for each disease (disease versus healthy controls at the gene expression and biological pathway levels, 2 conserved signatures across all diseases within each species (pan-disease signatures, and 3 conserved signatures between species for each disease and across all diseases (cross-species signatures. Results: A large number of differentially expressed genes were identified for each disease based on meta-analysis, with observed overlap among diseases both within and across species. Gene set/pathway enrichment of upregulated genes suggested conserved signatures (e.g., interferon across all human and mouse conditions. Conclusions: Our Jamboree exercise provides evidence that when enabled by appropriate tools, a "crowd" of biologists can work together to accelerate the pace by which the increasingly large amounts of public data can be reused and meta-analyzed for generating and testing hypotheses. Our encouraging experience suggests that a similar crowdsourcing approach can be used to explore other biological questions.

  7. Molecular Evolution of the Oxygen-Binding Hemerythrin Domain.

    Directory of Open Access Journals (Sweden)

    Claudia Alvarez-Carreño

    Full Text Available The evolution of oxygenic photosynthesis during Precambrian times entailed the diversification of strategies minimizing reactive oxygen species-associated damage. Four families of oxygen-carrier proteins (hemoglobin, hemerythrin and the two non-homologous families of arthropodan and molluscan hemocyanins are known to have evolved independently the capacity to bind oxygen reversibly, providing cells with strategies to cope with the evolutionary pressure of oxygen accumulation. Oxygen-binding hemerythrin was first studied in marine invertebrates but further research has made it clear that it is present in the three domains of life, strongly suggesting that its origin predated the emergence of eukaryotes.Oxygen-binding hemerythrins are a monophyletic sub-group of the hemerythrin/HHE (histidine, histidine, glutamic acid cation-binding domain. Oxygen-binding hemerythrin homologs were unambiguously identified in 367/2236 bacterial, 21/150 archaeal and 4/135 eukaryotic genomes. Overall, oxygen-binding hemerythrin homologues were found in the same proportion as single-domain and as long protein sequences. The associated functions of protein domains in long hemerythrin sequences can be classified in three major groups: signal transduction, phosphorelay response regulation, and protein binding. This suggests that in many organisms the reversible oxygen-binding capacity was incorporated in signaling pathways. A maximum-likelihood tree of oxygen-binding hemerythrin homologues revealed a complex evolutionary history in which lateral gene transfer, duplications and gene losses appear to have played an important role.Hemerythrin is an ancient protein domain with a complex evolutionary history. The distinctive iron-binding coordination site of oxygen-binding hemerythrins evolved first in prokaryotes, very likely prior to the divergence of Firmicutes and Proteobacteria, and spread into many bacterial, archaeal and eukaryotic species. The later evolution of the

  8. A unique bivalent binding and inhibition mechanism by the yatapoxvirus interleukin 18 binding protein.

    Directory of Open Access Journals (Sweden)

    Brian Krumm

    Full Text Available Interleukin 18 (IL18 is a cytokine that plays an important role in inflammation as well as host defense against microbes. Mammals encode a soluble inhibitor of IL18 termed IL18 binding protein (IL18BP that modulates IL18 activity through a negative feedback mechanism. Many poxviruses encode homologous IL18BPs, which contribute to virulence. Previous structural and functional studies on IL18 and IL18BPs revealed an essential binding hot spot involving a lysine on IL18 and two aromatic residues on IL18BPs. The aromatic residues are conserved among the very diverse mammalian and poxviruses IL18BPs with the notable exception of yatapoxvirus IL18BPs, which lack a critical phenylalanine residue. To understand the mechanism by which yatapoxvirus IL18BPs neutralize IL18, we solved the crystal structure of the Yaba-Like Disease Virus (YLDV IL18BP and IL18 complex at 1.75 Å resolution. YLDV-IL18BP forms a disulfide bonded homo-dimer engaging IL18 in a 2∶2 stoichiometry, in contrast to the 1∶1 complex of ectromelia virus (ECTV IL18BP and IL18. Disruption of the dimer interface resulted in a functional monomer, however with a 3-fold decrease in binding affinity. The overall architecture of the YLDV-IL18BP:IL18 complex is similar to that observed in the ECTV-IL18BP:IL18 complex, despite lacking the critical lysine-phenylalanine interaction. Through structural and mutagenesis studies, contact residues that are unique to the YLDV-IL18BP:IL18 binding interface were identified, including Q67, P116 of YLDV-IL18BP and Y1, S105 and D110 of IL18. Overall, our studies show that YLDV-IL18BP is unique among the diverse family of mammalian and poxvirus IL-18BPs in that it uses a bivalent binding mode and a unique set of interacting residues for binding IL18. However, despite this extensive divergence, YLDV-IL18BP binds to the same surface of IL18 used by other IL18BPs, suggesting that all IL18BPs use a conserved inhibitory mechanism by blocking a putative receptor-binding

  9. Predicting nucleic acid binding interfaces from structural models of proteins.

    Science.gov (United States)

    Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael

    2012-02-01

    The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. Copyright © 2011 Wiley Periodicals, Inc.

  10. Apolipoprotein B is a calcium binding protein

    International Nuclear Information System (INIS)

    Dashti, N.; Lee, D.M.; Mok, T.

    1986-01-01

    Human hepatocarcinoma Hep G2 cells were grown in culture medium containing [ 45 Ca 2+ ]. The secreted lipoproteins of d 45 Ca] from the gels showed that the peak of radioactivity corresponded to the apolipoprotein B band. The molar ratio of the incorporated [ 45 Ca 2+ ] and apolipoprotein B was close to unity. No radioactivity was found associated with any other secreted apolipoproteins. To confirm these findings, apolipoprotein B-containing lipoproteins were precipitated with anti-apolipoprotein B and high density lipoproteins were precipitated with anti-apolipoprotein A-I. Only the former precipitate was radioactive. These results suggest that apolipoprotein B is a calcium binding protein

  11. To bind or not to bind? Different temporal binding effects from voluntary pressing and releasing actions.

    Science.gov (United States)

    Zhao, Ke; Chen, Yu-Hsin; Yan, Wen-Jing; Fu, Xiaolan

    2013-01-01

    Binding effect refers to the perceptual attraction between an action and an outcome leading to a subjective compression of time. Most studies investigating binding effects exclusively employ the "pressing" action without exploring other types of actions. The present study addresses this issue by introducing another action, releasing action or the voluntary lifting of the finger/wrist, to investigate the differences between voluntary pressing and releasing actions. Results reveal that releasing actions led to robust yet short-lived temporal binding effects, whereas pressing condition had steady temporal binding effects up to super-seconds. The two actions also differ in sensitivity to changes in temporal contiguity and contingency, which could be attributed to the difference in awareness of action. Extending upon current models of "willed action," our results provide insights from a temporal point of view and support the concept of a dual system consisting of predictive motor control and top-down mechanisms.

  12. Spectroscopic characterization of furosemide binding to human carbonic anhydrase II.

    Science.gov (United States)

    Ranjbar, Samira; Ghobadi, Sirous; Khodarahmi, Reza; Nemati, Houshang

    2012-05-01

    This study reports the interaction between furosemide and human carbonic anhydrase II (hCA II) using fluorescence, UV-vis and circular dichroism (CD) spectroscopy. Fluorescence data indicated that furosemide quenches the intrinsic fluorescence of the enzyme via a static mechanism and hydrogen bonding and van der Walls interactions play the major role in the drug binding. The binding average distance between furosemide and hCA II was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity was also documented upon furosemide binding. Chemical modification of hCA II using N-bromosuccinimide indicated decrease of the number of accessible tryptophans in the presence of furosemide. CD results suggested the occurance of some alterations in α-helical content as well as tertiary structure of hCA II upon drug binding. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Identification of actin binding protein, ABP-280, as a binding partner of human Lnk adaptor protein.

    Science.gov (United States)

    He, X; Li, Y; Schembri-King, J; Jakes, S; Hayashi, J

    2000-08-01

    Human Lnk (hLnk) is an adaptor protein with multiple functional domains that regulates T cell activation signaling. In order to identify cellular Lnk binding partners, a yeast two-hybrid screening of human spleen cDNA library was carried out using human hLnk as bait. A polypeptide sequence identical to the C-terminal segment of the actin binding protein (ABP-280) was identified as a hLnk binding protein. The expressed hLnk and the FLAG tagged C-terminal 673 amino acid residues of ABP-280 or the endogenous ABP-280 in COS-7 cells could be co-immunoprecipitated using antibodies either to hLnk, FLAG or ABP-280, respectively. Furthermore, immunofluorescence confocal microscope showed that hLnk and ABP-280 co-localized at the plasma membrane and at juxtanuclear region of COS-7 cells. In Jurkat cells, the endogenous hLnk also associates with the endogenous ABP-280 indicating that the association of these two proteins is physiological. The interacting domains of both proteins were mapped using yeast two-hybrid assays. Our results indicate that hLnk binds to the residues 2006-2454 (repeats 19-23C) of ABP-280. The domain in hLnk that associates with ABP-280 was mapped to an interdomain region of 56 amino acids between pleckstrin homology and Src homology 2 domains. These results suggest that hLnk may exert its regulatory role through its association with ABP-280.

  14. The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide-Binding Domain.

    Science.gov (United States)

    Shengjuler, Djoshkun; Chan, Yan Mei; Sun, Simou; Moustafa, Ibrahim M; Li, Zhen-Lu; Gohara, David W; Buck, Matthias; Cremer, Paul S; Boehr, David D; Cameron, Craig E

    2017-12-05

    Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using nuclear magnetic resonance spectroscopy. The PIP-binding site was located on a highly dynamic α helix, which also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The Ties That Bind

    Science.gov (United States)

    Gloyn, Liz; Crewe, Vicky; King, Laura; Woodham, Anna

    2018-01-01

    Using an interdisciplinary research methodology across three archaeological and historical case studies, this article explores “family archives.” Four themes illustrate how objects held in family archives, curation practices, and intergenerational narratives reinforce a family’s sense of itself: people–object interactions, gender, socialization and identity formation, and the “life course.” These themes provide a framework for professional archivists to assist communities and individuals working with their own family archives. We argue that the family archive, broadly defined, encourages a more egalitarian approach to history. We suggest a multiperiod analysis draws attention to historical forms of knowledge and meaning-making practices over time. PMID:29593371

  16. The binding of fibrinogen to platelets in diabetes mellitus

    International Nuclear Information System (INIS)

    Minno, G. di; Cerbone, A.M.; Iride, C.; Mancini, M.

    1986-01-01

    Platelets from diabetics are known to be more sensitive in vitro to a variety of aggregating agents, to produce more prostaglandin endoperoxides and thromboxane and to bind more 125 I-fibrinogen than platelets from normal controls. Fibrinogen binding to platelets is a pre-requisite for platelet aggregation. Previous studies suggested a role for prostaglandins and/or thrombaxane A 2 in the exposure of fibrinogen receptors on platelets. The present study compares fibrinogen binding to hyperaggregable platelets from diabetic patients and to normal platelets when prostaglandin/thromboxane formation is suppressed by aspirin. It was found that pre-treatment with aspirin reduced collagen or thrombin-induced binding to platelets from none-retinopathic diabetics to the values seen in controls. By contrast, aspirin did not normalize binding to platelets obtained from retinopathic diabetics. The combination of aspirin with apyrase (an ADP scavenger) almost completely inhibited binding and aggregation of platelets from normal controls or non-retinophatic diabetics exposed to collagen or thrombin, whereas it only partially affected binding and aggregation of platelets from retinopathics. By using a monoclonal antibody (B59.2) to the platelet receptor for fibrinogen, we determined that this receptor was quantitatively and qualitatively the same on platelets from normal controls and diabetics. We conclude that increased fibrinogen binding and hyperaggregability of platelets from none-retinopathic diabetics is related to their capacity to form more prostaglandin endoperoxides/thromboxane than normal platelets. In contrast, hyperaggregability and increased binding of platelets from retinopathics appear at least partly related to a mechanism independent of ADP release and thromboxane synthesis. (Author)

  17. Characterization of binding of N'-nitrosonornicotine to protein

    International Nuclear Information System (INIS)

    Hughes, M.F.

    1986-01-01

    The NADPH-dependent activation of the carcinogenic nitrosamine, N'-nitrosonornicotine (NNN) to a reactive intermediate which binds covalently to protein was assessed using male Sprague-Dawley rat liver and lung microsomes. The NADPH-dependent covalent binding of [ 14 C]NNN to liver and lung microsomes was linear with time up to 90 and 45 min, respectively and was also linear with protein concentrations up to 3.0 and 2.0 mg/ml, respectively. The apparent K/sub m/ and V/sub max/ of the NADPH-dependent binding to liver microsomes were determined from the initial velocities. Addition of the thiols glutathione, cystein, N-acetylcysteine or 2-mercapthoethanol significantly decreased the non-NADPH-dependent binding to liver microsomal protein, but did not affect the NADPH-dependent binding. Glutathione was required in order to observe any NADPH-dependent binding to lung microsomal protein. In lung microsomes, SKF-525A significantly decreased the NADPH-dependent binding by 79%. Replacement of an air atmosphere with N 2 or CO:O 2 (8:2) significantly decreased the NADPH-dependent binding of [ 14 C]NNN to liver microsomal protein by 40% or 27% respectively. Extensive covalent binding of [ 14 C]NNN to liver and muscle microsomal protein occurred in the absence of an NADPH-generating system, in the presence of 50% methanol and also to bovine serum albumin, indicating a nonenzymatic reaction. These data indicate that cytochrome P-450 is at least in part responsible for the metabolic activation of the carcinogen NNN, but also suggest additional mechanisms of activation

  18. An effective suggestion method for keyword search of databases

    KAUST Repository

    Huang, Hai; Chen, Zonghai; Liu, Chengfei; Huang, He; Zhang, Xiangliang

    2016-01-01

    This paper solves the problem of providing high-quality suggestions for user keyword queries over databases. With the assumption that the returned suggestions are independent, existing query suggestion methods over databases score candidate

  19. Long chain fatty acids alter the interactive binding of ligands to the two principal drug binding sites of human serum albumin.

    Directory of Open Access Journals (Sweden)

    Keishi Yamasaki

    Full Text Available A wide variety of drugs bind to human serum albumin (HSA at its two principal sites, namely site I and site II. A number of reports indicate that drug binding to these two binding sites are not completely independent, and that interactions between ligands of these two discrete sites can play a role. In this study, the effect of the binding of long-chain fatty acids on the interactive binding between dansyl-L-asparagine (DNSA; site I ligand and ibuprofen (site II ligand at pH6.5 was examined. Binding experiments showed that the binding of sodium oleate (Ole to HSA induces conformational changes in the molecule, which, in turn, changes the individual binding of DNSA and ibuprofen, as well as the mode of interaction between these two ligands from a 'competitive-like' allosteric interaction in the case of the defatted HSA conformer to a 'nearly independent' binding in the case of non-defatted HSA conformer. Circular dichroism measurements indicated that ibuprofen and Ole are likely to modify the spatial orientation of DNSA at its binding site. Docking simulations suggest that the long-distance electric repulsion between DNSA and ibuprofen on defatted HSA contributes to a 'competitive-like' allosteric interaction, whereas extending the distance between ligands and/or increasing the flexibility or size of the DNSA binding site in fatted HSA evokes a change in the interaction mode to 'nearly independent' binding. The present findings provide further insights into the structural dynamics of HSA upon the binding of fatty acids, and its effects on drug binding and drug-drug interactions that occur on HSA.

  20. Development and characterization of 21 polymorphic microsatellite markers for the barren-ground shrew, Sorex ugyunak (Mammalia: Sorcidae), through next-generation sequencing, and cross-species amplification in the masked shrew, S. cinereus

    Science.gov (United States)

    Sonsthagen, Sarah A.; Sage, G. Kevin; Fowler, Megan C.; Hope, Andrew G.; Cook, J.A.; Talbot, Sandra L.

    2013-01-01

    We used next generation shotgun sequencing to develop 21 novel microsatellite markers for the barren-ground shrew (Sorex ugyunak), which were polymorphic among individuals from northern Alaska. The loci displayed moderate allelic diversity (averaging 6.81 alleles per locus) and heterozygosity (averaging 70 %). Two loci deviated from Hardy–Weinberg equilibrium (HWE) due to heterozygote deficiency. While the population did not deviate from HWE overall, it showed significant linkage disequilibrium suggesting this population is not in mutation-drift equilibrium. Nineteen of 21 loci were polymorphic in masked shrews (S. cinereus) from interior Alaska and exhibited linkage equilibrium and HWE overall. All loci yielded sufficient variability for use in population studies.

  1. Is high hypnotic suggestibility necessary for successful hypnotic pain intervention?

    Science.gov (United States)

    Milling, Leonard S

    2008-04-01

    Hypnotic suggestibility is a trait-like, individual difference variable reflecting the general tendency to respond to hypnosis and hypnotic suggestions. Research with standardized measures of hypnotic suggestibility has demonstrated that there are substantial individual differences in this variable. Higher suggestibility has been found to be associated with greater relief from hypnotic pain interventions. Although individuals in the high suggestibility range show the strongest response to hypnotic analgesia, people of medium suggestibility, who represent approximately one third of the population, also have been found to obtain significant relief from hypnosis. Thus, high hypnotic suggestibility is not necessary for successful hypnotic pain intervention. However, the available evidence does not support the efficacy of hypnotic pain interventions for people who fall in the low hypnotic suggestibility range. However, some studies suggest that these individuals may benefit from imaginative analgesia suggestions, or suggestions for pain reduction that are delivered while the person is not in hypnosis.

  2. Cation binding at the node of Ranvier: I. Localization of binding sites during development.

    Science.gov (United States)

    Zagoren, J C; Raine, C S; Suzuki, K

    1982-06-17

    Cations are known to bind to the node of Ranvier and the paranodal regions of myelinated fibers. The integrity of these specialized structures is essential for normal conduction. Sites of cation binding can be microscopically identified by the electrondense histochemical reaction product formed by the precipitate of copper sulfate/potassium ferrocyanide. This technique was used to study the distribution of cation binding during normal development of myelinating fibers. Sciatic nerves of C57B1 mice, at 1, 3, 5, 6, 7, 8, 9, 13, 16, 18, 24 and 30 days of age, were prepared for electron microscopy following fixation in phosphate-buffered 2.5% glutaraldehyde and 1% osmic acid, microdissection and incubation in phosphate-buffered 0.1 M cupric sulfate followed by 0.1 M potassium ferrocyanide. Localization of reaction product was studied by light and electron microscopy. By light microscopy, no reaction product was observed prior to 9 days of age. At 13 days, a few nodes and paranodes exhibited reaction product. This increased in frequency and intensity up to 30 days when almost all nodes or paranodes exhibited reaction product. Ultrastructurally, diffuse reaction product was first observed at 3 days of age in the axoplasm of the node, in the paranodal extracellular space of the terminal loops, in the Schwann cell proper and in the terminal loops of Schwann cell cytoplasm. When myelinated axons fulfilled the criteria for mature nodes, reaction product was no longer observed in the Schwann cell cytoplasm, while the intensity of reaction product in the nodal axoplasm and paranodal extracellular space of the terminal loops increased. Reaction product in the latter site appeared to be interrupted by the transverse bands. These results suggest that cation binding accompanies nodal maturity and that the Schwann cell may play a role in production or storage of the cation binding substance during myelinogenesis and development.

