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Sample records for reveals unique surface

  1. Two Unique Glioma Subtypes Revealed.

    PubMed

    Poh, Alissa

    2016-04-01

    A comprehensive analysis of 1,122 diffuse glioma samples from The Cancer Genome Atlas has revealed two new subtypes of this common brain cancer, with molecular and clinical features that diverge from the norm. The study findings also support the use of DNA methylation profiles to improve glioma classification and treatment.

  2. Piriform Spider Silk Sequences Reveal Unique Repetitive Elements

    PubMed Central

    Perry, David J.; Bittencourt, Daniela; Siltberg-Liberles, Jessica; Rech, Elibio L.; Lewis, Randolph V.

    2010-01-01

    Orb-weaving spider silk fibers are assembled from very large, highly repetitive proteins. The repeated segments contain, in turn, short, simple repetitive amino acid motifs that account for the physical and mechanical properties of the assembled fiber. Of the six orb-weaver silk fibroins, the piriform silk that makes the attachment discs, which lashes the joints of the web and attaches dragline silk to surfaces has not been previously characterized. Piriform silk protein cDNAs were isolated from phage libraries of three species, A. trifasciata, N. clavipes, and N. cruentata. The deduced amino acid sequences from these genes revealed two new repetitive motifs: an alternating proline motif where every other amino acid is proline, and a glutamine-rich motif of 6 to 8 amino acids. Similar to other spider silk proteins, the repeated segments are large (>200 amino acids) and highly homogenized within a species. There is also substantial sequence similarity across the genes from the three species with particular conservation of the repetitive motifs. Northern blot analysis revealed that the messenger RNA is larger than 11kb and is expressed exclusively in the piriform glands of the spider. Phylogenetic analysis of the C-terminal regions of the new proteins with published spidroins robustly shows that the pirifom sequences form an ortholog group. PMID:20954740

  3. Piriform spider silk sequences reveal unique repetitive elements.

    PubMed

    Perry, David J; Bittencourt, Daniela; Siltberg-Liberles, Jessica; Rech, Elibio L; Lewis, Randolph V

    2010-11-01

    Orb-weaving spider silk fibers are assembled from very large, highly repetitive proteins. The repeated segments contain, in turn, short, simple, and repetitive amino acid motifs that account for the physical and mechanical properties of the assembled fiber. Of the six orb-weaver silk fibroins, the piriform silk that makes the attachment discs, which lashes the joints of the web and attaches dragline silk to surfaces, has not been previously characterized. Piriform silk protein cDNAs were isolated from phage libraries of three species: A. trifasciata , N. clavipes , and N. cruentata . The deduced amino acid sequences from these genes revealed two new repetitive motifs: an alternating proline motif, where every other amino acid is proline, and a glutamine-rich motif of 6-8 amino acids. Similar to other spider silk proteins, the repeated segments are large (>200 amino acids) and highly homogenized within a species. There is also substantial sequence similarity across the genes from the three species, with particular conservation of the repetitive motifs. Northern blot analysis revealed that the mRNA is larger than 11 kb and is expressed exclusively in the piriform glands of the spider. Phylogenetic analysis of the C-terminal regions of the new proteins with published spidroins robustly shows that the piriform sequences form an ortholog group.

  4. Unique hues as revealed by unique-hue selecting versus partial hue-matching.

    PubMed

    Logvinenko, Alexander D; Geithner, Coryn

    2015-04-01

    Unique hues are usually defined as those that cannot be introspectively reduced to any other hue. According to a major dogma of color science, there are four unique hues: yellow, blue, red, and green. Yet only 55 of the 173 inexperienced observers who participated in our experiment selected exactly four Munsell papers that, according to their judgment, had a unique hue. The number of papers selected by the rest of the observers varied from zero to nine. We believe that such variability of unique hue selection is due to the ambiguity of the introspective criteria for hue uniqueness. Along with the traditional technique of unique hue selection, an alternative method based on partial hue-matching has also been used to establish the nomenclature of unique hues. The partial hue-matching method is based on observer judgments concerning the presence of a common hue in a pair of colors. Observers are not supposed to name (or make any other judgments of) this common hue. Without presupposing their number, the unique hues are derived from the observer's responses to a sample of color pairs. The results obtained by this new method generally support the classical notion of four unique hues.

  5. Diatom Proteomics Reveals Unique Acclimation Strategies to Mitigate Fe Limitation

    PubMed Central

    Nunn, Brook L.; Faux, Jessica F.; Hippmann, Anna A.; Maldonado, Maria T.; Harvey, H. Rodger; Goodlett, David R.; Boyd, Philip W.; Strzepek, Robert F.

    2013-01-01

    Phytoplankton growth rates are limited by the supply of iron (Fe) in approximately one third of the open ocean, with major implications for carbon dioxide sequestration and carbon (C) biogeochemistry. To date, understanding how alteration of Fe supply changes phytoplankton physiology has focused on traditional metrics such as growth rate, elemental composition, and biophysical measurements such as photosynthetic competence (Fv/Fm). Researchers have subsequently employed transcriptomics to probe relationships between changes in Fe supply and phytoplankton physiology. Recently, studies have investigated longer-term (i.e. following acclimation) responses of phytoplankton to various Fe conditions. In the present study, the coastal diatom, Thalassiosira pseudonana, was acclimated (10 generations) to either low or high Fe conditions, i.e. Fe-limiting and Fe-replete. Quantitative proteomics and a newly developed proteomic profiling technique that identifies low abundance proteins were employed to examine the full complement of expressed proteins and consequently the metabolic pathways utilized by the diatom under the two Fe conditions. A total of 1850 proteins were confidently identified, nearly tripling previous identifications made from differential expression in diatoms. Given sufficient time to acclimate to Fe limitation, T. pseudonana up-regulates proteins involved in pathways associated with intracellular protein recycling, thereby decreasing dependence on extracellular nitrogen (N), C and Fe. The relative increase in the abundance of photorespiration and pentose phosphate pathway proteins reveal novel metabolic shifts, which create substrates that could support other well-established physiological responses, such as heavily silicified frustules observed for Fe-limited diatoms. Here, we discovered that proteins and hence pathways observed to be down-regulated in short-term Fe starvation studies are constitutively expressed when T. pseudonana is acclimated (i

  6. Plastic-casting intrinsic-surface unique identifier (tag)

    SciTech Connect

    Palm, R.G.; De Volpi, A.

    1995-04-01

    This report describes the development of an authenticated intrinsic-surf ace tagging method for unique- identification of controlled items. Although developed for control of items limited by an arms control treaty, this method has other potential applications to keep track of critical or high-value items. Each tag (unique-identifier) consists of the intrinsic, microscopic surface topography of a small designated area on a controlled item. It is implemented by making a baseline plastic casting of the designated tag area and usually placing a cover (for example, a bar-code label) over this area to protect the surface from environmental alteration. The plastic casting is returned to a laboratory and prepared for high-resolution scanning electron microscope imaging. Several images are digitized and stored for use as a standard for authentication of castings taken during future inspections. Authentication is determined by numerically comparing digital images. Commercially available hardware and software are used for this tag. Tag parameters are optimized, so unique casting images are obtained from original surfaces, and images obtained from attempted duplicate surfaces are detected. This optimization uses the modulation transfer function, a first principle of image analysis, to determine the parameters. Surface duplication experiments confirmed the optimization.

  7. Uniqueness of electromagnetic inversion by local surface measurements

    NASA Astrophysics Data System (ADS)

    Liukkonen, J.

    1999-02-01

    Assume that a bounded body has been embedded in a homogeneous half-space. Our aim is to reconstruct the electromagnetic material parameters, namely the electric permittivity, conductivity and magnetic permeability, of the body from local field measurements on the surface of the half-space. All fields are supposed to be governed by time-harmonic Maxwell equations. We consider two kinds of initial data. The first data set consists of tangential electric and magnetic field vectors of a tangential magnetic dipole for all field and source points in an open subset of the surface. The second data set is one that we know locally on the surface - the admittance map - which, by definition, associates the tangential magnetic field with the tangential electric field. The purpose of this paper is to show that both of the data sets determine the material parameters uniquely.

  8. The Laccaria and Tuber Genomes Reveal Unique Signatures of Mycorrhizal Symbiosis Evolution (2010 JGI User Meeting)

    SciTech Connect

    Knapp, Steve

    2010-03-24

    Francis Martin from the French agricultural research institute INRA talks on how "The Laccaria and Tuber genomes reveal unique signatures of mycorrhizal symbiosis evolution" on March 24, 2010 at the 5th Annual DOE JGI User Meeting

  9. Interdependencies of Arctic land surface processes: A uniquely sensitive environment

    NASA Astrophysics Data System (ADS)

    Bowling, L. C.

    2007-12-01

    The circumpolar arctic drainage basin is composed of several distinct ecoregions including steppe grassland and cropland, boreal forest and tundra. Land surface hydrology throughout this diverse region shares several unique features such as dramatic seasonal runoff differences controlled by snowmelt and ice break-up; the storage of significant portions of annual precipitation as snow and in lakes and wetlands; and the effects of ephemeral and permanently frozen soils. These arctic land processes are delicately balanced with the climate and are therefore important indicators of change. The litany of recently-detected changes in the Arctic includes changes in snow precipitation, trends and seasonal shifts in river discharge, increases and decreases in the extent of surface water, and warming soil temperatures. Although not unique to the arctic, increasing anthropogenic pressures represent an additional element of change in the form of resource extraction, fire threat and reservoir construction. The interdependence of the physical, biological and social systems mean that changes in primary indicators have large implications for land cover, animal populations and the regional carbon balance, all of which have the potential to feed back and induce further change. In fact, the complex relationships between the hydrological processes that make the Artic unique also render observed historical change difficult to interpret and predict, leading to conflicting explanations. For example, a decrease in snow accumulation may provide less insulation to the underlying soil resulting in greater frost development and increased spring runoff. Similarly, melting permafrost and ground ice may lead to ground subsidence and increased surface saturation and methane production, while more complete thaw may enhance drainage and result in drier soil conditions. The threshold nature of phase change around the freezing point makes the system especially sensitive to change. In addition, spatial

  10. Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

    PubMed Central

    Rodriguez-Palacios, Alex; Kodani, Tomohiro; Kaydo, Lindsey; Pietropaoli, Davide; Corridoni, Daniele; Howell, Scott; Katz, Jeffry; Xin, Wei; Pizarro, Theresa T.; Cominelli, Fabio

    2015-01-01

    Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub-clusters of 3D-structure-patterns of IBD pathology, which we call 3D-stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes (‘cobblestones' versus ‘villous mini-aggregation') cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. In humans, stereomicroscopy reveals ‘liquefaction' lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn's disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD. PMID:26154811

  11. Unique developmental trajectories of cortical thickness and surface area.

    PubMed

    Wierenga, Lara M; Langen, Marieke; Oranje, Bob; Durston, Sarah

    2014-02-15

    There is evidence that the timing of developmental changes in cortical volume and thickness varies across the brain, although the processes behind these differences are not well understood. In contrast to volume and thickness, the regional developmental trajectories of cortical surface area have not yet been described. The present study used a combined cross-sectional and longitudinal design with 201 MRI-scans (acquired at 1.5-T) from 135 typically developing children and adolescents. Scans were processed using FreeSurfer software and the Desikan-Killiany atlas. Developmental trajectories were estimated using mixed model regression analysis. Within most regions, cortical thickness showed linear decreases with age, whereas both cortical volume and surface area showed curvilinear trajectories. On average, maximum surface area occurred later in development than maximum volume. Global gender differences were more pronounced in cortical volume and surface area than in average thickness. Our findings suggest that developmental trajectories of surface area and thickness differ across the brain, both in their pattern and their timing, and that they also differ from the developmental trajectory of global cortical volume. Taken together, these findings indicate that the development of surface area and thickness is driven by different processes, at least in part. PMID:24246495

  12. Transcriptomic Sequencing Reveals a Set of Unique Genes Activated by Butyrate-Induced Histone Modification.

    PubMed

    Li, Cong-Jun; Li, Robert W; Baldwin, Ransom L; Blomberg, Le Ann; Wu, Sitao; Li, Weizhong

    2016-01-01

    Butyrate is a nutritional element with strong epigenetic regulatory activity as a histone deacetylase inhibitor. Based on the analysis of differentially expressed genes in the bovine epithelial cells using RNA sequencing technology, a set of unique genes that are activated only after butyrate treatment were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network, using Ingenuity Pathways Analysis, indicated that these genes activated by butyrate treatment are related to major cellular functions, including cell morphological changes, cell cycle arrest, and apoptosis. Our results offered insight into the butyrate-induced transcriptomic changes and will accelerate our discerning of the molecular fundamentals of epigenomic regulation. PMID:26819550

  13. Transcriptomic Sequencing Reveals a Set of Unique Genes Activated by Butyrate-Induced Histone Modification

    PubMed Central

    Li, Cong-Jun; Li, Robert W.; Baldwin, Ransom L.; Blomberg, Le Ann; Wu, Sitao; Li, Weizhong

    2016-01-01

    Butyrate is a nutritional element with strong epigenetic regulatory activity as a histone deacetylase inhibitor. Based on the analysis of differentially expressed genes in the bovine epithelial cells using RNA sequencing technology, a set of unique genes that are activated only after butyrate treatment were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network, using Ingenuity Pathways Analysis, indicated that these genes activated by butyrate treatment are related to major cellular functions, including cell morphological changes, cell cycle arrest, and apoptosis. Our results offered insight into the butyrate-induced transcriptomic changes and will accelerate our discerning of the molecular fundamentals of epigenomic regulation. PMID:26819550

  14. Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata

    PubMed Central

    Krishna, Srikar; Nair, Aparna; Cheedipudi, Sirisha; Poduval, Deepak; Dhawan, Jyotsna; Palakodeti, Dasaradhi; Ghanekar, Yashoda

    2013-01-01

    Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem–loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping–pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration. PMID:23166307

  15. Molecular Characterization of Infectious Clones of the Minute Virus of Canines Reveals Unique Features of Bocaviruses▿

    PubMed Central

    Sun, Yuning; Chen, Aaron Yun; Cheng, Fang; Guan, Wuxiang; Johnson, F. Brent; Qiu, Jianming

    2009-01-01

    Minute virus of canines (MVC) is a member of the genus Bocavirus in the family Parvoviridae. We have molecularly cloned and sequenced the 5′- and 3′-terminal palindromes of MVC. The MVC genome, 5,404 nucleotides (nt) in length, shared an identity of 52.6% and 52.1% with that of human bocavirus and bovine parvovirus, respectively. It had distinct palindromic hairpins of 183 nt and 198 nt at the left-end and right-end termini of the genome, respectively. The left-end terminus was also found in two alternative orientations (flip or flop). Both termini shared extensive similarities with those of bovine parvovirus. Four full-length molecular clones constructed with different orientations of the left-end terminus proved to be infectious in Walter Reed canine cell/3873D (WRD) canine cells. Both MVC infection and transfection of the infectious clone in WRD cells revealed an identical RNA transcription profile that was similar to that of bovine parvovirus. Mutagenesis of the infectious clone demonstrated that the middle open reading frame encodes the NP1 protein. This protein, unique to the genus Bocavirus, was essential for MVC DNA replication. Moreover, the phospholipase A2 motif in the VP1 unique region was also critical for MVC infection. Thus, our studies revealed important information about the genus Bocavirus that may eventually help us to clone the human bocavirus and study its pathogenesis. PMID:19211770

  16. Structure analysis of archaeal AMP phosphorylase reveals two unique modes of dimerization.

    PubMed

    Nishitani, Yuichi; Aono, Riku; Nakamura, Akira; Sato, Takaaki; Atomi, Haruyuki; Imanaka, Tadayuki; Miki, Kunio

    2013-08-01

    AMP phosphorylase (AMPpase) catalyzes the initial reaction in a novel AMP metabolic pathway recently found in archaea, converting AMP and phosphate into adenine and ribose 1,5-bisphosphate. Gel-filtration chromatography revealed that AMPpase from Thermococcus kodakarensis (Tk-AMPpase) forms an exceptionally large macromolecular structure (>40-mers) in solution. To investigate its unique multimerization feature, we determined the first crystal structures of Tk-AMPpase, in the apo-form and in complex with substrates. Structures of two truncated forms of Tk-AMPpase (Tk-AMPpaseΔN84 and Tk-AMPpaseΔC10) clarified that this multimerization is achieved by two dimer interfaces within a single molecule: one by the central domain and the other by the C-terminal domain, which consists of an unexpected domain-swapping interaction. The N-terminal domain, characteristic of archaeal enzymes, is essential for enzymatic activity, participating in multimerization as well as domain closure of the active site upon substrate binding. Moreover, biochemical analysis demonstrated that the macromolecular assembly of Tk-AMPpase contributes to its high thermostability, essential for an enzyme from a hyperthermophile. Our findings unveil a unique archaeal nucleotide phosphorylase that is distinct in both function and structure from previously known members of the nucleoside phosphorylase II family.

  17. Revealing unique properties of the ribosome using a network based analysis

    PubMed Central

    David-Eden, Hilda; Mandel-Gutfreund, Yael

    2008-01-01

    The ribosome is a complex molecular machine that offers many potential sites for functional interference, therefore representing a major target for antibacterial drugs. The growing number of high-resolution structures of ribosomes from different organisms, in free form and in complex with various ligands, provides unique data for structural and comparative analyses of RNA structures. We model the ribosome structure as a network, where nucleotides are represented as nodes and intermolecular interactions as edges. As shown previously for proteins, we found that the major functional sites of the ribosome exhibit significantly high centrality measures. Specifically, we demonstrate that mutations that strongly affect ribosome function and assembly can be distinguished from mild mutations based on their network properties. Furthermore, we observed that closeness centrality of the rRNA nucleotides is highly conserved in the bacteria, suggesting the network representation as a comparative tool for the ribosome analysis. Finally, we suggest a global topology perspective to characterize functional sites and to reveal the unique properties of the ribosome. PMID:18625614

  18. Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis

    PubMed Central

    Liu, Wenjun; Zhang, Jiachao; Wu, Chunyan; Cai, Shunfeng; Huang, Weiqiang; Chen, Jing; XI, Xiaoxia; Liang, Zebin; Hou, Qiangchuan; Zhou, Bing; Qin, Nan; Zhang, Heping

    2016-01-01

    The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian’s gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment. PMID:27708392

  19. Revealing a steroid receptor ligand as a unique PPAR[gamma] agonist

    SciTech Connect

    Lin, Shengchen; Han, Ying; Shi, Yuzhe; Rong, Hui; Zheng, Songyang; Jin, Shikan; Lin, Shu-Yong; Lin, Sheng-Cai; Li, Yong

    2012-06-28

    Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPAR{gamma} agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPAR{gamma} target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPAR{gamma} ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPAR{gamma} ligands in the treatment of insulin resistance.

  20. The Complete Genome Sequences, Unique Mutational Spectra, and Developmental Potency of Adult Neurons Revealed by Cloning.

    PubMed

    Hazen, Jennifer L; Faust, Gregory G; Rodriguez, Alberto R; Ferguson, William C; Shumilina, Svetlana; Clark, Royden A; Boland, Michael J; Martin, Greg; Chubukov, Pavel; Tsunemoto, Rachel K; Torkamani, Ali; Kupriyanov, Sergey; Hall, Ira M; Baldwin, Kristin K

    2016-03-16

    Somatic mutation in neurons is linked to neurologic disease and implicated in cell-type diversification. However, the origin, extent, and patterns of genomic mutation in neurons remain unknown. We established a nuclear transfer method to clonally amplify the genomes of neurons from adult mice for whole-genome sequencing. Comprehensive mutation detection and independent validation revealed that individual neurons harbor ∼100 unique mutations from all classes but lack recurrent rearrangements. Most neurons contain at least one gene-disrupting mutation and rare (0-2) mobile element insertions. The frequency and gene bias of neuronal mutations differ from other lineages, potentially due to novel mechanisms governing postmitotic mutation. Fertile mice were cloned from several neurons, establishing the compatibility of mutated adult neuronal genomes with reprogramming to pluripotency and development. PMID:26948891

  1. The Complete Genome Sequences, Unique Mutational Spectra, and Developmental Potency of Adult Neurons Revealed by Cloning.

    PubMed

    Hazen, Jennifer L; Faust, Gregory G; Rodriguez, Alberto R; Ferguson, William C; Shumilina, Svetlana; Clark, Royden A; Boland, Michael J; Martin, Greg; Chubukov, Pavel; Tsunemoto, Rachel K; Torkamani, Ali; Kupriyanov, Sergey; Hall, Ira M; Baldwin, Kristin K

    2016-03-16

    Somatic mutation in neurons is linked to neurologic disease and implicated in cell-type diversification. However, the origin, extent, and patterns of genomic mutation in neurons remain unknown. We established a nuclear transfer method to clonally amplify the genomes of neurons from adult mice for whole-genome sequencing. Comprehensive mutation detection and independent validation revealed that individual neurons harbor ∼100 unique mutations from all classes but lack recurrent rearrangements. Most neurons contain at least one gene-disrupting mutation and rare (0-2) mobile element insertions. The frequency and gene bias of neuronal mutations differ from other lineages, potentially due to novel mechanisms governing postmitotic mutation. Fertile mice were cloned from several neurons, establishing the compatibility of mutated adult neuronal genomes with reprogramming to pluripotency and development.

  2. Dynamic functional network connectivity reveals unique and overlapping profiles of insula subdivisions.

    PubMed

    Nomi, Jason S; Farrant, Kristafor; Damaraju, Eswar; Rachakonda, Srinivas; Calhoun, Vince D; Uddin, Lucina Q

    2016-05-01

    The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data-driven approach were subjected to static- and dynamic functional network connectivity (s-FNC and d-FNC) analyses. Static-FNC analyses replicated previous work demonstrating a cognition-emotion-interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic-FNC analyses consisted of k-means clustering of sliding windows to identify variable insula connectivity states. The d-FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition-emotion-interoception division observed from the s-FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s-FNC and d-FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d-FNC approach can capture functional dynamics masked by s-FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. Hum Brain Mapp 37:1770-1787, 2016. © 2016 Wiley Periodicals, Inc. PMID:26880689

  3. An evolutionary analysis of flightin reveals a conserved motif unique and widespread in Pancrustacea.

    PubMed

    Soto-Adames, Felipe N; Alvarez-Ortiz, Pedro; Vigoreaux, Jim O

    2014-01-01

    Flightin is a thick filament protein that in Drosophila melanogaster is uniquely expressed in the asynchronous, indirect flight muscles (IFM). Flightin is required for the structure and function of the IFM and is indispensable for flight in Drosophila. Given the importance of flight acquisition in the evolutionary history of insects, here we study the phylogeny and distribution of flightin. Flightin was identified in 69 species of hexapods in classes Collembola (springtails), Protura, Diplura, and insect orders Thysanura (silverfish), Dictyoptera (roaches), Orthoptera (grasshoppers), Pthiraptera (lice), Hemiptera (true bugs), Coleoptera (beetles), Neuroptera (green lacewing), Hymenoptera (bees, ants, and wasps), Lepidoptera (moths), and Diptera (flies and mosquitoes). Flightin was also found in 14 species of crustaceans in orders Anostraca (water flea), Cladocera (brine shrimp), Isopoda (pill bugs), Amphipoda (scuds, sideswimmers), and Decapoda (lobsters, crabs, and shrimps). Flightin was not identified in representatives of chelicerates, myriapods, or any species outside Pancrustacea (Tetraconata, sensu Dohle). Alignment of amino acid sequences revealed a conserved region of 52 amino acids, referred herein as WYR, that is bound by strictly conserved tryptophan (W) and arginine (R) and an intervening sequence with a high content of tyrosines (Y). This motif has no homologs in GenBank or PROSITE and is unique to flightin and paraflightin, a putative flightin paralog identified in decapods. A third motif of unclear affinities to pancrustacean WYR was observed in chelicerates. Phylogenetic analysis of amino acid sequences of the conserved motif suggests that paraflightin originated before the divergence of amphipods, isopods, and decapods. We conclude that flightin originated de novo in the ancestor of Pancrustacea > 500 MYA, well before the divergence of insects (~400 MYA) and the origin of flight (~325 MYA), and that its IFM-specific function in Drosophila is a more

  4. An evolutionary analysis of flightin reveals a conserved motif unique and widespread in Pancrustacea.

    PubMed

    Soto-Adames, Felipe N; Alvarez-Ortiz, Pedro; Vigoreaux, Jim O

    2014-01-01

    Flightin is a thick filament protein that in Drosophila melanogaster is uniquely expressed in the asynchronous, indirect flight muscles (IFM). Flightin is required for the structure and function of the IFM and is indispensable for flight in Drosophila. Given the importance of flight acquisition in the evolutionary history of insects, here we study the phylogeny and distribution of flightin. Flightin was identified in 69 species of hexapods in classes Collembola (springtails), Protura, Diplura, and insect orders Thysanura (silverfish), Dictyoptera (roaches), Orthoptera (grasshoppers), Pthiraptera (lice), Hemiptera (true bugs), Coleoptera (beetles), Neuroptera (green lacewing), Hymenoptera (bees, ants, and wasps), Lepidoptera (moths), and Diptera (flies and mosquitoes). Flightin was also found in 14 species of crustaceans in orders Anostraca (water flea), Cladocera (brine shrimp), Isopoda (pill bugs), Amphipoda (scuds, sideswimmers), and Decapoda (lobsters, crabs, and shrimps). Flightin was not identified in representatives of chelicerates, myriapods, or any species outside Pancrustacea (Tetraconata, sensu Dohle). Alignment of amino acid sequences revealed a conserved region of 52 amino acids, referred herein as WYR, that is bound by strictly conserved tryptophan (W) and arginine (R) and an intervening sequence with a high content of tyrosines (Y). This motif has no homologs in GenBank or PROSITE and is unique to flightin and paraflightin, a putative flightin paralog identified in decapods. A third motif of unclear affinities to pancrustacean WYR was observed in chelicerates. Phylogenetic analysis of amino acid sequences of the conserved motif suggests that paraflightin originated before the divergence of amphipods, isopods, and decapods. We conclude that flightin originated de novo in the ancestor of Pancrustacea > 500 MYA, well before the divergence of insects (~400 MYA) and the origin of flight (~325 MYA), and that its IFM-specific function in Drosophila is a more

  5. Chætognath transcriptome reveals ancestral and unique features among bilaterians

    PubMed Central

    Marlétaz, Ferdinand; Gilles, André; Caubit, Xavier; Perez, Yvan; Dossat, Carole; Samain, Sylvie; Gyapay, Gabor; Wincker, Patrick; Le Parco, Yannick

    2008-01-01

    Background The chætognaths (arrow worms) have puzzled zoologists for years because of their astonishing morphological and developmental characteristics. Despite their deuterostome-like development, phylogenomic studies recently positioned the chætognath phylum in protostomes, most likely in an early branching. This key phylogenetic position and the peculiar characteristics of chætognaths prompted further investigation of their genomic features. Results Transcriptomic and genomic data were collected from the chætognath Spadella cephaloptera through the sequencing of expressed sequence tags and genomic bacterial artificial chromosome clones. Transcript comparisons at various taxonomic scales emphasized the conservation of a core gene set and phylogenomic analysis confirmed the basal position of chætognaths among protostomes. A detailed survey of transcript diversity and individual genotyping revealed a past genome duplication event in the chætognath lineage, which was, surprisingly, followed by a high retention rate of duplicated genes. Moreover, striking genetic heterogeneity was detected within the sampled population at the nuclear and mitochondrial levels but cannot be explained by cryptic speciation. Finally, we found evidence for trans-splicing maturation of transcripts through splice-leader addition in the chætognath phylum and we further report that this processing is associated with operonic transcription. Conclusion These findings reveal both shared ancestral and unique derived characteristics of the chætognath genome, which suggests that this genome is likely the product of a very original evolutionary history. These features promote chætognaths as a pivotal model for comparative genomics, which could provide new clues for the investigation of the evolution of animal genomes. PMID:18533022

  6. The Affymetrix DMET Plus Platform Reveals Unique Distribution of ADME-Related Variants in Ethnic Arabs

    PubMed Central

    Wakil, Salma M.; Nguyen, Cao; Muiya, Nzioka P.; Andres, Editha; Lykowska-Tarnowska, Agnieszka; Baz, Batoul; Meyer, Brian F.; Morahan, Grant

    2015-01-01

    Background. The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s), the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among individuals, but also between ethnic populations. Materials and Methods. We genotyped 600 Saudi individuals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs. Results. Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs) than those in other ethnic groups. Discussion. The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population. PMID:25802476

  7. The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods

    PubMed Central

    Cao, Zhijian; Yu, Yao; Wu, Yingliang; Hao, Pei; Di, Zhiyong; He, Yawen; Chen, Zongyun; Yang, Weishan; Shen, Zhiyong; He, Xiaohua; Sheng, Jia; Xu, Xiaobo; Pan, Bohu; Feng, Jing; Yang, Xiaojuan; Hong, Wei; Zhao, Wenjuan; Li, Zhongjie; Huang, Kai; Li, Tian; Kong, Yimeng; Liu, Hui; Jiang, Dahe; Zhang, Binyan; Hu, Jun; Hu, Youtian; Wang, Bin; Dai, Jianliang; Yuan, Bifeng; Feng, Yuqi; Huang, Wei; Xing, Xiaojing; Zhao, Guoping; Li, Xuan; Li, Yixue; Li, Wenxin

    2013-01-01

    Representing a basal branch of arachnids, scorpions are known as ‘living fossils’ that maintain an ancient anatomy and are adapted to have survived extreme climate changes. Here we report the genome sequence of Mesobuthus martensii, containing 32,016 protein-coding genes, the most among sequenced arthropods. Although M. martensii appears to evolve conservatively, it has a greater gene family turnover than the insects that have undergone diverse morphological and physiological changes, suggesting the decoupling of the molecular and morphological evolution in scorpions. Underlying the long-term adaptation of scorpions is the expansion of the gene families enriched in basic metabolic pathways, signalling pathways, neurotoxins and cytochrome P450, and the different dynamics of expansion between the shared and the scorpion lineage-specific gene families. Genomic and transcriptomic analyses further illustrate the important genetic features associated with prey, nocturnal behaviour, feeding and detoxification. The M. martensii genome reveals a unique adaptation model of arthropods, offering new insights into the genetic bases of the living fossils. PMID:24129506

  8. Comparative Analysis of 35 Basidiomycete Genomes Reveals Diversity and Uniqueness of the Phylum

    SciTech Connect

    Riley, Robert; Salamov, Asaf; Otillar, Robert; Fagnan, Kirsten; Boussau, Bastien; Brown, Daren; Henrissat, Bernard; Levasseur, Anthony; Held, Benjamin; Nagy, Laszlo; Floudas, Dimitris; Morin, Emmanuelle; Manning, Gerard; Baker, Scott; Martin, Francis; Blanchette, Robert; Hibbett, David; Grigoriev, Igor V.

    2013-03-11

    Fungi of the phylum Basidiomycota (basidiomycetes), make up some 37percent of the described fungi, and are important in forestry, agriculture, medicine, and bioenergy. This diverse phylum includes symbionts, pathogens, and saprobes including wood decaying fungi. To better understand the diversity of this phylum we compared the genomes of 35 basidiomycete fungi including 6 newly sequenced genomes. The genomes of basidiomycetes span extremes of genome size, gene number, and repeat content. A phylogenetic tree of Basidiomycota was generated using the Phyldog software, which uses all available protein sequence data to simultaneously infer gene and species trees. Analysis of core genes reveals that some 48percent of basidiomycete proteins are unique to the phylum with nearly half of those (22percent) comprising proteins found in only one organism. Phylogenetic patterns of plant biomass-degrading genes suggest a continuum rather than a sharp dichotomy between the white rot and brown rot modes of wood decay among the members of Agaricomycotina subphylum. There is a correlation of the profile of certain gene families to nutritional mode in Agaricomycotina. Based on phylogenetically-informed PCA analysis of such profiles, we predict that that Botryobasidium botryosum and Jaapia argillacea have properties similar to white rot species, although neither has liginolytic class II fungal peroxidases. Furthermore, we find that both fungi exhibit wood decay with white rot-like characteristics in growth assays. Analysis of the rate of discovery of proteins with no or few homologs suggests the high value of continued sequencing of basidiomycete fungi.

  9. The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods.

    PubMed

    Cao, Zhijian; Yu, Yao; Wu, Yingliang; Hao, Pei; Di, Zhiyong; He, Yawen; Chen, Zongyun; Yang, Weishan; Shen, Zhiyong; He, Xiaohua; Sheng, Jia; Xu, Xiaobo; Pan, Bohu; Feng, Jing; Yang, Xiaojuan; Hong, Wei; Zhao, Wenjuan; Li, Zhongjie; Huang, Kai; Li, Tian; Kong, Yimeng; Liu, Hui; Jiang, Dahe; Zhang, Binyan; Hu, Jun; Hu, Youtian; Wang, Bin; Dai, Jianliang; Yuan, Bifeng; Feng, Yuqi; Huang, Wei; Xing, Xiaojing; Zhao, Guoping; Li, Xuan; Li, Yixue; Li, Wenxin

    2013-01-01

    Representing a basal branch of arachnids, scorpions are known as 'living fossils' that maintain an ancient anatomy and are adapted to have survived extreme climate changes. Here we report the genome sequence of Mesobuthus martensii, containing 32,016 protein-coding genes, the most among sequenced arthropods. Although M. martensii appears to evolve conservatively, it has a greater gene family turnover than the insects that have undergone diverse morphological and physiological changes, suggesting the decoupling of the molecular and morphological evolution in scorpions. Underlying the long-term adaptation of scorpions is the expansion of the gene families enriched in basic metabolic pathways, signalling pathways, neurotoxins and cytochrome P450, and the different dynamics of expansion between the shared and the scorpion lineage-specific gene families. Genomic and transcriptomic analyses further illustrate the important genetic features associated with prey, nocturnal behaviour, feeding and detoxification. The M. martensii genome reveals a unique adaptation model of arthropods, offering new insights into the genetic bases of the living fossils.

  10. Metagenomic investigation of the geologically unique Hellenic Volcanic Arc reveals a distinctive ecosystem with unexpected physiology.

    PubMed

    Oulas, Anastasis; Polymenakou, Paraskevi N; Seshadri, Rekha; Tripp, H James; Mandalakis, Manolis; Paez-Espino, A David; Pati, Amrita; Chain, Patrick; Nomikou, Paraskevi; Carey, Steven; Kilias, Stephanos; Christakis, Christos; Kotoulas, Georgios; Magoulas, Antonios; Ivanova, Natalia N; Kyrpides, Nikos C

    2016-04-01

    Hydrothermal vents represent a deep, hot, aphotic biosphere where chemosynthetic primary producers, fuelled by chemicals from Earth's subsurface, form the basis of life. In this study, we examined microbial mats from two distinct volcanic sites within the Hellenic Volcanic Arc (HVA). The HVA is geologically and ecologically unique, with reported emissions of CO2 -saturated fluids at temperatures up to 220°C and a notable absence of macrofauna. Metagenomic data reveals highly complex prokaryotic communities composed of chemolithoautotrophs, some methanotrophs, and to our surprise, heterotrophs capable of anaerobic degradation of aromatic hydrocarbons. Our data suggest that aromatic hydrocarbons may indeed be a significant source of carbon in these sites, and instigate additional research into the nature and origin of these compounds in the HVA. Novel physiology was assigned to several uncultured prokaryotic lineages; most notably, a SAR406 representative is attributed with a role in anaerobic hydrocarbon degradation. This dataset, the largest to date from submarine volcanic ecosystems, constitutes a significant resource of novel genes and pathways with potential biotechnological applications. PMID:26487573

  11. Chasing the elusive Euryarchaeota class WSA2: genomes reveal a uniquely fastidious methyl-reducing methanogen.

    PubMed

    Nobu, Masaru Konishi; Narihiro, Takashi; Kuroda, Kyohei; Mei, Ran; Liu, Wen-Tso

    2016-10-01

    The ecophysiology of one candidate methanogen class WSA2 (or Arc I) remains largely uncharacterized, despite the long history of research on Euryarchaeota methanogenesis. To expand our understanding of methanogen diversity and evolution, we metagenomically recover eight draft genomes for four WSA2 populations. Taxonomic analyses indicate that WSA2 is a distinct class from other Euryarchaeota. None of genomes harbor pathways for CO2-reducing and aceticlastic methanogenesis, but all possess H2 and CO oxidation and energy conservation through H2-oxidizing electron confurcation and internal H2 cycling. As the only discernible methanogenic outlet, they consistently encode a methylated thiol coenzyme M methyltransferase. Although incomplete, all draft genomes point to the proposition that WSA2 is the first discovered methanogen restricted to methanogenesis through methylated thiol reduction. In addition, the genomes lack pathways for carbon fixation, nitrogen fixation and biosynthesis of many amino acids. Acetate, malonate and propionate may serve as carbon sources. Using methylated thiol reduction, WSA2 may not only bridge the carbon and sulfur cycles in eutrophic methanogenic environments, but also potentially compete with CO2-reducing methanogens and even sulfate reducers. These findings reveal a remarkably unique methanogen 'Candidatus Methanofastidiosum methylthiophilus' as the first insight into the sixth class of methanogens 'Candidatus Methanofastidiosa'.

  12. A novel sigma factor reveals a unique regulon controlling cell-specific recombination in Mycoplasma genitalium

    PubMed Central

    Torres-Puig, Sergi; Broto, Alicia; Querol, Enrique; Piñol, Jaume; Pich, Oscar Q.

    2015-01-01

    The Mycoplasma genitalium MG428 protein shows homology to members of the sigma-70 family of sigma factors. Herein, we found that MG428 activates transcription of recA, ruvA and ruvB as well as several genes with unknown function. Deletion of MG_428 or some of the up-regulated unknown genes led to severe recombination defects. Single cell analyses revealed that activation of the MG428-regulon is a rare event under laboratory growth conditions. A conserved sequence with sigma-70 promoter architecture (TTGTCA-N18/19-ATTWAT) was identified in the upstream region of all of the MG428-regulated genes or operons. Primer extension analyses demonstrated that transcription initiates immediately downstream of this sigma70-type promoter in a MG428-dependent manner. Furthermore, mutagenesis of the conserved −10 and −35 elements corroborated the requirement of these regions for promoter function. Therefore, a new mycoplasma promoter directs transcription of a unique recombination regulon. Additionally, MG428 was found to interact with the RNAP core enzyme, reinforcing the predicted role of this protein as an alternative sigma factor. Finally, our results indicate that MG428 contributes to the generation of genetic diversity in this model organism. Since recombination is an important mechanism to generate antigenic variation, MG428 emerges as a novel factor contributing to M. genitalium virulence. PMID:25925568

  13. A novel sigma factor reveals a unique regulon controlling cell-specific recombination in Mycoplasma genitalium.

    PubMed

    Torres-Puig, Sergi; Broto, Alicia; Querol, Enrique; Piñol, Jaume; Pich, Oscar Q

    2015-05-26

    The Mycoplasma genitalium MG428 protein shows homology to members of the sigma-70 family of sigma factors. Herein, we found that MG428 activates transcription of recA, ruvA and ruvB as well as several genes with unknown function. Deletion of MG_428 or some of the up-regulated unknown genes led to severe recombination defects. Single cell analyses revealed that activation of the MG428-regulon is a rare event under laboratory growth conditions. A conserved sequence with sigma-70 promoter architecture (TTGTCA-N(18/19)-ATTWAT) was identified in the upstream region of all of the MG428-regulated genes or operons. Primer extension analyses demonstrated that transcription initiates immediately downstream of this sigma70-type promoter in a MG428-dependent manner. Furthermore, mutagenesis of the conserved -10 and -35 elements corroborated the requirement of these regions for promoter function. Therefore, a new mycoplasma promoter directs transcription of a unique recombination regulon. Additionally, MG428 was found to interact with the RNAP core enzyme, reinforcing the predicted role of this protein as an alternative sigma factor. Finally, our results indicate that MG428 contributes to the generation of genetic diversity in this model organism. Since recombination is an important mechanism to generate antigenic variation, MG428 emerges as a novel factor contributing to M. genitalium virulence. PMID:25925568

  14. Metagenomic investigation of the geologically unique Hellenic Volcanic Arc reveals a distinctive ecosystem with unexpected physiology.

    PubMed

    Oulas, Anastasis; Polymenakou, Paraskevi N; Seshadri, Rekha; Tripp, H James; Mandalakis, Manolis; Paez-Espino, A David; Pati, Amrita; Chain, Patrick; Nomikou, Paraskevi; Carey, Steven; Kilias, Stephanos; Christakis, Christos; Kotoulas, Georgios; Magoulas, Antonios; Ivanova, Natalia N; Kyrpides, Nikos C

    2016-04-01

    Hydrothermal vents represent a deep, hot, aphotic biosphere where chemosynthetic primary producers, fuelled by chemicals from Earth's subsurface, form the basis of life. In this study, we examined microbial mats from two distinct volcanic sites within the Hellenic Volcanic Arc (HVA). The HVA is geologically and ecologically unique, with reported emissions of CO2 -saturated fluids at temperatures up to 220°C and a notable absence of macrofauna. Metagenomic data reveals highly complex prokaryotic communities composed of chemolithoautotrophs, some methanotrophs, and to our surprise, heterotrophs capable of anaerobic degradation of aromatic hydrocarbons. Our data suggest that aromatic hydrocarbons may indeed be a significant source of carbon in these sites, and instigate additional research into the nature and origin of these compounds in the HVA. Novel physiology was assigned to several uncultured prokaryotic lineages; most notably, a SAR406 representative is attributed with a role in anaerobic hydrocarbon degradation. This dataset, the largest to date from submarine volcanic ecosystems, constitutes a significant resource of novel genes and pathways with potential biotechnological applications.

  15. Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen.

    PubMed

    Adissu, Hibret A; Estabel, Jeanne; Sunter, David; Tuck, Elizabeth; Hooks, Yvette; Carragher, Damian M; Clarke, Kay; Karp, Natasha A; Newbigging, Susan; Jones, Nora; Morikawa, Lily; White, Jacqueline K; McKerlie, Colin

    2014-05-01

    The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.

  16. Systematic analyses reveal uniqueness and origin of the CFEM domain in fungi.

    PubMed

    Zhang, Zhen-Na; Wu, Qin-Yi; Zhang, Gui-Zhi; Zhu, Yue-Yan; Murphy, Robert W; Liu, Zhen; Zou, Cheng-Gang

    2015-08-10

    CFEM domain commonly occurs in fungal extracellular membrane proteins. To provide insights for understanding putative functions of CFEM, we investigate the evolutionary dynamics of CFEM domains by systematic comparative genomic analyses among diverse animals, plants, and more than 100 fungal species, which are representative across the entire group of fungi. We here show that CFEM domain is unique to fungi. Experiments using tissue culture demonstrate that the CFEM-containing ESTs in some plants originate from endophytic fungi. We also find that CFEM domain does not occur in all fungi. Its single origin dates to the most recent common ancestors of Ascomycota and Basidiomycota, instead of multiple origins. Although the length and architecture of CFEM domains are relatively conserved, the domain-number varies significantly among different fungal species. In general, pathogenic fungi have a larger number of domains compared to other species. Domain-expansion across fungal genomes appears to be driven by domain duplication and gene duplication via recombination. These findings generate a clear evolutionary trajectory of CFEM domains and provide novel insights into the functional exchange of CFEM-containing proteins from cell-surface components to mediators in host-pathogen interactions.

  17. Uranus' Southern Circulation Revealed by Voyager-2 Images: Asymmetric, Unique, Unexpected

    NASA Astrophysics Data System (ADS)

    Karkoschka, Erich

    2014-11-01

    The southern half of Uranus' southern hemisphere of Uranus has been exceptionally bland. Only a single discrete feature was detected in Voyager-2 images, and none has been seen in thousands of HST and ground-based images since. All other observed regions on Uranus and jovian planets have many features that defined circulation patterns of the jovian planets, but the circulation of Uranus south of -45 deg latitude has been unknown.We performed a reanalysis of Voyager images of Uranus that revealed dozens of discrete features instead of the single feature known before. We improved flatfielding, pad-pixel treatment, and nonlinearity correction. We greatly decreased noise by averaging up to 1600 images. The result is a rotational profile without major gaps.Uranus' high southern latitudes are exceptional in several aspects: 1) The rotational profile has sharp kinks while it is smooth elsewhere on the ice giants. This puts current ideas of a simple Hadley cell on each hemisphere into question. 2) The rotational profile has a large north-south asymmetry, an order of magnitude larger than elsewhere on the jovian planets. 3) Between -68 and -59 deg latitude, the rotational shear is some 30 times lower than at other latitudes. Here, winds speeds around 200 m/s are regular to the 0.1 m/s level. 4) The South Pole had a spot off center rotating 5 h faster than the interior, which has not been observed elsewhere on jovian planets. 5) Uranus revealed spirals winding around the whole planet more than once that indicate very regular meridional motions, to the 2 cm/s level. 6) The latitude at -84 deg was featureless even at a signal-to-noise ratio of 55,000, one of the blandest zones in nature.Some features show significant evolution within the 5-week observing period providing constraints on dynamics. Features also show distinct spectral characteristics in the 8-filter data set providing constraints on the physical nature of features and their altitude. We have the data to

  18. Giraffe genome sequence reveals clues to its unique morphology and physiology

    PubMed Central

    Agaba, Morris; Ishengoma, Edson; Miller, Webb C.; McGrath, Barbara C.; Hudson, Chelsea N.; Bedoya Reina, Oscar C.; Ratan, Aakrosh; Burhans, Rico; Chikhi, Rayan; Medvedev, Paul; Praul, Craig A.; Wu-Cavener, Lan; Wood, Brendan; Robertson, Heather; Penfold, Linda; Cavener, Douglas R.

    2016-01-01

    The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions. PMID:27187213

  19. Giraffe genome sequence reveals clues to its unique morphology and physiology.

    PubMed

    Agaba, Morris; Ishengoma, Edson; Miller, Webb C; McGrath, Barbara C; Hudson, Chelsea N; Bedoya Reina, Oscar C; Ratan, Aakrosh; Burhans, Rico; Chikhi, Rayan; Medvedev, Paul; Praul, Craig A; Wu-Cavener, Lan; Wood, Brendan; Robertson, Heather; Penfold, Linda; Cavener, Douglas R

    2016-01-01

    The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions. PMID:27187213

  20. Transcriptomic sequencing reveals a set of unique genes activated by butyrate-induced histone modification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate is a nutritional element with strong epigenetic regulatory activity as an inhibitor of histone deacetylases (HDACs). Based on the analysis of differentially expressed genes induced by butyrate in the bovine epithelial cell using deep RNA-sequencing technology (RNA-seq), a set of unique gen...

  1. Hemispheric asymmetries in word recognition as revealed by the orthographic uniqueness point effect.

    PubMed

    Izura, Cristina; Wright, Victoria C; Fouquet, Nathalie

    2014-01-01

    The orthographic uniqueness point (OUP) refers to the first letter of a word that, reading from left to right, makes the word unique. It has recently been proposed that OUPs might be relevant in word recognition and their influence could inform the long-lasting debate of whether - and to what extent - printed words are recognized serially or in parallel. The present study represents the first investigation of the neural and behavioral effects of OUP on visual word recognition. Behaviourally, late OUP words were identified faster and more accurately in a lexical decision task. Analysis of event-related potentials demonstrated a hemispheric asymmetry on the N170 component, with the left hemisphere appearing to be more sensitive to the position of the OUP within a word than the right hemisphere. These results suggest that processing of centrally presented words is likely to occur in a partially parallel manner, as an ends-in scanning process.

  2. Unique lipid anchor attaches Vi antigen capsule to the surface of Salmonella enterica serovar Typhi.

    PubMed

    Liston, Sean D; Ovchinnikova, Olga G; Whitfield, Chris

    2016-06-14

    Polysaccharide capsules are surface structures that are critical for the virulence of many Gram-negative pathogenic bacteria. Salmonella enterica serovar Typhi is the etiological agent of typhoid fever. It produces a capsular polysaccharide known as "Vi antigen," which is composed of nonstoichiometrically O-acetylated α-1,4-linked N-acetylgalactosaminuronic acid residues. This glycan is a component of currently available vaccines. The genetic locus for Vi antigen production is also present in soil bacteria belonging to the genus Achromobacter Vi antigen assembly follows a widespread general strategy with a characteristic glycan export step involving an ATP-binding cassette transporter. However, Vi antigen producers lack the enzymes that build the conserved terminal glycolipid characterizing other capsules using this method. Achromobacter species possess a Vi antigen-specific depolymerase enzyme missing in S enterica Typhi, and we exploited this enzyme to isolate acylated Vi antigen termini. Mass spectrometry analysis revealed a reducing terminal N-acetylhexosamine residue modified with two β-hydroxyl acyl chains. This terminal structure resembles one half of lipid A, the hydrophobic portion of bacterial lipopolysaccharides. The VexE protein encoded in the Vi antigen biosynthesis locus shares similarity with LpxL, an acyltransferase from lipid A biosynthesis. In the absence of VexE, Vi antigen is produced, but its physical properties are altered, its export is impaired, and a Vi capsule structure is not assembled on the cell surface. The structure of the lipidated terminus dictates a unique assembly mechanism and has potential implications in pathogenesis and vaccine production. PMID:27226298

  3. Existence and uniqueness of analytic solution for unsteady crystals with zero surface tension

    NASA Astrophysics Data System (ADS)

    Xie, Xuming

    2007-03-01

    We study the initial value problem for two-dimensional dendritic crystal growth with zero surface tension. If the initial data is analytic and close to Ivantsov steady solution, it is proved that unique analytic solution exists locally in time. The analysis is based on a Nirenberg Theorem on abstract Cauchy-Kovalevsky problem in properly chosen Banach spaces.

  4. Unique gene program of rat small resistance mesenteric arteries as revealed by deep RNA sequencing

    PubMed Central

    Reho, John J; Shetty, Amol; Dippold, Rachael P; Mahurkar, Anup; Fisher, Steven A

    2015-01-01

    Deep sequencing of RNA samples from rat small mesenteric arteries (MA) and aorta (AO) identified common and unique features of their gene programs. ∼5% of mRNAs were quantitatively differentially expressed in MA versus AO. Unique transcriptional control in MA smooth muscle is suggested by the selective or enriched expression of transcription factors Nkx2-3, HAND2, and Tcf21 (Capsulin). Enrichment in AO of PPAR transcription factors and their target genes of mitochondrial function, lipid metabolism, and oxidative phosphorylation is consistent with slow (oxidative) tonic smooth muscle. In contrast MA was enriched in contractile and calcium channel mRNAs suggestive of components of fast (glycolytic) phasic smooth muscle. Myosin phosphatase regulatory subunit paralogs Mypt1 and p85 were expressed at similar levels, while smooth muscle MLCK was the only such kinase expressed, suggesting functional redundancy of the former but not the latter in accordance with mouse knockout studies. With regard to vaso-regulatory signals, purinergic receptors P2rx1 and P2rx5 were reciprocally expressed in MA versus AO, while the olfactory receptor Olr59 was enriched in MA. Alox15, which generates the EDHF HPETE, was enriched in MA while eNOS was equally expressed, consistent with the greater role of EDHF in the smaller arteries. mRNAs that were not expressed at a level consistent with impugned function include skeletal myogenic factors, IKK2, nonmuscle myosin, and Gnb3. This screening analysis of gene expression in the small mesenteric resistance arteries suggests testable hypotheses regarding unique aspects of small artery function in the regional control of blood flow. PMID:26156969

  5. Parapoxvirus (PPV) of red deer reveals subclinical infection and confirms a unique species.

    PubMed

    Friederichs, Schirin; Krebs, Stefan; Blum, Helmut; Lang, Heike; Büttner, Mathias

    2015-06-01

    Parapoxvirus (PPV) infections are of worldwide importance, particularly in sheep and goat herds. Owing to the zoonotic potential of all PPV species, they are a permanent threat to human health as well. The virus is also known to affect wildlife, as reported for pinnipeds, red deer and several other wild ruminants. PPVs found in red deer have been claimed as a unique species according to certain genomic features. So far infection of wildlife has been recognized because of clinical manifestation such as inflammation, stomatitis or typical pox-like lesions in the skin or mucous membranes. Here we report the use of targeted molecular diagnostics for the presence of PPV genomes in tonsil swabs of apparently healthy red deer in the Bavarian Alps. Out of 1764 swabs, 0.79 % tested positive for PPV genome presence. From one sample, PPV was successfully isolated in cell culture. This virus became the subject of complete genome characterization using next generation sequencing and various subsidiary PCR protocols. Strikingly, about a quarter of all ORFs were found to be larger than the corresponding ORFs in the reference PPV genome sequences used for comparison. To our knowledge this is the first genome-wide analysis that confirms red deer PPV as a unique species within the genus Parapoxvirus in Europe. Persistence of PPV in Alpine red deer indicates a source for virus transmission to susceptible livestock and hunters. The findings provide a further example of wildlife animals playing an important role as an inconspicuous reservoir of zoonotic diseases.

  6. Electron microscopy reveals unique microfossil preservation in 1 billion-year-old lakes

    NASA Astrophysics Data System (ADS)

    Saunders, M.; Kong, C.; Menon, S.; Wacey, D.

    2014-06-01

    Electron microscopy was applied to the study of 1 billion-year-old microfossils from northwest Scotland in order to investigate their 3D morphology and mode of fossilization. 3D-FIB-SEM revealed high quality preservation of organic cell walls with only minor amounts of post-mortem decomposition, followed by variable degrees of morphological alteration (folding and compression of cell walls) during sediment compaction. EFTEM mapping plus SAED revealed a diverse fossilizing mineral assemblage including K-rich clay, Fe-Mg-rich clay and calcium phosphate, with each mineral occupying specific microenvironments in proximity to carbonaceous microfossil cell walls.

  7. Nanoscopic characterization of the water vapor-salt interfacial layer reveals a unique biphasic adsorption process.

    PubMed

    Yang, Liu; He, Jianfeng; Shen, Yi; Li, Xiaowei; Sun, Jielin; Czajkowsky, Daniel M; Shao, Zhifeng

    2016-01-01

    Our quantitative understanding of water adsorption onto salt surfaces under ambient conditions is presently quite poor owing to the difficulties in directly characterizing this interfacial layer under these conditions. Here we determine the thickness of the interfacial layer on NaCl at different relative humidities (RH) based on a novel application of atomic force spectroscopy and capillary condensation theory. In particular, we take advantage of the microsecond-timescale of the capillary condensation process to directly resolve the magnitude of its contribution in the tip-sample interaction, from which the interfacial water thickness is determined. Further, to correlate this thickness with salt dissolution, we also measure surface conductance under similar conditions. We find that below 30% RH, there is essentially only the deposition of water molecules onto this surface, typical of conventional adsorption onto solid surfaces. However, above 30% RH, adsorption is simultaneous with the dissolution of ions, unlike conventional adsorption, leading to a rapid increase of surface conductance. Thus, water adsorption on NaCl is an unconventional biphasic process in which the interfacial layer not only exhibits quantitative differences in thickness but also qualitative differences in composition. PMID:27527905

  8. Nanoscopic characterization of the water vapor-salt interfacial layer reveals a unique biphasic adsorption process

    NASA Astrophysics Data System (ADS)

    Yang, Liu; He, Jianfeng; Shen, Yi; Li, Xiaowei; Sun, Jielin; Czajkowsky, Daniel M.; Shao, Zhifeng

    2016-08-01

    Our quantitative understanding of water adsorption onto salt surfaces under ambient conditions is presently quite poor owing to the difficulties in directly characterizing this interfacial layer under these conditions. Here we determine the thickness of the interfacial layer on NaCl at different relative humidities (RH) based on a novel application of atomic force spectroscopy and capillary condensation theory. In particular, we take advantage of the microsecond-timescale of the capillary condensation process to directly resolve the magnitude of its contribution in the tip-sample interaction, from which the interfacial water thickness is determined. Further, to correlate this thickness with salt dissolution, we also measure surface conductance under similar conditions. We find that below 30% RH, there is essentially only the deposition of water molecules onto this surface, typical of conventional adsorption onto solid surfaces. However, above 30% RH, adsorption is simultaneous with the dissolution of ions, unlike conventional adsorption, leading to a rapid increase of surface conductance. Thus, water adsorption on NaCl is an unconventional biphasic process in which the interfacial layer not only exhibits quantitative differences in thickness but also qualitative differences in composition.

  9. Nanoscopic characterization of the water vapor-salt interfacial layer reveals a unique biphasic adsorption process

    PubMed Central

    Yang, Liu; He, Jianfeng; Shen, Yi; Li, Xiaowei; Sun, Jielin; Czajkowsky, Daniel M.; Shao, Zhifeng

    2016-01-01

    Our quantitative understanding of water adsorption onto salt surfaces under ambient conditions is presently quite poor owing to the difficulties in directly characterizing this interfacial layer under these conditions. Here we determine the thickness of the interfacial layer on NaCl at different relative humidities (RH) based on a novel application of atomic force spectroscopy and capillary condensation theory. In particular, we take advantage of the microsecond-timescale of the capillary condensation process to directly resolve the magnitude of its contribution in the tip-sample interaction, from which the interfacial water thickness is determined. Further, to correlate this thickness with salt dissolution, we also measure surface conductance under similar conditions. We find that below 30% RH, there is essentially only the deposition of water molecules onto this surface, typical of conventional adsorption onto solid surfaces. However, above 30% RH, adsorption is simultaneous with the dissolution of ions, unlike conventional adsorption, leading to a rapid increase of surface conductance. Thus, water adsorption on NaCl is an unconventional biphasic process in which the interfacial layer not only exhibits quantitative differences in thickness but also qualitative differences in composition. PMID:27527905

  10. Dawn at Ceres reveals an ammoniated surface

    NASA Astrophysics Data System (ADS)

    Pieters, Carle M.; De Sanctis, Maria Cristina; Ammannito, Eleonora; Raponi, Andrea; Combe, Jean-Philippe; McCord, Thomas B.; McSween, Harry; McFadden, Lucy A.; Marchi, Simone; Capaccioni, Fabrizio; Capria, Maria Teresa; Carrozzo, Giacomo; Ciarniello, Mauro; Longobardo, Andrea; Fonte, Sergio; Formisano, Michelangelo; Frigeri, Alessandro; Giardino, Marco; Magni, Gianfranco; Palomba, Enersto; Tosi, Federico; Turrini, Diego; Zambon, Francesca; Jaumann, Ralf; Feldman, William; Prettyman, Thomas; Toplis, Michael; Raymond, Carol A.; Russell, Christopher T.

    2015-11-01

    The Visible and Infrared Mapping Spectrometer (VIR) on board the Dawn spacecraft has observed Ceres’ surface and acquired spectra (0.5 to 5 µm) since January 2015. Here we report the average Ceres spectrum, including the important spectral range (2.6-2.9 µm) previously precluded from (telescopic) measurements due to telluric atmospheric absorptions. The VIR data confirm that the surface is very dark with an average albedo of 0.090 ±0.006 at 0.55 µm, consistent with Hubble Space Telescope data (Li et al., Icarus, 2006) and contains no prominent absorption features in the visible and near-Infrared at wavelengths less than 2.5 µm. Ceres’ average spectrum, however, is characterized by a prominent diagnostic absorption band at 2.7 µm along with weaker absorption bands observed between 3.05-3.1, 3.3-3.4 and 3.9-4 µm. We modeled the new VIR spectra of Ceres with various ices, meteorites, silicates, carbonates, and hydrates using Hapke theory. Results of the spectral modeling indicate that extensive water ice is not present in spectra representing the typical surface acquired to date at relatively low spatial resolution (<11 km/pixel). The best fit is obtained with a mixture of ammoniated phyllosilicates mixed with other clays, Mg-carbonates, serpentine, and a strongly absorbing material, such as magnetite (De Sanctis et al., Nature, 2015, in review). The presence of ammonia-bearing materials in the crust across much of the surface has implications for the origin of Ceres and its internal structure and evolution. At the time of this presentation the Dawn spacecraft will have also completed its high altitude mapping orbit to look for anticipated small-scale mineralogy variations across this remarkable dwarf planet.Acknowledgements: VIR is funded by the Italian Space Agency-ASI and was developed under the leadership of INAF, Rome-Italy. The instrument was built by Selex-Galileo, Florence-Italy. The analyses are supported by ASI, NASA, and the German Space Agency

  11. Polymer Supported Directed Differentiation Reveals a Unique Gene Signature Predicting Stable Hepatocyte Performance.

    PubMed

    Villarin, Baltasar Lucendo; Cameron, Kate; Szkolnicka, Dagmara; Rashidi, Hassan; Bates, Nicola; Kimber, Susan J; Flint, Oliver; Forbes, Stuart J; Iredale, John P; Bradley, Mark; Hay, David C

    2015-08-26

    In theory, pluripotent stem cells can give rise to all somatic cell types found in the human body. The ability to generate renewable sources of human cells has enormous potential to improve human health and wealth. One major obstacle to the routine deployment of stem cell-derived cells is their instability in culture. To tackle this issue a synthetic polymer surface is used.

  12. What determines the relationship between color naming, unique hues, and sensory singularities: Illuminations, surfaces, or photoreceptors?

    PubMed

    Witzel, Christoph; Cinotti, François; O'Regan, J Kevin

    2015-01-01

    The relationship between the sensory signal of the photoreceptors on one hand and color appearance and language on the other hand is completely unclear. A recent finding established a surprisingly accurate correlation between focal colors, unique hues, and so-called singularities in the laws governing how sensory signals for different surfaces change across illuminations. This article examines how this correlation with singularities depends on reflectances, illuminants, and cone sensitivities. Results show that this correlation holds for a large range of illuminants and for a large range of sensors, including sensors that are fundamentally different from human photoreceptors. In contrast, the spectral characteristics of the reflectance spectra turned out to be the key factor that determines the correlation between focal colors, unique hues, and sensory singularities. These findings suggest that the origins of color appearance and color language may be found in particular characteristics of the reflectance spectra that correspond to focal colors and unique hues.

  13. The genome sequence of Atlantic cod reveals a unique immune system.

    PubMed

    Star, Bastiaan; Nederbragt, Alexander J; Jentoft, Sissel; Grimholt, Unni; Malmstrøm, Martin; Gregers, Tone F; Rounge, Trine B; Paulsen, Jonas; Solbakken, Monica H; Sharma, Animesh; Wetten, Ola F; Lanzén, Anders; Winer, Roger; Knight, James; Vogel, Jan-Hinnerk; Aken, Bronwen; Andersen, Oivind; Lagesen, Karin; Tooming-Klunderud, Ave; Edvardsen, Rolf B; Tina, Kirubakaran G; Espelund, Mari; Nepal, Chirag; Previti, Christopher; Karlsen, Bård Ove; Moum, Truls; Skage, Morten; Berg, Paul R; Gjøen, Tor; Kuhl, Heiner; Thorsen, Jim; Malde, Ketil; Reinhardt, Richard; Du, Lei; Johansen, Steinar D; Searle, Steve; Lien, Sigbjørn; Nilsen, Frank; Jonassen, Inge; Omholt, Stig W; Stenseth, Nils Chr; Jakobsen, Kjetill S

    2011-08-10

    Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.

  14. Unique cellular effect of the herbicide bromoxynil revealed by electrophysiological studies using characean cells.

    PubMed

    Shimmen, Teruo

    2010-09-01

    In a previous paper, we proposed that the primary action of the herbicide bromoxynil (BX; 3,5-dibromo-4-hydroxybenzonitrile) is cytosol acidification, based on the fact that bromoxynil induced the inhibition of cytoplasmic streaming and cell death of Chara corallina in acidic external medium (Morimoto and Shimmen in J Plant Res 121:227-233, 2008). In the present study, electrophysiological analysis of the BX effect was carried out in internodal cells of C. corallina. Upon addition of BX, a large and rapid pH-dependent depolarization was induced, supporting our hypothesis. Ioxynil, which belongs to the same group as bromoxynil, also induced a large and rapid membrane depolarization in a pH-dependent manner. On the other hand, four herbicides belonging to other groups of herbicides did not induce such a membrane depolarization. Thus, BX has a unique cellular effect. The decrease in the electro-chemical potential gradient for H(+) across the plasma membrane appears to result in inhibition of cell growth and disturbance of intracellular homeostasis in the presence of BX.

  15. Unique Features of the Loblolly Pine (Pinus taeda L.) Megagenome Revealed Through Sequence Annotation

    PubMed Central

    Wegrzyn, Jill L.; Liechty, John D.; Stevens, Kristian A.; Wu, Le-Shin; Loopstra, Carol A.; Vasquez-Gross, Hans A.; Dougherty, William M.; Lin, Brian Y.; Zieve, Jacob J.; Martínez-García, Pedro J.; Holt, Carson; Yandell, Mark; Zimin, Aleksey V.; Yorke, James A.; Crepeau, Marc W.; Puiu, Daniela; Salzberg, Steven L.; de Jong, Pieter J.; Mockaitis, Keithanne; Main, Doreen; Langley, Charles H.; Neale, David B.

    2014-01-01

    The largest genus in the conifer family Pinaceae is Pinus, with over 100 species. The size and complexity of their genomes (∼20–40 Gb, 2n = 24) have delayed the arrival of a well-annotated reference sequence. In this study, we present the annotation of the first whole-genome shotgun assembly of loblolly pine (Pinus taeda L.), which comprises 20.1 Gb of sequence. The MAKER-P annotation pipeline combined evidence-based alignments and ab initio predictions to generate 50,172 gene models, of which 15,653 are classified as high confidence. Clustering these gene models with 13 other plant species resulted in 20,646 gene families, of which 1554 are predicted to be unique to conifers. Among the conifer gene families, 159 are composed exclusively of loblolly pine members. The gene models for loblolly pine have the highest median and mean intron lengths of 24 fully sequenced plant genomes. Conifer genomes are full of repetitive DNA, with the most significant contributions from long-terminal-repeat retrotransposons. In depth analysis of the tandem and interspersed repetitive content yielded a combined estimate of 82%. PMID:24653211

  16. Human Suv3 protein reveals unique features among SF2 helicases

    SciTech Connect

    Jedrzejczak, Robert; Wang, Jiawei; Dauter, Miroslawa; Szczesny, Roman J.; Stepien, Piotr P.; Dauter, Zbigniew

    2011-11-01

    Crystal structures of the human mitochondrial helicase hSuv3 in complex with AMPPNP and with a short strand of RNA are presented. Suv3 is a helicase that is involved in efficient turnover and surveillance of RNA in eukaryotes. In vitro studies show that human Suv3 (hSuv3) in complex with human polynucleotide phosphorylase has RNA degradosome activity. The enzyme is mainly localized in mitochondria, but small fractions are found in cell nuclei. Here, two X-ray crystallographic structures of human Suv3 in complex with AMPPNP, a nonhydrolysable analog of ATP, and with a short five-nucleotide strand of RNA are presented at resolutions of 2.08 and 2.9 Å, respectively. The structure of the enzyme is very similar in the two complexes and consists of four domains. Two RecA-like domains form the tandem typical of all helicases from the SF2 superfamily which together with the C-terminal all-helical domain makes a ring structure through which the nucleotide strand threads. The mostly helical N-terminal domain is positioned externally with respect to the core of the enzyme. Most of the typical helicase motifs are present in hSuv3, but the protein shows certain unique characteristics, suggesting that Suv3 enzymes may constitute a separate subfamily of helicases.

  17. Human Suv3 protein reveals unique features among SF2 helicases

    SciTech Connect

    Jedrzejczak, Robert; Wang, Jiawei; Dauter, Miroslawa; Szczesny, Roman J.; Stepien, Piotr P.; Dauter, Zbigniew

    2012-03-16

    Suv3 is a helicase that is involved in efficient turnover and surveillance of RNA in eukaryotes. In vitro studies show that human Suv3 (hSuv3) in complex with human polynucleotide phosphorylase has RNA degradosome activity. The enzyme is mainly localized in mitochondria, but small fractions are found in cell nuclei. Here, two X-ray crystallographic structures of human Suv3 in complex with AMPPNP, a nonhydrolysable analog of ATP, and with a short five-nucleotide strand of RNA are presented at resolutions of 2.08 and 2.9 {angstrom}, respectively. The structure of the enzyme is very similar in the two complexes and consists of four domains. Two RecA-like domains form the tandem typical of all helicases from the SF2 superfamily which together with the C-terminal all-helical domain makes a ring structure through which the nucleotide strand threads. The mostly helical N-terminal domain is positioned externally with respect to the core of the enzyme. Most of the typical helicase motifs are present in hSuv3, but the protein shows certain unique characteristics, suggesting that Suv3 enzymes may constitute a separate subfamily of helicases.

  18. Transmission electron microscopy of Tuberculina species (Helicobasidiales) reveals an unique mode of conidiogenesis within Basidiomycota.

    PubMed

    Aghayeva, Dilzara N; Lutz, Matthias; Piątek, Marcin

    2016-08-01

    Tuberculina species represent the asexual life stage of the plant-parasitic sexual genus Helicobasidium. Tuberculina species are distributed all over the world, living in antagonistic symbiosis with over 150 rust species from at least 15 genera. Within the Basidiomycota, besides the spermogonia of rust fungi, only Tuberculina species develop distinct fructifications in the haplophase. However, the knowledge of conidiogenesis in Tuberculina is meagre. Therefore, conidial development in Tuberculina maxima, Tuberculina persicina, and Tuberculina sbrozzii was studied using transmission electron microscopy, and compared to each other as well as to spermatia formation in rust fungi. Significant ultrastructural characteristics such as the movement of nuclei in the process of conidium formation, and formation of the initial and late stages of conidiogenesis are documented. The mode of conidiogenesis of Tuberculina species is unique within the Basidiomycota in that (1) it is realized by haploid fructifications, (2) it is holoblastic, without annellidic proliferation, (3) the nucleus of the conidiogenous cell moves towards the forming conidium, divides, and no daughter nucleus remains inside the conidiogenous cell, and (4) the conidiogenous cell retains only cytoplasmic residues after the development of a single conidium, and a successive conidium is not produced. PMID:27521632

  19. Human Suv3 protein reveals unique features among SF2 helicases

    PubMed Central

    Jedrzejczak, Robert; Wang, Jiawei; Dauter, Miroslawa; Szczesny, Roman J.; Stepien, Piotr P.; Dauter, Zbigniew

    2011-01-01

    Suv3 is a helicase that is involved in efficient turnover and surveillance of RNA in eukaryotes. In vitro studies show that human Suv3 (hSuv3) in complex with human polynucleotide phosphorylase has RNA degradosome activity. The enzyme is mainly localized in mitochondria, but small fractions are found in cell nuclei. Here, two X-ray crystallographic structures of human Suv3 in complex with AMPPNP, a nonhydrolysable analog of ATP, and with a short five-nucleotide strand of RNA are presented at resolutions of 2.08 and 2.9 Å, respectively. The structure of the enzyme is very similar in the two complexes and consists of four domains. Two RecA-like domains form the tandem typical of all helicases from the SF2 superfamily which together with the C-terminal all-helical domain makes a ring structure through which the nucleotide strand threads. The mostly helical N-terminal domain is positioned externally with respect to the core of the enzyme. Most of the typical helicase motifs are present in hSuv3, but the protein shows certain unique characteristics, suggesting that Suv3 enzymes may constitute a separate subfamily of helicases. PMID:22101826

  20. Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens.