  3. A mosquito hemolymph odorant-binding protein family member specifically binds juvenile hormone

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Il Hwan; Pham, Van; Jablonka, Willy; Goodman, Walter G.; Ribeiro, José M. C.; Andersen, John F.

    2017-07-27

    Juvenile hormone (JH) is a key regulator of insect development and reproduction. In adult mosquitoes, it is essential for maturation of the ovary and normal male reproductive behavior, but how JH distribution and activity is regulated after secretion is unclear. Here, we report a new type of specific JH-binding protein, given the name mosquito juvenile hormone-binding protein (mJHBP), which circulates in the hemolymph of pupal and adult Aedes aegypti males and females. mJHBP is a member of the odorant-binding protein (OBP) family, and orthologs are present in the genomes of Aedes, Culex, and Anopheles mosquito species. Using isothermal titration calorimetry, we show that mJHBP specifically binds JH II and JH III but not eicosanoids or JH derivatives. mJHBP was crystallized in the presence of JH III and found to have a double OBP domain structure reminiscent of salivary “long” D7 proteins of mosquitoes. We observed that a single JH III molecule is contained in the N-terminal domain binding pocket that is closed in an apparent conformational change by a C-terminal domain-derived α-helix. The electron density for the ligand indicated a high occupancy of the natural 10R enantiomer of JH III. Of note, mJHBP is structurally unrelated to hemolymph JHBP from lepidopteran insects. A low level of expression of mJHBP in Ae. aegypti larvae suggests that it is primarily active during the adult stage where it could potentially influence the effects of JH on egg development, mating behavior, feeding, or other processes.

  4. A mosquito hemolymph odorant-binding protein family member specifically binds juvenile hormone.

    Science.gov (United States)

    Kim, Il Hwan; Pham, Van; Jablonka, Willy; Goodman, Walter G; Ribeiro, José M C; Andersen, John F

    2017-09-15

    Juvenile hormone (JH) is a key regulator of insect development and reproduction. In adult mosquitoes, it is essential for maturation of the ovary and normal male reproductive behavior, but how JH distribution and activity is regulated after secretion is unclear. Here, we report a new type of specific JH-binding protein, given the name mosquito juvenile hormone-binding protein (mJHBP), which circulates in the hemolymph of pupal and adult Aedes aegypti males and females. mJHBP is a member of the odorant-binding protein (OBP) family, and orthologs are present in the genomes of Aedes , Culex , and Anopheles mosquito species. Using isothermal titration calorimetry, we show that mJHBP specifically binds JH II and JH III but not eicosanoids or JH derivatives. mJHBP was crystallized in the presence of JH III and found to have a double OBP domain structure reminiscent of salivary "long" D7 proteins of mosquitoes. We observed that a single JH III molecule is contained in the N-terminal domain binding pocket that is closed in an apparent conformational change by a C-terminal domain-derived α-helix. The electron density for the ligand indicated a high occupancy of the natural 10 R enantiomer of JH III. Of note, mJHBP is structurally unrelated to hemolymph JHBP from lepidopteran insects. A low level of expression of mJHBP in Ae. aegypti larvae suggests that it is primarily active during the adult stage where it could potentially influence the effects of JH on egg development, mating behavior, feeding, or other processes.

  5. Binding energies of cluster ions

    International Nuclear Information System (INIS)

    Parajuli, R.; Matt, S.; Scheier, P.; Echt, O.; Stamatovic, A.; Maerk, T.D.

    2002-01-01

    The binding energy of charged clusters may be measured by analyzing the kinetic energy released in the metastable decay of mass selected parent ions. Using finite heat bath theory to determine the binding energies of argon, neon, krypton, oxygen and nitrogen from their respective average kinetic energy released were carried out. A high-resolution double focussing two-sector mass spectrometer of reversed Nier-Johnson type geometry was used. MIKE ( mass-analysed ion kinetic energy) were measured to investigate decay reactions of mass-selected ions. For the inert gases neon (Ne n + ), argon (Ar n + ) and krypton (Kr n + ), it is found that the binding energies initially decrease with increasing size n and then level off at a value above the enthalpy of vaporization of the condensed phase. Oxygen cluster ions shown a characteristic dependence on cluster size (U-shape) indicating a change in the metastable fragmentation mechanism when going from the dimer to the decamer ion. (nevyjel)

  6. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    for zinc binding by the investigated amino acids, peptides and proteins. The thiol group or imidazole group containing amino acids, peptides and proteins which exhibited strong zinc binding ability were further selected for interacting with zinc salts in relation to zinc absorption. The interactions...... between the above selected food components and zinc citrate or zinc phytate will lead to the enhanced solubility of zinc citrate or zinc phytate. The main driving force for this observed solubility enhancement is the complex formation between zinc and investigated food components as revealed by isothermal...... titration calorimetry and quantum mechanical calculations. This is due to the zinc binding affinity of the relatively softer ligands (investigated food components) will become much stronger than citrate or phytate when they present together in aqueous solution. This mechanism indicates these food components...

  7. GPIHBP1 Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding

    DEFF Research Database (Denmark)

    Beigneux, Anne P; Fong, Loren G; Bensadoun, Andre

    2015-01-01

    lacked the ability to bind LPL but had a reduced propensity for forming dimers or multimers, suggesting that W109 might play a more direct role in binding LPL. In support of that idea, replacing W109 with any of 8 other amino acids abolished LPL binding-and often did so without promoting the formation...

  8. Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways.

    Science.gov (United States)

    Fantl, W J; Escobedo, J A; Martin, G A; Turck, C W; del Rosario, M; McCormick, F; Williams, L T

    1992-05-01

    The receptor for platelet-derived growth factor (PDGF) binds two proteins containing SH2 domains, GTPase activating protein (GAP) and phosphatidylinositol 3-kinase (PI3-kinase). The sites on the receptor that mediate this interaction were identified by using phosphotyrosine-containing peptides representing receptor sequences to block specifically binding of either PI3-kinase or GAP. These results suggested that PI3-kinase binds two phosphotyrosine residues, each located in a 5 aa motif with an essential methionine at the fourth position C-terminal to the tyrosine. Point mutations at these sites caused a selective elimination of PI3-kinase binding and loss of PDGF-stimulated DNA synthesis. Mutation of the binding site for GAP prevented the receptor from associating with or phosphorylating GAP, but had no effect on PI3-kinase binding and little effect on DNA synthesis. Therefore, GAP and PI3-kinase interact with the receptor by binding to different phosphotyrosine-containing sequence motifs.

  9. Nuclear thyroid hormone receptors in rabbit heart: reduced triiodothyronine binding in atrium compared with ventricle

    International Nuclear Information System (INIS)

    Banerjee, S.K.; Ulrich, J.M.; Kaldor, G.J.

    1988-01-01

    Radiolabeled triiodothyronine (T3) binding to isolated nuclei was measured to compare the binding characteristics of the nuclear receptors in rabbit ventricular and atrial muscle cells. Scatchard analysis of the binding data yielded a maximum binding capacity of 170 +/- 20 fmol per mg DNA and apparent dissociation constant of 525 +/- 100 pM for ventricular nuclei. The binding capacity and the dissociation constant for the atrial muscle cell nuclei were 55 +/- 10 fmol per mg DNA and 500 +/- 75 pM, respectively. The results suggest that the binding capacity for T3 receptor in the atrium is considerably lower than that found in the ventricle. The reduced binding capacity of the T3 receptor in the atrium might reflect differences in the nuclear T3 receptors between ventricle and atrium

  10. GTP-dependent binding and nuclear transport of RNA polymerase II by Npa3 protein

    DEFF Research Database (Denmark)

    Staresincic, Lidija; Walker, Jane; Dirac-Svejstrup, A Barbara

    2011-01-01

    in yeast extracts. Indeed, Npa3 depletion in vivo affects nuclear localization of RNAPII; the polymerase accumulates in the cytoplasm. Npa3 is a member of the GPN-LOOP family of GTPases. Npa3 mutants that either cannot bind GTP or that bind but cannot hydrolyze it are inviable and unable to support nuclear...... transport of RNAPII. Surprisingly, we were unable to detect interactions between Npa3 and proteins in the classical importin a/ß pathway for nuclear import. Interestingly, Npa3-RNAPII binding is significantly increased by the addition of GTP or its slowly hydrolyzable analogue guanosine 5'-3-O......-(thio)triphosphate (GTP¿S). Moreover, the Npa3 mutant that binds GTP, but cannot hydrolyze it, binds RNAPII even in the absence of added GTP, whereas the mutant that cannot bind GTP is unable to bind the polymerase. Together, our data suggest that Npa3 defines an unconventional pathway for nuclear import of RNAPII, which...

  11. MARs Wars: heterogeneity and clustering of DNA-binding domains in the nuclear matrix

    Directory of Open Access Journals (Sweden)

    Ioudinkova E. S.

    2009-12-01

    Full Text Available Aim. CO326 is a chicken nuclear scaffold/matrix attachment region (MAR associated with the nuclear matrix in several types of chicken cells. It contains a binding site for a sequence-specific DNA-binding protein, F326. We have studied its interaction with the nuclear matrix. Methods. We have used an in vitro MAR assay with isolated matrices from chicken HD3 cells. Results. We have found that an oligonucleotide binding site for the F326 inhibits binding of the CO326 to the nuclear matrix. At the same time, the binding of heterologous MARs is enhanced. Conclusions. Taken together, these data suggest that there exist several classes of MARs and MAR-binding domains and that the MAR-binding proteins may be clustered in the nuclear matrix.

  12. On the Effects of Suggested Prices in Gasoline Markets

    NARCIS (Netherlands)

    R.P. Faber (Riemer); M.C.W. Janssen (Maarten)

    2008-01-01

    textabstractThis article analyzes the role of suggested prices in the Dutch retail market for gasoline. Suggested prices are announced by large oil companies with the suggestion that retailers follow them. There are at least two competing rationales for the existence of suggested prices: they may

  13. The Effect of Memory Trace Strength on Suggestibility.

    Science.gov (United States)

    Pezdek, Kathy; Roe, Chantal

    1995-01-01

    Examined the conditions under which children's memory is resistant to suggestibility versus vulnerable to suggestibility. Results suggest that children have more accurate memory for an event that occurred to them frequently, and that they are less vulnerable to suggestive influences such as biased interviewing procedures than they would be for an…

  14. Skyrmions with low binding energies

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, Mike, E-mail: m.n.gillard@leeds.ac.uk; Harland, Derek, E-mail: d.g.harland@leeds.ac.uk; Speight, Martin, E-mail: speight@maths.leeds.ac.uk

    2015-06-15

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  15. Skyrmions with low binding energies

    International Nuclear Information System (INIS)

    Gillard, Mike; Harland, Derek; Speight, Martin

    2015-01-01

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values

  16. Skyrmions with low binding energies

    Directory of Open Access Journals (Sweden)

    Mike Gillard

    2015-06-01

    Full Text Available Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  17. Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role.

    Science.gov (United States)

    Miklós, István; Zádori, Zoltán

    2012-02-01

    HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (pHD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs.

  18. Bindings in working memory: The role of object-based attention.

    Science.gov (United States)

    Gao, Zaifeng; Wu, Fan; Qiu, Fangfang; He, Kaifeng; Yang, Yue; Shen, Mowei

    2017-02-01

    Over the past decade, it has been debated whether retaining bindings in working memory (WM) requires more attention than retaining constituent features, focusing on domain-general attention and space-based attention. Recently, we proposed that retaining bindings in WM needs more object-based attention than retaining constituent features (Shen, Huang, & Gao, 2015, Journal of Experimental Psychology: Human Perception and Performance, doi: 10.1037/xhp0000018 ). However, only unitized visual bindings were examined; to establish the role of object-based attention in retaining bindings in WM, more emperical evidence is required. We tested 4 new bindings that had been suggested requiring no more attention than the constituent features in the WM maintenance phase: The two constituent features of binding were stored in different WM modules (cross-module binding, Experiment 1), from auditory and visual modalities (cross-modal binding, Experiment 2), or temporally (cross-time binding, Experiments 3) or spatially (cross-space binding, Experiments 4-6) separated. In the critical condition, we added a secondary object feature-report task during the delay interval of the change-detection task, such that the secondary task competed for object-based attention with the to-be-memorized stimuli. If more object-based attention is required for retaining bindings than for retaining constituent features, the secondary task should impair the binding performance to a larger degree relative to the performance of constituent features. Indeed, Experiments 1-6 consistently revealed a significantly larger impairment for bindings than for the constituent features, suggesting that object-based attention plays a pivotal role in retaining bindings in WM.

  19. Photoaffinity labelling of high affinity dopamine binding proteins

    International Nuclear Information System (INIS)

    Ross, G.M.; McCarry, B.E.; Mishra, R.K.

    1986-01-01

    A photoactive analogue of the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) has been synthesized and used to photoaffinity label dopamine binding proteins prepared from bovine caudate nucleus. N-(3-]N'-4-azidobenzamidol]-aminopropyl)-aminopropyl)-ADTN (AzB-AP-ADTN) was incubated with caudate membranes and irradiated with UV light. Membranes were then repeatedly washed by centrifugation to remove excess photolabel. A binding assay, using ( 3 H)-SCH 23390 (a D 1 specific antagonist), was then performed to evaluate the loss of receptor density in the photolyzed preparation. AzB-AP-ADTN irreversibly blocked ( 3 H)-SCH 23390 binding in a dose-dependent manner. Scatchard analysis revealed a decrease in the B/sub max/, with no significant change in the K/sub d/, of ( 3 H)-SCH 23390 binding. Compounds which compete for D 1 receptor binding (such as dopamine, SKF 38393 or apomorphine), proteted the SCH 23390 binding site from inactivation. This data would suggest that the novel photoaffinity ligand, AzB-AP-ADTN, can covalently label the D 1 (adenylate cyclase linked) dopamine receptor

  20. Specific binding of atrial natriuretic factor in brain microvessels

    International Nuclear Information System (INIS)

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-01-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using 125 I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of 125 I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function

  1. Dynamic binding of visual features by neuronal/stimulus synchrony.

    Science.gov (United States)

    Iwabuchi, A

    1998-05-01

    When people see a visual scene, certain parts of the visual scene are treated as belonging together and we regard them as a perceptual unit, which is called a "figure". People focus on figures, and the remaining parts of the scene are disregarded as "ground". In Gestalt psychology this process is called "figure-ground segregation". According to current perceptual psychology, a figure is formed by binding various visual features in a scene, and developments in neuroscience have revealed that there are many feature-encoding neurons, which respond to such features specifically. It is not known, however, how the brain binds different features of an object into a coherent visual object representation. Recently, the theory of binding by neuronal synchrony, which argues that feature binding is dynamically mediated by neuronal synchrony of feature-encoding neurons, has been proposed. This review article portrays the problem of figure-ground segregation and features binding, summarizes neurophysiological and psychophysical experiments and theory relevant to feature binding by neuronal/stimulus synchrony, and suggests possible directions for future research on this topic.

  2. Comparison of the ligand binding properties of two homologous rat apocellular retinol-binding proteins expressed in Escherichia coli.

    Science.gov (United States)

    Levin, M S; Locke, B; Yang, N C; Li, E; Gordon, J I

    1988-11-25

    Cellular retinol-binding protein (CRBP) and cellular retinol-binding protein II (CRBP II) are 132-residue cytosolic proteins which have 56% amino acid sequence identity and bind all-trans-retinol as their endogenous ligand. They belong to a family of cytoplasmic proteins which have evolved to bind distinct hydrophobic ligands. Their patterns of tissue-specific and developmental regulation are distinct. We have compared the ligand binding properties of rat apo-CRBP and apo-CRBP II that have been expressed in Escherichia coli. Several observations indicate that the E. coli-derived apoproteins are structurally similar to the native rat proteins: they co-migrate on isoelectric focusing gels; and when complexed with all-trans-retinol, their absorption and excitation/emission spectra are nearly identical to those of the authentic rat holoproteins. Comparative lifetime and acrylamide quenching studies suggest that there are differences in the conformations of apo-CRBP and apo-CRBP II. The interaction of E. coli-derived apo-CRBP and apo-CRBP II with a variety of retinoids was analyzed using spectroscopic techniques. Both apoproteins formed high affinity complexes with all-trans-retinol (K'd approximately 10 nM). In direct binding assays, all-trans-retinal bound to both apoproteins (K'd approximately 50 nM for CRBP; K'd approximately 90 nM for CRBP II). However, all-trans-retinal could displace all-trans-retinol bound to CRBP II but not to CRBP. These observations suggests that there is a specific yet distinct interaction between these two proteins and all-trans-retinal. Apo-CRBP and apo-CRBP II did not demonstrate significant binding to either retinoic acid or methyl retinoate, an uncharged derivative of all-trans-retinoic acid. This indicates that the carboxymethyl group of methyl retinoate cannot be sterically accommodated in their binding pockets and that failure to bind retinoic acid probably is not simply due to the negative charge of its C-15 carboxylate group

  3. Interactions of dopaminergic agonists and antagonists with dopaminergic D3 binding sites in rat striatum. Evidence that [3H]dopamine can label a high affinity agonist-binding state of the D1 dopamine receptor

    International Nuclear Information System (INIS)

    Leff, S.E.; Creese, I.

    1985-01-01

    The interactions of dopaminergic agonists and antagonists with 3 H-agonist labeled D3 dopaminergic binding sites of rat striatum have been characterized by radioligand-binding techniques. When the binding of [ 3 H]dopamine and [ 3 H]apomorphine to D2 dopamine receptors is blocked by the inclusion of D2 selective concentrations of unlabeled spiroperidol or domperidone, these ligands appear to label selectively the previously termed D3 binding site. Antagonist/[ 3 H]dopamine competition curves are of uniformly steep slope (nH . 1.0), suggesting the presence of a single D3 binding site. The relative potencies of antagonists to inhibit D3 specific [ 3 H]dopamine binding are significantly correlated with their potencies to block D1 dopamine receptors as measured by the inhibition of both dopamine-stimulated adenylate cyclase and [ 3 H]flupentixol-binding activities. The affinities of agonists to inhibit D3 specific [ 3 H]dopamine binding are also correlated with estimates of these agonists affinities for the high affinity binding component of agonist/[ 3 H]flupentixol competition curves. Both D3 specific [ 3 H] dopamine binding and the high affinity agonist-binding component of dopamine/[ 3 H]flupentixol competition curves show a similar sensitivity to guanine nucleotides. Taken together, these data strongly suggest that the D3 binding site is related to a high affinity agonist-binding state of the D1 dopamine receptor

  4. Demonstration of specific binding sites for 3H-RRR-alpha-tocopherol on human erythrocytes

    International Nuclear Information System (INIS)

    Kitabchi, A.E.; Wimalasena, J.

    1982-01-01

    Previous work from our laboratory demonstrated specific binding sites for 3 H-RRR-alpha-tocopherol ( 3 H-d alpha T) in membranes of rat adrenal cells. As tocopherol deficiency is associated with increased susceptibility of red blood cells to hemolysis, we investigated tocopherol binding sites in human RBCs. Erythrocytes were found to have specific binding sites for 3 H-d alpha T that exhibited saturability and time and cell-concentration dependence as well as reversibility of binding. Kinetic studies of binding demonstrated two binding sites--one with high affinity (Ka of 2.6 x 10(7) M-1), low capacity (7,600 sites per cell) and the other with low affinity (1.2 x 10(6) M-1), high capacity (150,000 sites per cell). In order to localize the binding sites further, RBCs were fractionated and greater than 90% of the tocopherol binding was located in the membranes. Similar to the findings in intact RBCs, the membranes exhibited two binding sites with a respective Ka of 3.3 x 10(7) M-1 and 1.5 x 10(6) M-1. Specificity data for binding demonstrated 10% binding for RRR-gamma-tocopherol, but not other tocopherol analog exhibited competition for 3 H-d alpha T binding sites. Instability data suggested a protein nature for these binding sites. Preliminary studies on Triton X-100 solubilized fractions resolved the binding sites to a major component with an Mr of 65,000 and a minor component with an Mr of 125,000. We conclude that human erythrocyte membranes contain specific binding sites for RRR-alpha-tocopherol. These sites may be of physiologic significance in the function of tocopherol on the red blood cell membrane

  5. Characterization of cap binding proteins associated with the nucleus

    International Nuclear Information System (INIS)

    Patzelt, E.

    1986-04-01

    Eucaryotic mRNAs a carry 7-methylguanosine triphosphate residue (called cap structure) at their 5' terminus. The cap plays an important role in RNA recognition. Cap binding proteins (CBP) of HeLa cells were identified by photoaffinity labelling using the cap analogue γ-( 32 P)-(4-(benzoyl-phenyl)methylamido)-7-methylguanosine-5'-triphosphate (BP-m 7 GTP). Photoreaction of this cap analogue with HeLa cell initiation factors resulted in specific labelling of two polypeptides of Msub(r) 37000 and 26000. The latter was also labelled in crude initiation factors prepared from reticulocytes and is identical to the cap binding protein CBP I previously identified. These cap binding proteins were also affinity labelled in poliovirus infected cell extracts. Photoaffinity reaction with BP-m 7 GTP of whole HeLa cell homogenate showed three additional polypeptides with Msub(r) 120000, 89000 and 80000. These cap binding proteins were found to be associated with the nucleus and are therefore referred to as nuclear cap binding proteins, i.e. NCBP 1, NCBP 2 and NCBP 3. They were also present in splicing extracts. Photoaffinity labelling in these nuclear extracts was differentially inhibited by various cap analogues and capped mRNAs. Affinity chromatography on immobilized globin mRNA led to a partial separation of the three nuclear cap binding proteins. Chromatography on m 7 GTP-Sepharose resulted in a specific binding of NCBP 3. The different behaviour of the cap binding proteins suggests that they are functionally distinct and that they might be involved in different processes requiring cap recognition. (Author)

  6. Cellulose binding domain fusion proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  7. When is protein binding important?

    Science.gov (United States)

    Heuberger, Jules; Schmidt, Stephan; Derendorf, Hartmut

    2013-09-01

    The present paper is an ode to a classic citation by Benet and Hoener (2002. Clin Pharm Ther 71(3):115-121). The now classic paper had a huge impact on drug development and the way the issue of protein binding is perceived and interpreted. Although the authors very clearly pointed out the limitations and underlying assumptions for their delineations, these are too often overlooked and the classic paper's message is misinterpreted by broadening to cases that were not intended. Some members of the scientific community concluded from the paper that protein binding is not important. This was clearly not intended by the authors, as they finished their paper with a paragraph entitled: "When is protein binding important?" Misinterpretation of the underlying assumptions in the classic work can result in major pitfalls in drug development. Therefore, we revisit the topic of protein binding with the intention of clarifying when clinically relevant changes should be considered during drug development. Copyright © 2013 Wiley Periodicals, Inc.

  8. A conserved chloramphenicol binding site at the entrance to the ribosomal peptide exit tunnel

    DEFF Research Database (Denmark)

    Long, Katherine S; Porse, Bo T

    2003-01-01

    , of E.coli 23S rRNA and G2084 (2058 in E.coli numbering) in domain V of H.halobium 23S rRNA. The modification sites overlap with a portion of the macrolide binding site and cluster at the entrance to the peptide exit tunnel. The data correlate with the recently reported chloramphenicol binding site...... on an archaeal ribosome and suggest that a similar binding site is present on the E.coli ribosome....

  9. Conservation of transcription factor binding events predicts gene expression across species

    OpenAIRE

    Hemberg, Martin; Kreiman, Gabriel

    2011-01-01

    Recent technological advances have made it possible to determine the genome-wide binding sites of transcription factors (TFs). Comparisons across species have suggested a relatively low degree of evolutionary conservation of experimentally defined TF binding events (TFBEs). Using binding data for six different TFs in hepatocytes and embryonic stem cells from human and mouse, we demonstrate that evolutionary conservation of TFBEs within orthologous proximal promoters is closely linked to funct...

  10. Suggestibility and signal detection performance in hallucination-prone students.

    Science.gov (United States)

    Alganami, Fatimah; Varese, Filippo; Wagstaff, Graham F; Bentall, Richard P

    2017-03-01

    Auditory hallucinations are associated with signal detection biases. We examine the extent to which suggestions influence performance on a signal detection task (SDT) in highly hallucination-prone and low hallucination-prone students. We also explore the relationship between trait suggestibility, dissociation and hallucination proneness. In two experiments, students completed on-line measures of hallucination proneness (the revised Launay-Slade Hallucination Scale; LSHS-R), trait suggestibility (Inventory of Suggestibility) and dissociation (Dissociative Experiences Scale-II). Students in the upper and lower tertiles of the LSHS-R performed an auditory SDT. Prior to the task, suggestions were made pertaining to the number of expected targets (Experiment 1, N = 60: high vs. low suggestions; Experiment 2, N = 62, no suggestion vs. high suggestion vs. no voice suggestion). Correlational and regression analyses indicated that trait suggestibility and dissociation predicted hallucination proneness. Highly hallucination-prone students showed a higher SDT bias in both studies. In Experiment 1, both bias scores were significantly affected by suggestions to the same degree. In Experiment 2, highly hallucination-prone students were more reactive to the high suggestion condition than the controls. Suggestions may affect source-monitoring judgments, and this effect may be greater in those who have a predisposition towards hallucinatory experiences.

  11. Structural requirements of cholesterol for binding to Vibrio cholerae hemolysin.

    Science.gov (United States)

    Ikigai, Hajime; Otsuru, Hiroshi; Yamamoto, Koichiro; Shimamura, Tadakatsu

    2006-01-01

    Cholesterol is necessary for the conversion of Vibrio cholerae hemolysin (VCH) monomers into oligomers in liposome membranes. Using different sterols, we determined the stereochemical structures of the VCH-binding active groups present in cholesterol. The VCH monomers are bound to cholesterol, diosgenin, campesterol, and ergosterol, which have a hydroxyl group at position C-3 (3betaOH) in the A ring and a C-C double bond between positions C-5 and C-6 (C-C Delta(5)) in the B ring. They are not bound to epicholesterol and dihydrocholesterol, which form a covalent link with a 3alphaOH group and a C-C single bond between positions C-5 and C-6, respectively. This result suggests that the 3betaOH group and the C-CDelta(5) bond in cholesterol are required for VCH monomer binding. We further examined VCH oligomer binding to cholesterol. However, this oligomer did not bind to cholesterol, suggesting that the disappearance of the cholesterol-binding potential of the VCH oligomer might be a result of the conformational change caused by the conversion of the monomer into the oligomer. VCH oligomer formation was observed in liposomes containing sterols with the 3betaOH group and the C-C Delta(5) bond, and it correlated with the binding affinity of the monomer to each sterol. Therefore, it seems likely that monomer binding to membrane sterol leads to the assembly of the monomer. However, since oligomer formation was induced by liposomes containing either epicholesterol or dihydrocholesterol, the 3betaOH group and the C-C Delta(5) bond were not essential for conversion into the oligomer.

  12. Covalent bindings in proteins following UV-C irradiation

    International Nuclear Information System (INIS)

    Diezel, W.; Meffert, H.; Soennichsen, N.; Reinicke, C.

    1980-01-01

    Following a UV-C irradiation of catalase cross-linked catalase subunits could be detected by sodium dodecylsulfate gel electrophoresis. The subunits of aldolase were not cross-linked. The origin of covalent bindings in the catalase molecule is suggested to be effected by a free radical chain reaction induced by the heme component of catalase after UV-C irradiation. (author)

  13. Mycobacterium smegmatis Ku binds DNA without free ends.

    Science.gov (United States)

    Kushwaha, Ambuj K; Grove, Anne

    2013-12-01

    Ku is central to the non-homologous end-joining pathway of double-strand-break repair in all three major domains of life, with eukaryotic homologues being associated with more diversified roles compared with prokaryotic and archaeal homologues. Ku has a conserved central 'ring-shaped' core domain. While prokaryotic homologues lack the N- and C-terminal domains that impart functional diversity to eukaryotic Ku, analyses of Ku from certain prokaryotes such as Pseudomonas aeruginosa and Mycobacterium smegmatis have revealed the presence of distinct C-terminal extensions that modulate DNA-binding properties. We report in the present paper that the lysine-rich C-terminal extension of M. smegmatis Ku contacts the core protein domain as evidenced by an increase in DNA-binding affinity and a decrease in thermal stability and intrinsic tryptophan fluorescence upon its deletion. Ku deleted for this C-terminus requires free DNA ends for binding, but translocates to internal DNA sites. In contrast, full-length Ku can directly bind DNA without free ends, suggesting that this property is conferred by its C-terminus. Such binding to internal DNA sites may facilitate recruitment to sites of DNA damage. The results of the present study also suggest that extensions beyond the shared core domain may have independently evolved to expand Ku function.

  14. Binding of intrinsic and extrinsic features in working memory.

    Science.gov (United States)

    Ecker, Ullrich K H; Maybery, Murray; Zimmer, Hubert D

    2013-02-01

    There is ongoing debate concerning the mechanisms of feature binding in working memory. In particular, there is controversy regarding the extent to which these binding processes are automatic. The present article demonstrates that binding mechanisms differ depending on whether the to-be-integrated features are perceived as forming a coherent object. We presented a series of experiments that investigated the binding of color and shape, whereby color was either an intrinsic feature of the shape or an extrinsic feature of the shape's background. Results show that intrinsic color affected shape recognition, even when it was incidentally studied and irrelevant for the recognition task. In contrast, extrinsic color did not affect shape recognition, even when the association of color and shape was encoded and retrievable on demand. This strongly suggests that binding of intrinsic intra-item information but not extrinsic contextual information is obligatory in visual working memory. We highlight links to perception as well as implicit and explicit long-term memory, which suggest that the intrinsic-extrinsic dimension is a principle relevant to multiple domains of human cognition. 2013 APA, all rights reserved

  15. Decorin binds myostatin and modulates its activity to muscle cells

    International Nuclear Information System (INIS)

    Miura, Takayuki; Kishioka, Yasuhiro; Wakamatsu, Jun-ichi; Hattori, Akihito; Hennebry, Alex; Berry, Carole J.; Sharma, Mridula; Kambadur, Ravi; Nishimura, Takanori

    2006-01-01

    Myostatin, a member of TGF-β superfamily of growth factors, acts as a negative regulator of skeletal muscle mass. The mechanism whereby myostatin controls the proliferation and differentiation of myogenic cells is mostly clarified. However, the regulation of myostatin activity to myogenic cells after its secretion in the extracellular matrix (ECM) is still unknown. Decorin, a small leucine-rich proteoglycan, binds TGF-β and regulates its activity in the ECM. Thus, we hypothesized that decorin could also bind to myostatin and participate in modulation of its activity to myogenic cells. In order to test the hypothesis, we investigated the interaction between myostatin and decorin by surface plasmon assay. Decorin interacted with mature myostatin in the presence of concentrations of Zn 2+ greater than 10 μM, but not in the absence of Zn 2+ . Kinetic analysis with a 1:1 binding model resulted in dissociation constants (K D ) of 2.02 x 10 -8 M and 9.36 x 10 -9 M for decorin and the core protein of decorin, respectively. Removal of the glycosaminoglycan chain by chondroitinase ABC digestion did not affect binding, suggesting that decorin could bind to myostatin with its core protein. Furthermore, we demonstrated that immobilized decorin could rescue the inhibitory effect of myostatin on myoblast proliferation in vitro. These results suggest that decorin could trap myostatin and modulate its activity to myogenic cells in the ECM

  16. Disorganized Cortical Patches Suggest Prenatal Origin of Autism

    Science.gov (United States)

    ... 2014 Disorganized cortical patches suggest prenatal origin of autism NIH-funded study shows disrupted cell layering process ... study suggests that brain irregularities in children with autism can be traced back to prenatal development. “While ...

  17. Correlates of the Gudjonsson Suggestibility Scale in delinquent adolescents.

    Science.gov (United States)

    Muris, Peter; Meesters, Cor; Merckelbach, Harald

    2004-02-01

    Correlations between scores on the Gudjonsson Suggestibility Scale and a number of relevant personality characteristics, i.e., intelligence, memory, social inadequacy, social desirability, and fantasy proneness, were examined in a sample of 71 delinquent boys. Analysis showed that intelligence and memory were negatively related to suggestibility scores. That is, lower memory and intelligence were associated with higher suggestibility. No significant correlations were found between suggestibility and other personality characteristics.

  18. A Consumer-Driven Approach To Increase Suggestive Selling.

    Science.gov (United States)

    Rohn, Don; Austin, John; Sanford, Alison

    2003-01-01

    Discussion of the effectiveness of behavioral interventions in improving suggestive selling behavior of sales staff focuses on a study that examined the efficacy of a consumer-driven approach to improve suggestive selling behavior of three employees of a fast food franchise. Reports that consumer-driven intervention increased suggestive selling…

  19. Clarification of the Memory Artefact in the Assessment of Suggestibility

    Science.gov (United States)

    Willner, P.

    2008-01-01

    Aim: The Gudjonsson Suggestibility Scale (GSS) assesses suggestibility by asking respondents to recall a short story, followed by exposure to leading questions and pressure to change their responses. Suggestibility, as assessed by the GSS, appears to be elevated in people with intellectual disabilities (ID). This has been shown to reflect to some…

  20. Binding of C-reactive protein to human polymorphonuclear leukocytes: evidence for association of binding sites with Fc receptors

    International Nuclear Information System (INIS)

    Mueller, H.; Fehr, J.

    1986-01-01

    The functional similarities between C-reactive protein (CRP) and IgG raised the question as to whether human phagocytes are stimulated by CRP in the same way as by binding of antigen-complexes or aggregated IgG to their Fc receptors. Studies with the use of highly purified 125 I-labeled CRP showed specific and saturable binding to human polymorphonuclear leukocytes (PNM) with a K/sub D/ of 10.5 +/- 5.7 x 10 -8 M only when carried out in heat-inactivated plasma. The number of specific binding sites per cell was estimated at 1 to 3 x 10 6 . Competitive inhibition of CRP binding by antigen-complexed or aggregated IgG suggests CRP binding sites to be associated IgG suggests CRP binding sites to be associated with PMN Fc receptors. Only when assayed in heat-inactivated plasma did CRP binding induce adherence of cells to tissue culture dishes. However, no metabolic and potentially cytotoxic simulation of PMN was detected during CRP plasma-dependent attachment to surfaces: induction of aggregation, release of secondary granule constituents, and activation of the hexose monophosphate pathway were not observed. These results imply that CRP-PMN interactions is dependent on an additional factor present in heat-inactivated plasma and is followed only by a complement-independent increase in PMN attachment to surfaces. Because CRP was found to be deposits at sites of tissue injury, the CRP-mediated adherence of PMN may be an important step in localizing an inflammatory focus

  1. Comparison of nicotinic receptor binding and biotransformation of coniine in the rat and chick.

    Science.gov (United States)

    Forsyth, C S; Speth, R C; Wecker, L; Galey, F D; Frank, A A

    1996-12-31

    Coniine, an alkaloid from Conium maculatum (poison hemlock), is a known teratogen in many domestic species with maternal ingestion resulting in arthrogryposis of the offspring. We have previously shown that rats are not susceptible and rabbits only weakly susceptible to coniine-induced arthrogryposis. However, the chick embryo does provide a reproducible laboratory animal model of coniine-induced teratogenesis. The reason for this cross-species variation is unknown. The purpose of this study was to evaluate coniine binding to nicotinic receptors and to measure coniine metabolism in vitro between susceptible and non-susceptible species. Using the chick model, neither the peripheral nicotinic receptor antagonist d-tubocurarine chloride nor the central nicotinic receptor antagonist trimethaphan camsylate blocked the teratogenesis or lethality of 1.5% coniine (50 microliters/egg). Trimethaphan camsylate enhanced coniine-induced lethality in a dose-dependent manner. Neither nicotinic receptor blocker prevented nicotine sulfate-induced malformations but d-tubocurarine chloride did block lethality in a dose-dependent manner. Competition by coniine for [125I]-alpha-bungarotoxin to nicotinic receptors isolated from adult rat diaphragm and chick thigh muscle and competition by coniine for [3H]-cytisine to receptors from rat and chick brain were used to assess coniine binding to nicotinic receptors. The IC50 for coniine in rat diaphragm was 314 microM while that for chick leg muscle was 70 microM. For neuronal nicotinic receptors, the IC50s of coniine for maternal rat brain, fetal rat brain, and chick brain were 1100 microM, 820 microM, and 270 microM, respectively. There were no differences in coniine biotransformation in vitro by microsomes from rat or chick livers. Differences in apparent affinity of coniine for nicotinic receptors or differences in the quantity of the nicotinic receptor between the rat and chick may explain, in part, the differences in susceptibility of

  2. The Cobalamin-binding Protein in Zebrafish is an Intermediate Between the Three Cobalamin-binding Proteins in Human

    DEFF Research Database (Denmark)

    Greibe, Eva Holm; Fedosov, Sergey; Nexø, Ebba

    2012-01-01

    are the oldest evolutionary derivatives followed by IF and HC (the latter being present only in reptiles and most but not all mammals). Our findings suggest that the only cobalamin-binding protein in zebrafish is an intermediate between the three human cobalamin binders. These findings support the hypothesis...