    PubMed

    Liu, Guodong; Zhang, Lei; Wei, Xiaomin; Zou, Gen; Qin, Yuqi; Ma, Liang; Li, Jie; Zheng, Huajun; Wang, Shengyue; Wang, Chengshu; Xun, Luying; Zhao, Guo-Ping; Zhou, Zhihua; Qu, Yinbo

    2013-01-01

    Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species. PMID:23383313

  1. Genomic and Secretomic Analyses Reveal Unique Features of the Lignocellulolytic Enzyme System of Penicillium decumbens

    PubMed Central

    Qin, Yuqi; Ma, Liang; Li, Jie; Zheng, Huajun; Wang, Shengyue; Wang, Chengshu; Xun, Luying; Zhao, Guo-Ping; Zhou, Zhihua; Qu, Yinbo

    2013-01-01

    Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species. PMID:23383313

  2. Multilocus sequence typing of hospital-associated Enterococcus faecium from Brazil reveals their unique evolutionary history.

    PubMed

    Titze-de-Almeida, Ricardo; Van Belkum, Alex; Felipe, Maria Sueli Soares; Zanella, Rosemeire C; Top, Janetta; Willems, Rob J L

    2006-01-01

    We studied the genetic relationships between vancomycin-susceptible (n = 11) and -resistant Enterococcus faecium (VRE, n = 20) recovered from Brazil using a multilocus sequence typing (MLST) scheme. Grouping of allelic profiles revealed six clusters of related sequence types (STs) that differ in no more than two of the seven alleles. Of these, one cluster harbored 16 of the 20 isolates recovered during the first VRE outbreak in Brazil. The ampicillin and gentamicin resistance profiles were stable in the isolates that clustered within the groups I-III. Comparison with the allelic profiles of 139 E. faecium from different geographical regions and origins found in the international database http://www.mlst.net revealed that the Brazilian outbreak clone did not cluster in the previously named complex-17. This genetic complex contains hospital epidemic and clinical isolates recovered from different countries and continents. Twenty two of the 31 Brazilian isolates, including the VRE outbreak clone, clustered apart from the E. faecium isolates from the database, suggesting that these Brazilian isolates have a distinct evolutionary history. PMID:16922628

  3. Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens.

    PubMed

    Liu, Guodong; Zhang, Lei; Wei, Xiaomin; Zou, Gen; Qin, Yuqi; Ma, Liang; Li, Jie; Zheng, Huajun; Wang, Shengyue; Wang, Chengshu; Xun, Luying; Zhao, Guo-Ping; Zhou, Zhihua; Qu, Yinbo

    2013-01-01

    Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.

  4. Functional profiles reveal unique ecological roles of various biological soil crust organisms

    USGS Publications Warehouse

    Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

    2011-01-01

    1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

  5. Unique Features of a Japanese ‘Candidatus Liberibacter asiaticus’ Strain Revealed by Whole Genome Sequencing

    PubMed Central

    Katoh, Hiroshi; Miyata, Shin-ichi; Inoue, Hiromitsu; Iwanami, Toru

    2014-01-01

    Citrus greening (huanglongbing) is the most destructive disease of citrus worldwide. It is spread by citrus psyllids and is associated with phloem-limited bacteria of three species of α-Proteobacteria, namely, ‘Candidatus Liberibacter asiaticus’, ‘Ca. L. americanus’, and ‘Ca. L. africanus’. Recent findings suggested that some Japanese strains lack the bacteriophage-type DNA polymerase region (DNA pol), in contrast to the Floridian psy62 strain. The whole genome sequence of the pol-negative ‘Ca. L. asiaticus’ Japanese isolate Ishi-1 was determined by metagenomic analysis of DNA extracted from ‘Ca. L. asiaticus’-infected psyllids and leaf midribs. The 1.19-Mb genome has an average 36.32% GC content. Annotation revealed 13 operons encoding rRNA and 44 tRNA genes, but no typical bacterial pathogenesis-related genes were located within the genome, similar to the Floridian psy62 and Chinese gxpsy. In contrast to other ‘Ca. L. asiaticus’ strains, the genome of the Japanese Ishi-1 strain lacks a prophage-related region. PMID:25180586

  6. Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine.

    PubMed

    McEwen, B S; Olié, J P

    2005-06-01

    Recent studies have provided evidence that structural remodeling of certain brain regions is a feature of depressive illness, and the postulated underlying mechanisms contribute to the idea that there is more to antidepressant actions that can be explained exclusively by a monoaminergic hypothesis. This review summarizes recent neurobiological studies on the antidepressant, tianeptine (S-1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl) amino]-7 heptanoic acid, sodium salt), a compound with structural similarities to the tricyclic antidepressant agents, the efficacy and good tolerance of which have been clearly established. These studies have revealed that the neurobiological properties of tianeptine involve the dynamic interplay between numerous neurotransmitter systems, as well as a critical role of structural and functional plasticity in the brain regions that permit the full expression of emotional learning. Although the story is far from complete, the schema underlying the effect of tianeptine on central plasticity is the most thoroughly studied of any antidepressants. Effects of tianeptine on neuronal excitability, neuroprotection, anxiety, and memory have also been found. Together with clinical data on the efficacy of tianeptine as an antidepressant, these actions offer insights into how compounds like tianeptine may be useful in the treatment of neurobiological features of depressive disorders.

  7. Phosphoproteomic analysis of differentiating Leishmania parasites reveals a unique stage-specific phosphorylation motif.

    PubMed

    Tsigankov, Polina; Gherardini, Pier Federico; Helmer-Citterich, Manuela; Späth, Gerald F; Zilberstein, Dan

    2013-07-01

    Protists of the genus Leishmania are obligatory intracellular parasites that cause a wide range of cutaneous, mucocutaneous, and visceral diseases in humans. They cycle between phagolysosomes of mammalian macrophages and the sand fly midgut, proliferating as intracellular amastigotes and extracellular promastigotes, respectively. Exposure to a lysosomal environment, i.e. acidic pH and body temperature, signals promastigotes to differentiate into amastigotes. Time course analyses indicated that Leishmania differentiation is a highly regulated and coordinated process. However, the role of posttranslational events such as protein phosphorylation in this process is still unknown. Herein, we analyzed and compared the phosphoproteomes of L. donovani amastigotes and promastigotes using an axenic host-free system that simulates parasite differentiation. Shotgun phosphopeptide analysis revealed 1614 phosphorylation residues (p-sites) corresponding to 627 proteins. The analysis indicated that the majority of the p-sites are stage-specific. Serine phosphorylation in a previously identified trypanosomatid-specific "SF" motif was significantly enriched in amastigotes. We identified a few phosophotyrosines (pY), mostly in proteins known to participate in signal transduction pathways. The analysis indicated that Leishmania contains proteins with multiple p-sites that are phosphorylated at distinct stages of the life cycle. For over half of the phosphorylation events, changes in phosphoprotein abundance did not positively correlate with changes in protein abundance, suggesting functional regulation. This study compares, for the first time, the phosphoproteins of L. donovani axenic promastigotes and amastigotes and provides the largest data set of the Leishmania phosphoproteome to date.

  8. CDK1 structures reveal conserved and unique features of the essential cell cycle CDK

    PubMed Central

    Brown, Nicholas R.; Korolchuk, Svitlana; Martin, Mathew P.; Stanley, Will; Moukhametzianov, Rouslan; Noble, Martin E.M.; Endicott, Jane A.

    2015-01-01

    CDK1 is the only essential cell cycle CDK in human cells and is required for successful completion of M-phase. It is the founding member of the CDK family and is conserved across all eukaryotes. Here we report the crystal structures of complexes of CDK1–Cks1 and CDK1–cyclin B–Cks2. These structures confirm the conserved nature of the inactive monomeric CDK fold and its ability to be remodeled by cyclin binding. Relative to CDK2–cyclin A, CDK1–cyclin B is less thermally stable, has a smaller interfacial surface, is more susceptible to activation segment dephosphorylation, and shows differences in the substrate sequence features that determine activity. Both CDK1 and CDK2 are potential cancer targets for which selective compounds are required. We also describe the first structure of CDK1 bound to a potent ATP-competitive inhibitor and identify aspects of CDK1 structure and plasticity that might be exploited to develop CDK1-selective inhibitors. PMID:25864384

  9. CDK1 structures reveal conserved and unique features of the essential cell cycle CDK

    NASA Astrophysics Data System (ADS)

    Brown, Nicholas R.; Korolchuk, Svitlana; Martin, Mathew P.; Stanley, Will A.; Moukhametzianov, Rouslan; Noble, Martin E. M.; Endicott, Jane A.

    2015-04-01

    CDK1 is the only essential cell cycle CDK in human cells and is required for successful completion of M-phase. It is the founding member of the CDK family and is conserved across all eukaryotes. Here we report the crystal structures of complexes of CDK1-Cks1 and CDK1-cyclin B-Cks2. These structures confirm the conserved nature of the inactive monomeric CDK fold and its ability to be remodelled by cyclin binding. Relative to CDK2-cyclin A, CDK1-cyclin B is less thermally stable, has a smaller interfacial surface, is more susceptible to activation segment dephosphorylation and shows differences in the substrate sequence features that determine activity. Both CDK1 and CDK2 are potential cancer targets for which selective compounds are required. We also describe the first structure of CDK1 bound to a potent ATP-competitive inhibitor and identify aspects of CDK1 structure and plasticity that might be exploited to develop CDK1-selective inhibitors.

  10. A unique pulmonary microvascular endothelial cell niche revealed by Weibel-Palade bodies and Griffonia simplicifolia

    PubMed Central

    Stevens, Troy

    2014-01-01

    Abstract Pulmonary endothelium displays considerable heterogeneity along the vascular axis, from arteries to capillaries to veins. Griffonia simplicifolia is a lectin that recognizes pulmonary microvascular endothelium with preference over extra-alveolar endothelium in both arteries and veins, yet the precise vascular location where this phenotypic shift occurs is poorly resolved. We gelatin-filled the circulation and agarose-loaded the airways and then labeled the lung with Griffonia lectin to enable visualization of the endothelial transition zone. Endothelium in vessels with internal diameters less than 38 μm were uniformly Griffonia positive, whereas vessels with internal diameters greater than 60 μm were always Griffonia negative. Two populations of endothelium were identified in vessels ranging from 38 to 60 μm in diameter, including some that were positive and others that were negative for binding to G. simplicifolia. To better resolve this endothelial transition zone, we performed morphology studies to measure the distribution of Weibel-Palade bodies (WPbs), since WPbs are present in conduit vessel endothelium and absent in capillary endothelium. WPbs were found in endothelium with vascular dimensions as small as 18 μm in diameter but were not found in capillaries. Thus, we identify with precision that the endothelial phenotype transition from a cell that does not interact with Griffonia lectin to one that does occurs in blood vessels with internal diameters of approximately 38 μm, and we reveal an unappreciated vascular zone, between 18 and 38 μm in diameter, where endothelium both is Griffonia positive and possesses WPbs. PMID:25006426

  11. A unique pulmonary microvascular endothelial cell niche revealed by Weibel-Palade bodies and Griffonia simplicifolia.

    PubMed

    Wu, Songwei; Zhou, Chun; King, Judy A C; Stevens, Troy

    2014-03-01

    Pulmonary endothelium displays considerable heterogeneity along the vascular axis, from arteries to capillaries to veins. Griffonia simplicifolia is a lectin that recognizes pulmonary microvascular endothelium with preference over extra-alveolar endothelium in both arteries and veins, yet the precise vascular location where this phenotypic shift occurs is poorly resolved. We gelatin-filled the circulation and agarose-loaded the airways and then labeled the lung with Griffonia lectin to enable visualization of the endothelial transition zone. Endothelium in vessels with internal diameters less than 38 μm were uniformly Griffonia positive, whereas vessels with internal diameters greater than 60 μm were always Griffonia negative. Two populations of endothelium were identified in vessels ranging from 38 to 60 μm in diameter, including some that were positive and others that were negative for binding to G. simplicifolia. To better resolve this endothelial transition zone, we performed morphology studies to measure the distribution of Weibel-Palade bodies (WPbs), since WPbs are present in conduit vessel endothelium and absent in capillary endothelium. WPbs were found in endothelium with vascular dimensions as small as 18 μm in diameter but were not found in capillaries. Thus, we identify with precision that the endothelial phenotype transition from a cell that does not interact with Griffonia lectin to one that does occurs in blood vessels with internal diameters of approximately 38 μm, and we reveal an unappreciated vascular zone, between 18 and 38 μm in diameter, where endothelium both is Griffonia positive and possesses WPbs.

  12. Immunoprofiling reveals unique cell-specific patterns of wall epitopes in the expanding Arabidopsis stem.

    PubMed

    Hall, Hardy C; Cheung, Jingling; Ellis, Brian E

    2013-04-01

    The Arabidopsis inflorescence stem undergoes rapid directional growth, requiring massive axial cell-wall extension in all its tissues, but, at maturity, these tissues are composed of cell types that exhibit markedly different cell-wall structures. It is not clear whether the cell-wall compositions of these cell types diverge rapidly following axial growth cessation, or whether compositional divergence occurs at earlier stages in differentiation, despite the common requirement for cell-wall extensibility. To examine this question, seven cell types were assayed for the abundance and distribution of 18 major cell-wall glycan classes at three developmental stages along the developing inflorescence stem, using a high-throughput immunolabelling strategy. These stages represent a phase of juvenile growth, a phase displaying the maximum rate of stem extension, and a phase in which extension growth is ceasing. The immunolabelling patterns detected demonstrate that the cell-wall composition of most stem tissues undergoes pronounced changes both during and after rapid extension growth. Hierarchical clustering of the immunolabelling signals identified cell-specific binding patterns for some antibodies, including a sub-group of arabinogalactan side chain-directed antibodies whose epitope targets are specifically associated with the inter-fascicular fibre region during the rapid cell expansion phase. The data reveal dynamic, cell type-specific changes in cell-wall chemistry across diverse cell types during cell-wall expansion and maturation in the Arabidopsis inflorescence stem, and highlight the paradox between this structural diversity and the uniform anisotropic cell expansion taking place across all tissues during stem growth.

  13. On the Development of a Unique Arc Jet Test Apparatus for Control Surface Seal Evaluations

    NASA Technical Reports Server (NTRS)

    Finkbeiner, Joshua R.; Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; Robbie, Malcolm; Baker, Gus; Erker, Arthur

    2004-01-01

    NASA Glenn has developed a unique test apparatus capable of evaluating control surface seal and flap designs under simulated reentry heating conditions in NASA Johnson's arc jet test facility. The test apparatus is capable of testing a variety of seal designs with a variety of control surface materials and designs using modular components. The flap angle can be varied during testing, allowing modification of the seal environment while testing is in progress. The flap angle is varied using an innovative transmission system which limits heat transfer from the hot flap structure to the motor, all while keeping the components properly aligned regardless of thermal expansion. A combination of active and passive cooling is employed to prevent thermal damage to the test fixture while still obtaining the target seal temperature.

  14. Co-culture of osteocytes and neurons on a unique patterned surface

    PubMed Central

    Boggs, Mary E.; Thompson, William R.; Farach-Carson, Mary C.; Duncan, Randall L.; Beebe, Thomas P.

    2011-01-01

    Neural and skeletal communication is essential for the maintenance of bone mass and transmission of pain, yet the mechanism(s) of signal transduction between these tissues is unknown. The authors established a novel system to co-culture murine long bone osteocyte-like cells (MLO-Y4) and primary murine dorsal root ganglia (DRG) neurons. Assessment of morphology and maturation marker expression on perlecan domain IV peptide (PlnDIV) and collagen type-1 (Col1) demonstrated that PlnDIV was an optimal matrix for MLO-Y4 culture. A novel matrix-specificity competition assay was developed to expose these cells to several extracellular matrix proteins such as PlnDIV, Col1, and laminin (Ln). The competition assay showed that approximately 70% of MLOY4 cells preferred either PlnDIV or Col1 to Ln. To co-culture MLO-Y4 and DRG, we developed patterned surfaces using micro-contact printing to create 40 μm × 1 cm alternating stripes of PlnDIV and Ln or PlnDIV and Col1. Co-culture on PlnDIV/Ln surfaces demonstrated that these matrix molecules provided unique cues for each cell type, with MLO-Y4 preferentially attaching to the PlnDIV lanes and DRG neurons to the Ln lanes. Approximately 80% of DRG were localized to Ln. Cellular processes from MLO-Y4 were closely associated with axonal extensions of DRG neurons. Approximately 57% of neuronal processes were in close proximity to nearby MLO-Y4 cells at the PlnDIV-Ln interface. The surfaces in this new assay provided a unique model system with which to study the communication between osteocyte-like cells and neurons in an in vitro environment. PMID:22239813

  15. Platinum electrode modification: Unique surface carbonization approach to improve performance and sensitivity.

    PubMed

    Lee, Hwi Yong; Barber, Cedrick; Minerick, Adrienne R

    2015-08-01

    Many microfluidic devices, also known as lab-on-a-chip devices, employ electrochemical detection methods using microelectrodes. Miniaturizing electrodes inevitably reduces electrode sensitivity and decreases the S/N, which limits applications within microfluidic devices. However, microelectrode surface modification can increase the surface area and sensitivity. In the present work, we report substantial improvement in platinum electrode performance and sensitivity by coating with carbon from red blood cells. The larger goal of this work was to measure DC electrical resistances of red blood cell suspensions in a microchannel for hematocrit determination. It was observed that as current responses of red blood cell suspensions were measured, the platinum electrode performance (reproducibility and S/N) improved with time. The platinum electrode electrocatalytic activity for red blood cell current measurements improved by 140%. Systematic experimentation revealed that red blood cells adsorb and carbonize the platinum electrode surfaces. The electrode surfaces before and after performance improvements were analyzed by field emission scanning electron microscopy, energy dispersive spectrometry, and Raman spectrometry. The formed carbon layers on the electrode surfaces were found to be proteomic and increased surface area with a porous three-dimensional structure, thus improving performance and stabilizing currents.

  16. Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis

    SciTech Connect

    Truschel, S.T.; Heroux, A.; Sengupta, D.; Foote, A.; Macbeth, M. R.; Linstedt, A. D.

    2011-06-10

    Biogenesis of the ribbon-like membrane network of the mammalian Golgi requires membrane tethering by the conserved GRASP domain in GRASP65 and GRASP55, yet the tethering mechanism is not fully understood. Here, we report the crystal structure of the GRASP55 GRASP domain, which revealed an unusual arrangement of two tandem PDZ folds that more closely resemble prokaryotic PDZ domains. Biochemical and functional data indicated that the interaction between the ligand-binding pocket of PDZ1 and an internal ligand on PDZ2 mediates the GRASP self-interaction, and structural analyses suggest that this occurs via a unique mode of internal PDZ ligand recognition. Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.

  17. Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis

    SciTech Connect

    S Truschel; D Sengupta; A Foote; A Heroux; M Macbeth; A Linstedt

    2011-12-31

    Biogenesis of the ribbon-like membrane network of the mammalian Golgi requires membrane tethering by the conserved GRASP domain in GRASP65 and GRASP55, yet the tethering mechanism is not fully understood. Here, we report the crystal structure of the GRASP55 GRASP domain, which revealed an unusual arrangement of two tandem PDZ folds that more closely resemble prokaryotic PDZ domains. Biochemical and functional data indicated that the interaction between the ligand-binding pocket of PDZ1 and an internal ligand on PDZ2 mediates the GRASP self-interaction, and structural analyses suggest that this occurs via a unique mode of internal PDZ ligand recognition. Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.

  18. The Crystal Structure of Escherichia coli Spermidine Synthase SpeE Reveals a Unique Substrate-binding Pocket

    SciTech Connect

    Zhou, X.; Chua, T; Tkaczuk, K; Bujnicki, J; Sivaraman, J

    2010-01-01

    Polyamines are essential in all branches of life. Biosynthesis of spermidine, one of the most ubiquitous polyamines, is catalyzed by spermidine synthase (SpeE). Although the function of this enzyme from Escherichia coli has been thoroughly characterized, its structural details remain unknown. Here, we report the crystal structure of E. coli SpeE and study its interaction with the ligands by isothermal titration calorimetry and computational modelling. SpeE consists of two domains - a small N-terminal {beta}-strand domain, and a C-terminal catalytic domain that adopts a canonical methyltransferase (MTase) Rossmann fold. The protein forms a dimer in the crystal and in solution. Structural comparison of E. coli SpeE to its homologs reveals that it has a large and unique substrate-binding cleft that may account for its lower amine substrate specificity.

  19. Many unique characteristics revealed by the complete mitochondrial genome of the scorpion Tityus serrulatus (Lutz e Mello 1922) (Chelicerata; Arachnida).

    PubMed

    Martins, Ana Paula Vimieiro; Carmo, Anderson Oliveira do; Mesquita, Flavia Oliveira; Pimenta, Ricardo José Gonzaga; Chagas, Aline Torres de Azevedo; Kalapothakis, Evanguedes

    2016-09-01

    This is the first complete mitochondrial genome of a Tityus species, although it is the most medically important genus in South America. Tityus serrulatus (Brazilian yellow scorpion) mtDNA revealed the same gene arrangement of three out of four other mitogenomes published by now for the same family (Centruroides limpidus, Mesobuthus gibbosus, M. martensii and Buthus occitanus). However, it presented many unique characteristics such as possession of Cox1 gene, different from all other protein-coding genes of scorpion mtDNA, starts with an atypical start codon (CTG). Moreover, no tRNA gene have complete typical secondary structure and the Tytius genome presented three non-coding regions longer than 100bp. Also, it contains the smallest scorpion 16S gene reported by now. Phylogenetic analysis using concatenated homologous genes confirmed Buthidae as a monophyletic clade and supports a monophyletic group including T. serrulatus and the other American species, C. limpidus.

  20. Surface Morphology of Chalkboard Tips Captures the Uniqueness of the User's Hand Strokes

    NASA Astrophysics Data System (ADS)

    Monterola, Christopher; Crisologo, Irene; Tugaff, Jeric; Batac, Rene; Longjas, Anthony

    Penmanship has a high degree of uniqueness as exemplified by the standard use of hand signature as identifier in contract validations and property ownerships. In this work, we demonstrate that the distinctiveness of one's writing patterns is possibly embedded in the molding of chalk tips. Using conventional photometric stereo method, the three-dimensional surface features of blackboard chalk tips used in Math and Physics lectures are microscopically resolved. Principal component analysis (PCA) and neural networks (NN) are then combined in identifying the chalk user based on the extracted topography. We show that NN approach applied to eight lecturers allow average classification accuracy (ΦNN) equal to 100% and 71.5 ± 2.7% for the training and test sets, respectively. Test sets are chalks not seen previously by the trained NN and represent 25% or 93 of the 368 chalk samples used. We note that the NN test set prediction is more than five-fold higher than the proportional chance criterion (PCC, ΦPCC = 12.9%), strongly hinting to a high degree of unique correlation between the user's hand strokes and the chalk tip features. The result of NN is also about three-fold better than the standard methods of linear discriminant analysis (LDA, ΦLDA = 27.0 ± 4.2%) or classification and regression trees (CART, ΦCART = 17.3 ± 3.7%). While the procedure discussed is far from becoming a practical biometric tool, our work offers a fundamental perspective to the extent on which the uniqueness of hand strokes of humans can be exhibited.

  1. Surface-adaptable all-metal micro-four-point probe with unique configuration

    NASA Astrophysics Data System (ADS)

    Kim, J. K.; Choi, Y. S.; Lee, D. W.

    2015-07-01

    In this paper, we propose a surface-adaptable all-metal micro-four-point probe (μ4PP) with a unique configuration. The μ4PP consists of four independent metallic sub-cantilevers with sharp Cu tips, and an SU-8 body structure to support the sub-cantilevers. The tip height is approximately 15 μm, and the tips are fabricated by anisotropic wet-etching of silicon followed by Cu electroplating. Each metallic cantilever connected to the SU-8 body structure acts as a flexible spring, so that the conducting tip can make gentle, non-destructive contact with fragile surfaces. To enhance the adhesion between the metallic sub-cantilevers and the SU-8 body, mushroom-shaped Cu structures were fabricated using an under-baked and under-exposed photolithography process. Various μ4PPs were designed and fabricated to verify their diverse range of applications, and preliminary experiments were performed using these fabricated μ4PPs. The resultant flexibility and reliability were experimentally confirmed on several samples, such as a polymer cantilever, a graphene flake, and curved metallic surfaces. We also expect that the proposed μ4PP will be suitable for measuring the anisotropic characteristics of crystal materials or the Hall effect in semiconductors.

  2. Proteomic identification of unique photoreceptor disc components reveals the presence of PRCD, a protein linked to retinal degeneration

    PubMed Central

    Skiba, Nikolai P.; Spencer, William J.; Salinas, Raquel Y.; Lieu, Eric C.; Thompson, J. Will; Arshavsky, Vadim Y.

    2013-01-01

    Visual signal transduction takes place on the surface of flat membrane vesicles called photoreceptor discs, which reside inside the light-sensitive outer segment organelle of vertebrate photoreceptor cells. While biochemical studies have indicated that discs are built with a handful of highly specialized proteins, proteomic studies have yielded databases consisting of hundreds of entries. We addressed this controversy by employing protein correlation profiling which allows identification of unique components of organelles that can be fractionated but not purified to absolute homogeneity. We subjected discs to sequential steps of fractionation and identified the relative amounts of proteins in each fraction by label-free quantitative mass spectrometry. This analysis demonstrated that the photoreceptor disc proteome contains only eleven components, which satisfy the hallmark criterion for being unique disc-resident components: the retention of a constant molar ratio among themselves across fractionation steps. Remarkably, one of them is PRCD, a protein whose mutations have been shown to cause blindness, yet cellular localization remained completely unknown. Identification of PRCD as a novel disc-specific protein facilitates understanding its functional role and the pathobiological significance of its mutations. Our study provides a striking example how protein correlation profiling allows a distinction between constitutive components of cellular organelles and their inevitable contaminants. PMID:23672200

  3. Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship.

    PubMed

    Dungan, Jennifer R; Qin, Xuejun; Horne, Benjamin D; Carlquist, John F; Singh, Abanish; Hurdle, Melissa; Grass, Elizabeth; Haynes, Carol; Gregory, Simon G; Shah, Svati H; Hauser, Elizabeth R; Kraus, William E

    2016-01-01

    Survival bias may unduly impact genetic association with complex diseases; gene-specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP-specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs-rs1462845 and rs6788787-using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to-all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01-1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69-0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08-1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05-1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort-specific genotype effects

  4. Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship

    PubMed Central

    Qin, Xuejun; Horne, Benjamin D.; Carlquist, John F.; Singh, Abanish; Hurdle, Melissa; Grass, Elizabeth; Haynes, Carol; Gregory, Simon G.; Shah, Svati H.; Hauser, Elizabeth R.; Kraus, William E.

    2016-01-01

    Survival bias may unduly impact genetic association with complex diseases; gene-specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP-specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs—rs1462845 and rs6788787—using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to-all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01–1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69–0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08–1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05–1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort

  5. Global Transcriptional Analysis Reveals Unique and Shared Responses in Arabidopsis thaliana Exposed to Combined Drought and Pathogen Stress

    PubMed Central

    Gupta, Aarti; Sarkar, Ananda K.; Senthil-Kumar, Muthappa

    2016-01-01

    With frequent fluctuations in global climate, plants are exposed to co-occurring drought and pathogen infection and this combination adversely affects plant survival. In the past, some studies indicated that morpho-physiological responses of plants to the combined stress are different from the individual stressed plants. However, interaction of drought stressed plants with pathogen has not been widely studied at molecular level. Such studies are important to understand the defense pathways that operate as part of combined stress tolerance mechanism. In this study, Arabidopsis thaliana was exposed to individual drought stress, Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection and their combination. Using Affymetrix WT gene 1.0 ST array, global transcriptome profiling of leaves under individual drought stress and pathogen infection was compared with their combination. The results obtained from pathway mapping (KAAS and MAPMAN) demonstrated the modulation in defense pathways in A. thaliana under drought and host pathogen Pst DC3000 infection. Further, our study revealed “tailored” responses under combined stress and the time of occurrence of each stress during their concurrence has shown differences in transcriptome profile. Our results from microarray and RT-qPCR revealed regulation of 20 novel genes uniquely during the stress interaction. This study indicates that plants exposed to concurrent drought and pathogen stress experience a new state of stress. Thus, under frequently changing climatic conditions, time of occurrence of each stress in the interaction defines the plant responses and should thus be studied explicitly. PMID:27252712

  6. A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer

    PubMed Central

    Gallon, Matthew; Clairfeuille, Thomas; Steinberg, Florian; Mas, Caroline; Ghai, Rajesh; Sessions, Richard B.; Teasdale, Rohan D.; Collins, Brett M.; Cullen, Peter J.

    2014-01-01

    The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to-plasma membrane recycling of transmembrane cargos that contain a PSD95, Dlg1, zo-1 (PDZ)-binding motif. Here we describe the core interaction in SNX27-retromer assembly and its functional relevance for cargo sorting. Crystal structures and NMR experiments reveal that an exposed β-hairpin in the SNX27 PDZ domain engages a groove in the arrestin-like structure of the vacuolar protein sorting 26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain simultaneously binds PDZ-binding motifs and retromer-associated VPS26. Importantly, VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo selection. With disruption of SNX27 and retromer function linked to synaptic dysfunction and neurodegenerative disease, our work provides the first step, to our knowledge, in the molecular description of this important sorting complex, and more broadly describes a unique interaction between a PDZ domain and an arrestin-like fold. PMID:25136126

  7. Unique flow transitions and particle collection switching phenomena in a microchannel induced by surface acoustic waves

    NASA Astrophysics Data System (ADS)

    Tan, Ming K.; Yeo, Leslie Y.; Friend, James R.

    2010-12-01

    We present an experimental approach for controlled switching between uniform flow for pumping and vortical flow for mixing in a microchannel fabricated onto a piezoelectric substrate. For particle laden fluids, this arrangement permits a choice between transport and alignment of microparticles. Using surface acoustic waves with amplitudes beyond 1 nm, the transition from uniform to mixing flows occurs when the acoustic wavelength in the fluid is reduced to a dimension smaller than the channel width, i.e., λf≥Wch for uniform flow and λfsurface acoustic waves with amplitudes below 1 nm, particles in an initially homogeneous suspension agglomerate into equally spaced lines with a separation of λf/2. Switching the transducer between its fundamental resonant frequency f0 and its first harmonic frequency f1+˜2f0 causes a switch between uniform and mixing flow, while switching between large and small amplitude excitation allows one to choose whether to collect the particles in the flow along nodal lines parallel to the channel. These results are uniquely achieved without requiring the microfabrication of complex microchannel architectures and control schemes; the switching is simply achieved by adjusting two parameters: the acoustic excitation frequency and amplitude.

  8. Light and Electron Microscopy of the European Beaver (Castor fiber) Stomach Reveal Unique Morphological Features with Possible General Biological Significance

    PubMed Central

    Petryński, Wojciech; Palkowska, Katarzyna; Prusik, Magdalena; Targońska, Krystyna; Giżejewski, Zygmunt; Przybylska-Gornowicz, Barbara

    2014-01-01

    Anatomical, histological, and ultrastructural studies of the European beaver stomach revealed several unique morphological features. The prominent attribute of its gross morphology was the cardiogastric gland (CGG), located near the oesophageal entrance. Light microscopy showed that the CGG was formed by invaginations of the mucosa into the submucosa, which contained densely packed proper gastric glands comprised primarily of parietal and chief cells. Mucous neck cells represented <0.1% of cells in the CGG gastric glands and 22–32% of cells in the proper gastric glands of the mucosa lining the stomach lumen. These data suggest that chief cells in the CGG develop from undifferentiated cells that migrate through the gastric gland neck rather than from mucous neck cells. Classical chief cell formation (i.e., arising from mucous neck cells) occurred in the mucosa lining the stomach lumen, however. The muscularis around the CGG consisted primarily of skeletal muscle tissue. The cardiac region was rudimentary while the fundus/corpus and pyloric regions were equally developed. Another unusual feature of the beaver stomach was the presence of specific mucus with a thickness up to 950 µm (in frozen, unfixed sections) that coated the mucosa. Our observations suggest that the formation of this mucus is complex and includes the secretory granule accumulation in the cytoplasm of pit cells, the granule aggregation inside cells, and the incorporation of degenerating cells into the mucus. PMID:24727802

  9. Dual RNA Sequencing Reveals the Expression of Unique Transcriptomic Signatures in Lipopolysaccharide-Induced BV-2 Microglial Cells

    PubMed Central

    Kim, Sun Hwa; Park, Kyoung Sun; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

    2015-01-01

    transcriptomic analysis is the first to show a comparison of the family-wide differential expression of most known immune genes and also reveal transcription evidence of multiple gene families in BV-2 microglial cells. Collectively, these findings reveal unique transcriptomic signatures in BV-2 microglial cells required for homeostasis and effective immune responses. PMID:25811458

  10. Unique charge distribution in surface loops confers high velocity on the fast motor protein Chara myosin.

    PubMed

    Ito, Kohji; Yamaguchi, Yukie; Yanase, Kenji; Ichikawa, Yousuke; Yamamoto, Keiichi

    2009-12-22

    Most myosins have a positively charged loop 2 with a cluster of lysine residues that bind to the negatively charged N-terminal segment of actin. However, the net charge of loop 2 of very fast Chara myosin is zero and there is no lysine cluster in it. In contrast, Chara myosin has a highly positively charged loop 3. To elucidate the role of these unique surface loops of Chara myosin in its high velocity and high actin-activated ATPase activity, we have undertaken mutational analysis using recombinant Chara myosin motor domain. It was found that net positive charge in loop 3 affected V(max) and K(app) of actin activated ATPase activity, while it affected the velocity only slightly. The net positive charge in loop 2 affected K(app) and the velocity, although it did not affect V(max). Our results suggested that Chara myosin has evolved to have highly positively charged loop 3 for its high ATPase activity and have less positively charged loop 2 for its high velocity. Since high positive charge in loop 3 and low positive charge in loop 2 seem to be one of the reasons for Chara myosin's high velocity, we manipulated charge contents in loops 2 and 3 of Dictyostelium myosin (class II). Removing positive charge from loop 2 and adding positive charge to loop 3 of Dictyostelium myosin made its velocity higher than that of the wild type, suggesting that the charge strategy in loops 2 and 3 is widely applicable.

  11. RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome.

    PubMed

    Cui, Julia Yue; Klaassen, Curtis D

    2016-09-01

    entire hepatic transcriptome correlated with a marked change in the expression of many DNA and histone epigenetic modifiers. In conclusion, the present study has revealed known and novel, as well as common and unique targets of PXR and CAR in mouse liver following pharmacological activation using their prototypical ligands. Results from this study will further support the role of these receptors in regulating the homeostasis of xenobiotic and intermediary metabolism in the liver, and aid in distinguishing between PXR and CAR signaling at various physiological and pathophysiological conditions. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

  12. Direct measurements of chemical bonding at solid surfaces using a unique calorimetric method: Towards understanding surface chemistry in energy technologies

    NASA Astrophysics Data System (ADS)

    Farmer, Jason A.

    Measuring the heat released when gas phase species adsorb onto surfaces provides essential information about the energies of surface species and the reactions they undergo. Here, heats of adsorption of technologically-interesting surface species were measured using a unique microcalorimetric technique in ultrahigh vacuum. Specifically, systems were studied which are relevant to understanding and improving transition metal catalysts and organic electronics. Metal adsorption energies were measured which elucidate metal-to-oxide and metal-to-polymer interfacial binding, and molecule adsorption energies were measured to understand how catalyst structure influences the energies of adsorbed reaction intermediates. Oxide-supported metal nanoparticles form the basis for many industrial catalysts. Nanoparticle activity, selectivity and resistance to sintering can depend strongly on particle size, oxide support, and defects on the oxide. To investigate the dependence of catalytic properties on oxide surface defects, defects were introduced on MgO(100) and CeO2(111), and their affect on the adsorption energy of metal atoms and the energy of supported nanoparticles was measured. These measurements help to explain why transition metal catalysts sinter more slowly and maintain smaller particles when supported on CeO 2 compared to other oxides, and how surface defects influence nanoparticle formation and film growth on oxides. The effect of nanoparticle size on the adsorption energy of CO on different-sized Pd nanoparticles on Fe3O 4(111) was measured, providing the first direct evidence that the heat of adsorption of CO decreases with decreasing Pd nanoparticle size. Knowledge of the direction and magnitude of particle size effects is necessary for improving existing catalysts and designing new ones. The metal/polymer interface is important because it impacts charge injection, extraction, and transport in organic electronics. Large-scale energy production using polymer

  13. 4.0-Å resolution cryo-EM structure of the mammalian chaperonin TRiC/CCT reveals its unique subunit arrangement

    PubMed Central

    Cong, Yao; Baker, Matthew L.; Jakana, Joanita; Woolford, David; Miller, Erik J.; Reissmann, Stefanie; Kumar, Ramya N.; Redding-Johanson, Alyssa M.; Batth, Tanveer S.; Mukhopadhyay, Aindrila; Ludtke, Steven J.; Frydman, Judith; Chiu, Wah

    2010-01-01

    The essential double-ring eukaryotic chaperonin TRiC/CCT (TCP1-ring complex or chaperonin containing TCP1) assists the folding of ∼5–10% of the cellular proteome. Many TRiC substrates cannot be folded by other chaperonins from prokaryotes or archaea. These unique folding properties are likely linked to TRiC’s unique heterooligomeric subunit organization, whereby each ring consists of eight different paralogous subunits in an arrangement that remains uncertain. Using single particle cryo-EM without imposing symmetry, we determined the mammalian TRiC structure at 4.7-Å resolution. This revealed the existence of a 2-fold axis between its two rings resulting in two homotypic subunit interactions across the rings. A subsequent 2-fold symmetrized map yielded a 4.0-Å resolution structure that evinces the densities of a large fraction of side chains, loops, and insertions. These features permitted unambiguous identification of all eight individual subunits, despite their sequence similarity. Independent biochemical near-neighbor analysis supports our cryo-EM derived TRiC subunit arrangement. We obtained a Cα backbone model for each subunit from an initial homology model refined against the cryo-EM density. A subsequently optimized atomic model for a subunit showed ∼95% of the main chain dihedral angles in the allowable regions of the Ramachandran plot. The determination of the TRiC subunit arrangement opens the way to understand its unique function and mechanism. In particular, an unevenly distributed positively charged wall lining the closed folding chamber of TRiC differs strikingly from that of prokaryotic and archaeal chaperonins. These interior surface chemical properties likely play an important role in TRiC’s cellular substrate specificity. PMID:20194787

  14. 4.0-A resolution cryo-EM structure of the mammalian chaperonin TRiC/CCT reveals its unique subunit arrangement.

    PubMed

    Cong, Yao; Baker, Matthew L; Jakana, Joanita; Woolford, David; Miller, Erik J; Reissmann, Stefanie; Kumar, Ramya N; Redding-Johanson, Alyssa M; Batth, Tanveer S; Mukhopadhyay, Aindrila; Ludtke, Steven J; Frydman, Judith; Chiu, Wah

    2010-03-16

    The essential double-ring eukaryotic chaperonin TRiC/CCT (TCP1-ring complex or chaperonin containing TCP1) assists the folding of approximately 5-10% of the cellular proteome. Many TRiC substrates cannot be folded by other chaperonins from prokaryotes or archaea. These unique folding properties are likely linked to TRiC's unique heterooligomeric subunit organization, whereby each ring consists of eight different paralogous subunits in an arrangement that remains uncertain. Using single particle cryo-EM without imposing symmetry, we determined the mammalian TRiC structure at 4.7-A resolution. This revealed the existence of a 2-fold axis between its two rings resulting in two homotypic subunit interactions across the rings. A subsequent 2-fold symmetrized map yielded a 4.0-A resolution structure that evinces the densities of a large fraction of side chains, loops, and insertions. These features permitted unambiguous identification of all eight individual subunits, despite their sequence similarity. Independent biochemical near-neighbor analysis supports our cryo-EM derived TRiC subunit arrangement. We obtained a Calpha backbone model for each subunit from an initial homology model refined against the cryo-EM density. A subsequently optimized atomic model for a subunit showed approximately 95% of the main chain dihedral angles in the allowable regions of the Ramachandran plot. The determination of the TRiC subunit arrangement opens the way to understand its unique function and mechanism. In particular, an unevenly distributed positively charged wall lining the closed folding chamber of TRiC differs strikingly from that of prokaryotic and archaeal chaperonins. These interior surface chemical properties likely play an important role in TRiC's cellular substrate specificity. PMID:20194787

  15. Structural and Biochemical Characterization of Plasmodium falciparum 12 (Pf12) Reveals a Unique Interdomain Organization and the Potential for an Antiparallel Arrangement with Pf41*

    PubMed Central

    Tonkin, Michelle L.; Arredondo, Silvia A.; Loveless, Bianca C.; Serpa, Jason J.; Makepeace, Karl A. T.; Sundar, Natarajan; Petrotchenko, Evgeniy V.; Miller, Louis H.; Grigg, Michael E.; Boulanger, Martin J.

    2013-01-01

    Plasmodium falciparum is the most devastating agent of human malaria. A major contributor to its virulence is a complex lifecycle with multiple parasite forms, each presenting a different repertoire of surface antigens. Importantly, members of the 6-Cys s48/45 family of proteins are found on the surface of P. falciparum in every stage, and several of these antigens have been investigated as vaccine targets. Pf12 is the archetypal member of the 6-Cys protein family, containing just two s48/45 domains, whereas other members have up to 14 of these domains. Pf12 is strongly recognized by immune sera from naturally infected patients. Here we show that Pf12 is highly conserved and under purifying selection. Immunofluorescence data reveals a punctate staining pattern with an apical organization in late schizonts. Together, these data are consistent with an important functional role for Pf12 in parasite-host cell attachment or invasion. To infer the structural and functional diversity between Pf12 and the other 11 6-Cys domain proteins, we solved the 1.90 Å resolution crystal structure of the Pf12 ectodomain. Structural analysis reveals a unique organization between the membrane proximal and membrane distal domains and clear homology with the SRS-domain containing proteins of Toxoplasma gondii. Cross-linking and mass spectrometry confirm the previously identified Pf12-Pf41 heterodimeric complex, and analysis of individual cross-links supports an unexpected antiparallel organization. Collectively, the localization and structure of Pf12 and details of its interaction with Pf41 reveal important insight into the structural and functional properties of this archetypal member of the 6-Cys protein family. PMID:23511632

  16. The crystal structure of the adenylation enzyme VinN reveals a unique β-amino acid recognition mechanism.

    PubMed

    Miyanaga, Akimasa; Cieślak, Jolanta; Shinohara, Yuji; Kudo, Fumitaka; Eguchi, Tadashi

    2014-11-01

    Adenylation enzymes play important roles in the biosynthesis and degradation of primary and secondary metabolites. Mechanistic insights into the recognition of α-amino acid substrates have been obtained for α-amino acid adenylation enzymes. The Asp residue is invariant and is essential for the stabilization of the α-amino group of the substrate. In contrast, the β-amino acid recognition mechanism of adenylation enzymes is still unclear despite the importance of β-amino acid activation for the biosynthesis of various natural products. Herein, we report the crystal structure of the stand-alone adenylation enzyme VinN, which specifically activates (2S,3S)-3-methylaspartate (3-MeAsp) in vicenistatin biosynthesis. VinN has an overall structure similar to that of other adenylation enzymes. The structure of the complex with 3-MeAsp revealed that a conserved Asp(230) residue is used in the recognition of the β-amino group of 3-MeAsp similar to α-amino acid adenylation enzymes. A mutational analysis and structural comparison with α-amino acid adenylation enzymes showed that the substrate-binding pocket of VinN has a unique architecture to accommodate 3-MeAsp as a β-amino acid substrate. Thus, the VinN structure allows the first visualization of the interaction of an adenylation enzyme with a β-amino acid and provides new mechanistic insights into the selective recognition of β-amino acids in this family of enzymes. PMID:25246523

  17. Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host

    PubMed Central

    Leontovyč, Roman; Young, Neil D.; Korhonen, Pasi K.; Hall, Ross S.; Tan, Patrick; Mikeš, Libor; Kašný, Martin; Horák, Petr; Gasser, Robin B.

    2016-01-01

    To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes) of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts’ immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes. PMID:26863542

  18. The Crystal Structure of the Adenylation Enzyme VinN Reveals a Unique β-Amino Acid Recognition Mechanism*

    PubMed Central

    Miyanaga, Akimasa; Cieślak, Jolanta; Shinohara, Yuji; Kudo, Fumitaka; Eguchi, Tadashi

    2014-01-01

    Adenylation enzymes play important roles in the biosynthesis and degradation of primary and secondary metabolites. Mechanistic insights into the recognition of α-amino acid substrates have been obtained for α-amino acid adenylation enzymes. The Asp residue is invariant and is essential for the stabilization of the α-amino group of the substrate. In contrast, the β-amino acid recognition mechanism of adenylation enzymes is still unclear despite the importance of β-amino acid activation for the biosynthesis of various natural products. Herein, we report the crystal structure of the stand-alone adenylation enzyme VinN, which specifically activates (2S,3S)-3-methylaspartate (3-MeAsp) in vicenistatin biosynthesis. VinN has an overall structure similar to that of other adenylation enzymes. The structure of the complex with 3-MeAsp revealed that a conserved Asp230 residue is used in the recognition of the β-amino group of 3-MeAsp similar to α-amino acid adenylation enzymes. A mutational analysis and structural comparison with α-amino acid adenylation enzymes showed that the substrate-binding pocket of VinN has a unique architecture to accommodate 3-MeAsp as a β-amino acid substrate. Thus, the VinN structure allows the first visualization of the interaction of an adenylation enzyme with a β-amino acid and provides new mechanistic insights into the selective recognition of β-amino acids in this family of enzymes. PMID:25246523

  19. The Structure of the Poxvirus A33 Protein Reveals a Dimer of Unique C-Type Lectin-Like Domains

    SciTech Connect

    Su, Hua-Poo; Singh, Kavita; Gittis, Apostolos G.; Garboczi, David N.

    2010-11-03

    The current vaccine against smallpox is an infectious form of vaccinia virus that has significant side effects. Alternative vaccine approaches using recombinant viral proteins are being developed. A target of subunit vaccine strategies is the poxvirus protein A33, a conserved protein in the Chordopoxvirinae subfamily of Poxviridae that is expressed on the outer viral envelope. Here we have determined the structure of the A33 ectodomain of vaccinia virus. The structure revealed C-type lectin-like domains (CTLDs) that occur as dimers in A33 crystals with five different crystal lattices. Comparison of the A33 dimer models shows that the A33 monomers have a degree of flexibility in position within the dimer. Structural comparisons show that the A33 monomer is a close match to the Link module class of CTLDs but that the A33 dimer is most similar to the natural killer (NK)-cell receptor class of CTLDs. Structural data on Link modules and NK-cell receptor-ligand complexes suggest a surface of A33 that could interact with viral or host ligands. The dimer interface is well conserved in all known A33 sequences, indicating an important role for the A33 dimer. The structure indicates how previously described A33 mutations disrupt protein folding and locates the positions of N-linked glycosylations and the epitope of a protective antibody.

  20. The unique architecture and function of cellulose-interacting proteins in oomycetes revealed by genomic and structural analyses

    PubMed Central

    2012-01-01

    Background Oomycetes are fungal-like microorganisms evolutionary distinct from true fungi, belonging to the Stramenopile lineage and comprising major plant pathogens. Both oomycetes and fungi express proteins able to interact with cellulose, a major component of plant and oomycete cell walls, through the presence of carbohydrate-binding module belonging to the family 1 (CBM1). Fungal CBM1-containing proteins were implicated in cellulose degradation whereas in oomycetes, the Cellulose Binding Elicitor Lectin (CBEL), a well-characterized CBM1-protein from Phytophthora parasitica, was implicated in cell wall integrity, adhesion to cellulosic substrates and induction of plant immunity. Results To extend our knowledge on CBM1-containing proteins in oomycetes, we have conducted a comprehensive analysis on 60 fungi and 7 oomycetes genomes leading to the identification of 518 CBM1-containing proteins. In plant-interacting microorganisms, the larger number of CBM1-protein coding genes is expressed by necrotroph and hemibiotrophic pathogens, whereas a strong reduction of these genes is observed in symbionts and biotrophs. In fungi, more than 70% of CBM1-containing proteins correspond to enzymatic proteins in which CBM1 is associated with a catalytic unit involved in cellulose degradation. In oomycetes more than 90% of proteins are similar to CBEL in which CBM1 is associated with a non-catalytic PAN/Apple domain, known to interact with specific carbohydrates or proteins. Distinct Stramenopile genomes like diatoms and brown algae are devoid of CBM1 coding genes. A CBM1-PAN/Apple association 3D structural modeling was built allowing the identification of amino acid residues interacting with cellulose and suggesting the putative interaction of the PAN/Apple domain with another type of glucan. By Surface Plasmon Resonance experiments, we showed that CBEL binds to glycoproteins through galactose or N-acetyl-galactosamine motifs. Conclusions This study provides insight into the

  1. Proteomic screening of variola virus reveals a unique NF-kappaB inhibitor that is highly conserved among pathogenic orthopoxviruses.

    PubMed

    Mohamed, Mohamed R; Rahman, Masmudur M; Lanchbury, Jerry S; Shattuck, Donna; Neff, Chris; Dufford, Max; van Buuren, Nick; Fagan, Katharine; Barry, Michele; Smith, Scott; Damon, Inger; McFadden, Grant

    2009-06-01

    Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDNA libraries. Several protein-protein interactions were identified, including an interaction between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-kappaB1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-kappaB1/p105. Orthologs of G1R are present in a variety of pathogenic orthopoxviruses, but not in vaccinia virus, and expression of any one of these viral proteins blocks NF-kappaB signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses.

  2. Surface analysis reveals biogenic oxidation of sub-bituminous coal by Pseudomonas fluorescens.

    PubMed

    Hazrin-Chong, Nur Hazlin; Marjo, Christopher E; Das, Theerthankar; Rich, Anne M; Manefield, Mike

    2014-01-01

    Direct analysis of the colonised surface on coal using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) revealed the nature of bacteria-mediated oxidation at the coal surface. Unique oxidation peaks generated by the presence of Pseudomonas fluorescens on coal was shown through ATR-FTIR measurements, and ATR-FTIR imaging illustrated that this peak was only observed within the region of coal colonised by bacteria. Contact angle measurements and surface free energy of adhesion calculations showed that the adhesion between P. fluorescens and coal was thermodynamically favourable, and scanning electron microscopy (SEM) exhibited individual cell or monolayer cluster attachment on coal. Furthermore, Gaussian peak fitting of peroxidase-treated coal ATR-FTIR spectra revealed that peroxidase or related enzymes produced by P. fluorescens may be responsible for coal oxidation. This study demonstrated the usefulness and practicality of ATR-FTIR for analysing coal oxidation by P. fluorescens and may well be applied to other microbe-driven modifications of coal for its rapidity and reliability.

  3. Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity

    PubMed Central

    Olp, Landon N.; Jeanniard, Adrien; Marimo, Clemence; West, John T.

    2015-01-01

    ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries—where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap since it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment protocol followed by Illumina deep-sequencing, we generated and analyzed 16 unique Zambian, KS-derived, KSHV genomes. We enriched KSHV DNA over cellular DNA 1,851 to 18,235-fold. Enrichment provided coverage levels up to 24,740-fold; therefore, supporting highly confident polymorphism analysis. Multiple alignment of the 16 newly sequenced KSHV genomes showed low level variability across the entire central conserved region. This variability resulted in distinct phylogenetic clustering between Zambian KSHV genomic sequences and those derived from Western countries. Importantly, the phylogenetic segregation of Zambian from Western sequences occurred irrespective of inclusion of the highly variable genes K1 and K15. We also show that four genes within the more conserved region of the KSHV genome contained polymorphisms that partially, but not fully, contributed to the unique Zambian KSHV whole-genome phylogenetic structure. Taken together, our data suggest that the whole KSHV genome should be taken into consideration for accurate viral characterization. IMPORTANCE Our results represent the largest number of KSHV whole-genomic sequences published to date and the first time that multiple genomes have been sequenced from sub-Saharan Africa, a geographic area

  4. Analyses of Compact Trichinella Kinomes Reveal a MOS-Like Protein Kinase with a Unique N-Terminal Domain.

    PubMed

    Stroehlein, Andreas J; Young, Neil D; Korhonen, Pasi K; Chang, Bill C H; Sternberg, Paul W; La Rosa, Giuseppe; Pozio, Edoardo; Gasser, Robin B

    2016-01-01

    Parasitic worms of the genus Trichinella (phylum Nematoda; class Enoplea) represent a complex of at least twelve taxa that infect a range of different host animals, including humans, around the world. They are foodborne, intracellular nematodes, and their life cycles differ substantially from those of other nematodes. The recent characterization of the genomes and transcriptomes of all twelve recognized taxa of Trichinella now allows, for the first time, detailed studies of their molecular biology. In the present study, we defined, curated, and compared the protein kinase complements (kinomes) of Trichinella spiralis and T. pseudospiralis using an integrated bioinformatic workflow employing transcriptomic and genomic data sets. We examined how variation in the kinome might link to unique aspects of Trichinella morphology, biology, and evolution. Furthermore, we utilized in silico structural modeling to discover and characterize a novel, MOS-like kinase with an unusual, previously undescribed N-terminal domain. Taken together, the present findings provide a basis for comparative investigations of nematode kinomes, and might facilitate the identification of Enoplea-specific intervention and diagnostic targets. Importantly, the in silico modeling approach assessed here provides an exciting prospect of being able to identify and classify currently unknown (orphan) kinases, as a foundation for their subsequent structural and functional investigation. PMID:27412987

  5. First in situ observations of the deep-sea squid Grimalditeuthis bonplandi reveal unique use of tentacles

    PubMed Central

    Hoving, Hendrik J. T.; Zeidberg, Louis D.; Benfield, Mark C.; Bush, Stephanie L.; Robison, Bruce H.; Vecchione, Michael

    2013-01-01

    The deep-sea squid Grimalditeuthis bonplandi has tentacles unique among known squids. The elastic stalk is extremely thin and fragile, whereas the clubs bear no suckers, hooks or photophores. It is unknown whether and how these tentacles are used in prey capture and handling. We present, to our knowledge, the first in situ observations of this species obtained by remotely operated vehicles (ROVs) in the Atlantic and North Pacific. Unexpectedly, G. bonplandi is unable to rapidly extend and retract the tentacle stalk as do other squids, but instead manoeuvres the tentacles by undulation and flapping of the clubs’ trabecular protective membranes. These tentacle club movements superficially resemble the movements of small marine organisms and suggest the possibility that G. bonplandi uses aggressive mimicry by the tentacle clubs to lure prey, which we find to consist of crustaceans and cephalopods. In the darkness of the meso- and bathypelagic zones the flapping and undulatory movements of the tentacle may: (i) stimulate bioluminescence in the surrounding water, (ii) create low-frequency vibrations and/or (iii) produce a hydrodynamic wake. Potential prey of G. bonplandi may be attracted to one or more of these as signals. This singular use of the tentacle adds to the diverse foraging and feeding strategies known in deep-sea cephalopods. PMID:23986106

  6. Identification and characterization of a periplasmic trilactone esterase, Cee, revealed unique features of ferric enterobactin acquisition in Campylobacter

    PubMed Central

    Zeng, Ximin; Mo, Yiming; Xu, Fuzhou; Lin, Jun

    2012-01-01

    Summary Ferric enterobactin (FeEnt) acquisition is a highly efficient and conserved iron scavenging system in Gram-negative bacteria. Recently, we have characterized two FeEnt receptors (CfrA and CfrB) in Campylobacter jejuni and C. coli, the enteric human pathogens that do not produce any siderophores. In this study, whole genome sequencing and comparative genomic analysis identified a unique Ent trilactone esterase Cee (Cj1376) in C. jejuni. Genomic analysis and biochemical assay strongly suggested that Cee is the sole trilactone esterase in C. jejuni. Thin layer chromatography and HPLC analyses showed high efficiency of the purified Cee to hydrolyze Ent. Three Cee homologs previously characterized from other bacteria (IroE, IroD, and Fes) were also purified and analyzed together with Cee, indicating that Cee, Fes, and IroD displayed similar hydrolysis dynamics for both apo and ferric forms of Ent while IroE catalyzed Ent inefficiently. Unlike cytoplasmic Fes and IroD, Cee is localized in the periplasm as demonstrated by immunoblotting using Cee-specific antibodies. Genetic manipulation of diverse Campylobacter strains demonstrated that Cee is not only essential for CfrB-dependent FeEnt acquisition but also involved in CfrA-dependent pathway. Together, this study identified and characterized a novel periplasmic trilactone esterase and suggested a new model of FeEnt acquisition in Campylobacter. PMID:23278903

  7. Analyses of Compact Trichinella Kinomes Reveal a MOS-Like Protein Kinase with a Unique N-Terminal Domain

    PubMed Central

    Stroehlein, Andreas J.; Young, Neil D.; Korhonen, Pasi K.; Chang, Bill C. H.; Sternberg, Paul W.; La Rosa, Giuseppe; Pozio, Edoardo; Gasser, Robin B.

    2016-01-01

    Parasitic worms of the genus Trichinella (phylum Nematoda; class Enoplea) represent a complex of at least twelve taxa that infect a range of different host animals, including humans, around the world. They are foodborne, intracellular nematodes, and their life cycles differ substantially from those of other nematodes. The recent characterization of the genomes and transcriptomes of all twelve recognized taxa of Trichinella now allows, for the first time, detailed studies of their molecular biology. In the present study, we defined, curated, and compared the protein kinase complements (kinomes) of Trichinella spiralis and T. pseudospiralis using an integrated bioinformatic workflow employing transcriptomic and genomic data sets. We examined how variation in the kinome might link to unique aspects of Trichinella morphology, biology, and evolution. Furthermore, we utilized in silico structural modeling to discover and characterize a novel, MOS-like kinase with an unusual, previously undescribed N-terminal domain. Taken together, the present findings provide a basis for comparative investigations of nematode kinomes, and might facilitate the identification of Enoplea-specific intervention and diagnostic targets. Importantly, the in silico modeling approach assessed here provides an exciting prospect of being able to identify and classify currently unknown (orphan) kinases, as a foundation for their subsequent structural and functional investigation. PMID:27412987

  8. Proteomic screening of variola virus reveals a unique NF-κB inhibitor that is highly conserved among pathogenic orthopoxviruses

    PubMed Central

    Mohamed, Mohamed R.; Rahman, Masmudur M.; Lanchbury, Jerry S.; Shattuck, Donna; Neff, Chris; Dufford, Max; van Buuren, Nick; Fagan, Katharine; Barry, Michele; Smith, Scott; Damon, Inger; McFadden, Grant

    2009-01-01

    Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDNA libraries. Several protein–protein interactions were identified, including an interaction between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-κB1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-κB1/p105. Orthologs of G1R are present in a variety of pathogenic orthopoxviruses, but not in vaccinia virus, and expression of any one of these viral proteins blocks NF-κB signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses. PMID:19451633

  9. The low density lipoprotein receptor-related protein 1: Unique tissue-specific functions revealed by selective gene knockout studies

    PubMed Central

    Lillis, Anna P.; Van Duyn, Lauren B.; Murphy-Ullrich, Joanne E.; Strickland, Dudley K.

    2008-01-01

    The low-density lipoprotein (LDL) receptor-related protein (originally called LRP, but now referred to as LRP1) is a large endocytic receptor that is widely expressed in several tissues. LRP1 is a member of the LDL receptor family that plays diverse roles in various biological processes including lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes and cellular entry of bacterial toxins and viruses. Deletion of the LRP1 gene leads to lethality in mice, revealing a critical, but as of yet, undefined role in development. Tissue-specific gene deletion studies reveal an important contribution of LRP1 in the vasculature, central nervous system, in macrophages and in adipocytes. Three important properties of LRP1 dictate its diverse role in physiology: first, its ability to recognize more than thirty distinct ligands; second, its ability to bind a large number of cytoplasmic adaptor proteins via determinants located on its cytoplasmic domain in a phosphorylation-specific manner; and third, its ability to associate with and modulate the activity of other transmembrane receptors such as integrins and receptor tyrosine kinases. PMID:18626063

  10. Functional characterization of flavobacteria rhodopsins reveals a unique class of light-driven chloride pump in bacteria.

    PubMed

    Yoshizawa, Susumu; Kumagai, Yohei; Kim, Hana; Ogura, Yoshitoshi; Hayashi, Tetsuya; Iwasaki, Wataru; DeLong, Edward F; Kogure, Kazuhiro

    2014-05-01

    Light-activated, ion-pumping rhodopsins are broadly distributed among many different bacteria and archaea inhabiting the photic zone of aquatic environments. Bacterial proton- or sodium-translocating rhodopsins can convert light energy into a chemiosmotic force that can be converted into cellular biochemical energy, and thus represent a widespread alternative form of photoheterotrophy. Here we report that the genome of the marine flavobacterium Nonlabens marinus S1-08(T) encodes three different types of rhodopsins: Nonlabens marinus rhodopsin 1 (NM-R1), Nonlabens marinus rhodopsin 2 (NM-R2), and Nonlabens marinus rhodopsin 3 (NM-R3). Our functional analysis demonstrated that NM-R1 and NM-R2 are light-driven outward-translocating H(+) and Na(+) pumps, respectively. Functional analyses further revealed that the light-activated NM-R3 rhodopsin pumps Cl(-) ions into the cell, representing the first chloride-pumping rhodopsin uncovered in a marine bacterium. Phylogenetic analysis revealed that NM-R3 belongs to a distinct phylogenetic lineage quite distant from archaeal inward Cl(-)-pumping rhodopsins like halorhodopsin, suggesting that different types of chloride-pumping rhodopsins have evolved independently within marine bacterial lineages. Taken together, our data suggest that similar to haloarchaea, a considerable variety of rhodopsin types with different ion specificities have evolved in marine bacteria, with individual marine strains containing as many as three functionally different rhodopsins.

  11. Comparative Transcriptional Profiling of 3 Murine Models of SLE Nephritis Reveals Both Unique and Shared Regulatory Networks

    PubMed Central

    Zhang, Weijia; Kretzler, Matthias; Davidson, Anne

    2013-01-01

    Objective To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease. Methods Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR. Results 955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss. Conclusions These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune–mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis. PMID:24167575

  12. Unique Regulatory Properties of Heterotetrameric Inositol 1,4,5-Trisphosphate Receptors Revealed by Studying Concatenated Receptor Constructs.

    PubMed

    Chandrasekhar, Rahul; Alzayady, Kamil J; Wagner, Larry E; Yule, David I

    2016-03-01

    The ability of inositol 1,4,5-trisphosphate receptors (IP3R) to precisely initiate and generate a diverse variety of intracellular Ca(2+) signals is in part mediated by the differential regulation of the three subtypes (R1, R2, and R3) by key functional modulators (IP3, Ca(2+), and ATP). However, the contribution of IP3R heterotetramerization to Ca(2+) signal diversity has largely been unexplored. In this report, we provide the first definitive biochemical evidence of endogenous heterotetramer formation. Additionally, we examine the contribution of individual subtypes within defined concatenated heterotetramers to the shaping of Ca(2+) signals. Under conditions where key regulators of IP3R function are optimal for Ca(2+) release, we demonstrate that individual monomers within heteromeric IP3Rs contributed equally toward generating a distinct 'blended' sensitivity to IP3 that is likely dictated by the unique IP3 binding affinity of the heteromers. However, under suboptimal conditions where [ATP] were varied, we found that one subtype dictated the ATP regulatory properties of heteromers. We show that R2 monomers within a heterotetramer were both necessary and sufficient to dictate the ATP regulatory properties. Finally, the ATP-binding site B in R2 critical for ATP regulation was mutated and rendered non-functional to address questions relating to the stoichiometry of IP3R regulation. Two intact R2 monomers were sufficient to maintain ATP regulation in R2 homotetramers. In summary, we demonstrate that heterotetrameric IP3R do not necessarily behave as the sum of the constituent subunits, and these properties likely extend the versatility of IP3-induced Ca(2+) signaling in cells expressing multiple IP3R isoforms.

  13. In situ X-ray diffraction monitoring of a mechanochemical reaction reveals a unique topology metal-organic framework.

    PubMed

    Katsenis, Athanassios D; Puškarić, Andreas; Štrukil, Vjekoslav; Mottillo, Cristina; Julien, Patrick A; Užarević, Krunoslav; Pham, Minh-Hao; Do, Trong-On; Kimber, Simon A J; Lazić, Predrag; Magdysyuk, Oxana; Dinnebier, Robert E; Halasz, Ivan; Friščić, Tomislav

    2015-03-23

    Chemical and physical transformations by milling are attracting enormous interest for their ability to access new materials and clean reactivity, and are central to a number of core industries, from mineral processing to pharmaceutical manufacturing. While continuous mechanical stress during milling is thought to create an environment supporting nonconventional reactivity and exotic intermediates, such speculations have remained without proof. Here we use in situ, real-time powder X-ray diffraction monitoring to discover and capture a metastable, novel-topology intermediate of a mechanochemical transformation. Monitoring the mechanochemical synthesis of an archetypal metal-organic framework ZIF-8 by in situ powder X-ray diffraction reveals unexpected amorphization, and on further milling recrystallization into a non-porous material via a metastable intermediate based on a previously unreported topology, herein named katsenite (kat). The discovery of this phase and topology provides direct evidence that milling transformations can involve short-lived, structurally unusual phases not yet accessed by conventional chemistry.

  14. In situ X-ray diffraction monitoring of a mechanochemical reaction reveals a unique topology metal-organic framework

    NASA Astrophysics Data System (ADS)

    Katsenis, Athanassios D.; Puškarić, Andreas; Štrukil, Vjekoslav; Mottillo, Cristina; Julien, Patrick A.; Užarević, Krunoslav; Pham, Minh-Hao; Do, Trong-On; Kimber, Simon A. J.; Lazić, Predrag; Magdysyuk, Oxana; Dinnebier, Robert E.; Halasz, Ivan; Friščić, Tomislav

    2015-03-01

    Chemical and physical transformations by milling are attracting enormous interest for their ability to access new materials and clean reactivity, and are central to a number of core industries, from mineral processing to pharmaceutical manufacturing. While continuous mechanical stress during milling is thought to create an environment supporting nonconventional reactivity and exotic intermediates, such speculations have remained without proof. Here we use in situ, real-time powder X-ray diffraction monitoring to discover and capture a metastable, novel-topology intermediate of a mechanochemical transformation. Monitoring the mechanochemical synthesis of an archetypal metal-organic framework ZIF-8 by in situ powder X-ray diffraction reveals unexpected amorphization, and on further milling recrystallization into a non-porous material via a metastable intermediate based on a previously unreported topology, herein named katsenite (kat). The discovery of this phase and topology provides direct evidence that milling transformations can involve short-lived, structurally unusual phases not yet accessed by conventional chemistry.

  15. Phylogenetic analysis of canine distemper virus in South America clade 1 reveals unique molecular signatures of the local epidemic.

    PubMed

    Fischer, Cristine D B; Gräf, Tiago; Ikuta, Nilo; Lehmann, Fernanda K M; Passos, Daniel T; Makiejczuk, Aline; Silveira, Marcos A T; Fonseca, André S K; Canal, Cláudio W; Lunge, Vagner R

    2016-07-01

    Canine distemper virus (CDV) is a highly contagious pathogen for domestic dogs and several wild carnivore species. In Brazil, natural infection of CDV in dogs is very high due to the large non-vaccinated dog population, a scenario that calls for new studies on the molecular epidemiology. This study investigates the phylodynamics and amino-acid signatures of CDV epidemic in South America by analyzing a large dataset compiled from publicly available sequences and also by collecting new samples from Brazil. A population of 175 dogs with canine distemper (CD) signs was sampled, from which 89 were positive for CDV, generating 42 new CDV sequences. Phylogenetic analysis of the new and publicly available sequences revealed that Brazilian sequences mainly clustered in South America 1 (SA1) clade, which has its origin estimated to the late 1980's. The reconstruction of the demographic history in SA1 clade showed an epidemic expanding until the recent years, doubling in size every nine years. SA1 clade epidemic distinguished from the world CDV epidemic by the emergence of the R580Q strain, a very rare and potentially detrimental substitution in the viral genome. The R580Q substitution was estimated to have happened in one single evolutionary step in the epidemic history in SA1 clade, emerging shortly after introduction to the continent. Moreover, a high prevalence (11.9%) of the Y549H mutation was observed among the domestic dogs sampled here. This finding was associated (p<0.05) with outcome-death and higher frequency in mixed-breed dogs, the later being an indicator of a continuous exchange of CDV strains circulating among wild carnivores and domestic dogs. The results reported here highlight the diversity of the worldwide CDV epidemic and reveal local features that can be valuable for combating the disease.

  16. Iapetus: unique surface properties and a global color dichotomy from Cassini imaging.

    PubMed

    Denk, Tilmann; Neukum, Gerhard; Roatsch, Thomas; Porco, Carolyn C; Burns, Joseph A; Galuba, Götz G; Schmedemann, Nico; Helfenstein, Paul; Thomas, Peter C; Wagner, Roland J; West, Robert A

    2010-01-22

    Since 2004, Saturn's moon Iapetus has been observed repeatedly with the Imaging Science Subsystem of the Cassini spacecraft. The images show numerous impact craters down to the resolution limit of approximately 10 meters per pixel. Small, bright craters within the dark hemisphere indicate a dark blanket thickness on the order of meters or less. Dark, equator-facing and bright, poleward-facing crater walls suggest temperature-driven water-ice sublimation as the process responsible for local albedo patterns. Imaging data also reveal a global color dichotomy, wherein both dark and bright materials on the leading side have a substantially redder color than the respective trailing-side materials. This global pattern indicates an exogenic origin for the redder leading-side parts and suggests that the global color dichotomy initiated the thermal formation of the global albedo dichotomy. PMID:20007863

  17. Hydrogen uptake on film surfaces produced by a unique codeposition process

    NASA Astrophysics Data System (ADS)

    Salazar, Kenneth V.; Carroll, David W.; Trkula, Mitchell; Sandoval, Cynthia W.

    2003-05-01

    Hydrogen uptake on several different film surfaces has been achieved by deposition of a conventional hydrogen gettering system via a novel combination of physical vapor deposition (PVD) and chemical vapor deposition (CVD) processes. We decided to use a conventional hydrogen gettering system, developed by Smith and Schicker [J.R. Schicker, AS/KCD Project No. EPN-047620, May 1994], that uses an acetylenic organic compound mixed with carbon supported palladium metal. The organic material, 1,4-bis-(phenylethynyl) benzene (DEB), is mixed with palladium and carbon by employing conventional solid state ceramic preparative techniques. Our novel codeposition process combines PVD and CVD techniques for fabricating thin-film coatings of the palladium-catalyzed DEB hydrogen gettering system. Hydrogen uptake was confirmed by 1H NMR and our novel process lends itself well to placing hydrogen getter onto complex shapes and substrates of various compositions.

  18. E. coli metabolic protein aldehyde-alcohol dehydrogenase-E binds to the ribosome: a unique moonlighting action revealed

    PubMed Central

    Shasmal, Manidip; Dey, Sandip; Shaikh, Tanvir R.; Bhakta, Sayan; Sengupta, Jayati

    2016-01-01

    It is becoming increasingly evident that a high degree of regulation is involved in the protein synthesis machinery entailing more interacting regulatory factors. A multitude of proteins have been identified recently which show regulatory function upon binding to the ribosome. Here, we identify tight association of a metabolic protein aldehyde-alcohol dehydrogenase E (AdhE) with the E. coli 70S ribosome isolated from cell extract under low salt wash conditions. Cryo-EM reconstruction of the ribosome sample allows us to localize its position on the head of the small subunit, near the mRNA entrance. Our study demonstrates substantial RNA unwinding activity of AdhE which can account for the ability of ribosome to translate through downstream of at least certain mRNA helices. Thus far, in E. coli, no ribosome-associated factor has been identified that shows downstream mRNA helicase activity. Additionally, the cryo-EM map reveals interaction of another extracellular protein, outer membrane protein C (OmpC), with the ribosome at the peripheral solvent side of the 50S subunit. Our result also provides important insight into plausible functional role of OmpC upon ribosome binding. Visualization of the ribosome purified directly from the cell lysate unveils for the first time interactions of additional regulatory proteins with the ribosome. PMID:26822933

  19. E. coli metabolic protein aldehyde-alcohol dehydrogenase-E binds to the ribosome: a unique moonlighting action revealed.

    PubMed

    Shasmal, Manidip; Dey, Sandip; Shaikh, Tanvir R; Bhakta, Sayan; Sengupta, Jayati

    2016-01-01

    It is becoming increasingly evident that a high degree of regulation is involved in the protein synthesis machinery entailing more interacting regulatory factors. A multitude of proteins have been identified recently which show regulatory function upon binding to the ribosome. Here, we identify tight association of a metabolic protein aldehyde-alcohol dehydrogenase E (AdhE) with the E. coli 70S ribosome isolated from cell extract under low salt wash conditions. Cryo-EM reconstruction of the ribosome sample allows us to localize its position on the head of the small subunit, near the mRNA entrance. Our study demonstrates substantial RNA unwinding activity of AdhE which can account for the ability of ribosome to translate through downstream of at least certain mRNA helices. Thus far, in E. coli, no ribosome-associated factor has been identified that shows downstream mRNA helicase activity. Additionally, the cryo-EM map reveals interaction of another extracellular protein, outer membrane protein C (OmpC), with the ribosome at the peripheral solvent side of the 50S subunit. Our result also provides important insight into plausible functional role of OmpC upon ribosome binding. Visualization of the ribosome purified directly from the cell lysate unveils for the first time interactions of additional regulatory proteins with the ribosome. PMID:26822933

  20. Metagenomic Analysis of the Pygmy Loris Fecal Microbiome Reveals Unique Functional Capacity Related to Metabolism of Aromatic Compounds

    PubMed Central

    Xu, Bo; Xu, Weijiang; Yang, Fuya; Li, Junjun; Yang, Yunjuan; Tang, Xianghua; Mu, Yuelin; Zhou, Junpei; Huang, Zunxi

    2013-01-01

    The animal gastrointestinal tract contains a complex community of microbes, whose composition ultimately reflects the co-evolution of microorganisms with their animal host. An analysis of 78,619 pyrosequencing reads generated from pygmy loris fecal DNA extracts was performed to help better understand the microbial diversity and functional capacity of the pygmy loris gut microbiome. The taxonomic analysis of the metagenomic reads indicated that pygmy loris fecal microbiomes were dominated by Bacteroidetes and Proteobacteria phyla. The hierarchical clustering of several gastrointestinal metagenomes demonstrated the similarities of the microbial community structures of pygmy loris and mouse gut systems despite their differences in functional capacity. The comparative analysis of function classification revealed that the metagenome of the pygmy loris was characterized by an overrepresentation of those sequences involved in aromatic compound metabolism compared with humans and other animals. The key enzymes related to the benzoate degradation pathway were identified based on the Kyoto Encyclopedia of Genes and Genomes pathway assignment. These results would contribute to the limited body of primate metagenome studies and provide a framework for comparative metagenomic analysis between human and non-human primates, as well as a comparative understanding of the evolution of humans and their microbiome. However, future studies on the metagenome sequencing of pygmy loris and other prosimians regarding the effects of age, genetics, and environment on the composition and activity of the metagenomes are required. PMID:23457582

  1. Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection.

    PubMed

    Mesquita, Rafael D; Vionette-Amaral, Raquel J; Lowenberger, Carl; Rivera-Pomar, Rolando; Monteiro, Fernando A; Minx, Patrick; Spieth, John; Carvalho, A Bernardo; Panzera, Francisco; Lawson, Daniel; Torres, André Q; Ribeiro, Jose M C; Sorgine, Marcos H F; Waterhouse, Robert M; Montague, Michael J; Abad-Franch, Fernando; Alves-Bezerra, Michele; Amaral, Laurence R; Araujo, Helena M; Araujo, Ricardo N; Aravind, L; Atella, Georgia C; Azambuja, Patricia; Berni, Mateus; Bittencourt-Cunha, Paula R; Braz, Gloria R C; Calderón-Fernández, Gustavo; Carareto, Claudia M A; Christensen, Mikkel B; Costa, Igor R; Costa, Samara G; Dansa, Marilvia; Daumas-Filho, Carlos R O; De-Paula, Iron F; Dias, Felipe A; Dimopoulos, George; Emrich, Scott J; Esponda-Behrens, Natalia; Fampa, Patricia; Fernandez-Medina, Rita D; da Fonseca, Rodrigo N; Fontenele, Marcio; Fronick, Catrina; Fulton, Lucinda A; Gandara, Ana Caroline; Garcia, Eloi S; Genta, Fernando A; Giraldo-Calderón, Gloria I; Gomes, Bruno; Gondim, Katia C; Granzotto, Adriana; Guarneri, Alessandra A; Guigó, Roderic; Harry, Myriam; Hughes, Daniel S T; Jablonka, Willy; Jacquin-Joly, Emmanuelle; Juárez, M Patricia; Koerich, Leonardo B; Lange, Angela B; Latorre-Estivalis, José Manuel; Lavore, Andrés; Lawrence, Gena G; Lazoski, Cristiano; Lazzari, Claudio R; Lopes, Raphael R; Lorenzo, Marcelo G; Lugon, Magda D; Majerowicz, David; Marcet, Paula L; Mariotti, Marco; Masuda, Hatisaburo; Megy, Karine; Melo, Ana C A; Missirlis, Fanis; Mota, Theo; Noriega, Fernando G; Nouzova, Marcela; Nunes, Rodrigo D; Oliveira, Raquel L L; Oliveira-Silveira, Gilbert; Ons, Sheila; Orchard, Ian; Pagola, Lucia; Paiva-Silva, Gabriela O; Pascual, Agustina; Pavan, Marcio G; Pedrini, Nicolás; Peixoto, Alexandre A; Pereira, Marcos H; Pike, Andrew; Polycarpo, Carla; Prosdocimi, Francisco; Ribeiro-Rodrigues, Rodrigo; Robertson, Hugh M; Salerno, Ana Paula; Salmon, Didier; Santesmasses, Didac; Schama, Renata; Seabra-Junior, Eloy S; Silva-Cardoso, Livia; Silva-Neto, Mario A C; Souza-Gomes, Matheus; Sterkel, Marcos; Taracena, Mabel L; Tojo, Marta; Tu, Zhijian Jake; Tubio, Jose M C; Ursic-Bedoya, Raul; Venancio, Thiago M; Walter-Nuno, Ana Beatriz; Wilson, Derek; Warren, Wesley C; Wilson, Richard K; Huebner, Erwin; Dotson, Ellen M; Oliveira, Pedro L

    2015-12-01

    Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods. PMID:26627243

  2. Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection

    PubMed Central

    Mesquita, Rafael D.; Vionette-Amaral, Raquel J.; Lowenberger, Carl; Rivera-Pomar, Rolando; Monteiro, Fernando A.; Minx, Patrick; Spieth, John; Carvalho, A. Bernardo; Panzera, Francisco; Lawson, Daniel; Torres, André Q.; Ribeiro, Jose M. C.; Sorgine, Marcos H. F.; Waterhouse, Robert M.; Abad-Franch, Fernando; Alves-Bezerra, Michele; Amaral, Laurence R.; Araujo, Helena M.; Aravind, L.; Atella, Georgia C.; Azambuja, Patricia; Berni, Mateus; Bittencourt-Cunha, Paula R.; Braz, Gloria R. C.; Calderón-Fernández, Gustavo; Carareto, Claudia M. A.; Christensen, Mikkel B.; Costa, Igor R.; Costa, Samara G.; Dansa, Marilvia; Daumas-Filho, Carlos R. O.; De-Paula, Iron F.; Dias, Felipe A.; Dimopoulos, George; Emrich, Scott J.; Esponda-Behrens, Natalia; Fampa, Patricia; Fernandez-Medina, Rita D.; da Fonseca, Rodrigo N.; Fontenele, Marcio; Fronick, Catrina; Fulton, Lucinda A.; Gandara, Ana Caroline; Garcia, Eloi S.; Genta, Fernando A.; Giraldo-Calderón, Gloria I.; Gomes, Bruno; Gondim, Katia C.; Granzotto, Adriana; Guarneri, Alessandra A.; Guigó, Roderic; Harry, Myriam; Hughes, Daniel S. T.; Jablonka, Willy; Jacquin-Joly, Emmanuelle; Juárez, M. Patricia; Koerich, Leonardo B.; Lange, Angela B.; Latorre-Estivalis, José Manuel; Lavore, Andrés; Lawrence, Gena G.; Lazoski, Cristiano; Lazzari, Claudio R.; Lopes, Raphael R.; Lorenzo, Marcelo G.; Lugon, Magda D.; Marcet, Paula L.; Mariotti, Marco; Masuda, Hatisaburo; Megy, Karine; Missirlis, Fanis; Mota, Theo; Noriega, Fernando G.; Nouzova, Marcela; Nunes, Rodrigo D.; Oliveira, Raquel L. L.; Oliveira-Silveira, Gilbert; Ons, Sheila; Orchard, Ian; Pagola, Lucia; Paiva-Silva, Gabriela O.; Pascual, Agustina; Pavan, Marcio G.; Pedrini, Nicolás; Peixoto, Alexandre A.; Pereira, Marcos H.; Pike, Andrew; Polycarpo, Carla; Prosdocimi, Francisco; Ribeiro-Rodrigues, Rodrigo; Robertson, Hugh M.; Salerno, Ana Paula; Salmon, Didier; Santesmasses, Didac; Schama, Renata; Seabra-Junior, Eloy S.; Silva-Cardoso, Livia; Silva-Neto, Mario A. C.; Souza-Gomes, Matheus; Sterkel, Marcos; Taracena, Mabel L.; Tojo, Marta; Tu, Zhijian Jake; Tubio, Jose M. C.; Ursic-Bedoya, Raul; Venancio, Thiago M.; Walter-Nuno, Ana Beatriz; Wilson, Derek; Warren, Wesley C.; Wilson, Richard K.; Huebner, Erwin; Dotson, Ellen M.; Oliveira, Pedro L.

    2015-01-01

    Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods. PMID:26627243

  3. Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection.

    PubMed

    Mesquita, Rafael D; Vionette-Amaral, Raquel J; Lowenberger, Carl; Rivera-Pomar, Rolando; Monteiro, Fernando A; Minx, Patrick; Spieth, John; Carvalho, A Bernardo; Panzera, Francisco; Lawson, Daniel; Torres, André Q; Ribeiro, Jose M C; Sorgine, Marcos H F; Waterhouse, Robert M; Montague, Michael J; Abad-Franch, Fernando; Alves-Bezerra, Michele; Amaral, Laurence R; Araujo, Helena M; Araujo, Ricardo N; Aravind, L; Atella, Georgia C; Azambuja, Patricia; Berni, Mateus; Bittencourt-Cunha, Paula R; Braz, Gloria R C; Calderón-Fernández, Gustavo; Carareto, Claudia M A; Christensen, Mikkel B; Costa, Igor R; Costa, Samara G; Dansa, Marilvia; Daumas-Filho, Carlos R O; De-Paula, Iron F; Dias, Felipe A; Dimopoulos, George; Emrich, Scott J; Esponda-Behrens, Natalia; Fampa, Patricia; Fernandez-Medina, Rita D; da Fonseca, Rodrigo N; Fontenele, Marcio; Fronick, Catrina; Fulton, Lucinda A; Gandara, Ana Caroline; Garcia, Eloi S; Genta, Fernando A; Giraldo-Calderón, Gloria I; Gomes, Bruno; Gondim, Katia C; Granzotto, Adriana; Guarneri, Alessandra A; Guigó, Roderic; Harry, Myriam; Hughes, Daniel S T; Jablonka, Willy; Jacquin-Joly, Emmanuelle; Juárez, M Patricia; Koerich, Leonardo B; Lange, Angela B; Latorre-Estivalis, José Manuel; Lavore, Andrés; Lawrence, Gena G; Lazoski, Cristiano; Lazzari, Claudio R; Lopes, Raphael R; Lorenzo, Marcelo G; Lugon, Magda D; Majerowicz, David; Marcet, Paula L; Mariotti, Marco; Masuda, Hatisaburo; Megy, Karine; Melo, Ana C A; Missirlis, Fanis; Mota, Theo; Noriega, Fernando G; Nouzova, Marcela; Nunes, Rodrigo D; Oliveira, Raquel L L; Oliveira-Silveira, Gilbert; Ons, Sheila; Orchard, Ian; Pagola, Lucia; Paiva-Silva, Gabriela O; Pascual, Agustina; Pavan, Marcio G; Pedrini, Nicolás; Peixoto, Alexandre A; Pereira, Marcos H; Pike, Andrew; Polycarpo, Carla; Prosdocimi, Francisco; Ribeiro-Rodrigues, Rodrigo; Robertson, Hugh M; Salerno, Ana Paula; Salmon, Didier; Santesmasses, Didac; Schama, Renata; Seabra-Junior, Eloy S; Silva-Cardoso, Livia; Silva-Neto, Mario A C; Souza-Gomes, Matheus; Sterkel, Marcos; Taracena, Mabel L; Tojo, Marta; Tu, Zhijian Jake; Tubio, Jose M C; Ursic-Bedoya, Raul; Venancio, Thiago M; Walter-Nuno, Ana Beatriz; Wilson, Derek; Warren, Wesley C; Wilson, Richard K; Huebner, Erwin; Dotson, Ellen M; Oliveira, Pedro L

    2015-12-01

    Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.

  4. Unique features revealed by the genome sequence of Acinetobacter sp. ADP1, a versatile and naturally transformation competent bacterium.

    PubMed

    Barbe, Valérie; Vallenet, David; Fonknechten, Nuria; Kreimeyer, Annett; Oztas, Sophie; Labarre, Laurent; Cruveiller, Stéphane; Robert, Catherine; Duprat, Simone; Wincker, Patrick; Ornston, L Nicholas; Weissenbach, Jean; Marlière, Philippe; Cohen, Georges N; Médigue, Claudine

    2004-01-01

    Acinetobacter sp. strain ADP1 is a nutritionally versatile soil bacterium closely related to representatives of the well-characterized Pseudomonas aeruginosa and Pseudomonas putida. Unlike these bacteria, the Acinetobacter ADP1 is highly competent for natural transformation which affords extraordinary convenience for genetic manipulation. The circular chromosome of the Acinetobacter ADP1, presented here, encodes 3325 predicted coding sequences, of which 60% have been classified based on sequence similarity to other documented proteins. The close evolutionary proximity of Acinetobacter and Pseudomonas species, as judged by the sequences of their 16S RNA genes and by the highest level of bidirectional best hits, contrasts with the extensive divergence in the GC content of their DNA (40 versus 62%). The chromosomes also differ significantly in size, with the Acinetobacter ADP1 chromosome <60% of the length of the Pseudomonas counterparts. Genome analysis of the Acinetobacter ADP1 revealed genes for metabolic pathways involved in utilization of a large variety of compounds. Almost all of these genes, with orthologs that are scattered in other species, are located in five major 'islands of catabolic diversity', now an apparent 'archipelago of catabolic diversity', within one-quarter of the overall genome. Acinetobacter ADP1 displays many features of other aerobic soil bacteria with metabolism oriented toward the degradation of organic compounds found in their natural habitat. A distinguishing feature of this genome is the absence of a gene corresponding to pyruvate kinase, the enzyme that generally catalyzes the terminal step in conversion of carbohydrates to pyruvate for respiration by the citric acid cycle. This finding supports the view that the cycle itself is centrally geared to the catabolic capabilities of this exceptionally versatile organism. PMID:15514110

  5. An Ultra-specific Avian Antibody to Phosphorylated Tau Protein Reveals a Unique Mechanism for Phosphoepitope Recognition

    PubMed Central

    Shih, Heather H.; Tu, Chao; Cao, Wei; Klein, Anne; Ramsey, Renee; Fennell, Brian J.; Lambert, Matthew; Ní Shúilleabháin, Deirdre; Autin, Bénédicte; Kouranova, Eugenia; Laxmanan, Sri; Braithwaite, Steven; Wu, Leeying; Ait-Zahra, Mostafa; Milici, Anthony J.; Dumin, Jo Ann; LaVallie, Edward R.; Arai, Maya; Corcoran, Christopher; Paulsen, Janet E.; Gill, Davinder; Cunningham, Orla; Bard, Joel; Mosyak, Lydia; Finlay, William J. J.

    2012-01-01

    Highly specific antibodies to phosphoepitopes are valuable tools to study phosphorylation in disease states, but their discovery is largely empirical, and the molecular mechanisms mediating phosphospecific binding are poorly understood. Here, we report the generation and characterization of extremely specific recombinant chicken antibodies to three phosphoepitopes on the Alzheimer disease-associated protein tau. Each antibody shows full specificity for a single phosphopeptide. The chimeric IgG pT231/pS235_1 exhibits a KD of 0.35 nm in 1:1 binding to its cognate phosphopeptide. This IgG is murine ortholog-cross-reactive, specifically recognizing the pathological form of tau in brain samples from Alzheimer patients and a mouse model of tauopathy. To better understand the underlying binding mechanisms allowing such remarkable specificity, we determined the structure of pT231/pS235_1 Fab in complex with its cognate phosphopeptide at 1.9 Å resolution. The Fab fragment exhibits novel complementarity determining region (CDR) structures with a “bowl-like” conformation in CDR-H2 that tightly and specifically interacts with the phospho-Thr-231 phosphate group, as well as a long, disulfide-constrained CDR-H3 that mediates peptide recognition. This binding mechanism differs distinctly from either peptide- or hapten-specific antibodies described to date. Surface plasmon resonance analyses showed that pT231/pS235_1 binds a truly compound epitope, as neither phosphorylated Ser-235 nor free peptide shows any measurable binding affinity. PMID:23148212

  6. A unique in vivo experimental approach reveals metabolic adaptation of the probiotic Propionibacterium freudenreichii to the colon environment

    PubMed Central

    2013-01-01

    Background Propionibacterium freudenreichii is a food grade bacterium consumed both in cheeses and in probiotic preparations. Its promising probiotic potential, relying largely on the active release of beneficial metabolites within the gut as well as the expression of key surface proteins involved in immunomodulation, deserves to be explored more deeply. Adaptation to the colon environment is requisite for the active release of propionibacterial beneficial metabolites and constitutes a bottleneck for metabolic activity in vivo. Mechanisms allowing P. freudenreichii to adapt to digestive stresses have been only studied in vitro so far. Our aim was therefore to study P. freudenreichii metabolic adaptation to intra-colonic conditions in situ. Results We maintained a pure culture of the type strain P. freudenreichii CIRM BIA 1, contained in a dialysis bag, within the colon of vigilant piglets during 24 hours. A transcriptomic analysis compared gene expression to identify the metabolic pathways induced by this environment, versus control cultures maintained in spent culture medium. We observed drastic changes in the catabolism of sugars and amino-acids. Glycolysis, the Wood-Werkman cycle and the oxidative phosphorylation pathways were down-regulated but induction of specific carbohydrate catabolisms and alternative pathways were induced to produce NADH, NADPH, ATP and precursors (utilizing of propanediol, gluconate, lactate, purine and pyrimidine and amino-acids). Genes involved in stress response were down-regulated and genes specifically expressed during cell division were induced, suggesting that P. freudenreichii adapted its metabolism to the conditions encountered in the colon. Conclusions This study constitutes the first molecular demonstration of P. freudenreichii activity and physiological adaptation in vivo within the colon. Our data are likely specific to our pig microbiota composition but opens an avenue towards understanding probiotic action within the gut

  7. Uniquely Acquired Vintage Seismic Reflection Data Reveal the Stratigraphic and Tectonic History of the Montana Disturbed Belt, USA

    NASA Astrophysics Data System (ADS)

    Speece, M. A.; Link, C. A.; Stickney, M.

    2011-12-01

    techniques including linear noise suppression of the air wave and ground roll, refraction statics, and prestack migration. Reprocessing of these data using state-of-the-art seismic reflection processing techniques will provide a detailed picture of the stratigraphy and tectonic framework for this region. Moreover, extended correlations of the Vibroseis records to Moho depths might reveal new insights on crustal thickness and provide a framework for understanding crustal thickening during the Laramide Orogeny as well as later Cenozoic extension.

  8. Flood damage claims reveal insights about surface runoff in Switzerland

    NASA Astrophysics Data System (ADS)

    Bernet, D. B.; Prasuhn, V.; Weingartner, R.

    2015-12-01

    A few case studies in Switzerland exemplify that not only overtopping water bodies frequently cause damages to buildings. Reportedly, a large share of the total loss due to flooding in Switzerland goes back to surface runoff that is formed and is propagating outside of regular watercourses. Nevertheless, little is known about when, where and why such surface runoff occurs. The described process encompasses surface runoff formation, followed by unchannelised overland flow until a water body is reached. It is understood as a type of flash flood, has short response times and occurs diffusely in the landscape. Thus, the process is difficult to observe and study directly. A promising source indicating surface runoff indirectly are houseowners' damage claims recorded by Swiss Public Insurance Companies for Buildings (PICB). In most of Switzerland, PICB hold a monopoly position and insure (almost) every building. Consequently, PICB generally register all damages to buildings caused by an insured natural hazard (including surface runoff) within the respective zones. We have gathered gapless flood related claim records of most of all Swiss PICB covering more than the last two decades on average. Based on a subset, we have developed a methodology to differentiate claims related to surface runoff from other causes. This allows us to assess the number of claims as well as total loss related to surface runoff and compare these to the numbers of overtopping watercourses. Furthermore, with the good data coverage, we are able to analyze surface runoff related claims in space and time, from which we can infer spatial and temporal characteristics of surface runoff. Although the delivered data of PICB are heterogeneous and, consequently, time-consuming to harmonize, our first results show that exploiting these damage claim records is feasible and worthwhile to learn more about surface runoff in Switzerland.

  9. Synthesis, characterization, and evaluation of a superficially porous particle with unique, elongated pore channels normal to the surface.

    PubMed

    Wei, Ta-Chen; Mack, Anne; Chen, Wu; Liu, Jia; Dittmann, Monika; Wang, Xiaoli; Barber, William E

    2016-04-01

    In recent years, superficially porous particles (SPPs) have drawn great interest because of their special particle characteristics and improvement in separation efficiency. Superficially porous particles are currently manufactured by adding silica nanoparticles onto solid cores using either a multistep multilayer process or one-step coacervation process. The pore size is mainly controlled by the size of the silica nanoparticles and the tortuous pore channel geometry is determined by how those nanoparticles randomly aggregate. Such tortuous pore structure is also similar to that of all totally porous particles used in HPLC today. In this article, we report on the development of a next generation superficially porous particle with a unique pore structure that includes a thinner shell thickness and ordered pore channels oriented normal to the particle surface. The method of making the new superficially porous particles is a process called pseudomorphic transformation (PMT), which is a form of micelle templating. Porosity is no longer controlled by randomly aggregated nanoparticles but rather by micelles that have an ordered liquid crystal structure. The new particle possesses many advantages such as a narrower particle size distribution, thinner porous layer with high surface area and, most importantly, highly ordered, non-tortuous pore channels oriented normal to the particle surface. This PMT process has been applied to make 1.8-5.1μm SPPs with pore size controlled around 75Å and surface area around 100m(2)/g. All particles with different sizes show the same unique pore structure with tunable pore size and shell thickness. The impact of the novel pore structure on the performance of these particles is characterized by measuring van Deemter curves and constructing kinetic plots. Reduced plate heights as low as 1.0 have been achieved on conventional LC instruments. This indicates higher efficiency of such particles compared to conventional totally porous and

  10. Advances in cell surface glycoengineering reveal biological function.

    PubMed

    Nischan, Nicole; Kohler, Jennifer J

    2016-08-01

    Cell surface glycans are critical mediators of cell-cell, cell-ligand, and cell-pathogen interactions. By controlling the set of glycans displayed on the surface of a cell, it is possible to gain insight into the biological functions of glycans. Moreover, control of glycan expression can be used to direct cellular behavior. While genetic approaches to manipulate glycosyltransferase gene expression are available, their utility in glycan engineering has limitations due to the combinatorial nature of glycan biosynthesis and the functional redundancy of glycosyltransferase genes. Biochemical and chemical strategies offer valuable complements to these genetic approaches, notably by enabling introduction of unnatural functionalities, such as fluorophores, into cell surface glycans. Here, we describe some of the most recent developments in glycoengineering of cell surfaces, with an emphasis on strategies that employ novel chemical reagents. We highlight key examples of how these advances in cell surface glycan engineering enable study of cell surface glycans and their function. Exciting new technologies include synthetic lipid-glycans, new chemical reporters for metabolic oligosaccharide engineering to allow tandem and in vivo labeling of glycans, improved chemical and enzymatic methods for glycoproteomics, and metabolic glycosyltransferase inhibitors. Many chemical and biochemical reagents for glycan engineering are commercially available, facilitating their adoption by the biological community.

  11. Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold.

    PubMed

    Feliciano, Patricia R; Drennan, Catherine L; Nonato, M Cristina

    2016-08-30

    Fumarate hydratases (FHs) are essential metabolic enzymes grouped into two classes. Here, we present the crystal structure of a class I FH, the cytosolic FH from Leishmania major, which reveals a previously undiscovered protein fold that coordinates a catalytically essential [4Fe-4S] cluster. Our 2.05 Å resolution data further reveal a dimeric architecture for this FH that resembles a heart, with each lobe comprised of two domains that are arranged around the active site. Besides the active site, where the substrate S-malate is bound bidentate to the unique iron of the [4Fe-4S] cluster, other binding pockets are found near the dimeric enzyme interface, some of which are occupied by malonate, shown here to be a weak inhibitor of this enzyme. Taken together, these data provide a framework both for investigations of the class I FH catalytic mechanism and for drug design aimed at fighting neglected tropical diseases.

  12. Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold.

    PubMed

    Feliciano, Patricia R; Drennan, Catherine L; Nonato, M Cristina

    2016-08-30

    Fumarate hydratases (FHs) are essential metabolic enzymes grouped into two classes. Here, we present the crystal structure of a class I FH, the cytosolic FH from Leishmania major, which reveals a previously undiscovered protein fold that coordinates a catalytically essential [4Fe-4S] cluster. Our 2.05 Å resolution data further reveal a dimeric architecture for this FH that resembles a heart, with each lobe comprised of two domains that are arranged around the active site. Besides the active site, where the substrate S-malate is bound bidentate to the unique iron of the [4Fe-4S] cluster, other binding pockets are found near the dimeric enzyme interface, some of which are occupied by malonate, shown here to be a weak inhibitor of this enzyme. Taken together, these data provide a framework both for investigations of the class I FH catalytic mechanism and for drug design aimed at fighting neglected tropical diseases. PMID:27528683

  13. Characterization of the Genomic Xist Locus in Rodents Reveals Conservation of Overall Gene Structure and Tandem Repeats but Rapid Evolution of Unique Sequence

    PubMed Central

    Nesterova, Tatyana B.; Slobodyanyuk, Sergey Ya.; Elisaphenko, Eugene A.; Shevchenko, Alexander I.; Johnston, Colette; Pavlova, Marina E.; Rogozin, Igor B.; Kolesnikov, Nikolay N.; Brockdorff, Neil; Zakian, Suren M.

    2001-01-01

    The Xist locus plays a central role in the regulation of X chromosome inactivation in mammals, although its exact mode of action remains to be elucidated. Evolutionary studies are important in identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, and detailed characterization of the Xist gene from four closely related species of common vole (field mouse), Microtus arvalis. Our analysis reveals that there is overall conservation of Xist gene structure both between different vole species and relative to mouse and human Xist/XIST. Within transcribed sequence, there is significant conservation over five short regions of unique sequence and also over Xist-specific tandem repeats. The majority of unique sequences, however, are evolving at an unexpectedly high rate. This is also evident from analysis of flanking sequences, which reveals a very high rate of rearrangement and invasion of dispersed repeats. We discuss these results in the context of Xist gene function and evolution. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AJ310127–AJ310130 and AJ311670.] PMID:11337478

  14. Unique signature of bivalent analyte surface plasmon resonance model: A model governed by non-linear differential equations

    NASA Astrophysics Data System (ADS)

    Tiwari, Purushottam; Wang, Xuewen; Darici, Yesim; He, Jin; Uren, Aykut

    Surface plasmon resonance (SPR) is a biophysical technique for the quantitative analysis of bimolecular interactions. Correct identification of the binding model is crucial for the interpretation of SPR data. Bivalent SPR model is governed by non-linear differential equations, which, in general, have no analytical solutions. Therefore, an analytical based approach cannot be employed in order to identify this particular model. There exists a unique signature in the bivalent analyte model, existence of an `optimal analyte concentration', which can distinguish this model from other biphasic models. The unambiguous identification and related analysis of the bivalent analyte model is demonstrated by using theoretical simulations and experimentally measured SPR sensorgrams. Experimental SPR sensorgrams were measured by using Biacore T200 instrument available in Biacore Molecular Interaction Shared Resource facility, supported by NIH Grant P30CA51008, at Georgetown University.

  15. Molecular dynamics reveal BCR-ABL1 polymutants as a unique mechanism of resistance to PAN-BCR-ABL1 kinase inhibitor therapy

    PubMed Central

    Gibbons, Don L.; Pricl, Sabrina; Posocco, Paola; Laurini, Erik; Fermeglia, Maurizio; Sun, Hanshi; Talpaz, Moshe; Donato, Nicholas; Quintás-Cardama, Alfonso

    2014-01-01

    The acquisition of mutations within the BCR-ABL1 kinase domain is frequently associated with tyrosine kinase inhibitor (TKI) failure in chronic myeloid leukemia. Sensitive sequencing techniques have revealed a high prevalence of compound BCR-ABL1 mutations (polymutants) in patients failing TKI therapy. To investigate the molecular consequences of such complex mutant proteins with regards to TKI resistance, we determined by cloning techniques the presence of polymutants in a cohort of chronic-phase patients receiving imatinib followed by dasatinib therapy. The analysis revealed a high frequency of polymutant BCR-ABL1 alleles even after failure of frontline imatinib, and also the progressive exhaustion of the pool of unmutated BCR-ABL1 alleles over the course of sequential TKI therapy. Molecular dynamics analyses of the most frequent polymutants in complex with TKIs revealed the basis of TKI resistance. Modeling of BCR-ABL1 in complex with the potent pan-BCR-ABL1 TKI ponatinib highlighted potentially effective therapeutic strategies for patients carrying these recalcitrant and complex BCR-ABL1 mutant proteins while unveiling unique mechanisms of escape to ponatinib therapy. PMID:24550512

  16. A Computer-Assisted 3D Model for Analyzing the Aggregation of Tumorigenic Cells Reveals Specialized Behaviors and Unique Cell Types that Facilitate Aggregate Coalescence

    PubMed Central

    Scherer, Amanda; Kuhl, Spencer; Wessels, Deborah; Lusche, Daniel F.; Hanson, Brett; Ambrose, Joseph; Voss, Edward; Fletcher, Emily; Goldman, Charles; Soll, David R.

    2015-01-01

    We have developed a 4D computer-assisted reconstruction and motion analysis system, J3D-DIAS 4.1, and applied it to the reconstruction and motion analysis of tumorigenic cells in a 3D matrix. The system is unique in that it is fast, high-resolution, acquires optical sections using DIC microscopy (hence there is no associated photoxicity), and is capable of long-term 4D reconstruction. Specifically, a z-series at 5 μm increments can be acquired in less than a minute on tissue samples embedded in a 1.5 mm thick 3D Matrigel matrix. Reconstruction can be repeated at intervals as short as every minute and continued for 30 days or longer. Images are converted to mathematical representations from which quantitative parameters can be derived. Application of this system to cancer cells from established lines and fresh tumor tissue has revealed unique behaviors and cell types not present in non-tumorigenic lines. We report here that cells from tumorigenic lines and tumors undergo rapid coalescence in 3D, mediated by specific cell types that we have named “facilitators” and “probes.” A third cell type, the “dervish”, is capable of rapid movement through the gel and does not adhere to it. These cell types have never before been described. Our data suggest that tumorigenesis in vitro is a developmental process involving coalescence facilitated by specialized cells that culminates in large hollow spheres with complex architecture. The unique effects of select monoclonal antibodies on these processes demonstrate the usefulness of the model for analyzing the mechanisms of anti-cancer drugs. PMID:25790299

  17. The structure of Aquifex aeolicus ribosomal protein S8 reveals a unique subdomain that contributes to an extremely tight association with 16S rRNA.

    PubMed

    Menichelli, Elena; Edgcomb, Stephen P; Recht, Michael I; Williamson, James R

    2012-01-20

    The assembly of ribonucleoprotein complexes occurs under a broad range of conditions, but the principles that promote assembly and allow function at high temperature are poorly understood. The ribosomal protein S8 from Aquifex aeolicus (AS8) is unique in that there is a 41-residue insertion in the consensus S8 sequence. In addition, AS8 exhibits an unusually high affinity for the 16S ribosomal RNA, characterized by a picomolar dissociation constant that is approximately 26,000-fold tighter than the equivalent interaction from Escherichia coli. Deletion analysis demonstrated that binding to the minimal site on helix 21 occurred at the same nanomolar affinity found for other bacterial species. The additional affinity required the presence of a three-helix junction between helices 20, 21, and 22. The crystal structure of AS8 was solved, revealing the helix-loop-helix geometry of the unique AS8 insertion region, while the core of the molecule is conserved with known S8 structures. The AS8 structure was modeled onto the structure of the 30S ribosomal subunit from E. coli, suggesting the possibility that the unique subdomain provides additional backbone and side-chain contacts between the protein and an unpaired base within the three-way junction of helices 20, 21, and 22. Point mutations in the protein insertion subdomain resulted in a significantly reduced RNA binding affinity with respect to wild-type AS8. These results indicate that the AS8-specific subdomain provides additional interactions with the three-way junction that contribute to the extremely tight binding to ribosomal RNA.

  18. Structural Characterization of Proline-rich Tyrosine Kinase 2 (PYK2) Reveals a Unique (DFG-out) Conformation and Enables Inhibitor Design

    SciTech Connect

    Han, Seungil; Mistry, Anil; Chang, Jeanne S.; Cunningham, David; Griffor, Matt; Bonnette, Peter C.; Wang, Hong; Chrunyk, Boris A.; Aspnes, Gary E.; Walker, Daniel P.; Brosius, Arthur D.; Buckbinder, Leonard; Pfizer

    2009-05-21

    Proline-rich tyrosine kinase 2 (PYK2) is a cytoplasmic, non-receptor tyrosine kinase implicated in multiple signaling pathways. It is a negative regulator of osteogenesis and considered a viable drug target for osteoporosis treatment. The high-resolution structures of the human PYK2 kinase domain with different inhibitor complexes establish the conventional bilobal kinase architecture and show the conformational variability of the DFG loop. The basis for the lack of selectivity for the classical kinase inhibitor, PF-431396, within the FAK family is explained by our structural analyses. Importantly, the novel DFG-out conformation with two diarylurea inhibitors (BIRB796, PF-4618433) reveals a distinct subclass of non-receptor tyrosine kinases identifiable by the gatekeeper Met-502 and the unique hinge loop conformation of Leu-504. This is the first example of a leucine residue in the hinge loop that blocks the ATP binding site in the DFG-out conformation. Our structural, biophysical, and pharmacological studies suggest that the unique features of the DFG motif, including Leu-504 hinge-loop variability, can be exploited for the development of selective protein kinase inhibitors.

  19. Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a non-forensic sample

    PubMed Central

    Yoder, Keith J.; Porges, Eric C.; Decety, Jean

    2016-01-01

    Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a non-forensic sample are linked to amygdala response to violence, the current study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self-Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. PMID:25557777

  20. A Unique Set of 11,008 Onion Expressed Sequence Tags Reveals Expressed Sequence and Genomic Differences between the Monocot Orders Asparagales and PoalesW⃞

    PubMed Central

    Kuhl, Joseph C.; Cheung, Foo; Yuan, Qiaoping; Martin, William; Zewdie, Yayeh; McCallum, John; Catanach, Andrew; Rutherford, Paul; Sink, Kenneth C.; Jenderek, Maria; Prince, James P.; Town, Christopher D.; Havey, Michael J.

    2004-01-01

    Enormous genomic resources have been developed for plants in the monocot order Poales; however, it is not clear how representative the Poales are for the monocots as a whole. The Asparagales are a monophyletic order sister to the lineage carrying the Poales and possess economically important plants such as asparagus, garlic, and onion. To assess the genomic differences between the Asparagales and Poales, we generated 11,008 unique ESTs from a normalized cDNA library of onion. Sequence analyses of these ESTs revealed microsatellite markers, single nucleotide polymorphisms, and homologs of transposable elements. Mean nucleotide similarity between rice and the Asparagales was 78% across coding regions. Expressed sequence and genomic comparisons revealed strong differences between the Asparagales and Poales for codon usage and mean GC content, GC distribution, and relative GC content at each codon position, indicating that genomic characteristics are not uniform across the monocots. The Asparagales were more similar to eudicots than to the Poales for these genomic characteristics. PMID:14671025

  1. Unique gold sponges: biopolymer-assisted hydrothermal synthesis and potential application as surface-enhanced Raman scattering substrates

    NASA Astrophysics Data System (ADS)

    Gao, Shuyan; Zhang, Hongjie; Wang, Xiaomei; Yang, Jianhui; Zhou, Liang; Peng, Chunyun; Sun, Dehui; Li, Meiye

    2005-11-01

    In this paper we describe a biopolymer-assisted hydrothermal approach to the synthesis of gold sponges. This is carried out by transferring a hyaluronic acid potassium salt/HAuCl4 aqueous solution into a stainless steel autoclave with a Teflon liner and heating in an oven at 180 °C for 6 h. Here, hyaluronic acid potassium salt plays three roles in the synthesis, namely, stabilization, reduction, and as a soft template. Field emission scanning electron microscopy images, energy-dispersive x-ray spectroscopy, and x-ray diffraction reveal that the materials obtained consist of an interconnected framework of face-centred cubic metallic gold filaments, which is approximately 0.6 µm in width and composed of fused micrometre-sized particles that enclose pores 1-4 µm in size. The test of surface-enhanced Raman scattering (SERS) from 4-mercaptobenzoic acid shows that the prepared gold sponges are an active SERS substrate. This is largely because they had an increased number of particle junctions, which are SERS active sites. This route can also be extended to the fabrication of silver sponges, which are composed of fused crystallites with diameters of 200-400 nm that enclosed pores 0.4-2 µm in size. The test of SERS from Rhodamine 6G also reveals that the prepared silver sponges are likewise an excellent SERS substrate.

  2. IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin

    PubMed Central

    Daou, Nadine; Buisson, Christophe; Gohar, Michel; Vidic, Jasmina; Bierne, Hélène; Kallassy, Mireille; Lereclus, Didier; Nielsen-LeRoux, Christina

    2009-01-01

    The human opportunistic pathogen Bacillus cereus belongs to the B. cereus group that includes bacteria with a broad host spectrum. The ability of these bacteria to colonize diverse hosts is reliant on the presence of adaptation factors. Previously, an IVET strategy led to the identification of a novel B. cereus protein (IlsA, Iron-regulated leucine rich surface protein), which is specifically expressed in the insect host or under iron restrictive conditions in vitro. Here, we show that IlsA is localized on the surface of B. cereus and hence has the potential to interact with host proteins. We report that B. cereus uses hemoglobin, heme and ferritin, but not transferrin and lactoferrin. In addition, affinity tests revealed that IlsA interacts with both hemoglobin and ferritin. Furthermore, IlsA directly binds heme probably through the NEAT domain. Inactivation of ilsA drastically decreases the ability of B. cereus to grow in the presence of hemoglobin, heme and ferritin, indicating that IlsA is essential for iron acquisition from these iron sources. In addition, the ilsA mutant displays a reduction in growth and virulence in an insect model. Hence, our results indicate that IlsA is a key factor within a new iron acquisition system, playing an important role in the general virulence strategy adapted by B. cereus to colonize susceptible hosts. PMID:19956654

  3. Top-down proteomics reveals a unique protein S-thiolation switch in Salmonella Typimurium in response to infection-like conditions

    SciTech Connect

    Ansong, Charles; Wu, Si; Meng, Da; Liu, Xiaowen; Brewer, Heather M.; Kaiser, Brooke LD; Nakayasu, Ernesto S.; Cort, John R.; Pevzner, Pavel A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.; Pasa-Tolic, Ljiljana

    2013-06-18

    Characterization of the mature protein complement in cells is crucial for a better understanding of cellular processes on a systems-wide scale. Bottom-up proteomic approaches often lead to loss of critical information about an endogenous protein’s actual state due to post translational modifications (PTMs) and other processes. Top-down approaches that involve analysis of the intact protein can address this concern but present significant analytical challenges related to the separation quality needed, measurement sensitivity, and speed that result in low throughput and limited coverage. Here we used single-dimension ultra high pressure liquid chromatography mass spectrometry to investigate the comprehensive ‘intact’ proteome of the Gram negative bacterial pathogen Salmonella Typhimurium. Top-down proteomics analysis revealed 563 unique proteins including 1665 proteoforms generated by PTMs, representing the largest microbial top-down dataset reported to date. Our analysis not only confirmed several previously recognized aspects of Salmonella biology and bacterial PTMs in general, but also revealed several novel biological insights. Of particular interest was differential utilization of the protein S-thiolation forms S-glutathionylation and S-cysteinylation in response to infection-like conditions versus basal conditions, which was corroborated by changes in corresponding biosynthetic pathways. This differential utilization highlights underlying metabolic mechanisms that modulate changes in cellular signaling, and represents to our knowledge the first report of S-cysteinylation in Gram negative bacteria. The demonstrated utility of our simple proteome-wide intact protein level measurement strategy for gaining biological insight should promote broader adoption and applications of top-down proteomics approaches.

  4. Complexity in Climatic Controls on Plant Species Distribution: Satellite Data Reveal Unique Climate for Giant Sequoia in the California Sierra Nevada

    NASA Astrophysics Data System (ADS)

    Waller, Eric Kindseth

    governing the distribution? Detailed aspects of the local climate warranted more investigation. Chapter 4 investigates the climate associated with the frequent cloud formation over the western slopes of the southern Sierra Nevada: the "sequoia belt". This region is climatically distinct in a number of ways, all of which could be factors in influencing the distribution of giant sequoia and other species. Satellite and micrometeorological flux tower data reveal characteristics of the sequoia belt that were not evident with surface climate measurements and maps derived from them. Results have implications for species distributions everywhere, but especially in rugged mountains, where climates are complex and poorly mapped. Chapter 5 summarizes some of the main conclusions from the work and suggests directions for related future research. (Abstract shortened by UMI.).

  5. Structures of the Bacillus subtilis glutamine synthetase dodecamer reveal large intersubunit catalytic conformational changes linked to a unique feedback inhibition mechanism.

    PubMed

    Murray, David S; Chinnam, Nagababu; Tonthat, Nam Ky; Whitfill, Travis; Wray, Lewis V; Fisher, Susan H; Schumacher, Maria A

    2013-12-13

    Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in nitrogen metabolism. There are two main bacterial GS isoenzymes, GSI-α and GSI-β. GSI-α enzymes, which have not been structurally characterized, are uniquely feedback-inhibited by Gln. To gain insight into GSI-α function, we performed biochemical and cellular studies and obtained structures for all GSI-α catalytic and regulatory states. GSI-α forms a massive 600-kDa dodecameric machine. Unlike other characterized GS, the Bacillus subtilis enzyme undergoes dramatic intersubunit conformational alterations during formation of the transition state. Remarkably, these changes are required for active site construction. Feedback inhibition arises from a hydrogen bond network between Gln, the catalytic glutamate, and the GSI-α-specific residue, Arg(62), from an adjacent subunit. Notably, Arg(62) must be ejected for proper active site reorganization. Consistent with these findings, an R62A mutation abrogates Gln feedback inhibition but does not affect catalysis. Thus, these data reveal a heretofore unseen restructuring of an enzyme active site that is coupled with an isoenzyme-specific regulatory mechanism. This GSI-α-specific regulatory network could be exploited for inhibitor design against Gram-positive pathogens.

  6. The first venomous crustacean revealed by transcriptomics and functional morphology: remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin.

    PubMed

    von Reumont, Björn M; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A

    2014-01-01

    Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species.

  7. Structure of the Trichomonas vaginalis Myb3 DNA-binding domain bound to a promoter sequence reveals a unique C-terminal β-hairpin conformation.

    PubMed

    Wei, Shu-Yi; Lou, Yuan-Chao; Tsai, Jia-Yin; Ho, Meng-Ru; Chou, Chun-Chi; Rajasekaran, M; Hsu, Hong-Ming; Tai, Jung-Hsiang; Hsiao, Chwan-Deng; Chen, Chinpan

    2012-01-01

    Trichomonas vaginalis Myb3 transcription factor (tvMyb3) recognizes the MRE-1 promoter sequence and regulates ap65-1 gene, which encodes a hydrogenosomal malic enzyme that may play a role in the cytoadherence of the parasite. Here, we identified tvMyb3(53-180) as the essential fragment for DNA recognition and report the crystal structure of tvMyb3(53-180) bound to MRE-1 DNA. The N-terminal fragment adopts the classical conformation of an Myb DNA-binding domain, with the third helices of R2 and R3 motifs intercalating in the major groove of DNA. The C-terminal extension forms a β-hairpin followed by a flexible tail, which is stabilized by several interactions with the R3 motif and is not observed in other Myb proteins. Interestingly, this unique C-terminal fragment does not stably connect with DNA in the complex structure but is involved in DNA binding, as demonstrated by NMR chemical shift perturbation, (1)H-(15)N heteronuclear-nuclear Overhauser effect and intermolecular paramagnetic relaxation enhancement. Site-directed mutagenesis also revealed that this C-terminal fragment is crucial for DNA binding, especially the residue Arg(153) and the fragment K(170)KRK(173). We provide a structural basis for MRE-1 DNA recognition and suggest a possible post-translational regulation of tvMyb3 protein. PMID:21908401

  8. Nanoscale periodic modulations on sodium chloride surface revealed by tuning fork atomic force microscopy.

    PubMed

    Clark, Kendal W; Qin, Shengyong; Zhang, X-G; Li, An-Ping

    2012-05-11

    The sodium chloride surface is one of the most common platforms for the study of catalysts, thin film growth, and atmospheric aerosols. Here we report a nanoscale periodic modulation pattern on the surface of a cleaved NaCl single crystal, revealed by non-contact atomic force microscopy with a tuning fork sensor. The surface pattern shows two orthogonal domains, extending over the entire cleavage surface. The spatial modulations exhibit a characteristic period of 5.4 nm, along <110> crystallographic directions of the NaCl. The modulations are robust in vacuum, not affected by the tip-induced electric field or gentle annealing (<300 °C); however, they are eliminated after exposure to water and an atomically flat surface can be recovered by subsequent thermal annealing after water exposure. A strong electrostatic charging is revealed on the cleavage surface which may facilitate the formation of the observed metastable surface reconstruction.

  9. Nanoscale periodic modulations on sodium chloride surface revealed by tuning fork atomic force microscopy.

    PubMed

    Clark, Kendal W; Qin, Shengyong; Zhang, X-G; Li, An-Ping

    2012-05-11

    The sodium chloride surface is one of the most common platforms for the study of catalysts, thin film growth, and atmospheric aerosols. Here we report a nanoscale periodic modulation pattern on the surface of a cleaved NaCl single crystal, revealed by non-contact atomic force microscopy with a tuning fork sensor. The surface pattern shows two orthogonal domains, extending over the entire cleavage surface. The spatial modulations exhibit a characteristic period of 5.4 nm, along <110> crystallographic directions of the NaCl. The modulations are robust in vacuum, not affected by the tip-induced electric field or gentle annealing (<300 °C); however, they are eliminated after exposure to water and an atomically flat surface can be recovered by subsequent thermal annealing after water exposure. A strong electrostatic charging is revealed on the cleavage surface which may facilitate the formation of the observed metastable surface reconstruction. PMID:22513484

  10. Characterization of Dye-decolorizing Peroxidase (DyP) from Thermomonospora curvata Reveals Unique Catalytic Properties of A-type DyPs.

    PubMed

    Chen, Chao; Shrestha, Ruben; Jia, Kaimin; Gao, Philip F; Geisbrecht, Brian V; Bossmann, Stefan H; Shi, Jishu; Li, Ping

    2015-09-18

    Dye-decolorizing peroxidases (DyPs) comprise a new family of heme peroxidases, which has received much attention due to their potential applications in lignin degradation. A new DyP from Thermomonospora curvata (TcDyP) was identified and characterized. Unlike other A-type enzymes, TcDyP is highly active toward a wide range of substrates including model lignin compounds, in which the catalytic efficiency with ABTS (kcat(app)/Km(app) = (1.7 × 10(7)) m(-1) s(-1)) is close to that of fungal DyPs. Stopped-flow spectroscopy was employed to elucidate the transient intermediates as well as the catalytic cycle involving wild-type (wt) and mutant TcDyPs. Although residues Asp(220) and Arg(327) are found necessary for compound I formation, His(312) is proposed to play roles in compound II reduction. Transient kinetics of hydroquinone (HQ) oxidation by wt-TcDyP showed that conversion of the compound II to resting state is a rate-limiting step, which will explain the contradictory observation made with the aspartate mutants of A-type DyPs. Moreover, replacement of His(312) and Arg(327) has significant effects on the oligomerization and redox potential (E°') of the enzyme. Both mutants were found to promote the formation of dimeric state and to shift E°' to a more negative potential. Not only do these results reveal the unique catalytic property of the A-type DyPs, but they will also facilitate the development of these enzymes as lignin degraders.

  11. The First Venomous Crustacean Revealed by Transcriptomics and Functional Morphology: Remipede Venom Glands Express a Unique Toxin Cocktail Dominated by Enzymes and a Neurotoxin

    PubMed Central

    von Reumont, Björn M.; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A.

    2014-01-01

    Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species. PMID:24132120

  12. A Systems Biological Approach Reveals Multiple Crosstalk Mechanism between Gram-Positive and Negative Bacterial Infections: An Insight into Core Mechanism and Unique Molecular Signatures

    PubMed Central

    Thangam, Berla; Ahmed, Shiek S. S. J.

    2014-01-01

    Background Bacterial infections remain a major threat and a leading cause of death worldwide. Most of the bacterial infections are caused by gram-positive and negative bacteria, which are recognized by Toll-like receptor (TLR) 2 and 4, respectively. Activation of these TLRs initiates multiple pathways that subsequently lead to effective immune response. Although, both the TLRs share common signaling mechanism yet they may exhibit specificity as well, resulting in the release of diverse range of inflammatory mediators which could be used as candidate biomolecules for bacterial infections. Results We adopted systems biological approach to identify signaling pathways mediated by TLRs to determine candidate molecules associated with bacterial infections. We used bioinformatics concepts, including literature mining to construct protein-protein interaction network, prioritization of TLRs specific nodes using microarray data and pathway analysis. Our constructed PPI network for TLR 2 (nodes: 4091 and edges: 66068) and TLR 4 (node: 4076 and edges: 67898) showed 3207 common nodes, indicating that both the TLRs might share similar signaling events that are attributed to cell migration, MAPK pathway and several inflammatory cascades. Our results propose the potential collaboration between the shared signaling pathways of both the receptors may enhance the immune response against invading pathogens. Further, to identify candidate molecules, the TLRs specific nodes were prioritized using microarray differential expressed genes. Of the top prioritized TLR 2 molecules, 70% were co-expressed. A similar trend was also observed within TLR 4 nodes. Further, most of these molecules were preferentially found in blood plasma for feasible diagnosis. Conclusions The analysis reveals the common and unique mechanism regulated by both the TLRs that provide a broad perspective of signaling events in bacterial infections. Further, the identified candidate biomolecules could potentially aid

  13. Genetic analysis of the Replication Protein A large subunit family in Arabidopsis reveals unique and overlapping roles in DNA repair, meiosis and DNA replication

    PubMed Central

    Aklilu, Behailu B.; Soderquist, Ryan S.; Culligan, Kevin M.

    2014-01-01

    Replication Protein A (RPA) is a heterotrimeric protein complex that binds single-stranded DNA. In plants, multiple genes encode the three RPA subunits (RPA1, RPA2 and RPA3), including five RPA1-like genes in Arabidopsis. Phylogenetic analysis suggests two distinct groups composed of RPA1A, RPA1C, RPA1E (ACE group) and RPA1B, RPA1D (BD group). ACE-group members are transcriptionally induced by ionizing radiation, while BD-group members show higher basal transcription and are not induced by ionizing radiation. Analysis of rpa1 T-DNA insertion mutants demonstrates that although each mutant line is likely null, all mutant lines are viable and display normal vegetative growth. The rpa1c and rpa1e single mutants however display hypersensitivity to ionizing radiation, and combination of rpa1c and rpa1e results in additive hypersensitivity to a variety of DNA damaging agents. Combination of the partially sterile rpa1a with rpa1c results in complete sterility, incomplete synapsis and meiotic chromosome fragmentation, suggesting an early role for RPA1C in promoting homologous recombination. Combination of either rpa1c and/or rpa1e with atr revealed additive hypersensitivity phenotypes consistent with each functioning in unique repair pathways. In contrast, rpa1b rpa1d double mutant plants display slow growth and developmental defects under non-damaging conditions. We show these defects in the rpa1b rpa1d mutant are likely the result of defective DNA replication leading to reduction in cell division. PMID:24335281

  14. Characterization of Dye-decolorizing Peroxidase (DyP) from Thermomonospora curvata Reveals Unique Catalytic Properties of A-type DyPs*

    PubMed Central

    Chen, Chao; Shrestha, Ruben; Jia, Kaimin; Gao, Philip F.; Geisbrecht, Brian V.; Bossmann, Stefan H.; Shi, Jishu; Li, Ping

    2015-01-01

    Dye-decolorizing peroxidases (DyPs) comprise a new family of heme peroxidases, which has received much attention due to their potential applications in lignin degradation. A new DyP from Thermomonospora curvata (TcDyP) was identified and characterized. Unlike other A-type enzymes, TcDyP is highly active toward a wide range of substrates including model lignin compounds, in which the catalytic efficiency with ABTS (kcatapp/Kmapp = (1.7 × 107) m−1 s−1) is close to that of fungal DyPs. Stopped-flow spectroscopy was employed to elucidate the transient intermediates as well as the catalytic cycle involving wild-type (wt) and mutant TcDyPs. Although residues Asp220 and Arg327 are found necessary for compound I formation, His312 is proposed to play roles in compound II reduction. Transient kinetics of hydroquinone (HQ) oxidation by wt-TcDyP showed that conversion of the compound II to resting state is a rate-limiting step, which will explain the contradictory observation made with the aspartate mutants of A-type DyPs. Moreover, replacement of His312 and Arg327 has significant effects on the oligomerization and redox potential (E°′) of the enzyme. Both mutants were found to promote the formation of dimeric state and to shift E°′ to a more negative potential. Not only do these results reveal the unique catalytic property of the A-type DyPs, but they will also facilitate the development of these enzymes as lignin degraders. PMID:26205819

  15. Mechanism of Bacterial Cell-Surface Attachment Revealed by the Structure of Cellulosomal Type II Cohesin-dockerin Complex

    SciTech Connect

    Adams,J.; Pal, G.; Jia, Z.; Smith, S.

    2006-01-01

    Bacterial cell-surface attachment of macromolecular complexes maintains the microorganism in close proximity to extracellular substrates and allows for optimal uptake of hydrolytic byproducts. The cellulosome is a large multienzyme complex used by many anaerobic bacteria for the efficient degradation of plant cell-wall polysaccharides. The mechanism of cellulosome retention to the bacterial cell surface involves a calcium-mediated protein-protein interaction between the dockerin (Doc) module from the cellulosomal scaffold and a cohesin (Coh) module of cell-surface proteins located within the proteoglycan layer. Here, we report the structure of an ultra-high-affinity (K{sub a} = 1.44 x 10{sup 10} M{sup 1-}) complex between type II Doc, together with its neighboring X module from the cellulosome scaffold of Clostridium thermocellum, and a type II Coh module associated with the bacterial cell surface. Identification of X module-Doc and X module-Coh contacts reveal roles for the X module in Doc stability and enhanced Coh recognition. This extremely tight interaction involves one face of the Coh and both helices of the Doc and comprises significant hydrophobic character and a complementary extensive hydrogen-bond network. This structure represents a unique mechanism for cell-surface attachment in anaerobic bacteria and provides a rationale for discriminating between type I and type II Coh modules.

  16. Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals

    PubMed Central

    Wiszniewsky, Anna; Ritter, Manuel; Goreish, Ibtisam A.; Atti El Mekki, Misk El Yemen A.; Arriens, Sandra; Pfarr, Kenneth; Fimmers, Rolf; Doenhoff, Mike; Hoerauf, Achim; Layland, Laura E.

    2016-01-01

    Background In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways

  17. Structure of the N-terminal oligomerization domain of DnaD reveals a unique tetramerization motif and provides insights into scaffold formation.

    PubMed

    Schneider, S; Zhang, W; Soultanas, P; Paoli, M

    2008-03-01

    DnaD is a primosomal protein that remodels supercoiled plasmids. It binds to supercoiled forms and converts them to open forms without nicking. During this remodeling process, all the writhe is converted to twist and the plasmids are held around the periphery of large scaffolds made up of DnaD molecules. This DNA-remodeling function is the sum of a scaffold-forming activity on the N-terminal domain and a DNA-dependent oligomerization activity on the C-terminal domain. We have determined the crystal structure of the scaffold-forming N-terminal domain, which reveals a winged-helix architecture, with additional structural elements extending from both N- and C-termini. Four monomers form dimers that join into a tetramer. The N-terminal extension mediates dimerization and tetramerization, with extensive interactions and distinct interfaces. The wings and helices of the winged-helix domains remain exposed on the surface of the tetramer. Structure-guided mutagenesis and atomic force microscopy imaging indicate that these elements, together with the C-terminal extension, are involved in scaffold formation. Based upon our data, we propose a model for the DnaD-mediated scaffold formation. PMID:18206906

  18. Population Structure and Comparative Genome Hybridization of European Flor Yeast Reveal a Unique Group of Saccharomyces cerevisiae Strains with Few Gene Duplications in Their Genome

    PubMed Central

    Legras, Jean-Luc; Erny, Claude; Charpentier, Claudine

    2014-01-01

    Wine biological aging is a wine making process used to produce specific beverages in several countries in Europe, including Spain, Italy, France, and Hungary. This process involves the formation of a velum at the surface of the wine. Here, we present the first large scale comparison of all European flor strains involved in this process. We inferred the population structure of these European flor strains from their microsatellite genotype diversity and analyzed their ploidy. We show that almost all of these flor strains belong to the same cluster and are diploid, except for a few Spanish strains. Comparison of the array hybridization profile of six flor strains originating from these four countries, with that of three wine strains did not reveal any large segmental amplification. Nonetheless, some genes, including YKL221W/MCH2 and YKL222C, were amplified in the genome of four out of six flor strains. Finally, we correlated ICR1 ncRNA and FLO11 polymorphisms with flor yeast population structure, and associate the presence of wild type ICR1 and a long Flo11p with thin velum formation in a cluster of Jura strains. These results provide new insight into the diversity of flor yeast and show that combinations of different adaptive changes can lead to an increase of hydrophobicity and affect velum formation. PMID:25272156

  19. Surface-based morphometry reveals distinct cortical thickness and surface area profiles in Williams syndrome.

    PubMed

    Green, Tamar; Fierro, Kyle C; Raman, Mira M; Saggar, Manish; Sheau, Kristen E; Reiss, Allan L

    2016-04-01

    Morphometric investigations of brain volumes in Williams syndrome (WS) consistently show significant reductions in gray matter volume compared to controls. Cortical thickness (CT) and surface area (SA) are two constituent parts of cortical gray matter volume that are considered genetically distinguishable features of brain morphology. Yet, little is known about the independent contribution of cortical CT and SA to these volumetric differences in WS. Thus, our objectives were: (i) to evaluate whether the microdeletion in chromosome 7 associated with WS has a distinct effect on CT and SA, and (ii) to evaluate age-related variations in CT and SA within WS. We compared CT and SA values in 44 individuals with WS to 49 age- and sex-matched typically developing controls. Between-group differences in CT and SA were evaluated across two age groups: young (age range 6.6-18.9 years), and adults (age range 20.2-51.5 years). Overall, we found contrasting effects of WS on cortical thickness (increases) and surface area (decreases). With respect to brain topography, the between-group pattern of CT differences showed a scattered pattern while the between-group surface area pattern was widely distributed throughout the brain. In the adult subgroup, we observed a cluster of increases in cortical thickness in WS across the brain that was not observed in the young subgroup. Our findings suggest that extensive early reductions in surface area are the driving force for the overall reduction in brain volume in WS. The age-related cortical thickness findings might reflect delayed or even arrested development of specific brain regions in WS.

  20. Revealing the Restructured Surface of Li[Mn2]O4

    DOE PAGESBeta

    Amos, Charles D.; Roldan, Manuel A.; Varela, Maria; Goodenough, John B.; Ferreira, Paulo J.

    2016-03-29

    The spinel Revealing the Restructured Surface of Li[Mn2]O4 is a candidate cathode for a Li-ion battery, but its capacity fades over a charge/discharge cycle of Li1–x[Mn2]O4 (0 < x < 1) that is associated with a loss of Mn to the organic-liquid electrolyte. It is known that the disproportionation reaction 2Mn3+ = Mn2+ + Mn4+ occurs at the surface of a Mn spinel, and it is important to understand the atomic structure and composition of the surface of Revealing the Restructured Surface of Li[Mn2]O4 in order to understand how Mn loss occurs. We report a study of the surface reconstructionmore » of Revealing the Restructured Surface of Li[Mn2]O4 by aberration-corrected scanning transmission electron microscopy. The atomic structure coupled with Mn-valence and the distribution of the atomic ratio of oxygen obtained by electron energy loss spectroscopy reveals a thin, stable surface layer of Mn3O4, a subsurface region of Li1+x[Mn2]O4 with retention of bulk Li[Mn2]O4. We conclude that this observation is compatible with the disproportionation reaction coupled with oxygen deficiency and a displacement of surface Li+ from the Mn3O4 surface phase. These results provide a critical step toward understanding how Mn is lost from Li[Mn2]O4, once inside a battery.« less

  1. Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved α-helix for Act1 binding and IL-17 signaling

    SciTech Connect

    Zhang, Bing; Liu, Caini; Qian, Wen; Han, Yue; Li, Xiaoxia; Deng, Junpeng

    2014-05-01

    Crystal structure of the SEFIR domain from human IL-17 receptor A provides new insights into IL-17 signaling. Interleukin 17 (IL-17) cytokines play a crucial role in mediating inflammatory and autoimmune diseases. A unique intracellular signaling domain termed SEFIR is found within all IL-17 receptors (IL-17Rs) as well as the key adaptor protein Act1. SEFIR-mediated protein–protein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 Å resolution crystal structure of the SEFIR domain of IL-17RA, the most commonly shared receptor for IL-17 cytokine signaling, is reported. The structure includes the complete SEFIR domain and an additional α-helical C-terminal extension, which pack tightly together to form a compact unit. Structural comparison between the SEFIR domains of IL-17RA and IL-17RB reveals substantial differences in protein topology and folding. The uniquely long insertion between strand βC and helix αC in IL-17RA SEFIR is mostly well ordered, displaying a helix (αCC′{sub ins}) and a flexible loop (CC′). The DD′ loop in the IL-17RA SEFIR structure is much shorter; it rotates nearly 90° with respect to the counterpart in the IL-17RB SEFIR structure and shifts about 12 Å to accommodate the αCC′{sub ins} helix without forming any knots. Helix αC was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIR–SEFIR association via helix αC is a conserved and signature mechanism specific for IL-17 signaling. The structure also suggests that the downstream motif of IL-17RA SEFIR together with helix αC could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.

  2. A deformable nanoplasmonic membrane reveals universal correlations between plasmon resonance and surface enhanced Raman scattering.

    PubMed

    Kang, Minhee; Kim, Jae-Jun; Oh, Young-Jae; Park, Sang-Gil; Jeong, Ki-Hun

    2014-07-01

    A quantitative correlation between plasmon resonance and surface enhanced Raman scattering (SERS) signals is revealed by using a novel active plasmonic method, that is, a deformable nanoplasmonic membrane. A single SERS peak has the maximum gain at the corresponding plasmon resonance wavelength, which has the maximum extinction product of an excitation and the corresponding Raman scattering wavelengths.

  3. Bacterial populations on brewery filling hall surfaces as revealed by next-generation sequencing.

    PubMed

    Priha, Outi; Raulio, Mari; Maukonen, Johanna; Vehviläinen, Anna-Kaisa; Storgårds, Erna

    2016-01-01

    Due to the presence of moisture and nutrients, brewery filling line surfaces are susceptible to unwanted microbial attachment. Knowledge of the attaching microbes will aid in designing hygienic control of the process. In this study the bacterial diversity present on brewery filling line surfaces was revealed by next generation sequencing. The two filling lines studied maintained their characteristic bacterial community throughout three sampling times (13-163 days). On the glass bottle line, γ-proteobacteria dominated (35-82% of all OTUs), whereas on the canning line α-, β- and γ-proteobacteria and actinobacteria were most common. The most frequently detected genera were Acinetobacter, Propinobacterium and Pseudomonas. The halophilic genus Halomonas was commonly detected, which might be due to its tolerance to alkaline foam cleaners. This study has revealed a detailed overall picture of the bacterial groups present on filling line surfaces. Further effort should be given to determine the efficacy of washing procedures on different bacterial groups. PMID:27064426

  4. A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis.

    PubMed

    Sugii, Yuh; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Kumon, Kazuki; Mizutani, Akifumi; Seno, Akimasa; Tokutaka, Heizo; Kudoh, Takayuki; Seno, Masaharu

    2016-01-01

    To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer.

  5. A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis

    PubMed Central

    Sugii, Yuh; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Kumon, Kazuki; Mizutani, Akifumi; Seno, Akimasa; Tokutaka, Heizo; Kudoh, Takayuki; Seno, Masaharu

    2016-01-01

    To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer. PMID:26966393

  6. The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant.

    PubMed

    Bos, Ineke G A; Lubbers, Yvonne T P; Roem, Dorina; Abrahams, Jan Pieter; Hack, C Erik; Eldering, Eric

    2003-08-01

    C1-inhibitor (C1-Inh) is a serine protease inhibitor (serpin) with a unique, non-conserved N-terminal domain of unknown function. Genetic deficiency of C1-Inh causes hereditary angioedema. A novel type of mutation (Delta 3) in exon 3 of the C1-Inh gene, resulting in deletion of Asp62-Thr116 in this unique domain, was encountered in a hereditary angioedema pedigree. Because the domain is supposedly not essential for inhibitory activity, the unexpected loss-of-function of this deletion mutant was further investigated. The Delta 3 mutant and three additional mutants starting at Pro76, Gly98, and Ser115, lacking increasing parts of the N-terminal domain, were produced recombinantly. C1-Inh76 and C1-Inh98 retained normal conformation and interaction kinetics with target proteases. In contrast, C1-Inh115 and Delta 3, which both lack the connection between the serpin and the non-serpin domain via two disulfide bridges, were completely non-functional because of a complex-like and multimeric conformation, as demonstrated by several criteria. The Delta 3 mutant also circulated in multimeric form in plasma from affected family members. The C1-Inh mutant reported here is unique in that deletion of an entire amino acid stretch from a domain not shared by other serpins leads to a loss-of-function. The deletion in the unique N-terminal domain results in a "multimerization phenotype" of C1-Inh, because of diminished stability of the central beta-sheet. This phenotype, as well as the location of the disulfide bridges between the serpin and the non-serpin domain of C1-Inh, suggests that the function of the N-terminal region may be similar to one of the effects of heparin in antithrombin III, maintenance of the metastable serpin conformation.

  7. Properties of X-ray resonant scattering in the Bragg case revealed on the Riemann surface.

    PubMed

    Saka, Takashi

    2016-07-01

    Continuing the work described in the previous paper [Saka (2016). Acta Cryst. A72, 338-348], the dynamical theory for perfect crystals in the Bragg case is reformulated using the Riemann surface. In particular, diffraction under resonant scattering conditions is investigated. The characteristic features of the dispersion surface and the rocking curve are analytically revealed using four parameters, which are the real and imaginary parts of two quantities specifying the degree of departure from the exact Bragg conditions and the reflection strength. Characteristic properties that have been deduced through numerical analysis are derived analytically using these four parameters. Visualization of the geometric relationships between the four parameters on the Riemann surface is useful for understanding many properties such as symmetry and sharpness of the rocking curve under special conditions. Therefore, employing the Riemann surface is instructive for numerical analysis and useful for understanding dynamical diffraction in the Bragg case. PMID:27357849

  8. Monoclonal antibody to a unique surface epitope of the human filaria Brugia malayi identifies infective larvae in mosquito vectors.

    PubMed Central

    Carlow, C K; Franke, E D; Lowrie, R C; Partono, F; Philipp, M

    1987-01-01

    We describe properties of an IgM monoclonal antibody (NEB-D1E5) raised against the human filarial parasite Brugia malayi. The antibody reacts with a stage- and species-specific determinant located on the surface of the infective-stage larva, as determined by indirect immunofluorescence. To use this reagent in epidemiological field studies, we developed an enzyme-linked immunoassay with which B. malayi larvae can be differentiated from other filarial parasites in mosquito vectors, including the morphologically indistinguishable parasite of animals Brugia pahangi. The immunoenzyme assay was 91-94% specific and 90-97% sensitive when performed on infected mosquitoes. In the absence of mosquito tissue, the levels of specificity and sensitivity increased to 100% and 97.5-100%, respectively. Binding of antibody to the surface of living larvae was abrogated by treatment of the worms with the enzymes pronase and proteinase K and with the detergents Triton X-100, octyl beta-D-glucopyranoside, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulphonate (CHAPS). In contrast, treatment with trypsin, endoglycosidase-F, O-Glycanase, N-Glycanase, lipase, various phospholipases, boiling, 2-mercaptoethanol at 37 degrees C, or periodate did not reduce the antigenicity of the larval surface to antibody NEB-D1E5. These results suggest that the species-specific epitope is a peptide domain attached to a hydrophobic anchoring residue. Images PMID:2443912

  9. Revealing Surface Waters on an Antifreeze Protein by Fusion Protein Crystallography Combined with Molecular Dynamic Simulations.