  3. Investigation of three flavonoids binding to bovine serum albumin using molecular fluorescence technique

    International Nuclear Information System (INIS)

    Bi Shuyun; Yan Lili; Pang Bo; Wang Yu

    2012-01-01

    The three flavonoids including naringenin, hesperetin and apigenin binding to bovine serum albumin (BSA) at pH 7.4 was studied by fluorescence quenching, synchronous fluorescence and UV-vis absorption spectroscopic techniques. The results obtained revealed that naringenin, hesperetin and apigenin strongly quenched the intrinsic fluorescence of BSA. The Stern-Volmer curves suggested that these quenching processes were all static quenching processes. At 291 K, the value and the order of the binding constant were K A n aringenin) =4.08x10 4 A(hesperetin) =5.40x10 4 ∼K A(apigenin) =5.32x10 4 L mol -1 . The main binding force between the flavonoid and BSA was hydrophobic and electrostatic force. According to the Foerster theory of non-radiation energy transfer, the binding distances (r 0 ) were obtained as 3.36, 3.47 and 3.30 nm for naringenin-BSA, hesperetin-BSA and apigenin-BSA, respectively. The effect of some common ions such as Fe 3+ , Cu 2+ , Mg 2+ , Mn 2+ , Zn 2+ and Ca 2+ on the binding was also studied in detail. The competition binding was also performed. The apparent binding constant (K' A ) obtained suggested that one flavonoid had an obvious effect on the binding of another flavonoid to protein when they coexisted in BSA solution. - Highlights: → Quenchings of BSA fluorescence by the flavonoids was all static quenchings. → Synchronous fluorescence was applied to study the structural change of BSA. → Binding constant, binding site and binding force were determined. → Competition binding experiments were performed. → One flavonoid had an obvious effect on the binding of another one to BSA.

  4. A peek into tropomyosin binding and unfolding on the actin filament.

    Directory of Open Access Journals (Sweden)

    Abhishek Singh

    Full Text Available BACKGROUND: Tropomyosin is a prototypical coiled coil along its length with subtle variations in structure that allow interactions with actin and other proteins. Actin binding globally stabilizes tropomyosin. Tropomyosin-actin interaction occurs periodically along the length of tropomyosin. However, it is not well understood how tropomyosin binds actin. PRINCIPAL FINDINGS: Tropomyosin's periodic binding sites make differential contributions to two components of actin binding, cooperativity and affinity, and can be classified as primary or secondary sites. We show through mutagenesis and analysis of recombinant striated muscle alpha-tropomyosins that primary actin binding sites have a destabilizing coiled-coil interface, typically alanine-rich, embedded within a non-interface recognition sequence. Introduction of an Ala cluster in place of the native, more stable interface in period 2 and/or period 3 sites (of seven increased the affinity or cooperativity of actin binding, analysed by cosedimentation and differential scanning calorimetry. Replacement of period 3 with period 5 sequence, an unstable region of known importance for cooperative actin binding, increased the cooperativity of binding. Introduction of the fluorescent probe, pyrene, near the mutation sites in periods 2 and 3 reported local instability, stabilization by actin binding, and local unfolding before or coincident with dissociation from actin (measured using light scattering, and chain dissociation (analyzed using circular dichroism. CONCLUSIONS: This, and previous work, suggests that regions of tropomyosin involved in binding actin have non-interface residues specific for interaction with actin and an unstable interface that is locally stabilized upon binding. The destabilized interface allows residues on the coiled-coil surface to obtain an optimal conformation for interaction with actin by increasing the number of local substates that the side chains can sample. We suggest

  5. Calculation of protein-ligand binding affinities.

    Science.gov (United States)

    Gilson, Michael K; Zhou, Huan-Xiang

    2007-01-01

    Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

  6. Penicillin-binding proteins in Actinobacteria.

    Science.gov (United States)

    Ogawara, Hiroshi

    2015-04-01

    Because some Actinobacteria, especially Streptomyces species, are β-lactam-producing bacteria, they have to have some self-resistant mechanism. The β-lactam biosynthetic gene clusters include genes for β-lactamases and penicillin-binding proteins (PBPs), suggesting that these are involved in self-resistance. However, direct evidence for the involvement of β-lactamases does not exist at the present time. Instead, phylogenetic analysis revealed that PBPs in Streptomyces are distinct in that Streptomyces species have much more PBPs than other Actinobacteria, and that two to three pairs of similar PBPs are present in most Streptomyces species examined. Some of these PBPs bind benzylpenicillin with very low affinity and are highly similar in their amino-acid sequences. Furthermore, other low-affinity PBPs such as SCLAV_4179 in Streptomyces clavuligerus, a β-lactam-producing Actinobacterium, may strengthen further the self-resistance against β-lactams. This review discusses the role of PBPs in resistance to benzylpenicillin in Streptomyces belonging to Actinobacteria.

  7. An effective suggestion method for keyword search of databases

    KAUST Repository

    Huang, Hai

    2016-09-09

    This paper solves the problem of providing high-quality suggestions for user keyword queries over databases. With the assumption that the returned suggestions are independent, existing query suggestion methods over databases score candidate suggestions individually and return the top-k best of them. However, the top-k suggestions have high redundancy with respect to the topics. To provide informative suggestions, the returned k suggestions are expected to be diverse, i.e., maximizing the relevance to the user query and the diversity with respect to topics that the user might be interested in simultaneously. In this paper, an objective function considering both factors is defined for evaluating a suggestion set. We show that maximizing the objective function is a submodular function maximization problem subject to n matroid constraints, which is an NP-hard problem. An greedy approximate algorithm with an approximation ratio O((Formula presented.)) is also proposed. Experimental results show that our suggestion outperforms other methods on providing relevant and diverse suggestions. © 2016 Springer Science+Business Media New York

  8. Placebo-suggestion modulates conflict resolution in the Stroop Task.

    Directory of Open Access Journals (Sweden)

    Pedro A Magalhães De Saldanha da Gama

    Full Text Available Here, we ask whether placebo-suggestion (without any form of hypnotic induction can modulate the resolution of cognitive conflict. Naïve participants performed a Stroop Task while wearing an EEG cap described as a "brain wave" machine. In Experiment 1, participants were made to believe that the EEG cap would either enhance or decrease their color perception and performance on the Stroop task. In Experiment 2, participants were explicitly asked to imagine that their color perception and performance would be enhanced or decreased (non-hypnotic imaginative suggestion. We observed effects of placebo-suggestion on Stroop interference on accuracy: interference was decreased with positive suggestion and increased with negative suggestion compared to baseline. Intra-individual variability was also increased under negative suggestion compared to baseline. Compliance with the instruction to imagine a modulation of performance, on the other hand, did not influence accuracy and only had a negative impact on response latencies and on intra-individual variability, especially in the congruent condition of the Stroop Task. Taken together, these results demonstrate that expectations induced by a placebo-suggestion can modulate our ability to resolve cognitive conflict, either facilitating or impairing response accuracy depending on the suggestion's contents. Our results also demonstrate a dissociation between placebo-suggestion and non-hypnotic imaginative suggestion.

  9. A non-multimacrocyclic heteroditopic receptor that cooperatively binds and effectively extracts KAcO salt.

    Science.gov (United States)

    Zakrzewski, Maciej; Kwietniewska, Natalia; Walczak, Wojciech; Piątek, Piotr

    2018-06-06

    Prepared in only three synthetic steps, a non-multimacrocyclic heteroditopic receptor binds potassium salts of halides and carboxylates with unusually high cooperativity, suggesting salt binding as associated ion-pairs. Unprecedented extraction of highly hydrophilic KAcO salt from water to organic solution is also demonstrated.

  10. Validity of a Test of Children's Suggestibility for Predicting Responses to Two Interview Situations Differing in Their Degree of Suggestiveness.

    Science.gov (United States)

    Finnila, Katarina; Mahlberg, Nina; Santtila, Pekka; Sandnabba, Kenneth; Niemi, Pekka

    2003-01-01

    Examined the relative contributions of internal and external sources of variation in children's suggestibility in interrogative situations. Found that internal sources of individual differences in suggestibility measured on a suggestibility test did influence children's answers during an interview, but that external sources or interview styles had…

  11. Probing protein phosphatase substrate binding

    DEFF Research Database (Denmark)

    Højlys-Larsen, Kim B.; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen

    2012-01-01

    Proteomics and high throughput analysis for systems biology can benefit significantly from solid-phase chemical tools for affinity pull-down of proteins from complex mixtures. Here we report the application of solid-phase synthesis of phosphopeptides for pull-down and analysis of the affinity...... profile of the integrin-linked kinase associated phosphatase (ILKAP), a member of the protein phosphatase 2C (PP2C) family. Phosphatases can potentially dephosphorylate these phosphopeptide substrates but, interestingly, performing the binding studies at 4 °C allowed efficient binding to phosphopeptides......, without the need for phosphopeptide mimics or phosphatase inhibitors. As no proven ILKAP substrates were available, we selected phosphopeptide substrates among known PP2Cδ substrates including the protein kinases: p38, ATM, Chk1, Chk2 and RSK2 and synthesized directly on PEGA solid supports through a BAL...

  12. Human plasminogen binding protein tetranectin

    DEFF Research Database (Denmark)

    Kastrup, J S; Rasmussen, H; Nielsen, B B

    1997-01-01

    The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals...... to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates...

  13. Metacognition of agency is reduced in high hypnotic suggestibility.

    Science.gov (United States)

    Terhune, Devin B; Hedman, Love R A

    2017-11-01

    A disruption in the sense of agency is the primary phenomenological feature of response to hypnotic suggestions but its cognitive basis remains elusive. Here we tested the proposal that distorted volition during response to suggestions arises from poor metacognition pertaining to the sources of one's control. Highly suggestible and control participants completed a motor task in which performance was reduced through surreptitious manipulations of cursor lag and stimuli speed. Highly suggestible participants did not differ from controls in performance or metacognition of performance, but their sense of agency was less sensitive to cursor lag manipulations, suggesting reduced awareness that their control was being manipulated. These results indicate that highly suggestible individuals have aberrant metacognition of agency and may be a valuable population for studying distortions in the sense of agency. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Comprehensive human transcription factor binding site map for combinatory binding motifs discovery.

    Directory of Open Access Journals (Sweden)

    Arnoldo J Müller-Molina

    Full Text Available To know the map between transcription factors (TFs and their binding sites is essential to reverse engineer the regulation process. Only about 10%-20% of the transcription factor binding motifs (TFBMs have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory "DNA words." From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%-far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of "DNA words," newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters.

  15. Mitarbeiteranreizsysteme und Innovationserfolg (Employee suggestion schemes and innovation success)

    OpenAIRE

    Czarnitzki, Dirk; Kraft, Kornelius

    2008-01-01

    "We discuss the determinants of a successful implementation of an employee suggestion scheme and other measures to stimulate innovation success. Subsequently the effects of the employee suggestion schemes are investigated empirically. We analyse the realisation of cost reductions and alternatively sales expansion due to quality improvements. It turns out that employee suggestion schemes have a positive effect on cost efficiency and sales growth. Delegation of decision authority reduces produc...

  16. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  17. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    James, W.P.T.; Branch, W.J.; Southgate, D.A.T.

    1978-01-01

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  18. Binding of resveratrol with sodium caseinate in aqueous solutions.

    Science.gov (United States)

    Acharya, Durga P; Sanguansri, Luz; Augustin, Mary Ann

    2013-11-15

    The interaction between resveratrol (Res) and sodium caseinate (Na-Cas) has been studied by measuring fluorescence quenching of the protein by resveratrol. Quenching constants were determined using Stern-Volmer equation, which suggests that both dynamic and static quenching occur between Na-Cas and Res. Binding constants for the complexation between Na-Cas and Res were determined at different temperatures. The large binding constants (3.7-5.1×10(5)M(-1)) suggest that Res has strong affinity for Na-Cas. This affinity decreases as the temperature is raised from 25 to 37°C. The binding involves both hydrogen bonding and hydrophobic interaction, as suggested by negative enthalpy change and positive entropy change for the binding reaction. The present study indicates that Na-Cas, a common food protein, may be used as a carrier of Res, a bioactive polyphenol which is insoluble in both water and oils. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Clarification of the memory artefact in the assessment of suggestibility.

    Science.gov (United States)

    Willner, P

    2008-04-01

    The Gudjonsson Suggestibility Scale (GSS) assesses suggestibility by asking respondents to recall a short story, followed by exposure to leading questions and pressure to change their responses. Suggestibility, as assessed by the GSS, appears to be elevated in people with intellectual disabilities (ID). This has been shown to reflect to some extent the fact that people with ID have poor recall of the story; however, there are discrepancies in this relationship. The aim of the present study was to investigate whether a closer match between memory and suggestibility would be found using a measure of recognition memory rather than free recall. Three modifications to the procedure were presented to users of a learning disabilities day service. In all three experiments, a measure of forced-choice recognition memory was built into the suggestibility test. In experiments 1 and 2, the GSS was presented using either divided presentation (splitting the story into two halves, with memory and suggestibility tests after each half) or multiple presentation (the story was presented three times before presentation of the memory and suggestibility tests). Participants were tested twice, once with the standard version of the test and once with one of the modified versions. In experiment 3, an alternative suggestibility scale (ASS3) was created, based on real events in a learning disabilities day service. The ASS3 was presented to one group of participants who had been present at the events, and a second group who attended a different day service, to whom the events were unfamiliar. As observed previously, suggestibility was not closely related to free recall performance: recall was increased equally by all three manipulations, but they produced, respectively, no effect, a modest effect and a large effect on suggestibility. However, the effects on suggestibility were closely related to performance on the forced-choice recognition memory task: divided presentation of the GSS2 had no

  20. A parallel form of the Gudjonsson Suggestibility Scale.

    Science.gov (United States)

    Gudjonsson, G H

    1987-09-01

    The purpose of this study is twofold: (1) to present a parallel form of the Gudjonsson Suggestibility Scale (GSS, Form 1); (2) to study test-retest reliabilities of interrogative suggestibility. Three groups of subjects were administered the two suggestibility scales in a counterbalanced order. Group 1 (28 normal subjects) and Group 2 (32 'forensic' patients) completed both scales within the same testing session, whereas Group 3 (30 'forensic' patients) completed the two scales between one week and eight months apart. All the correlations were highly significant, giving support for high 'temporal consistency' of interrogative suggestibility.

  1. Treating ADHD With Suggestion: Neurofeedback and Placebo Therapeutics.

    Science.gov (United States)

    Thibault, Robert T; Veissière, Samuel; Olson, Jay A; Raz, Amir

    2018-06-01

    We propose that clinicians can use suggestion to help treat conditions such as ADHD. We use EEG neurofeedback as a case study, alongside evidence from a recent pilot experiment utilizing a sham MRI scanner to highlight the therapeutic potential of suggestion-based treatments. The medical literature demonstrates that many practitioners already prescribe treatments that hardly outperform placebo comparators. Moreover, the sham MRI experiment showed that, even with full disclosure of the procedure, suggestion alone can reduce the symptomatology of ADHD. Non-deceptive suggestion-based treatments, especially those drawing on accessories from neuroscience, may offer a safe complement and potential alternative to current standard of care for individuals with ADHD.

  2. Dissociative tendencies and individual differences in high hypnotic suggestibility.

    Science.gov (United States)

    Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

    2011-03-01

    Inconsistencies in the relationship between dissociation and hypnosis may result from heterogeneity among highly suggestible individuals, in particular the existence of distinct highly suggestible subtypes that are of relevance to models of psychopathology and the consequences of trauma. This study contrasted highly suggestible subtypes high or low in dissociation on measures of hypnotic responding, cognitive functioning, and psychopathology. Twenty-one low suggestible (LS), 19 low dissociative highly suggestible (LDHS), and 11 high dissociative highly suggestible (HDHS) participants were administered hypnotic suggestibility scales and completed measures of free recall, working memory capacity, imagery, fantasy-proneness, psychopathology, and exposure to stressful life events. HDHS participants were more responsive to positive and negative hallucination suggestions and experienced greater involuntariness during hypnotic responding. They also exhibited impaired working memory capacity, elevated pathological fantasy and dissociative symptomatology, and a greater incidence of exposure to stressful life events. In contrast, LDHS participants displayed superior object visual imagery. These results provide further evidence for two highly suggestible subtypes: a dissociative subtype characterised by deficits in executive functioning and a predisposition to psychopathology, and a subtype that exhibits superior imagery and no observable deficits in functioning.

  3. Evidence for a non-opioid sigma binding site din the guinea-pig myenteric plexus

    International Nuclear Information System (INIS)

    Roman, F.; Pascaud, X.; Vauche, D.; Junien, J.

    1988-01-01

    The presence of a binding site to (+)-( 3 H)SKF 10,047 was demonstrated in a guinea-pig myenteric plexus (MYP) membrane preparation. Specific binding to this receptor was saturable, reversible, linear with protein concentration and consisted of two components, a high affinity site and a low affinity site. Morphine and naloxone 10 -4 M were unable to displace (+)-( 3 H)SKF 10,047 binding. Haloperidol, imipramine, ethylketocyclazocine and propranolol were among the most potent compounds to inhibit this specific binding. These results suggest the presence of a non-opioid haloperidol sensitive sigma receptor in the MYP of the guinea-pig

  4. The Collagen-Binding Adhesin Is a Virulence Factor in Staphylococcus aureus Keratitis

    Science.gov (United States)

    Rhem, Marcus N.; Lech, Elizabeth M.; Patti, Joseph M.; McDevitt, Damien; Höök, Magnus; Jones, Dan B.; Wilhelmus, Kirk R.

    2000-01-01

    A collagen-binding strain of Staphylococcus aureus produced suppurative inflammation in a rabbit model of soft contact lens-associated bacterial keratitis more often than its collagen-binding-negative isogenic mutant. Reintroduction of the cna gene on a multicopy plasmid into the mutant helped it regain its corneal adherence and infectivity. The topical application of a collagen-binding peptide before bacterial challenge decreased S. aureus adherence to deepithelialized corneas. These data suggest that the collagen-binding adhesin is involved in the pathogenesis of S. aureus infection of the cornea. PMID:10816547

  5. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  6. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  7. Anion binding in biological systems

    International Nuclear Information System (INIS)

    Feiters, Martin C; Meyer-Klaucke, Wolfram; Kostenko, Alexander V; Soldatov, Alexander V; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Kuepper, Frithjof C; Hollenstein, Kaspar; Locher, Kaspar P; Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R

    2009-01-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L 3 (2p 3/2 ) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  8. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  9. Cross-species amplification of human microsatellite markers in pig ...

    Indian Academy of Sciences (India)

    Author Affiliations. Sapna Godavarthi1 Archana Jayaraman1 Ajay Gaur1. Laboratory for the Conservation of Endangered Species (LaCONES), Centre for Cellular and Molecular Biology Annexe 1, Attapur, Hyderabad 500 048, India ...