    PubMed

    Sun, Tianjun; Gauthier, Sherry Y; Campbell, Robert L; Davies, Peter L

    2015-10-01

    Antifreeze proteins (AFPs) adsorb to ice through an extensive, flat, relatively hydrophobic surface. It has been suggested that this ice-binding site (IBS) organizes surface waters into an ice-like clathrate arrangement that matches and fuses to the quasi-liquid layer on the ice surface. On cooling, these waters join the ice lattice and freeze the AFP to its ligand. Evidence for the generality of this binding mechanism is limited because AFPs tend to crystallize with their IBS as a preferred protein-protein contact surface, which displaces some bound waters. Type III AFP is a 7 kDa globular protein with an IBS made up two adjacent surfaces. In the crystal structure of the most active isoform (QAE1), the part of the IBS that docks to the primary prism plane of ice is partially exposed to solvent and has clathrate waters present that match this plane of ice. The adjacent IBS, which matches the pyramidal plane of ice, is involved in protein-protein crystal contacts with few surface waters. Here we have changed the protein-protein contacts in the ice-binding region by crystallizing a fusion of QAE1 to maltose-binding protein. In this 1.9 Å structure, the IBS that fits the pyramidal plane of ice is exposed to solvent. By combining crystallography data with MD simulations, the surface waters on both sides of the IBS were revealed and match well with the target ice planes. The waters on the pyramidal plane IBS were loosely constrained, which might explain why other isoforms of type III AFP that lack the prism plane IBS are less active than QAE1. The AFP fusion crystallization method can potentially be used to force the exposure to solvent of the IBS on other AFPs to reveal the locations of key surface waters.

  10. Revealing Surface States in In-Doped SnTe Nanoplates with Low Bulk Mobility.

    PubMed

    Shen, Jie; Xie, Yujun; Cha, Judy J

    2015-06-10

    Indium (In) doping in topological crystalline insulator SnTe induces superconductivity, making In-doped SnTe a candidate for a topological superconductor. SnTe nanostructures offer well-defined nanoscale morphology and high surface-to-volume ratios to enhance surface effects. Here, we study In-doped SnTe nanoplates, In(x)Sn(1-x)Te, with x ranging from 0 to 0.1 and show they superconduct. More importantly, we show that In doping reduces the bulk mobility of In(x)Sn(1-x)Te such that the surface states are revealed in magnetotransport despite the high bulk carrier density. This is manifested by two-dimensional linear magnetoresistance in high magnetic fields, which is independent of temperature up to 10 K. Aging experiments show that the linear magnetoresistance is sensitive to ambient conditions, further confirming its surface origin. We also show that the weak antilocalization observed in In(x)Sn(1-x)Te nanoplates is a bulk effect. Thus, we show that nanostructures and reducing the bulk mobility are effective strategies to reveal the surface states and test for topological superconductors.

  11. Cryovolcanic Features on Titan's Surface as Revealed by the Cassini RADAR

    NASA Technical Reports Server (NTRS)

    Lopes, R. M.; Elachi, C.; Stofan, E.; Paganelli, F.; Wood, C.; Kirk, R.; Lorenz, R.; Fortes, A. D.; Lunine, J.

    2005-01-01

    The Cassini Titan Radar Mapper obtained Synthetic Aperture radar images of about 1.1% of Titan's surface during the spacecraft s first targeted fly-by on October 26, 2004 (referred to as the Ta fly-by). These images revealed that Titan is very complex geologically. Features identified include a possible volcanic dome or shield, craters that appear to be of volcanic origin, and extensive flows. We will discuss these features and others that will likely be revealed during Cassini s T3 Titan fly-by of February 15, 2005, during which a swath covering comparable amount of the surface will be obtained. Additional information is included in the original extended abstract.

  12. Interspecific comparison of constitutive ash phloem phenolic chemistry reveals compounds unique to manchurian ash, a species resistant to emerald ash borer.

    PubMed

    Whitehill, Justin G A; Opiyo, Stephen O; Koch, Jennifer L; Herms, Daniel A; Cipollini, Donald F; Bonello, Pierluigi

    2012-05-01

    The emerald ash borer (Agrilus planipennis, EAB) is an invasive wood-borer indigenous to Asia and is responsible for widespread ash (Fraxinus spp.) mortality in the U.S. and Canada. Resistance and susceptibility to EAB varies among Fraxinus spp., which is a result of their co-evolutionary history with the pest. We characterized constitutive phenolic profiles and lignin levels in the phloem of green, white, black, blue, European, and Manchurian ash. Phloem was sampled twice during the growing season, coinciding with phenology of early and late instar EAB. We identified 66 metabolites that displayed a pattern of variation, which corresponded strongly with phylogeny. Previously identified lignans and lignan derivatives were confirmed to be unique to Manchurian ash, and may contribute to its high level of resistance to EAB. Other compounds that had been considered unique to Manchurian ash, including hydroxycoumarins and the phenylethanoids calceolarioside A and B, were detected in closely related, but susceptible species, and thus are unlikely to contribute to EAB resistance of Manchurian ash. The distinct phenolic profile of blue ash may contribute to its relatively high resistance to EAB.

  13. Alluvial Fans on Titan Reveal Atmosphere and Surface Interactions and Material Transport

    NASA Astrophysics Data System (ADS)

    Radebaugh, J.; Ventra, D.; Lorenz, R. D.; Farr, T. G.; Kirk, R. L.; Hayes, A.; Malaska, M. J.; Birch, S.; Liu, Z. Y. C.; Lunine, J. I.; Barnes, J. W.; Le Gall, A. A.; Lopes, R. M. C.; Stofan, E. R.; Wall, S. D.; Paillou, P.

    2015-12-01

    Alluvial fans, important depositional systems that record how sediment is stored and moved on planetary surfaces, are found on the surface of Titan, a body of significantly different materials and process rates than Earth. As seen by Cassini's Synthetic Aperture Radar (SAR) images at 350 m resolution, fans on Titan are found globally and are variable in size, shape and relationship to adjacent landforms. Their morphologies and SAR characteristics, which reveal roughness, textural patterns and other material properties, show similarities with fans in Death Valley seen by SAR and indicate there are regions of high relative relief locally, in the Ganesa, Xanadu and equatorial mountain belt regions. The Leilah Fluctus fans near Ganesa are ~30 km x 15 km, similar to the largest Death Valley fans, and revealing mountainous topography adjacent to plains. Others have gentle slopes over hundreds of kilometers, as in the high southern latitude lakes regions or the Mezzoramia southern midlatitudes, where a fan system is 200 km x 150 km, similar to the Qarn Alam fan emerging into the Rub al Khali in Oman. Additionally, there is evidence for a range of particle sizes, from relatively coarse (~2 cm or more) to fine, revealing long-term duration and variability in erosion by methane rainfall and transport. Some features have morphologies consistent with proximality to high-relief source areas and highly ephemeral runoff, while others appear to draw larger catchment areas and are perhaps characterized by more prolonged episodes of flow. The presence of many fans indicates the longevity of rainfall and erosion in Titan's surface processes and reveals that sediment transport and the precipitation that drives it are strongly episodic. Alluvial fans join rivers, lakes, eroded mountains, sand dunes and dissolution features in the list of surface morphologies derived from atmospheric and fluvial processes similar to those on Earth, strengthening comparisons between the two planetary

  14. Crystal structure analysis reveals Pseudomonas PilY1 as an essential calcium-dependent regulator of bacterial surface motility

    SciTech Connect

    Orans, Jillian; Johnson, Michael D.L.; Coggan, Kimberly A.; Sperlazza, Justin R.; Heiniger, Ryan W.; Wolfgang, Matthew C.; Redinbo, Matthew R.

    2010-09-21

    Several bacterial pathogens require the 'twitching' motility produced by filamentous type IV pili (T4P) to establish and maintain human infections. Two cytoplasmic ATPases function as an oscillatory motor that powers twitching motility via cycles of pilus extension and retraction. The regulation of this motor, however, has remained a mystery. We present the 2.1 {angstrom} resolution crystal structure of the Pseudomonas aeruginosa pilus-biogenesis factor PilY1, and identify a single site on this protein required for bacterial translocation. The structure reveals a modified {beta}-propeller fold and a distinct EF-hand-like calcium-binding site conserved in pathogens with retractile T4P. We show that preventing calcium binding by PilY1 using either an exogenous calcium chelator or mutation of a single residue disrupts Pseudomonas twitching motility by eliminating surface pili. In contrast, placing a lysine in this site to mimic the charge of a bound calcium interferes with motility in the opposite manner - by producing an abundance of nonfunctional surface pili. Our data indicate that calcium binding and release by the unique loop identified in the PilY1 crystal structure controls the opposing forces of pilus extension and retraction. Thus, PilY1 is an essential, calcium-dependent regulator of bacterial twitching motility.

  15. Revealing the Reconstructed Surface of Li[Mn2]O4.

    PubMed

    Amos, Charles D; Roldan, Manuel A; Varela, Maria; Goodenough, John B; Ferreira, Paulo J

    2016-05-11

    The spinel Li[Mn2]O4 is a candidate cathode for a Li-ion battery, but its capacity fades over a charge/discharge cycle of Li1-x[Mn2]O4 (0 < x < 1) that is associated with a loss of Mn to the organic-liquid electrolyte. It is known that the disproportionation reaction 2Mn(3+) = Mn(2+) + Mn(4+) occurs at the surface of a Mn spinel, and it is important to understand the atomic structure and composition of the surface of Li[Mn2]O4 in order to understand how Mn loss occurs. We report a study of the surface reconstruction of Li[Mn2]O4 by aberration-corrected scanning transmission electron microscopy. The atomic structure coupled with Mn-valence and the distribution of the atomic ratio of oxygen obtained by electron energy loss spectroscopy reveals a thin, stable surface layer of Mn3O4, a subsurface region of Li1+x[Mn2]O4 with retention of bulk Li[Mn2]O4. This observation is compatible with the disproportionation reaction coupled with oxygen deficiency and a displacement of surface Li(+) from the Mn3O4 surface phase. These results provide a critical step toward understanding how Mn is lost from Li[Mn2]O4, once inside a battery. PMID:27022834

  16. Soil surface temperatures reveal moderation of the urban heat island effect by trees and shrubs.

    PubMed

    Edmondson, J L; Stott, I; Davies, Z G; Gaston, K J; Leake, J R

    2016-01-01

    Urban areas are major contributors to air pollution and climate change, causing impacts on human health that are amplified by the microclimatological effects of buildings and grey infrastructure through the urban heat island (UHI) effect. Urban greenspaces may be important in reducing surface temperature extremes, but their effects have not been investigated at a city-wide scale. Across a mid-sized UK city we buried temperature loggers at the surface of greenspace soils at 100 sites, stratified by proximity to city centre, vegetation cover and land-use. Mean daily soil surface temperature over 11 months increased by 0.6 °C over the 5 km from the city outskirts to the centre. Trees and shrubs in non-domestic greenspace reduced mean maximum daily soil surface temperatures in the summer by 5.7 °C compared to herbaceous vegetation, but tended to maintain slightly higher temperatures in winter. Trees in domestic gardens, which tend to be smaller, were less effective at reducing summer soil surface temperatures. Our findings reveal that the UHI effects soil temperatures at a city-wide scale, and that in their moderating urban soil surface temperature extremes, trees and shrubs may help to reduce the adverse impacts of urbanization on microclimate, soil processes and human health. PMID:27641002

  17. Bacterial community analysis of beef cattle feedlots reveals that pen surface is distinct from feces.

    PubMed

    Durso, Lisa M; Harhay, Gregory P; Smith, Timothy P L; Bono, James L; DeSantis, Todd Z; Clawson, Michael L

    2011-05-01

    The surface of beef cattle feedlot pens is commonly conceptualized as being packed uncomposted manure. Despite the important role that the feedlot pen may play in the transmission of veterinary and zoonotic pathogens, the bacterial ecology of feedlot surface material is not well understood. Our present study characterized the bacterial communities of the beef cattle feedlot pen surface material using 3647 full-length 16S rDNA sequences, and we compared the community composition of feedlot pens to the fecal source material. The feedlot surface composite was represented by members of the phylum Actinobacteria (42%), followed by Firmicutes (24%), Bacteroidetes (24%), and Proteobacteria (9%). The feedlot pen surface material bacterial communities were clearly distinct from those of the feces from animals in the same pen. Comparisons with previously published results of feces from the animals in the same pen reveal that, of 139 genera identified, only 25 were present in both habitats. These results indicate that, microbiologically, the feedlot pen surface material is separate and distinct from the fecal source material, suggesting that bacteria that originate in cattle feces face different selection pressures and survival challenges during their tenure in the feedlot pen, as compared to their residence in the gastrointestinal tract.

  18. Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed

    PubMed Central

    Lane, Amy L.; Nyadong, Leonard; Galhena, Asiri S.; Shearer, Tonya L.; Stout, E. Paige; Parry, R. Mitchell; Kwasnik, Mark; Wang, May D.; Hay, Mark E.; Fernandez, Facundo M.; Kubanek, Julia

    2009-01-01

    Organism surfaces represent signaling sites for attraction of allies and defense against enemies. However, our understanding of these signals has been impeded by methodological limitations that have precluded direct fine-scale evaluation of compounds on native surfaces. Here, we asked whether natural products from the red macroalga Callophycus serratus act in surface-mediated defense against pathogenic microbes. Bromophycolides and callophycoic acids from algal extracts inhibited growth of Lindra thalassiae, a marine fungal pathogen, and represent the largest group of algal antifungal chemical defenses reported to date. Desorption electrospray ionization mass spectrometry (DESI-MS) imaging revealed that surface-associated bromophycolides were found exclusively in association with distinct surface patches at concentrations sufficient for fungal inhibition; DESI-MS also indicated the presence of bromophycolides within internal algal tissue. This is among the first examples of natural product imaging on biological surfaces, suggesting the importance of secondary metabolites in localized ecological interactions, and illustrating the potential of DESI-MS in understanding chemically-mediated biological processes. PMID:19366672

  19. Soil surface temperatures reveal moderation of the urban heat island effect by trees and shrubs

    PubMed Central

    Edmondson, J. L.; Stott, I.; Davies, Z. G.; Gaston, K. J.; Leake, J. R.

    2016-01-01

    Urban areas are major contributors to air pollution and climate change, causing impacts on human health that are amplified by the microclimatological effects of buildings and grey infrastructure through the urban heat island (UHI) effect. Urban greenspaces may be important in reducing surface temperature extremes, but their effects have not been investigated at a city-wide scale. Across a mid-sized UK city we buried temperature loggers at the surface of greenspace soils at 100 sites, stratified by proximity to city centre, vegetation cover and land-use. Mean daily soil surface temperature over 11 months increased by 0.6 °C over the 5 km from the city outskirts to the centre. Trees and shrubs in non-domestic greenspace reduced mean maximum daily soil surface temperatures in the summer by 5.7 °C compared to herbaceous vegetation, but tended to maintain slightly higher temperatures in winter. Trees in domestic gardens, which tend to be smaller, were less effective at reducing summer soil surface temperatures. Our findings reveal that the UHI effects soil temperatures at a city-wide scale, and that in their moderating urban soil surface temperature extremes, trees and shrubs may help to reduce the adverse impacts of urbanization on microclimate, soil processes and human health. PMID:27641002

  20. Transcriptome analysis reveals unique C4-like photosynthesis and oil body formation in an arachidonic acid-rich microalga Myrmecia incisa Reisigl H4301

    PubMed Central

    2013-01-01

    Background Arachidonic acid (ArA) is important for human health because it is one of the major components of mammalian brain membrane phospholipids. The interest in ArA inspired the search for a new sustainable source, and the green microalga Myrmecia incisa Reisigl H4301 has been found a potential ArA-producer due to a high content of intracellular ArA. To gain more molecular information about metabolism pathways, including the biosynthesis of ArA in the non-model microalga, a transcriptomic analysis was performed. Results The 454 pyrosequencing generated 371,740 high-quality reads, which were assembled into 51,908 unique sequences consisting of 22,749 contigs and 29,159 singletons. A total of 11,873 unique sequences were annotated through BLAST analysis, and 3,733 were assigned to Gene Ontology (GO) categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis uncovered a C4-like photosynthesis pathway in M. incisa. The biosynthesis pathways of lipid particularly those of ArA and triacylglycerol (TAG) were analyzed in detail, and TAG was proposed to be accumulated in oil bodies in the cytosol with the help of caleosin or oil globule-associated proteins. In addition, the carotenoid biosynthesis pathways are discussed. Conclusion This transcriptomic analysis of M. incisa enabled a global understanding of mechanisms involved in photosynthesis, de novo biosynthesis of ArA, metabolism of carotenoids, and accumulation of TAG in M. incisa. These findings provided a molecular basis for the research and possibly economic exploitation of this ArA-rich microalga. PMID:23759028

  1. Extracellular-signal regulated kinase 8 of Trypanosoma brucei uniquely phosphorylates its proliferating cell nuclear antigen homolog and reveals exploitable properties.

    PubMed

    Valenciano, Ana L; Knudsen, Giselle M; Mackey, Zachary B

    2016-10-17

    The Trypanosoma brucei subspecies T. brucei gambiense and T. brucei rhodesiense are vector-borne pathogens that cause sleeping sickness also known as Human African Trypanosomiasis (HAT), which is fatal if left untreated. The drugs that treat HAT are ineffective and cause toxic side effects. One strategy for identifying safer and more effective HAT drugs is to therapeutically exploit essential gene targets in T. brucei. Genes that make up a basic mitogen-activated protein kinase (MAPK) network are present in T. brucei. Tb927.10.5140 encodes an essential MAPK that is homologous to the human extracellular-signal regulated kinase 8 (HsERK8) which forms a tight complex with the replication factor proliferating cell nuclear antigen (PCNA) to stabilize intracellular PCNA levels. Here we demonstrate that (TbPCNA) is uniquely phos-phorylated on serine (S) and threonine (T) residues in T. brucei and that TbERK8 phosphorylates TbPCNA at each of these residues. The ability of an ERK8 homolog to phosphorylate a PCNA homolog is a novel biochemical property that is first demonstrated here in T. brucei and may be unique to this pathogen. We demonstrate that the potent HsERK8 inhibitor Ro318220, has an IC50 for TbERK8 that is several hundred times higher than its reported IC50 for HsERK8. This indicated that the active sites of TbERK8 and HsERK8 can be selectively inhibited, which provides a rational basis for discovering inhibitors that specifically target this essential parasite MAPK to kill the parasite.

  2. Extracellular-signal regulated kinase 8 of Trypanosoma brucei uniquely phosphorylates its proliferating cell nuclear antigen homolog and reveals exploitable properties

    PubMed Central

    Valenciano, Ana L.; Knudsen, Giselle M.; Mackey, Zachary B.

    2016-01-01

    ABSTRACT The Trypanosoma brucei subspecies T. brucei gambiense and T. brucei rhodesiense are vector-borne pathogens that cause sleeping sickness also known as Human African Trypanosomiasis (HAT), which is fatal if left untreated. The drugs that treat HAT are ineffective and cause toxic side effects. One strategy for identifying safer and more effective HAT drugs is to therapeutically exploit essential gene targets in T. brucei. Genes that make up a basic mitogen-activated protein kinase (MAPK) network are present in T. brucei. Tb927.10.5140 encodes an essential MAPK that is homologous to the human extracellular-signal regulated kinase 8 (HsERK8) which forms a tight complex with the replication factor proliferating cell nuclear antigen (PCNA) to stabilize intracellular PCNA levels. Here we demonstrate that (TbPCNA) is uniquely phos-phorylated on serine (S) and threonine (T) residues in T. brucei and that TbERK8 phosphorylates TbPCNA at each of these residues. The ability of an ERK8 homolog to phosphorylate a PCNA homolog is a novel biochemical property that is first demonstrated here in T. brucei and may be unique to this pathogen. We demonstrate that the potent HsERK8 inhibitor Ro318220, has an IC50 for TbERK8 that is several hundred times higher than its reported IC50 for HsERK8. This indicated that the active sites of TbERK8 and HsERK8 can be selectively inhibited, which provides a rational basis for discovering inhibitors that specifically target this essential parasite MAPK to kill the parasite. PMID:27589575

  3. In Situ X-Ray Probing Reveals Fingerprints of Surface Platinum Oxide

    SciTech Connect

    Friebel, Daniel

    2011-08-24

    In situ x-ray absorption spectroscopy (XAS) at the Pt L{sub 3} edge is a useful probe for Pt-O interactions at polymer electrolyte membrane fuel cell (PEMFC) cathodes. We show that XAS using the high energy resolution fluorescence detection (HERFD) mode, applied to a well-defined monolayer Pt/Rh(111) sample where the bulk penetrating hard x-rays probe only surface Pt atoms, provides a unique sensitivity to structure and chemical bonding at the Pt-electrolyte interface. Ab initio multiple-scattering calculations using the FEFF8 code and complementary extended x-ray absorption fine structure (EXAFS) results indicate that the commonly observed large increase of the white-line at high electrochemical potentials on PEMFC cathodes originates from platinum oxide formation, whereas previously proposed chemisorbed oxygen-containing species merely give rise to subtle spectral changes.

  4. Nanoporous PdZr surface alloy as highly active non-platinum electrocatalyst toward oxygen reduction reaction with unique structure stability and methanol-tolerance

    NASA Astrophysics Data System (ADS)

    Duan, Huimei; Xu, Caixia

    2016-06-01

    Nanoporous (NP) PdZr alloy with controllable bimetallic ratio is successfully fabricated by a simple dealloying method. By leaching out the more reactive Al from PdZrAl precursor alloy, NP-PdZr alloy with smaller ligament size was generated, characterized by the nanoscaled interconnected network skeleton and hollow channels extending in all three dimensions. Upon voltammetric scan in acid solution, the dissolution of surface Zr atoms generates the highly active Pd-Zr surface alloy with a nearly pure Pd surface and Pd-Zr alloy core. The NP-Pd80Zr20 surface alloy exhibits markedly enhanced specific and mass activities as well as higher catalytic stability toward oxygen reduction reaction (ORR) compared with NP-Pd and the state-of-the-art Pt/C catalysts. In addition, the NP-Pd80Zr20 surface alloy shows a better selectivity for ORR than methanol in the 0.1 M HClO4 and 0.1 M methanol mixed solution. X-ray photoelectron spectroscopy and density functional theory calculations both demonstrate that the weakened Pd-O bond and improved ORR performances in turn depend on the downshifted d-band center of Pd due to the alloying Pd with Zr (20 at.%). The as-made NP-PdZr alloy holds prospective applications as a cathode electrocatalyst in fuel-cell-related technologies with the advantages of superior overall ORR performances, unique structure stability, and easy preparation.

  5. Nucleotide sequence of shallot virus X RNA reveals a 5'-proximal cistron closely related to those of potexviruses and a unique arrangement of the 3'-proximal cistrons.

    PubMed

    Kanyuka, K V; Vishnichenko, V K; Levay, K E; Kondrikov DYu; Ryabov, E V; Zavriev, S K

    1992-10-01

    The 8890 nucleotide RNA sequence of shallot virus X (ShVX), a new virus isolated from shallot, has been determined. The sequence contains six open reading frames (ORFs) which encode putative proteins (in the 5' to 3' direction) of M(r) 194528 (ORF1), 26333 (ORF2), 11245 (ORF3), 42209 (ORF4), 28486 (ORF5) and 14741 (ORF6). The ORF1 protein was found to be highly homologous to the putative potexvirus RNA replicases; ORF2, -3, -5 and -6 proteins also have analogues among the potex- and/or carlavirus-encoded proteins. ORF3 is followed by an AUG-lacking frame coding for an amino acid sequence homologous to that of the 7K to 8K proteins of the triple gene block of the above-mentioned viruses. The putative ORF4 protein has no reliable homology with proteins in the database. The results obtained testify that, except for the unique 42K protein gene, the ShVX genome combines a number of elements typical of both carla- and potexviruses.

  6. Characterization of the mouse DAX-1 gene reveals evolutionary conservation of a unique amino-terminal motif and widespread expression in mouse tissue.

    PubMed

    Bae, D S; Schaefer, M L; Partan, B W; Muglia, L

    1996-09-01

    The human genetic disorder adrenal hypoplasia congenita with hypogonadotropic hypogonadism results from mutations in the recently isolated DAX-1 gene, a member of the nuclear hormone receptor superfamily. To study the role of DAX-1 in adrenal development and activation of the hypothalamic pituitary-gonadal axis, animal model systems will be essential. Here, we report the isolation and characterization of the mouse DAX-1 gene and its tissue-specific pattern of expression. The mouse DAX-1 gene codes for a 472-amino acid protein, with 75% overall nucleotide sequence homology to its human homolog. The 3.5 amino-terminal repeats of a unique motif with probable DNA-binding activity have been conserved between mouse and human, although highest conservation in the DAX-1 peptide exists in the carboxy-terminal ligand-binding domain. The DAX-1 gene remains X-linked in the mouse, consistent with its potential role in sex determination. We have developed a sensitive reverse transcription-PCR assay that detects DAX-1 messenger RNA in the central nervous system, pituitary, lung, heart, spleen, kidney, and thymus in addition to the adrenal and testis DAX-1 expression noted for the human DAX-1 gene. Future studies using mouse models of altered DAX-1 expression will be critical in defining the role of this factor in tissue- and development-specific gene regulation.

  7. Complete genome and gene expression analyses of Asaia bogorensis reveal unique responses to culture with mammalian cells as a potential opportunistic human pathogen

    PubMed Central

    Kawai, Mikihiko; Higashiura, Norie; Hayasaki, Kimie; Okamoto, Naruhei; Takami, Akiko; Hirakawa, Hideki; Matsushita, Kazunobu; Azuma, Yoshinao

    2015-01-01

    Asaia bogorensis, a member of acetic acid bacteria (AAB), is an aerobic bacterium isolated from flowers and fruits, as well as an opportunistic pathogen that causes human peritonitis and bacteraemia. Here, we determined the complete genomic sequence of the As. bogorensis type strain NBRC 16594, and conducted comparative analyses of gene expression under different conditions of co-culture with mammalian cells and standard AAB culture. The genome of As. bogorensis contained 2,758 protein-coding genes within a circular chromosome of 3,198,265 bp. There were two complete operons encoding cytochrome bo3-type ubiquinol terminal oxidases: cyoABCD-1 and cyoABCD-2. The cyoABCD-1 operon was phylogenetically common to AAB genomes, whereas the cyoABCD-2 operon belonged to a lineage distinctive from the cyoABCD-1 operon. Interestingly, cyoABCD-1 was less expressed under co-culture conditions than under the AAB culture conditions, whereas the converse was true for cyoABCD-2. Asaia bogorensis shared pathogenesis-related genes with another pathogenic AAB, Granulibacter bethesdensis, including a gene coding pathogen-specific large bacterial adhesin and additional genes for the inhibition of oxidation and antibiotic resistance. Expression alteration of the respiratory chain and unique hypothetical genes may be key traits that enable the bacterium to survive under the co-culture conditions. PMID:26358298

  8. A Novel MHC-I Surface Targeted for Binding by the MCMV m06 Immunoevasin Revealed by Solution NMR.

    PubMed

    Sgourakis, Nikolaos G; May, Nathan A; Boyd, Lisa F; Ying, Jinfa; Bax, Ad; Margulies, David H

    2015-11-27

    As part of its strategy to evade detection by the host immune system, murine cytomegalovirus (MCMV) encodes three proteins that modulate cell surface expression of major histocompatibility complex class I (MHC-I) molecules: the MHC-I homolog m152/gp40 as well as the m02-m16 family members m04/gp34 and m06/gp48. Previous studies of the m04 protein revealed a divergent Ig-like fold that is unique to immunoevasins of the m02-m16 family. Here, we engineer and characterize recombinant m06 and investigate its interactions with full-length and truncated forms of the MHC-I molecule H2-L(d) by several techniques. Furthermore, we employ solution NMR to map the interaction footprint of the m06 protein on MHC-I, taking advantage of a truncated H2-L(d), "mini-H2-L(d)," consisting of only the α1α2 platform domain. Mini-H2-L(d) refolded in vitro with a high affinity peptide yields a molecule that shows outstanding NMR spectral features, permitting complete backbone assignments. These NMR-based studies reveal that m06 binds tightly to a discrete site located under the peptide-binding platform that partially overlaps with the β2-microglobulin interface on the MHC-I heavy chain, consistent with in vitro binding experiments showing significantly reduced complex formation between m06 and β2-microglobulin-associated MHC-I. Moreover, we carry out NMR relaxation experiments to characterize the picosecond-nanosecond dynamics of the free mini-H2-L(d) MHC-I molecule, revealing that the site of interaction is highly ordered. This study provides insight into the mechanism of the interaction of m06 with MHC-I, suggesting a structural manipulation of the target MHC-I molecule at an early stage of the peptide-loading pathway. PMID:26463211

  9. Atmospheric Drivers of Greenland Surface Melt Revealed by Self Organizing Maps

    NASA Astrophysics Data System (ADS)

    Mioduszewski, J.; Rennermalm, A. K.; Hammann, A. C.; Tedesco, M.; Noble, E. U.; Stroeve, J. C.; Mote, T. L.

    2015-12-01

    Recent acceleration in summer surface melt on the Greenland ice sheet (GrIS) has occurred concurrently with a rapidly warming Arctic and has been connected to persistent, anomalous circulation patterns over Greenland. To identify patterns that favor enhanced GrIS surface melt and their decadal changes, we first develop a summer Arctic synoptic climatology by employing a nonlinear classification technique known as the self organizing map (SOM). This is applied to daily JJA sea level pressure (SLP) and 500 hPa geopotential height fields obtained from the Modern Era Retrospective Analysis for Research and Applications (MERRA) reanalysis product from 1979 to 2014. Model output from Modèle Atmosphérique Régional (MAR) is used to relate meteorological conditions and subsequent Greenland surface melt anomalies to particular circulation regimes. Results demonstrate that circulation patterns featuring positive SLP anomalies from Greenland to the Beaufort Sea support the largest positive surface melt anomalies, particularly over western Greenland. These patterns facilitate strong meridional transport of heat and moisture, contrasted by a dominant zonal flow across the North Atlantic during periods of low surface melt. Additionally, composites of energy balance components reveal that melt events are favored under clear conditions generating positive shortwave radiation anomalies rather than increased downwelling longwave radiation occurring with increased cloud cover. Sea surface temperature anomalies suggest that there may be a linkage between surface melt and recent sea ice loss around Greenland, though a causal relationship is not established. We assess decadal shifts in the SOM nodes, finding an increased frequency of upper level patterns favoring higher 500 hPa geopotential heights primarily over Greenland. The observed increases in GrIS melt through the time period coincides with this shift in SOM node frequency.

  10. The surface and interior evolution of Ceres revealed by fractures and secondary crater chains

    NASA Astrophysics Data System (ADS)

    Scully, Jennifer E. C.; Buczkowski, Debra; Schmedemann, Nico; King, Scott; O'Brien, David P.; Castillo-Rogez, Julie; Raymond, Carol; Marchi, Simone; Russell, Christopher T.; Mitri, Giuseppe; Bland, Michael T.

    2016-10-01

    Dawn became the first spacecraft to visit and orbit Ceres, a dwarf planet and the largest body in the asteroid belt (radius ~470 km) (Russell et al., 2016). Before Dawn's arrival, telescopic observations and thermal evolution modeling indicated Ceres was differentiated, with an average density of 2,100 kg/m3 (e.g. McCord & Sotin, 2005; Castillo-Rogez & McCord, 2010). Moreover, pervasive viscous relaxation in a water-ice-rich outer layer was predicted to erase most features on Ceres' surface (Bland, 2013). However, a full understanding of Ceres' surface and interior evolution remained elusive. On the basis of global geologic mapping, we identify prevalent ≥1 km wide linear features that formed: 1) as the surface expression of subsurface fractures, and 2) as material ejected during impact-crater formation impacted and scoured the surface, forming secondary crater chains. The formation and preservation of these linear features indicates Ceres' outer layer is relatively strong, and is not dominated by viscous relaxation as predicted. The fractures also give us insights into Ceres' interior: their spacing indicates the fractured layer is ~30 km thick, and we interpret the fractures formed because of uplift and extension induced by an upwelling region, which is consistent with geodynamic modeling (King et al., 2016). In addition, we find that some secondary crater chains do not form radial patterns around their source impact craters, and are located in a different hemisphere from their source impact craters, because of Ceres' fast rotation (period of ~9 hours) and relatively small radius. Our results show Ceres has a surface and outer layer with characteristics that are different than predicted, and underwent complex surface and interior evolution. Our fuller understanding of Ceres, based on Dawn data, gives us important insights into the evolution of bodies in the asteroid belt, and provides unique constraints that can be used to evaluate predictions of the surface

  11. The crystal structure of an HSL-homolog EstE5 complex with PMSF reveals a unique configuration that inhibits the nucleophile Ser144 in catalytic triads.

    PubMed

    Nam, Ki Hyun; Kim, Soo-Jin; Priyadarshi, Amit; Kim, Hyun Sook; Hwang, Kwang Yeon

    2009-11-13

    The esterase/lipase family (EC 3.1.1.3/EC 3.1.1.1) represents a diverse group of hydrolases that catalyze the cleavage of ester bonds and are widely distributed in animals, plants and microorganisms. Among these enzymes, hormone-sensitive lipases, play a critical role in the regulation of rodent fat cell lipolysis and are regarded as adipose tissue-specific enzymes. Recently, we reported the structural and biological characterization of EstE5 from the metagenome library [K.H. Nam, M.Y. Kim, S.J. Kim, A. Priyadarshi, W.H. Lee, K.Y. Hwang, Structural and functional analysis of a novel EstE5 belonging to the subfamily of hormone-sensitive lipase, Biochem. Biophys. Res. Commun. 379 (2009) 553-556]. The structure of this protein revealed that it belongs to the HSL-family. Here, we report the inhibition of the activity of the HSL-homolog EstE5 protein as determined by the use of esterase/lipase inhibitors. Our results revealed that the EstE5 protein is significantly inhibited by PMSF. In addition, this is the first study to identify the crystal structures of EstE5-PMSF at 2.4 and 2.5A among the HSL-homolog structures. This structural configuration is similar to that adopted when serine proteases are inhibited by PMSF. The results presented here provide valuable information regarding the properties of the HSL-family.

  12. Large Scale Full-Length cDNA Sequencing Reveals a Unique Genomic Landscape in a Lepidopteran Model Insect, Bombyx mori

    PubMed Central

    Suetsugu, Yoshitaka; Futahashi, Ryo; Kanamori, Hiroyuki; Kadono-Okuda, Keiko; Sasanuma, Shun-ichi; Narukawa, Junko; Ajimura, Masahiro; Jouraku, Akiya; Namiki, Nobukazu; Shimomura, Michihiko; Sezutsu, Hideki; Osanai-Futahashi, Mizuko; Suzuki, Masataka G; Daimon, Takaaki; Shinoda, Tetsuro; Taniai, Kiyoko; Asaoka, Kiyoshi; Niwa, Ryusuke; Kawaoka, Shinpei; Katsuma, Susumu; Tamura, Toshiki; Noda, Hiroaki; Kasahara, Masahiro; Sugano, Sumio; Suzuki, Yutaka; Fujiwara, Haruhiko; Kataoka, Hiroshi; Arunkumar, Kallare P.; Tomar, Archana; Nagaraju, Javaregowda; Goldsmith, Marian R.; Feng, Qili; Xia, Qingyou; Yamamoto, Kimiko; Shimada, Toru; Mita, Kazuei

    2013-01-01

    The establishment of a complete genomic sequence of silkworm, the model species of Lepidoptera, laid a foundation for its functional genomics. A more complete annotation of the genome will benefit functional and comparative studies and accelerate extensive industrial applications for this insect. To realize these goals, we embarked upon a large-scale full-length cDNA collection from 21 full-length cDNA libraries derived from 14 tissues of the domesticated silkworm and performed full sequencing by primer walking for 11,104 full-length cDNAs. The large average intron size was 1904 bp, resulting from a high accumulation of transposons. Using gene models predicted by GLEAN and published mRNAs, we identified 16,823 gene loci on the silkworm genome assembly. Orthology analysis of 153 species, including 11 insects, revealed that among three Lepidoptera including Monarch and Heliconius butterflies, the 403 largest silkworm-specific genes were composed mainly of protective immunity, hormone-related, and characteristic structural proteins. Analysis of testis-/ovary-specific genes revealed distinctive features of sexual dimorphism, including depletion of ovary-specific genes on the Z chromosome in contrast to an enrichment of testis-specific genes. More than 40% of genes expressed in specific tissues mapped in tissue-specific chromosomal clusters. The newly obtained FL-cDNA sequences enabled us to annotate the genome of this lepidopteran model insect more accurately, enhancing genomic and functional studies of Lepidoptera and comparative analyses with other insect orders, and yielding new insights into the evolution and organization of lepidopteran-specific genes. PMID:23821615

  13. Large scale full-length cDNA sequencing reveals a unique genomic landscape in a lepidopteran model insect, Bombyx mori.

    PubMed

    Suetsugu, Yoshitaka; Futahashi, Ryo; Kanamori, Hiroyuki; Kadono-Okuda, Keiko; Sasanuma, Shun-ichi; Narukawa, Junko; Ajimura, Masahiro; Jouraku, Akiya; Namiki, Nobukazu; Shimomura, Michihiko; Sezutsu, Hideki; Osanai-Futahashi, Mizuko; Suzuki, Masataka G; Daimon, Takaaki; Shinoda, Tetsuro; Taniai, Kiyoko; Asaoka, Kiyoshi; Niwa, Ryusuke; Kawaoka, Shinpei; Katsuma, Susumu; Tamura, Toshiki; Noda, Hiroaki; Kasahara, Masahiro; Sugano, Sumio; Suzuki, Yutaka; Fujiwara, Haruhiko; Kataoka, Hiroshi; Arunkumar, Kallare P; Tomar, Archana; Nagaraju, Javaregowda; Goldsmith, Marian R; Feng, Qili; Xia, Qingyou; Yamamoto, Kimiko; Shimada, Toru; Mita, Kazuei

    2013-09-04

    The establishment of a complete genomic sequence of silkworm, the model species of Lepidoptera, laid a foundation for its functional genomics. A more complete annotation of the genome will benefit functional and comparative studies and accelerate extensive industrial applications for this insect. To realize these goals, we embarked upon a large-scale full-length cDNA collection from 21 full-length cDNA libraries derived from 14 tissues of the domesticated silkworm and performed full sequencing by primer walking for 11,104 full-length cDNAs. The large average intron size was 1904 bp, resulting from a high accumulation of transposons. Using gene models predicted by GLEAN and published mRNAs, we identified 16,823 gene loci on the silkworm genome assembly. Orthology analysis of 153 species, including 11 insects, revealed that among three Lepidoptera including Monarch and Heliconius butterflies, the 403 largest silkworm-specific genes were composed mainly of protective immunity, hormone-related, and characteristic structural proteins. Analysis of testis-/ovary-specific genes revealed distinctive features of sexual dimorphism, including depletion of ovary-specific genes on the Z chromosome in contrast to an enrichment of testis-specific genes. More than 40% of genes expressed in specific tissues mapped in tissue-specific chromosomal clusters. The newly obtained FL-cDNA sequences enabled us to annotate the genome of this lepidopteran model insect more accurately, enhancing genomic and functional studies of Lepidoptera and comparative analyses with other insect orders, and yielding new insights into the evolution and organization of lepidopteran-specific genes.

  14. Mars surface diversity as revealed by the OMEGA/Mars Express observations.

    PubMed

    Bibring, Jean-Pierre; Langevin, Yves; Gendrin, Aline; Gondet, Brigitte; Poulet, François; Berthé, Michel; Soufflot, Alain; Arvidson, Ray; Mangold, Nicolas; Mustard, John; Drossart, P

    2005-03-11

    The Observatoire pour la Minéralogie, l'Eau, les Glaces, et l'Activité (OMEGA) investigation, on board the European Space Agency Mars Express mission, is mapping the surface composition of Mars at a 0.3- to 5-kilometer resolution by means of visible-near-infrared hyperspectral reflectance imagery. The data acquired during the first 9 months of the mission already reveal a diverse and complex surface mineralogy, offering key insights into the evolution of Mars. OMEGA has identified and mapped mafic iron-bearing silicates of both the northern and southern crust, localized concentrations of hydrated phyllosilicates and sulfates but no carbonates, and ices and frosts with a water-ice composition of the north polar perennial cap, as for the south cap, covered by a thin carbon dioxide-ice veneer.

  15. Lectin staining and flow cytometry reveals female-induced sperm acrosome reaction and surface carbohydrate reorganization

    PubMed Central

    Kekäläinen, Jukka; Larma, Irma; Linden, Matthew; Evans, Jonathan P.

    2015-01-01

    All cells are covered by glycans, an individually unique layer of oligo- and polysaccharides that are critical moderators of self-recognition and other cellular-level interactions (e.g. fertilization). The functional similarity between these processes suggests that gamete surface glycans may also have an important, but currently overlooked, role in sexual selection. Here we develop a user-friendly methodological approach designed to facilitate future tests of this possibility. Our proposed method is based on flow cytometric quantification of female-induced sperm acrosome reaction and sperm surface glycan modifications in the Mediterranean mussel Mytilus galloprovincialis. In this species, as with many other taxa, eggs release water-soluble factors that attract conspecific sperm (chemoattraction) and promote potentially measurable changes in sperm behavior and physiology. We demonstrate that flow cytometry is able to identify sperm from other seawater particles as well as accurately measure both acrosome reaction and structural modifications in sperm glycans. This methodological approach can increase our understanding of chemically-moderated gamete-level interactions and individual-specific gamete recognition in Mytilus sp. and other taxa with similar, easily identifiable acrosome structure. Our approach is also likely to be applicable to several other species, since carbohydrate-mediated cellular-level interactions between gametes are universal among externally and internally fertilizing species. PMID:26470849

  16. A plasmon-driven selective surface catalytic reaction revealed by surface-enhanced Raman scattering in an electrochemical environment.

    PubMed

    Cui, Lin; Wang, Peijie; Fang, Yurui; Li, Yuanzuo; Sun, Mengtao

    2015-07-06

    Plasmonic catalytic reactions of molecules with single amine or nitro groups have been investigated in recent years. However, plasmonic catalysis of molecules with multiple amine and/or nitro groups is still unknown. In this paper, plasmon-driven catalytic reactions of 4,4'-dinitroazobenzene (DNAB), 4,4'-diaminoazobenzene (DAAB) and 4-nitro-4'-aminoazobenzene (NAAB) are investigated using electrochemical surface-enhanced Raman scattering (SERS) spectroscopy. The results reveal that a plasmon-driven reduction reaction occurred for DNAB and NAAB in which the NO2 group was reduced to NH2, while the plasmon-driven oxidation reaction of NH2 did not occur. This result demonstrates that plasmon-driven reduction reactions are much easier than plasmon-driven oxidization reactions in electrochemical environments. The molecular resonance may also play an important role in plasmon-driven catalytic reactions. These findings provide us with a deeper understanding of plasmon-driven catalytic reactions.

  17. Nanoscale electrochemical patterning reveals the active sites for catechol oxidation at graphite surfaces.

    PubMed

    Patel, Anisha N; McKelvey, Kim; Unwin, Patrick R

    2012-12-19

    Graphite-based electrodes (graphite, graphene, and nanotubes) are used widely in electrochemistry, and there is a long-standing view that graphite step edges are needed to catalyze many reactions, with the basal surface considered to be inert. In the present work, this model was tested directly for the first time using scanning electrochemical cell microscopy reactive patterning and shown to be incorrect. For the electro-oxidation of dopamine as a model process, the reaction rate was measured at high spatial resolution across a surface of highly oriented pyrolytic graphite. Oxidation products left behind in a pattern defined by the scanned electrochemical cell served as surface-site markers, allowing the electrochemical activity to be correlated directly with the graphite structure on the nanoscale. This process produced tens of thousands of electrochemical measurements at different locations across the basal surface, unambiguously revealing it to be highly electrochemically active, with step edges providing no enhanced activity. This new model of graphite electrodes has significant implications for the design of carbon-based biosensors, and the results are additionally important for understanding electrochemical processes on related sp(2)-hybridized materials such as pristine graphene and nanotubes.

  18. Compositional variability across Mercury's surface revealed by MESSENGER measurements of variations in thermal neutron count rates

    NASA Astrophysics Data System (ADS)

    Peplowski, P. N.; Lawrence, D. J.; Goldsten, J. O.; Nittler, L. R.; Solomon, S. C.

    2013-12-01

    Measurements by MESSENGER's Gamma-Ray and Neutron Spectrometer (GRNS) have revealed variations in the flux of thermal neutrons across Mercury's northern hemisphere. These variations are interpreted to originate from spatial variations in surface elemental composition. In particular, the measurements are sensitive to the near-surface abundances of elements that absorb thermal neutrons, including major rock-forming elements such as Fe and Ti, minor elements such as Mn and Cl, and rare-earth elements such as Gd and Sm. We have constructed a map of thermal neutron variability across the surface and compared it with known variations in elemental composition and with the distribution of geologic units. Development of the map included the derivation of the macroscopic thermal neutron absorption cross section across the surface, a quantity whose value and variability provides useful constraints on the formation and geochemical evolution of Mercury's crust. Finally, by combining the thermal neutron measurements with previously reported elemental measurements from the GRNS and MESSENGER's X-Ray Spectrometer, we have derived constraints on the abundances of neutron-absorbing elements, including previously unreported limits for some minor and rare-earth elements.

  19. 3'-coterminal subgenomic RNAs and putative cis-acting elements of Grapevine leafroll-associated virus 3 reveals 'unique' features of gene expression strategy in the genus Ampelovirus

    PubMed Central

    2010-01-01

    Background The family Closteroviridae comprises genera with monopartite genomes, Closterovirus and Ampelovirus, and with bipartite and tripartite genomes, Crinivirus. By contrast to closteroviruses in the genera Closterovirus and Crinivirus, much less is known about the molecular biology of viruses in the genus Ampelovirus, although they cause serious diseases in agriculturally important perennial crops like grapevines, pineapple, cherries and plums. Results The gene expression and cis-acting elements of Grapevine leafroll-associated virus 3 (GLRaV-3; genus Ampelovirus) was examined and compared to that of other members of the family Closteroviridae. Six putative 3'-coterminal subgenomic (sg) RNAs were abundantly present in grapevine (Vitis vinifera) infected with GLRaV-3. The sgRNAs for coat protein (CP), p21, p20A and p20B were confirmed using gene-specific riboprobes in Northern blot analysis. The 5'-termini of sgRNAs specific to CP, p21, p20A and p20B were mapped in the 18,498 nucleotide (nt) virus genome and their leader sequences determined to be 48, 23, 95 and 125 nt, respectively. No conserved motifs were found around the transcription start site or in the leader sequence of these sgRNAs. The predicted secondary structure analysis of sequences around the start site failed to reveal any conserved motifs among the four sgRNAs. The GLRaV-3 isolate from Washington had a 737 nt long 5' nontranslated region (NTR) with a tandem repeat of 65 nt sequence and differed in sequence and predicted secondary structure with a South Africa isolate. Comparison of the dissimilar sequences of the 5'NTRs did not reveal any common predicted structures. The 3'NTR was shorter and more conserved. The lack of similarity among the cis-acting elements of the diverse viruses in the family Closteroviridae is another measure of the complexity of their evolution. Conclusions The results indicate that transcription regulation of GLRaV-3 sgRNAs appears to be different from members of the

  20. MicroRNA Profiling Reveals Unique miRNA Signatures in IGF-1 Treated Embryonic Striatal Stem Cell Fate Decisions in Striatal Neurogenesis In Vitro

    PubMed Central

    Pati, Soumya; Supeno, Nor Entan; Muthuraju, Sangu; Abdul Hadi, Raisah; Ghani, Abdul Rahman Izaini; Idris, Fauziah Mohamad; Maletic-Savatic, Mirjana; Abdullah, Jafri Malin; Jaafar, Hasnan

    2014-01-01

    The striatum is considered to be the central processing unit of the basal ganglia in locomotor activity and cognitive function of the brain. IGF-1 could act as a control switch for the long-term proliferation and survival of EGF + bFGF-responsive cultured embryonic striatal stem cell (ESSC), while LIF imposes a negative impact on cell proliferation. The IGF-1-treated ESSCs also showed elevated hTERT expression with demonstration of self-renewal and trilineage commitment (astrocytes, oligodendrocytes, and neurons). In order to decipher the underlying regulatory microRNA (miRNA)s in IGF-1/LIF-treated ESSC-derived neurogenesis, we performed in-depth miRNA profiling at 12 days in vitro and analyzed the candidates using the Partek Genome Suite software. The annotated miRNA fingerprints delineated the differential expressions of miR-143, miR-433, and miR-503 specific to IGF-1 treatment. Similarly, the LIF-treated ESSCs demonstrated specific expression of miR-326, miR-181, and miR-22, as they were nonsignificant in IGF-treated ESSCs. To elucidate the possible downstream pathways, we performed in silico mapping of the said miRNAs into ingenuity pathway analysis. Our findings revealed the important mRNA targets of the miRNAs and suggested specific interactomes. The above studies introduced a new genre of miRNAs for ESSC-based neuroregenerative therapeutic applications. PMID:25254208

  1. 187-gene phylogeny of protozoan phylum Amoebozoa reveals a new class (Cutosea) of deep-branching, ultrastructurally unique, enveloped marine Lobosa and clarifies amoeba evolution.

    PubMed

    Cavalier-Smith, Thomas; Chao, Ema E; Lewis, Rhodri

    2016-06-01

    Monophyly of protozoan phylum Amoebozoa, and subdivision into subphyla Conosa and Lobosa each with different cytoskeletons, are well established. However early diversification of non-ciliate lobose amoebae (Lobosa) is poorly understood. To clarify it we used recently available transcriptomes to construct a 187-gene amoebozoan tree for 30 species, the most comprehensive yet. This robustly places new genus Atrichosa (formerly lumped with Trichosphaerium) within lobosan class Tubulinea, not Discosea as previously supposed. We identified an earliest diverging lobosan clade comprising marine amoebae armoured by porose scaliform cell-envelopes, here made a novel class Cutosea with two pseudopodially distinct new families. Cutosea comprise Sapocribrum, ATCC PRA-29 misidentified as 'Pessonella', plus from other evidence Squamamoeba. We confirm that Acanthamoeba and ATCC 50982 misidentified as Stereomyxa ramosa are closely related. Discosea have a strongly supported major subclade comprising Thecamoebida plus Glycostylida (suborders Dactylopodina, Stygamoebina; Vannellina) phylogenetically distinct from Centramoebida. Stygamoeba is sister to Dactylopodina. Himatismenida are either sister to Centramoebida or deeper branching. Discosea usually appear holophyletic (rarely paraphyletic). Paramoeba transcriptomes include prokinetoplastid Perkinsela-like endosymbiont sequences. Cunea, misidentified as Mayorella, is closer to Paramoeba than Vexillifera within holophyletic Dactylopodina. Taxon-rich site-heterogeneous rDNA trees confirm cutosan distinctiveness, allow improved conosan taxonomy, and reveal previous dictyostelid tree misrooting. PMID:27001604

  2. 187-gene phylogeny of protozoan phylum Amoebozoa reveals a new class (Cutosea) of deep-branching, ultrastructurally unique, enveloped marine Lobosa and clarifies amoeba evolution.

    PubMed

    Cavalier-Smith, Thomas; Chao, Ema E; Lewis, Rhodri

    2016-06-01

    Monophyly of protozoan phylum Amoebozoa, and subdivision into subphyla Conosa and Lobosa each with different cytoskeletons, are well established. However early diversification of non-ciliate lobose amoebae (Lobosa) is poorly understood. To clarify it we used recently available transcriptomes to construct a 187-gene amoebozoan tree for 30 species, the most comprehensive yet. This robustly places new genus Atrichosa (formerly lumped with Trichosphaerium) within lobosan class Tubulinea, not Discosea as previously supposed. We identified an earliest diverging lobosan clade comprising marine amoebae armoured by porose scaliform cell-envelopes, here made a novel class Cutosea with two pseudopodially distinct new families. Cutosea comprise Sapocribrum, ATCC PRA-29 misidentified as 'Pessonella', plus from other evidence Squamamoeba. We confirm that Acanthamoeba and ATCC 50982 misidentified as Stereomyxa ramosa are closely related. Discosea have a strongly supported major subclade comprising Thecamoebida plus Glycostylida (suborders Dactylopodina, Stygamoebina; Vannellina) phylogenetically distinct from Centramoebida. Stygamoeba is sister to Dactylopodina. Himatismenida are either sister to Centramoebida or deeper branching. Discosea usually appear holophyletic (rarely paraphyletic). Paramoeba transcriptomes include prokinetoplastid Perkinsela-like endosymbiont sequences. Cunea, misidentified as Mayorella, is closer to Paramoeba than Vexillifera within holophyletic Dactylopodina. Taxon-rich site-heterogeneous rDNA trees confirm cutosan distinctiveness, allow improved conosan taxonomy, and reveal previous dictyostelid tree misrooting.

  3. The Genome of the Anaerobic Fungus Orpinomyces sp. Strain C1A Reveals the Unique Evolutionary History of a Remarkable Plant Biomass Degrader

    PubMed Central

    Youssef, Noha H.; Couger, M. B.; Struchtemeyer, Christopher G.; Liggenstoffer, Audra S.; Prade, Rolf A.; Najar, Fares Z.; Atiyeh, Hasan K.; Wilkins, Mark R.

    2013-01-01

    Anaerobic gut fungi represent a distinct early-branching fungal phylum (Neocallimastigomycota) and reside in the rumen, hindgut, and feces of ruminant and nonruminant herbivores. The genome of an anaerobic fungal isolate, Orpinomyces sp. strain C1A, was sequenced using a combination of Illumina and PacBio single-molecule real-time (SMRT) technologies. The large genome (100.95 Mb, 16,347 genes) displayed extremely low G+C content (17.0%), large noncoding intergenic regions (73.1%), proliferation of microsatellite repeats (4.9%), and multiple gene duplications. Comparative genomic analysis identified multiple genes and pathways that are absent in Dikarya genomes but present in early-branching fungal lineages and/or nonfungal Opisthokonta. These included genes for posttranslational fucosylation, the production of specific intramembrane proteases and extracellular protease inhibitors, the formation of a complete axoneme and intraflagellar trafficking machinery, and a near-complete focal adhesion machinery. Analysis of the lignocellulolytic machinery in the C1A genome revealed an extremely rich repertoire, with evidence of horizontal gene acquisition from multiple bacterial lineages. Experimental analysis indicated that strain C1A is a remarkable biomass degrader, capable of simultaneous saccharification and fermentation of the cellulosic and hemicellulosic fractions in multiple untreated grasses and crop residues examined, with the process significantly enhanced by mild pretreatments. This capability, acquired during its separate evolutionary trajectory in the rumen, along with its resilience and invasiveness compared to prokaryotic anaerobes, renders anaerobic fungi promising agents for consolidated bioprocessing schemes in biofuels production. PMID:23709508

  4. A Phox2- and Hand2-dependent Hand1 cis-regulatory element reveals a unique gene dosage requirement for Hand2 during sympathetic neurogenesis.

    PubMed

    Vincentz, Joshua W; VanDusen, Nathan J; Fleming, Andrew B; Rubart, Michael; Firulli, Beth A; Howard, Marthe J; Firulli, Anthony B

    2012-02-01

    Neural crest cell specification and differentiation to a sympathetic neuronal fate serves as an important model for neurogenesis and depends upon the function of both bHLH transcription factors, notably Hand2, and homeodomain transcription factors, including Phox2b. Here, we define a 1007 bp cis-regulatory element 5' of the Hand1 gene sufficient to drive reporter expression within the sympathetic chain of transgenic mice. Comparative genomic analyses uncovered evolutionarily conserved consensus-binding sites within this element, which chromatin immunoprecipitation and electrophoretic mobility shift assays confirm are bound by Hand2 and Phox2b. Mutational analyses revealed that the conserved Phox2 and E-box binding sites are necessary for proper cis-regulatory element activity, and expression analyses on both Hand2 conditionally null and hypomorphic backgrounds demonstrate that Hand2 is required for reporter activation in a gene dosage-dependent manner. We demonstrate that Hand2 and Hand1 differentially bind the E-boxes in this cis-regulatory element, establishing molecular differences between these two factors. Finally, we demonstrate that Hand1 is dispensable for normal tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) expression in sympathetic neurons, even when Hand2 gene dosage is concurrently reduced by half. Together, these data define a tissue-specific Hand1 cis-regulatory element controlled by two factors essential for the development of the sympathetic nervous system and provide in vivo regulatory evidence to support previous findings that Hand2, rather than Hand1, is predominantly responsible for regulating TH, DBH, and Hand1 expression in developing sympathetic neurons.

  5. The history of hepatitis C virus (HCV): Basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control.

    PubMed

    Bukh, Jens

    2016-10-01

    The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected individuals as a continuously evolving quasispecies destined to escape host immune responses and applied antivirals. Despite the inability to culture patient viruses directly in the laboratory, efforts to define the infectious genome of HCV resulted in development of experimental recombinant in vivo and in vitro systems, including replicons and infectious cultures in human hepatoma cell lines. And HCV has become a model virus defining new paradigms in virology, immunology and biology. For example, HCV research discovered that a virus could be completely dependent on microRNA for its replication since microRNA-122 is critical for the HCV life cycle. A number of other host molecules critical for HCV entry and replication have been identified. Thus, basic HCV research revealed important molecules for development of host targeting agents (HTA). The identification and characterization of HCV encoded proteins and their functional units contributed to the development of highly effective direct acting antivirals (DAA) against the NS3 protease, NS5A and the NS5B polymerase. In combination, these inhibitors have since 2014 permitted interferon-free therapy with cure rates above 90% among patients with chronic HCV infection; however, viral resistance represents a challenge. Worldwide control of HCV will most likely require the development of a prophylactic vaccine, and numerous candidates have been pursued. Research characterizing features critical for antibody-based virus neutralization and T cell based virus elimination from infected cells is essential for this effort. If the world community promotes an ambitious approach by applying current DAA broadly, continues to develop

  6. The history of hepatitis C virus (HCV): Basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control.

    PubMed

    Bukh, Jens

    2016-10-01

    The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected individuals as a continuously evolving quasispecies destined to escape host immune responses and applied antivirals. Despite the inability to culture patient viruses directly in the laboratory, efforts to define the infectious genome of HCV resulted in development of experimental recombinant in vivo and in vitro systems, including replicons and infectious cultures in human hepatoma cell lines. And HCV has become a model virus defining new paradigms in virology, immunology and biology. For example, HCV research discovered that a virus could be completely dependent on microRNA for its replication since microRNA-122 is critical for the HCV life cycle. A number of other host molecules critical for HCV entry and replication have been identified. Thus, basic HCV research revealed important molecules for development of host targeting agents (HTA). The identification and characterization of HCV encoded proteins and their functional units contributed to the development of highly effective direct acting antivirals (DAA) against the NS3 protease, NS5A and the NS5B polymerase. In combination, these inhibitors have since 2014 permitted interferon-free therapy with cure rates above 90% among patients with chronic HCV infection; however, viral resistance represents a challenge. Worldwide control of HCV will most likely require the development of a prophylactic vaccine, and numerous candidates have been pursued. Research characterizing features critical for antibody-based virus neutralization and T cell based virus elimination from infected cells is essential for this effort. If the world community promotes an ambitious approach by applying current DAA broadly, continues to develop

  7. Structure of the Legionella Virulence Factor, SidC Reveals a Unique PI(4)P-Specific Binding Domain Essential for Its Targeting to the Bacterial Phagosome

    PubMed Central

    Luo, Xi; Wasilko, David J.; Liu, Yao; Sun, Jiayi; Wu, Xiaochun; Luo, Zhao-Qing; Mao, Yuxin

    2015-01-01

    The opportunistic intracellular pathogen Legionella pneumophila is the causative agent of Legionnaires’ disease. L. pneumophila delivers nearly 300 effector proteins into host cells for the establishment of a replication-permissive compartment known as the Legionella-containing vacuole (LCV). SidC and its paralog SdcA are two effectors that have been shown to anchor on the LCV via binding to phosphatidylinositol-4-phosphate [PI(4)P] to facilitate the recruitment of ER proteins to the LCV. We recently reported that the N-terminal SNL (SidC N-terminal E3 Ligase) domain of SidC is a ubiquitin E3 ligase, and its activity is required for the recruitment of ER proteins to the LCV. Here we report the crystal structure of SidC (1-871). The structure reveals that SidC contains four domains that are packed into an arch-like shape. The P4C domain (PI(4)P binding of SidC) comprises a four α-helix bundle and covers the ubiquitin ligase catalytic site of the SNL domain. Strikingly, a pocket with characteristic positive electrostatic potentials is formed at one end of this bundle. Liposome binding assays of the P4C domain further identified the determinants of phosphoinositide recognition and membrane interaction. Interestingly, we also found that binding with PI(4)P stimulates the E3 ligase activity, presumably due to a conformational switch induced by PI(4)P from a closed form to an open active form. Mutations of key residues involved in PI(4)P binding significantly reduced the association of SidC with the LCV and abolished its activity in the recruitment of ER proteins and ubiquitin signals, highlighting that PI(4)P-mediated targeting of SidC is critical to its function in the remodeling of the bacterial phagosome membrane. Finally, a GFP-fusion with the P4C domain was demonstrated to be specifically localized to PI(4)P-enriched compartments in mammalian cells. This domain shows the potential to be developed into a sensitive and accurate PI(4)P probe in living cells. PMID

  8. Unique Ecophysiology among U(VI)-Reducing Bacteria as Revealed by Evaluation of Oxygen Metabolism in Anaeromyxobacter dehalogenans Strain 2CP-C▿ †

    PubMed Central

    Thomas, Sara H.; Sanford, Robert A.; Amos, Benjamin K.; Leigh, Mary Beth; Cardenas, Erick; Löffler, Frank E.

    2010-01-01

    Anaeromyxobacter spp. respire soluble hexavalent uranium, U(VI), leading to the formation of insoluble U(IV), and are present at the uranium-contaminated Oak Ridge Integrated Field Research Challenge (IFC) site. Pilot-scale in situ bioreduction of U(VI) has been accomplished in area 3 of the Oak Ridge IFC site following biostimulation, but the susceptibility of the reduced material to oxidants (i.e., oxygen) compromises long-term U immobilization. Following oxygen intrusion, attached Anaeromyxobacter dehalogenans cells increased approximately 5-fold from 2.2 × 107 ± 8.6 × 106 to 1.0 × 108 ± 2.2 × 107 cells per g of sediment collected from well FW101-2. In the same samples, the numbers of cells of Geobacter lovleyi, a population native to area 3 and also capable of U(VI) reduction, decreased or did not change. A. dehalogenans cells captured via groundwater sampling (i.e., not attached to sediment) were present in much lower numbers (<1.3 × 104 ± 1.1 × 104 cells per liter) than sediment-associated cells, suggesting that A. dehalogenans cells occur predominantly in association with soil particles. Laboratory studies confirmed aerobic growth of A. dehalogenans strain 2CP-C at initial oxygen partial pressures (pO2) at and below 0.18 atm. A negative linear correlation [μ = (−0.09 × pO2) + 0.051; R2 = 0.923] was observed between the instantaneous specific growth rate μ and pO2, indicating that this organism should be classified as a microaerophile. Quantification of cells during aerobic growth revealed that the fraction of electrons released in electron donor oxidation and used for biomass production (fs) decreased from 0.52 at a pO2 of 0.02 atm to 0.19 at a pO2 of 0.18 atm. Hence, the apparent fraction of electrons utilized for energy generation (i.e., oxygen reduction) (fe) increased from 0.48 to 0.81 with increasing pO2, suggesting that oxygen is consumed in a nonrespiratory process at a high pO2. The ability to tolerate high oxygen concentrations

  9. Structure of Est3 reveals a bimodal surface with differential roles in telomere replication

    PubMed Central

    Rao, Timsi; Lubin, Johnathan W.; Armstrong, Geoffrey S.; Tucey, Timothy M.; Lundblad, Victoria; Wuttke, Deborah S.

    2014-01-01

    Telomerase is essential for continuous cellular proliferation. Substantial insights have come from studies of budding yeast telomerase, which consists of a catalytic core in association with two regulatory proteins, ever shorter telomeres 1 and 3 (Est1 and Est3). We report here a high-resolution structure of the Est3 telomerase subunit determined using a recently developed strategy that combines minimal NMR experimental data with Rosetta de novo structure prediction algorithms. Est3 adopts an overall protein fold which is structurally similar to that adopted by the shelterin component TPP1. However, the characteristics of the surface of the experimentally determined Est3 structure are substantially different from those predicted by prior homology-based models of Est3. Structure-guided mutagenesis of the complete surface of the Est3 protein reveals two adjacent patches on a noncanonical face of the protein that differentially mediate telomere function. Mapping these two patches on the Est3 structure defines a set of shared features between Est3 and HsTPP1, suggesting an analogous multifunctional surface on TPP1. PMID:24344315

  10. Structure of Est3 reveals a bimodal surface with differential roles in telomere replication.

    PubMed

    Rao, Timsi; Lubin, Johnathan W; Armstrong, Geoffrey S; Tucey, Timothy M; Lundblad, Victoria; Wuttke, Deborah S

    2014-01-01

    Telomerase is essential for continuous cellular proliferation. Substantial insights have come from studies of budding yeast telomerase, which consists of a catalytic core in association with two regulatory proteins, ever shorter telomeres 1 and 3 (Est1 and Est3). We report here a high-resolution structure of the Est3 telomerase subunit determined using a recently developed strategy that combines minimal NMR experimental data with Rosetta de novo structure prediction algorithms. Est3 adopts an overall protein fold which is structurally similar to that adopted by the shelterin component TPP1. However, the characteristics of the surface of the experimentally determined Est3 structure are substantially different from those predicted by prior homology-based models of Est3. Structure-guided mutagenesis of the complete surface of the Est3 protein reveals two adjacent patches on a noncanonical face of the protein that differentially mediate telomere function. Mapping these two patches on the Est3 structure defines a set of shared features between Est3 and HsTPP1, suggesting an analogous multifunctional surface on TPP1.

  11. Crystal structure of two CD46 domains reveals an extended measles virus-binding surface.

    PubMed Central

    Casasnovas, J M; Larvie, M; Stehle, T

    1999-01-01

    Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide. The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 A resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface. Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition. A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46. PMID:10357804

  12. T Cell Immunoglobulin Mucin-3 Crystal Structure Reveals a Galectin-9-Independent Ligand-Binding Surface

    SciTech Connect

    Cao,E.; Zang, X.; Ramagopal, U.; Mukhopadhaya, A.; Fedorov, A.; Fedorov, E.; Zencheck, W.; Lary, J.; Cole, J.; et al.

    2007-01-01

    The T cell immunoglobulin mucin (Tim) family of receptors regulates effector CD4+ T cell functions and is implicated in autoimmune and allergic diseases. Tim-3 induces immunological tolerance, and engagement of the Tim-3 immunoglobulin variable (IgV) domain by galectin-9 is important for appropriate termination of T helper 1-immune responses. The 2 {angstrom} crystal structure of the Tim-3 IgV domain demonstrated that four cysteines, which are invariant within the Tim family, form two noncanonical disulfide bonds, resulting in a surface not present in other immunoglobulin superfamily members. Biochemical and biophysical studies demonstrated that this unique structural feature mediates a previously unidentified galectin-9-independent binding process and suggested that this structural feature is conserved within the entire Tim family. The current work provided a graphic example of the relationship between sequence, structure, and function and suggested that the interplay between multiple Tim-3-binding activities contributes to the regulated assembly of signaling complexes required for effective Th1-mediated immunity.

  13. Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes

    SciTech Connect

    Kanai,R.; Kar, K.; Anthony, K.; Gould, L.; Ledizet, M.; Fikrig, E.; Marasco, W.; Koski, R.; Modis, Y.

    2006-01-01

    West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics.

  14. Surface plasmon delocalization in silver nanoparticle aggregates revealed by subdiffraction supercontinuum hot spots

    PubMed Central

    Borys, Nicholas J.; Shafran, Eyal; Lupton, John M.

    2013-01-01

    The plasmonic resonances of nanostructured silver films produce exceptional surface enhancement, enabling reproducible single-molecule Raman scattering measurements. Supporting a broad range of plasmonic resonances, these disordered systems are difficult to investigate with conventional far-field spectroscopy. Here, we use nonlinear excitation spectroscopy and polarization anisotropy of single optical hot spots of supercontinuum generation to track the transformation of these plasmon modes as the mesoscopic structure is tuned from a film of discrete nanoparticles to a semicontinuous layer of aggregated particles. We demonstrate how hot spot formation from diffractively-coupled nanoparticles with broad spectral resonances transitions to that from spatially delocalized surface plasmon excitations, exhibiting multiple excitation resonances as narrow as 13 meV. Photon-localization microscopy reveals that the delocalized plasmons are capable of focusing multiple narrow radiation bands over a broadband range to the same spatial region within 6 nm, underscoring the existence of novel plasmonic nanoresonators embedded in highly disordered systems. PMID:23807624

  15. Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes.

    PubMed

    Kanai, Ryuta; Kar, Kalipada; Anthony, Karen; Gould, L Hannah; Ledizet, Michel; Fikrig, Erol; Marasco, Wayne A; Koski, Raymond A; Modis, Yorgo

    2006-11-01

    West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics.

  16. Revealing the spatial variability of water fluxes at the groundwater-surface water interface

    NASA Astrophysics Data System (ADS)

    Binley, Andrew; Ullah, Sami; Heathwaite, A. Louise; Heppell, Catherine; Byrne, Patrick; Lansdown, Katrina; Trimmer, Mark; Zhang, Hao

    2013-07-01

    There is widespread recognition that the groundwater-surface water interface can have significant influence on the pattern and form of the transfer of nutrient-rich groundwater to rivers. Characterizing and quantifying this influence is critical for successful management of water resources in many catchments, particularly those threatened by rising nitrate levels in groundwater. Building on previous experimental investigations in one such catchment: the River Leith, UK, we report on a multimeasurement, multiscale program aimed at developing a conceptualization of groundwater-surface water flow pathways along a 200 m reach. Key to this conceptualization is the quantification of vertical and horizontal water fluxes, which is achieved through a series of Darcian flow estimates coupled with in-stream piezometer tracer dilution tests. These data, enhanced by multilevel measurements of chloride concentration in riverbed pore water and water-borne geophysical surveying, reveal a contrast in the contribution of flow components along the reach. In the upper section of the reach, a localized connectivity to regional groundwater, that appears to suppress the hyporheic zone, is identified. Further downstream, horizontal (lateral and longitudinal) flows appear to contribute more to the total subsurface flow at the groundwater-surface water interface. Although variation in hydraulic conductivity of the riverbed is observed, localized variation that can account for the spatial variability in flow pathways is not evident. The study provides a hydrological conceptualization for the site, which is essential for future studies which address biogeochemical processes, in relation to nitrogen retention/release. Such a conceptualization would not have been possible without a multiexperimental program.

  17. Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae

    PubMed Central

    Hathroubi, S.; Hancock, M. A.; Langford, P. R.; Tremblay, Y. D. N.; Labrie, J.

    2015-01-01

    Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA. PMID:26483403

  18. fMRI Analysis-by-Synthesis Reveals a Dorsal Hierarchy That Extracts Surface Slant

    PubMed Central

    Ban, Hiroshi

    2015-01-01

    The brain's skill in estimating the 3-D orientation of viewed surfaces supports a range of behaviors, from placing an object on a nearby table, to planning the best route when hill walking. This ability relies on integrating depth signals across extensive regions of space that exceed the receptive fields of early sensory neurons. Although hierarchical selection and pooling is central to understanding of the ventral visual pathway, the successive operations in the dorsal stream are poorly understood. Here we use computational modeling of human fMRI signals to probe the computations that extract 3-D surface orientation from binocular disparity. To understand how representations evolve across the hierarchy, we developed an inference approach using a series of generative models to explain the empirical fMRI data in different cortical areas. Specifically, we simulated the responses of candidate visual processing algorithms and tested how well they explained fMRI responses. Thereby we demonstrate a hierarchical refinement of visual representations moving from the representation of edges and figure–ground segmentation (V1, V2) to spatially extensive disparity gradients in V3A. We show that responses in V3A are little affected by low-level image covariates, and have a partial tolerance to the overall depth position. Finally, we show that responses in V3A parallel perceptual judgments of slant. This reveals a relatively short computational hierarchy that captures key information about the 3-D structure of nearby surfaces, and more generally demonstrates an analysis approach that may be of merit in a diverse range of brain imaging domains. PMID:26156985

  19. Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae.

    PubMed

    Hathroubi, S; Hancock, M A; Bossé, J T; Langford, P R; Tremblay, Y D N; Labrie, J; Jacques, M

    2016-01-01

    Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA. PMID:26483403

  20. Revealing remodeler function: Varied and unique

    NASA Astrophysics Data System (ADS)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  1. Structure of the hypothetical protein Ton1535 from Thermococcus onnurineus NA1 reveals unique structural properties by a left-handed helical turn in normal α-solenoid protein.

    PubMed

    Jeong, Jae-Hee; Kim, Yi-Seul; Rojvirija, Catleya; Cha, Hyung Jin; Kim, Yeon-Gil; Ha, Sung Chul

    2014-06-01

    The crystal structure of Ton1535, a hypothetical protein from Thermococcus onnurineus NA1, was determined at 2.3 Å resolution. With two antiparallel α-helices in a helix-turn-helix motif as a repeating unit, Ton1535 consists of right-handed coiled N- and C-terminal regions that are stacked together using helix bundles containing a left-handed helical turn. One left-handed helical turn in the right-handed coiled structure produces two unique structural properties. One is the presence of separated concave grooves rather than one continuous concave groove, and the other is the contribution of α-helices on the convex surfaces of the N-terminal region to the extended surface of the concave groove of the C-terminal region and vice versa.

  2. Reactions in elastomeric nanoreactors reveal the role of force on the kinetics of the Huisgen reaction on surfaces.

    PubMed

    Han, Xu; Bian, Shudan; Liang, Yong; Houk, K N; Braunschweig, Adam B

    2014-07-30

    The force dependence of the copper-free Huisgen cycloaddition between an alkyne and a surface-bound azide was examined in elastomeric nanoreactors. These studies revealed that pressure and chain length are critical factors that determine the reaction rate. These experiments demonstrate the central role of pressure and surface structure on interfacial processes that are increasingly important in biology, materials science, and nanotechnology.

  3. Spontaneous Mutation Reveals Influence of Exopolysaccharide on Lactobacillus johnsonii Surface Characteristics

    PubMed Central

    Horn, Nikki; Wegmann, Udo; Dertli, Enes; Mulholland, Francis; Collins, Samuel R. A.; Waldron, Keith W.; Bongaerts, Roy J.; Mayer, Melinda J.; Narbad, Arjan

    2013-01-01

    As a competitive exclusion agent, Lactobacillus johnsonii FI9785 has been shown to prevent the colonization of selected pathogenic bacteria from the chicken gastrointestinal tract. During growth of the bacterium a rare but consistent emergence of an altered phenotype was noted, generating smooth colonies in contrast to the wild type rough form. A smooth colony variant was isolated and two-dimensional gel analysis of both strains revealed a protein spot with different migration properties in the two phenotypes. The spot in both gels was identified as a putative tyrosine kinase (EpsC), associated with a predicted exopolysaccharide gene cluster. Sequencing of the epsC gene from the smooth mutant revealed a single substitution (G to A) in the coding strand, resulting in the amino acid change D88N in the corresponding gene product. A native plasmid of L. johnsonii was engineered to produce a novel vector for constitutive expression and this was used to demonstrate that expression of the wild type epsC gene in the smooth mutant produced a reversion to the rough colony phenotype. Both the mutant and epsC complemented strains had increased levels of exopolysaccharides compared to the wild type strain, indicating that the rough phenotype is not solely associated with the quantity of exopolysaccharide. Another gene in the cluster, epsE, that encoded a putative undecaprenyl-phosphate galactosephosphotransferase, was deleted in order to investigate its role in exopolysaccharide biosynthesis. The ΔepsE strain exhibited a large increase in cell aggregation and a reduction in exopolysaccharide content, while plasmid complementation of epsE restored the wild type phenotype. Flow cytometry showed that the wild type and derivative strains exhibited clear differences in their adhesive ability to HT29 monolayers in tissue culture, demonstrating an impact of EPS on surface properties and bacteria-host interactions. PMID:23544114

  4. Dunes on Titan: A major landform revealing atmospheric and surface processes

    NASA Astrophysics Data System (ADS)

    Radebaugh, Jani; Lorenz, Ralph; Arnold, Karl; Savage, Christopher; Williams, Brigitte

    The surface of Saturn’s moon Titan is covered in features that herald an active atmosphere and perhaps interior, such as dunes, rivers, lakes, mountain chains, and possible cryovolcanoes. Examining the geomorphology of these features helps us approach an understanding of the processes that are occurring or have occurred in the atmosphere and subsurface. A major landform on Titan is dunes, composed of organic sands ultimately derived from upper atmospheric processing of methane, subsequently perhaps eroded from organic sedimentary layers by methane rainfall and fluvial flow. Dunes fill vast fields, termed sand seas, similar to those observed in the Sahara, Namibia, and the Arabian peninsula. The equatorial region of Titan contains five separate sand seas as observed by the Cassini Synthetic Aperture Radar (SAR), Imaging Science Subsystem (ISS) and Visual and Infrared Mapping Spectrometer (VIMS) instruments. Together these sand seas cover 14 percent of the surface, totaling 12 million km2, and each have areas on the scale of the Saharan Great Sand Sea. They adjoin each other through sediment pathways around landmasses, and these large-scale connections as well as individual dune interactions with topography indicate a general transport of sediment from west to east. Measurements of dune height, width and spacing in Cassini SAR images reveal all of Titan’s thousands of linear dunes are of the same population. This indicates there was general uniformity in the wind and sediment supply conditions that led to the current dune forms. Variations in the parametric values result from deviations from these conditions, in some locations where elevated terrains have deflected winds. Dunes and sand seas are among the stratigraphically youngest features on Titan, showing little evidence of being affected by impact cratering or fluvial flow. However, individual dunes may be relatively stable, as the reorganization time scale for these features on Earth can be tens to hundreds

  5. Chromatogram Handler: A unique computer program that efficiently processes data generated in liquid chromatographic investigations of organic ligand adsorption on mineral surfaces

    NASA Astrophysics Data System (ADS)

    Kreller, David I.; Young, Stephen P.; Mendez, Eladio A.; McGunigale, Samantha L.

    2012-09-01

    We describe a unique C# computer program developed in our laboratory to efficiently manipulate data generated when a novel liquid chromatographic (LC) 'pulsed addition' technique is used to study organic ligand interactions with mineral surfaces. We are not aware of the existence of a program of this nature elsewhere. Geochemically-relevant ligands studied include dissolved organic matter (DOM) mixtures and single component low molecular weight organic acids. Although our LC system has three optical (absorbance and fluorescence) detection channels, the utility can process data from experiments in which data was collected in one, two or three detection channels. If not automated, data management and processing for the technique is prohibitively complex and time-consuming, due large data volumes and the number of operations involved. The input for the utility in a processing run is the set of detector output files generated during an LC experiment. During processing, the utility generates an MS Excel output file within which, for each detection channel: (i) chromatographic peak areas and peak retention times are determined, (ii) area-normalized per-injection and cumulative adsorption densities are calculated, and (iii) graphical representations of various quantities calculated from the raw data are automatically generated. When processing data from experiments with multiple detection channels, the utility additionally prepares graphs that compare recovery values calculated from data in different detection channels, and calculates (and plots) spectroscopic/chromatographic indices which are ratios of signals in various detection channels. The utility was programmed to perform these additional operations on data from multi-channel experiments because (i) 'Interchannel' comparisons of recovery provide insight into the differing surface behavior of distinct DOM sub-fractions, and (ii) the spectroscopic indices provide a useful new form of data that provides insight into

  6. Ag@Au concave cuboctahedra: A unique probe for monitoring Au-catalyzed reduction and oxidation reactions by surface-enhanced Raman spectroscopy

    DOE PAGESBeta

    Zhang, Jiawei; Winget, Sarah A.; Wu, Yiren; Su, Dong; Sun, Xiaojun; Xie, Zhao -Xiong; Qin, Dong

    2016-01-26

    In this paper, we report a facile synthesis of Ag@Au concave cuboctahedra by titrating aqueous HAuCl4 into a suspension of Ag cuboctahedra in the presence of ascorbic acid (AA), NaOH, and poly(vinylpyrrolidone) (PVP) at room temperature. Initially, the Au atoms derived from the reduction of Au3+ by AA are conformally deposited on the entire surface of a Ag cuboctahedron. Upon the formation of a complete Au shell, however, the subsequently formed Au atoms are preferentially deposited onto the Au{100} facets, resulting in the formation of a Ag@Au cuboctahedron with concave structures at the sites of {111} facets. The concave cuboctahedramore » embrace excellent SERS activity that is more than 70-fold stronger than that of the original Ag cuboctahedra at an excitation wavelength of 785 nm. The concave cuboctahedra also exhibit remarkable stability in the presence of an oxidant such as H2O2 because of the protection by a complete Au shell. These two unique attributes enable in-situ SERS monitoring of the reduction of 4-nitrothiophenol (4-NTP) to 4-aminothiophenol (4-ATP) by NaBH4 through a 4,4'-dimercaptoazobenzene (trans-DMAB) intermediate and the subsequent oxidation of 4-ATP back to trans-DMAB upon the introduction of H2O2.« less

  7. Ag@Au Concave Cuboctahedra: A Unique Probe for Monitoring Au-Catalyzed Reduction and Oxidation Reactions by Surface-Enhanced Raman Spectroscopy.

    PubMed

    Zhang, Jiawei; Winget, Sarah A; Wu, Yiren; Su, Dong; Sun, Xiaojun; Xie, Zhao-Xiong; Qin, Dong

    2016-02-23

    We report a facile synthesis of Ag@Au concave cuboctahedra by titrating aqueous HAuCl4 into a suspension of Ag cuboctahedra in the presence of ascorbic acid (AA), NaOH, and poly(vinylpyrrolidone) (PVP) at room temperature. Initially, the Au atoms derived from the reduction of Au(3+) by AA are conformally deposited on the entire surface of a Ag cuboctahedron. Upon the formation of a complete Au shell, however, the subsequently formed Au atoms are preferentially deposited onto the Au{100} facets, resulting in the formation of a Ag@Au cuboctahedron with concave structures at the sites of {111} facets. The concave cuboctahedra embrace excellent SERS activity that is more than 70-fold stronger than that of the original Ag cuboctahedra at an excitation wavelength of 785 nm. The concave cuboctahedra also exhibit remarkable stability in the presence of an oxidant such as H2O2 because of the protection by a complete Au shell. These two unique attributes enable in situ SERS monitoring of the reduction of 4-nitrothiophenol (4-NTP) to 4-aminothiophenol (4-ATP) by NaBH4 through a 4,4'-dimercaptoazobenzene (trans-DMAB) intermediate and the subsequent oxidation of 4-ATP back to trans-DMAB upon the introduction of H2O2.

  8. Hepatitis B virus-associated diffuse large B-cell lymphoma: unique clinical features, poor outcome, and hepatitis B surface antigen-driven origin.

    PubMed

    Deng, Lijuan; Song, Yuqin; Young, Ken H; Hu, Shimin; Ding, Ning; Song, Weiwei; Li, Xianghong; Shi, Yunfei; Huang, Huiying; Liu, Weiping; Zheng, Wen; Wang, Xiaopei; Xie, Yan; Lin, Ningjing; Tu, Meifeng; Ping, Lingyan; Ying, Zhitao; Zhang, Chen; Sun, Yingli; Zhu, Jun

    2015-09-22

    While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known more than this epidemiologic evidence. We studied a cohort of 587 patients with DLBCL for HBV infection status, clinicopathologic features, and the immunoglobulin variable region in HBV surface antigen (HBsAg)-positive patients. Eighty-one (81/587, 13.8%) patients were HBsAg-positive. Compared with HBsAg-negative DLBCL, HBsAg-positive DLBCL displayed a younger median onset age (45 vs. 55 years), more frequent involvement of spleen or retroperitoneal lymph node (40.7% vs. 16.0% and 61.7% vs. 31.0% respectively, both p < 0.001), more advanced disease (stage III/IV: 76.5% vs 59.5%, p = 0.003), and significantly worse outcome (2-year overall survival: 47% versus 70%, p < 0.001). In HBsAg-positive DLBCL patients, almost all (45/47, 96%) amino acid sequences of heavy and light chain complementarity determining region 3 exhibited a high homology to antibodies specific for HBsAg, and the majority (45/50, 90%) of IgHV and IgLV genes were mutated. We conclude that 13.8% of DLBCL cases are HBV-associated in HBV-endemic China and show unique clinical features and poor outcomes. Furthermore, our study strongly suggests that HBV-associated DLBCL might arise from HBV antigen-selected B cells.

  9. Interglacial Surface Ocean Temperatures Reveal Strong Ocean-Atmosphere Linkages Between the Subtropical and Subpolar Regions

    NASA Astrophysics Data System (ADS)

    Kandiano, E.; Bauch, H. A.; Fahl, K.; Helmke, J.; Roehl, U.

    2008-12-01

    Investigating ocean-atmospheric processes of past interglaciations may provide a better understanding of the climatic development of the present warm period. Here we present a detailed reconstruction of the meridional sea surface temperature (SST) across MIS 11 using three sites: ODP 958 (off NW Africa), ODP 975 (western Mediterranean Sea) and M23414 (subpolar NE Atlantic). Sea surface temperatures (SST) were derived from foraminiferal assemblages and alkenones, further supported by planktic and benthic O-isotope records as well as by iron content, the latter as indicator for Saharan dust export and continental dryness. On a large scale, reconstructed SSTs reveal a close synchronism of environmental changes between all three sites. It shows that, before full interglacial conditions became established, there was a long-lasting, glacial- interglacial transition with a total temperature increase of about 10°C in the subtropical as well as in the subpolar North Atlantic. After the main glacial-interglacial transition was over, SSTs continued to rise and reached their maximum during, what could be considered, the upper main phase of high sea-level stand in MIS 11. In the western Mediterranean SSTs show several cooling events with amplitudes of up to 4°C during the early full-interglacial warm period. Off NW Africa this phase is characterized by rather humid conditions, as inferred from strongly decreased values of iron in the sediments, and successive changes in the foraminiferal assemblages. We assume that these rather wet conditions at the lower latitudes were related to an intensification of the West African monsoon that increased summer moisture flux over Northwest Africa and runoff into the Mediterranean. At the same time increased abundance of subtropical, deep- dwelling foraminiferal species are found in the subpolar region implying a strong linkage between the subtropical atmospheric circulation regime over NW Africa and the northward propagation, of

  10. Seismic structure of the southern Apennines as revealed by waveform modelling of regional surface waves

    NASA Astrophysics Data System (ADS)

    Ökeler, Ahmet; Gu, Yu Jeffrey; Lerner-Lam, Arthur; Steckler, Michael S.

    2009-09-01

    We investigate the crust and upper-mantle structures beneath the southern Apennine mountain chain using three-component seismograms from the Calabria-Apennine-Tyrrhenian/Subduction-Collision-Accretion Network (CAT/SCAN) array. Surface wave waveforms from three moderate-sized (Mw > 5.0) regional earthquakes are modelled using multiple frequencies (0.03-0.06 and 0.05-0.2 Hz) and both forward and linearized-inversion algorithms. Our best-fitting shear velocity models clearly reflect the major tectonic units where, for example, the average seismic structure at depths above 50 km beneath Apulia is substantially faster than beneath the Apennine mountain chain. We identify a prominent low-velocity channel under the mountain belt at depths below ~25-30 km and a secondary low-velocity zone at 6-12 km depth near Mt Vulture (a once active volcano). Speed variations between Love and Rayleigh waves provide further constraints on the fabric and dynamic processes. Our analysis indicates that the crustal low-velocity zones are highly anisotropic (maximum 14 per cent) and allow transversely polarized shear waves to travel faster than vertically polarized shear waves. The upper crustal anomaly reveals a layer of highly deformed rocks caused by past collisions and by the active normal faults cutting across the thrust sheets, whereas hot mantle upwelling may be responsible for a high-temperature, partially molten lower crust beneath the southern Apennines.

  11. Re-analysis of human immunodeficiency virus type 1 isolates from Cyprus and Greece, initially designated 'subtype I', reveals a unique complex A/G/H/K/? mosaic pattern.

    PubMed

    Paraskevis, D; Magiorkinis, M; Vandamme, A M; Kostrikis, L G; Hatzakis, A

    2001-03-01

    Human immunodeficiency virus type 1 (HIV-1) has been classified into three main groups and 11 distinct subtypes. Moreover, several circulating recombinant forms (CRFs) of HIV-1 have been recently documented to have spread widely causing extensive HIV-1 epidemics. A subtype, initially designated I (CRF04_cpx), was documented in Cyprus and Greece and was found to comprise regions of sequence derived from subtypes A and G as well as regions of unclassified sequence. Re-analysis of the three full-length CRF04_cpx sequences that were available revealed a mosaic genomic organization of unique complexity comprising regions of sequence from at least five distinct subtypes, A, G, H, K and unclassified regions. These strains account for approximately 2% of the total HIV-1-infected population in Greece, thus providing evidence of the great capability of HIV-1 to recombine and produce highly divergent strains which can be spread successfully through different infection routes.

  12. Structural constraints for the binding of short peptides to claudin-4 revealed by surface plasmon resonance.

    PubMed

    Ling, Jun; Liao, Hailing; Clark, Robin; Wong, Mandy Sze Man; Lo, David D

    2008-11-01

    Claudin family transmembrane proteins play an important role in tight junction structure and function in epithelial cells. Among the 24 isoforms identified in mice and humans, claudin-4 and -3 serve as the receptor for Clostridium perfringens enterotoxin (Cpe). The second extracellular loop (Ecl2) of claudin-4 is responsible for the binding to the C-terminal 30 amino acids of Cpe (Cpe30). To define the structural constraints for the claudin-4/Cpe30 interaction, a surface plasmon resonance (SPR) method was developed. GST fusions with claudin-4 revealed that Ecl2 with the downstream transmembrane domain of claudin-4 reconstituted the basic structural requirement for optimal binding activity to Cpe30, with affinity in the nanomolar range. Two 12-mer peptides selected by phage display against claudin-4-transfected CHO cells and a 12-mer Cpe mutant peptide also showed significant affinity for claudin-4 with this SPR assay, suggesting that a short peptide can establish stable contact with Ecl2 with nanomolar affinity. Alignment of these short peptides unveiled a common Ecl2 binding motif: . Whereas the short peptides bound native claudin-4 on transfected CHO cells in pull-down assays, only the larger Cpe30 peptide affected trans-epithelial electrical resistance (TER) in peptide-treated Caco-2BBe monolayers. Importantly, Cpe30 retained its binding to claudin-4 when fused to the C terminus of influenza hemagglutinin, demonstrating that its binding activity can be maintained in a different biochemical context. These studies may help in the design of assays for membrane receptor interactions with soluble ligands, and in applying new targeting ligands to delivering attached "cargo" proteins. PMID:18782762

  13. Direct surface analysis coupled to high-resolution mass spectrometry reveals heterogeneous composition of the cuticle of Hibiscus trionum petals.

    PubMed

    Giorio, Chiara; Moyroud, Edwige; Glover, Beverley J; Skelton, Paul C; Kalberer, Markus

    2015-10-01

    Plant cuticle, which is the outermost layer covering the aerial parts of all plants including petals and leaves, can present a wide range of patterns that, combined with cell shape, can generate unique physical, mechanical, or optical properties. For example, arrays of regularly spaced nanoridges have been found on the dark (anthocyanin-rich) portion at the base of the petals of Hibiscus trionum. Those ridges act as a diffraction grating, producing an iridescent effect. Because the surface of the distal white region of the petals is smooth and noniridescent, a selective chemical characterization of the surface of the petals on different portions (i.e., ridged vs smooth) is needed to understand whether distinct cuticular patterns correlate with distinct chemical compositions of the cuticle. In the present study, a rapid screening method has been developed for the direct surface analysis of Hibiscus trionum petals using liquid extraction surface analysis (LESA) coupled with high-resolution mass spectrometry. The optimized method was used to characterize a wide range of plant metabolites and cuticle monomers on the upper (adaxial) surface of the petals on both the white/smooth and anthocyanic/ridged regions, and on the lower (abaxial) surface, which is entirely smooth. The main components detected on the surface of the petals are low-molecular-weight organic acids, sugars, and flavonoids. The ridged portion on the upper surface of the petal is enriched in long-chain fatty acids, which are constituents of the wax fraction of the cuticle. These compounds were not detected on the white/smooth region of the upper petal surface or on the smooth lower surface. PMID:26335385

  14. Nanochemistry at the atomic scale revealed in hydrogen-induced semiconductor surface metallization

    NASA Astrophysics Data System (ADS)

    Derycke, Vincent; Soukiassian, Patrick G.; Amy, Fabrice; Chabal, Yves J.; D'Angelo, Marie D.; Enriquez, Hanna B.; Silly, Mathieu G.

    2003-04-01

    Passivation of semiconductor surfaces against chemical attack can be achieved by terminating the surface-dangling bonds with a monovalent atom such as hydrogen. Such passivation invariably leads to the removal of all surface states in the bandgap, and thus to the termination of non-metallic surfaces. Here we report the first observation of semiconductor surface metallization induced by atomic hydrogen. This result, established by using photo-electron and photo-absorption spectroscopies and scanning tunnelling techniques, is achieved on a Si-terminated cubic silicon carbide (SiC) surface. It results from competition between hydrogen termination of surface-dangling bonds and hydrogen-generated steric hindrance below the surface. Understanding the ingredient for hydrogen-stabilized metallization directly impacts the ability to eliminate electronic defects at semiconductor interfaces critical for microelectronics, provides a means to develop electrical contacts on high-bandgap chemically passive materials, particularly for interfacing with biological systems, and gives control of surfaces for lubrication, for example of nanomechanical devices.

  15. Nanochemistry at the atomic scale revealed in hydrogen-induced semiconductor surface metallization.

    PubMed

    Derycke, Vincent; Soukiassian, Patrick G; Amy, Fabrice; Chabal, Yves J; D'angelo, Marie D; Enriquez, Hanna B; Silly, Mathieu G

    2003-04-01

    Passivation of semiconductor surfaces against chemical attack can be achieved by terminating the surface-dangling bonds with a monovalent atom such as hydrogen. Such passivation invariably leads to the removal of all surface states in the bandgap, and thus to the termination of non-metallic surfaces. Here we report the first observation of semiconductor surface metallization induced by atomic hydrogen. This result, established by using photo-electron and photo-absorption spectroscopies and scanning tunnelling techniques, is achieved on a Si-terminated cubic silicon carbide (SiC) surface. It results from competition between hydrogen termination of surface-dangling bonds and hydrogen-generated steric hindrance below the surface. Understanding the ingredient for hydrogen-stabilized metallization directly impacts the ability to eliminate electronic defects at semiconductor interfaces critical for microelectronics, provides a means to develop electrical contacts on high-bandgap chemically passive materials, particularly for interfacing with biological systems, and gives control of surfaces for lubrication, for example of nanomechanical devices.

  16. Surface hardening induced by high flux plasma in tungsten revealed by nano-indentation

    NASA Astrophysics Data System (ADS)

    Terentyev, D.; Bakaeva, A.; Pardoen, T.; Favache, A.; Zhurkin, E. E.

    2016-08-01

    Surface hardness of tungsten after high flux deuterium plasma exposure has been characterized by nanoindentation. The effect of plasma exposure was rationalized on the basis of available theoretical models. Resistance to plastic penetration is enhanced within the 100 nm sub-surface region, attributed to the pinning of geometrically necessary dislocations on nanometric deuterium cavities - signature of plasma-induced defects and deuterium retention. Sub-surface extension of thereby registered plasma-induced damage is in excellent agreement with the results of alternative measurements. The study demonstrates suitability of nano-indentation to probe the impact of deposition of plasma-induced defects in tungsten on near surface plasticity under ITER-relevant plasma exposure conditions.

  17. Surface force measurements between titanium dioxide surfaces prepared by atomic layer deposition in electrolyte solutions reveal non-DLVO interactions: influence of water and argon plasma cleaning.

    PubMed

    Walsh, Rick B; Evans, Drew; Craig, Vincent S J

    2014-03-01

    Surface force measurements between titania surfaces in electrolyte solutions have previously revealed an unexplained long-range repulsive force at high pH, not described by Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory. Here, the surface forces between titania surfaces produced by atomic layer deposition (ALD) and cleaned using a variety of methods have been measured to determine the influence of the cleaning protocol on the measured forces and test the hypothesis that water plasma cleaning of the surface results in non-DLVO forces at high pH. For argon plasma and water plasma cleaned surfaces, a diffuse double layer repulsion and van der Waals attraction is observed near the isoelectric point. At high pH, the force remained repulsive up until contact, and no van der Waals attraction or adhesion was observed. Differences in the measured forces are explained by modification of the surface chemistry during cleaning, which alters the density of charged groups on the surface, but this cannot explain the observed disagreement with DLVO theory at high pH. PMID:24548170

  18. Physicochemical state of the nanotopographic surface of commercially pure titanium following anodization-hydrothermal treatment reveals significantly improved hydrophilicity and surface energy profiles.

    PubMed

    Takebe, Jun; Ito, Shigeki; Miura, Shingo; Miyata, Kyohei; Ishibashi, Kanji

    2012-01-01

    A method of coating commercially pure titanium (cpTi) implants with a highly crystalline, thin hydroxyapatite (HA) layer using discharge anodic oxidation followed by hydrothermal treatment (Spark discharged Anodic oxidation treatment ; SA-treated cpTi) has been reported for use in clinical dentistry. We hypothesized that a thin HA layer with high crystallinity and nanostructured anodic titanium oxide film on such SA-treated cpTi implant surfaces might be a crucial function of their surface-specific potential energy. To test this, we analyzed anodic oxide (AO) cpTi and SA-treated cpTi disks by SEM and AFM. Contact angles and surface free energy of each disk surface was measured using FAMAS software. High-magnification SEM and AFM revealed the nanotopographic structure of the anodic titanium oxide film on SA-treated cpTi; however, this was not observed on the AO cpTi surface. The contact angle and surface free energy measurements were also significantly different between AO cpTi and SA-treated cpTi surfaces (Tukey's, P<0.05). These data indicated that the change of physicochemical properties of an anodic titanium oxide film with HA crystals on an SA-treated cpTi surface may play a key role in the phenomenon of osteoconduction during the process of osseointegration.

  19. Finding needles in haystacks: scanning tunneling microscopy reveals the complex reactivity of Si(100) surfaces.

    PubMed

    Skibinski, Erik S; Hines, Melissa A

    2015-07-21

    Many chemical reactions-etching, growth, and catalytic-produce highly faceted surfaces. Examples range from the atomically flat silicon surfaces produced by anisotropic etchants to the wide variety of faceted nanoparticles, including cubes, wires, plates, tetrapods, and more. This faceting is a macroscopic manifestation of highly site-specific surface reactions. In this Account, we show that these site-specific reactions literally write a record of their chemical reactivity in the morphology of the surface-a record that can be quantified with scanning tunneling microscopy. Paradoxically, the sites targeted by these highly site-specific reactions are extremely rare. This paradox can be understood from a simple kinetic argument. An etchant that produces atomically flat surfaces must rapidly etch every surface site except the terrace atoms on the perfectly flat surface. As a result, the etch morphology is dominated by the least reactive species (here, the terrace sites), not the most reactive species. In contrast, the most interesting chemical species-the site where the reaction occurs most rapidly and most selectively-is the hardest one to find. This highly reactive site, the key to the reaction, is the needle in the haystack, often occurring in densities far below 1% of a monolayer and thus invisible to surface spectroscopies. This kinetic argument is quite general and applies to a wide variety of reactions, not just etching reactions. Understanding these highly site-specific reactions requires a combination of experimental and computational techniques with both exquisite defect sensitivity and high chemical sensitivity. In this Account, we present examples of highly site-specific chemistry on the technologically important face of silicon, Si(100). In one example, we show that the high reactivity of one particular surface site, a silicon dihydride bound to a silicon monohydride, or an "α-dihydride", provides a fundamental explanation for anisotropic silicon etching

  20. The surface morphology of human B lymphocytes as revealed by immunoelectron microscopy

    PubMed Central

    1975-01-01

    Surface immunoglobulins (sIg) were detected on human lymphocytes by immunoelectron microscopy with peroxidase-conjugated antibodies. Blood, marrow, and thymus cells from normal individuals and patients with lymphoproliferative disorders were examined. Samples were fixed before exposure to specific reagents. Normal lymphocyts with detectable sIg, i.e. B lymphocytes, were characterized by a villous surface; nonlabeled blood lymphocytes and thymocytes were smooth cells. Intermediate cells were also found which in sections appeared moderately villous and labeled, thus identified as B lymphocytes. Further evidence for a relationship between villous surface and sIg was given by the finding of a few lymphocytes with polar concentration of labeled microvilli. In chronic lymphocytic leukemia patients, most cells exhibited a villous surface with parallel variations of the number of microvilli and of anti-immunoglobulin-binding capacity. However, some labeled smooth blastic cells were also observed. On the other hand, abnormal lymphocytes from Sezary's syndrome which could exhibit segments of villous membrane had no detectable sIg. This study confirms that in most cases human B lymphocytes have a characteristic surface appearance and that the detection of sIg in normal lymphocytes correlates with the presence of microvilli. PMID:123001

  1. Chemical heterogeneity on Mercury's surface revealed by the MESSENGER X-Ray Spectrometer

    NASA Astrophysics Data System (ADS)

    Weider, Shoshana Z.; Nittler, Larry R.; Starr, Richard D.; McCoy, Timothy J.; Stockstill-Cahill, Karen R.; Byrne, Paul K.; Denevi, Brett W.; Head, James W.; Solomon, Sean C.

    2012-10-01

    We present the analysis of 205 spatially resolved measurements of the surface composition of Mercury from MESSENGER's X-Ray Spectrometer. The surface footprints of these measurements are categorized according to geological terrain. Northern smooth plains deposits and the plains interior to the Caloris basin differ compositionally from older terrain on Mercury. The older terrain generally has higher Mg/Si, S/Si, and Ca/Si ratios, and a lower Al/Si ratio than the smooth plains. Mercury's surface mineralogy is likely dominated by high-Mg mafic minerals (e.g., enstatite), plagioclase feldspar, and lesser amounts of Ca, Mg, and/or Fe sulfides (e.g., oldhamite). The compositional difference between the volcanic smooth plains and the older terrain reflects different abundances of these minerals and points to the crystallization of the smooth plains from a more chemically evolved magma source. High-degree partial melts of enstatite chondrite material provide a generally good compositional and mineralogical match for much of the surface of Mercury. An exception is Fe, for which the low surface abundance on Mercury is still higher than that of melts from enstatite chondrites and may indicate an exogenous contribution from meteoroid impacts.

  2. Biomembrane interactions reveal the mechanism of action of surface-immobilized host defense IDR-1010 peptide.

    PubMed

    Gao, Guangzheng; Cheng, John T J; Kindrachuk, Jason; Hancock, Robert E W; Straus, Suzana K; Kizhakkedathu, Jayachandran N

    2012-02-24

    Dissecting the mechanism of action of surface-tethered antimicrobial and immunomodulatory peptides is critical to the design of optimized anti-infection coatings on biomedical devices. To address this, we compared the biomembrane interactions of host defense peptide IDR-1010cys (1) in free form, (2) as a soluble polymer conjugate, and (3) with one end tethered to a solid support with model bacterial and mammalian lipid membranes. Our results show that IDR-1010cys in all three distinct forms interacted with bacterial and mammalian lipid vesicles, but the extent of the interactions as monitored by the induction of secondary structure varied. The enhanced interaction of surface-tethered peptides is well correlated with their very good antimicrobial activities. Our results demonstrate that there may be a difference in the mechanism of action of surface-tethered versus free IDR-1010cys.

  3. Surface oxidation of tin chalcogenide nanocrystals revealed by 119Sn-Mössbauer spectroscopy.

    PubMed

    de Kergommeaux, Antoine; Faure-Vincent, Jérôme; Pron, Adam; de Bettignies, Rémi; Malaman, Bernard; Reiss, Peter

    2012-07-18

    Narrow band gap tin(II) chalcogenide (SnS, SnSe, SnTe) nanocrystals are of high interest for optoelectronic applications such as thin film solar cells or photodetectors. However, charge transfer and charge transport processes strongly depend on nanocrystals' surface quality. Using (119)Sn-Mössbauer spectroscopy, which is the most sensitive tool for probing the Sn oxidation state, we show that SnS nanocrystals exhibit a Sn((IV))/Sn((II)) ratio of around 20:80 before and 40:60 after five minutes exposure to air. Regardless of the tin or sulfur precursors used, similar results are obtained using six different synthesis protocols. The Sn((IV)) content before air exposure arises from surface related SnS(2) and Sn(2)S(3) species as well as from surface Sn atoms bound to oleic acid ligands. The increase of the Sn((IV)) content upon air exposure results from surface oxidation. Full oxidation of the SnS nanocrystals without size change is achieved by annealing at 500 °C in air. With the goal to prevent surface oxidation, SnS nanocrystals are capped with a cadmium-phosphonate complex. A broad photoluminescence signal centered at 600 nm indicates successful capping, which however does not reduce the air sensitivity. Finally we demonstrate that SnSe nanocrystals exhibit a very similar behavior with a Sn((IV))/Sn((II)) ratio of 43:57 after air exposure. In the case of SnTe nanocrystals, the ratio of 55:45 is evidence of a more pronounced tendency for oxidation. These results demonstrate that prior to their use in optoelectronics further surface engineering of tin chalcogenide nanocrystals is required, which otherwise have to be stored and processed under inert atmosphere.

  4. Atmospheric Drivers of Greenland Surface Melt Revealed by Self-Organizing Maps

    NASA Technical Reports Server (NTRS)

    Mioduszewski, J. R.; Rennermalm, A. K.; Hammann, A.; Tedesco, M.; Noble, E. U.; Stroeve, J. C.; Mote, T. L.

    2016-01-01

    Recent acceleration in surface melt on the Greenland ice sheet (GrIS) has occurred concurrently with a rapidly warming Arctic and has been connected to persistent, anomalous atmospheric circulation patterns over Greenland. To identify synoptic setups favoring enhanced GrIS surface melt and their decadal changes, we develop a summer Arctic synoptic climatology by employing self-organizing maps. These are applied to daily 500 hPa geopotential height fields obtained from the Modern Era Retrospective Analysis for Research and Applications reanalysis, 1979-2014. Particular circulation regimes are related to meteorological conditions and GrIS surface melt estimated with outputs from the Modèle Atmosphérique Régional. Our results demonstrate that the largest positive melt anomalies occur in concert with positive height anomalies near Greenland associated with wind, temperature, and humidity patterns indicative of strong meridional transport of heat and moisture. We find an increased frequency in a 500 hPa ridge over Greenland coinciding with a 63% increase in GrIS melt between the 1979-1988 and 2005-2014 periods, with 75.0% of surface melt changes attributed to thermodynamics, 17% to dynamics, and 8.0% to a combination. We also confirm that the 2007-2012 time period has the largest dynamic forcing relative of any period but also demonstrate that increased surface energy fluxes, temperature, and moisture separate from dynamic changes contributed more to melt even during this period. This implies that GrIS surface melt is likely to continue to increase in response to an ever warmer future Arctic, regardless of future atmospheric circulation patterns.

  5. Surface area and cortical thickness descriptors reveal different attributes of the structural human brain networks.

    PubMed

    Sanabria-Diaz, Gretel; Melie-García, Lester; Iturria-Medina, Yasser; Alemán-Gómez, Yasser; Hernández-González, Gertrudis; Valdés-Urrutia, Lourdes; Galán, Lídice; Valdés-Sosa, Pedro

    2010-05-01

    Recently, a related morphometry-based connection concept has been introduced using local mean cortical thickness and volume to study the underlying complex architecture of the brain networks. In this article, the surface area is employed as a morphometric descriptor to study the concurrent changes between brain structures and to build binarized connectivity graphs. The statistical similarity in surface area between pair of regions was measured by computing the partial correlation coefficient across 186 normal subjects of the Cuban Human Brain Mapping Project. We demonstrated that connectivity matrices obtained follow a small-world behavior for two different parcellations of the brain gray matter. The properties of the connectivity matrices were compared to the matrices obtained using the mean cortical thickness for the same cortical parcellations. The topology of the cortical thickness and surface area networks were statistically different, demonstrating that both capture distinct properties of the interaction or different aspects of the same interaction (mechanical, anatomical, chemical, etc.) between brain structures. This finding could be explained by the fact that each descriptor is driven by distinct cellular mechanisms as result of a distinct genetic origin. To our knowledge, this is the first time that surface area is used to study the morphological connectivity of brain networks. PMID:20083210

  6. Revealing the role of catechol moieties in the interactions between peptides and inorganic surfaces.

    PubMed

    Das, Priyadip; Reches, Meital

    2016-08-18

    Catechol (1,2-dihydroxy benzene) moieties are being widely used today in new adhesive technologies. Understanding their mechanism of action is therefore of high importance for developing their applications in materials science. This paper describes a single-molecule study of the interactions between catechol-related amino acid residues and a well-defined titanium dioxide (TiO2) surface. It is the first quantified measurement of the adhesion of these residues with a well-defined TiO2 surface. Single-molecule force spectroscopy measurements with AFM determined the role of different substitutions of the catechol moiety on the aromatic ring in the adhesion to the surface. These results shed light on the nature of interactions between these residues and inorganic metal oxide surfaces. This information is important for the design and fabrication of catechol-based materials such as hydrogels, coatings, and composites. Specifically, the interaction with TiO2 is important for the development of solar cells. PMID:27503417

  7. Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses.

    PubMed

    Song, Hao; Qi, Jianxun; Haywood, Joel; Shi, Yi; Gao, George F

    2016-05-01

    The association of Zika virus (ZIKV) infections with microcephaly has resulted in an ongoing public-health emergency. Here we report the crystal structure of a C-terminal fragment of ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune evasion. Comparison with West Nile and dengue virus NS1 structures reveals conserved features but diverse electrostatic characteristics at host-interaction interfaces, thus possibly implying different modes of flavivirus pathogenesis.

  8. Rapid regional surface uplift of the northern Altiplano plateau revealed by multiproxy paleoclimate reconstruction

    NASA Astrophysics Data System (ADS)

    Kar, Nandini; Garzione, Carmala N.; Jaramillo, Carlos; Shanahan, Timothy; Carlotto, Victor; Pullen, Alex; Moreno, Federico; Anderson, Veronica; Moreno, Enrique; Eiler, John

    2016-08-01

    The central Altiplano is inferred to have experienced ∼ 2.5 ± 1km surface uplift between ∼10 and 6 Ma, while the southern Altiplano experienced a similar magnitude of surface uplift that began earlier, between ∼16 and 9 Ma. To properly constrain the along strike timing of the Altiplano plateau surface uplift, it is necessary to know how and when the northernmost part of the Altiplano plateau evolved. We reconstruct the paleoclimate and infer the corresponding paleoelevation from the Miocene-Pliocene deposits of the Descanso-Yauri basin (14-15°S) in the northernmost part of the Altiplano plateau using 4 different proxies, including carbonate clumped isotope composition (i.e., Δ47 values), carbonate δ18Oc, leaf wax δDwax and pollen assemblages from paleosol, lacustrine and palustrine carbonates and organic-rich sediments. The isotopic signatures reflect past climate conditions of mean annual air temperature (Δ47) and meteoric water isotope values (δ18Oc, δDwax). Our results show that the northernmost plateau remained at low elevation (0.9 ± 0.8 to 2.1 ± 0.9km) until late Miocene time (∼9 Ma) characterized by ∼15 °C warmer than modern temperature (mean annual air temperature of 23 ± 4 °C, 2σ), low elevation vegetation and precipitation signature with reconstructed □ δ18Omw (VSMOW) of - 8.3 ± 2.0 ‰ (2 σ) from carbonate (δ18Oc) and - 8.6 ± 1.8 ‰ (2 σ) from leaf wax (δDwax). Modern elevations of 4 km were not reached until 5.4 ± 1.0Ma, as indicated by a negative shift in δDwax (VSMOW) from - 143.4 ± 12.8 ‰ (2 σ) to - 209.2 ± 21.1 ‰ (2 σ) between 9.1 ± 0.7 and 5.4 ± 1.0Ma. The timing of surface uplift of the northernmost Altiplano is consistent with the evidence for late Miocene surface uplift of the central Altiplano (16-19°S) between 10 and 6 Ma, and indicates that regional scale uplift in the northern-central plateau significantly postdates the onset of surface uplift in the southern Altiplano (19-22°S) between ∼16

  9. Revealing the fate of cell surface human P-glycoprotein (ABCB1): The lysosomal degradation pathway.

    PubMed

    Katayama, Kazuhiro; Kapoor, Khyati; Ohnuma, Shinobu; Patel, Atish; Swaim, William; Ambudkar, Indu S; Ambudkar, Suresh V

    2015-10-01

    P-glycoprotein (P-gp) transports a variety of chemically dissimilar amphipathic compounds including anticancer drugs. Although mechanisms of P-gp drug transport are widely studied, the pathways involving its internalization are poorly understood. The present study is aimed at elucidating the pathways involved in degradation of cell surface P-gp. The fate of P-gp at the cell surface was determined by biotinylating cell surface proteins followed by flow cytometry and Western blotting. Our data shows that the half-life of endogenously expressed P-gp is 26.7±1.1 h in human colorectal cancer HCT-15 cells. Treatment of cells with Bafilomycin A1 (BafA1) a vacuolar H+ ATPase inhibitor increased the half-life of P-gp at the cell surface to 36.1±0.5 h. Interestingly, treatment with the proteasomal inhibitors MG132, MG115 or lactacystin alone did not alter the half-life of the protein. When cells were treated with both lysosomal and proteasomal inhibitors (BafA1 and MG132), the half-life was further prolonged to 39-50 h. Functional assays done with rhodamine 123 or calcein-AM, fluorescent substrates of P-gp, indicated that the transport function of P-gp was not affected by either biotinylation or treatment with BafA1 or proteasomal inhibitors. Immunofluorescence studies done with the antibody against lysosomal marker LAMP1 and the P-gp-specific antibody UIC2 in permeabilized cells indicated that intracellular P-gp is primarily localized in the lysosomal compartment. Our results suggest that the lysosomal degradation system could be targeted to increase the sensitivity of P-gp- expressing cancer cells towards chemotherapeutic drugs.

  10. Cryovolcanic features on Titan's surface as revealed by the Cassini Titan Radar Mapper

    USGS Publications Warehouse

    Lopes, R.M.C.; Mitchell, K.L.; Stofan, E.R.; Lunine, J.I.; Lorenz, R.; Paganelli, F.; Kirk, R.L.; Wood, C.A.; Wall, S.D.; Robshaw, L.E.; Fortes, A.D.; Neish, C.D.; Radebaugh, J.; Reffet, E.; Ostro, S.J.; Elachi, C.; Allison, M.D.; Anderson, Y.; Boehmer, R.; Boubin, G.; Callahan, P.; Encrenaz, P.; Flamini, E.; Francescetti, G.; Gim, Y.; Hamilton, G.; Hensley, S.; Janssen, M.A.; Johnson, W.T.K.; Kelleher, K.; Muhleman, D.O.; Ori, G.; Orosei, R.; Picardi, G.; Posa, F.; Roth, L.E.; Seu, R.; Shaffer, S.; Soderblom, L.A.; Stiles, B.; Vetrella, S.; West, R.D.; Wye, L.; Zebker, H.A.

    2007-01-01

    The Cassini Titan Radar Mapper obtained Synthetic Aperture Radar images of Titan's surface during four fly-bys during the mission's first year. These images show that Titan's surface is very complex geologically, showing evidence of major planetary geologic processes, including cryovolcanism. This paper discusses the variety of cryovolcanic features identified from SAR images, their possible origin, and their geologic context. The features which we identify as cryovolcanic in origin include a large (180 km diameter) volcanic construct (dome or shield), several extensive flows, and three calderas which appear to be the source of flows. The composition of the cryomagma on Titan is still unknown, but constraints on rheological properties can be estimated using flow thickness. Rheological properties of one flow were estimated and appear inconsistent with ammonia-water slurries, and possibly more consistent with ammonia-water-methanol slurries. The extent of cryovolcanism on Titan is still not known, as only a small fraction of the surface has been imaged at sufficient resolution. Energetic considerations suggest that cryovolcanism may have been a dominant process in the resurfacing of Titan. ?? 2006 Elsevier Inc.

  11. Oxygen anomaly in near surface carbon dioxide reveals deep stratospheric intrusion.

    PubMed

    Liang, Mao-Chang; Mahata, Sasadhar

    2015-01-01

    Stratosphere-troposphere exchange could be enhanced by tropopause folding, linked to variability in the subtropical jet stream. Relevant to tropospheric biogeochemistry is irreversible transport from the stratosphere, associated with deep intrusions. Here, oxygen anomalies in near surface air CO2 are used to study the irreversible transport from the stratosphere, where the triple oxygen isotopes of CO2 are distinct from those originating from the Earth's surface. We show that the oxygen anomaly in CO2 is observable at sea level and the magnitude of the signal increases during the course of our sampling period (September 2013-February 2014), concordant with the strengthening of the subtropical jet system and the East Asia winter monsoon. The trend of the anomaly is found to be 0.1‰/month (R(2) = 0.6) during the jet development period in October. Implications for utilizing the oxygen anomaly in CO2 for CO2 biogeochemical cycle study and stratospheric intrusion flux at the surface are discussed. PMID:26081178

  12. Chemical Heterogeneity on Mercury's Surface Revealed by the MESSENGER X-ray Spectrometer

    NASA Technical Reports Server (NTRS)

    Weider, Shoshana Z.; Nittler, Larry R.; Starr, Richard D.; McCoy, Timothy J.; Stockstill-Cahill, Karen R.; Byrne, Paul K.; Denevi, Brett W.; Head, James W.; Solomon, Sean C.

    2012-01-01

    We present the analysis of 205 spatially resolved measurements of the surfacecomposition of Mercury from MESSENGERs X-Ray Spectrometer. The surfacefootprints of these measurements are categorized according to geological terrain. Northernsmooth plains deposits and the plains interior to the Caloris basin differ compositionallyfrom older terrain on Mercury. The older terrain generally has higher MgSi, SSi, andCaSi ratios, and a lower AlSi ratio than the smooth plains. Mercurys surface mineralogyis likely dominated by high-Mg mafic minerals (e.g., enstatite), plagioclase feldspar, andlesser amounts of Ca, Mg, andor Fe sulfides (e.g., oldhamite). The compositionaldifference between the volcanic smooth plains and the older terrain reflects differentabundances of these minerals and points to the crystallization of the smooth plains from amore chemically evolved magma source. High-degree partial melts of enstatite chondritematerial provide a generally good compositional and mineralogical match for much ofthe surface of Mercury. An exception is Fe, for which the low surface abundance onMercury is still higher than that of melts from enstatite chondrites and may indicate anexogenous contribution from meteoroid impacts.

  13. Binding of the Galanthus nivalis agglutinin to thymocytes reveals alterations in surface glycosylation during T-cell development.

    PubMed

    Sinkora, J; Kolínská, J; Reháková, Z; Cerný, J; Doubravská, L

    2002-02-01

    Surface binding of the Galanthus nivalis agglutinin (GNA) to thymocyte subsets has been studied in pigs and rodents by multicolour flow cytometry. In all the species examined, analogous staining profiles have been recorded. Counter-staining with anti-CD3epsilon, anti-CD4 and anti-CD8 monoclonal antibodies (MoAb) revealed that a significant increase of the GNA targets on the cell surface occurred during early thymocyte differentiation and reached its maximum at the level of the CD3loCD4+CD8+ small cortical thymocyte. This was followed by a decrease in the GNA binding capacity upon terminal maturation to the single positive thymocytes. PAGE analysis has revealed a dominant GNA-binding glycoprotein (molar mass approx. 90 kDa) present on thymocyte plasma membranes and absent on the surface of splenic lymphocytes, although both the whole cell lysates from both organs contained GNA ligands of the same size. Our findings are in agreement with previous data showing that immature thymocytes differ from their mature counterparts and peripheral T lymphocytes in the surface glycosylation pattern, and support the hypothesis that lectin-glycoprotein interaction plays a significant role in the cell-to-cell crosstalk in the thymic cortex.

  14. HUBBLE REVEALS HUGE CRATER ON THE SURFACE OF THE ASTEROID VESTA

    NASA Technical Reports Server (NTRS)

    2002-01-01

    [left] A NASA Hubble Space Telescope image of the asteroid Vesta, taken in May 1996 when the asteroid was 110 million miles from Earth. The asymmetry of the asteroid and 'nub' and the south pole is suggestive that it suffered a large impact event. The image was digitally restored to yield an effective scale of six miles per pixel (picture element). [center] A color-encoded elevation map of Vesta clearly shows the giant 285- mile diameter impact basin and 'bull's-eye' central peak. The map was constructed from 78 Wide Field Planetary Camera 2 pictures. Surface topography was estimated by noting irregularities along the limb and at the terminator (day/night boundary) where shadows are enhanced by the low Sun angle. [right] A 3-D computer model of the asteroid Vesta synthesized from Hubble topographic data. The crater's 8-mile high central peak can clearly be seen near the pole. The surface texture on the model is artificial, and is not representative of the true brightness variations on the asteroid. Elevation features have not been exaggerated. Photo Credit: Ben Zellner (Georgia Southern University), Peter Thomas (Cornell University), NASA

  15. Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration

    PubMed Central

    Sekiya, Tetsuji; Holley, Matthew C.; Hashido, Kento; Ono, Kazuya; Shimomura, Koichiro; Horie, Rie T.; Hamaguchi, Kiyomi; Yoshida, Atsuhiro; Sakamoto, Tatsunori; Ito, Juichi

    2015-01-01

    Cell transplantation therapy has long been investigated as a therapeutic intervention for neurodegenerative disorders, including spinal cord injury, Parkinson’s disease, and amyotrophic lateral sclerosis. Indeed, patients have high hopes for a cell-based therapy. However, there are numerous practical challenges for clinical translation. One major problem is that only very low numbers of donor cells survive and achieve functional integration into the host. Glial scar tissue in chronic neurodegenerative disorders strongly inhibits regeneration, and this inhibition must be overcome to accomplish successful cell transplantation. Intraneural cell transplantation is considered to be the best way to deliver cells to the host. We questioned this view with experiments in vivo on a rat glial scar model of the auditory system. Our results show that intraneural transplantation to the auditory nerve, preceded by chondroitinase ABC (ChABC)-treatment, is ineffective. There is no functional recovery, and almost all transplanted cells die within a few weeks. However, when donor cells are placed on the surface of a ChABC-treated gliotic auditory nerve, they autonomously migrate into it and recapitulate glia- and neuron-guided cell migration modes to repair the auditory pathway and recover auditory function. Surface transplantation may thus pave the way for improved functional integration of donor cells into host tissue, providing a less invasive approach to rescue clinically important neural tracts. PMID:26080415

  16. Superresolution fluorescence mapping of single-nanoparticle catalysts reveals spatiotemporal variations in surface reactivity

    PubMed Central

    Zhang, Yuwei; Lucas, J. Matthew; Song, Ping; Beberwyck, Brandon; Fu, Qiang; Xu, Weilin; Alivisatos, A. Paul

    2015-01-01

    For the practical application of nanocatalysts, it is desirable to understand the spatiotemporal fluctuations of nanocatalytic activity at the single-nanoparticle level. Here we use time-lapsed superresolution mapping of single-molecule catalysis events on individual nanoparticles to observe time-varying changes in the spatial distribution of catalysis events on Sb-doped TiO2 nanorods and Au triangle nanoplates. Compared with the active sites on well-defined surface facets, the defects of the nanoparticle catalysts possess higher intrinsic reactivity but lower stability. Corners and ends are more reactive but also less stable than flat surfaces. Averaged over time, the most stable sites dominate the total apparent activity of single nanocatalysts. However, the active sites with higher intrinsic activity but lower stability show activity at earlier time points before deactivating. Unexpectedly, some active sites are found to recover their activity (“self-healing”) after deactivation, which is probably due to desorption of the adsorbate. Our superresolution measurement of different types of active catalytic sites, over both space and time, leads to a more comprehensive understanding of reactivity patterns and may enable the design of new and more productive heterogeneous catalysts. PMID:26150516

  17. Eye movements reveal distinct encoding patterns for number and cumulative surface area in random dot arrays

    PubMed Central

    Odic, Darko; Halberda, Justin

    2015-01-01

    Humans can quickly and intuitively represent the number of objects in a scene using visual evidence through the Approximate Number System (ANS). But the computations that support the encoding of visual number—the transformation from the retinal input into ANS representations—remain controversial. Two types of number encoding theories have been proposed: those arguing that number is encoded through a dedicated, enumeration computation, and those arguing that visual number is inferred from nonnumber specific visual features, such as surface area, density, convex hull, etc. Here, we attempt to adjudicate between these two theories by testing participants on both a number and a cumulative area task while also tracking their eye-movements. We hypothesize that if approximate number and surface area depend on distinct encoding computations, saccadic signatures should be distinct for the two tasks, even if the visual stimuli are identical. Consistent with this hypothesis, we find that discriminating number versus cumulative area modulates both where participants look (i.e., participants spend more time looking at the more numerous set in the number task and the larger set in the cumulative area task), and how participants look (i.e., cumulative area encoding shows fewer, longer saccades, while number encoding shows many short saccades and many switches between targets). We further identify several saccadic signatures that are associated with task difficulty and correct versus incorrect trials for both dimensions. These results suggest distinct encoding algorithms for number and cumulative area extraction, and thereby distinct representations of these dimensions. PMID:26575191

  18. Coseismic landslides reveal near-surface rock strength in a high-relief tectonically active setting

    USGS Publications Warehouse

    Gallen, Sean F; Clark, Marin K; Godt, Jonathan W.

    2014-01-01

    We present quantitative estimates of near-surface rock strength relevant to landscape evolution and landslide hazard assessment for 15 geologic map units of the Longmen Shan, China. Strength estimates are derived from a novel method that inverts earthquake peak ground acceleration models and coseismic landslide inventories to obtain material proper- ties and landslide thickness. Aggregate rock strength is determined by prescribing a friction angle of 30° and solving for effective cohesion. Effective cohesion ranges are from 70 kPa to 107 kPa for 15 geologic map units, and are approximately an order of magnitude less than typical laboratory measurements, probably because laboratory tests on hand-sized specimens do not incorporate the effects of heterogeneity and fracturing that likely control near-surface strength at the hillslope scale. We find that strength among the geologic map units studied varies by less than a factor of two. However, increased weakening of units with proximity to the range front, where precipitation and active fault density are the greatest, suggests that cli- matic and tectonic factors overwhelm lithologic differences in rock strength in this high-relief tectonically active setting.

  19. Light scattered by model phantom bacteria reveals molecular interactions at their surface

    NASA Astrophysics Data System (ADS)

    Ghetta, A.; Prosperi, D.; Mantegazza, F.; Panza, L.; Riva, S.; Bellini, T.

    2005-11-01

    Testing molecular interactions is an ubiquitous need in modern biology and molecular medicine. Here, we present a qualitative and quantitative method rooted in the basic properties of the scattering of light, enabling detailed measurement of ligand-receptor interactions occurring on the surface of colloids. The key factor is the use of receptor-coated nanospheres matched in refractive index with water and therefore optically undetectable ("phantom") when not involved in adhesion processes. At the occurrence of ligand binding at the receptor sites, optically unmatched material adsorbs on the nanoparticle surface, giving rise to an increment in their scattering cross section up to a maximum corresponding to saturated binding sites. The analysis of the scattering growth pattern enables extracting the binding affinity. This label-free method has been assessed through the determination of the binding constant of the antibiotic vancomycin with the tripeptide L-Lys-D-Ala-D-Ala and of the vancomycin dimerization constant. We shed light on the role of chelate effect and molecular hindrance in the activity of this glycopeptide. binding affinity | nanoparticles | vancomycin | ligand-receptor recognition

  20. 10Be surface exposure dating reveals strong active deformation in the central Andean backarc interior

    NASA Astrophysics Data System (ADS)

    García Morabito, Ezequiel; Terrizzano, Carla; Zech, Roland; Willett, Sean; Yamin, Marcela; Haghipour, Negar; Wuethrich, Lorenz; Christl, Marcus; María Cortes, José; Ramos, Victor

    2016-04-01

    Understanding the deformation associated with active thrust wedges is essential to evaluate seismic hazard. How is active faulting distributed throughout the wedge, and how much deformation is taken up by individual structures? We address these questions for our study region, the central Andean backarc of Argentina. We combined a structural and geomorphological approach with surface exposure dating (10Be) of alluvial fans and strath terraces in two key localities at ~32° S: the Cerro Salinas, located in the active orogenic front of the Precordillera, and the Barreal block in the interior of the Andean mountain range. We analysed 22 surface samples and 6 depth profiles. At the thrust front, the oldest terrace (T1) yields an age of 100-130 ka, the intermediate terrace (T2) between 40-95 ka, and the youngest terrace (T3) an age of ~20 ka. In the Andean interior, T1´ dates to 117-146 ka, T2´ to ~70 ka, and T3´ to ~20 ka, all calculations assuming negligible erosion and using the scaling scheme for spallation based on Lal 1991, Stone 2000. Vertical slip rates of fault offsets are 0.3-0.5 mm/yr and of 0.6-1.2 mm/yr at the thrust front and in the Andean interior, respectively. Our results highlight: i) fault activity related to the growth of the Andean orogenic wedge is not only limited to a narrow thrust front zone. Internal structures have been active during the last 150 ka, ii) deformation rates in the Andean interior are comparable or even higher that those estimated and reported along the emerging thrust front, iii) distribution of active faulting seems to account for unsteady state conditions, and iv) seismic hazards may be more relevant in the internal parts of the Andean orogen than assumed so far. References Lal, D., 1991: Cosmic ray labeling of erosion surfaces: In situ nuclide production rates and erosion models. Earth and Planetary Science Letters 104: 424-439. Stone, J.O., 2000: Air pressure and cosmogenic isotope production. Journal of Geophysical

  1. Sources of mercury to San Francisco Bay surface sediment as revealed by mercury stable isotopes

    USGS Publications Warehouse

    Gehrke, Gretchen E.; Blum, Joel D.; Marvin-DePasquale, Mark

    2011-01-01

    Mercury (Hg) concentrations and isotopic compositions were examined in shallow-water surface sediment (0–2 cm) from San Francisco (SF) Bay to determine the extent to which historic Hg mining contributes to current Hg contamination in SF Bay, and to assess the use of Hg isotopes to trace sources of contamination in estuaries. Inter-tidal and wetland sediment had total Hg (HgT) concentrations ranging from 161 to 1529 ng/g with no simple gradients of spatial variation. In contrast, inter-tidal and wetland sediment displayed a geographic gradient of δ202Hg values, ranging from -0.30% in the southern-most part of SF Bay (draining the New Almaden Hg District) to -0.99% in the northern-most part of SF Bay near the Sacramento–San Joaquin River Delta. Similar to SF Bay inter-tidal sediment, surface sediment from the Alviso Slough channel draining into South SF Bay had a δ202Hg value of -0.29%, while surface sediment from the Cosumnes River and Sacramento–San Joaquin River Delta draining into north SF Bay had lower average δ202Hg values of -0.90% and -0.75%, respectively. This isotopic trend suggests that Hg-contaminated sediment from the New Almaden Hg District mixes with Hg-contaminated sediment from a low δ202Hg source north of SF Bay. Tailings and thermally decomposed ore (calcine) from the New Idria Hg mine in the California Coast Range had average δ202Hg values of -0.37 and +0.03%, respectively, showing that Hg calcination fractionates Hg isotopes resulting in Hg contamination from Hg(II) mine waste products with higher δ202Hg values than metallic Hg(0) produced from Hg mines. Thus, there is evidence for at least two distinct isotopic signals for Hg contamination in SF Bay: Hg associated with calcine waste materials at Hg mines in the Coast Range, such as New Almaden and New Idria; and Hg(0) produced from these mines and used in placer gold mines and/or in other industrial processes in the Sierra Nevada region and SF Bay area.

  2. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; Johns, Douglas G.; Charles, M. Arthur; Ren, Gang

    2015-03-01

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

  3. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    SciTech Connect

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; Johns, Douglas G.; Charles, M. Arthur; Ren, Gang

    2015-03-04

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

  4. The evolution of the clear air convective layer revealed by surface-based remote sensors

    NASA Technical Reports Server (NTRS)

    Noonkester, V. R.

    1976-01-01

    Results are reported for simultaneous observations of the growth and decay of the clear-air convective mixing layer near a coastline, which were made with an FM-CW radar, a high-power narrow-beam S-band radar, and an acoustic echo sounder. The main purpose of this study was to determine the relationship between the rise rate of the convective depth and the lapse rate of temperature, particularly in the morning hours. The results indicate that the three remote sensors can provide excellent mutually supporting data on the convective depth. It is found that this depth is well behaved during the day and that its rise rate varies roughly linearly with the inverse square root of the temperature lapse rate during the morning. The data suggest that some models concerning the rise rate require modification, since these models imply that the surface heat flux would have to be unreasonably large to produce the observed relationship.

  5. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    DOE PAGESBeta

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; et al

    2015-03-04

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobicmore » environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.« less

  6. Lead isotopes in marine surface sediments reveal historical use of leaded fuel.

    PubMed

    Larsen, Martin M; Blusztajn, Jerzy S; Andersen, Ole; Dahllöf, Ingela

    2012-11-01

    Analyses of lead (Pb) isotopes have been performed in terrestrial and fresh water environments to estimate historical uses of leaded fuel, but so far this method has not been employed in studies of world-wide marine surface sediments. We analyzed Pb and its isotopes in 23 surface sediments from four continents collected during the Galathea 3 expedition in 2006-2007. To enhance the anthropogenic signal, a partial digestion using nitric acid was performed. The concentrations of Pb, Th, U and Al were determined with an ICP-Quadrupole MS, and Pb-isotope ratios with an ICP-multi-collector MS. The samples could be divided into three groups: Harbor areas in larger cities with concentrations of 150 to 265 mg kg(-1) dry weight, smaller towns with concentrations between 20 and 40 mg kg(-1) dry weight, and remotely located sites with concentrations below 15 mg kg(-1) dry weight. Pb-isotope ratios were compared to literature values for gasoline and local or geological background values, and the contribution of leaded-gasoline to total concentrations was calculated for contaminated sites using both a one-dimensional and a novel two-dimensional (vector) method. The North American sites had Pb-isotope ratios corresponding to the US leaded gasoline, with 24-88% of the Pb from leaded gasoline. Samples from Oceania showed Pb-isotope ratios corresponding to Australian gasoline, with 60% attributed to leaded gasoline in Sydney and 21% in Christchurch. Outside Cape Town, 15 to 46% of Pb in sediments was from leaded gasoline.

  7. Revealing the carbohydrate pattern on a cell surface by super-resolution imaging

    NASA Astrophysics Data System (ADS)

    Chen, Junling; Gao, Jing; Wu, Jiazhen; Zhang, Min; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Tian, Zhiyuan; Wang, Hongda

    2015-02-01

    Carbohydrates are involved in various physiological and pathological activities including cell adhesion, signal transduction and tumor invasion. The distribution of carbohydrates is the molecular basis of their multiple functions, but remains poorly understood. Here, we employed direct stochastic optical reconstruction microscopy (dSTORM) to visualize the pattern of N-acetylglucosamine (N-GlcNAc) on Vero cell membranes at the nanometer level of resolution. We found that N-GlcNAcs exist in irregular clusters on the apical membrane with an average cluster area of about 0.37 μm2. Most of these N-GlcNAc clusters are co-localized with lipid rafts by dual-color dSTORM imaging, suggesting that carbohydrates are closely associated with lipid rafts as the functional domains. Our results demonstrate that super-resolution imaging is capable of characterizing the distribution of carbohydrates on the cellular surface at the molecular level.Carbohydrates are involved in various physiological and pathological activities including cell adhesion, signal transduction and tumor invasion. The distribution of carbohydrates is the molecular basis of their multiple functions, but remains poorly understood. Here, we employed direct stochastic optical reconstruction microscopy (dSTORM) to visualize the pattern of N-acetylglucosamine (N-GlcNAc) on Vero cell membranes at the nanometer level of resolution. We found that N-GlcNAcs exist in irregular clusters on the apical membrane with an average cluster area of about 0.37 μm2. Most of these N-GlcNAc clusters are co-localized with lipid rafts by dual-color dSTORM imaging, suggesting that carbohydrates are closely associated with lipid rafts as the functional domains. Our results demonstrate that super-resolution imaging is capable of characterizing the distribution of carbohydrates on the cellular surface at the molecular level. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05970k

  8. Interactions of arsenic with calcite surfaces revealed by in situ nanoscale imaging

    NASA Astrophysics Data System (ADS)

    Renard, François; Putnis, Christine V.; Montes-Hernandez, German; Ruiz-Agudo, Encarnacion; Hovelmann, Jörn; Sarret, Géraldine

    2015-06-01

    Arsenic dissolved in water represents a key environmental and health challenge because several million people are under the threat of contamination. In calcareous environments calcite may play an important role in arsenic solubility and transfer in water. Arsenic-calcite interactions remain controversial, especially for As(III) which was proposed to be either incorporated as such, or as As(V) after oxidation. Here, we provide the first time-lapse in situ study of the evolution of the (10-14) calcite cleavage surface morphology during dissolution and growth in the presence of solutions with various amounts of As(III) or As(V) at room temperature and pH range 6-11 using a flow-through cell connected to an atomic force microscope (AFM). Reaction products were then characterized by Raman spectroscopy. In parallel, co-precipitation experiments with either As(III) or As(V) were performed in batch reactors, and the speciation of arsenic in the resulting solids was studied by X-ray absorption spectroscopy (XAS). For As(V), AFM results showed that it interacts strongly with the calcite surface, and XAS results showed that As(V) was mostly incorporated in the calcite structure. For As(III), AFM results showed much less impact on calcite growth and dissolution and less incorporation was observed. This was confirmed by XAS results that indicate that As(III) was partly oxidized into As(V) before being incorporated into calcite and the resulting calcite contained 36% As(III) and 64% As(V). All these experimental results confirm that As(V) has a much stronger interaction with calcite than As(III) and that calcite may represent an important reservoir for arsenic in various geological environments.

  9. Pronounced Surface Band Bending of Thin-Film Silicon Revealed by Modeling Core Levels Probed with Hard X-rays.

    PubMed

    Wippler, David; Wilks, Regan G; Pieters, Bart E; van Albada, Sacha J; Gerlach, Dominic; Hüpkes, Jürgen; Bär, Marcus; Rau, Uwe

    2016-07-13

    Enhancing the probing depth of photoemission studies by using hard X-rays allows the investigation of buried interfaces of real-world device structures. However, it also requires the consideration of photoelectron-signal attenuation when evaluating surface effects. Here, we employ a computational model incorporating surface band bending and exponential photoelectron-signal attenuation to model depth-dependent spectral changes of Si 1s and Si 2s core level lines. The data were acquired from hydrogenated boron-doped microcrystalline thin-film silicon, which is applied in silicon-based solar cells. The core level spectra, measured by hard X-ray photoelectron spectroscopy using different excitation energies, reveal the presence of a 0.29 nm thick surface oxide layer. In the silicon film a downward surface band bending of eVbb = -0.65 eV over ∼6 nm obtained via inverse modeling explains the observed core level shifts and line broadening. Moreover, the computational model allows the extraction of the "real" Si 1s and Si 2s bulk core level binding energies as 1839.13 and 150.39 eV, and their natural Lorentzian line widths as 496 and 859 meV, respectively. These values significantly differ from those directly extracted from the measured spectra. Because band bending usually occurs at material surfaces we highly recommend the detailed consideration of signal integration over depth for quantitative statements from depth-dependent measurements.

  10. Revealing the surface and bulk regimes of isothermal graphene growth on Ni with in situ kinetic measurements and modeling

    SciTech Connect

    Puretzky, Alexander A; Merkulov, Igor A; Rouleau, Christopher M; Eres, Gyula; Geohegan, David B

    2014-01-01

    In situ optical diagnostics are used to reveal the isothermal nucleation and growth mechanisms of graphene on Ni across a wide temperature range (560 C < T < 840 C) by chemical vapor deposition from single, sub-second pulses of acetylene. An abrupt, two-orders of magnitude change in growth times (~ 100s to 1s) is revealed at T = 680 C. Below and above this temperature, similar sigmoidal kinetics are measured and attributed to autocatalytic growth reactions but by two different mechanisms, surface assembly and dissolution/precipitation, respectively. These data are used to develop a simple and general kinetic model for graphene growth that includes the nucleation phase and includes the effects of carbon solubility in metals, describes delayed nucleation, and allows the interpretation of the competition between surface and bulk growth modes. The sharp transition in growth kinetics at T = 680 C is explained by a change in defect site density required for nucleation due to a transition in the carbon-induced mobility of the Ni surface. The easily-implemented optical reflectivity diagnostics and the simple kinetic model described here allow a pathway to optimize the growth of graphene on metals with arbitrary carbon solubility.

  11. Non-cellulosic polysaccharides help to reveal the history of thick organic surface layers on calcareous Alpine soils

    NASA Astrophysics Data System (ADS)

    Prietzel, Jörg; Spielvogel, Sandra

    2015-04-01

    We investigated the potential of non-cellulosic polysaccharides (NCP) as biomarkers to identify the plant types that dominate present and past litter input into organic surface covers on calcareous Alpine soils and to reveal historic vegetation changes. At two sites in the Alps, NCP monomers were quantified in different organs of site-dominating plants, the Oa horizon of four Folic Leptosols, and different sections of thick organic surface layers of four Folic Histosols on calcareous bedrock. The dominating plant types at our study sites differ markedly in their NCP composition and (galactose + mannose)/(arabinose + xylose) [GM/AX] ratio (grasses and sedges: 0.2; dicots Fagus and Vaccinium: 0.2-0.6; conifers Abies, Picea, Pinus: 0.7-2.4; mosses: 5). For all except one soil, the NCP signature of the uppermost Oa horizon reflects the present vegetation. For all Histosol O horizons, NCP signatures indicate a dominance of conifer litter throughout their development (up to 1,500 years). Different NCP and GM/AX depth profiles reflect specific patterns of O layer genesis. From those results we conclude that NCP and GM/AX depth profiles in organic surface covers of soils provide important information about dominating litter sources in the past and can be valuable tools to reveal historic vegetation and/ or land use changes.