  10. Cross-species applicability of chicken microsatellite markers for ...

    African Journals Online (AJOL)

    We obtained blood samples of 57 Indian ducks (Anas platyrhynchos) belonging to three indigenous duck populations of geographically distinct locations of the country and genotyped them using chicken microsatellite markers. Twenty three of the 30 loci were amplified and 17 loci yielded high success rate (> 91%).

  11. Superior Cross-Species Reference Genes: A Blueberry Case Study

    Science.gov (United States)

    Die, Jose V.; Rowland, Lisa J.

    2013-01-01

    The advent of affordable Next Generation Sequencing technologies has had major impact on studies of many crop species, where access to genomic technologies and genome-scale data sets has been extremely limited until now. The recent development of genomic resources in blueberry will enable the application of high throughput gene expression approaches that should relatively quickly increase our understanding of blueberry physiology. These studies, however, require a highly accurate and robust workflow and make necessary the identification of reference genes with high expression stability for correct target gene normalization. To create a set of superior reference genes for blueberry expression analyses, we mined a publicly available transcriptome data set from blueberry for orthologs to a set of Arabidopsis genes that showed the most stable expression in a developmental series. In total, the expression stability of 13 putative reference genes was evaluated by qPCR and a set of new references with high stability values across a developmental series in fruits and floral buds of blueberry were identified. We also demonstrated the need to use at least two, preferably three, reference genes to avoid inconsistencies in results, even when superior reference genes are used. The new references identified here provide a valuable resource for accurate normalization of gene expression in Vaccinium spp. and may be useful for other members of the Ericaceae family as well. PMID:24058469

  12. Superior cross-species reference genes: a blueberry case study.

    Directory of Open Access Journals (Sweden)

    Jose V Die

    Full Text Available The advent of affordable Next Generation Sequencing technologies has had major impact on studies of many crop species, where access to genomic technologies and genome-scale data sets has been extremely limited until now. The recent development of genomic resources in blueberry will enable the application of high throughput gene expression approaches that should relatively quickly increase our understanding of blueberry physiology. These studies, however, require a highly accurate and robust workflow and make necessary the identification of reference genes with high expression stability for correct target gene normalization. To create a set of superior reference genes for blueberry expression analyses, we mined a publicly available transcriptome data set from blueberry for orthologs to a set of Arabidopsis genes that showed the most stable expression in a developmental series. In total, the expression stability of 13 putative reference genes was evaluated by qPCR and a set of new references with high stability values across a developmental series in fruits and floral buds of blueberry were identified. We also demonstrated the need to use at least two, preferably three, reference genes to avoid inconsistencies in results, even when superior reference genes are used. The new references identified here provide a valuable resource for accurate normalization of gene expression in Vaccinium spp. and may be useful for other members of the Ericaceae family as well.

  13. A Plea for Cross-species Social Neuroscience

    NARCIS (Netherlands)

    Keysers, Christian; Gazzola, Valeria

    2017-01-01

    Over the past two decades, the question of how our brain makes us sensitive to the state of conspecifics and how that affects our behaviour has undergone a profound change. Twenty years ago what would now be called social neuroscience was focused on the visual processing of facial expressions and

  14. Cross-species amplification of microsatellites in genera ...

    Indian Academy of Sciences (India)

    species in Chinese freshwater polyculture system. Accord- ing to several recent ... cephala transcriptome database were chosen to test their utility for ..... 2012BAD26B00) and Fundamental Research Funds for the Central. Universities (no.

  15. Ethical perception of cross-species gene transfer in plant

    African Journals Online (AJOL)

    Jane

    2011-09-30

    Sep 30, 2011 ... The research finding is useful to understand the social construct of the ethical ... periconceptional use of supplements to combat nutrient deficiencies in such area ... among the Malaysian public in the Klang Valley region and to compare ... policy makers, NGOs, media, religious scholars, university students.

  16. Phenotype ontologies and cross-species analysis for translational research.

    Directory of Open Access Journals (Sweden)

    Peter N Robinson

    2014-04-01

    Full Text Available The use of model organisms as tools for the investigation of human genetic variation has significantly and rapidly advanced our understanding of the aetiologies underlying hereditary traits. However, while equivalences in the DNA sequence of two species may be readily inferred through evolutionary models, the identification of equivalence in the phenotypic consequences resulting from comparable genetic variation is far from straightforward, limiting the value of the modelling paradigm. In this review, we provide an overview of the emerging statistical and computational approaches to objectively identify phenotypic equivalence between human and model organisms with examples from the vertebrate models, mouse and zebrafish. Firstly, we discuss enrichment approaches, which deem the most frequent phenotype among the orthologues of a set of genes associated with a common human phenotype as the orthologous phenotype, or phenolog, in the model species. Secondly, we introduce and discuss computational reasoning approaches to identify phenotypic equivalences made possible through the development of intra- and interspecies ontologies. Finally, we consider the particular challenges involved in modelling neuropsychiatric disorders, which illustrate many of the remaining difficulties in developing comprehensive and unequivocal interspecies phenotype mappings.

  17. Assembled cross-species perchlorate dose-response data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set contains dose-response data for perchlorate exposure in multiple species. These data were assembled from peer-reviewed studies. Species included in...

  18. Echinococcus granulosus fatty acid binding proteins subcellular localization.

    Science.gov (United States)

    Alvite, Gabriela; Esteves, Adriana

    2016-05-01

    Two fatty acid binding proteins, EgFABP1 and EgFABP2, were isolated from the parasitic platyhelminth Echinococcus granulosus. These proteins bind fatty acids and have particular relevance in flatworms since de novo fatty acids synthesis is absent. Therefore platyhelminthes depend on the capture and intracellular distribution of host's lipids and fatty acid binding proteins could participate in lipid distribution. To elucidate EgFABP's roles, we investigated their intracellular distribution in the larval stage by a proteomic approach. Our results demonstrated the presence of EgFABP1 isoforms in cytosolic, nuclear, mitochondrial and microsomal fractions, suggesting that these molecules could be involved in several cellular processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cholinergic receptor binding in the frontal cortex of suicide victims

    International Nuclear Information System (INIS)

    Stanley, M.

    1986-01-01

    Because there is a high incidence of individuals diagnosed as having an affective disorder who subsequently commit suicide, the author thought it would be of interest to determine QNB binding in the brains of a large sample of suicide victims, and to compare the findings with a well-matched control group. Brain samples were obtained at autopsy from 22 suicide victims and 22 controls. Frontal cortex samples were diseected, frozen, and stored until assayed. Samples of tissue homogenate were incubated in duplicate with 10 concentrations of tritium-QNB. Specific binding was determined with and without atropine. The results confirmed previous studies in which no changes were noted in suicide versus control brains. While the findings neither disprove nor support the cholinergic hypothesis of depression, they do suggest that the neurochemical basis for the in vivo observations of increased responsivity of depressed individuals to muscarinic cholinergic agents might not involve changes in receptors estimated by QNB binding

  20. Binding of Serotonin to Lipid Membranes

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Wang, Chunhua; Cruys-Bagger, Nicolaj

    2013-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a prevalent neurotransmitter throughout the animal kingdom. It exerts its effect through the specific binding to the serotonin receptor, but recent research has suggested that neural transmission may also be affected by its nonspecific interactions...... with the lipid matrix of the synaptic membrane. However, membrane–5-HT interactions remain controversial and superficially investigated. Fundamental knowledge of this interaction appears vital in discussions of putative roles of 5-HT, and we have addressed this by thermodynamic measurements and molecular...... dynamics (MD) simulations. 5-HT was found to interact strongly with lipid bilayers (partitioning coefficient ∼1200 in mole fraction units), and this is highly unusual for a hydrophilic solute like 5-HT which has a bulk, oil–water partitioning coefficient well below unity. It follows that membrane affinity...

  1. SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G.

    Science.gov (United States)

    Bergmann, Simone; Eichhorn, Inga; Kohler, Thomas P; Hammerschmidt, Sven; Goldmann, Oliver; Rohde, Manfred; Fulde, Marcus

    2017-01-01

    The M protein of Streptococcus canis (SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particular S. canis isolate to bind to IgG significantly correlates with a scm -positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S. gordonii and Western Blot analysis with purified recombinant SCM proteins confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM-IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and goats. Similar to other streptococcal IgG-binding proteins, the interaction between SCM and IgG occurs via the conserved Fc domain and is, therefore, non-opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial surface specifically prevents opsonization by C1q, which might constitute another anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of different truncated SCM fragments defined a region of 52 amino acids located in the central part of the mature SCM protein which is important for IgG binding. This binding region is highly conserved among SCM proteins derived from different S. canis isolates but differs significantly from IgG-Fc receptors of S. pyogenes and S. dysgalactiae sub. equisimilis , respectively. In summary, we present an additional role of SCM in the pathogen-host interaction of S. canis . The detailed analysis of the SCM-IgG interaction should contribute to a better understanding of the complex roles of M proteins in streptococcal pathogenesis.

  2. Neurogranin alters the structure and calcium binding properties of calmodulin.

    Science.gov (United States)

    Hoffman, Laurel; Chandrasekar, Anuja; Wang, Xu; Putkey, John A; Waxham, M Neal

    2014-05-23

    Neurogranin (Ng) is a member of the IQ motif class of calmodulin (CaM)-binding proteins, and interactions with CaM are its only known biological function. In this report we demonstrate that the binding affinity of Ng for CaM is weakened by Ca(2+) but to a lesser extent (2-3-fold) than that previously suggested from qualitative observations. We also show that Ng induced a >10-fold decrease in the affinity of Ca(2+) binding to the C-terminal domain of CaM with an associated increase in the Ca(2+) dissociation rate. We also discovered a modest, but potentially important, increase in the cooperativity in Ca(2+) binding to the C-lobe of CaM in the presence of Ng, thus sharpening the threshold for the C-domain to become Ca(2+)-saturated. Domain mapping using synthetic peptides indicated that the IQ motif of Ng is a poor mimetic of the intact protein and that the acidic sequence just N-terminal to the IQ motif plays an important role in reproducing Ng-mediated decreases in the Ca(2+) binding affinity of CaM. Using NMR, full-length Ng was shown to make contacts largely with residues in the C-domain of CaM, although contacts were also detected in residues in the N-terminal domain. Together, our results can be consolidated into a model where Ng contacts residues in the N- and C-lobes of both apo- and Ca(2+)-bound CaM and that although Ca(2+) binding weakens Ng interactions with CaM, the most dramatic biochemical effect is the impact of Ng on Ca(2+) binding to the C-terminal lobe of CaM. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Hypnotic suggestibility predicts the magnitude of the imaginative word blindness suggestion effect in a non-hypnotic context.

    Science.gov (United States)

    Parris, Benjamin A; Dienes, Zoltan

    2013-09-01

    The present study investigated how the magnitude the word blindness suggestion effect on Stroop interference depended on hypnotic suggestibility when given as an imaginative suggestion (i.e. not post-hypnotic suggestion) and under conditions in which hypnosis was not mentioned. Hypnotic suggestibility is shown to be a significant predictor of the magnitude of the imaginative word blindness suggestion effect under these conditions. This is therefore the first study to show a linear relationship between the imaginative word blindness suggestion effect and hypnotic suggestibility across the whole hypnotizability spectrum. The results replicate previous findings showing that highs respond to the word blindness suggestion to a greater extent than lows but extend previous work by showing that the advantage for those higher on the hypnotizability spectrum occurs even in a non-hypnotic context. Negative attitudes about hypnosis may not explain the failure to observe similar effects of the word blindness suggestion in less hypnotizable individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Critical Success Factors of Suggestions Systems. | Marx | IFE ...

    African Journals Online (AJOL)

    A literature study approach is followed to establish which factors contribute to the success and failure of various suggestion systems. It was found ... The value of the paper firstly, shows the importance of creativity and innovation within the organisation's own culture and the framework of a formal suggestion system. Secondly ...

  5. Manufacturer Suggested Retail Prices, Loss Aversion and Competition

    NARCIS (Netherlands)

    Fabrizi, Simona; Lippert, Steffen; Puppe, Clemens; Rosenkranz, S.

    2016-01-01

    We study a model of vertical relations with imperfect retail competition in which a fraction of the consumers display reference-dependent demand with respect to the manufacturer’s suggested retail price. We demonstrate that in equilibrium the suggestion will either be undercut or complied with by

  6. Enhancing business intelligence by means of suggestive reviews.

    Science.gov (United States)

    Qazi, Atika; Raj, Ram Gopal; Tahir, Muhammad; Cambria, Erik; Syed, Karim Bux Shah

    2014-01-01

    Appropriate identification and classification of online reviews to satisfy the needs of current and potential users pose a critical challenge for the business environment. This paper focuses on a specific kind of reviews: the suggestive type. Suggestions have a significant influence on both consumers' choices and designers' understanding and, hence, they are key for tasks such as brand positioning and social media marketing. The proposed approach consists of three main steps: (1) classify comparative and suggestive sentences; (2) categorize suggestive sentences into different types, either explicit or implicit locutions; (3) perform sentiment analysis on the classified reviews. A range of supervised machine learning approaches and feature sets are evaluated to tackle the problem of suggestive opinion mining. Experimental results for all three tasks are obtained on a dataset of mobile phone reviews and demonstrate that extending a bag-of-words representation with suggestive and comparative patterns is ideal for distinguishing suggestive sentences. In particular, it is observed that classifying suggestive sentences into implicit and explicit locutions works best when using a mixed sequential rule feature representation. Sentiment analysis achieves maximum performance when employing additional preprocessing in the form of negation handling and target masking, combined with sentiment lexicons.

  7. Confidence Judgments in Children's and Adults' Event Recall and Suggestibility.

    Science.gov (United States)

    Roebers, Claudia M.

    2002-01-01

    Three studies investigated the role of 8- and 10-year-olds' and adults' metacognitive monitoring and control processes for unbiased event recall tasks and suggestibility. Findings suggested strong tendencies to overestimate confidence regardless of age and question format. Children did not lack principal metacognitive competencies when questions…

  8. Theory-of-Mind Development Influences Suggestibility and Source Monitoring

    Science.gov (United States)

    Bright-Paul, Alexandra; Jarrold, Christopher; Wright, Daniel B.

    2008-01-01

    According to the mental-state reasoning model of suggestibility, 2 components of theory of mind mediate reductions in suggestibility across the preschool years. The authors examined whether theory-of-mind performance may be legitimately separated into 2 components and explored the memory processes underlying the associations between theory of mind…

  9. The Effects of Repeated Experience on Children's Suggestibility.

    Science.gov (United States)

    Powell, Martine B.; Roberts, Kim P.; Ceci, Stephen J.; Hembrooke, Helene

    1999-01-01

    Examined effect of suggestive questions on 3- to 5-year-olds' and 6- to 8-year-olds' recall of the final occurrence of repeated event. Found that relative to reports of children experiencing single occurrence, reports about fixed items of repeated events were less contaminated by false suggestions. Children's age and delay of interview were…

  10. Enhancement of suggestibility and imaginative ability with nitrous oxide.

    Science.gov (United States)

    Whalley, M G; Brooks, G B

    2009-05-01

    Imaginative suggestibility, a trait closely related to hypnotic suggestibility, is modifiable under some circumstances. Nitrous oxide (laughing gas) is commonly used for sedation in dentistry and is reported to be more effective when combined with appropriate suggestions. The aim of this study was to determine whether nitrous oxide inhalation alters imaginative suggestibility and imagery vividness. Thirty participants were tested twice in a within-subjects design, once during inhalation of 25% nitrous oxide and once during inhalation of air plus oxygen. Before the study, participants' expectancies regarding the effects of nitrous oxide were assessed. Participants were blinded to drug administration. During each session, participants were verbally administered detailed measures of imagination and suggestibility: the Sheehan-Betts Quality of Mental Imagery scale and the Stanford Hypnotic Susceptibility Scale Form C, minus the hypnotic induction. Imaginative suggestibility and imaginative ability (imagery vividness) were both elevated in the nitrous oxide condition. This effect was unrelated to participants' expectations regarding the effects of the drug. Nitrous oxide increased imaginative suggestibility and imaginative ability. Possible explanations of these findings are discussed with respect to the effects of N-methyl-d-aspartate antagonists and to other pharmacological effects upon suggestibility and imagination.

  11. Effects of Counselor Facilitative Level on Client Suggestibility

    Science.gov (United States)

    Murphy, Harry B.; Rowe, Wayne

    1977-01-01

    University students (N=48) were individually tested for suggestibility in one of three conditions. Results indicated subjects of higher rated experimenters would demonstrate more suggestibility than subjects of lower rated experimenters. Results did not indicate that subject interaction with lower rated experimenters would elicit less…

  12. A Temporal Discriminability Account of Children's Eyewitness Suggestibility

    Science.gov (United States)

    Bright-Paul, Alexandra; Jarrold, Christopher

    2009-01-01

    Children's suggestibility is typically measured using a three-stage "event-misinformation-test" procedure. We examined whether suggestibility is influenced by the time delays imposed between these stages, and in particular whether the temporal discriminability of sources (event and misinformation) predicts performance. In a novel approach, the…

  13. Enhancing Business Intelligence by Means of Suggestive Reviews

    Science.gov (United States)

    Qazi, Atika

    2014-01-01

    Appropriate identification and classification of online reviews to satisfy the needs of current and potential users pose a critical challenge for the business environment. This paper focuses on a specific kind of reviews: the suggestive type. Suggestions have a significant influence on both consumers' choices and designers' understanding and, hence, they are key for tasks such as brand positioning and social media marketing. The proposed approach consists of three main steps: (1) classify comparative and suggestive sentences; (2) categorize suggestive sentences into different types, either explicit or implicit locutions; (3) perform sentiment analysis on the classified reviews. A range of supervised machine learning approaches and feature sets are evaluated to tackle the problem of suggestive opinion mining. Experimental results for all three tasks are obtained on a dataset of mobile phone reviews and demonstrate that extending a bag-of-words representation with suggestive and comparative patterns is ideal for distinguishing suggestive sentences. In particular, it is observed that classifying suggestive sentences into implicit and explicit locutions works best when using a mixed sequential rule feature representation. Sentiment analysis achieves maximum performance when employing additional preprocessing in the form of negation handling and target masking, combined with sentiment lexicons. PMID:25054188

  14. Faecal analysis suggests generalist diets in three species of ...

    African Journals Online (AJOL)

    The overlap in other arthropod taxa ingested was low across species and seasons, suggesting an opportunistic component to their foraging behaviour. We distinguished plant matter in faecal samples of all species in all seasons, reflecting either voluntary or accidental ingestion. The results of this study suggest that the ...

  15. Enhancing Business Intelligence by Means of Suggestive Reviews

    Directory of Open Access Journals (Sweden)

    Atika Qazi

    2014-01-01

    Full Text Available Appropriate identification and classification of online reviews to satisfy the needs of current and potential users pose a critical challenge for the business environment. This paper focuses on a specific kind of reviews: the suggestive type. Suggestions have a significant influence on both consumers’ choices and designers’ understanding and, hence, they are key for tasks such as brand positioning and social media marketing. The proposed approach consists of three main steps: (1 classify comparative and suggestive sentences; (2 categorize suggestive sentences into different types, either explicit or implicit locutions; (3 perform sentiment analysis on the classified reviews. A range of supervised machine learning approaches and feature sets are evaluated to tackle the problem of suggestive opinion mining. Experimental results for all three tasks are obtained on a dataset of mobile phone reviews and demonstrate that extending a bag-of-words representation with suggestive and comparative patterns is ideal for distinguishing suggestive sentences. In particular, it is observed that classifying suggestive sentences into implicit and explicit locutions works best when using a mixed sequential rule feature representation. Sentiment analysis achieves maximum performance when employing additional preprocessing in the form of negation handling and target masking, combined with sentiment lexicons.

  16. Simple suggestions for including vertical physics in oil spill models

    International Nuclear Information System (INIS)

    D'Asaro, Eric; University of Washington, Seatle, WA

    2001-01-01

    Current models of oil spills include no vertical physics. They neglect the effect of vertical water motions on the transport and concentration of floating oil. Some simple ways to introduce vertical physics are suggested here. The major suggestion is to routinely measure the density stratification of the upper ocean during oil spills in order to develop a database on the effect of stratification. (Author)

  17. Cross-modal working memory binding and word recognition skills: how specific is the link?

    Science.gov (United States)

    Wang, Shinmin; Allen, Richard J

    2018-04-01

    Recent research has suggested that the creation of temporary bound representations of information from different sources within working memory uniquely relates to word recognition abilities in school-age children. However, it is unclear to what extent this link is attributable specifically to the binding ability for cross-modal information. This study examined the performance of Grade 3 (8-9 years old) children on binding tasks requiring either temporary association formation of two visual items (i.e., within-modal binding) or pairs of visually presented abstract shapes and auditorily presented nonwords (i.e., cross-modal binding). Children's word recognition skills were related to performance on the cross-modal binding task but not on the within-modal binding task. Further regression models showed that cross-modal binding memory was a significant predictor of word recognition when memory for its constituent elements, general abilities, and crucially, within-modal binding memory were taken into account. These findings may suggest a specific link between the ability to bind information across modalities within working memory and word recognition skills.

  18. Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.

    Science.gov (United States)

    Handing, Katarzyna B; Shabalin, Ivan G; Szlachta, Karol; Majorek, Karolina A; Minor, Wladek

    2016-03-01

    Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Using suggestion to model different types of automatic writing.

    Science.gov (United States)

    Walsh, E; Mehta, M A; Oakley, D A; Guilmette, D N; Gabay, A; Halligan, P W; Deeley, Q

    2014-05-01

    Our sense of self includes awareness of our thoughts and movements, and our control over them. This feeling can be altered or lost in neuropsychiatric disorders as well as in phenomena such as "automatic writing" whereby writing is attributed to an external source. Here, we employed suggestion in highly hypnotically suggestible participants to model various experiences of automatic writing during a sentence completion task. Results showed that the induction of hypnosis, without additional suggestion, was associated with a small but significant reduction of control, ownership, and awareness for writing. Targeted suggestions produced a double dissociation between thought and movement components of writing, for both feelings of control and ownership, and additionally, reduced awareness of writing. Overall, suggestion produced selective alterations in the control, ownership, and awareness of thought and motor components of writing, thus enabling key aspects of automatic writing, observed across different clinical and cultural settings, to be modelled. Copyright © 2014. Published by Elsevier Inc.

  20. The impact of hypnotic suggestibility in clinical care settings.

    Science.gov (United States)

    Montgomery, Guy H; Schnur, Julie B; David, Daniel

    2011-07-01

    Hypnotic suggestibility has been described as a powerful predictor of outcomes associated with hypnotic interventions. However, there have been no systematic approaches to quantifying this effect across the literature. This meta-analysis evaluates the magnitude of the effect of hypnotic suggestibility on hypnotic outcomes in clinical settings. PsycINFO and PubMed were searched from their inception through July 2009. Thirty-four effects from 10 studies and 283 participants are reported. Results revealed a statistically significant overall effect size in the small to medium range (r = .24; 95% Confidence Interval = -0.28 to 0.75), indicating that greater hypnotic suggestibility led to greater effects of hypnosis interventions. Hypnotic suggestibility accounted for 6% of the variance in outcomes. Smaller sample size studies, use of the SHCS, and pediatric samples tended to result in larger effect sizes. The authors question the usefulness of assessing hypnotic suggestibility in clinical contexts.

  1. Binding of indomethacin methyl ester to cyclooxygenase-2. A computational study.

    Science.gov (United States)

    Sárosi, Menyhárt-Botond

    2018-06-05

    Inhibitors selective towards the second isoform of prostaglandin synthase (cyclooxygenase, COX-2) are promising nonsteroidal anti-inflammatory drugs and antitumor medications. Methylation of the carboxylate group in the relatively nonselective COX inhibitor indomethacin confers significant COX-2 selectivity. Several other modifications converting indomethacin into a COX-2 selective inhibitor have been reported. Earlier experimental and computational studies on neutral indomethacin derivatives suggest that the methyl ester derivative likely binds to COX-2 with a similar binding mode as that observed for the parent indomethacin. However, docking studies followed by molecular dynamics simulations revealed two possible binding modes in COX-2 for indomethacin methyl ester, which differs from the experimental binding mode found for indomethacin. Both alternative binding modes might explain the observed COX-2 selectivity of indomethacin methyl ester. Graphical abstract Binding of indomethacin methyl ester to cyclooxygenase-2.

  2. Removal of glycosaminoglycans from bovine granulosa cells contributes to increased binding of hydrogen-3 heparin

    Energy Technology Data Exchange (ETDEWEB)

    Ax, R.L.; Stodd, C.M.; Boehm, S.K.; Bellin, M.E.

    1986-02-01

    Granulosa cells from small or large bovine follicles were pretreated with enzymes that hydrolyze various glycosaminoglycans, and binding of (/sup 3/H)-heparin to the granulosa was measured. Binding of (/sup 3/H) heparin increased significantly after enzymatic pretreatments with chondroitinase ABC and fungal hyaluronidase, and similar results were obtained with granulosa from small and large follicles. No changes in binding of (/sup 3/H) heparin were detected after hydrolyses with chondroitinase AC and heparinase in either follicle size. Heparitinase, which hydrolyzes heparan sulfate, led to a significant 50% increase in binding of (/sup 3/H) heparin to granulosa from large follicles but was without effect in small follicles. These results suggest that the lower binding of (/sup 3/H) heparin, which has been reported with follicular enlargement, may be due to heparan sulfate occupying or obstructing binding sites for heparin on granulosa from large follicles.

  3. Characterization of [3H] oxymorphone binding sites in mouse brain

    DEFF Research Database (Denmark)

    Yoo, Ji Hoon; Borsodi, Anna; Tóth, Géza

    2017-01-01

    Oxymorphone, one of oxycodone's metabolic products, is a potent opioid receptor agonist which is thought to contribute to the analgesic effect of its parent compound and may have high potential abuse liability. Nonetheless, the in vivo pharmacological binding profile of this drug is still unclear....... This study uses mice lacking mu (MOP), kappa (KOP) or delta (DOP) opioid receptors as well as mice lacking all three opioid receptors to provide full characterisation of oxymorphone binding sites in the brain. Saturation binding studies using [3H]oxymorphone revealed high affinity binding sites in mouse......]Oxymorphone binding was completely abolished across the majority of the brain regions in mice lacking MOP as well as in mice lacking all three opioid receptors. DOP and KOP knockout mice retained [3H]oxymorphone binding sites suggesting oxymorphone may not target DOP or KOP. These results confirm that the MOP...

  4. Identification of nucleic acid binding sites on translin-associated factor X (TRAX protein.

    Directory of Open Access Journals (Sweden)

    Gagan Deep Gupta

    Full Text Available Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity.

  5. Identification of Nucleic Acid Binding Sites on Translin-Associated Factor X (TRAX) Protein

    Science.gov (United States)

    Gupta, Gagan Deep; Kumar, Vinay

    2012-01-01

    Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity. PMID:22427937

  6. Binding of radiolabelled luteinizing hormone to intact and ovariectomised rat uterus

    International Nuclear Information System (INIS)

    Sen, S.; Bhattacharya, S.

    1992-01-01

    Binding of ovine LH to uterine tissue preparation from intact and ovariectomised rat clearly indicates that uterus possesses specific binding sites for LH. Binding characteristics of LH to uterine tissue preparation from intact rat showed saturability with high affinity and low capacity. Scatchard plot analysis showed dissociation constant of the specific binding site to be 0.12 x 10 -9 mol/l and the number of binding sites was 2.31±0.05 fmol/mg protein. Ovariectomy did not change the binding affinity but effected a decrease in the number of binding sites (1.7 ± 0.08 f mol/mg protein). LH treatment of ovariectomized (ovx) rat had no effect on binding affinity but significantly increased the number of binding sites (3.23 ± 0.1 f mol/mg protein). Reduction of uterine weight due to ovariectomy and marked increase of ovx rat uterine weight by LH administration indicate a source of estrogen in ovx rat. An in vitro uterine tissue slice (from intact and ovx rat) incubation showed depletion of 17 β-estradiol (E 2 ) content in ovx rat which significantly elevated on LH addition. Data suggest the LH binding to rat uterine tissue has biological relevance. (author). 16 refs., 4 figs. 1 tab

  7. How Native and Alien Metal Cations Bind ATP: Implications for Lithium as a Therapeutic Agent

    Science.gov (United States)

    Dudev, Todor; Grauffel, Cédric; Lim, Carmay

    2017-02-01

    Adenosine triphosphate (ATP), the major energy currency of the cell, exists in solution mostly as ATP-Mg. Recent experiments suggest that Mg2+ interacts with the highly charged ATP triphosphate group and Li+ can co-bind with the native Mg2+ to form ATP-Mg-Li and modulate the neuronal purine receptor response. However, it is unclear how the negatively charged ATP triphosphate group binds Mg2+ and Li+ (i.e. which phosphate group(s) bind Mg2+/Li+) and how the ATP solution conformation depends on the type of metal cation and the metal-binding mode. Here, we reveal the preferred ATP-binding mode of Mg2+/Li+ alone and combined: Mg2+ prefers to bind ATP tridentately to each of the three phosphate groups, but Li+ prefers to bind bidentately to the terminal two phosphates. We show that the solution ATP conformation depends on the cation and its binding site/mode, but it does not change significantly when Li+ binds to Mg2+-loaded ATP. Hence, ATP-Mg-Li, like Mg2+-ATP, can fit in the ATP-binding site of the host enzyme/receptor, activating specific signaling pathways.

  8. dsRNA binding properties of RDE-4 and TRBP reflect their distinct roles in RNAi.

    Science.gov (United States)

    Parker, Greg S; Maity, Tuhin Subhra; Bass, Brenda L

    2008-12-26

    Double-stranded RNA (dsRNA)-binding proteins facilitate Dicer functions in RNA interference. Caenorhabditis elegans RDE-4 facilitates cleavage of long dsRNA to small interfering RNA (siRNA), while human trans-activation response RNA-binding protein (TRBP) functions downstream to pass siRNA to the RNA-induced silencing complex. We show that these distinct in vivo roles are reflected in in vitro binding properties. RDE-4 preferentially binds long dsRNA, while TRBP binds siRNA with an affinity that is independent of dsRNA length. These properties are mechanistically based on the fact that RDE-4 binds cooperatively, via contributions from multiple domains, while TRBP binds noncooperatively. Our studies offer a paradigm for how dsRNA-binding proteins, which are not sequence specific, discern dsRNA length. Additionally, analyses of the ability of RDE-4 deletion constructs and RDE-4/TRBP chimeras to reconstitute Dicer activity suggest RDE-4 promotes activity using its dsRNA-binding motif 2 to bind dsRNA, its linker region to interact with Dicer, and its C-terminus for Dicer activation.

  9. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Wolverton, C.

    2007-01-01

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  10. Polymeric competitive protein binding adsorbents for radioassay

    International Nuclear Information System (INIS)

    Adams, R.J.

    1976-01-01

    Serum protein comprising specific binding proteins such as antibodies, B 12 intrinsic factor, thyroxin binding globulin and the like may be copolymerized with globulin constituents of serum by the action of ethylchloroformate to form readily packed insoluble precipitates which, following purification as by washing, are eminently suited for employment as competitive binding protein absorbents in radioassay procedures. 10 claims, no drawings

  11. Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

    Science.gov (United States)

    Radoux, Chris J; Olsson, Tjelvar S G; Pitt, Will R; Groom, Colin R; Blundell, Tom L

    2016-05-12

    Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores. For ligand-bound structures, they provide an intuitive visual guide within the binding site, directing medicinal chemists where to grow the molecule and alerting them to suboptimal interactions within the original hit. The fragment hotspot map calculation is validated using experimental binding positions of 21 fragments and subsequent lead molecules. The ligands are found in high scoring areas of the fragment hotspot maps, with fragment atoms having a median percentage rank of 97%. Protein kinase B and pantothenate synthetase are examined in detail. In each case, the fragment hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a fragment-based drug design project.

  12. Steroid production and estrogen binding in flowers of Gladiolus

    International Nuclear Information System (INIS)

    Adler, J.H.; Wolfe, G.R.; Janik, J.R.

    1987-01-01

    The bioconversion of 3 H-cholesterol to steroids was examined in excised tissue from the pistils and bracts of Gladiolus. Ovary-ovule and stigma-style tissues produce a compound with chromatographic properties on reverse phase HPLC similar to 17β-estradiol (E 2 ). The stigma-style fraction also produced a compound that chromatographed similarly to progesterone. Bracts and the oxidation controls produced no radiolabeled compounds which were chromatographically similar to E 2 . An endogenous E 2 binding protein was partially characterized from the ovules. The protein binds E 2 , estriol, and diethylstilbesterol whereas testosterone and progesterone do not bind. The total specific binding capacities in the cytosolic and nuclear fractions are 1.6 and 2.2 femtomoles of estradiol per mg of tissue. The dissociation constant is 1.1 x 10 -9 M -1 for both subcellular fractions. The protein-estradiol complex has a sedimentation coefficient of 4.7 +/- 0.1S. The tissue specific biosynthesis of estrogens and the presence of a steroid binding protein similar to a Type 1 estrogen receptor found in mammals is suggestive of a role for steroids in pistil ontogeny

  13. Hyper-binding only apparent under fully implicit test conditions.

    Science.gov (United States)

    Campbell, Karen L; Hasher, Lynn

    2018-02-01

    We have previously shown that older adults hyper-bind, or form more extraneous associations than younger adults. For instance, when asked to perform a 1-back task on pictures superimposed with distracting words, older adults inadvertently form associations between target-distractor pairs and implicitly transfer these associations to a later paired associate learning task (showing a boost in relearning of preserved over disrupted pairs). We have argued that younger adults are better at suppressing the distracting words and thus, do not form these extraneous associations in the first place. However, an alternative explanation is that younger adults simply fail to access these associations during relearning, possibly because of their superior ability to form boundaries between episodes or shift mental contexts between tasks. In this study, we aimed to both replicate this original implicit transfer effect in older adults and to test whether younger adults show evidence of hyper-binding when informed about the relevance of past information. Our results suggest that regardless of the test conditions, younger adults do not hyper-bind. In contrast, older adults showed hyper-binding under (standard) implicit instructions, but not when made aware of a connection between tasks. These results replicate the original hyper-binding effect and reiterate its implicit nature. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Integration of tools for binding archetypes to SNOMED CT.

    Science.gov (United States)

    Sundvall, Erik; Qamar, Rahil; Nyström, Mikael; Forss, Mattias; Petersson, Håkan; Karlsson, Daniel; Ahlfeldt, Hans; Rector, Alan

    2008-10-27

    The Archetype formalism and the associated Archetype Definition Language have been proposed as an ISO standard for specifying models of components of electronic healthcare records as a means of achieving interoperability between clinical systems. This paper presents an archetype editor with support for manual or semi-automatic creation of bindings between archetypes and terminology systems. Lexical and semantic methods are applied in order to obtain automatic mapping suggestions. Information visualisation methods are also used to assist the user in exploration and selection of mappings. An integrated tool for archetype authoring, semi-automatic SNOMED CT terminology binding assistance and terminology visualization was created and released as open source. Finding the right terms to bind is a difficult task but the effort to achieve terminology bindings may be reduced with the help of the described approach. The methods and tools presented are general, but here only bindings between SNOMED CT and archetypes based on the openEHR reference model are presented in detail.

  15. Quantification of progesterone binding in mammary tissue of pregnant ewes

    International Nuclear Information System (INIS)

    Smith, J.J.; Capuco, A.V.; Akers, R.M.

    1987-01-01

    Progestin-binding sites in mammary tissue from 14 prepartum, multiparous ewes at 50, 80, 115, and 140 d of gestation were demonstrated by the binding of [ 3 H] R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) to ovine mammary cytosol in the presence of sodium molybdate and excess cortisol. Homogenization extracted 89% of total mammary receptors (nuclear) into cytosol. Binding was specific for progestins and was of high affinity. The average dissociation constant for [ 3 H] R5020 specifically bound to receptors extracted into mammary cytosol was 1.9 (+/- .4) x 10 -9 M (n = 14) and did not change significantly over the test period. However, binding capacities (fmol/mg cytosolic protein) differed according to stage of gestation with averages of 125 +/- 53, 149 +/- 26, 656 +/- 216, 57 +/- 22 at 50, 80, 115, and 140 d of pregnancy, respectively. Increased number of progestin-binding sites at 115 d of gestation (whether data are expressed per unit of tissue weight, DNA, or cytosolic protein) suggests that an increase per mammary epithelial cell may be necessary to produce the full lobuloalveolar proliferation observed at this stage of gestation

  16. Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

    Science.gov (United States)

    de Jongh, Harmen H. J.; Robles, Carlos López; Nordlee, Julie A.; Lee, Poi-Wah; Baumert, Joseph L.; Hamilton, Robert G.; Taylor, Steve L.; Koppelman, Stef J.

    2013-01-01

    Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein's digestibility is not affected by such processing. PMID:23878817

  17. Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

    Directory of Open Access Journals (Sweden)

    Harmen H. J. de Jongh

    2013-01-01

    Full Text Available Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa, the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein’s digestibility is not affected by such processing.

  18. Localization of substance P binding sites in submucous plexus of guinea pig ileum, using whole-mount autoradiography

    International Nuclear Information System (INIS)

    Burcher, E.; Bornstein, J.C.