  12. Revealing the nature of trapping sites in nanocrystalline titanium dioxide by selective surface modification.

    SciTech Connect

    Dimitrijevic, N. M.; Saponjic, Z. V.; Bartels, D. M.; Thurnauer, M. C.; Tiede, D. M.; Rajh, T.; Chemistry

    2003-07-31

    Excess electrons in nanocrystalline TiO{sub 2} were studied in bare and dopamine-capped TiO{sub 2} nanoparticles by electron-beam pulse radiolysis. Reaction of hydrated electrons with dopamine-capped TiO{sub 2} nanoparticles was found to be at the diffusion-controlled limit, k = 1 x 10{sup 11} M{sup -1} s{sup -1}, while the reaction with 1-hydroxy-1-methylethyl radicals, (CH{sub 3}){sub 2}{dot C}OH, was 2 orders of magnitude slower, k = 4 x 10{sup 8} M{sup -1} s{sup -1}. The reactions result in injection of electrons into the conduction band of TiO{sub 2} nanoparticles. Optical absorption spectra of injected excess electrons in dopamine-capped nanoparticles display monotonic featureless wavelength dependence up to 1800 nm. In contrast, bare particles have shown two preferential optical transitions with energies in the visible region ({lambda}{sub max} = 670 nm and {lambda}{sub max} = 900 nm). Flat band potential of dopamine-capped TiO{sub 2} nanoparticles was shifted by 100 mV to more negative values. The strong coupling of dopamine to surface Ti atoms was also found to improve the separation of photogenerated charges. This was demonstrated by the enhanced efficiency of photogenerated electrons in reducing silver cations to metallic silver in systems linked via a dopamine bridge, compared to the same systems linked through carboxyl groups.

  13. Unique Vibrational Features as a Direct Probe of Specific Antigen-Antibody Recognition at the Surface of a Solid-Supported Hybrid Lipid Bilayer.

    PubMed

    Lis, Dan; Cecchet, Francesca

    2016-09-01

    Here, we demonstrate how sum frequency generation (SFG), a vibrational spectroscopy based on a nonlinear three-photon mixing process, may provide a direct and unique fingerprint of bio-recognition; This latter can be detected with an intrinsically discriminating unspecific adsorption, thanks to the high sensitivity of the second-order nonlinear optical (NLO) response to preferential molecular orientation and symmetry properties. As a proof of concept, we have detected the biological event at the solid/liquid interface of a model bio-active antigen platform, based on a solid-supported hybrid lipid bilayer (ss-HLB) of a 2,4-dinitrophenyl (DNP) lipid, towards a monoclonal mouse anti-DNP complementary antibody. PMID:27324112

  14. Drosophila melanogaster mini spindles TOG3 utilizes unique structural elements to promote domain stability and maintain a TOG1- and TOG2-like tubulin-binding surface.

    PubMed

    Howard, Amy E; Fox, Jaime C; Slep, Kevin C

    2015-04-17

    Microtubule-associated proteins regulate microtubule (MT) dynamics spatially and temporally, which is essential for proper formation of the bipolar mitotic spindle. The XMAP215 family is comprised of conserved microtubule-associated proteins that use an array of tubulin-binding tumor overexpressed gene (TOG) domains, consisting of six (A-F) Huntingtin, elongation factor 3, protein phosphatase 2A, target of rapamycin (HEAT) repeats, to robustly increase MT plus-end polymerization rates. Recent work showed that TOG domains have differentially conserved architectures across the array, with implications for position-dependent TOG domain tubulin binding activities and function within the XMAP215 MT polymerization mechanism. Although TOG domains 1, 2, and 4 are well described, structural and mechanistic information characterizing TOG domains 3 and 5 is outstanding. Here, we present the structure and characterization of Drosophila melanogaster Mini spindles (Msps) TOG3. Msps TOG3 has two unique features as follows: the first is a C-terminal tail that stabilizes the ultimate four HEAT repeats (HRs), and the second is a unique architecture in HR B. Structural alignments of TOG3 with other TOG domain structures show that the architecture of TOG3 is most similar to TOG domains 1 and 2 and diverges from TOG4. Docking TOG3 onto recently solved Stu2 TOG1· and TOG2·tubulin complex structures suggests that TOG3 uses similarly conserved tubulin-binding intra-HEAT loop residues to engage α- and β-tubulin. This indicates that TOG3 has maintained a TOG1- and TOG2-like TOG-tubulin binding mode despite structural divergence. The similarity of TOG domains 1-3 and the divergence of TOG4 suggest that a TOG domain array with polarized structural diversity may play a key mechanistic role in XMAP215-dependent MT polymerization activity.

  15. A Homology Model Reveals Novel Structural Features and an Immunodominant Surface Loop/Opsonic Target in the Treponema pallidum BamA Ortholog TP_0326

    PubMed Central

    Luthra, Amit; Anand, Arvind; Hawley, Kelly L.; LeDoyt, Morgan; La Vake, Carson J.; Caimano, Melissa J.; Cruz, Adriana R.; Salazar, Juan C.

    2015-01-01

    ABSTRACT We recently demonstrated that TP_0326 is a bona fide rare outer membrane protein (OMP) in Treponema pallidum and that it possesses characteristic BamA bipartite topology. Herein, we used immunofluorescence analysis (IFA) to show that only the β-barrel domain of TP_0326 contains surface-exposed epitopes in intact T. pallidum. Using the solved structure of Neisseria gonorrhoeae BamA, we generated a homology model of full-length TP_0326. Although the model predicts a typical BamA fold, the β-barrel harbors features not described in other BamAs. Structural modeling predicted that a dome comprised of three large extracellular loops, loop 4 (L4), L6, and L7, covers the barrel's extracellular opening. L4, the dome's major surface-accessible loop, contains mainly charged residues, while L7 is largely neutral and contains a polyserine tract in a two-tiered conformation. L6 projects into the β-barrel but lacks the VRGF/Y motif that anchors L6 within other BamAs. IFA and opsonophagocytosis assay revealed that L4 is surface exposed and an opsonic target. Consistent with B cell epitope predictions, immunoblotting and enzyme-linked immunosorbent assay (ELISA) confirmed that L4 is an immunodominant loop in T. pallidum-infected rabbits and humans with secondary syphilis. Antibody capture experiments using Escherichia coli expressing OM-localized TP_0326 as a T. pallidum surrogate further established the surface accessibility of L4. Lastly, we found that a naturally occurring substitution (Leu593 → Gln593) in the L4 sequences of T. pallidum strains affects antibody binding in sera from syphilitic patients. Ours is the first study to employ a “structure-to-pathogenesis” approach to map the surface topology of a T. pallidum OMP within the context of syphilitic infection. IMPORTANCE Previously, we reported that TP_0326 is a bona fide rare outer membrane protein (OMP) in Treponema pallidum and that it possesses the bipartite topology characteristic of a BamA ortholog

  16. Orthogonal Click Conjugation to the Liposomal Surface Reveals the Stability of the Lipid Anchorage as Crucial for Targeting.

    PubMed

    Fritz, Thomas; Voigt, Matthias; Worm, Matthias; Negwer, Inka; Müller, Sophie S; Kettenbach, Kathrin; Ross, Tobias L; Roesch, Frank; Koynov, Kaloian; Frey, Holger; Helm, Mark

    2016-08-01

    Synthetic access to multiple surface decorations are a bottleneck in the development of liposomes for receptor mediated targeting. This opens a complex multiparameter space, exploration of which is severely limited in terms of sample numbers and turnaround times. Here, we unlock this technological barrier by a combination of a milligram-scale liposome formulation using dual centrifugation and orthogonal click chemistry on the liposomal surface. Application of these techniques to conceptually new amphiphilic compounds, which feature norbornene and alkyne groups at the apex of sterically stabilizing, hyperbranched polyglycerol moieties, revealed a particular influence of the membrane anchor of functional amphiphiles. Folic acid residues clicked to cholesterol-based amphiphiles were inefficient in folate-mediated cell targeting, while dialkyl-anchored amphiphiles remained stable in the liposomal membrane and imparted efficient targeting properties. These findings are of specific importance considering the popularity of cholesterol as a lipophilic anchor.

  17. Orthogonal Click Conjugation to the Liposomal Surface Reveals the Stability of the Lipid Anchorage as Crucial for Targeting.

    PubMed

    Fritz, Thomas; Voigt, Matthias; Worm, Matthias; Negwer, Inka; Müller, Sophie S; Kettenbach, Kathrin; Ross, Tobias L; Roesch, Frank; Koynov, Kaloian; Frey, Holger; Helm, Mark

    2016-08-01

    Synthetic access to multiple surface decorations are a bottleneck in the development of liposomes for receptor mediated targeting. This opens a complex multiparameter space, exploration of which is severely limited in terms of sample numbers and turnaround times. Here, we unlock this technological barrier by a combination of a milligram-scale liposome formulation using dual centrifugation and orthogonal click chemistry on the liposomal surface. Application of these techniques to conceptually new amphiphilic compounds, which feature norbornene and alkyne groups at the apex of sterically stabilizing, hyperbranched polyglycerol moieties, revealed a particular influence of the membrane anchor of functional amphiphiles. Folic acid residues clicked to cholesterol-based amphiphiles were inefficient in folate-mediated cell targeting, while dialkyl-anchored amphiphiles remained stable in the liposomal membrane and imparted efficient targeting properties. These findings are of specific importance considering the popularity of cholesterol as a lipophilic anchor. PMID:27403892

  18. Ligand-surface interactions and surface oxidation of colloidal PbSe quantum dots revealed by thin-film positron annihilation methods

    NASA Astrophysics Data System (ADS)

    Shi, Wenqin; Eijt, Stephan W. H.; Suchand Sandeep, C. S.; Siebbeles, Laurens D. A.; Houtepen, Arjan J.; Kinge, Sachin; Brück, Ekkes; Barbiellini, Bernardo; Bansil, Arun

    2016-02-01

    Positron Two Dimensional Angular Correlation of Annihilation Radiation (2D-ACAR) measurements reveal modifications of the electronic structure and composition at the surfaces of PbSe quantum dots (QDs), deposited as thin films, produced by various ligands containing either oxygen or nitrogen atoms. In particular, the 2D-ACAR measurements on thin films of colloidal PbSe QDs capped with oleic acid ligands yield an increased intensity in the electron momentum density (EMD) at high momenta compared to PbSe quantum dots capped with oleylamine. Moreover, the EMD of PbSe QDs is strongly affected by the small ethylenediamine ligands, since these molecules lead to small distances between QDs and favor neck formation between near neighbor QDs, inducing electronic coupling between neighboring QDs. The high sensitivity to the presence of oxygen atoms at the surface can be also exploited to monitor the surface oxidation of PbSe QDs upon exposure to air. Our study clearly demonstrates that positron annihilation spectroscopy applied to thin films can probe surface transformations of colloidal semiconductor QDs embedded in functional layers.

  19. Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef

    PubMed Central

    Matheson, Nicholas J.; Sumner, Jonathan; Wals, Kim; Rapiteanu, Radu; Weekes, Michael P.; Vigan, Raphael; Weinelt, Julia; Schindler, Michael; Antrobus, Robin; Costa, Ana S.H.; Frezza, Christian; Clish, Clary B.; Neil, Stuart J.D.; Lehner, Paul J.

    2015-01-01

    Summary Critical cell surface immunoreceptors downregulated during HIV infection have previously been identified using non-systematic, candidate approaches. To gain a comprehensive, unbiased overview of how HIV infection remodels the T cell surface, we took a distinct, systems-level, quantitative proteomic approach. >100 plasma membrane proteins, many without characterized immune functions, were downregulated during HIV infection. Host factors targeted by the viral accessory proteins Vpu or Nef included the amino acid transporter SNAT1 and the serine carriers SERINC3/5. We focused on SNAT1, a β-TrCP-dependent Vpu substrate. SNAT1 antagonism was acquired by Vpu variants from the lineage of SIVcpz/HIV-1 viruses responsible for pandemic AIDS. We found marked SNAT1 induction in activated primary human CD4+ T cells, and used Consumption and Release (CoRe) metabolomics to identify alanine as an endogenous SNAT1 substrate required for T cell mitogenesis. Downregulation of SNAT1 therefore defines a unique paradigm of HIV interference with immunometabolism. PMID:26439863

  20. Sea surface temperature variability off southern Brazil and Uruguay as revealed from historical data since 1854

    NASA Astrophysics Data System (ADS)

    Zavialov, Peter O.; Wainer, Ilana; Absy, JoãO. M.

    1999-09-01

    About 300,000 quality-controlled local reports from ships of opportunity were complemented with the data extracted from global data records to compile monthly series of sea surface temperature (SST) for the period 1854 to 1994 on a grid 1° × 1° in latitude and longitude. These historical data are used to investigate the variability off the coast of southern Brazil and Uruguay in a broad range of temporal scales from seasonal to secular. With respect to behavior at these scales, three distinct areas can be identified in the study region. The first one, located over the shelf and controlled by winter invasions of subantarctic water along with Rio de la Plata and Patos-Mirim discharges, is characterized by large annual range of SST (7° to over 10°C), energetic mean square variability (from 1.4 to 2.2°C2, after removal of seasonal signal), and an extremely high secular trend toward warming (1.2 to 1.6°C per 100 years), especially in the proximity of the estuaries. The second one, an area of the Brazil Current influence, exhibits smaller annual range (5° to 7°C) and mean square variability (1 to 1.4°C2). The secular trend is from 1° to 1.2°C per 100 years, smaller than observed in the shelf, but still high compared to the global average. The third area, which encompasses the eastern deep ocean part of the region away from the influence of either major currents or coastal discharges, exhibits less energetic variability at all examined scales, as compared to the rest of the region. Everywhere in the region, 50 to 80% of interannual variability is associated with periods smaller than 10 years; however, compared to the rest of the region, the shelf zone is characterized by a relatively large contribution from decadal and interdecadal scales. In austral winter a thermal front forms in the study region, separating warm tropical water associated with the Brazil Current and cold subantarctic water flowing northward on the shelf with an admixture of coastal

  1. Portrait of the Polana-Eulalia family complex: Surface homogeneity revealed from near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Pinilla-Alonso, Noemí; de León, J.; Walsh, K. J.; Campins, H.; Lorenzi, V.; Delbo, M.; DeMeo, F.; Licandro, J.; Landsman, Z.; Lucas, M. P.; Alí-Lagoa, V.; Burt, B.

    2016-08-01

    The inner asteroid belt is an important source of near-Earth asteroids (NEAs). Dynamical studies of the inner asteroid belt have identified several families overlapping in proper orbital elements, including the Polana and Eulalia families that contain a large fraction of the low-albedo asteroids in this region. We present results from two coordinated observational campaigns to characterize this region through near-infrared (NIR) spectroscopy. These campaigns ran from August 2012 to May 2014 and used the NASA Infrared Telescope Facility and the Telescopio Nazionale Galileo. The observations focused on objects within these families or in the background, with low albedo (pv ≤ 0.1) and low inclination (iP ≤ 7°). We observed 63 asteroids (57 never before observed in the NIR): 61 low-albedo objects and two interlopers, both compatible with S- or E- taxonomical types. We found our sample to be spectrally homogeneous in the NIR. The sample shows a continuum of neutral to moderately-red concave-up spectra, very similar within the uncertainties. Only one object in the sample, asteroid (3429) Chuvaev, has a blue spectrum, with a slope (S‧ = - 1.33 ± 0.21%/1000 Å) significantly different from the average spectrum (S‧ = 0.68 ± 0.68%/1000 Å). This spectral homogeneity is independent of membership in families or the background population. Furthermore, we show that the Eulalia and Polana families cannot be distinguished using NIR data. We also searched for rotational variability on the surface of (495) Eulalia which we do not detect. (495) Eulalia shows a red concave-up spectrum with an average slope S‧ = 0.91 ± 0.60%/1000 Å, very similar to the average slope of our sample. The spectra of two targets of sample-return missions, (101955) Bennu, target of NASA's OSIRIS-Rex and (162173) 1999 JU3 target of the Japanese Space Agency's Hayabusa-2, are very similar to our average spectrum, which would be compatible with an origin in this region of the inner belt.

  2. Surface plasmon resonance reveals a different pattern of proinsulin autoantibodies concentration and affinity in diabetic patients.

    PubMed

    Trabucchi, Aldana; Guerra, Luciano L; Faccinetti, Natalia I; Iacono, Rubén F; Poskus, Edgardo; Valdez, Silvina N

    2012-01-01

    Type 1 diabetes mellitus (DM) is characterized by autoimmune aggression against pancreatic beta cells resulting in absolute deficiency of insulin secretion. The first detectable sign of emerging autoimmunity during the preclinical asymptomatic period is the appearance of diabetes-related autoantibodies. In children at risk for type 1 DM, high-affinity Insulin autoantibodies reactive to proinsulin, are associated with diabetes risk. Autoantibodies are usually measured by radioligand binding assay (RBA) that provides quasi-quantitative values reflecting potency (product between concentration and affinity) of specific autoantibodies. Aiming to improve the characterization of the specific humoral immune response, we selected surface plasmon resonance (SPR) as an alternative method to measure proinsulin autoantibodies (PAA). This novel technology has allowed real time detection of antibodies interaction and kinetic analysis. Herein, we have employed SPR to characterize the PAA present in sera from 28 childhood-onset (mean age 8.31±4.20) and 23 adult-onset diabetic patients (≥65 years old, BMI<30) in terms of concentration and affinity. When evaluating comparatively samples from both groups, childhood-onset diabetic patients presented lower PAA concentrations and higher affinities (median 67.12×10(-9) M and 3.50×10(7) M(-1), respectively) than the adults (median 167.4×10(-9) M and 0.84×10(7) M(-1), respectively). These results are consistent with those from the reference method RBA (Standard Deviation score median 9.49 for childhood-onset group and 5.04 for adult-onset group) where the binding can be directly related to the intrinsic affinity of the antibody, suggesting that there is a different etiopathogenic pathway between both types of clinical presentation of the disease. This technology has shown to be a useful tool for the characterization of PAAs parameters as an alternative to radioimmunoassay, with high versatility and reproducibility associated to low

  3. Loss of PAX8 in high-grade serous ovarian cancer reduces cell survival despite unique modes of action in the fallopian tube and ovarian surface epithelium.

    PubMed

    Rodgers, Laura H; Ó hAinmhire, Eoghainín; Young, Alexandria N; Burdette, Joanna E

    2016-05-31

    High-grade serous carcinoma (HGSC) is the most common and lethal form of ovarian cancer. PAX8 is a transcription factor expressed in fallopian tube epithelial cells and in 80-96% of HGSC tumors. The ovarian surface epithelium (OSE) only acquires PAX8 expression after malignant transformation. In this study, forced PAX8 expression in OSE cells increased proliferation and migration through upregulation of EMT factors such as N-cadherin and Fibronectin. OSE cells expressing PAX8 also had an increase in the FOXM1 pathway, but PAX8 alone was not sufficient to drive tumorigenesis. PAX8 knockdown in the oviductal epithelium cells did not decrease expression of the FOXM1 pathway and induced only a slight decrease in cell proliferation. No changes in migration, cell cycle, or apoptosis were detected after PAX8 knockdown in oviductal cells. Finally, PAX8 knockdown in HGSC cell lines resulted in increased apoptosis and decreased FOXM1 levels. The results presented here suggest that PAX8 has a cell specific role in governing proliferation and migration in nontransformed ovarian surface epithelium cells compared to the oviductal cells, but its reduction in serous cancer cell lines provides a common mechanism for reducing cell survival.

  4. Sea surface density gradients in the Nordic Seas during the Holocene as revealed by paired microfossil and isotope proxies

    NASA Astrophysics Data System (ADS)

    Van Nieuwenhove, Nicolas; Hillaire-Marcel, Claude; Bauch, Henning A.; Vernal, Anne

    2016-03-01

    We attempt to assess the Holocene surface-subsurface seawater density gradient on millennial time scale based on the reconstruction of potential density (σθ) by combining data from dinoflagellate cyst assemblages and planktic foraminiferal (Neogloboquadrina pachyderma (s)) stable oxygen isotopes (δ18Oc). Following several calibration exercises, the likeliness of favorable seasonal preconditioning to open ocean convection is evaluated. The reconstructed σθ values reveal unfavorable conditions for vertical convection in the western Nordic Seas prior to ~7-6.5 ka B.P., with a westward increase and persistence of surface water buoyancy. Active overturning became more likely after 6.5 ka B.P. as suggested by a reduced and recurrently inverted vertical σθ gradient, while intermittent eastward spreading of lower density surface waters continued to modulate the area of potential overturning. Despite some reservation regarding the accuracy of the σθ values reconstructed, the documentation of relative changes of σθ gradients through time and space is suggested as a helpful tool for the appraisal of past overturning likeliness.

  5. A Human Pluripotent Stem Cell Surface N-Glycoproteome Resource Reveals Markers, Extracellular Epitopes, and Drug Targets

    PubMed Central

    Boheler, Kenneth R.; Bhattacharya, Subarna; Kropp, Erin M.; Chuppa, Sandra; Riordon, Daniel R.; Bausch-Fluck, Damaris; Burridge, Paul W.; Wu, Joseph C.; Wersto, Robert P.; Chan, Godfrey Chi Fung; Rao, Sridhar; Wollscheid, Bernd; Gundry, Rebekah L.

    2014-01-01

    Summary Detailed knowledge of cell-surface proteins for isolating well-defined populations of human pluripotent stem cells (hPSCs) would significantly enhance their characterization and translational potential. Through a chemoproteomic approach, we developed a cell-surface proteome inventory containing 496 N-linked glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). Against a backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of interest for hPSCs were revealed. The >30 positive and negative markers verified here by orthogonal approaches provide experimental justification for the rational selection of pluripotency and lineage markers, epitopes for cell isolation, and reagents for the characterization of putative hiPSC lines. Comparative differences between the chemoproteomic-defined surfaceome and the transcriptome-predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1 inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs from mixed cultures. PMID:25068131

  6. Repeat Terrestrial LiDAR Scanning at Kilauea Volcano Reveals Basaltic Lava Lake Surface Slope, Structure and Micro-pistoning

    NASA Astrophysics Data System (ADS)

    Anderson, S. W.; LeWinter, A. L.; Finnegan, D. C.; Patrick, M. R.; Orr, T. R.

    2014-12-01

    In an attempt to better understand the spatial and temporal relationships between lava lake behavior and its surface topography, we conducted repeat, high-speed terrestrial LiDAR surveys of Kīlauea Volcano's Overlook Crater lava lake surface on January 16, 2013 and December 17, 2013. These scans revealed large- and fine-scale structure not visible in other topographic data sets. For both surveys, the LiDAR sensor was located directly above the Overlook Crater on the edge of the Halema'uma'u Crater, and was tilted 45o towards the lava lake. On January 16, 2013, five-second scans were collected every 2-minutes over 200-minutes, resulting in ~25 points/ m2, and covering the lower walls of the Overlook Crater and the lava lake surface. Similarly, on December 17, 2013, one-second scans were collected every 30-seconds over 240-minutes during a transient deflation-inflation deformation event, resulting in ~6 points/m2. In addition, high-resolution scans of the crater walls and lava lake were captured at the start of both surveys. We derived a number of products and measurements from these 3-dimensional time-lapse data. The slope of the lava lake was measured in each scan, and it fluctuates as lake convection regime, areas of upwelling and downflow, and crustal plate velocities vary. Areas of upwelling were consistently ~0.6m higher than areas of downwelling at any point in time, and the migration of areas of upwelling on the lake surface were coincident with areas of intense outgassing. Velocities of lava lake crustal plates averaged 0.354 m/s near the center of the lake surface on December 17, 2013. From the high-resolution scans collected at the start of both surveys we measured sub-meter lava lake fluctuations over time that may illustrate micro-pistoning in the magma column. These preliminary results raise several questions: 1) do lava lake slopes change spatially and temporally, and what eruption variables are linked to such changes; 2) do lava lake levels change

  7. Study of the Individual Cytochrome b[subscript 5] and Cytochrome b[subscript 5] Reductase Domains of Ncb5or Reveals a Unique Heme Pocket and a Possible Role of the CS Domain

    SciTech Connect

    Deng, Bin; Parthasarathy, Sudharsan; Wang, WenFang; Gibney, Brian R.; Battaile, Kevin P.; Lovell, Scott; Benson, David R.; Zhu, Hao

    2010-09-22

    NADH cytochrome b{sub 5} oxidoreductase (Ncb5or) is found in animals and contains three domains similar to cytochrome b{sub 5} (b{sub 5}), CHORD-SGT1 (CS), and cytochrome b{sub 5} reductase (b{sub 5}R). Ncb5or has an important function, as suggested by the diabetes and lipoatrophy phenotypes in Ncb5or null mice. To elucidate the structural and functional properties of human Ncb5or, we generated its individual b{sub 5} and b{sub 5}R domains (Ncb5or-b{sub 5} and Ncb5or-b{sub 5}R, respectively) and compared them with human microsomal b{sub 5} (Cyb5A) and b{sub 5}R (Cyb5R3). A 1.25 {angstrom} x-ray crystal structure of Ncb5or-b{sub 5} reveals nearly orthogonal planes of the imidazolyl rings of heme-ligating residues His{sup 89} and His{sup 112}, consistent with a highly anisotropic low spin EPR spectrum. Ncb5or is the first member of the cytochrome b{sub 5} family shown to have such a heme environment. Like other b{sub 5} family members, Ncb5or-b{sub 5} has two helix-loop-helix motifs surrounding heme. However, Ncb5or-b{sub 5} differs from Cyb5A with respect to location of the second heme ligand (His{sup 112}) and of polypeptide conformation in its vicinity. Electron transfer from Ncb5or-b{sub 5}R to Ncb5or-b{sub 5} is much less efficient than from Cyb5R3 to Cyb5A, possibly as a consequence of weaker electrostatic interactions. The CS linkage probably obviates the need for strong interactions between b{sub 5} and b{sub 5}R domains in Ncb5or. Studies with a construct combining the Ncb5or CS and b{sub 5}R domains suggest that the CS domain facilitates docking of the b{sub 5} and b{sub 5}R domains. Trp{sup 114} is an invariant surface residue in all known Ncb5or orthologs but appears not to contribute to electron transfer from the b{sub 5}R domain to the b{sub 5} domain.

  8. Study of the Individual Cytochrome b5 and Cytochrome b5 Reductase Domains of Ncb5or Reveals a Unique Heme Pocket and a Possible Role of the CS Domain*

    PubMed Central

    Deng, Bin; Parthasarathy, Sudharsan; Wang, WenFang; Gibney, Brian R.; Battaile, Kevin P.; Lovell, Scott; Benson, David R.; Zhu, Hao

    2010-01-01

    NADH cytochrome b5 oxidoreductase (Ncb5or) is found in animals and contains three domains similar to cytochrome b5 (b5), CHORD-SGT1 (CS), and cytochrome b5 reductase (b5R). Ncb5or has an important function, as suggested by the diabetes and lipoatrophy phenotypes in Ncb5or null mice. To elucidate the structural and functional properties of human Ncb5or, we generated its individual b5 and b5R domains (Ncb5or-b5 and Ncb5or-b5R, respectively) and compared them with human microsomal b5 (Cyb5A) and b5R (Cyb5R3). A 1.25 Å x-ray crystal structure of Ncb5or-b5 reveals nearly orthogonal planes of the imidazolyl rings of heme-ligating residues His89 and His112, consistent with a highly anisotropic low spin EPR spectrum. Ncb5or is the first member of the cytochrome b5 family shown to have such a heme environment. Like other b5 family members, Ncb5or-b5 has two helix-loop-helix motifs surrounding heme. However, Ncb5or-b5 differs from Cyb5A with respect to location of the second heme ligand (His112) and of polypeptide conformation in its vicinity. Electron transfer from Ncb5or-b5R to Ncb5or-b5 is much less efficient than from Cyb5R3 to Cyb5A, possibly as a consequence of weaker electrostatic interactions. The CS linkage probably obviates the need for strong interactions between b5 and b5R domains in Ncb5or. Studies with a construct combining the Ncb5or CS and b5R domains suggest that the CS domain facilitates docking of the b5 and b5R domains. Trp114 is an invariant surface residue in all known Ncb5or orthologs but appears not to contribute to electron transfer from the b5R domain to the b5 domain. PMID:20630863

  9. Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.

    PubMed

    Deng, Bin; Parthasarathy, Sudharsan; Wang, WenFang; Gibney, Brian R; Battaile, Kevin P; Lovell, Scott; Benson, David R; Zhu, Hao

    2010-09-24

    NADH cytochrome b(5) oxidoreductase (Ncb5or) is found in animals and contains three domains similar to cytochrome b(5) (b(5)), CHORD-SGT1 (CS), and cytochrome b(5) reductase (b(5)R). Ncb5or has an important function, as suggested by the diabetes and lipoatrophy phenotypes in Ncb5or null mice. To elucidate the structural and functional properties of human Ncb5or, we generated its individual b(5) and b(5)R domains (Ncb5or-b(5) and Ncb5or-b(5)R, respectively) and compared them with human microsomal b(5) (Cyb5A) and b(5)R (Cyb5R3). A 1.25 Å x-ray crystal structure of Ncb5or-b(5) reveals nearly orthogonal planes of the imidazolyl rings of heme-ligating residues His(89) and His(112), consistent with a highly anisotropic low spin EPR spectrum. Ncb5or is the first member of the cytochrome b(5) family shown to have such a heme environment. Like other b(5) family members, Ncb5or-b(5) has two helix-loop-helix motifs surrounding heme. However, Ncb5or-b(5) differs from Cyb5A with respect to location of the second heme ligand (His(112)) and of polypeptide conformation in its vicinity. Electron transfer from Ncb5or-b(5)R to Ncb5or-b(5) is much less efficient than from Cyb5R3 to Cyb5A, possibly as a consequence of weaker electrostatic interactions. The CS linkage probably obviates the need for strong interactions between b(5) and b(5)R domains in Ncb5or. Studies with a construct combining the Ncb5or CS and b(5)R domains suggest that the CS domain facilitates docking of the b(5) and b(5)R domains. Trp(114) is an invariant surface residue in all known Ncb5or orthologs but appears not to contribute to electron transfer from the b(5)R domain to the b(5) domain. PMID:20630863

  10. Sorting single satellite cells from individual myofibers reveals heterogeneity in cell-surface markers and myogenic capacity.

    PubMed

    Chapman, Matthew R; Balakrishnan, Karthik R; Li, Ju; Conboy, Michael J; Huang, Haiyan; Mohanty, Swomitra K; Jabart, Eric; Hack, James; Conboy, Irina M; Sohn, Lydia L

    2013-04-01

    Traditional cell-screening techniques such as FACS and MACS are better suited for large numbers of cells isolated from bulk tissue and cannot easily screen stem or progenitor cells from minute populations found in their physiological niches. Furthermore, these techniques rely upon irreversible antibody binding, potentially altering cell properties, including gene expression and regenerative capacity. To address these challenges, we have developed a novel, label-free stem-cell analysis and sorting platform capable of quantifying cell-surface marker expression of single functional organ stem cells directly isolated from their micro-anatomical niche. Using our unique platform, we have discovered a remarkable heterogeneity in both the regenerative capacity and expression of CXCR4, β1-integrin, Sca-1, M-cadherin, Syndecan-4, and Notch-1 in freshly isolated muscle stem (satellite) cells residing on different, single myofibers and have identified a small population of Sca-1(+)/Myf5(+) myogenic satellite cells. Our results demonstrate the utility of our single-cell platform for uncovering and functionally characterizing stem-cell heterogeneity in the organ microniche.

  11. Surface plasmon resonance imaging reveals multiple binding modes of Agrobacterium transformation mediator VirE2 to ssDNA.

    PubMed

    Kim, Sanghyun; Zbaida, David; Elbaum, Michael; Leh, Hervé; Nogues, Claude; Buckle, Malcolm

    2015-07-27

    VirE2 is the major secreted protein of Agrobacterium tumefaciens in its genetic transformation of plant hosts. It is co-expressed with a small acidic chaperone VirE1, which prevents VirE2 oligomerization. After secretion into the host cell, VirE2 serves functions similar to a viral capsid in protecting the single-stranded transferred DNA en route to the nucleus. Binding of VirE2 to ssDNA is strongly cooperative and depends moreover on protein-protein interactions. In order to isolate the protein-DNA interactions, imaging surface plasmon resonance (SPRi) studies were conducted using surface-immobilized DNA substrates of length comparable to the protein-binding footprint. Binding curves revealed an important influence of substrate rigidity with a notable preference for poly-T sequences and absence of binding to both poly-A and double-stranded DNA fragments. Dissociation at high salt concentration confirmed the electrostatic nature of the interaction. VirE1-VirE2 heterodimers also bound to ssDNA, though by a different mechanism that was insensitive to high salt. Neither VirE2 nor VirE1-VirE2 followed the Langmuir isotherm expected for reversible monomeric binding. The differences reflect the cooperative self-interactions of VirE2 that are suppressed by VirE1. PMID:26044711

  12. Single Particle Tracking reveals two distinct environments for CD4 receptors at the surface of living T lymphocytes

    SciTech Connect

    Mascalchi, Patrice; Lamort, Anne Sophie; Salome, Laurence; Dumas, Fabrice

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer We studied the diffusion of single CD4 receptors on living lymphocytes. Black-Right-Pointing-Pointer This study reveals that CD4 receptors have either a random or confined diffusion. Black-Right-Pointing-Pointer The dynamics of unconfined CD4 receptors was accelerated by a temperature raise. Black-Right-Pointing-Pointer The dynamics of confined CD4 receptors was unchanged by a temperature raise. Black-Right-Pointing-Pointer Our results suggest the existence of two different environments for CD4 receptors. -- Abstract: We investigated the lateral diffusion of the HIV receptor CD4 at the surface of T lymphocytes at 20 Degree-Sign C and 37 Degree-Sign C by Single Particle Tracking using Quantum Dots. We found that the receptors presented two major distinct behaviors that were not equally affected by temperature changes. About half of the receptors showed a random diffusion with a diffusion coefficient increasing upon raising the temperature. The other half of the receptors was permanently or transiently confined with unchanged dynamics on raising the temperature. These observations suggest that two distinct subpopulations of CD4 receptors with different environments are present at the surface of living T lymphocytes.

  13. Proteomics Analysis Reveals Distinct Corona Composition on Magnetic Nanoparticles with Different Surface Coatings: Implications for Interactions with Primary Human Macrophages.

    PubMed

    Vogt, Carmen; Pernemalm, Maria; Kohonen, Pekka; Laurent, Sophie; Hultenby, Kjell; Vahter, Marie; Lehtiö, Janne; Toprak, Muhammet S; Fadeel, Bengt

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising contrast agents for magnetic resonance imaging. The influence of different surface coatings on the biocompatibility of SPIONs has been addressed, but the potential impact of the so-called corona of adsorbed proteins on the surface of SPIONs on their biological behavior is less well studied. Here, we determined the composition of the plasma protein corona on silica-coated versus dextran-coated SPIONs using mass spectrometry-based proteomics approaches. Notably, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs.

  14. Proteomics Analysis Reveals Distinct Corona Composition on Magnetic Nanoparticles with Different Surface Coatings: Implications for Interactions with Primary Human Macrophages.

    PubMed

    Vogt, Carmen; Pernemalm, Maria; Kohonen, Pekka; Laurent, Sophie; Hultenby, Kjell; Vahter, Marie; Lehtiö, Janne; Toprak, Muhammet S; Fadeel, Bengt

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising contrast agents for magnetic resonance imaging. The influence of different surface coatings on the biocompatibility of SPIONs has been addressed, but the potential impact of the so-called corona of adsorbed proteins on the surface of SPIONs on their biological behavior is less well studied. Here, we determined the composition of the plasma protein corona on silica-coated versus dextran-coated SPIONs using mass spectrometry-based proteomics approaches. Notably, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs. PMID:26444829

  15. Proteomics Analysis Reveals Distinct Corona Composition on Magnetic Nanoparticles with Different Surface Coatings: Implications for Interactions with Primary Human Macrophages

    PubMed Central

    Vogt, Carmen; Pernemalm, Maria; Kohonen, Pekka; Laurent, Sophie; Hultenby, Kjell; Vahter, Marie; Lehtiö, Janne; Toprak, Muhammet S.; Fadeel, Bengt

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising contrast agents for magnetic resonance imaging. The influence of different surface coatings on the biocompatibility of SPIONs has been addressed, but the potential impact of the so-called corona of adsorbed proteins on the surface of SPIONs on their biological behavior is less well studied. Here, we determined the composition of the plasma protein corona on silica-coated versus dextran-coated SPIONs using mass spectrometry-based proteomics approaches. Notably, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs. PMID:26444829

  16. Surface plasmon resonance imaging reveals multiple binding modes of Agrobacterium transformation mediator VirE2 to ssDNA

    PubMed Central

    Kim, Sanghyun; Zbaida, David; Elbaum, Michael; Leh, Hervé; Nogues, Claude; Buckle, Malcolm

    2015-01-01

    VirE2 is the major secreted protein of Agrobacterium tumefaciens in its genetic transformation of plant hosts. It is co-expressed with a small acidic chaperone VirE1, which prevents VirE2 oligomerization. After secretion into the host cell, VirE2 serves functions similar to a viral capsid in protecting the single-stranded transferred DNA en route to the nucleus. Binding of VirE2 to ssDNA is strongly cooperative and depends moreover on protein–protein interactions. In order to isolate the protein–DNA interactions, imaging surface plasmon resonance (SPRi) studies were conducted using surface-immobilized DNA substrates of length comparable to the protein-binding footprint. Binding curves revealed an important influence of substrate rigidity with a notable preference for poly-T sequences and absence of binding to both poly-A and double-stranded DNA fragments. Dissociation at high salt concentration confirmed the electrostatic nature of the interaction. VirE1–VirE2 heterodimers also bound to ssDNA, though by a different mechanism that was insensitive to high salt. Neither VirE2 nor VirE1–VirE2 followed the Langmuir isotherm expected for reversible monomeric binding. The differences reflect the cooperative self-interactions of VirE2 that are suppressed by VirE1. PMID:26044711

  17. Diversity patterns of Rhizobiaceae communities inhabiting soils, root surfaces and nodules reveal a strong selection of rhizobial partners by legumes.

    PubMed

    Miranda-Sánchez, Fabiola; Rivera, Javier; Vinuesa, Pablo

    2016-09-01

    Current knowledge about rhizobial diversity patterns in non-nodule habitats is scarce, limiting our understanding of basic aspects of rhizobial ecology like competitiveness for nodule occupancy and host effects on community structure. We used a combination of cultivation-dependent and independent approaches to analyse alpha and beta diversity patterns of Rhizobiaceae communities from a conserved seasonally dry tropical forest site in central Mexico and two nearby agricultural fields. Lineage-specific recA amplicon libraries were generated from soil DNA and their sequences compared with those from root surface and nodule isolates recovered in trapping experiments from two native Acacia species and two Phaseolus vulgaris cultivars. Rarefaction analyses revealed that Rhizobiaceae diversity in soils is larger than on root surfaces, and smallest in nodules. A 'rare biosphere'-like distribution of species was found in the three habitats. Multivariate statistical analyses demonstrated that the plant genus exerted a stronger influence than the land-usage regime on the diversity of rhizobia associated with hosts. Rhizobium etli was the dominant Rhizobiaceae found in the soil libraries. It dominated nodulation of Acacia spp. and predominately harboured symbiovar mimosae-like nodC genes. A novel Rhizobium lineage (Rsp1) dominated bean nodulation. Specialist and generalist genotypes for host nodulation were detected in both species. PMID:26395550

  18. Landsat imagery: a unique resource

    USGS Publications Warehouse

    Miller, H.; Sexton, N.; Koontz, L.

    2011-01-01

    Landsat satellites provide high-quality, multi-spectral imagery of the surface of the Earth. These moderate-resolution, remotely sensed images are not just pictures, but contain many layers of data collected at different points along the visible and invisible light spectrum. These data can be manipulated to reveal what the Earth’s surface looks like, including what types of vegetation are present or how a natural disaster has impacted an area (Fig. 1).

  19. Unique Biosignatures in Caves of All Lithologies

    NASA Astrophysics Data System (ADS)

    Boston, P. J.; Schubert, K. E.; Gomez, E.; Conrad, P. G.

    2015-10-01

    Unique maze-like microbial communities on cave surfaces on all lithologies all over the world are an excellent candidate biosignatures for life detection missions into caves and other extraterrestrial environments.

  20. Surface structure of CdSe Nanorods revealed by combined X-rayabsorption fine structure measurements and ab-initio calculations

    SciTech Connect

    Aruguete, Deborah A.; Marcus, Matthew A.; Li, Liang-shi; Williamson, Andrew; Fakra, Sirine; Gygi, Francois; Galli, Giulia; Alivisatos, A. Paul

    2006-01-27

    We report orientation-specific, surface-sensitive structural characterization of colloidal CdSe nanorods with extended X-ray absorption fine structure spectroscopy and ab-initio density functional theory calculations. Our measurements of crystallographically-aligned CdSe nanorods show that they have reconstructed Cd-rich surfaces. They exhibit orientation-dependent changes in interatomic distances which are qualitatively reproduced by our calculations. These calculations reveal that the measured interatomic distance anisotropy originates from the nanorod surface.

  1. GR uniqueness and deformations

    NASA Astrophysics Data System (ADS)

    Krasnov, Kirill

    2015-10-01

    In the metric formulation gravitons are described with the parity symmetric S + 2 ⊗ S - 2 representation of Lorentz group. General Relativity is then the unique theory of interacting gravitons with second order field equations. We show that if a chiral S + 3 ⊗ S - representation is used instead, the uniqueness is lost, and there is an infinite-parametric family of theories of interacting gravitons with second order field equations. We use the language of graviton scattering amplitudes, and show how the uniqueness of GR is avoided using simple dimensional analysis. The resulting distinct from GR gravity theories are all parity asymmetric, but share the GR MHV amplitudes. They have new all same helicity graviton scattering amplitudes at every graviton order. The amplitudes with at least one graviton of opposite helicity continue to be determinable by the BCFW recursion.

  2. Structural analysis and insertion study reveal the ideal sites for surface displaying foreign peptides on a betanodavirus-like particle.

    PubMed

    Xie, Junfeng; Li, Kunpeng; Gao, Yuanzhu; Huang, Runqing; Lai, Yuxiong; Shi, Yan; Yang, Shaowei; Zhu, Guohua; Zhang, Qinfen; He, Jianguo

    2016-01-01

    Betanodavirus infection causes fatal disease of viral nervous necrosis in many cultured marine and freshwater fish worldwide and the virus-like particles (VLP) are effective vaccines against betanodavirus. But vaccine and viral vector designs of betanodavirus VLP based on their structures remain lacking. Here, the three-dimensional structure of orange-spotted grouper nervous necrosis virus (OGNNV) VLP (RBS) at 3.9 Å reveals the organization of capsid proteins (CP). Based on the structural results, seven putative important sites were selected to genetically insert a 6× histidine (His)-tag for VLP formation screen, resulting in four His-tagged VLP (HV) at positions N-terminus, Ala220, Pro292 and C-terminus. The His-tags of N-terminal HV (NHV) were concealed inside virions while those of 220HV and C-terminal HV (CHV) were displayed at the outer surface. NHV, 220HV and CHV maintained the same cell entry ability as RBS in the Asian sea bass (SB) cell line, indicating that their similar surface structures can be recognized by the cellular entry receptor(s). For application of vaccine design, chromatography-purified CHV could provoke NNV-specific antibody responses as strong as those of RBS in a sea bass immunization assay. Furthermore, in carrying capacity assays, N-terminus and Ala220 can only carry short peptides and C-terminus can even accommodate large protein such as GFP to generate fluorescent VLP (CGV). For application of a viral vector, CGV could be real-time visualized to enter SB cells in invasion study. All the results confirmed that the C-terminus of CP is a suitable site to accommodate foreign peptides for vaccine design and viral vector development. PMID:26754256

  3. Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140

    SciTech Connect

    Mehta, Kinjal Rajesh; Chan, Yan M.; Lee, Man X.; Yang, Ching Yao; Voloshchuk, Natalya; Montclare, Jin Kim

    2010-09-24

    Research highlights: {yields} Mutagenesis of the tGCN5 core region reveals two residues important for function. {yields} Developed a fluorescent lysate-based activity assay to assess mutants. {yields} Surface-exposed residues F90 and R140 of tGCN5 are critical for H3 acetylation. -- Abstract: Tetrahymena General Control Non-Derepressor 5 (tGCN5) is a critical regulator of gene transcription via acetylation of histones. Since the acetylation ability has been attributed to the 'core region', we perform mutagenesis of residues within the tGCN5 'core region' in order to identify those critical for function and stability. Residues that do not participate in catalysis are identified, mutated and characterized for activity, structure and thermodynamic stability. Variants I107V, Q114L, A121T and A130S maintain the acetylation function relative to wild-type tGCN5, while variants F90Y, F112R and R140H completely abolish function. Of the three non-functional variants, since F112 is mutated into a non-homologous charged residue, a loss in function is expected. However, the remaining two variants are mutated into homologous residues, suggesting that F90 and R140 are critical for the activity of tGCN5. While mutation to homologous residue maintains acetylation of histone H3 for the majority of the variants, the two surface-exposed residues, F90 and R140, appear to be essential for tGCN5 function, structure or stability.

  4. Improvement of surface ECG recording in adult zebrafish reveals that the value of this model exceeds our expectation.

    PubMed

    Liu, Chi Chi; Li, Li; Lam, Yun Wah; Siu, Chung Wah; Cheng, Shuk Han

    2016-01-01

    The adult zebrafish has been used to model the electrocardiogram (ECG) for human cardiovascular studies. Nonetheless huge variations are observed among studies probably because of the lack of a reliable and reproducible recording method. In our study, an adult zebrafish surface ECG recording technique was improved using a multi-electrode method and by pre-opening the pericardial sac. A convenient ECG data analysis method without wavelet transform was also established. Intraperitoneal injection of KCl in zebrafish induced an arrhythmia similar to that of humans, and the arrhythmia was partially rescued by calcium gluconate. Amputation and cryoinjury of the zebrafish heart induced ST segment depression and affected QRS duration after injury. Only cryoinjury decelerated the heart rate. Different changes were also observed in the QT interval during heart regeneration in these two injury models. We also characterized the electrocardiophysiology of breakdance zebrafish mutant with a prolonged QT interval, that has not been well described in previous studies. Our study provided a reliable and reproducible means to record zebrafish ECG and analyse data. The detailed characterization of the cardiac electrophysiology of zebrafish and its mutant revealed that the potential of the zebrafish in modeling the human cardiovascular system exceeds expectations. PMID:27125643

  5. Improvement of surface ECG recording in adult zebrafish reveals that the value of this model exceeds our expectation

    PubMed Central

    Liu, Chi Chi; Li, Li; Lam, Yun Wah; Siu, Chung Wah; Cheng, Shuk Han

    2016-01-01

    The adult zebrafish has been used to model the electrocardiogram (ECG) for human cardiovascular studies. Nonetheless huge variations are observed among studies probably because of the lack of a reliable and reproducible recording method. In our study, an adult zebrafish surface ECG recording technique was improved using a multi-electrode method and by pre-opening the pericardial sac. A convenient ECG data analysis method without wavelet transform was also established. Intraperitoneal injection of KCl in zebrafish induced an arrhythmia similar to that of humans, and the arrhythmia was partially rescued by calcium gluconate. Amputation and cryoinjury of the zebrafish heart induced ST segment depression and affected QRS duration after injury. Only cryoinjury decelerated the heart rate. Different changes were also observed in the QT interval during heart regeneration in these two injury models. We also characterized the electrocardiophysiology of breakdance zebrafish mutant with a prolonged QT interval, that has not been well described in previous studies. Our study provided a reliable and reproducible means to record zebrafish ECG and analyse data. The detailed characterization of the cardiac electrophysiology of zebrafish and its mutant revealed that the potential of the zebrafish in modeling the human cardiovascular system exceeds expectations. PMID:27125643

  6. Irreversible adsorption-driven assembly of nanoparticles at fluid interfaces revealed by a dynamic surface tension probe.

    PubMed

    Bizmark, Navid; Ioannidis, Marios A; Henneke, Dale E

    2014-01-28

    Adsorption-driven self-assembly of nanoparticles at fluid interfaces is a promising bottom-up approach for the preparation of advanced functional materials and devices. Full realization of its potential requires quantitative understanding of the parameters controlling the self-assembly, the structure of nanoparticles at the interface, the barrier properties of the assembly, and the rate of particle attachment. We argue that models of dynamic surface or interfacial tension (DST) appropriate for molecular species break down when the adsorption energy greatly exceeds the mean energy of thermal fluctuations and validate alternative models extending the application of generalized random sequential adsorption theory to nanoparticle adsorption at fluid interfaces. Using a model colloidal system of hydrophobic, charge-stabilized ethyl cellulose nanoparticles at neutral pH, we demonstrate the potential of DST measurements to reveal information on the energy of adsorption, the adsorption rate constant, and the energy of particle-interface interaction at different degrees of nanoparticle coverage of the interface. These findings have significant implications for the quantitative description of nanoparticle adsorption at fluid interfaces.

  7. Unique Access to Learning

    ERIC Educational Resources Information Center

    Goble, Don

    2009-01-01

    This article describes the many learning opportunities that broadcast technology students at Ladue Horton Watkins High School in St. Louis, Missouri, experience because of their unique access to technology and methods of learning. Through scaffolding, stepladder techniques, and trial by fire, students learn to produce multiple television programs,…

  8. Whole exome sequencing in a case of sporadic multiple meningioma reveals shared NF2, FAM109B, and TPRXL mutations, together with unique SMARCB1 alterations in a subset of tumor nodules.

    PubMed

    Torres-Martín, Miguel; Kusak, M Elena; Isla, Alberto; Burbano, Rommel R; Pinto, Giovanny R; Melendez, Barbara; Castresana, Javier S; Rey, Juan A

    2015-06-01

    Meningiomas are common intracranial tumors derived from arachnoid cells. Multiple meningiomas are occasionally present even in patients with no history of neurofibromatosis type 2, a condition that can cause the formation of this neoplasm. Previous studies have shown that most multiple meningiomas are monoclonal in origin. In this study, exome sequencing was performed on four meningiomas and the corresponding peripheral blood DNA from a 61-year-old woman with sporadic multiple meningioma. At least three common mutational events (at the NF2, FAM109B, and TPRXL genes) were detected in the tumors' DNA when they were compared with the lymphocyte DNA from the patient as control. Additionally, an array of unique mutations was detected in each tumor, including in SMARCB1 in two of the samples, a gene whose alteration leads to the development of meningioma. Mutations in other genes, such as IRS4, GULP1, NHSL1, and C10orf53, accounted for one alteration in each meningioma nodule. Our data suggest a monoclonal origin of the meningiomas in this patient, although the numerous alterations contained in each sample indicated multiple secondary variable changes in each tumor nodule. Whether the alterations described in this work are drivers of tumorigenesis or are simply passengers requires further study. PMID:25981829

  9. Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma.

    PubMed

    Bohling, Sandra D; Jenson, Stephen D; Crockett, David K; Schumacher, Jonathan A; Elenitoba-Johnson, Kojo S J; Lim, Megan S

    2008-03-01

    Anaplastic large cell lymphoma (ALCL) comprises a group of non-Hodgkin lymphomas characterized by the expression of the CD30/Ki-1 antigen. A subset of ALCL is characterized by chromosomal translocations involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2. While the most common translocation is the t(2;5)(p23;q35) involving the nucleophosmin (NPM) gene on chromosome 5, up to 12 other translocations partners of the ALK gene have been identified. One of these is the t(1;2)(q25;p23) which results in the formation of the chimeric protein TPM3-ALK. While several of the signaling pathways induced by NPM-ALK have been elucidated, those involved in ALCLs harboring TPM3-ALK are largely unknown. In order to investigate the expression profiles of ALCLs carrying the NPM-ALK and TPM3-ALK fusions, we carried out cDNA microarray analysis of two ALCL tissue samples, one expressing the NPM-ALK fusion protein and the other the TPM3-ALK fusion protein. RNA was extracted from snap-frozen tissues, labeled with fluorescent dyes and analyzed using cDNAs microarray containing approximately 9,200 genes and expressed sequence tags (ESTs). Quantitative fluorescence RT-PCR was performed to validate the cDNA microarray data on nine selected gene targets. Our results show a significant overlap of genes deregulated in the NPM-ALK and TPM-ALK positive lymphomas. These deregulated genes are involved in diverse cellular functions, such as cell cycle regulation, apoptosis, proliferation, and adhesion. Interestingly, a subset of the genes was distinct in their expression pattern in the two types of lymphomas. More importantly, many genes that were not previously associated with ALK positive lymphomas were identified. Our results demonstrate the overlapping and unique transcriptional patterns associated with the NPM-ALK and TPM3-ALK fusions in ALCL.

  10. Sexual dimorphism of sulcal morphology of the ferret cerebrum revealed by MRI-based sulcal surface morphometry.

    PubMed

    Sawada, Kazuhiko; Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Aoki, Ichio

    2015-01-01

    The present study quantitatively assessed sexual dimorphism of cortical convolution and sulcal morphology in young adult ferrets by MRI-based sulcal surface morphometry. Ex vivo T1-weighted (short TR/TE) MRI of the ferret cerebrum was acquired with high spatial resolution at 7-tesla. The degree of cortical convolution, evaluated quantitatively based on 3D MRI data by sulcation index (SI), was significantly greater in males (0.553 ± 0.036) than in females (0.502 ± 0.043) (p < 0.001). The rostrocaudal distribution of the cortical convolution revealed a greater convolution in the frontal region of the cortex in males than in females and by a posterior extension of the convolution in the temporo-parieto-occipital region of males. Although the cerebral width in the frontal region was not different between sexes, the rhinal fissure and rostral region of splenial sulcus were more infolded in males than in females. On the contrary, the cerebral width was greater in males in the temporo-parieto-occipital region, and male-prominent posterior extension of infolding was noted in the lateral sulcus, caudal suprasylvian sulcus, pesudosylvian sulcus, hippocampal sulcus, and the caudal region of splenial sulcus. Notably, the caudal descending region of lateral sulcus was clearly infolded in males, but obscured in females. The present results suggest a region-related sexual dimorphism of the sulcal infolding, which is reflected by local cortical expansion in the ferret cerebrum. In particular, male-favored sulcal infolding with expansion of the temporo-parieto-occipital neocortex may be relevant to the human cerebral cortex regarding visuo-spatial and emotion processing, which are known to differ between sexes. The present results will provide fundamental information assessing sex-related changes in the regional sulcal infolding, when ferrets with experimentally-induced gyrification abnormality will be used as models for male-prevalent or male-earlier-onset neurodevelopmental

  11. Sexual dimorphism of sulcal morphology of the ferret cerebrum revealed by MRI-based sulcal surface morphometry

    PubMed Central

    Sawada, Kazuhiko; Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Aoki, Ichio

    2015-01-01

    The present study quantitatively assessed sexual dimorphism of cortical convolution and sulcal morphology in young adult ferrets by MRI-based sulcal surface morphometry. Ex vivo T1-weighted (short TR/TE) MRI of the ferret cerebrum was acquired with high spatial resolution at 7-tesla. The degree of cortical convolution, evaluated quantitatively based on 3D MRI data by sulcation index (SI), was significantly greater in males (0.553 ± 0.036) than in females (0.502 ± 0.043) (p < 0.001). The rostrocaudal distribution of the cortical convolution revealed a greater convolution in the frontal region of the cortex in males than in females and by a posterior extension of the convolution in the temporo-parieto-occipital region of males. Although the cerebral width in the frontal region was not different between sexes, the rhinal fissure and rostral region of splenial sulcus were more infolded in males than in females. On the contrary, the cerebral width was greater in males in the temporo-parieto-occipital region, and male-prominent posterior extension of infolding was noted in the lateral sulcus, caudal suprasylvian sulcus, pesudosylvian sulcus, hippocampal sulcus, and the caudal region of splenial sulcus. Notably, the caudal descending region of lateral sulcus was clearly infolded in males, but obscured in females. The present results suggest a region-related sexual dimorphism of the sulcal infolding, which is reflected by local cortical expansion in the ferret cerebrum. In particular, male-favored sulcal infolding with expansion of the temporo-parieto-occipital neocortex may be relevant to the human cerebral cortex regarding visuo-spatial and emotion processing, which are known to differ between sexes. The present results will provide fundamental information assessing sex-related changes in the regional sulcal infolding, when ferrets with experimentally-induced gyrification abnormality will be used as models for male-prevalent or male-earlier-onset neurodevelopmental

  12. The Plasmodium vivax Merozoite Surface Protein 3β Sequence Reveals Contrasting Parasite Populations in Southern and Northwestern Thailand

    PubMed Central

    Kuamsab, Napaporn; Sattabongkot, Jetsumon; Sirichaisinthop, Jeeraphat; Jongwutiwes, Somchai; Cui, Liwang

    2014-01-01

    Background Malaria control efforts have a significant impact on the epidemiology and parasite population dynamics. In countries aiming for malaria elimination, malaria transmission may be restricted to limited transmission hot spots, where parasite populations may be isolated from each other and experience different selection forces. Here we aim to examine the Plasmodium vivax population divergence in geographically isolated transmission zones in Thailand. Methodology We employed the P. vivax merozoite surface protein 3β (PvMSP3β) as a molecular marker for characterizing P. vivax populations based on the extensive diversity of this gene in Southeast Asian parasite populations. To examine two parasite populations with different transmission levels in Thailand, we obtained 45 P. vivax isolates from Tak Province, northwestern Thailand, where the annual parasite incidence (API) was more than 2%, and 28 isolates from Yala and Narathiwat Provinces, southern Thailand, where the API was less than 0.02%. We sequenced the PvMSP3β gene and examined its genetic diversity and molecular evolution between the parasite populations. Principal Findings Of 58 isolates containing single PvMSP3β alleles, 31 sequence types were identified. The overall haplotype diversity was 0.77±0.06 and nucleotide diversity 0.0877±0.0054. The northwestern vivax malaria population exhibited extensive haplotype diversity (HD) of PvMSP3β (HD = 1.0). In contrast, the southern parasite population displayed a single PvMSP3β allele (HD = 0), suggesting a clonal population expansion. This result revealed that the extent of allelic diversity in P. vivax populations in Thailand varies among endemic areas. Conclusion Malaria parasite populations in a given region may vary significantly in genetic diversity, which may be the result of control and influenced by the magnitude of malaria transmission intensity. This is an issue that should be taken into account for the implementation of P. vivax

  13. Comparative Analysis of the 15.5kD Box C/D snoRNP Core Protein in the Primitive Eukaryote Giardia lamblia Reveals Unique Structural and Functional Features

    SciTech Connect

    Biswas, Shyamasri; Buhrman, Greg; Gagnon, Keith; Mattos, Carla; Brown, II, Bernard A.; Maxwell, E. Stuart

    2012-07-11

    Box C/D ribonucleoproteins (RNP) guide the 2'-O-methylation of targeted nucleotides in archaeal and eukaryotic rRNAs. The archaeal L7Ae and eukaryotic 15.5kD box C/D RNP core protein homologues initiate RNP assembly by recognizing kink-turn (K-turn) motifs. The crystal structure of the 15.5kD core protein from the primitive eukaryote Giardia lamblia is described here to a resolution of 1.8 {angstrom}. The Giardia 15.5kD protein exhibits the typical {alpha}-{beta}-{alpha} sandwich fold exhibited by both archaeal L7Ae and eukaryotic 15.5kD proteins. Characteristic of eukaryotic homologues, the Giardia 15.5kD protein binds the K-turn motif but not the variant K-loop motif. The highly conserved residues of loop 9, critical for RNA binding, also exhibit conformations similar to those of the human 15.5kD protein when bound to the K-turn motif. However, comparative sequence analysis indicated a distinct evolutionary position between Archaea and Eukarya. Indeed, assessment of the Giardia 15.5kD protein in denaturing experiments demonstrated an intermediate stability in protein structure when compared with that of the eukaryotic mouse 15.5kD and archaeal Methanocaldococcus jannaschii L7Ae proteins. Most notable was the ability of the Giardia 15.5kD protein to assemble in vitro a catalytically active chimeric box C/D RNP utilizing the archaeal M. jannaschii Nop56/58 and fibrillarin core proteins. In contrast, a catalytically competent chimeric RNP could not be assembled using the mouse 15.5kD protein. Collectively, these analyses suggest that the G. lamblia 15.5kD protein occupies a unique position in the evolution of this box C/D RNP core protein retaining structural and functional features characteristic of both archaeal L7Ae and higher eukaryotic 15.5kD homologues.

  14. Roles of oxygen for methanol adsorption on polycrystalline copper surface revealed by sum frequency generation imaging microscopy

    NASA Astrophysics Data System (ADS)

    Fang, Ming; Santos, Greggy; Chen, Xiaole; Baldelli, Steven

    2016-06-01

    The adsorption of atmospheric pressure methanol on the polycrystalline copper surface has been studied by a combination of sum frequency generation imaging microscopy (SFGIM) and temperature programmed desorption (TPD). Methoxy species can be generated by exposing the polycrystalline copper surface to methanol vapor at room temperature. SFGIM results demonstrate that oxygen promotes the surface adsorption of methanol and the increase in the amount of methoxy produced on copper surface. SFGIM orientation analysis suggests the methoxy monolayer is oriented closer to the surface normal with introduction of oxygen. Employing the image statistical analysis approach, the heterogeneities and conformation distribution of methoxy monolayers on copper surface with and without oxygen adsorption are compared. These results illustrate SFGIM indeed could provide more insight for understanding the heterogeneous metal/metal oxide surface in the molecular level.

  15. C and Cl isotope fractionation of 1,2-dichloroethane displays unique δ¹³C/δ³⁷Cl patterns for pathway identification and reveals surprising C-Cl bond involvement in microbial oxidation.

    PubMed

    Palau, Jordi; Cretnik, Stefan; Shouakar-Stash, Orfan; Höche, Martina; Elsner, Martin; Hunkeler, Daniel

    2014-08-19

    This study investigates dual element isotope fractionation during aerobic biodegradation of 1,2-dichloroethane (1,2-DCA) via oxidative cleavage of a C-H bond (Pseudomonas sp. strain DCA1) versus C-Cl bond cleavage by S(N)2 reaction (Xanthobacter autotrophicus GJ10 and Ancylobacter aquaticus AD20). Compound-specific chlorine isotope analysis of 1,2-DCA was performed for the first time, and isotope fractionation (ε(bulk)(Cl)) was determined by measurements of the same samples in three different laboratories using two gas chromatography-isotope ratio mass spectrometry systems and one gas chromatography-quadrupole mass spectrometry system. Strongly pathway-dependent slopes (Δδ13C/Δδ37Cl), 0.78 ± 0.03 (oxidation) and 7.7 ± 0.2 (S(N)2), delineate the potential of the dual isotope approach to identify 1,2-DCA degradation pathways in the field. In contrast to different ε(bulk)(C) values [-3.5 ± 0.1‰ (oxidation) and -31.9 ± 0.7 and -32.0 ± 0.9‰ (S(N)2)], the obtained ε(bulk)(Cl) values were surprisingly similar for the two pathways: -3.8 ± 0.2‰ (oxidation) and -4.2 ± 0.1 and -4.4 ± 0.2‰ (S(N)2). Apparent kinetic isotope effects (AKIEs) of 1.0070 ± 0.0002 (13C-AKIE, oxidation), 1.068 ± 0.001 (13C-AKIE, S(N)2), and 1.0087 ± 0.0002 (37Cl-AKIE, S(N)2) fell within expected ranges. In contrast, an unexpectedly large secondary 37Cl-AKIE of 1.0038 ± 0.0002 reveals a hitherto unrecognized involvement of C-Cl bonds in microbial C-H bond oxidation. Our two-dimensional isotope fractionation patterns allow for the first time reliable 1,2-DCA degradation pathway identification in the field, which unlocks the full potential of isotope applications for this important groundwater contaminant.

  16. Is Life Unique?

    PubMed Central

    Abel, David L.

    2011-01-01

    Is life physicochemically unique? No. Is life unique? Yes. Life manifests innumerable formalisms that cannot be generated or explained by physicodynamics alone. Life pursues thousands of biofunctional goals, not the least of which is staying alive. Neither physicodynamics, nor evolution, pursue goals. Life is largely directed by linear digital programming and by the Prescriptive Information (PI) instantiated particularly into physicodynamically indeterminate nucleotide sequencing. Epigenomic controls only compound the sophistication of these formalisms. Life employs representationalism through the use of symbol systems. Life manifests autonomy, homeostasis far from equilibrium in the harshest of environments, positive and negative feedback mechanisms, prevention and correction of its own errors, and organization of its components into Sustained Functional Systems (SFS). Chance and necessity—heat agitation and the cause-and-effect determinism of nature’s orderliness—cannot spawn formalisms such as mathematics, language, symbol systems, coding, decoding, logic, organization (not to be confused with mere self-ordering), integration of circuits, computational success, and the pursuit of functionality. All of these characteristics of life are formal, not physical. PMID:25382119

  17. Transition from distributional to ergodic behavior in an inhomogeneous diffusion process: Method revealing an unknown surface diffusivity.

    PubMed

    Akimoto, Takuma; Seki, Kazuhiko

    2015-08-01

    Diffusion of molecules in cells plays an important role in providing a biological reaction on the surface by finding a target on the membrane surface. The water retardation (slow diffusion) near the target assists the searching molecules to recognize the target. Here, we consider effects of the surface diffusivity on the effective diffusivity, where diffusion on the surface is slower than that in bulk. We show that the ensemble-averaged mean-square displacements increase linearly with time when the desorption rate from the surface is finite, which is valid even when the diffusion on the surface is anomalous (subdiffusion). Moreover, this slow diffusion on the surface affects the fluctuations of the time-averaged mean-square displacements (TAMSDs). We find that fluctuations of the TAMSDs remain large when the measurement time is smaller than a characteristic time, and decays according to an increase of the measurement time for a relatively large measurement time. Therefore, we find a transition from nonergodic (distributional) to ergodic diffusivity in a target search process. Moreover, this fluctuation analysis provides a method to estimate an unknown surface diffusivity.

  18. Nanoscale Pulling of Type IV Pili Reveals Their Flexibility and Adhesion to Surfaces over Extended Lengths of the Pili.

    PubMed

    Lu, Shun; Giuliani, Maximiliano; Harvey, Hanjeong; Burrows, Lori L; Wickham, Robert A; Dutcher, John R

    2015-06-16

    Type IV pili (T4P) are very thin protein filaments that extend from and retract into bacterial cells, allowing them to interact with and colonize a broad array of chemically diverse surfaces. The physical aspects that allow T4P to mediate adherence to many different surfaces remain unclear. Atomic force microscopy (AFM) nanoscale pulling experiments were used to measure the mechanical properties of T4P of a mutant strain of Pseudomonas aeruginosa PAO1 unable to retract its T4P. After adhering bacteria to the end of an AFM cantilever and approaching surfaces of mica, gold, or polystyrene, we observed adhesion of the T4P to all of the surfaces. Pulling of single and multiple T4P on retraction of the cantilever from the surfaces could be described using the worm-like chain (WLC) model. Distinct peaks in the measured distributions of the best-fit values of the persistence length Lp on two different surfaces provide strong evidence for close-packed bundling of very flexible T4P. In addition, we observed force plateaus indicating that adhesion of the T4P to both hydrophilic and hydrophobic surfaces occurs along extended lengths of the T4P. These data shed new light, to our knowledge, on T4P flexibility and support a low-affinity, high-avidity adhesion mechanism that mediates bacteria-surface interactions. PMID:26083926

  19. Nutrient sampling slam: high resolution surface-water sampling in streams reveals patterns in groundwater chemistry and flow paths

    EPA Science Inventory

    The groundwater–surface water interface (GSWI), consisting of shallow groundwater adjacent to stream channels, is a hot spot for nitrogen removal processes, a storage zone for other solutes, and a target for restoration activities. Characterizing groundwater-surface water intera...

  20. Nanoscale Pulling of Type IV Pili Reveals Their Flexibility and Adhesion to Surfaces over Extended Lengths of the Pili

    PubMed Central

    Lu, Shun; Giuliani, Maximiliano; Harvey, Hanjeong; Burrows, Lori L.; Wickham, Robert A.; Dutcher, John R.