    1988-01-01

    Whole mounts of guinea pig ileum submucosa were incubated with radiolabeled tachykinins, and binding sites were visualized using autoradiography. Very dense specific binding for [ 125 I]-Bolton-Hunter substance P (BHSP) was observed over ganglia of the submucous plexus, with weaker binding over internodal strands. Dense specific binding was also seen over occasional strands of circular muscle, with weak binding over clumps of mucosa. Although very weak binding was seen over some large blood vessels, no binding was associated with smaller blood vessels. Localization of binding was absent in whole-mounts coincubated with 1 microM substance P, used to define nonspecific binding. Localization of BHSP-specific binding was also abolished in whole-mounts coincubated with 1 nM substance P, but not with 1 nM neurokinin B, suggesting that binding was probably to an NK-1 tachykinin receptor. In whole-mounts incubated in [ 125 I]-iodohistidyl neurokinin A (INKA) or [ 125 I]-Bolton-Hunter neurokinin B (BHNKB), no specific binding over ganglia was observed. These binding sites for BHSP are probably identical with the neuronal substance P receptors mediating mucosal ion transport

  19. Age and interviewer behavior as predictors of interrogative suggestibility.

    Science.gov (United States)

    Dukala, Karolina; Polczyk, Romuald

    2014-05-01

    The main objective was to explore the influence of interviewer behavior-abrupt versus friendly-and the age of participants on interrogative suggestibility. The study involved 42 young adults and 50 elderly participants. The Gudjonsson Suggestibility Scale 2 was used. Data analysis involved a 2-factor between-subjects design (interviewer behavior × age) and mediation analysis. The scores of elderly participants were significantly lower than younger adults on memory indices and significantly higher on some suggestibility indexes. Some suggestibility indices in the abrupt experimental condition were higher than those in the friendly experimental condition. Elderly participants who were interviewed under the abrupt condition were more likely to change their answers after receiving negative feedback than younger adults. Memory quality was a mediator of the relationship between age and the tendency to yield to suggestive questions. Self-appraisal of memory was a mediator between both age and interviewer behavior and the tendency to change answers after negative feedback. Mechanisms of the relationship between age, interviewer behavior, and suggestibility are discussed on the basis of the mediational analyses. The findings suggest that a friendly manner should be adopted when interrogating witnesses.

  20. Structural and functional correlates of hypnotic depth and suggestibility.

    Science.gov (United States)

    McGeown, William Jonathan; Mazzoni, Giuliana; Vannucci, Manila; Venneri, Annalena

    2015-02-28

    This study explores whether self-reported depth of hypnosis and hypnotic suggestibility are associated with individual differences in neuroanatomy and/or levels of functional connectivity. Twenty-nine people varying in suggestibility were recruited and underwent structural, and after a hypnotic induction, functional magnetic resonance imaging at rest. We used voxel-based morphometry to assess the correlation of grey matter (GM) and white matter (WM) against the independent variables: depth of hypnosis, level of relaxation and hypnotic suggestibility. Functional networks identified with independent components analysis were regressed with the independent variables. Hypnotic depth ratings were positively correlated with GM volume in the frontal cortex and the anterior cingulate cortex (ACC). Hypnotic suggestibility was positively correlated with GM volume in the left temporal-occipital cortex. Relaxation ratings did not correlate significantly with GM volume and none of the independent variables correlated with regional WM volume measures. Self-reported deeper levels of hypnosis were associated with less connectivity within the anterior default mode network. Taken together, the results suggest that the greater GM volume in the medial frontal cortex and ACC, and lower connectivity in the DMN during hypnosis facilitate experiences of greater hypnotic depth. The patterns of results suggest that hypnotic depth and hypnotic suggestibility should not be considered synonyms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Structural and functional cerebral correlates of hypnotic suggestibility.

    Directory of Open Access Journals (Sweden)

    Alexa Huber

    Full Text Available Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

  2. Structural and functional cerebral correlates of hypnotic suggestibility.

    Science.gov (United States)

    Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo

    2014-01-01

    Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

  3. Mechanisms of eyewitness suggestibility: tests of the explanatory role hypothesis.

    Science.gov (United States)

    Rindal, Eric J; Chrobak, Quin M; Zaragoza, Maria S; Weihing, Caitlin A

    2017-10-01

    In a recent paper, Chrobak and Zaragoza (Journal of Experimental Psychology: General, 142(3), 827-844, 2013) proposed the explanatory role hypothesis, which posits that the likelihood of developing false memories for post-event suggestions is a function of the explanatory function the suggestion serves. In support of this hypothesis, they provided evidence that participant-witnesses were especially likely to develop false memories for their forced fabrications when their fabrications helped to explain outcomes they had witnessed. In three experiments, we test the generality of the explanatory role hypothesis as a mechanism of eyewitness suggestibility by assessing whether this hypothesis can predict suggestibility errors in (a) situations where the post-event suggestions are provided by the experimenter (as opposed to fabricated by the participant), and (b) across a variety of memory measures and measures of recollective experience. In support of the explanatory role hypothesis, participants were more likely to subsequently freely report (E1) and recollect the suggestions as part of the witnessed event (E2, source test) when the post-event suggestion helped to provide a causal explanation for a witnessed outcome than when it did not serve this explanatory role. Participants were also less likely to recollect the suggestions as part of the witnessed event (on measures of subjective experience) when their explanatory strength had been reduced by the presence of an alternative explanation that could explain the same outcome (E3, source test + warning). Collectively, the results provide strong evidence that the search for explanatory coherence influences people's tendency to misremember witnessing events that were only suggested to them.

  4. Oscillatory mechanisms of process binding in memory.

    Science.gov (United States)

    Klimesch, Wolfgang; Freunberger, Roman; Sauseng, Paul

    2010-06-01

    A central topic in cognitive neuroscience is the question, which processes underlie large scale communication within and between different neural networks. The basic assumption is that oscillatory phase synchronization plays an important role for process binding--the transient linking of different cognitive processes--which may be considered a special type of large scale communication. We investigate this question for memory processes on the basis of different types of oscillatory synchronization mechanisms. The reviewed findings suggest that theta and alpha phase coupling (and phase reorganization) reflect control processes in two large memory systems, a working memory and a complex knowledge system that comprises semantic long-term memory. It is suggested that alpha phase synchronization may be interpreted in terms of processes that coordinate top-down control (a process guided by expectancy to focus on relevant search areas) and access to memory traces (a process leading to the activation of a memory trace). An analogous interpretation is suggested for theta oscillations and the controlled access to episodic memories. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  5. Binding and thermodynamics of REV peptide-ctDNA interaction.

    Science.gov (United States)

    Upadhyay, Santosh Kumar

    2017-03-01

    The thermodynamics of DNA-ligand binding is important as it provides useful information to understand the details of binding processes. HIV-1 REV response element (RRE) located in the env coding region of the viral genome is reported to be well conserved across different HIV-1 isolates. In this study, the binding characteristics of Calf thymus DNA (ctDNA) and REV peptide from HIV-1 were investigated using spectroscopic (UV-visible, fluorescence, and circular dichroism (CD)) and isothermal titration calorimetric (ITC) techniques. Thermal stability and ligand binding properties of the ctDNA revealed that native ctDNA had a T m of 75.5 °C, whereas the ctDNA-REV peptide complex exhibited an incremental shift in the T m by 8 °C, indicating thermal stability of the complex. CD data indicated increased ellipticity due to large conformational changes in ctDNA molecule upon binding with REV peptide and two binding stoichiometric modes are apparent. The ctDNA experienced condensation due to large conformational changes in the presence of REV peptide and positive B→Ψ transition was observed at higher molar charge ratios. Fluorescence studies performed at several ligand concentrations revealed a gradual decrease in the fluorescence intensity of EtBr-bound ctDNA in response to increasing ligand concentrations. The fluorescence data further confirmed two stoichiometric modes of binding for ctDNA-REV peptide complex as previously observed with CD studies. The binding enthalpies were determined using ITC in the temperature range of 293 K-308 K. The ITC binding isotherm was exothermic at all temperatures examined, with low ΔH values indicating that the ctDNA-REV peptide interaction is driven largely by entropy. The heat capacity change (ΔC p ) was insignificant, an unusual finding in the area of DNA-peptide interaction studies. The variation in the values obtained for ΔH, ΔS, and ΔG with temperature further suggests that ctDNA-REV peptide interaction is entropically

  6. Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human

    International Nuclear Information System (INIS)

    MacDonald, P.N.; Ong, D.E.; Bok, D.

    1990-01-01

    Brain is not generally recognized as an organ that requires vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A-deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur

  7. Analysis of RNA binding by the dengue virus NS5 RNA capping enzyme.

    Directory of Open Access Journals (Sweden)

    Brittney R Henderson

    Full Text Available Flaviviruses are small, capped positive sense RNA viruses that replicate in the cytoplasm of infected cells. Dengue virus and other related flaviviruses have evolved RNA capping enzymes to form the viral RNA cap structure that protects the viral genome and directs efficient viral polyprotein translation. The N-terminal domain of NS5 possesses the methyltransferase and guanylyltransferase activities necessary for forming mature RNA cap structures. The mechanism for flavivirus guanylyltransferase activity is currently unknown, and how the capping enzyme binds its diphosphorylated RNA substrate is important for deciphering how the flavivirus guanylyltransferase functions. In this report we examine how flavivirus NS5 N-terminal capping enzymes bind to the 5' end of the viral RNA using a fluorescence polarization-based RNA binding assay. We observed that the K(D for RNA binding is approximately 200 nM Dengue, Yellow Fever, and West Nile virus capping enzymes. Removal of one or both of the 5' phosphates reduces binding affinity, indicating that the terminal phosphates contribute significantly to binding. RNA binding affinity is negatively affected by the presence of GTP or ATP and positively affected by S-adensyl methoninine (SAM. Structural superpositioning of the dengue virus capping enzyme with the Vaccinia virus VP39 protein bound to RNA suggests how the flavivirus capping enzyme may bind RNA, and mutagenesis analysis of residues in the putative RNA binding site demonstrate that several basic residues are critical for RNA binding. Several mutants show differential binding to 5' di-, mono-, and un-phosphorylated RNAs. The mode of RNA binding appears similar to that found with other methyltransferase enzymes, and a discussion of diphosphorylated RNA binding is presented.

  8. Functional connectivity supporting the selective maintenance of feature-location binding in visual working memory

    Directory of Open Access Journals (Sweden)

    Sachiko eTakahama

    2014-06-01

    Full Text Available Information on an object’s features bound to its location is very important for maintaining object representations in visual working memory. Interactions with dynamic multi-dimensional objects in an external environment require complex cognitive control, including the selective maintenance of feature-location binding. Here, we used event-related functional magnetic resonance imaging to investigate brain activity and functional connectivity related to the maintenance of complex feature-location binding. Participants were required to detect task-relevant changes in feature-location binding between objects defined by color, orientation, and location. We compared a complex binding task requiring complex feature-location binding (color-orientation-location with a simple binding task in which simple feature-location binding, such as color-location, was task-relevant and the other feature was task-irrelevant. Univariate analyses showed that the dorsolateral prefrontal cortex (DLPFC, hippocampus, and frontoparietal network were activated during the maintenance of complex feature-location binding. Functional connectivity analyses indicated cooperation between the inferior precentral sulcus (infPreCS, DLPFC, and hippocampus during the maintenance of complex feature-location binding. In contrast, the connectivity for the spatial updating of simple feature-location binding determined by reanalyzing the data from Takahama et al. (2010 demonstrated that the superior parietal lobule (SPL cooperated with the DLPFC and hippocampus. These results suggest that the connectivity for complex feature-location binding does not simply reflect general memory load and that the DLPFC and hippocampus flexibly modulate the dorsal frontoparietal network, depending on the task requirements, with the infPreCS involved in the maintenance of complex feature-location binding and the SPL involved in the spatial updating of simple feature-location binding.

  9. Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRα[S

    Science.gov (United States)

    Fang, Changming; Filipp, Fabian V.; Smith, Jeffrey W.

    2012-01-01

    Ursodeoxycholic acid (UDCA, ursodiol) is used to prevent damage to the liver in patients with primary biliary cirrhosis. The drug also prevents the progression of colorectal cancer and the recurrence of high-grade colonic dysplasia. However, the molecular mechanism by which UDCA elicits its beneficial effects is not entirely understood. The aim of this study was to determine whether ileal bile acid binding protein (IBABP) has a role in mediating the effects of UDCA. We find that UDCA binds to a single site on IBABP and increases the affinity for major human bile acids at a second binding site. As UDCA occupies one of the bile acid binding sites on IBABP, it reduces the cooperative binding that is often observed for the major human bile acids. Furthermore, IBABP is necessary for the full activation of farnesoid X receptor α (FXRα) by bile acids, including UDCA. These observations suggest that IBABP may have a role in mediating some of the intestinal effects of UDCA. PMID:22223860

  10. Effects of flow changes on radiotracer binding: Simultaneous measurement of neuroreceptor binding and cerebral blood flow modulation.

    Science.gov (United States)

    Sander, Christin Y; Mandeville, Joseph B; Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M; Rosen, Bruce R

    2017-01-01

    The potential effects of changes in blood flow on the delivery and washout of radiotracers has been an ongoing question in PET bolus injection studies. This study provides practical insight into this topic by experimentally measuring cerebral blood flow (CBF) and neuroreceptor binding using simultaneous PET/MRI. Hypercapnic challenges (7% CO 2 ) were administered to non-human primates in order to induce controlled increases in CBF, measured with pseudo-continuous arterial spin labeling. Simultaneously, dopamine D 2 /D 3 receptor binding of [ 11 C]raclopride or [ 18 F]fallypride was monitored with dynamic PET. Experiments showed that neither time activity curves nor quantification of binding through binding potentials ( BP ND ) were measurably affected by CBF increases, which were larger than two-fold. Simulations of experimental procedures showed that even large changes in CBF should have little effect on the time activity curves of radiotracers, given a set of realistic assumptions. The proposed method can be applied to experimentally assess the flow sensitivity of other radiotracers. Results demonstrate that CBF changes, which often occur due to behavioral tasks or pharmacological challenges, do not affect PET [ 11 C]raclopride or [ 18 F]fallypride binding studies and their quantification. The results from this study suggest flow effects may have limited impact on many PET neuroreceptor tracers with similar properties.

  11. Polar bear hemoglobin and human Hb A0: same 2,3-diphosphoglycerate binding site but asymmetry of the binding?

    Science.gov (United States)

    Pomponi, Massimo; Bertonati, Claudia; Patamia, Maria; Marta, Maurizio; Derocher, Andrew E; Lydersen, Christian; Kovacs, Kit M; Wiig, Oystein; Bårdgard, Astrid J

    2002-11-01

    Polar bear (Ursus maritimus) hemoglobin (Hb) shows a low response to 2,3-diphosphoglycerate (2,3-DPG), compared to human Hb A0, even though these proteins have the same 2,3-DPG-binding site. In addition, polar bear Hb shows a high response to chloride and an alkaline Bohr effect (deltalog P50/deltapH) that is significantly greater than that of human Hb A0. The difference in sequence Pro (Hb A0)-->Gly (polar bear Hb) at position A2 in the A helix seems to be critical for reduced binding of 2,3-DPG. Our results also show that the A2 position may influence not only the flexibility of the A helix, but that differences in flexibility of the first turn of the A helix may affect the unloading of oxygen for the intrinsic ligand affinities of the alpha and beta chains. However, preferential binding to either chain can only take place if there is appreciable asymmetric binding of the phosphoric effector. Regarding this point, 31P NMR data suggest a loss of symmetry of the 2,3-DPG-binding site in the deoxyHb-2,3-DPG complex.

  12. Lifelong learning in aviation and medicine; Comments and suggestions

    NARCIS (Netherlands)

    Boshuizen, Els

    2011-01-01

    Boshuizen, H. P. A. (2010, 25-27 August). Lifelong learning in aviation and medicine; Comments and suggestions. Discussion at the 5th EARLI-SIG14 Learning and Professional Development, Munich, Germany.

  13. Belief in the paranormal and suggestion in the seance room.

    Science.gov (United States)

    Wiseman, Richard; Greening, Emma; Smith, Matthew

    2003-08-01

    In Experiment 1, participants took part in a fake seance. An actor suggested that a table was levitating when, in fact, it remained stationary. After the seance, approximately one third of participants incorrectly reported that the table had moved. Results also showed a significant relationship between the reported movement of the table and belief in the paranormal, with a greater percentage of believers than disbelievers, reporting that the table had moved. Experiment 2 varied whether the suggestion was consistent, or inconsistent, with participants' belief in the paranormal. Results again showed that believers were more susceptible to suggestion than disbelievers, but only when the suggestion was consistent with their belief in the paranormal. Approximately one fifth of participants believed that the fake seances contained genuine paranormal phenomena.

  14. Neurogenesis suggests independent evolution of opercula in serpulid polychaetes

    DEFF Research Database (Denmark)

    Brinkmann, Nora; Wanninger, Andreas

    2009-01-01

    BACKGROUND: The internal phylogenetic relationships of Annelida, one of the key lophotrochozoan lineages, are still heavily debated. Recent molecular analyses suggest that morphologically distinct groups, such as the polychaetes, are paraphyletic assemblages, thus questioning the homology...

  15. Suggested benchmarks for shape optimization for minimum stress concentration

    DEFF Research Database (Denmark)

    Pedersen, Pauli

    2008-01-01

    Shape optimization for minimum stress concentration is vital, important, and difficult. New formulations and numerical procedures imply the need for good benchmarks. The available analytical shape solutions rely on assumptions that are seldom satisfied, so here, we suggest alternative benchmarks...

  16. Baby Teeth Link Autism and Heavy Metals, NIH Study Suggests

    Science.gov (United States)

    ... Release Thursday, June 1, 2017 Baby teeth link autism and heavy metals, NIH study suggests Cross-section ... Sinai Health System Baby teeth from children with autism contain more toxic lead and less of the ...

  17. Using Neurolinguistic Programming: Some Suggestions for the Remedial Teacher.

    Science.gov (United States)

    Burton, Grace M.