    2015-01-01

    Type IV pili (T4P) are very thin protein filaments that extend from and retract into bacterial cells, allowing them to interact with and colonize a broad array of chemically diverse surfaces. The physical aspects that allow T4P to mediate adherence to many different surfaces remain unclear. Atomic force microscopy (AFM) nanoscale pulling experiments were used to measure the mechanical properties of T4P of a mutant strain of Pseudomonas aeruginosa PAO1 unable to retract its T4P. After adhering bacteria to the end of an AFM cantilever and approaching surfaces of mica, gold, or polystyrene, we observed adhesion of the T4P to all of the surfaces. Pulling of single and multiple T4P on retraction of the cantilever from the surfaces could be described using the worm-like chain (WLC) model. Distinct peaks in the measured distributions of the best-fit values of the persistence length Lp on two different surfaces provide strong evidence for close-packed bundling of very flexible T4P. In addition, we observed force plateaus indicating that adhesion of the T4P to both hydrophilic and hydrophobic surfaces occurs along extended lengths of the T4P. These data shed new light, to our knowledge, on T4P flexibility and support a low-affinity, high-avidity adhesion mechanism that mediates bacteria-surface interactions. PMID:26083926

  1. In Situ Experiments To Reveal the Role of Surface Feature Sidewalls in the Cassie–Wenzel Transition

    PubMed Central

    2014-01-01

    Waterproof and self-cleaning surfaces continue to attract much attention as they can be instrumental in various different technologies. Such surfaces are typically rough, allowing liquids to contact only the outermost tops of their asperities, with air being entrapped underneath. The formed solid–liquid–air interface is metastable and, hence, can be forced into a completely wetted solid surface. A detailed understanding of the wetting barrier and the dynamics of this transition is critically important for the practical use of the related surfaces. Toward this aim, wetting transitions were studied in situ at a set of patterned perfluoropolyether dimethacrylate (PFPEdma) polymer surfaces exhibiting surface features with different types of sidewall profiles. PFPEdma is intrinsically hydrophobic and exhibits a refractive index very similar to water. Upon immersion of the patterned surfaces into water, incident light was differently scattered at the solid–liquid–air and solid–liquid interface, which allows for distinguishing between both wetting states by dark-field microscopy. The wetting transition observed with this methodology was found to be determined by the sidewall profiles of the patterned structures. Partial recovery of the wetting was demonstrated to be induced by abrupt and continuous pressure reductions. A theoretical model based on Laplace’s law was developed and applied, allowing for the analytical calculation of the transition barrier and the potential to revert the wetting upon pressure reduction. PMID:25496232

  2. In situ experiments to reveal the role of surface feature sidewalls in the Cassie-Wenzel transition.

    PubMed

    Hensel, René; Finn, Andreas; Helbig, Ralf; Killge, Sebastian; Braun, Hans-Georg; Werner, Carsten

    2014-12-23

    Waterproof and self-cleaning surfaces continue to attract much attention as they can be instrumental in various different technologies. Such surfaces are typically rough, allowing liquids to contact only the outermost tops of their asperities, with air being entrapped underneath. The formed solid-liquid-air interface is metastable and, hence, can be forced into a completely wetted solid surface. A detailed understanding of the wetting barrier and the dynamics of this transition is critically important for the practical use of the related surfaces. Toward this aim, wetting transitions were studied in situ at a set of patterned perfluoropolyether dimethacrylate (PFPEdma) polymer surfaces exhibiting surface features with different types of sidewall profiles. PFPEdma is intrinsically hydrophobic and exhibits a refractive index very similar to water. Upon immersion of the patterned surfaces into water, incident light was differently scattered at the solid-liquid-air and solid-liquid interface, which allows for distinguishing between both wetting states by dark-field microscopy. The wetting transition observed with this methodology was found to be determined by the sidewall profiles of the patterned structures. Partial recovery of the wetting was demonstrated to be induced by abrupt and continuous pressure reductions. A theoretical model based on Laplace's law was developed and applied, allowing for the analytical calculation of the transition barrier and the potential to revert the wetting upon pressure reduction. PMID:25496232

  3. Structure Function Studies of Vaccinia Virus Host Range Protein K1 Reveal a Novel Functional Surface for Ankyrin Repeat Proteins

    SciTech Connect

    Li, Yongchao; Meng, Xiangzhi; Xiang, Yan; Deng, Junpeng

    2010-06-15

    Poxvirus host tropism at the cellular level is regulated by virus-encoded host range proteins acting downstream of virus entry. The functioning mechanisms of most host range proteins are unclear, but many contain multiple ankyrin (ANK) repeats, a motif that is known for ligand interaction through a concave surface. We report here the crystal structure of one of the ANK repeat-containing host range proteins, the vaccinia virus K1 protein. The structure, at a resolution of 2.3 {angstrom}, showed that K1 consists entirely of ANK repeats, including seven complete ones and two incomplete ones, one each at the N and C terminus. Interestingly, Phe82 and Ser83, which were previously shown to be critical for K1's function, are solvent exposed and located on a convex surface, opposite the consensus ANK interaction surface. The importance of this convex surface was further supported by our additional mutagenesis studies. We found that K1's host range function was negatively affected by substitution of either Asn51 or Cys47 and completely abolished by substitution of both residues. Cys47 and Asn51 are also exposed on the convex surface, spatially adjacent to Phe82 and Ser83. Altogether, our data showed that K1 residues on a continuous convex ANK repeat surface are critical for the host range function, suggesting that K1 functions through ligand interaction and does so with a novel ANK interaction surface.

  4. Paired windward and leeward biogeochemical time series reveal consistent surface ocean CO2 trends across the Hawaiian Ridge

    NASA Astrophysics Data System (ADS)

    Dore, John E.; Church, Matthew J.; Karl, David M.; Sadler, Daniel W.; Letelier, Ricardo M.

    2014-09-01

    Sustained time series have provided compelling evidence for progressive acidification of the surface oceans through exchange with the growing atmospheric reservoir of carbon dioxide. However, few long-term programs exist, and extrapolation of results from one site to larger oceanic expanses is hampered by the lack of spatial coverage inherent to Eulerian sampling. Since 1988, the Hawaii Ocean Time-series program has sampled CO2 system variables nearly monthly at Station ALOHA, a deep ocean site windward and 115 km north of the island of Oahu. Surface measurements have also been made at Station Kahe, a leeward site 12 km from the island and on the opposite side of the Hawaiian Ridge. Despite having different physical settings, the sites exhibit identical rates of surface pCO2 increase and hydrogen ion accumulation, suggesting that atmospheric forcing dominates over local dynamics in determining the CO2 trend in the surface waters of the North Pacific subtropical gyre.

  5. Dynamic and unique nucleolar microenvironment revealed by fluorescence correlation spectroscopy.

    PubMed

    Park, Hweon; Han, Sung-Sik; Sako, Yasushi; Pack, Chan-Gi

    2015-03-01

    Organization and functions of the nucleolus is maintained by mobilities and interactions of nucleolar factors. Because the nucleolus is a densely packed structure, molecular crowding effects determined by the molecular concentrations and mobilities in the nucleolus should also be important for regulating nucleolar organization and functions. However, such molecular property of nucleolar organization is not fully understood. To understand the biophysical property of nucleolar organization, the diffusional behaviors of inert green fluorescent protein (GFP) oligomers with or without nuclear localization signals (NLSs) were analyzed under various conditions by fluorescence correlation spectroscopy. Our result demonstrates that the mobility of GFPs inside the nucleolus and the nucleoplasm can be represented by single free diffusion under normal conditions, even though the mobility in the nucleolus is considerably slower than that in the chromatin region. Moreover, the free diffusion of GFPs is found to be significantly size- and NLS-dependent only in the nucleolus. Interestingly, the mobility in the nucleolus is highly sensitive to ATP depletion, as well as actinomycin D (ActD) treatment. In contrast, the ultra-structure of the nucleolus was not significantly changed by ATP depletion but was changed by ActD treatment. These results suggest that the nucleolus behaves similarly to an open aqueous-phase medium with an increased molecular crowding effect that depends on both energy and transcription.

  6. Genome analysis of the platypus reveals unique signatures of evolution

    PubMed Central

    Warren, Wesley C.; Hillier, LaDeana W.; Marshall Graves, Jennifer A.; Birney, Ewan; Ponting, Chris P.; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T.; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P.; Miethke, Pat; Waters, Paul D.; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S.; López-Otín, Carlos; Ordóñez, Gonzalo R.; Eichler, Evan E.; Chen, Lin; Cheng, Ze; Deakin, Janine E.; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T.; Wakefield, Matthew J.; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A.; Smit, Arian F. A.; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A.; Walker, Jerilyn A.; Konkel, Miriam K.; Harris, Robert S.; Whittington, Camilla M.; Wong, Emily S. W.; Gemmell, Neil J.; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M.; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P.; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J.; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M.; Sharp, Julie A.; Nicholas, Kevin R.; Ray, David A.; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H.; Taylor, James; Jones, Russell C.; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N.; Pohl, Craig S.; Smith, Scott M.; Hou, Shunfeng; Renfree, Marilyn B.; Mardis, Elaine R.; Wilson, Richard K.

    2009-01-01

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. PMID:18464734

  7. Surface activity and molecular organization of metallacarboranes at the air-water interface revealed by nonlinear optics.

    PubMed

    Gassin, Pierre-Marie; Girard, Luc; Martin-Gassin, Gaelle; Brusselle, Damien; Jonchère, Alban; Diat, Olivier; Viñas, Clara; Teixidor, Francesc; Bauduin, Pierre

    2015-03-01

    Because of their amphiphilic structure, surfactants adsorb at the water-air interface with their hydrophobic tails pointing out of the water and their polar heads plunging into the liquid phase. Unlike classical surfactants, metallabisdicarbollides (MCs) do not have a well-defined amphiphilic structure. They are nanometer-sized inorganic anions with an ellipsoidal shape composed of two carborane semicages sandwiching a metal ion. However, MCs have been shown to share many properties with surfactants, such as self-assembly in water (formation of micelles and vesicles), formation of lamellar lyotropic phases, and surface activity. By combining second harmonic generation and surface tension measurement, we show here that cobaltabis(dicarbollide) anion {[(C2B9H11)2Co](-) also named [COSAN](-)} with H(+) as a counterion, the most representative metallacarborane, adsorbs vertically at the water surface with its long axis normal to the surface. This vertical molecular orientation facilitates the formation of intermolecular and nonconventional dihydrogen bonds such as the B-H(δ-)···(δ+)H-C bond that has recently been proven to be at the origin of the self-assembly of MCs in water. Therefore, it appears here that lateral dihydrogen bonds are also involved in the surface activity of MCs.

  8. COMETARY SCIENCE. CHO-bearing organic compounds at the surface of 67P/Churyumov-Gerasimenko revealed by Ptolemy.

    PubMed

    Wright, I P; Sheridan, S; Barber, S J; Morgan, G H; Andrews, D J; Morse, A D

    2015-07-31

    The surface and subsurface of comets preserve material from the formation of the solar system. The properties of cometary material thus provide insight into the physical and chemical conditions during their formation. We present mass spectra taken by the Ptolemy instrument 20 minutes after the initial touchdown of the Philae lander on the surface of comet 67P/Churyumov-Gerasimenko. Regular mass distributions indicate the presence of a sequence of compounds with additional -CH2- and -O- groups (mass/charge ratios 14 and 16, respectively). Similarities with the detected coma species of comet Halley suggest the presence of a radiation-induced polymer at the surface. Ptolemy measurements also indicate an apparent absence of aromatic compounds such as benzene, a lack of sulfur-bearing species, and very low concentrations of nitrogenous material.

  9. CHO-bearing organic compounds at the surface of 67P/Churyumov-Gerasimenko revealed by Ptolemy

    NASA Astrophysics Data System (ADS)

    Wright, I. P.; Sheridan, S.; Barber, S. J.; Morgan, G. H.; Andrews, D. J.; Morse, A. D.

    2015-07-01

    The surface and subsurface of comets preserve material from the formation of the solar system. The properties of cometary material thus provide insight into the physical and chemical conditions during their formation. We present mass spectra taken by the Ptolemy instrument 20 minutes after the initial touchdown of the Philae lander on the surface of comet 67P/Churyumov-Gerasimenko. Regular mass distributions indicate the presence of a sequence of compounds with additional -CH2- and -O- groups (mass/charge ratios 14 and 16, respectively). Similarities with the detected coma species of comet Halley suggest the presence of a radiation-induced polymer at the surface. Ptolemy measurements also indicate an apparent absence of aromatic compounds such as benzene, a lack of sulfur-bearing species, and very low concentrations of nitrogenous material.

  10. COMETARY SCIENCE. CHO-bearing organic compounds at the surface of 67P/Churyumov-Gerasimenko revealed by Ptolemy.

    PubMed

    Wright, I P; Sheridan, S; Barber, S J; Morgan, G H; Andrews, D J; Morse, A D

    2015-07-31

    The surface and subsurface of comets preserve material from the formation of the solar system. The properties of cometary material thus provide insight into the physical and chemical conditions during their formation. We present mass spectra taken by the Ptolemy instrument 20 minutes after the initial touchdown of the Philae lander on the surface of comet 67P/Churyumov-Gerasimenko. Regular mass distributions indicate the presence of a sequence of compounds with additional -CH2- and -O- groups (mass/charge ratios 14 and 16, respectively). Similarities with the detected coma species of comet Halley suggest the presence of a radiation-induced polymer at the surface. Ptolemy measurements also indicate an apparent absence of aromatic compounds such as benzene, a lack of sulfur-bearing species, and very low concentrations of nitrogenous material. PMID:26228155

  11. Revealing surface oxidation on the organic semi-conducting single crystal rubrene with time of flight secondary ion mass spectroscopy.

    PubMed

    Thompson, Robert J; Fearn, Sarah; Tan, Ke Jie; Cramer, Hans George; Kloc, Christian L; Curson, Neil J; Mitrofanov, Oleg

    2013-04-14

    To address the question of surface oxidation in organic electronics the chemical composition at the surface of single crystalline rubrene is spatially profiled and analyzed using Time of Flight - Secondary Ion Mass Spectroscopy (ToF-SIMS). It is seen that a uniform oxide (C42H28O) covers the surface while there is an increased concentration of peroxide (C42H28O2) located at crystallographic defects. By analyzing the effects of different primary ions, temperature and sputtering agents the technique of ToF-SIMS is developed as a valuable tool for the study of chemical composition variance both at and below the surface of organic single crystals. The primary ion beams C60(3+) and Bi3(+) are found to be most appropriate for mass spectroscopy and spatial profiling respectively. Depth profiling of the material is successfully undertaken maintaining the molecular integrity to a depth of ~5 μm using an Ar cluster ion source as the sputtering agent. PMID:23455651

  12. Preeruptive inflation and surface interferometric coherence characteristics revealed by satellite radar interferometry at Makushin Volcano, Alaska: 1993-2000

    USGS Publications Warehouse

    Lu, Zhiming; Power, J.A.; McConnell, V.S.; Wicks, C.; Dzurisin, D.

    2002-01-01

    Pilot reports in January 1995 and geologic field observations from the summer of 1996 indicate that a relatively small explosive eruption of Makushin, one of the more frequently active volcanoes in the Aleutian arc of Alaska, occured on 30 January 1995. Several independent radar interferograms that each span the time period from October 1993 to September 1995 show evidence of ???7 cm of uplift centered on the volcano's east flank, which we interpret as preeruptive inflation of a ???7-km-deep magma source (??V = 0.022 km3). Subsequent interferograms for 1995-2000, a period that included no reported eruptive activity, show no evidence of additional ground deformation. Interferometric coherence at C band is found to persist for 3 years or more on lava flow and other rocky surfaces covered with short grass and sparsely distributed tall grass and for at least 1 year on most pyroclastic deposits. On lava flow and rocky surfaces with dense tall grass and on alluvium, coherence lasts for a few months. Snow and ice surfaces lose coherence within a few days. This extended timeframe of coherence over a variety of surface materials makes C band radar interferometry an effective tool for studying volcano deformation in Alaska and other similar high-latitude regions.

  13. Patterns of river width and surface area newly revealed by the satellite-derived North American River Width (NARWidth) dataset

    NASA Astrophysics Data System (ADS)

    Allen, G. H.; Pavelsky, T.

    2014-12-01

    The total surface area of rivers and streams is a key quantity for estimating gaseous emissions from fluvial networks to the atmosphere. Presently, the most sophisticated evaluations of continental-scale river surface area rely on: 1) calculating river width from digital elevation models (DEMs) by scaling width to upstream drainage area via downstream hydraulic geometry (DHG) relationships; 2) extrapolating river width and length from large to small river basins using Horton ratios; and 3) extrapolating empirical relationships between climate and percentage water cover to from low- to high-latitude basins where hydrologically conditioned topographic data does not exist. Here we use the recently developed North American River Width (NARWidth) dataset to estimate the total surface area of North American rivers and streams. NARWidth is the first fine-resolution, continental-scale river centerline and width database. The database is derived from Landsat satellite imagery and contains measurements of >2.4×105 km of rivers wider than 30 m at mean annual discharge. We find that datasets that estimate river width by applying DHG relationships to DEMs underestimate the abundance of wide rivers and do not capture the widest rivers observed by NARWidth. We attribute these differences to: 1) the tendency of stream gauges to be located at stable, single channel sites, leading to a potential bias of measured river width relative to the representative river width throughout a river's entire length; and 2) physiographic conditions that are not captured by DHG and can cause substantial deviation from strict width-discharge relationships. We then calculate the total surface area of North American rivers by extrapolating the strong observed relationship between total river surface area and width at different widths (r2>0.996 for 100-2000 m widths) to narrow rivers and streams. We find that the total surface area of North American rivers is ~1.38×105 km2 for all rivers wider than 1

  14. Martian Alteration in Unique Meteorite NWA 8159?

    NASA Astrophysics Data System (ADS)

    Hallis, L. J.; Simpson, S.; Mark, D.; Lee, M. R.

    2016-08-01

    This study aims to determine if the olivine alteration in martian meteorite NWA 8159 has a martian origin. If so, the unique nature of this meteorite presents evidence for aqueous processes at a new time and location on the martian surface.

  15. Problems at the Leading Edge of Space Weathering as Revealed by TEM Combined with Surface Science Techniques

    NASA Technical Reports Server (NTRS)

    Christoffersen, R.; Dukes, C. A.; Keller, L. P.; Rahman, Z.; Baragiola, R. A.

    2015-01-01

    Both transmission electron micros-copy (TEM) and surface analysis techniques such as X-ray photoelectron spectroscopy (XPS) were instrumen-tal in making the first characterizations of material generated by space weathering in lunar samples [1,2]. Without them, the nature of nanophase metallic Fe (npFe0) correlated with the surface of lunar regolith grains would have taken much longer to become rec-ognized and understood. Our groups at JSC and UVa have been using both techniques in a cross-correlated way to investigate how the solar wind contributes to space weathering [e.g., 3]. These efforts have identified a number of ongoing problems and knowledge gaps. Key insights made by UVa group leader Raul Barag-iola during this work are gratefully remembered.

  16. Some characterizations of unique extremality

    NASA Astrophysics Data System (ADS)

    Yao, Guowu

    2008-07-01

    In this paper, it is shown that some necessary characteristic conditions for unique extremality obtained by Zhu and Chen are also sufficient and some sufficient ones by them actually imply that the uniquely extremal Beltrami differentials have a constant modulus. In addition, some local properties of uniquely extremal Beltrami differentials are given.

  17. Discovery of the surface polarity gradient on iridescent Morpho butterfly scales reveals a mechanism of their selective vapor response

    PubMed Central

    Potyrailo, Radislav A.; Starkey, Timothy A.; Vukusic, Peter; Ghiradella, Helen; Vasudev, Milana; Bunning, Timothy; Naik, Rajesh R.; Tang, Zhexiong; Larsen, Michael; Deng, Tao; Zhong, Sheng; Palacios, Manuel; Grande, James C.; Zorn, Gilad; Goddard, Gregory; Zalubovsky, Sergey

    2013-01-01

    For almost a century, the iridescence of tropical Morpho butterfly scales has been known to originate from 3D vertical ridge structures of stacked periodic layers of cuticle separated by air gaps. Here we describe a biological pattern of surface functionality that we have found in these photonic structures. This pattern is a gradient of surface polarity of the ridge structures that runs from their polar tops to their less-polar bottoms. This finding shows a biological pattern design that could stimulate numerous technological applications ranging from photonic security tags to self-cleaning surfaces, gas separators, protective clothing, sensors, and many others. As an important first step, this biomaterial property and our knowledge of its basis has allowed us to unveil a general mechanism of selective vapor response observed in the photonic Morpho nanostructures. This mechanism of selective vapor response brings a multivariable perspective for sensing, where selectivity is achieved within a single chemically graded nanostructured sensing unit, rather than from an array of separate sensors. PMID:24019497

  18. Diminished swelling of cross-linked aromatic oligoamide surfaces revealing a new fouling mechanism of reverse-osmosis membranes.

    PubMed

    Ying, Wang; Kumar, Rajender; Herzberg, Moshe; Kasher, Roni

    2015-06-01

    Swelling of the active layer of reverse osmosis (RO) membranes has an important effect on permeate water flux. The effects of organic- and biofouling on the swelling of the RO membrane active layer and the consequent changes of permeate flux are examined here. A cross-linked aromatic oligoamide film that mimics the surface chemistry of an RO polyamide membrane was synthesized stepwise on gold-coated surfaces. Foulant adsorption to the oligoamide film and its swelling were measured with a quartz crystal microbalance, and the effects of fouling on the membrane's performance were evaluated. The foulants were extracellular polymeric substances (EPS) extracted from fouled RO membranes and organic compounds of ultrafiltration permeate (UFP) from a membrane bioreactor used to treat municipal wastewater. The adsorbed foulants affected the swelling of the cross-linked oligoamide film differently. EPS had little effect on the swelling of the oligoamide film, whereas UFP significantly impaired swelling. Permeate flux declined more rapidly under UFP fouling than it did under EPS. Foulant adsorption was shown to diminish swelling of the aromatic oligoamide surfaces. Among the already known RO membrane fouling mechanisms, a novel RO fouling mechanism is proposed, in which foulant-membrane interactions hinder membrane swelling and thus increase hydraulic resistance.

  19. Chicago's unique state center

    SciTech Connect

    Stamm, R.H.

    1985-01-01

    The system as designed is probably as energy and cost effective as could have been designed in the spring of 1980. It is complex. Fortunately, the operating crew is excellent in both technical capability and attitudes. The system is currently in the start-up mode. The temperature control system is not complete. There are a few glitches, but no major problems. The authors anticipate being able to operate the system as an example of what can be accomplished without excessive first costs in load shifting, energy conservation, and perhaps most importantly reducing operating costs. The thermal storage technology has changed dramatically since the spring of 1980. In the future the system probably would not build ice on the heat transfer surface and use a daily cycle, but would use icemakers and a larger tank to take advantage of the off-peak rates over weekends and holidays. Nearly double the cooling load can be handled totally off peak with the same installed compressor, condenser, and evaporator capacity. The refrigeration valving would be handled differently to afford simpler control.

  20. Right temporopolar activation associated with unique perception.

    PubMed

    Asari, Tomoki; Konishi, Seiki; Jimura, Koji; Chikazoe, Junichi; Nakamura, Noriko; Miyashita, Yasushi

    2008-05-15

    Unique mode of perception, or the ability to see things differently from others, is one of the psychological resources required for creative mental activities. Behavioral studies using ambiguous visual stimuli have successfully induced diverse responses from subjects, and the unique responses defined in this paradigm were observed in higher frequency in the artistic population as compared to the nonartistic population. However, the neural substrates that underlie such unique perception have yet to be investigated. In the present study, ten ambiguous figures were used as stimuli. The subjects were instructed to say what the figures looked like during functional MRI scanning. The responses were classified as "frequent", "infrequent" or "unique" responses based on the appearance frequency of the same response in an independent age- and gender-matched control group. An event-related analysis contrasting unique vs. frequent responses revealed the greatest activation in the right temporal pole, which survived a whole brain multiple comparison. An alternative parametric modulation analysis was also performed to show that potentially confounding perceptual effects deriving from differences in visual stimuli make no significant contribution to this temporopolar activation. Previous neuroimaging and neuropsychological studies have shown the involvement of the temporal pole in perception-emotion linkage. Thus, our results suggest that unique perception is produced by the integration of perceptual and emotional processes, and this integration might underlie essential parts of creative mental activities.

  1. Surface circulation patterns in the Sicily Channel and Ionian Sea as revealed by MODIS chlorophyll images from 2003 to 2007

    NASA Astrophysics Data System (ADS)

    Ciappa, Achille Carlo

    2009-09-01

    The surface circulation in the Sicily Channel and in the Ionian Sea is investigated using MODerate-resolution Infrared Spectro-radiometer (MODIS) chlorophyll-a images collected from 2003 to 2007. The use of chlorophyll as surface tracer in the area is verified by comparison with satellite altimeter measurements available during the same period. The interaction between waters with different concentrations of chlorophyll adds new particulars to the surface circulation of the Atlantic Water (AW) in the study area. In the Sicily Channel, warm anticyclonic structures located in the southern end drive the AW flow along their northern boundary to the south-east, towards the Libyan coast. In winter, the anticyclonic structures contract in a stable nucleus (the Sidra gyre) close to the African coast allowing AW intrusion over the Tunisian shelf (Atlantic Tunisian Current). In summer, the anticyclonic structure expands westwards, limiting the Atlantic Tunisian Current, and northwards, grazing the Atlantic Ionian Stream. It also fragments, allowing occasional AW intrusion into the central part of the Sicily Channel along different pathways. Due to the activity of the Sidra gyre, no evidence of the extension of the Atlantic Tunisian Current along the Libyan coast (east of 15°E) is found in the observation period. AW spreads into the central Ionian for long periods in summer but rarely in winter. It reaches the northern Ionian Sea via anticyclonic eddies (already observed in thermal imagery) departing from the northern and eastern border of the anticyclonic structure, captured by the prevalent clockwise offshore circulation in the northern Ionian (except in summer 2003). The deduced circulation is in agreement with recent studies based on the altimetric Mean Dynamic Topography and trajectories of drifters released in the Sicily Channel in recent years.

  2. Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions.

    PubMed

    Laine, Elodie; Carbone, Alessandra

    2015-12-01

    Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins and binding to multiple partners. Contrary to machine learning approaches, our method combines in a rational and very straightforward way three sequence- and structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties and local geometry. The implemented strategy yields very precise predictions for a wide range of protein-protein interfaces and discriminates them from small-molecule binding sites. Beyond its predictive power, the approach permits to dissect interaction surfaces and unravel their complexity. We show how the analysis of the predicted patches can foster new strategies for PPIs modulation and interaction surface redesign. The approach is implemented in JET2, an automated tool based on the Joint Evolutionary Trees (JET) method for sequence-based protein interface prediction. JET2 is freely available at www.lcqb.upmc.fr/JET2.

  3. Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions

    PubMed Central

    Laine, Elodie; Carbone, Alessandra

    2015-01-01

    Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins and binding to multiple partners. Contrary to machine learning approaches, our method combines in a rational and very straightforward way three sequence- and structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties and local geometry. The implemented strategy yields very precise predictions for a wide range of protein-protein interfaces and discriminates them from small-molecule binding sites. Beyond its predictive power, the approach permits to dissect interaction surfaces and unravel their complexity. We show how the analysis of the predicted patches can foster new strategies for PPIs modulation and interaction surface redesign. The approach is implemented in JET2, an automated tool based on the Joint Evolutionary Trees (JET) method for sequence-based protein interface prediction. JET2 is freely available at www.lcqb.upmc.fr/JET2. PMID:26690684

  4. A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization*

    PubMed Central

    Pischedda, Francesca; Szczurkowska, Joanna; Cirnaru, Maria Daniela; Giesert, Florian; Vezzoli, Elena; Ueffing, Marius; Sala, Carlo; Francolini, Maura; Hauck, Stefanie M.; Cancedda, Laura; Piccoli, Giovanni

    2014-01-01

    A complex and still not comprehensively resolved panel of transmembrane proteins regulates the outgrowth and the subsequent morphological and functional development of neuronal processes. In order to gain a more detailed description of these events at the molecular level, we have developed a cell surface biotinylation assay to isolate, detect, and quantify neuronal membrane proteins. When we applied our assay to investigate neuron maturation in vitro, we identified 439 differentially expressed proteins, including 20 members of the immunoglobulin superfamily. Among these candidates, we focused on Negr1, a poorly described cell adhesion molecule. We demonstrated that Negr1 controls the development of neurite arborization in vitro and in vivo. Given the tight correlation existing among synaptic cell adhesion molecules, neuron maturation, and a number of neurological disorders, our assay results are a useful tool that can be used to support the understanding of the molecular bases of physiological and pathological brain function. PMID:24382801

  5. A cell surface biotinylation assay to reveal membrane-associated neuronal cues: Negr1 regulates dendritic arborization.

    PubMed

    Pischedda, Francesca; Szczurkowska, Joanna; Cirnaru, Maria Daniela; Giesert, Florian; Vezzoli, Elena; Ueffing, Marius; Sala, Carlo; Francolini, Maura; Hauck, Stefanie M; Cancedda, Laura; Piccoli, Giovanni

    2014-03-01

    A complex and still not comprehensively resolved panel of transmembrane proteins regulates the outgrowth and the subsequent morphological and functional development of neuronal processes. In order to gain a more detailed description of these events at the molecular level, we have developed a cell surface biotinylation assay to isolate, detect, and quantify neuronal membrane proteins. When we applied our assay to investigate neuron maturation in vitro, we identified 439 differentially expressed proteins, including 20 members of the immunoglobulin superfamily. Among these candidates, we focused on Negr1, a poorly described cell adhesion molecule. We demonstrated that Negr1 controls the development of neurite arborization in vitro and in vivo. Given the tight correlation existing among synaptic cell adhesion molecules, neuron maturation, and a number of neurological disorders, our assay results are a useful tool that can be used to support the understanding of the molecular bases of physiological and pathological brain function.

  6. Satellite-based measurements of surface deformation reveal fluid flow associated with the geological storage of carbon dioxide

    SciTech Connect

    Vasco, D.W.; Rucci, A.; Ferretti, A.; Novali, F.; Bissell, R.; Ringrose, P.; Mathieson, A.; Wright, I.

    2009-10-15

    Interferometric Synthetic Aperture Radar (InSAR), gathered over the In Salah CO{sub 2} storage project in Algeria, provides an early indication that satellite-based geodetic methods can be effective in monitoring the geological storage of carbon dioxide. An injected volume of 3 million tons of carbon dioxide, from one of the first large-scale carbon sequestration efforts, produces a measurable surface displacement of approximately 5 mm/year. Using geophysical inverse techniques we are able to infer flow within the reservoir layer and within a seismically detected fracture/ fault zone intersecting the reservoir. We find that, if we use the best available elastic Earth model, the fluid flow need only occur in the vicinity of the reservoir layer. However, flow associated with the injection of the carbon dioxide does appear to extend several kilometers laterally within the reservoir, following the fracture/fault zone.

  7. Single-Molecule Imaging of Nav1.6 on the Surface of Hippocampal Neurons Reveals Somatic Nanoclusters.

    PubMed

    Akin, Elizabeth J; Solé, Laura; Johnson, Ben; Beheiry, Mohamed El; Masson, Jean-Baptiste; Krapf, Diego; Tamkun, Michael M

    2016-09-20

    Voltage-gated sodium (Nav) channels are responsible for the depolarizing phase of the action potential in most nerve cells, and Nav channel localization to the axon initial segment is vital to action potential initiation. Nav channels in the soma play a role in the transfer of axonal output information to the rest of the neuron and in synaptic plasticity, although little is known about Nav channel localization and dynamics within this neuronal compartment. This study uses single-particle tracking and photoactivation localization microscopy to analyze cell-surface Nav1.6 within the soma of cultured hippocampal neurons. Mean-square displacement analysis of individual trajectories indicated that half of the somatic Nav1.6 channels localized to stable nanoclusters ∼230 nm in diameter. Strikingly, these domains were stabilized at specific sites on the cell membrane for >30 min, notably via an ankyrin-independent mechanism, indicating that the means by which Nav1.6 nanoclusters are maintained in the soma is biologically different from axonal localization. Nonclustered Nav1.6 channels showed anomalous diffusion, as determined by mean-square-displacement analysis. High-density single-particle tracking of Nav channels labeled with photoactivatable fluorophores in combination with Bayesian inference analysis was employed to characterize the surface nanoclusters. A subpopulation of mobile Nav1.6 was observed to be transiently trapped in the nanoclusters. Somatic Nav1.6 nanoclusters represent a new, to our knowledge, type of Nav channel localization, and are hypothesized to be sites of localized channel regulation. PMID:27653482

  8. Hidden phases revealed at the surface of double-layered S r3(Ru1-xM nx) 2O7

    NASA Astrophysics Data System (ADS)

    Chen, Chen; Kim, Jisun; Nascimento, V. B.; Diao, Zhenyu; Teng, Jing; Hu, Biao; Li, Guorong; Liu, Fangyang; Zhang, Jiandi; Jin, Rongying; Plummer, E. W.

    2016-08-01

    Double-layered S r3R u2O7 has received phenomenal consideration because it exhibits a plethora of exotic phases when perturbed. New phases emerge with the application of pressure, magnetic field, or doping. Here, we show that creating a surface is an alternative and effective way to reveal hidden phases that are different from those seen in the bulk by investigating the surface properties of S r3(Ru1-xM nx) 2O7 . Driven by the tilt distortion of Ru O6 octahedra, the surface of S r3R u2O7 is less metallic than the bulk. In contrast, because of the vanishing of tilt and enhanced rotation with Mn doping, the surface of S r3(Ru0.84Mn0.16 ) 2O7 is metallic, while the bulk is insulating. Our result demonstrates that the electronic and structural properties at the surface are intimately coupled and consistent with quasitwo-dimensional character.

  9. Unique sugar metabolic pathways of bifidobacteria.

    PubMed

    Fushinobu, Shinya

    2010-01-01

    Bifidobacteria have many beneficial effects for human health. The gastrointestinal tract, where natural colonization of bifidobacteria occurs, is an environment poor in nutrition and oxygen. Therefore, bifidobacteria have many unique glycosidases, transporters, and metabolic enzymes for sugar fermentation to utilize diverse carbohydrates that are not absorbed by host humans and animals. They have a unique, effective central fermentative pathway called bifid shunt. Recently, a novel metabolic pathway that utilizes both human milk oligosaccharides and host glycoconjugates was found. The galacto-N-biose/lacto-N-biose I metabolic pathway plays a key role in colonization in the infant gastrointestinal tract. These pathways involve many unique enzymes and proteins. This review focuses on their molecular mechanisms, as revealed by biochemical and crystallographic studies.

  10. High resolution electrolyte for thinning InP by anodic dissolution and its applications to EC-V profiling, defect revealing and surface passivation

    NASA Technical Reports Server (NTRS)

    Faur, Maria; Faur, Mircea; Weinberg, Irving; Goradia, Manju; Vargas, Carlos

    1991-01-01

    An extensive experimental study was conducted using various electrolytes in an effort to find an appropriate electrolyte for anodic dissolution of InP. From the analysis of electrochemical characteristics in the dark and under different illumination levels, x ray photoelectron spectroscopy and SEM/Nomarski inspection of the surfaces, it was determined that the anodic dissolution of InP front surface layers by FAP electrolyte is a very good choice for rendering smooth surfaces, free of oxides and contaminants and with good electrical characteristics. The FAP electrolyte, based on HF, CH3COOH, and H2O2 appears to be inherently superior to previously reported electrolytes for performing accurate EC-V profiling of InP at current densities of up to 0.3 mA/sq cm. It can also be used for accurate electrochemical revealing of either precipitates or dislocation density with application to EPD mapping as a function of depth, and for defect revealing of multilayer InP structures at any depth and/or at the interfaces.

  11. Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes.

    PubMed

    Mallanna, Sunil K; Cayo, Max A; Twaroski, Kirk; Gundry, Rebekah L; Duncan, Stephen A

    2016-09-13

    When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes. Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation. FACS purification of hepatocyte-like cells expressing SLC10A1, CLRN3, or AADAC demonstrated enrichment of cells with hepatocyte characteristics. Moreover, transcriptome analyses revealed that cells expressing the liver gene regulatory network were enriched while cells expressing a pluripotent stem cell network were depleted. In conclusion, we report an extensive catalog of cell-surface N-linked glycoproteins expressed in primary hepatocytes and identify cell-surface proteins that facilitate the purification of homogeneous populations of iPSC-derived hepatocyte-like cells.

  12. Dynamics of Soil Deflation Features in Kangerlussuaq, Greenland Revealed by Variations in Lichen Diameters on Exposed Surfaces

    NASA Astrophysics Data System (ADS)

    Heindel, R. C.; Kelly, M. A.; Virginia, R. A.

    2013-12-01

    Little is known about the pervasive soil deflation features in the Kangerlussuaq region, West Greenland, an area deglaciated between ~6,800 and 150 years ago. While the majority of the landscape is vegetated with low-lying shrubs and graminoids, wind erosion has removed loess and vegetation from distinct patches ranging in size from a few to tens of meters across, leaving the underlying glacial till or bedrock exposed. Although previous work has considered aeolian landforms and regional loess deposition along the Watson River Valley, these deflation features have not been investigated in detail. We aim to determine both the timing and mechanisms of formation of the deflation features and will examine whether these mechanisms were related to regional climatic conditions, such as increased aridity, to fluctuations in the Greenland Ice Sheet, or to other factors. Our ongoing research investigating these features includes geomorphic mapping using field observations and satellite imagery, lichenometry of the exposed surfaces, and cosmogenic nuclide dating of boulders and bedrock within and near the deflation features. Here we present initial results from our lichenometry studies. During the summer of 2013, we measured maximum lichen (Rhizocarpon sp.) diameters on boulder and bedrock surfaces in 15 soil deflation features located between Kangerlussuaq and the ice sheet margin. Lichen diameters vary from only a few millimeters at the outer margins of deflation features to multiple centimeters (maximum ~50 mm) in the centers of the unvegetated patches. This distinct pattern suggests that the outer margins of the soil deflation features are currently active. Based on a previously established lichen growth curve for Rhizocarpon sp. in West Greenland, our results indicate that the features are expanding at a rate of ~1.5 m per 100 yrs. In addition, the large lichen diameters (~40-50 mm) that occur in the centers of deflation features suggest that the formation mechanism has

  13. Uniqueness Theorem for Black Objects

    SciTech Connect

    Rogatko, Marek

    2010-06-23

    We shall review the current status of uniqueness theorem for black objects in higher dimensional spacetime. At the beginning we consider static charged asymptotically flat spacelike hypersurface with compact interior with both degenerate and non-degenerate components of the event horizon in n-dimensional spacetime. We gave some remarks concerning partial results in proving uniqueness of stationary axisymmetric multidimensional solutions and winding numbers which can uniquely characterize the topology and symmetry structure of black objects.

  14. Mechanical Perturbations of the Walking Surface Reveal Unaltered Axial Trunk Stiffness in Chronic Low Back Pain Patients

    PubMed Central

    Meijer, Onno G.

    2016-01-01

    Introduction Patients with chronic low back pain (CLBP) often demonstrate altered timing of thorax rotations in the transverse plane during gait. Increased axial trunk stiffness has been claimed to cause this movement pattern. Objectives The objective of this study was to assess whether axial trunk stiffness is increased in gait in CLBP patients. Methods 15 CLBP patients and 15 healthy controls walked on a treadmill that imposed rotational perturbations in the transverse plane. The effect of these perturbations on transverse pelvis, thorax and trunk (thorax relative to pelvis) rotations was evaluated in terms of residual rotations, i.e., the deviation of these movements from the unperturbed patterns. In view of the heterogeneity of the CLBP group, we additionally performed a subgroup comparison between seven patients and seven controls with maximal between-group contrast for timing of thorax rotations. Results Rotations of the walking surface had a clear effect on transverse pelvis, thorax and trunk rotations in all groups. No significant between-group differences on residual transverse pelvis, thorax and trunk rotations were observed. Conclusion Axial trunk stiffness in gait does not appear to be increased in CLBP. Altered timing of thorax rotations in CLBP does not seem to be a result of increased axial trunk stiffness. PMID:27310528

  15. Binding and movement of individual Cel7A cellobiohydrolases on crystalline cellulose surfaces revealed by single-molecule fluorescence imaging.

    PubMed

    Jung, Jaemyeong; Sethi, Anurag; Gaiotto, Tiziano; Han, Jason J; Jeoh, Tina; Gnanakaran, Sandrasegaram; Goodwin, Peter M

    2013-08-16

    The efficient catalytic conversion of biomass to bioenergy would meet a large portion of energy requirements in the near future. A crucial step in this process is the enzyme-catalyzed hydrolysis of cellulose to glucose that is then converted into fuel such as ethanol by fermentation. Here we use single-molecule fluorescence imaging to directly monitor the movement of individual Cel7A cellobiohydrolases from Trichoderma reesei (TrCel7A) on the surface of insoluble cellulose fibrils to elucidate molecular level details of cellulase activity. The motion of multiple, individual TrCel7A cellobiohydrolases was simultaneously recorded with ∼15-nm spatial resolution. Time-resolved localization microscopy provides insights on the activity of TrCel7A on cellulose and informs on nonproductive binding and diffusion. We measured single-molecule residency time distributions of TrCel7A bound to cellulose both in the presence of and absence of cellobiose the major product and a potent inhibitor of Cel7A activity. Combining these results with a kinetic model of TrCel7A binding provides microscopic insight into interactions between TrCel7A and the cellulose substrate. PMID:23818525

  16. An overview of the Gulf of Batabanó (Cuba): Environmental features as revealed by surface sediment characterisation

    NASA Astrophysics Data System (ADS)

    Alonso-Hernández, Carlos M.; Conte, Fabio; Misic, Cristina; Barsanti, Mattia; Gómez-Batista, Miguel; Díaz-Asencio, Misael; Covazzi-Harriague, Anabella; Pannacciulli, Federica G.

    2011-05-01

    The main environmental features of the Gulf of Batabanó, Cuba, Caribbean, were investigated through the analyses of surface sediments collected at 23 sites. In order to highlight the potential threats affecting the sedimentary compartment of this area, samples were analysed for: granulometry, mineralogy, heavy metals concentration (As, Cd, Cu, Mn, Ni, Pb, Zn), organic carbon, total nitrogen and radionuclides. Findings were compared with published data and "grey" literature. Results showed: granulometric homogeneity and a widespread carbonatic condition all over the gulf, probably due to stable bathymetry and lack of terrigenous input (except for the La Coloma basin); a rather pristine environment for what concerns heavy metals pollution, except for La Coloma where a large arsenic input was recorded; very low levels of natural and artificial radioactivity; a relevant quantity of sedimentary organic matter, providing biota with useful substrate for feeding and enhancing the food-web development while indirectly supplying lobster fisheries. Combined data highlighted the impact of the Dique Sur in reducing terrigenous input in the coastal area. Future studies should focus on dating of sediment cores for identifying and quantifying the changes acting in the gulf and on investigating the origins of the large arsenic input to La Coloma.

  17. Petroleum pollution in surface sediments of Daya Bay, South China, revealed by chemical fingerprinting of aliphatic and alicyclic hydrocarbons

    NASA Astrophysics Data System (ADS)

    Gao, Xuelu; Chen, Shaoyong

    2008-10-01

    Nine surface sediments collected from Daya Bay have been Soxhlet-extracted with 2:1 (v/v) dichloromethane-methanol. The non-aromatic hydrocarbon (NAH) fraction of solvent extractable organic matter (EOM) and some bulk geochemical parameters have been analyzed to determine petroleum pollution of the bay. The NAH content varies from 32 to 276 μg g -1 (average 104 μg g -1) dry sediment and accounts for 5.8-64.1% (average 41.6%) of the EOM. n-Alkanes with carbon number ranging from 15 to 35 are identified to be derived from both biogenic and petrogenic sources in varying proportions. The contribution of marine authigenic input to the sedimentary n-alkanes is lower than the allochthonous input based on the average n-C 31/ n-C 19 alkane ratio. 25.6-46.5% of the n-alkanes, with a mean of 35.6%, are contributed by vascular plant wax. Results of unresolved complex mixture, isoprenoid hydrocarbons, hopanes and steranes also suggest possible petroleum contamination. There is strong evidence of a common petroleum contamination source in the bay.

  18. Projections for headwater catchments of the Tarim River reveal glacier retreat and decreasing surface water availability but uncertainties are large

    NASA Astrophysics Data System (ADS)

    Duethmann, Doris; Menz, Christoph; Jiang, Tong; Vorogushyn, Sergiy

    2016-05-01

    In the Tarim River Basin, water resources from the mountain areas play a key role due to the extremely arid climate of the lowlands. This study presents an analysis of future climate change impacts on glaciers and surface water availability for headwater catchments of the Aksu River, the most important tributary to the Tarim River. We applied a glacio-hydrological model that underwent a comprehensive multivariable and multiobjective model calibration and evaluation, based on daily and interannual discharge variations and glacier mass changes. Transient glacier geometry changes are simulated using the Δh-approach. For the ensemble-based projections, we considered three different emission scenarios, nine global climate models (GCMs) and two regional climate models, and different hydrological model parameters derived from the multiobjective calibration. The results show a decline in glacier area of ‑90% to ‑32% until 2099 (reference ∼2008) (based on the 5–95 percentile range of the ensemble). Glacier melt is anticipated to further increase or stay at a high level during the first decades of the 21st century, but then declines because of decreased glacier extents. Overall discharge in the Aksu headwaters is expected to be increased in the period 2010–2039 (reference 1971–2000), but decreased in 2070–2099. Seasonally, projections show an increase in discharge in spring and early summer throughout the 21st century. Discharge changes in mid to late summer are more variable, with increases or decreases depending on the considered period and GCM. Uncertainties are largely caused by differences between the different GCMs, with further important contributions from different emission scenarios in the second half of the 21st century. Contributions from the hydrological model parameters to the ensemble uncertainty were generally found to be small.

  19. Projections for headwater catchments of the Tarim River reveal glacier retreat and decreasing surface water availability but uncertainties are large

    NASA Astrophysics Data System (ADS)

    Duethmann, Doris; Menz, Christoph; Jiang, Tong; Vorogushyn, Sergiy

    2016-05-01

    In the Tarim River Basin, water resources from the mountain areas play a key role due to the extremely arid climate of the lowlands. This study presents an analysis of future climate change impacts on glaciers and surface water availability for headwater catchments of the Aksu River, the most important tributary to the Tarim River. We applied a glacio-hydrological model that underwent a comprehensive multivariable and multiobjective model calibration and evaluation, based on daily and interannual discharge variations and glacier mass changes. Transient glacier geometry changes are simulated using the Δh-approach. For the ensemble-based projections, we considered three different emission scenarios, nine global climate models (GCMs) and two regional climate models, and different hydrological model parameters derived from the multiobjective calibration. The results show a decline in glacier area of -90% to -32% until 2099 (reference ˜2008) (based on the 5-95 percentile range of the ensemble). Glacier melt is anticipated to further increase or stay at a high level during the first decades of the 21st century, but then declines because of decreased glacier extents. Overall discharge in the Aksu headwaters is expected to be increased in the period 2010-2039 (reference 1971-2000), but decreased in 2070-2099. Seasonally, projections show an increase in discharge in spring and early summer throughout the 21st century. Discharge changes in mid to late summer are more variable, with increases or decreases depending on the considered period and GCM. Uncertainties are largely caused by differences between the different GCMs, with further important contributions from different emission scenarios in the second half of the 21st century. Contributions from the hydrological model parameters to the ensemble uncertainty were generally found to be small.

  20. Amygdalar enlargement associated with unique perception.

    PubMed

    Asari, Tomoki; Konishi, Seiki; Jimura, Koji; Chikazoe, Junichi; Nakamura, Noriko; Miyashita, Yasushi

    2010-01-01

    Interference by amygdalar activity in perceptual processes has been reported in many previous studies. Consistent with these reports, previous clinical studies have shown amygdalar volume change in multiple types of psychotic disease presenting with unusual perception. However, the relationship between variation in amygdalar volume in the normal population and the tendency toward unusual or unique perception has never been investigated. To address this issue, we defined an index to represent the tendency toward unique perception using ambiguous stimuli: subjects were instructed to state what the figures looked like to them, and "unique responses" were defined depending on the appearance frequency of the same responses in an age- and gender-matched control group. The index was defined as the ratio of unique responses to total responses per subject. We obtained structural brain images and values of the index from sixty-eight normal subjects. Voxel-based morphometry analyses revealed a positive correlation between amygdalar volume and the index. Since previous reports have indicated that unique responses were observed at higher frequency in the artistic population than in the nonartistic normal population, this positive correlation suggests that amygdalar enlargement in the normal population might be related to creative mental activity.

  1. Nature of the Jurassic Magnetic Quiet Zone revealed by the sea-surface, mid-water, and near-source magnetic sensor data in the western Pacific.

    NASA Astrophysics Data System (ADS)

    Tominaga, M.; Tivey, M.; Sager, W. W.

    2015-12-01

    rate calculated from the new Hawaiian sea surface level synthetic block model, coincides with the anomalously high reversal rate for the Japanese lineations, suggesting that reversal rates are highest during periods with the lowest anomaly amplitudes, indicating a very unique period of geomagnetic field behavior in the Earth's history.

  2. Exploring Unique Roles for Psychologists

    ERIC Educational Resources Information Center

    Ahmed, Mohiuddin; Boisvert, Charles M.

    2005-01-01

    This paper presents comments on "Psychological Treatments" by D. H. Barlow. Barlow highlighted unique roles that psychologists can play in mental health service delivery by providing psychological treatments--treatments that psychologists would be uniquely qualified to design and deliver. In support of Barlow's position, the authors draw from…

  3. On the Meaning of Uniqueness

    ERIC Educational Resources Information Center

    Shipman, Barbara A.

    2013-01-01

    This article analyzes four questions on the meaning of uniqueness that have contrasting answers in common language versus mathematical language. The investigations stem from a scenario in which students interpreted uniqueness according to a definition from standard English, that is, different from the mathematical meaning, in defining an injective…

  4. Genetic structure of Plasmodium vivax using the merozoite surface protein 1 icb5-6 fragment reveals new hybrid haplotypes in southern Mexico

    PubMed Central

    2014-01-01

    Background Plasmodium vivax is a protozoan parasite with an extensive worldwide distribution, being highly prevalent in Asia as well as in Mesoamerica and South America. In southern Mexico, P. vivax transmission has been endemic and recent studies suggest that these parasites have unique biological and genetic features. The msp1 gene has shown high rate of nucleotide substitutions, deletions, insertions, and its mosaic structure reveals frequent events of recombination, maybe between highly divergent parasite isolates. Methods The nucleotide sequence variation in the polymorphic icb5-6 fragment of the msp1 gene of Mexican and worldwide isolates was analysed. To understand how genotype diversity arises, disperses and persists in Mexico, the genetic structure and genealogical relationships of local isolates were examined. To identify new sequence hybrids and their evolutionary relationships with other P. vivax isolates circulating worldwide two haplotype networks were constructed questioning that two portions of the icb5-6 have different evolutionary history. Results Twelve new msp1 icb5-6 haplotypes of P. vivax from Mexico were identified. These nucleotide sequences show mosaic structure comprising three partially conserved and two variable subfragments and resulted into five different sequence types. The variable subfragment sV1 has undergone recombination events and resulted in hybrid sequences and the haplotype network allocated the Mexican haplotypes to three lineages, corresponding to the Sal I and Belem types, and other more divergent group. In contrast, the network from icb5-6 fragment but not sV1 revealed that the Mexican haplotypes belong to two separate lineages, none of which are closely related to Sal I or Belem sequences. Conclusions These results suggest that the new hybrid haplotypes from southern Mexico were the result of at least three different recombination events. These rearrangements likely resulted from the recombination between haplotypes of

  5. Uniqueness of the momentum map

    NASA Astrophysics Data System (ADS)

    Esposito, Chiara; Nest, Ryszard

    2016-08-01

    We give a detailed discussion of existence and uniqueness of the momentum map associated to Poisson Lie actions, which was defined by Lu. We introduce a weaker notion of momentum map, called infinitesimal momentum map, which is defined on one-forms and we analyze its integrability to the Lu's momentum map. Finally, the uniqueness of the Lu's momentum map is studied by describing, explicitly, the tangent space to the space of momentum maps.

  6. Genomic and Surface Proteomic Analysis of the Canine Pathogen Staphylococcus pseudintermedius Reveals Proteins That Mediate Adherence to the Extracellular Matrix ▿

    PubMed Central

    Bannoehr, Jeanette; Ben Zakour, Nouri L.; Reglinski, Mark; Inglis, Neil F.; Prabhakaran, Sabitha; Fossum, Even; Smith, David G.; Wilson, Gillian J.; Cartwright, Robyn A.; Haas, Juergen; Hook, Magnus; van den Broek, Adri H. M.; Thoday, Keith L.; Fitzgerald, J. Ross

    2011-01-01

    Cell wall-associated (CWA) proteins made by Gram-positive pathogens play a fundamental role in pathogenesis. Staphylococcus pseudintermedius is a major animal pathogen responsible for the canine skin disease bacterial pyoderma. Here, we describe the bioinformatic analysis of the family of 18 predicted CWA proteins encoded in the genome of S. pseudintermedius strain ED99 and determine their distribution among a phylogenetically diverse panel of S. pseudintermedius clinical isolates and closely related species of the Staphylococcus intermedius group. In parallel, we employed a proteomic approach to identify proteins presented on the surface of strain ED99 in vitro, revealing a total of 60 surface-localized proteins in one or more phases of growth, including 6 of the 18 genome-predicted CWA proteins. Based on these analyses, we selected two CWA proteins (SpsD and SpsL) encoded by all strains examined and investigated their capacity to mediate adherence to extracellular matrix proteins. We discovered that SpsD and SpsL mediated binding of a heterologous host, Lactococcus lactis, to fibrinogen and fibronectin and that SpsD mediated binding to cytokeratin 10, a major constituent of mammalian skin. Of note, the interaction with fibrinogen was host-species dependent, suggestive of a role for SpsD and SpsL in the host tropism of S. pseudintermedius. Finally, we identified IgG specific for SpsD and SpsL in sera from dogs with bacterial pyoderma, implying that both proteins are expressed during infection. The combined genomic and proteomic approach employed in the current study has revealed novel host-pathogen interactions which represent candidate therapeutic targets for the control of bacterial pyoderma. PMID:21576333

  7. Immunophenotyping of Waldenströms macroglobulinemia cell lines reveals distinct patterns of surface antigen expression: potential biological and therapeutic implications.

    PubMed

    Paulus, Aneel; Chitta, Kasyapa S; Wallace, Paul K; Advani, Pooja P; Akhtar, Sharoon; Kuranz-Blake, Maja; Ailawadhi, Sikander; Chanan-Khan, Asher A

    2015-01-01

    Waldenströms macroglobulinemia (WM) is a subtype of Non-Hodgkin's lymphoma in which the tumor cell population is markedly heterogeneous, consisting of immunoglobulin-M secreting B-lymphocytes, plasmacytoid lymphocytes and plasma cells. Due to rarity of disease and scarcity of reliable preclinical models, many facets of WM molecular and phenotypic architecture remain incompletely understood. Currently, there are 3 human WM cell lines that are routinely used in experimental studies, namely, BCWM.1, MWCL-1 and RPCI-WM1. During establishment of RPCI-WM1, we observed loss of the CD19 and CD20 antigens, which are typically present on WM cells. Intrigued by this observation and in an effort to better define the immunophenotypic makeup of this cell line, we conducted a more comprehensive analysis for the presence or absence of other cell surface antigens that are present on the RPCI-WM1 model, as well as those on the two other WM cell lines, BCWM.1 and MWCL-1. We examined expression of 65 extracellular and 4 intracellular antigens, comprising B-cell, plasma cell, T-cell, NK-cell, myeloid and hematopoietic stem cell surface markers by flow cytometry analysis. RPCI-WM1 cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced expression of CD28, CD38 and CD184, antigens that were differentially expressed on BCWM.1 and MWCL-1 cells. Due to increased expression of CD184/CXCR4 and CD38, RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or anti-CD38 targeted therapies that are actively being developed for treatment of hematologic cancers. Overall, differences in surface antigen expression across the 3 cell lines may reflect the tumor clone population predominant in the index patients, from whom the cell lines were developed. Our analysis defines the utility of the most commonly employed WM cell lines as based on their immunophenotype profiles, highlighting unique differences that can be further studied for therapeutic exploit

  8. Surface Creep Along the East Anatolian Fault (Turkey) Revealed by InSAR Time Series: Implications for Seismic Hazard and Mechanism of Creep

    NASA Astrophysics Data System (ADS)

    Senturk, S.; Cakir, Z.; Ergintav, S.; Dogan, U.; Cetin, S.; Akoglu, A. M.; Meghraoui, M.; Karabulut, H.

    2015-12-01

    Forming the boundary between the Anatolian and Arabian plates in Turkey, the East Anatolian Fault (EAF) is a major tectonic structure in the Eastern Mediterranean region. Together with its conjugate, the North Anatolian Fault (NAF), it accommodates the westward motion of the Anatolian plate with respect to Eurasia. Although it has been associated only with small-to-moderate sized earthquakes in the instrumental period and relatively quiet compared to the North Anatolian Fault, the EAF produced devastating large (M > 7) earthquakes in the historical time (Ambraseys et al., 1998). Analysis of historical seismicity (Nalbant et al., 2001) suggests that a seismic gap exists between the Lake of Hazar and Bingöl, referred here as to Palu seismic gap (PSG) We estimate the interseismic velocity field along the BSG using the Persistent Scatterer InSAR technique (Hooper, 2008). ENVISAT ASAR data acquired between 2003 and 2010 on three adjacent descending and overlapping tracks (T035, T264 and T493) are use to map the interseismic strain accumulation. The results reveal that the 100-km-long section of the Palu segment is exhibiting aseismic creep at the surface. The creep rate varies along the fault reaching, at some places, to the far field GPS-based plate velocity (i.e., 10 ± 0.3 mm/y; Reilinger et al., 2006), implying that significant portion of the elastic strain has been released aseismically. Preliminary modelling with elastic dislocations suggests that some sections of the fault may be creeping from surface down to the entire seismogenic crust. Geology of the fault zone is dominated by ophiolitic and volcanic rocks characterized by weak phyllosilicate minerals, suggesting that aseismic slip is promoted by minerals with low frictional properties. Furthermore, to monitor the surface creep, a GPS network has been established along the Palu segment. One survey has so far been realized and we expect the reliable results in 2 years (supported by TUBITAK no: 114Y250 project).

  9. Vance Tartar: a unique biologist.

    PubMed

    Frankel, J; Whiteley, A H

    1993-01-01

    Vance Tartar (1911-1991) has made major discoveries concerning morphogenesis, patterning, and nucleocytoplasmic relations in the giant ciliate Stentor coeruleus, mostly by means of hand-grafting using glass microneedles. This article provides a chronological account of the major events of Vance Tartar's life, a brief description of some of his major scientific achievements, and a discussion of his distinctive personality and multifaceted interests. It concludes with a consideration of how his unique style of life and work contributed to his equally unique scientific contributions. PMID:8457795

  10. The liberal illusion of uniqueness.

    PubMed

    Stern, Chadly; West, Tessa V; Schmitt, Peter G

    2014-01-01

    In two studies, we demonstrated that liberals underestimate their similarity to other liberals (i.e., display truly false uniqueness), whereas moderates and conservatives overestimate their similarity to other moderates and conservatives (i.e., display truly false consensus; Studies 1 and 2). We further demonstrated that a fundamental difference between liberals and conservatives in the motivation to feel unique explains this ideological distinction in the accuracy of estimating similarity (Study 2). Implications of the accuracy of consensus estimates for mobilizing liberal and conservative political movements are discussed. PMID:24247730

  11. COPD: Unique to Older Adults

    MedlinePlus

    ... Multiple Health Problems Prevention Join our e-newsletter! Aging & Health A to Z COPD Unique to Older Adults This section provides information ... not a weakness or a normal part of aging. Most people feel better with ... help you can, so that your COPD does not prevent you from living your life ...

  12. Milton: A New, Unique Pallasite

    NASA Technical Reports Server (NTRS)

    Jones, R. H.; Wasson, J. T.; Larson, T.; Sharp, Z. D.

    2003-01-01

    The Milton pallasite was found in Missouri, U.S.A. in October, 2000. It consists of a single stone that originally weighed approximately 2040 g. The chemistry of the olivine and metal phases, plus the oxygen isotope ratios of the olivines, differ significantly from other pallasites, making Milton unique. Unfortunately, the meteorite is heavily fractured and weathered.

  13. Rufus Choate: A Unique Orator.

    ERIC Educational Resources Information Center

    Markham, Reed

    Rufus Choate, a Massachusetts lawyer and orator, has been described as a "unique and romantic phenomenon" in America's history. Born in 1799 in Essex, Massachusetts, Choate graduated from Dartmouth College and attended Harvard Law School. Choate's goal was to be the top in his profession. Daniel Webster was Choate's hero. Choate became well…

  14. Uniquely identifying wheat plant structures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Uniquely naming wheat (Triticum aestivum L. em Thell) plant parts is useful for communicating plant development research and the effects of environmental stresses on normal wheat development. Over the past 30+ years, several naming systems have been proposed for wheat shoot, leaf, spike, spikelet, ...

  15. Using an Unmanned Arial Vehicle (UAV) and a thermal infrared camera to estimate temperature differences on a lake surface, revealing incoming groundwater seepage.

    NASA Astrophysics Data System (ADS)

    Hoffmann, Helene; Müller, Sascha; Friborg, Thomas

    2014-05-01

    UAVs are at the budding stage of becoming efficient tools in geosciences due to their fast coverage of large areas, creating opportunities to collect comprehensive amounts of spatially distributed data. In this survey a fixed-wing UAV is equipped with a thermal infrared camera (Optris PI 450) conducting spatially distributed measurements of radiometric surface temperature, from a small groundwater-fed lake. We hypothesis that larger temperature differences in the lake surface will reveal locations of incoming groundwater seepage. During wintertime, warmer groundwater will have great incentive to rise to the lake surface without significant mixing with colder lake water and hence enable detection of incoming groundwater seepage with surface measurements. The investigated area is a 300x150 m section of Lake Vaeng in southern Jutland, Denmark. Detecting areas of groundwater seepage into lakes and quantifying these fluxes are of great importance not only for water budgets but also in relation to lake environments. Incoming groundwater might be a large nutrient source in lakes. GPS coordinates from the UAV are correlated with each thermal image based on UTC time stamps. Geo-reference is further improved with ground control points in the form of 0.2x0.2 m aluminum foil rectangles. Aluminum stands out clearly in thermal images and using seven of these ground control points, evenly distributed in the investigated area, led to an accuracy of 0.3 m. Using the Structure from Motion photogrammetric technique, a point cloud model is produced and camera positions along with intrinsic and extrinsic properties are established. Distinct temperature differences of 1.5 C have been detected along the south-eastern shore of Lake Vaeng. The location of these hotspots is in agreement with temperature differences measured with Distributed Temperature Sensing (DTS) system - indicating zones of groundwater seepage into the lake. In addition to faster execution of large spatially distributed

  16. Lectin mapping reveals stage-specific display of surface carbohydrates in in vitro and haemolymph-derived cells of the entomopathogenic fungus Beauveria bassiana.

    PubMed

    Wanchoo, Arun; Lewis, Michael W; Keyhani, Nemat O

    2009-09-01

    carbohydrate epitopes, displaying binding only to the GNL, PNA and WGA lectins. Ultrastructural examination of the haemolymph-derived cells revealed the presence of a highly ordered outermost brush-like structure not present on any of the in vitro cells. Haemolymph-derived hyphal bodies placed into rich broth medium showed expression of several surface carbohydrate epitopes, most notably showing increased PNA binding and strong binding by the RCA lectin. These data indicate robust and diverse production of carbohydrate epitopes on different developmental stages of fungal cells and provide evidence that surface carbohydrates are elaborated in infection-specific patterns. PMID:19608611

  17. Optical Measurements Reveal Interplay Between Surface and Bottom Processes Involving Phytoplankton, Organic Carbon, Iron, Light, and Oxygen in Two Stratified Mesotrophic Lakes

    NASA Astrophysics Data System (ADS)

    Hargreaves, B. R.; Vaidya, A.; Wiles, K. A.

    2009-12-01

    Water column distribution of phytoplankton, organic carbon, particulate and dissolved iron are described through detailed vertical optical measurements that include downwelling cosine irradiance, turbidity, dissolved oxygen, fluorescence by CDOM, Chl-a, phycobilin pigments, and diffuse attenuation for several UV wavebands, plus pH, temperature, and specific conductance. These measurements were completed with a group of profiling instruments during summer in two mid-latitude small lakes. Special calibration allowed for correcting the impact of CDOM and turbidity on the pigment fluorescence signals. These in situ data were combined with laboratory analysis of discrete water column samples for methanol-extracted chlorophyll-a, spectral absorbance of particles, concentration of particulates (dry mass and ash-free mass), total particulate and "dissolved" iron, DOC and CDOM (the "dissolved fraction" passes through a GF/F filter). Surface processes revealed by these measurement include solar heating and photobleaching of CDOM (partly distributed by wind-driven mixing), and nonphotochemical quenching of phytoplankton chlorophyll-a fluorescence. Bottom processes revealed by these measurements include oxygen consumption by net heterotrophic metabolism, release of DOC, CDOM, and iron from anoxic bottom sediments, and the development of a biological community structured by the light and temperature gradients and absence or scarcity of dissolved oxygen near the bottom. The iron associated with CDOM and particles in the deep samples substantially increased the latter's DOC-specific absorption once there was an opportunity for oxidation. A model for mass-specific spectral absorption of particulates accounts for the contribution of organic matter and iron associated with the particles. A detailed hydrologic budget for one of the lakes will allow the water column processes to be explored further by accounting for inputs and outputs of water and organic carbon (via precipitation

  18. The Identification and Functional Characterization of WxL Proteins from Enterococcus faecium Reveal Surface Proteins Involved in Extracellular Matrix Interactions

    PubMed Central

    Galloway-Peña, Jessica R.; Liang, Xiaowen; Singh, Kavindra V.; Yadav, Puja; Chang, Chungyu; La Rosa, Sabina Leanti; Shelburne, Samuel; Ton-That, Hung; Höök, Magnus

    2014-01-01

    The WxL domain recently has been identified as a novel cell wall binding domain found in numerous predicted proteins within multiple Gram-positive bacterial species. However, little is known about the function of proteins containing this novel domain. Here, we identify and characterize 6 Enterococcus faecium proteins containing the WxL domain which, by reverse transcription-PCR (RT-PCR) and genomic analyses, are located in three similarly organized operons, deemed WxL loci A, B, and C. Western blotting, electron microscopy, and enzyme-linked immunosorbent assays (ELISAs) determined that genes of WxL loci A and C encode antigenic, cell surface proteins exposed at higher levels in clinical isolates than in commensal isolates. Secondary structural analyses of locus A recombinant WxL domain-containing proteins found they are rich in β-sheet structure and disordered segments. Using Biacore analyses, we discovered that recombinant WxL proteins from locus A bind human extracellular matrix proteins, specifically type I collagen and fibronectin. Proteins encoded by locus A also were found to bind to each other, suggesting a novel cell surface complex. Furthermore, bile salt survival assays and animal models using a mutant from which all three WxL loci were deleted revealed the involvement of WxL operons in bile salt stress and endocarditis pathogenesis. In summary, these studies extend our understanding of proteins containing the WxL domain and their potential impact on colonization and virulence in E. faecium and possibly other Gram-positive bacterial species. PMID:25512313

  19. Unique MSV for every job

    SciTech Connect

    Not Available

    1985-06-01

    Consafe is now using a computer-aided design and drafting system adapting its multipurpose support vessels (MSVS) to specific user requirements. The vessels are based on the concept of standard container modules adapted into living quarters, workshops, service units, offices with each application for a specific project demanding a unique mix. There is also the need for constant refurbishment program as service conditions take their toll on the modules. The computer-aided design system is described.

  20. Negative staining and immunoelectron microscopy of adhesion-deficient mutants of Streptococcus salivarius reveal that the adhesive protein antigens are separate classes of cell surface fibril.

    PubMed Central

    Weerkamp, A H; Handley, P S; Baars, A; Slot, J W

    1986-01-01

    The subcellular distribution of the cell wall-associated protein antigens of Streptococcus salivarius HB, which are involved in specific adhesive properties of the cells, was studied. Mutants which had lost the adhesive properties and lacked the antigens at the cell surface were compared with the parent strain. Immunoelectron microscopy of cryosections of cells labeled with affinity-purified, specific antisera and colloidal gold-protein A complexes was used to locate the antigens. Antigen C (AgC), a glycoprotein involved in attachment to host surfaces, was mainly located in the fibrillar layer outside the cell wall. A smaller amount of label was also found throughout the cytoplasmic area in the form of small clusters of gold particles, which suggests a macromolecular association. Mutant HB-7, which lacks the wall-associated AgC, accumulated AgC reactivity intracellularly. Intracellular AgC was often found associated with isolated areas of increased electron density, but sometimes seemed to fill the entire interior of the cell. Antigen B (AgB), a protein responsible for interbacterial coaggregation, was also located in the fibrillar layer, although its distribution differed from that of the wall-associated AgC since AgB was found predominantly in the peripheral areas. A very small amount of label was also found in the cytoplasmic area as discrete gold particles. Mutant HB-V5, which lacks wall-associated AgB, was not labeled in the fibrillar coat, but showed the same weak intracellular label as the parent strain. Immunolabeling with serum against AgD, another wall-associated protein but of unknown function, demonstrated its presence in the fibrillar layer of strain HB. Negatively stained preparations of whole cells of wild-type S. salivarius and mutants that had lost wall-associated AgB or AgC revealed that two classes of short fibrils are carried on the cell surface at the same time. AgB and AgC are probably located on separate classes of short, protease

  1. Crystal Structures of Mite Allergens Der f 1 and Der p 1 Reveal Differences in Surface-Exposed Residues that May Influence Antibody Binding

    SciTech Connect

    Chruszcz, Maksymilian; Chapman, Martin D.; Vailes, Lisa D.; Stura, Enrico A.; Saint-Remy, Jean-Marie; Minor, Wladek; Pomés, Anna

    2009-12-01

    The Group 1 mite allergens, Der f 1 and Der p 1, are potent allergens excreted by Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively. The human IgE antibody responses to the Group 1 allergens show more cross-reactivity than the murine IgG antibody responses which are largely species-specific. Here, we report the crystal structure of the mature form of Der f 1, which was isolated from its natural source, and a new, high-resolution structure of mature recombinant Der p 1. Unlike Der p 1, Der f 1 is monomeric both in the crystalline state and in solution. Moreover, no metal binding is observed in the structure of Der f 1, despite the fact that all amino acids involved in Ca{sup 2+} binding in Der p 1 are completely conserved in Der f 1. Although Der p 1 and Der f 1 share extensive sequence identity, comparison of the crystal structures of both allergens revealed structural features which could explain the differences in murine and human IgE antibody responses to these allergens. There are structural differences between Der f 1 and Der p 1 which are unevenly distributed on the allergens' surfaces. This uneven spatial arrangement of conserved versus altered residues could explain both the specificity and cross-reactivity of antibodies against Der f 1 and Der p 1.

  2. Revealing Mercury

    NASA Astrophysics Data System (ADS)

    Prockter, L. M.; Solomon, S. C.; Head, J. W.; Watters, T. R.; Murchie, S. L.; Robinson, M. S.; Chapman, C. R.; McNutt, R. L.