    1986-01-01

    The use of neurolinguistic programming techniques is suggested as a means of enhancing rapport with students. Mirroring, digital mirroring, analog mirroring, metaphors, knowing persons, and how these aid in presenting content are each discussed. (MNS)

  18. MANAGING TIGHT BINDING RECEPTORS FOR NEW SPEARATIONS TECHNOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    DARYLE H BUSCH RICHARD S GIVENS

    2004-12-10

    Much of the earth's pollution involves compounds of the metallic elements, including actinides, strontium, cesium, technetium, and RCRA metals. Metal ions bind to molecules called ligands, which are the molecular tools that can manipulate the metal ions under most conditions. This DOE-EMSP sponsored program strives (1) to provide the foundations for using the most powerful ligands in transformational separations technologies and (2) to produce seminal examples of their applications to separations appropriate to the DOE EM mission. These ultra tight-binding ligands can capture metal ions in the most competitive of circumstances (from mineralized sites, lesser ligands, and even extremely dilute solutions), but they react so slowly that they are useless in traditional separations methodologies. Two attacks on this problem are underway. The first accommodates to the challenging molecular lethargy by developing a seminal slow separations methodology termed the soil poultice. The second designs ligands that are only tight-binding while wrapped around the targeted metal ion, but can be put in place by switch-binding and removed by switch-release. We envision a kind of molecular switching process to accelerate the union between metal ion and tight-binding ligand. Molecular switching processes are suggested for overcoming the slow natural equilibration rate with which ultra tight-binding ligands combine with metal ions. Ligands that bind relatively weakly combine with metal ions rapidly, so the trick is to convert a ligand from a weak, rapidly binding species to a powerful, slow releasing ligand--during the binding of the ligand to the metal ion. Such switch-binding ligands must react with themselves, and the reaction must take place under the influence of the metal ion. For example, our generation 1 ligands showed that a well-designed linear ligand with ends that readily combine, forms a cyclic molecule when it wraps around a metal ion. Our generation 2 ligands are

  19. Regulating professional behavior: codes of ethics or law? Suggested criteria.

    Science.gov (United States)

    Libman, Liron A

    2013-09-01

    This paper suggests considering a few parameters when making policy decisions as to the proper "tool" to regulate professional behavior: law or professional ethics. This is done on the background of understanding the place of codes of professional ethics between "pure" ethics and law. Suggested criteria are then illustrated using a few examples. Further discourse may reveal additional factors to support a more rational process of decision-making in this field.

  20. Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes

    DEFF Research Database (Denmark)

    Westgate, G E; Weaver, A C; Couchman, J R

    1985-01-01

    immunofluorescent staining for BPA is linear at the basement membrane zone (BMZ) of skin and many other epithelial tissues. At higher magnification however, we observed a punctate staining pattern for BPA which was regular in appearance and suggested localization of BPA to discrete structures at the BMZ. Subsequent...... intracellularly both in vivo and in vitro. We suggest that BPA is not normally a lamina lucida component, but that it may form part of a linkage between the cytoskeleton and the basement membrane....

  1. Quantitative analysis of TALE-DNA interactions suggests polarity effects.

    Science.gov (United States)

    Meckler, Joshua F; Bhakta, Mital S; Kim, Moon-Soo; Ovadia, Robert; Habrian, Chris H; Zykovich, Artem; Yu, Abigail; Lockwood, Sarah H; Morbitzer, Robert; Elsäesser, Janett; Lahaye, Thomas; Segal, David J; Baldwin, Enoch P

    2013-04-01

    Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ≈ NN > NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10(3)-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches 'standard' RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5'-T. Another surprising observation was that base mismatches at the 5' end of the target site had more disruptive effects on affinity than those at the 3' end, particularly in designed TALEs. These results provide evidence that TALE-DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones.

  2. Binding of MCM-interacting proteins to ATP-binding site in MCM6

    Directory of Open Access Journals (Sweden)

    Hosoi A

    2016-03-01

    Full Text Available Atsutoshi Hosoi, Taku Sakairi, Yukio Ishimi Graduate School of Science and Engineering, Ibaraki University, Mito, Ibaraki, Japan Abstract: The function of MCM2–7 complex that is a DNA helicase in DNA replication may be regulated by various MCM-interacting proteins, including CDC45, RPA, TIM, TIPIN, Claspin, MCM10, and MCM-BP. It has been shown by immunoprecipitation that human MCM6 interacts with all these proteins in coexpressed insect cells. To determine the region in MCM6 to interact with these proteins, we prepared various truncated forms of MCM6 and examined the interaction of these MCM6 fragments with the MCM-interacting proteins. All these proteins bound to C-terminal half of MCM6, and CDC45, RPA2, TIM, TIPIN, MCM-BP, and MCM10 bound to the fragments containing ATP-binding motifs. CDC45 and RPA2 bound to the smallest fragment containing Walker motif A. Only MCM-BP is bound to the N-terminal half of MCM6. Site-directed mutagenesis study suggests that hydrophobic interaction is involved in the interaction of MCM6 with CDC45 and TIM. These results suggest a possibility that MCM-interacting proteins regulate MCM2–7 function by modulating the ATP-binding ability of the MCM2–7. Keywords: DNA helicase, DNA replication, checkpoint, MCM2–7 proteins

  3. [3H]nitrendipine binding to adrenal capsular membranes

    International Nuclear Information System (INIS)

    Finkel, M.S.; Aguilera, G.; Catt, K.J.; Keiser, H.R.

    1984-01-01

    The physiologic regulation of aldosterone secretion is dependent on extracellular calcium and appears to be mediated by increases in cytosolic free calcium concentration in the zona glomerulosa cell. A specific role for voltage-dependent calcium channels was suggested by previous studies with the calcium channel antagonist verapamil. The authors therefore studied the [ 3 H]nitrendipine calcium channel binding site in adrenal capsules. These studies revealed a single class of saturable, high affinity sites with K/sub D/ = .26 +/- .04 nM and B/sub max/ = 105 +/- 5.7 fmol/mg protein. Specific binding of [ 3 H]nitrendipine was inhibited by calcium channel antagonists with potencies nitrendipine = nifedipine >> verapamil, while diltiazem had no inhibitory effect. In the rat, binding sites for [ 3 H]nitrendipine were located in the adrenal capsule and medulla and were undetectable in the zona fasciculata. Physiologic studies with collagenase-dispersed adrenal glomerulosa cells demonstrated that nifedipine selectively inhibited angiotensin-II and potassium-stimulated steroidogenesis. These observations suggest both a pharmacologic and physiologic role for the nitrendipine binding site in aldosterone production. 17 references, 2 figures, 1 table

  4. Structural and binding studies of SAP-1 protein with heparin.

    Science.gov (United States)

    Yadav, Vikash K; Mandal, Rahul S; Puniya, Bhanwar L; Kumar, Rahul; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2015-03-01

    SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (KD = 158 nm). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity. © 2014 John Wiley & Sons A/S.

  5. Experimental and theoretical investigation of bezafibrate binding to serum albumins

    Energy Technology Data Exchange (ETDEWEB)

    Gałęcki, Krystian, E-mail: kgalecki87@gmail.com [Technical University of Lodz, Lodz (Poland); Hunter, Kelsey [Glasgow Caledonian University, Glasgow, Scotland (United Kingdom); Daňková, Gabriela [Masarykova Univerzita, Brno (Czech Republic); Rivera, Elsy [University of Houston-Downtown, Houston (United States); Tung, Lo Wing [The Hong Kong Polytechnic University (Hong Kong); Mc Sherry, Kenneth [Trinity College Dublin, Dublin (Ireland)

    2016-09-15

    The purpose of this investigation was to provide insight into the possible mechanism of the intermolecular interactions between antilipemic agent bezafibrate and serum albumins (SAs) including human (HSA) and bovine (BSA). The aim was to indicate the most probable sight of these interactions. Both experimental (spectroscopic) and theoretical methods were applied. It was determined that bezafibrate binds to SAs in one specific binding site, the fatty acid binding site 6. The results obtained from the steady-state and time-resolved fluorescence experiments suggested that existing two distinct stable conformations of the proteins with different exposure to the quencher. The dominate conformer of HSA and BSA characterized by the Stern–Volmer quenching constant (from ratio F{sub 0}/F) equal to 1.24·10{sup 4} and 8.48·10{sup 3} M{sup −1} at 298 K, respectively. The docking results and calculated thermodynamics parameters may be suggested that the binding process is spontaneous and might involve van der Waals and hydrogen bonding forces.

  6. Structure of Drosophila Oskar reveals a novel RNA binding protein

    Science.gov (United States)

    Yang, Na; Yu, Zhenyu; Hu, Menglong; Wang, Mingzhu; Lehmann, Ruth; Xu, Rui-Ming

    2015-01-01

    Oskar (Osk) protein plays critical roles during Drosophila germ cell development, yet its functions in germ-line formation and body patterning remain poorly understood. This situation contrasts sharply with the vast knowledge about the function and mechanism of osk mRNA localization. Osk is predicted to have an N-terminal LOTUS domain (Osk-N), which has been suggested to bind RNA, and a C-terminal hydrolase-like domain (Osk-C) of unknown function. Here, we report the crystal structures of Osk-N and Osk-C. Osk-N shows a homodimer of winged-helix–fold modules, but without detectable RNA-binding activity. Osk-C has a lipase-fold structure but lacks critical catalytic residues at the putative active site. Surprisingly, we found that Osk-C binds the 3′UTRs of osk and nanos mRNA in vitro. Mutational studies identified a region of Osk-C important for mRNA binding. These results suggest possible functions of Osk in the regulation of stability, regulation of translation, and localization of relevant mRNAs through direct interaction with their 3′UTRs, and provide structural insights into a novel protein–RNA interaction motif involving a hydrolase-related domain. PMID:26324911

  7. Mapping small molecule binding data to structural domains.

    Science.gov (United States)

    Kruger, Felix A; Rostom, Raghd; Overington, John P

    2012-01-01

    Large-scale bioactivity/SAR Open Data has recently become available, and this has allowed new analyses and approaches to be developed to help address the productivity and translational gaps of current drug discovery. One of the current limitations of these data is the relative sparsity of reported interactions per protein target, and complexities in establishing clear relationships between bioactivity and targets using bioinformatics tools. We detail in this paper the indexing of targets by the structural domains that bind (or are likely to bind) the ligand within a full-length protein. Specifically, we present a simple heuristic to map small molecule binding to Pfam domains. This profiling can be applied to all proteins within a genome to give some indications of the potential pharmacological modulation and regulation of all proteins. In this implementation of our heuristic, ligand binding to protein targets from the ChEMBL database was mapped to structural domains as defined by profiles contained within the Pfam-A database. Our mapping suggests that the majority of assay targets within the current version of the ChEMBL database bind ligands through a small number of highly prevalent domains, and conversely the majority of Pfam domains sampled by our data play no currently established role in ligand binding. Validation studies, carried out firstly against Uniprot entries with expert binding-site annotation and secondly against entries in the wwPDB repository of crystallographic protein structures, demonstrate that our simple heuristic maps ligand binding to the correct domain in about 90 percent of all assessed cases. Using the mappings obtained with our heuristic, we have assembled ligand sets associated with each Pfam domain. Small molecule binding has been mapped to Pfam-A domains of protein targets in the ChEMBL bioactivity database. The result of this mapping is an enriched annotation of small molecule bioactivity data and a grouping of activity classes

  8. Evaluation of the improvement suggestion system in a nuclear facility

    International Nuclear Information System (INIS)

    Carnaval, Joao Paulo Rodrigues; Moraes, Geice Almeida

    2017-01-01

    This work evaluated methods for processing improvement suggestions of a nuclear factory, with the intention to verify those which best fits to the company purposes. Two methods for processing improvement suggestions were applied in the studied organization. The first one was guided to the processing suggestions by specific independent sectors of the company and the second one was conducted to the processing of suggestions by a multidisciplinary team. It has been concluded that a multidisciplinary team focused on research and development would be the best option to the implementation of improvement suggestions and technological innovation on this facility, instead of multi sector processing which revealed to be excessive bureaucratic before the expected goals. This study can be used by nuclear facilities to optimize an existing system of improvements analysis or even guide them for the implantation of a new one. It is more significant for the companies certified on ISO and OHSAS standards for the quality management, environmental and safety and occupational health systems which requires that the continuous improvement must exist and to be demonstrated. But it is also relevant for nuclear plants aiming to implement an Integrated Management System certified on ISO Standards. (author)

  9. Hypnosis, hypnotic suggestibility, memory, and involvement in films.

    Science.gov (United States)

    Maxwell, Reed; Lynn, Steven Jay; Condon, Liam

    2015-05-01

    Our research extends studies that have examined the relation between hypnotic suggestibility and experiential involvement and the role of an hypnotic induction in enhancing experiential involvement (e.g., absorption) in engaging tasks. Researchers have reported increased involvement in reading (Baum & Lynn, 1981) and music-listening (Snodgrass & Lynn, 1989) tasks during hypnosis. We predicted a similar effect for film viewing: greater experiential involvement in an emotional (The Champ) versus a non-emotional (Scenes of Toronto) film. We tested 121 participants who completed measures of absorption and trait dissociation and the Harvard Group Scale of Hypnotic Susceptibility and then viewed the two films after either an hypnotic induction or a non-hypnotic task (i.e., anagrams). Experiential involvement varied as a function of hypnotic suggestibility and film clip. Highly suggestible participants reported more state depersonalization than less suggestible participants, and depersonalization was associated with negative affect; however, we observed no significant correlation between hypnotic suggestibility and trait dissociation. Although hypnosis had no effect on memory commission or omission errors, contrary to the hypothesis that hypnosis facilitates absorption in emotionally engaging tasks, the emotional film was associated with more commission and omission errors compared with the non-emotional film. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Evaluation of the improvement suggestion system in a nuclear facility

    Energy Technology Data Exchange (ETDEWEB)

    Carnaval, Joao Paulo Rodrigues; Moraes, Geice Almeida, E-mail: joaocarnaval@inb.gov.br, E-mail: geice@inb.gov.br [Industrias Nucleares do Brasil S.A (INB), Resende, RJ (Brazil)

    2017-11-01

    This work evaluated methods for processing improvement suggestions of a nuclear factory, with the intention to verify those which best fits to the company purposes. Two methods for processing improvement suggestions were applied in the studied organization. The first one was guided to the processing suggestions by specific independent sectors of the company and the second one was conducted to the processing of suggestions by a multidisciplinary team. It has been concluded that a multidisciplinary team focused on research and development would be the best option to the implementation of improvement suggestions and technological innovation on this facility, instead of multi sector processing which revealed to be excessive bureaucratic before the expected goals. This study can be used by nuclear facilities to optimize an existing system of improvements analysis or even guide them for the implantation of a new one. It is more significant for the companies certified on ISO and OHSAS standards for the quality management, environmental and safety and occupational health systems which requires that the continuous improvement must exist and to be demonstrated. But it is also relevant for nuclear plants aiming to implement an Integrated Management System certified on ISO Standards. (author)

  11. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xueqing; Chang, Bianca W. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Mans, Ben J. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Agricultural Research Council, Onderstepoort 0110 (South Africa); Ribeiro, Jose M. C.; Andersen, John F., E-mail: jandersen@niaid.nih.gov [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States)

    2013-01-01

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity.

  12. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    International Nuclear Information System (INIS)

    Xu, Xueqing; Chang, Bianca W.; Mans, Ben J.; Ribeiro, Jose M. C.; Andersen, John F.

    2013-01-01

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity

  13. Evaluation of patients with symptoms suggestive of chronic polyneuropathy

    DEFF Research Database (Denmark)

    Johannsen, L; Smith, T; Havsager, A M

    2001-01-01

    OBJECTIVES: The aim of this study was to determine the diagnostic yield and to describe the spectrum of diagnosis encountered by evaluation of patients with symptoms suggestive of chronic polyneuropathy. METHODS: We prospectively evaluated 198 patients referred to a department of neurology...... with symptoms suggestive of polyneuropathy. The evaluation included nerve conduction studies with near-nerve technique, quantitative examination of temperature sensation, blood tests, chest x-rays, and skin biopsies as well as diagnostic tests for differential diagnoses. RESULTS: Polyneuropathy was found in 147......%), drugs (5%), connective tissue disease (3%), and a number of less frequent conditions. A previously undiagnosed condition was found in 30% of the patients with polyneuropathy. CONCLUSION: Evaluation of patients with symptoms suggestive of polyneuropathy reveals a high fraction of patients with previously...

  14. Career Path Suggestion using String Matching and Decision Trees

    Science.gov (United States)

    Nagpal, Akshay; P. Panda, Supriya

    2015-05-01

    High school and college graduates seemingly are often battling for the courses they should major in order to achieve their target career. In this paper, we worked on suggesting a career path to a graduate to reach his/her dream career given the current educational status. Firstly, we collected the career data of professionals and academicians from various career fields and compiled the data set by using the necessary information from the data. Further, this was used as the basis to suggest the most appropriate career path for the person given his/her current educational status. Decision trees and string matching algorithms were employed to suggest the appropriate career path for a person. Finally, an analysis of the result has been done directing to further improvements in the model.

  15. Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations

    Science.gov (United States)

    Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J.

    2017-11-01

    Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

  16. Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

    Science.gov (United States)

    Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J

    2017-11-01

    Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

  17. Exposure to suggestion and creation of false auditory memories.

    Science.gov (United States)

    Vernon, B; Nelson, E

    2000-02-01

    The experiment investigated the possibility of creating false auditory memory through exposure to suggestion. Research by Loftus and others has indicated that, through suggestion, false memories can be created. Participants viewed a short film and were given a 9-item questionnaire. Eight questions were used as filler while one question asked respondents to recall a phrase one character had said. Although the character actually said nothing, 23 of 30 respondents recalled having heard him speak and specifically recalled his words. This statistically significant result shows that auditory memories can also be created.

  18. Persistent Web References – Best Practices and New Suggestions

    DEFF Research Database (Denmark)

    Zierau, Eld; Nyvang, Caroline; Kromann, Thomas Hvid

    In this paper, we suggest adjustments to best practices for persistent web referencing; adjustments that aim at preservation and long time accessibility of web referenced resources in general, but with focus on web references in web archives. Web referencing is highly relevant and crucial...... refer to archive URLs which depends on the web archives access implementations. A major part of the suggested adjustments is a new web reference standard for archived web references (called wPID), which is a supplement to the current practices. The purpose of the standard is to support general, global...

  19. Suggested guidelines for gas emission monitoring at danish landfills

    DEFF Research Database (Denmark)

    Kjeldsen, Peter; Scheutz, Charlotte

    2015-01-01

    Landfill gas is produced on waste disposal sites receiving organic waste resulting in emission of methane. Regulation requires that the landfill gas is managed in order to reduce emissions, but very few suggestions exist to how the landfill gas management activities are monitored, what requirements...... to the ability of the landfill gas management to reduce the emission should be set up, and how criteria are developed for when the monitoring activities can be terminated. Monitoring procedures are suggested centred on a robust method for measuring the total methane emission from the site, and quantitative...

  20. Children's suggestibility research: Things to know before interviewing a child

    Directory of Open Access Journals (Sweden)

    Amelia Courtney Hritz

    2015-01-01

    Full Text Available Children's testimony is often the only evidence of alleged abuse. Thus, the importance of conducting forensic interviews that are free from bias and misleading information is immense, as these could lead to false reports. In the current paper, we review unexpected findings in children's suggestibility that illustrate the difficulty in distinguishing between false and accurate reports. We explore situations in which a younger person's memory account may be more accurate than that of an adult, when a single suggestive interview may be as detrimental as multiple interviews, and when children can make inaccurate reports spontaneously. We conclude with recommendations for interviewers to decrease false reporting by both children and adults.