    2009-04-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, developed under NASA's Discovery Program, launched in August 2004. En route to insertion into orbit about Mercury in 2011, MESSENGER flies by Mercury three times. The first and second of these encounters were accomplished in January and October of 2008. These flybys viewed portions of Mercury's surface that were not observed by Mariner 10 during its reconnaissance of somewhat less than half of the planet in 1974-1975. All MESSENGER instruments operated during each flyby and returned a wealth of new data. Many of the new observations were focused on the planet's geology, including monochrome imaging at resolutions as high as 100 m/pixel, multispectral imaging in 11 filters at resolutions as high as 500 m/pixel, laser altimetry tracks extending over several thousands of kilometers, and high-resolution spectral measurements of several types of terrain. Here we present an overview of the first inferences on the global geology of Mercury from the MESSENGER observations. Whereas evidence for volcanism was equivocal from Mariner 10 data, the new MESSENGER images and altimetry provide compelling evidence that volcanism was widespread and protracted on Mercury. Color imaging reveals three common spectral units on the surface: a higher-reflectance, relatively red material occurring as a distinct class of smooth plains, typically with distinct embayment relationships interpreted to indicate volcanic emplacement; a lower-reflectance, relatively blue material typically excavated by impact craters and therefore inferred to be more common at depth; and a spectrally intermediate terrain that constitutes much of the uppermost crust. Three more minor spectral units are also seen: fresh crater ejecta, reddish material associated with rimless depressions interpreted to be volcanic centers, and high-reflectance deposits seen in some crater floors. Preliminary measurements of crater size

  3. Studies on the Contribution of Human Cytomegalovirus UL21a and UL97 to Viral Growth and Inactivation of the Anaphase-Promoting Complex/Cyclosome (APC/C) E3 Ubiquitin Ligase Reveal a Unique Cellular Mechanism for Downmodulation of the APC/C Subunits APC1, APC4, and APC5

    PubMed Central

    Clark, Elizabeth

    2015-01-01

    ABSTRACT Human cytomegalovirus (HCMV) deregulates the cell cycle by several means, including inactivation of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. Viral proteins UL97 and UL21a, respectively, affect the APC/C by phosphorylation of APC/C coactivator Cdh1 and by inducing the degradation of subunits APC4 and APC5, which along with APC1 form the APC/C platform subcomplex. The aim of this study was to further characterize the mechanism of APC/C inactivation and define the relative contributions of UL21a and UL97 to APC/C substrate accumulation and to viral growth. We show that in uninfected cells, UL21a but not UL97 can disrupt APC/C function, leading to the accumulation of substrates. We find that UL21a is necessary and sufficient to induce the degradation of APC1, in addition to the previously reported APC4 and APC5. We also demonstrate that there is a previously unreported cellular mechanism for a specific decrease in the levels of all three platform subunits, APC1, APC4, and APC5, upon the depletion of any one of these subunits or of subunit APC8. Finally, we show that at a low multiplicity of infection, either UL97 or UL21a can partially complement a growth-defective mutant virus lacking both UL21a and UL97, with significantly greater benefit afforded by the expression of both proteins. This double mutant also can be partially rescued by inactivation of the APC/C using small interfering RNAs against specific subunits. These results further our understanding of HCMV's interaction with the cell cycle machinery and reveal a new cellular pattern of APC/C subunit downmodulation. IMPORTANCE HCMV lytic infection subverts the host cell cycle machinery in multiple ways. A major effect is inactivation of the APC/C, which plays a central role in the control of cell cycle progression. This study provides further insight into the mechanism of inactivation. We discovered that the APC1 subunit, which along with APC4 and APC5 form the platform

  4. Suomi satellite brings to light a unique frontier of nighttime environmental sensing capabilities.

    PubMed

    Miller, Steven D; Mills, Stephen P; Elvidge, Christopher D; Lindsey, Daniel T; Lee, Thomas F; Hawkins, Jeffrey D

    2012-09-25

    Most environmental satellite radiometers use solar reflectance information when it is available during the day but must resort at night to emission signals from infrared bands, which offer poor sensitivity to low-level clouds and surface features. A few sensors can take advantage of moonlight, but the inconsistent availability of the lunar source limits measurement utility. Here we show that the Day/Night Band (DNB) low-light visible sensor on the recently launched Suomi National Polar-orbiting Partnership (NPP) satellite has the unique ability to image cloud and surface features by way of reflected airglow, starlight, and zodiacal light illumination. Examples collected during new moon reveal not only meteorological and surface features, but also the direct emission of airglow structures in the mesosphere, including expansive regions of diffuse glow and wave patterns forced by tropospheric convection. The ability to leverage diffuse illumination sources for nocturnal environmental sensing applications extends the advantages of visible-light information to moonless nights.

  5. A composite sea surface temperature record of the northern South China Sea for the past 2,500 years: A unique look into seasonality and seasonal climate changes during warm and cold periods

    NASA Astrophysics Data System (ADS)

    Yan, H.; Soon, W.

    2015-12-01

    High-resolution late Holocene climate records that can resolve seasonality are essential for confirming past climatic dynamics, understanding the late 20th century global warming and predicting future climate. Here a new composite record of the sea surface temperature, SST, variation in the northern South China Sea (SCS) during the late Holocene is constructed by combining seven seasonally-resolved coral and T. gigas Sr/Ca-based SST time-windows with the instrumental SST record from modern interval between 1990 and 2000. This composite multi-proxy marine record, together with the reconstructions from mainland China and tropical western Pacific, indicates that the late Holocene warm periods, the Roman Warm Period (RWP) and Medieval Warm Period (MWP), were prominently imprinted and documented in the climatic and environmental history of the East Asia-Western Pacific region. Meanwhile, substantial and significant SST seasonality variations during the late Holocene were observed in the composite record. The observed increase in seasonality (or amplitude of seasonal cycles) during the cold periods around our study area was probably caused by the different amplitudes between winter versus summer SST variations in northern SCS, with much larger SST variation during winters than during summers for the late Holocene. In addition, the distinctive warm, cold and neutral climatic episodes identified in our northern SCS composite SST record correspond well with other paleo reconstructions from mainland China and especially well with the Northern Hemisphere-wide composites by Moberg et al. (2005) and Ljungqvist (2010). The overall agreement however also calls for more information and insights on how seasonal temperatures and their ranges vary on multidecadal to bicentennial timescales.

  6. Impacts of cyclones on the phytoplankton chlorophyll and sea surface temperature spatial and temporal dynamics in the Barents Sea as revealed from space

    NASA Astrophysics Data System (ADS)

    Fedorova, Anastasiia; Morozov, Evgeny; Kondrik, Dmitry; Rubchenia, Andrey; Pozdnyakov, Dmitry

    2014-05-01

    area 3. no recordable changes in SST and chl. Importantly, the increases in chl concentration were observed not only during the periods of high biological activity of the phytoplankton in the Barents Sea (mid-May- June and mid-August) but even during the periods of low productivity (April-early May and July-late August). Our analyses of the temporal and spatial modulations of chl and SST fields indicate that they are related to a wealth of factors, first and foremost, the cyclone parameters (baric deepness, wind speed above the water surface, the translation speed), the Atlantic water circulation pathways across the sea, the bottom relief, and cloudiness conditions. The causal mechanisms of the revealed SST and chl modulations have thus been identified for each specific case, and the entire phenomenon general regularities were established. On balance, the cases of cycle-driven increase in chl proved to be prevalent and thus our findings imply that with the ongoing amplification of climate warming at high northern latitudes, the increase in chlorophyll discussed above is potentially capable of boosting the primary productivity in the Arctic Ocean.

  7. The unique biochemistry of methanogenesis.

    PubMed

    Deppenmeier, Uwe

    2002-01-01

    Methanogenic archaea have an unusual type of metabolism because they use H2 + CO2, formate, methylated C1 compounds, or acetate as energy and carbon sources for growth. The methanogens produce methane as the major end product of their metabolism in a unique energy-generating process. The organisms received much attention because they catalyze the terminal step in the anaerobic breakdown of organic matter under sulfate-limiting conditions and are essential for both the recycling of carbon compounds and the maintenance of the global carbon flux on Earth. Furthermore, methane is an important greenhouse gas that directly contributes to climate changes and global warming. Hence, the understanding of the biochemical processes leading to methane formation are of major interest. This review focuses on the metabolic pathways of methanogenesis that are rather unique and involve a number of unusual enzymes and coenzymes. It will be shown how the previously mentioned substrates are converted to CH4 via the CO2-reducing, methylotrophic, or aceticlastic pathway. All catabolic processes finally lead to the formation of a mixed disulfide from coenzyme M and coenzyme B that functions as an electron acceptor of certain anaerobic respiratory chains. Molecular hydrogen, reduced coenzyme F420, or reduced ferredoxin are used as electron donors. The redox reactions as catalyzed by the membrane-bound electron transport chains are coupled to proton translocation across the cytoplasmic membrane. The resulting electrochemical proton gradient is the driving force for ATP synthesis as catalyzed by an A1A0-type ATP synthase. Other energy-transducing enzymes involved in methanogenesis are the membrane-integral methyltransferase and the formylmethanofuran dehydrogenase complex. The former enzyme is a unique, reversible sodium ion pump that couples methyl-group transfer with the transport of Na+ across the membrane. The formylmethanofuran dehydrogenase is a reversible ion pump that catalyzes

  8. The Unique American Vision of Childhood

    NASA Astrophysics Data System (ADS)

    Ozturk, Mehmet Ali; Debelak, Charles

    2008-01-01

    The present article scrutinizes "the unique American vision of childhood" (UAVC) as a phenomenon undermining high academic expectations and good work ethics, and in turn, contributing to the generally low academic achievement of U.S. students compared to their counterparts in other advanced countries. It starts with a definition of UAVC, followed by a discussion of how influential it has been. The article goes on to state three reasons why UAVC is troublesome and misleading, especially in an era of global competition. Excuses devised by the proponents for UAVC's adverse effects are also revealed. The article ends with recommendations for future research and a conclusion elaborating on the consequences of UAVC and the likelihood that other countries might adopt a similar mentality.

  9. Estetrol: a unique steroid in human pregnancy.

    PubMed

    Holinka, Christian F; Diczfalusy, Egon; Coelingh Bennink, Herjan J T

    2008-05-01

    Estetrol (E(4)) is an estrogenic steroid molecule synthesized exclusively by the fetal liver during human pregnancy and reaching the maternal circulation through the placenta. Its function is presently unknown. After its discovery in the mid-1960s, E(4) research revealed rather unique properties of this steroid and spawned a large body of state-of-the art publications. Nevertheless, 20 years later experimental work was virtually abandoned. In recent years based on new data, E(4) has experienced a vita nova, a revival of preclinical and clinical research activities with the goal to elucidate its physiological function and explore its potential for therapeutic use in humans. This review is intended to offer an historical account of the discovery of E(4) and the preclinical studies conducted during the heyday of E(4) research that ended in the mid-1980s. PMID:18462934

  10. Unique features of space reactors

    SciTech Connect

    Buden, D.

    1990-01-01

    Space reactors are designed to meet a unique set of requirements; they must be sufficiently compact to be launched in a rocket to their operational location, operate for many years without maintenance and servicing, operate in extreme environments, and reject heat by radiation to space. To meet these restrictions, operating temperatures are much greater than in terrestrial power plants, and the reactors tend to have a fast neutron spectrum. Currently, a new generation of space reactor power plants is being developed. The major effort is in the SP-100 program, where the power plant is being designed for seven years of full power, and no maintenance operation at a reactor outlet operating temperature of 1350 K. 8 refs., 3 figs., 1 tab.

  11. The Probabilities of Unique Events

    PubMed Central

    Khemlani, Sangeet S.; Lotstein, Max; Johnson-Laird, Phil

    2012-01-01

    Many theorists argue that the probabilities of unique events, even real possibilities such as President Obama's re-election, are meaningless. As a consequence, psychologists have seldom investigated them. We propose a new theory (implemented in a computer program) in which such estimates depend on an intuitive non-numerical system capable only of simple procedures, and a deliberative system that maps intuitions into numbers. The theory predicts that estimates of the probabilities of conjunctions should often tend to split the difference between the probabilities of the two conjuncts. We report two experiments showing that individuals commit such violations of the probability calculus, and corroborating other predictions of the theory, e.g., individuals err in the same way even when they make non-numerical verbal estimates, such as that an event is highly improbable. PMID:23056224

  12. Split liver transplantation: What's unique?

    PubMed

    Dalal, Aparna R

    2015-09-24

    The intraoperative management of split liver transplantation (SLT) has some unique features as compared to routine whole liver transplantations. Only the liver has this special ability to regenerate that confers benefits in survival and quality of life for two instead of one by splitting livers. Primary graft dysfunction may result from small for size syndrome. Graft weight to recipient body weight ratio is significant for both trisegmental and hemiliver grafts. Intraoperative surgical techniques aim to reduce portal hyperperfusion and decrease venous portal pressure. Ischemic preconditioning can be instituted to protect against ischemic reperfusion injury which impacts graft regeneration. Advancement of the technique of SLT is essential as use of split cadaveric grafts expands the donor pool and potentially has an excellent future. PMID:26421261

  13. Unique applications of fluoroepoxy materials

    NASA Technical Reports Server (NTRS)

    Lee, Sheng Yen

    1991-01-01

    The following subject areas are covered: (1) fluoroepoxy and curing agents; (2) an excellent moisture vapor barrier coating; (3) as adhesives to bond Teflon without any surface treatment; (4) a new method to make thermosetting fluoropolymer foam; and (5) as a new antifoaming agent for epoxy material manufacturing and processing.

  14. Unique metabolites protect earthworms against plant polyphenols

    PubMed Central

    Liebeke, Manuel; Strittmatter, Nicole; Fearn, Sarah; Morgan, A. John; Kille, Peter; Fuchser, Jens; Wallis, David; Palchykov, Vitalii; Robertson, Jeremy; Lahive, Elma; Spurgeon, David J.; McPhail, David; Takáts, Zoltán; Bundy, Jacob G.

    2015-01-01

    All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils. It is unknown how earthworms, the major component of animal biomass in many soils, cope with high-polyphenol diets. Here, we show that earthworms possess a class of unique surface-active metabolites in their gut, which we term ‘drilodefensins'. These compounds counteract the inhibitory effects of polyphenols on earthworm gut enzymes, and high-polyphenol diets increase drilodefensin concentrations in both laboratory and field populations. This shows that drilodefensins protect earthworms from the harmful effects of ingested polyphenols. We have identified the key mechanism for adaptation to a dietary challenge in an animal group that has a major role in organic matter recycling in soils worldwide. PMID:26241769

  15. Unique metabolites protect earthworms against plant polyphenols.

    PubMed

    Liebeke, Manuel; Strittmatter, Nicole; Fearn, Sarah; Morgan, A John; Kille, Peter; Fuchser, Jens; Wallis, David; Palchykov, Vitalii; Robertson, Jeremy; Lahive, Elma; Spurgeon, David J; McPhail, David; Takáts, Zoltán; Bundy, Jacob G

    2015-01-01

    All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils. It is unknown how earthworms, the major component of animal biomass in many soils, cope with high-polyphenol diets. Here, we show that earthworms possess a class of unique surface-active metabolites in their gut, which we term 'drilodefensins'. These compounds counteract the inhibitory effects of polyphenols on earthworm gut enzymes, and high-polyphenol diets increase drilodefensin concentrations in both laboratory and field populations. This shows that drilodefensins protect earthworms from the harmful effects of ingested polyphenols. We have identified the key mechanism for adaptation to a dietary challenge in an animal group that has a major role in organic matter recycling in soils worldwide. PMID:26241769

  16. Unique metabolites protect earthworms against plant polyphenols.

    PubMed

    Liebeke, Manuel; Strittmatter, Nicole; Fearn, Sarah; Morgan, A John; Kille, Peter; Fuchser, Jens; Wallis, David; Palchykov, Vitalii; Robertson, Jeremy; Lahive, Elma; Spurgeon, David J; McPhail, David; Takáts, Zoltán; Bundy, Jacob G

    2015-08-04

    All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils. It is unknown how earthworms, the major component of animal biomass in many soils, cope with high-polyphenol diets. Here, we show that earthworms possess a class of unique surface-active metabolites in their gut, which we term 'drilodefensins'. These compounds counteract the inhibitory effects of polyphenols on earthworm gut enzymes, and high-polyphenol diets increase drilodefensin concentrations in both laboratory and field populations. This shows that drilodefensins protect earthworms from the harmful effects of ingested polyphenols. We have identified the key mechanism for adaptation to a dietary challenge in an animal group that has a major role in organic matter recycling in soils worldwide.

  17. Carbon sources in suspended particles and surface sediments from the Beaufort Sea revealed by molecular lipid biomarkers and compound-specific isotope analysis

    NASA Astrophysics Data System (ADS)

    Tolosa, I.; Fiorini, S.; Gasser, B.; Martín, J.; Miquel, J. C.

    2013-03-01

    Molecular lipid biomarkers (hydrocarbons, alcohols, sterols and fatty acids) and compound-specific isotope analysis of suspended particulate organic matter (SPM) and surface sediments of the Mackenzie Shelf and slope (southeast Beaufort Sea, Arctic Ocean) were studied in summer 2009. The concentrations of the molecular lipid markers, characteristic of known organic matter sources, were grouped and used as proxies to evaluate the relative importance of fresh algal, detrital algal, fossil, C3 terrestrial plants, bacterial and zooplankton material in the organic matter (OM) of this area. Fossil and detrital algal contributions were the major fractions of the freshwater SPM from the Mackenzie River with ~34% each of the total molecular biomarkers. Fresh algal, C3 terrestrial, bacterial and zooplanktonic components represented much lower percentages, 17, 10, 4 and <1%, respectively. In marine SPM from the Mackenzie slope, the major contributions were fresh and detrital algal components (>80%), with a minor contribution of fossil and C3 terrestrial biomarkers. Characterization of the sediments revealed a major sink of refractory algal material mixed with some fresh algal material, fossil hydrocarbons and a small input of C3 terrestrial sources. In particular, the sediments from the shelf and at the mouth of the Amundsen Gulf presented the highest contribution of detrital algal material (60-75%), whereas those from the slope contained the highest proportion of fossil (40%) and C3 terrestrial plant material (10%). Overall, considering that the detrital algal material is marine derived, autochthonous sources contributed more than allochthonous sources to the OM lipid pool. Using the ratio of an allochthonous biomarker (normalized to total organic carbon, TOC) found in the sediments to those measured at the river mouth water, we estimated that the fraction of terrestrial material preserved in the sediments accounted for 30-40% of the total carbon in the inner shelf sediments

  18. CYP1B1: a unique gene with unique characteristics.

    PubMed

    Faiq, Muneeb A; Dada, Rima; Sharma, Reetika; Saluja, Daman; Dada, Tanuj

    2014-01-01

    CYP1B1, a recently described dioxin inducible oxidoreductase, is a member of the cytochrome P450 superfamily involved in the metabolism of estradiol, retinol, benzo[a]pyrene, tamoxifen, melatonin, sterols etc. It plays important roles in numerous physiological processes and is expressed at mRNA level in many tissues and anatomical compartments. CYP1B1 has been implicated in scores of disorders. Analyses of the recent studies suggest that CYP1B1 can serve as a universal/ideal cancer marker and a candidate gene for predictive diagnosis. There is plethora of literature available about certain aspects of CYP1B1 that have not been interpreted, discussed and philosophized upon. The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation. Also CYP1B1 is very difficult to express in heterologous expression systems, thereby, halting its functional studies. Here we review and analyze these exceptional and startling characteristics of CYP1B1 with inputs from our own experiences in order to get a better insight into its molecular biology in health and disease. This may help to further understand the etiopathomechanistic aspects of CYP1B1 mediated diseases paving way for better research strategies and improved clinical management. PMID:25658124

  19. Respiratory infections unique to Asia.

    PubMed

    Tsang, Kenneth W; File, Thomas M

    2008-11-01

    Asia is a highly heterogeneous region with vastly different cultures, social constitutions and populations affected by a wide spectrum of respiratory diseases caused by tropical pathogens. Asian patients with community-acquired pneumonia differ from their Western counterparts in microbiological aetiology, in particular the prominence of Gram-negative organisms, Mycobacterium tuberculosis, Burkholderia pseudomallei and Staphylococcus aureus. In addition, the differences in socioeconomic and health-care infrastructures limit the usefulness of Western management guidelines for pneumonia in Asia. The importance of emerging infectious diseases such as severe acute respiratory syndrome and avian influenza infection remain as close concerns for practising respirologists in Asia. Specific infections such as melioidosis, dengue haemorrhagic fever, scrub typhus, leptospirosis, salmonellosis, penicilliosis marneffei, malaria, amoebiasis, paragonimiasis, strongyloidiasis, gnathostomiasis, trinchinellosis, schistosomiasis and echinococcosis occur commonly in Asia and manifest with a prominent respiratory component. Pulmonary eosinophilia, endemic in parts of Asia, could occur with a wide range of tropical infections. Tropical eosinophilia is believed to be a hyper-sensitivity reaction to degenerating microfilariae trapped in the lungs. This article attempts to address the key respiratory issues in these respiratory infections unique to Asia and highlight the important diagnostic and management issues faced by practising respirologists.

  20. Symbols are not uniquely human.

    PubMed

    Ribeiro, Sidarta; Loula, Angelo; de Araújo, Ivan; Gudwin, Ricardo; Queiroz, João

    2007-01-01

    Modern semiotics is a branch of logics that formally defines symbol-based communication. In recent years, the semiotic classification of signs has been invoked to support the notion that symbols are uniquely human. Here we show that alarm-calls such as those used by African vervet monkeys (Cercopithecus aethiops), logically satisfy the semiotic definition of symbol. We also show that the acquisition of vocal symbols in vervet monkeys can be successfully simulated by a computer program based on minimal semiotic and neurobiological constraints. The simulations indicate that learning depends on the tutor-predator ratio, and that apprentice-generated auditory mistakes in vocal symbol interpretation have little effect on the learning rates of apprentices (up to 80% of mistakes are tolerated). In contrast, just 10% of apprentice-generated visual mistakes in predator identification will prevent any vocal symbol to be correctly associated with a predator call in a stable manner. Tutor unreliability was also deleterious to vocal symbol learning: a mere 5% of "lying" tutors were able to completely disrupt symbol learning, invariably leading to the acquisition of incorrect associations by apprentices. Our investigation corroborates the existence of vocal symbols in a non-human species, and indicates that symbolic competence emerges spontaneously from classical associative learning mechanisms when the conditioned stimuli are self-generated, arbitrary and socially efficacious. We propose that more exclusive properties of human language, such as syntax, may derive from the evolution of higher-order domains for neural association, more removed from both the sensory input and the motor output, able to support the gradual complexification of grammatical categories into syntax.

  1. Uniqueness of two-loop master contours

    NASA Astrophysics Data System (ADS)

    Caron-Huot, Simon; Larsen, Kasper J.

    2012-10-01

    Generalized-unitarity calculations of two-loop amplitudes are performed by expanding the amplitude in a basis of master integrals and then determining the coefficients by taking a number of generalized cuts. In this paper, we present a complete classification of the solutions to the maximal cut of integrals with the double-box topology. The ideas presented here are expected to be relevant for all two-loop topologies as well. We find that these maximal-cut solutions are naturally associated with Riemann surfaces whose topology is determined by the number of states at the vertices of the double-box graph. In the case of four massless external momenta we find that, once the geometry of these Riemann surfaces is properly understood, there are uniquely defined master contours producing the coefficients of the double-box integrals in the basis decomposition of the two-loop amplitude. This is in perfect analogy with the situation in one-loop generalized unitarity. In addition, we point out that the chiral integrals recently introduced by Arkani-Hamed et al. can be used as master integrals for the double-box contributions to the two-loop amplitudes in any gauge theory. The infrared finiteness of these integrals allow for their coefficients as well as their integrated expressions to be evaluated in strictly four dimensions, providing significant technical simplification. We evaluate these integrals at four points and obtain remarkably compact results.

  2. Emergent photovoltage on SmB6 surface upon bulk-gap evolution revealed by pump-and-probe photoemission spectroscopy

    PubMed Central

    Ishida, Y.; Otsu, T.; Shimada, T.; Okawa, M.; Kobayashi, Y.; Iga, F.; Takabatake, Y.; Shin, S.

    2015-01-01

    Recent studies suggest that an exemplary Kondo insulator SmB6 belongs to a new class of topological insulators (TIs), in which non-trivial spin-polarized metallic states emerge on surface upon the formation of Kondo hybridization gap in the bulk. Remarkably, the bulk resistivity reaches more than 20 Ω cm at 4 K, making SmB6 a candidate for a so-called bulk-insulating TI. We here investigate optical-pulse responses of SmB6 by pump-and-probe photoemission spectroscopy. Surface photovoltage effect is observed below ~90 K. This indicates that an optically-active band bending region develops beneath the novel metallic surface upon the bulk-gap evolution. The photovoltaic effect persists for >200 µs, which is long enough to be detected by electronics devices, and could be utilized for optical gating of the novel metallic surface. PMID:25640966

  3. Interior Evolution of Ceres Revealed by Dawn

    NASA Astrophysics Data System (ADS)

    Raymond, Carol A.; Park, Ryan S.; Konopliv, Alex S.; Bland, Michael T.; Marchi, Simone; Castillo-Rogez, Julie C.; McCord, Thomas B.; Jaumann, Ralf; Russell, Christopher T.; Prettyman, Thomas H.

    2015-11-01

    Dawn's exploration of Ceres has revealed its geophysical characteristics, informing the processes that have shaped it. Dawn has determined the average diameter of Ceres to be 940 km, smaller than the previously estimated 975 km [1]. This implies a density of 2160 kg/m3, indicating that Ceres is less differentiated than predicted [2]. The low-degree gravity field is consistent with the body being in hydrostatic equilibrium and the magnitude of J2 implies some central condensation. Ceres' entire surface is cratered, implying the lack of a thick (10's of km) water ice layer at the surface. Variability in Ceres' crater morphology indicates that the near-surface layer has variable strength and rheology, likely due to heterogeneity in the near-surface mixture of rock, ice and salt. The lack of a number of expected large impact basins on Ceres can be interpreted to be the result of viscous relaxation, resurfacing or a combination of both. These data provide insights into Ceres' thermal evolution and mechanical properties, which appear to be unique to this warm, icy body.[1] Thomas, P. C., et al., Differentiation of the asteroid Ceres as revealed by its shape, Nature, 437, 224-226, 2005; [2] McCord et al., Ceres: Its Origin, Evolution and Structure and Dawn's Potential Contribution, Space Sci Rev DOI 10.1007/s11214-010-9729-9, 2011.

  4. Surface Proteome Analysis of a Natural Isolate of Lactococcus lactis Reveals the Presence of Pili Able to Bind Human Intestinal Epithelial Cells*

    PubMed Central

    Meyrand, Mickael; Guillot, Alain; Goin, Mélodie; Furlan, Sylviane; Armalyte, Julija; Kulakauskas, Saulius; Cortes-Perez, Naima G.; Thomas, Ginette; Chat, Sophie; Péchoux, Christine; Dupres, Vincent; Hols, Pascal; Dufrêne, Yves F.; Trugnan, Germain; Chapot-Chartier, Marie-Pierre

    2013-01-01

    Surface proteins of Gram-positive bacteria play crucial roles in bacterial adhesion to host tissues. Regarding commensal or probiotic bacteria, adhesion to intestinal mucosa may promote their persistence in the gastro-intestinal tract and their beneficial effects to the host. In this study, seven Lactococcus lactis strains exhibiting variable surface physico-chemical properties were compared for their adhesion to Caco-2 intestinal epithelial cells. In this test, only one vegetal isolate TIL448 expressed a high-adhesion phenotype. A nonadhesive derivative was obtained by plasmid curing from TIL448, indicating that the adhesion determinants were plasmid-encoded. Surface-exposed proteins in TIL448 were analyzed by a proteomic approach consisting in shaving of the bacterial surface with trypsin and analysis of the released peptides by LC-MS/MS. As the TIL448 complete genome sequence was not available, the tryptic peptides were identified by a mass matching approach against a database including all Lactococcus protein sequences and the sequences deduced from partial DNA sequences of the TIL448 plasmids. Two surface proteins, encoded by plasmids in TIL448, were identified as candidate adhesins, the first one displaying pilin characteristics and the second one containing two mucus-binding domains. Inactivation of the pilin gene abolished adhesion to Caco-2 cells whereas inactivation of the mucus-binding protein gene had no effect on adhesion. The pilin gene is located inside a cluster of four genes encoding two other pilin-like proteins and one class-C sortase. Synthesis of pili was confirmed by immunoblotting detection of high molecular weight forms of pilins associated to the cell wall as well as by electron and atomic force microscopy observations. As a conclusion, surface proteome analysis allowed us to detect pilins at the surface of L. lactis TIL448. Moreover we showed that pili appendages are formed and involved in adhesion to Caco-2 intestinal epithelial cells

  5. Comparison of the structural and chemical composition of two unique micro/nanostructures produced by femtosecond laser interactions on nickel

    SciTech Connect

    Zuhlke, Craig A.; Anderson, Troy P.; Alexander, Dennis R.

    2013-09-16

    The structural and chemical composition of two unique microstructures formed on nickel, with nanoscale features, produced using femtosecond laser surface processing (FLSP) techniques is reported in this paper. These two surface morphologies, termed mounds and nanoparticle-covered pyramids, are part of a larger class of self-organized micro/nanostructured surfaces formed using FLSP. Cross-sections of the structures produced using focused ion beam milling techniques were analyzed with a transmission electron microscope. Both morphologies have a solid core with a layer of nanoparticles on the surface. Energy dispersive X-ray spectroscopy by scanning transmission electron microscopy studies reveal that the nanoparticles are a nickel oxide, while the core material is pure nickel.

  6. De novo sequencing of Astyanax mexicanus surface fish and Pachón cavefish transcriptomes reveals enrichment of mutations in cavefish putative eye genes.

    PubMed

    Hinaux, Hélène; Poulain, Julie; Da Silva, Corinne; Noirot, Céline; Jeffery, William R; Casane, Didier; Rétaux, Sylvie

    2013-01-01

    Astyanax mexicanus, a teleost species with surface dwelling (surface fish) and cave adapted (cavefish) morphs, is an important model system in evolutionary developmental biology (evodevo). Astyanax cavefish differ from surface fish in numerous traits, including the enhancement of non-visual sensory systems, and the loss of eyes and pigmentation. The genetic bases for these differences are not fully understood as genomic and transcriptomic data are lacking. We here present de novo transcriptome sequencing of embryonic and larval stages of a surface fish population and a cavefish population originating from the Pachón cave using the Sanger method. This effort represents the first large scale sequence and clone resource for the Astyanax research community. The analysis of these sequences show low levels of polymorphism in cavefish compared to surface fish, confirming previous studies on a small number of genes. A high proportion of the genes mutated in cavefish are known to be expressed in the zebrafish visual system. Such a high number of mutations in cavefish putative eye genes may be explained by relaxed selection for vision during the evolution in the absence of light. Based on these sequence differences, we provide a list of 11 genes that are potential candidates for having a role in cavefish visual system degeneration. PMID:23326453

  7. Characterization of Missouri surface waters near point sources of pollution reveals potential novel atmospheric route of exposure for bisphenol A and wastewater hormonal activity pattern.

    PubMed

    Kassotis, Christopher D; Alvarez, David A; Taylor, Julia A; vom Saal, Frederick S; Nagel, Susan C; Tillitt, Donald E

    2015-08-15

    Surface water contamination by chemical pollutants increasingly threatens water quality around the world. Among the many contaminants found in surface water, there is growing concern regarding endocrine disrupting chemicals, based on their ability to interfere with some aspect of hormone action in exposed organisms, including humans. This study assessed water quality at several sites across Missouri (near wastewater treatment plants and airborne release sites of bisphenol A) based on hormone receptor activation potencies and chemical concentrations present in the surface water. We hypothesized that bisphenol A and ethinylestradiol would be greater in water near permitted airborne release sites and wastewater treatment plant inputs, respectively, and that these two compounds would be responsible for the majority of activities in receptor-based assays conducted with water collected near these sites. Concentrations of bisphenol A and ethinylestradiol were compared to observed receptor activities using authentic standards to assess contribution to total activities, and quantitation of a comprehensive set of wastewater compounds was performed to better characterize each site. Bisphenol A concentrations were found to be elevated in surface water near permitted airborne release sites, raising questions that airborne releases of BPA may influence nearby surface water contamination and may represent a previously underestimated source to the environment and potential for human exposure. Estrogen and androgen receptor activities of surface water samples were predictive of wastewater input, although the lower sensitivity of the ethinylestradiol ELISA relative to the very high sensitivity of the bioassay approaches did not allow a direct comparison. Wastewater-influenced sites also had elevated anti-estrogenic and anti-androgenic equivalence, while sites without wastewater discharges exhibited no antagonist activities. PMID:25917777

  8. Characterization of Missouri surface waters near point sources of pollution reveals potential novel atmospheric route of exposure for bisphenol A and wastewater hormonal activity pattern

    USGS Publications Warehouse

    Kassotis, Christopher D.; Alvarez, David A.; Taylor, Julia A.; vom Saal, Frederick S.; Nagel, Susan C.; Tillitt, Donald E.

    2015-01-01

    Surface water contamination by chemical pollutants increasingly threatens water quality around the world. Among the many contaminants found in surface water, there is growing concern regarding endocrine disrupting chemicals, based on their ability to interfere with some aspect of hormone action in exposed organisms, including humans. This study assessed water quality at several sites across Missouri (near wastewater treatment plants and airborne release sites of bisphenol A) based on hormone receptor activation potencies and chemical concentrationspresent in the surface water. We hypothesized that bisphenol A and ethinylestradiol would be greater in water near permitted airborne release sites and wastewater treatment plant inputs, respectively, and that these two compounds would be responsible for the majority of activities in receptor-based assays conducted with water collected near these sites. Concentrations of bisphenol A and ethinylestradiol were compared to observed receptor activities using authentic standards to assess contribution to total activities, and quantitation of a comprehensive set of wastewater compounds was performed to better characterize each site. Bisphenol A concentrations were found to be elevated in surface water near permitted airborne release sites, raising questions that airborne releases of BPA may influence nearby surface water contamination and may represent a previously underestimated source to the environment and potential for human exposure. Estrogen and androgen receptor activities of surface water samples were predictive of wastewater input, although the lower sensitivity of the ethinylestradiol ELISA relative to the very high sensitivity of the bioassay approaches did not allow a direct comparison. Wastewater-influenced sites also had elevated anti-estrogenic and anti-androgenic equivalence, while sites without wastewater discharges exhibited no antagonist activities.

  9. Characterization of Missouri surface waters near point sources of pollution reveals potential novel atmospheric route of exposure for bisphenol A and wastewater hormonal activity pattern.

    PubMed

    Kassotis, Christopher D; Alvarez, David A; Taylor, Julia A; vom Saal, Frederick S; Nagel, Susan C; Tillitt, Donald E

    2015-08-15

    Surface water contamination by chemical pollutants increasingly threatens water quality around the world. Among the many contaminants found in surface water, there is growing concern regarding endocrine disrupting chemicals, based on their ability to interfere with some aspect of hormone action in exposed organisms, including humans. This study assessed water quality at several sites across Missouri (near wastewater treatment plants and airborne release sites of bisphenol A) based on hormone receptor activation potencies and chemical concentrations present in the surface water. We hypothesized that bisphenol A and ethinylestradiol would be greater in water near permitted airborne release sites and wastewater treatment plant inputs, respectively, and that these two compounds would be responsible for the majority of activities in receptor-based assays conducted with water collected near these sites. Concentrations of bisphenol A and ethinylestradiol were compared to observed receptor activities using authentic standards to assess contribution to total activities, and quantitation of a comprehensive set of wastewater compounds was performed to better characterize each site. Bisphenol A concentrations were found to be elevated in surface water near permitted airborne release sites, raising questions that airborne releases of BPA may influence nearby surface water contamination and may represent a previously underestimated source to the environment and potential for human exposure. Estrogen and androgen receptor activities of surface water samples were predictive of wastewater input, although the lower sensitivity of the ethinylestradiol ELISA relative to the very high sensitivity of the bioassay approaches did not allow a direct comparison. Wastewater-influenced sites also had elevated anti-estrogenic and anti-androgenic equivalence, while sites without wastewater discharges exhibited no antagonist activities.

  10. Effect of polymer properties and adherend surfaces on adhesion

    NASA Technical Reports Server (NTRS)

    Dwight, D. W.; Wightman, J. P.

    1976-01-01

    High temperature polymer surface characteristics associated with joint strength were evaluated. Selected samples represented composite adherends, aluminum filler and fiber glass carrier cloth. Detailed analysis of fractured joint surfaces revealed unique characteristics typical of the specific adhesive formulations and test conditions. A fracture mechanism model was developed for correlating macroscopic shear strength and microstructure of fracture surfaces. Applications were made to unpublished data on polyimides and fluoropolymers.

  11. Direct and indirect effects of atmospheric conditions and soil moisture on surface energy partitioning revealed by a prolonged drought at a temperate forest site

    SciTech Connect

    Gu, Lianhong; Meyers, T. P.; Pallardy, Stephen G.; Hanson, Paul J; Yang, Bai; Heuer, Mark; Hosman, K. P.; Riggs, Jeffery S; Sluss, Daniel Wayne; Wullschleger, Stan D

    2006-01-01

    The purpose of this paper is to examine the mechanism that controls the variation of surface energy partitioning between latent and sensible heat fluxes at a temperate deciduous forest site in central Missouri, USA. Taking advantage of multiple micrometeorological and ecophysiological measurements and a prolonged drought in the middle of the 2005 growing season at this site, we studied how soil moisture, atmospheric vapor pressure deficit (VPD), and net radiation affected surface energy partitioning. We stratified these factors to minimize potential confounding effects of correlation among them. We found that all three factors had direct effects on surface energy partitioning, but more important, all three factors also had crucial indirect effects. The direct effect of soil moisture was characterized by a rapid decrease in Bowen ratio with increasing soil moisture when the soil was dry and by insensitivity of Bowen ratio to variations in soil moisture when the soil was wet. However, the rate of decrease in Bowen ratio when the soil was dry and the level of soil moisture above which Bowen ratio became insensitive to changes in soil moisture depended on atmospheric conditions. The direct effect of increased net radiation was to increase Bowen ratio. The direct effect of VPD was very nonlinear: Increased VPD decreased Bowen ratio at low VPD but increased Bowen ratio at high VPD. The indirect effects were much more complicated. Reduced soil moisture weakened the influence of VPD but enhanced the influence of net adiation on surface energy partitioning. Soil moisture also controlled how net radiation influenced the relationship between surface energy partitioning and VPD and how VPD affected the relationship between surface energy partitioning and net radiation. Furthermore, both increased VPD and increased net radiation enhanced the sensitivity of Bowen ratio to changes in soil moisture and the effect of drought on surface energy partitioning. The direct and indirect

  12. The Placenta Harbors a Unique Microbiome

    PubMed Central

    Aagaard, Kjersti; Ma, Jun; Antony, Kathleen M.; Ganu, Radhika; Petrosino, Joseph; Versalovic, James

    2016-01-01

    Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA–based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001). PMID:24848255

  13. Unique Ganglioside Recognition Strategies for Clostridial Neurotoxins

    SciTech Connect

    Benson, Marc A.; Fu, Zhuji; Kim, Jung-Ja P.; Baldwin, Michael R.

    2012-03-15

    Botulinum neurotoxins (BoNTs) and tetanus neurotoxin are the causative agents of the paralytic diseases botulism and tetanus, respectively. The potency of the clostridial neurotoxins (CNTs) relies primarily on their highly specific binding to nerve terminals and cleavage of SNARE proteins. Although individual CNTs utilize distinct proteins for entry, they share common ganglioside co-receptors. Here, we report the crystal structure of the BoNT/F receptor-binding domain in complex with the sugar moiety of ganglioside GD1a. GD1a binds in a shallow groove formed by the conserved peptide motif E ... H ... SXWY ... G, with additional stabilizing interactions provided by two arginine residues. Comparative analysis of BoNT/F with other CNTs revealed several differences in the interactions of each toxin with ganglioside. Notably, exchange of BoNT/F His-1241 with the corresponding lysine residue of BoNT/E resulted in increased affinity for GD1a and conferred the ability to bind ganglioside GM1a. Conversely, BoNT/E was not able to bind GM1a, demonstrating a discrete mechanism of ganglioside recognition. These findings provide a structural basis for ganglioside binding among the CNTs and show that individual toxins utilize unique ganglioside recognition strategies.

  14. Genomic Characterization of Variable Surface Antigens Reveals a Telomere Position Effect as a Prerequisite for RNA Interference-Mediated Silencing in Paramecium tetraurelia

    PubMed Central

    Baranasic, Damir; Oppermann, Timo; Cheaib, Miriam; Cullum, John; Schmidt, Helmut

    2014-01-01

    ABSTRACT Antigenic or phenotypic variation is a widespread phenomenon of expression of variable surface protein coats on eukaryotic microbes. To clarify the mechanism behind mutually exclusive gene expression, we characterized the genetic properties of the surface antigen multigene family in the ciliate Paramecium tetraurelia and the epigenetic factors controlling expression and silencing. Genome analysis indicated that the multigene family consists of intrachromosomal and subtelomeric genes; both classes apparently derive from different gene duplication events: whole-genome and intrachromosomal duplication. Expression analysis provides evidence for telomere position effects, because only subtelomeric genes follow mutually exclusive transcription. Microarray analysis of cultures deficient in Rdr3, an RNA-dependent RNA polymerase, in comparison to serotype-pure wild-type cultures, shows cotranscription of a subset of subtelomeric genes, indicating that the telomere position effect is due to a selective occurrence of Rdr3-mediated silencing in subtelomeric regions. We present a model of surface antigen evolution by intrachromosomal gene duplication involving the maintenance of positive selection of structurally relevant regions. Further analysis of chromosome heterogeneity shows that alternative telomere addition regions clearly affect transcription of closely related genes. Consequently, chromosome fragmentation appears to be of crucial importance for surface antigen expression and evolution. Our data suggest that RNAi-mediated control of this genetic network by trans-acting RNAs allows rapid epigenetic adaptation by phenotypic variation in combination with long-term genetic adaptation by Darwinian evolution of antigen genes. PMID:25389173

  15. Characterization of the Caenorhabditis elegans UDP-galactopyranose mutase homolog glf-1 reveals an essential role for galactofuranose metabolism in nematode surface coat synthesis.

    PubMed

    Novelli, Jacopo F; Chaudhary, Kshitiz; Canovas, Julie; Benner, Jack S; Madinger, Catherine L; Kelly, Paul; Hodgkin, Jonathan; Carlow, Clotilde K S

    2009-11-15

    Galactofuranose (Gal(f)), the furanoic form of d-galactose produced by UDP-galactopyranose mutases (UGMs), is present in surface glycans of some prokaryotes and lower eukaryotes. Absence of the Gal(f) biosynthetic pathway in vertebrates and its importance in several pathogens make UGMs attractive drug targets. Since the existence of Gal(f) in nematodes has not been established, we investigated the role of the Caenorhabditis elegans UGM homolog glf-1 in worm development. glf-1 mutants display significant late embryonic and larval lethality, and other phenotypes indicative of defective surface coat synthesis, the glycan-rich outermost layer of the nematode cuticle. The glf homolog from the protozoan Leishmania major partially complements C. elegans glf-1. glf-1 mutants rescued by L. major glf, which behave as glf-1 hypomorphs, display resistance to infection by Microbacterium nematophilum, a pathogen of rhabditid nematodes thought to bind to surface coat glycans. To confirm the presence of Gal(f) in C. elegans, we analyzed C. elegans nucleotide sugar pools using online electrospray ionization-mass spectrometry (ESI-MS). UDP-Gal(f) was detected in wild-type animals while absent in glf-1 deletion mutants. Our data indicate that Gal(f) likely has a pivotal role in maintenance of surface integrity in nematodes, supporting investigation of UGM as a drug target in parasitic species.

  16. New ion microprobe U-Pb analyses on unpolished zircon surfaces and polished grain interiors from the 28 Ma Fish Canyon Tuff reveal a protracted crystallization history

    NASA Astrophysics Data System (ADS)

    Coble, M. A.

    2013-12-01

    U-Pb analyses on surfaces and polished interiors of Oligocene Fish Canyon Tuff (FCT) zircon are investigated to better constrain the disparity in FCT ages measured by different isotopic techniques. FCT sanidine is a widely used geochronology standard for K-Ar and 40Ar/39Ar analyses with reported ages ranging from ~27.6-28.3 Ma. In comparison, published U-Pb ID-TIMS zircon ages using chemical or mechanical abrasion methods range from ~28.2 to 28.6 Ma. New 206U-238Pb SHRIMP-RG ion microprobe ages were obtained on untreated, unpolished FCT zircon surfaces as well as from polished zircon interiors. FCT zircon was mounted with primary age standard Temora-2 (416.8 Ma) and secondary zircon standard early-erupted Bishop Tuff (0.767 Ma) by pressing euhedral grains into pliable indium metal leaving the exterior surfaces exposed. The high spatial resolution of the ion-microprobe produced analytical pits 25-30 μm in diameter and 4-6 μm deep (~8 to 9 nA primary O2- beam), allowing only the youngest portion of the zircon to be targeted, while avoiding abundant mineral and glass inclusions pervasive in FCT zircons. The 230Th-corrected 206Pb-238U weighted mean age for FCT zircon surfaces is 28.03×0.17 Ma (2σ, n=38, MSWD=1.07, Th/Urock=2.2) and for Bishop Tuff zircon surfaces is 0.763×0.006 Ma (2σ, n=25, MSWD=0.88, Th/Urock=2.81) analyzed over three analytical sessions. Calculated ages for FCT zircon surfaces are insensitive to common-Pb correction due to high radiogenic yield (average 98.2% radiogenic 206Pb corrected using 207Pb). Following analysis of zircon surfaces, the mount was polished to expose the interior of FCT zircons and reanalyzed. 230Th-corrected 206Pb-238U ages for FCT zircon interiors range from 28.0 to 29.5 Ma, with a weighted mean age of 28.68×0.15 Ma (2σ, n=54, MSWD=2.6, Th/Urock=2.2). Using an age of 418.4 Ma for Temora-2 (Mattinson, 2010) increases the ages for FCT zircon by 0.10 My. Despite this added uncertainty in standardization and the imprecision

  17. Exposure to ambient black carbon derived from a unique inventory and high-resolution model.

    PubMed

    Wang, Rong; Tao, Shu; Balkanski, Yves; Ciais, Philippe; Boucher, Olivier; Liu, Junfeng; Piao, Shilong; Shen, Huizhong; Vuolo, Maria Raffaella; Valari, Myrto; Chen, Han; Chen, Yuanchen; Cozic, Anne; Huang, Ye; Li, Bengang; Li, Wei; Shen, Guofeng; Wang, Bin; Zhang, Yanyan

    2014-02-18

    Black carbon (BC) is increasingly recognized as a significant air pollutant with harmful effects on human health, either in its own right or as a carrier of other chemicals. The adverse impact is of particular concern in those developing regions with high emissions and a growing population density. The results of recent studies indicate that BC emissions could be underestimated by a factor of 2-3 and this is particularly true for the hot-spot Asian region. Here we present a unique inventory at 10-km resolution based on a recently published global fuel consumption data product and updated emission factor measurements. The unique inventory is coupled to an Asia-nested (∼50 km) atmospheric model and used to calculate the global population exposure to BC with fully quantified uncertainty. Evaluating the modeled surface BC concentrations against observations reveals great improvement. The bias is reduced from -88% to -35% in Asia when the unique inventory and higher-resolution model replace a previous inventory combined with a coarse-resolution model. The bias can be further reduced to -12% by downscaling to 10 km using emission as a proxy. Our estimated global population-weighted BC exposure concentration constrained by observations is 2.14 μg⋅m(-3); 130% higher than that obtained using less detailed inventories and low-resolution models. PMID:24469822

  18. Clinical EPR: Unique Opportunities and Some Challenges

    PubMed Central

    Swartz, Harold M.; Williams, Benjamin B.; Zaki, Bassem I.; Hartford, Alan C.; Jarvis, Lesley A.; Chen, Eunice; Comi, Richard J.; Ernstoff, Marc S.; Hou, Huagang; Khan, Nadeem; Swarts, Steven G.; Flood, Ann B.; Kuppusamy, Periannan

    2014-01-01

    Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of important applications such as oxygen measurement, is challenged with several factors including the need for instrumentation customized for human subjects, probe and regulatory constraints. This paper describes the rationale and development of the first clinical EPR systems for two important clinical applications, namely, measurement of tissue oxygen (oximetry), and radiation dose (dosimetry) in humans. The clinical spectrometers operate at 1.2 GHz frequency and use surface loop resonators capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2 measurements can be carried out noninvasively and repeatedly after placement of an oxygen-sensitive paramagnetic material (currently India ink) at the site of interest. Our EPR dosimetry system is capable of measuring radiation-induced free radicals in the tooth of irradiated human subjects to determine the exposure dose. These developments offer potential opportunities for clinical dosimetry and oximetry, which include guiding therapy for individual patients with tumors or vascular disease, by monitoring of tissue oxygenation. Further work is in progress to translate this unique technology to routine clinical practice. PMID:24439333

  19. Coupling of proton source and sink via H+-migration along the membrane surface as revealed by double patch-clamp experiments.

    PubMed

    Antonenko, Y N; Pohl, P

    1998-06-12

    Long-range proton transfer along the surface of black lipid bilayers was observed between two integral membrane channels (gramicidins), one operating as a proton source, the other as a sink, by patch-clamp technique. In contrast, potassium ions were shown to equilibrate with the aqueous bulk phase before being consumed. Both channels opened and closed simultaneously only if the charge between them was carried by protons. In this case an anomalous high conductance between two patched membrane fragments was measured, each of them containing one single gramicidin channel. The coupled state disappeared when the distance between these two channels was increased above the critical value. The latter was shown to increase with the channel lifetime. Our results support the idea of the 'localized' proton coupling, in which protons that have been pumped across membranes migrate along the membrane surface to reach another membrane protein that utilizes the established pH gradient. PMID:9650589

  20. Structure of the TbBILBO1 Protein N-terminal Domain from Trypanosoma brucei Reveals an Essential Requirement for a Conserved Surface Patch*

    PubMed Central

    Vidilaseris, Keni; Morriswood, Brooke; Kontaxis, Georg; Dong, Gang

    2014-01-01

    TbBILBO1 is the only known component of the flagellar pocket collar, a cytoskeletal barrier element found in trypanosomes. The N-terminal domain (NTD) of TbBILBO1 was found to be dispensable for targeting of the protein in vivo. However, overexpression of constructs lacking the NTD caused complete growth inhibition, implying an essential requirement for this domain. A high resolution structure of the NTD of TbBILBO1 showed that it forms a ubiquitin-like fold with a conserved surface patch. Mutagenesis of this patch recapitulated the phenotypic effects of deleting the entire domain and was found to cause cell death. The surface patch on the NTD of TbBILBO1 is therefore a potential drug target. PMID:24362019

  1. Refined modeling and 14C plateau tuning reveal consistent patterns of glacial and deglacial 14C reservoir ages of surface waters in low-latitude Atlantic

    NASA Astrophysics Data System (ADS)

    Balmer, Sven; Sarnthein, Michael; Mudelsee, Manfred; Grootes, Pieter M.

    2016-08-01

    Modeling studies predict that changes in radiocarbon (14C) reservoir ages of surface waters during the last deglacial episode will reflect changes in both atmospheric 14C concentration and ocean circulation including the Atlantic Meridional Overturning Circulation. Tests of these models require the availability of accurate 14C reservoir ages in well-dated late Quaternary time series. We here test two models using plateau-tuned 14C time series in multiple well-placed sediment core age-depth sequences throughout the lower latitudes of the Atlantic Ocean. 14C age plateau tuning in glacial and deglacial sequences provides accurate calendar year ages that differ by as much as 500-2500 years from those based on assumed global reservoir ages around 400 years. This study demonstrates increases in local Atlantic surface reservoir ages of up to 1000 years during the Last Glacial Maximum, ages that reflect stronger trades off Benguela and summer winds off southern Brazil. By contrast, surface water reservoir ages remained close to zero in the Cariaco Basin in the southern Caribbean due to lagoon-style isolation and persistently strong atmospheric CO2 exchange. Later, during the early deglacial (16 ka) reservoir ages decreased to a minimum of 170-420 14C years throughout the South Atlantic, likely in response to the rapid rise in atmospheric pCO2 and Antarctic temperatures occurring then. Changes in magnitude and geographic distribution of 14C reservoir ages of peak glacial and deglacial surface waters deviate from the results of Franke et al. (2008) but are generally consistent with those of the more advanced ocean circulation model of Butzin et al. (2012).

  2. Transcriptomic analysis reveals new regulatory roles of Clp signaling in secondary-metabolite biosynthesis and surface motility in Lysobacter enzymogenes OH11

    PubMed Central

    Wang, Yansheng; Zhao, Yuxin; Zhang, Juan; Zhao, Yangyang; Shen, Yan; Su, Zhenhe; Xu, Gaoge; Du, Liangcheng; Huffman, Justin M.; Venturi, Vittorio; Qian, Guoliang; Liu, Fengquan

    2014-01-01

    Lysobacter enzymogenes is a bacterial biological-control agent emerging as a new source of antibiotic metabolites, such as HSAF (Heat-Stable Antifungal Factor) and the antibacterial factor WAP-8294A2. The regulatory mechanism(s) for antibiotic-metabolite biosynthesis remains largely unknown in L. enzymogenes. Clp, a cAMP-receptor-like protein, is shown to function as a global regulator in modulating biocontol-associated traits in L. enzymogenes. However, the genetic basis of Clp signaling remains unclear. Here, we utilized transcriptome/microarray analysis to determine the Clp regulon in L. enzymogenes. We showed that Clp is a global regulator in gene expression, as the transcription of 775 genes belonging to 19 functional groups was differentially controlled by Clp signaling. Analysis of the Clp regulon detected previously characterized Clp-modulated functions as well as novel loci. These include novel loci involved in antibiotic-metabolite biosynthesis and surface motility in L. enzymogenes. We further showed experimentally that Clp signaling played a positive role in regulating the biosynthesis of HSAF and WAP-8294A2, as well as surface motility which is a Type-IV-pilus-dependent trait. The regulation by Clp signaling of antibiotic (HSAF and WAP-8294A2) biosynthesis and surface motility was found to be independent. Importantly, we identified a factor Lat (Lysobacter acetyltransferase), a homologue of histone acetyltransferase Hpa2, which was regulated by Clp and involved in HSAF biosynthesis, but not associated with WAP-8294A2 production and surface motility. Overall, our study provided new insights into the regulatory role and molecular mechanism of Clp signaling in L. enzymogenes. PMID:25236801

  3. Crystal structure of the DdrB/ssDNA complex from Deinococcus radiodurans reveals a DNA binding surface involving higher-order oligomeric states

    PubMed Central

    Sugiman-Marangos, Seiji N.; Peel, John K.; Weiss, Yoni M.; Ghirlando, Rodolfo; Junop, Murray S.

    2013-01-01

    The ability of Deinococcus radiodurans to recover from extensive DNA damage is due in part to its ability to efficiently repair its genome, even following severe fragmentation by hundreds of double-strand breaks. The single-strand annealing pathway plays an important role early during the recovery process, making use of a protein, DdrB, shown to greatly stimulate ssDNA annealing. Here, we report the structure of DdrB bound to ssDNA to 2.3 Å. Pentameric DdrB was found to assemble into higher-order structures that coat ssDNA. To gain further mechanistic insight into the protein's function, a number of point mutants were generated altering both DNA binding and higher order oligomerization. This work not only identifies higher-order DdrB associations but also suggests the presence of an extended DNA binding surface running along the ‘top’ surface of a DdrB pentamer and continuing down between two individual subunits of the ring structure. Together this work sheds new insight into possible mechanisms for DdrB function in which higher-order assemblies of DdrB pentamers assist in the pairing of complementary ssDNA using an extended DNA binding surface. PMID:23975200

  4. High-resolution, three-dimensional modeling of human leukocyte antigen class I structure and surface electrostatic potential reveals the molecular basis for alloantibody binding epitopes.

    PubMed

    Kosmoliaptsis, Vasilis; Dafforn, Timothy R; Chaudhry, Afzal N; Halsall, David J; Bradley, J Andrew; Taylor, Craig J

    2011-11-01

    The potential of human leukocyte antigens (HLA) to stimulate humoral alloimmunity depends on the orientation, accessibility and physiochemical properties of polymorphic amino acids. We have generated high-resolution structural and physiochemical models of all common HLA class I alleles and analyzed the impact of amino acid polymorphisms on surface electrostatic potential. Atomic resolution three-dimensional structural models of HLA class I molecules were generated using the MODELLER computer algorithm. The molecular surface electrostatic potential was calculated using the DelPhi program. To confirm that electrostatic surface topography reflects known HLA B cell epitopes, we examined Bw4 and Bw6 and ascertained the impact of amino acid polymorphisms on their tertiary and physiochemical composition. The HLA protein structures generated performed well when subjected to stereochemical and energy-based testing for structural integrity. The electrostatic pattern and conformation of Bw4 and Bw6 epitopes are maintained among HLA molecules even when expressed in a different structural context. Importantly, variation in epitope amino acid composition does not always translate into a different electrostatic motif, providing an explanation for serologic cross-reactivity. Mutations of critical amino acids that abrogate antibody binding also induce distinct changes in epitope electrostatic properties. In conclusion, high-resolution structural modeling provides a physiochemical explanation for serologic patterns of antibody binding and provides novel insights into HLA immunogenicity. PMID:21840357

  5. The unique characteristics of the Neusiedler See: special area for climate change effects

    NASA Astrophysics Data System (ADS)

    Dinka, Mária; Ágoston-Szabó, Edit; Berczik, Árpád

    2013-04-01

    It is evident that among the surface waters the extremely shallow lakes (1-5 m) are exposed particularly intensive to the effects of climate change. Among the European greater shallow lakes, the Austrian-Hungarian cross-border Lake Fertő/Neusiedler See, with an area of 309 km2, is expected to respond spatially in different ways and with different consequences to the climate change. The continuous water body of Lake Fertő/Neusiedler See (except of the shoreline reeds) is characterised by inner reed stands with variable extension, braking up the water surface into the large open water areas, inner ponds, varied channels/connections. The investigation series of our more than three decades research, conducted on the 75 km2 Hungarian part of the lake, revealed that these water areas separated by reeds have different physical features as well as different water- and sediment chemical characterisitcs, which is tipically reflected in the biological diversity and community compositions. All of these, of course undergoes on almost continuous status change under the influence of seasonal dynamics and the actual changes in the weather. This very rare, unique mosaicity exhibiting on a larger water surface needs a special attention in the climate change impact assesments and it promises the recognition of basic hydrobiological knowleges and of more possibilities with applied orientation. Therefore shows this poster the mosaicity of Lake Fertő/Neusiedler See revealed by our research.

  6. Atomic Force Microscopy Stiffness Tomography on Living Arabidopsis thaliana Cells Reveals the Mechanical Properties of Surface and Deep Cell-Wall Layers during Growth

    PubMed Central

    Radotić, Ksenija; Roduit, Charles; Simonović, Jasna; Hornitschek, Patricia; Fankhauser, Christian; Mutavdžić, Dragosav; Steinbach, Gabor; Dietler, Giovanni; Kasas, Sandor

    2012-01-01

    Cell-wall mechanical properties play a key role in the growth and the protection of plants. However, little is known about genuine wall mechanical properties and their growth-related dynamics at subcellular resolution and in living cells. Here, we used atomic force microscopy (AFM) stiffness tomography to explore stiffness distribution in the cell wall of suspension-cultured Arabidopsis thaliana as a model of primary, growing cell wall. For the first time that we know of, this new imaging technique was performed on living single cells of a higher plant, permitting monitoring of the stiffness distribution in cell-wall layers as a function of the depth and its evolution during the different growth phases. The mechanical measurements were correlated with changes in the composition of the cell wall, which were revealed by Fourier-transform infrared (FTIR) spectroscopy. In the beginning and end of cell growth, the average stiffness of the cell wall was low and the wall was mechanically homogenous, whereas in the exponential growth phase, the average wall stiffness increased, with increasing heterogeneity. In this phase, the difference between the superficial and deep wall stiffness was highest. FTIR spectra revealed a relative increase in the polysaccharide/lignin content. PMID:22947854

  7. Nanopatterning of metal-coated silicon surfaces via ion beam irradiation: Real time x-ray studies reveal the effect of silicide bonding

    SciTech Connect

    El-Atwani, Osman; Gonderman, Sean; Suslova, Anastassiya; Fowler, Justin; El-Atwani, Mohamad; DeMasi, Alexander; Ludwig, Karl; Paul Allain, Jean

    2013-03-28

    We investigated the effect of silicide formation on ion-induced nanopatterning of silicon with various ultrathin metal coatings. Silicon substrates coated with 10 nm Ni, Fe, and Cu were irradiated with 200 eV argon ions at normal incidence. Real time grazing incidence small angle x-ray scattering (GISAXS) and x-ray fluorescence (XRF) were performed during the irradiation process and real time measurements revealed threshold conditions for nanopatterning of silicon at normal incidence irradiation. Three main stages of the nanopatterning process were identified. The real time GISAXS intensity of the correlated peaks in conjunction with XRF revealed that the nanostructures remain for a time period after the removal of the all the metal atoms from the sample depending on the binding energy of the metal silicides formed. Ex-situ XPS confirmed the removal of all metal impurities. In-situ XPS during the irradiation of Ni, Fe, and Cu coated silicon substrates at normal incidence demonstrated phase separation and the formation of different silicide phases that occur upon metal-silicon mixing. Silicide formation leads to nanostructure formation due the preferential erosion of the non-silicide regions and the weakening of the ion induced mass redistribution.

  8. Generalized two-dimensional perturbation correlation infrared spectroscopy reveals mechanisms for the development of surface charge and recalcitrance in plant-derived biochars.

    PubMed

    Harvey, Omar R; Herbert, Bruce E; Kuo, Li-Jung; Louchouarn, Patrick

    2012-10-01

    Fundamental knowledge of how biochars develop surface-charge and resistance to environmental degradation is crucial to their production for customized applications or understanding their functions in the environment. Two-dimensional perturbation-based correlation infrared spectroscopy (2D-PCIS) was used to study the biochar formation process in three taxonomically different plant biomass, under oxygen-limited conditions along a heat-treatment-temperature gradient (HTT; 200-650 °C). Results from 2D-PCIS pointed to the systematic, HTT-induced defragmenting of lignocellulose H-bonding network and demethylenation/demethylation, oxidation, or dehydroxylation/dehydrogenation of lignocellulose fragments as the primary reactions controlling biochar properties along the HTT gradient. The cleavage of OH(...)O-type H-bonds, oxidation of free primary hydroxyls to carboxyls (carboxylation; HTT ≤ 500 °C), and their subsequent dehydrogenation/dehydroxylation (HTT > 500 °C) controlled surface charge on the biochars; while the dehydrogenation of methylene groups, which yielded increasingly condensed structures (R-CH(2)-R →R═CH-R →R═C═R), controlled biochar recalcitrance. Variations in biochar properties across plant biomass type were attributable to taxa-specific transformations. For example, apparent inefficiencies in the cleavage of wood-specific H-bonds, and their subsequent oxidation to carboxyls, lead to lower surface charge in wood biochars (compared to grass biochars). Both nontaxa and taxa-specific transformations highlighted by 2D-PCIS could have significant implications for biochar functioning in fire-impacted or biochar-amended systems. PMID:22950676

  9. Generalized Two-Dimensional Perturbation Correlation Infrared Spectroscopy reveals Mechanisms for the Development of Surface Charge and Recalcitrance in Plant-derived Biochars

    SciTech Connect

    Harvey, Omar R.; Herbert, Bruce; Kuo, Li-Jung; Louchouarn, Patrick

    2012-09-05

    Fundamental knowledge of how biochars develop surface-charge and resistance to environmental degradation (or recalcitrance) is crucial to their production for customized applications or, understanding their functions in the environment. Two-dimensional perturbation-based correlation infrared spectroscopy (2D-PCIS) was used to study the biochar formation process in three taxonomically-different plant biomass, under oxygen-limited conditions along a heat-treatment-temperature gradient (HTT; 200-650 oC). Results from 2D-PCIS pointed to the systematic, HTT-induced defragmenting of lignocellulose H-bonding network, and demethylenation/demethylation, oxidation or dehydroxylation/dehydrogenation of lignocellulose fragments as the primary reactions controlling biochar properties along the HTT gradient. The cleavage of OH O-type H-bonds, oxidation of free primary hydroxyls (HTT≤500 oC), and their subsequent dehydrogenation/dehydroxylation (HTT>500 oC) controlled surface charge on the biochars; while the dehydrogenation of methylene groups, which yielded increasingly condensed structures (R-CH2-R →R=CH-R →R=C=R), controlled biochar recalcitrance. Variations in biochar properties across plant biomass type were attributable to taxa-specific transformations. For example, apparent inefficiencies in the cleavage of wood-specific H-bonds, and their subsequent oxidation to carboxyls, lead to lower surface charge in wood biochars (compared to grass biochars). Both non-taxa and taxa-specific transformations highlighted by 2D-PCIS could have significant implications for biochar functioning in fire-impacted or biochar-amended systems.

  10. Display of E. coli Alkaline Phosphatase pIII or pVIII Fusions on Phagemid Surfaces Reveals Monovalent Decoration with Active Molecules

    PubMed Central

    Weichel, Michael; Jaussi, Rolf; Rhyner, Claudio; Crameri, Reto

    2008-01-01

    Active alkaline phosphatase of Escherichia coli (PhoA, EC 3.1.3.1) was displayed via the leucine zipper element of the Jun-Fos heterodimer on the surface of filamentous phage and the kinetic parameters Km and kcat were determined. The phoA gene was cloned downstream of fos while jun was inserted upstream of pIII or pVIII, alternatively, in the pJuFo phagemid vector. Both fusion genes are regulated by independent lacZ promoters. PhoA displayed on the phagemid pIII surface exhibited a Km of 11.2 µM with 4-nitrophenyl phosphate as substrate, which is consistent with data published for soluble PhoA. Based on these data we calculated the decoration of pJuFo phagemid with PhoA using the minor and major coat proteins pIII and pVIII as fusion partners under variable inducing conditions. We found that, even if the promoters are fully induced at a concentration of 1000 µM IPTG, the phagemids display maximally one copy of PhoA-Fos-Jun-coat protein fusion, irrespective of whether the protein is presented via pIII or pVIII. However, since PhoA is displayed in a native-like fashion, as deduced from the kinetic parameters of the enzymatic reaction, the pJuFo technology provides a versatile tool for the functional screening of complex cDNA libraries displayed on the phagemids' surface. PMID:18949073

  11. Spontaneous Decoding of the Timing and Content of Human Object Perception from Cortical Surface Recordings Reveals Complementary Information in the Event-Related Potential and Broadband Spectral Change.

    PubMed

    Miller, Kai J; Schalk, Gerwin; Hermes, Dora; Ojemann, Jeffrey G; Rao, Rajesh P N

    2016-01-01

    The link between object perception and neural activity in visual cortical areas is a problem of fundamental importance in neuroscience. Here we show that electrical potentials from the ventral temporal cortical surface in humans contain sufficient information for spontaneous and near-instantaneous identification of a subject's perceptual state. Electrocorticographic (ECoG) arrays were placed on the subtemporal cortical surface of seven epilepsy patients. Grayscale images of faces and houses were displayed rapidly in random sequence. We developed a template projection approach to decode the continuous ECoG data stream spontaneously, predicting the occurrence, timing and type of visual stimulus. In this setting, we evaluated the independent and joint use of two well-studied features of brain signals, broadband changes in the frequency power spectrum of the potential and deflections in the raw potential trace (event-related potential; ERP). Our ability to predict both the timing of stimulus onset and the type of image was best when we used a combination of both the broadband response and ERP, suggesting that they capture different and complementary aspects of the subject's perceptual state. Specifically, we were able to predict the timing and type of 96% of all stimuli, with less than 5% false positive rate and a ~20ms error in timing. PMID:26820899

  12. Spontaneous Decoding of the Timing and Content of Human Object Perception from Cortical Surface Recordings Reveals Complementary Information in the Event-Related Potential and Broadband Spectral Change

    PubMed Central

    Miller, Kai J.; Schalk, Gerwin; Hermes, Dora; Ojemann, Jeffrey G.; Rao, Rajesh P. N.

    2016-01-01

    The link between object perception and neural activity in visual cortical areas is a problem of fundamental importance in neuroscience. Here we show that electrical potentials from the ventral temporal cortical surface in humans contain sufficient information for spontaneous and near-instantaneous identification of a subject’s perceptual state. Electrocorticographic (ECoG) arrays were placed on the subtemporal cortical surface of seven epilepsy patients. Grayscale images of faces and houses were displayed rapidly in random sequence. We developed a template projection approach to decode the continuous ECoG data stream spontaneously, predicting the occurrence, timing and type of visual stimulus. In this setting, we evaluated the independent and joint use of two well-studied features of brain signals, broadband changes in the frequency power spectrum of the potential and deflections in the raw potential trace (event-related potential; ERP). Our ability to predict both the timing of stimulus onset and the type of image was best when we used a combination of both the broadband response and ERP, suggesting that they capture different and complementary aspects of the subject’s perceptual state. Specifically, we were able to predict the timing and type of 96% of all stimuli, with less than 5% false positive rate and a ~20ms error in timing. PMID:26820899

  13. Pre-LGM ice dynamics of the Greenland Ice Sheet in Uummannaq Fjord West Greenland, revealed by blockfields, tors and till mantled surfaces

    NASA Astrophysics Data System (ADS)

    Rea, Brice; Roberts, David; Lane, Tim; Rhodés, Angel; Schnabel, Christoph

    2013-04-01

    The future response of the Greenland Ice Sheet has been the focus of much recent modelling work but in order to fully understand the dynamics of this ice mass it is also imperative that the past behaviour of the ice sheet is understood. Indeed it is only through successful hindcasts of past ice geometries and dynamics that confidence in predictions can be achieved. In most glaciated environments determining ice dynamics prior to the Last Glacial Maximum (LGM) and subsequent deglaciation are non-trivial. They rely on fortuitous preservation, more restricted ice cover at LGM than previously or protective cold based ice cover. Here results are presented from hypsometric surfaces in the Uummannaq Fjord region of West Greenland which can provide constrains on the dynamics of ice cover prior to and including the LGM. Uummanaq Fjord is a classic landscape of selective linear erosion containing deeply incised troughs juxtaposed with high elevation plateau where relief approaches 3 km in places. Excavations were made in a number of summit blockfields with samples collected. Results from a morphometric landscape analyses a presented, using both landscape hypsometry and an elevation-range slope-map approach to identify hypsometric surfaces. The hypsometric surfaces are divided into those which are now denuded and classified as regions of areal scour, those with a blockfield cover and areas which are still ice covered. A number of sites have been visited and excavations were made into blockfields. Data are presented indicating minimum depths, granulometry and mineralogy of blockfields which allowed a further subdivision into allochthonous and autochotonous blockfields. Samples were also collected for cosmogenic nuclide exposure analyses and indicate that blockfield boulders and tors exhibit ages extending significantly beyond the LGM. Based on equilibrium profile reconstructions of the LGM ice sheet (constrained by onshore and offshore geomorphology and cosmogenic and 14C ages

  14. Constructing Dense Graphs with Unique Hamiltonian Cycles

    ERIC Educational Resources Information Center

    Lynch, Mark A. M.

    2012-01-01

    It is not difficult to construct dense graphs containing Hamiltonian cycles, but it is difficult to generate dense graphs that are guaranteed to contain a unique Hamiltonian cycle. This article presents an algorithm for generating arbitrarily large simple graphs containing "unique" Hamiltonian cycles. These graphs can be turned into dense graphs…

  15. Observation of strain-controlled electronic modulations revealed by Fermi surface superstructures in strongly correlated LaNiO3 films

    NASA Astrophysics Data System (ADS)

    Yoo, Hyangkeun; Hyun, Seungill; Moreschini, Luca; Kim, Hyeong-Do; Chang, Youngjun; Sohn, Changhee; Jeong, Dawoon; Sinn, Soobin; Kim, Yongsu; Bostwick, Aaron; Rotenberg, Eli; Shim, Jihoon; Noh, Taewon

    2014-03-01

    Control over the electronic properties of strongly correlated electron systems can be achieved by exploiting the misfit strain that exists in epitaxial films on lattice mismatched substrates. Here, we report a systematic investigation of electronic structures in strongly correlated LaNiO3 films under different strain states, using in situ angle-resolved photoemission spectroscopy and the dynamical mean field theory. LaNiO3 film shows a change of a Fermi surface (FS) topology, driven by interplay between strong electron-electron correlations and misfit strain effects. Additionally, different from compressive strain case, a FS with tensile strain has a large flat region to induce strong FS nesting. As a result, different FS superstructures are observed in the compressive and tensile strain cases, and their origins are attributed to charge disproportionation and spin density waves, respectively. The more details will be discussed in the presentation.

  16. High resolution measurements of methane and carbon dioxide in surface waters over a natural seep reveal dynamics of dissolved phase air-sea flux.

    PubMed

    Du, Mengran; Yvon-Lewis, Shari; Garcia-Tigreros, Fenix; Valentine, David L; Mendes, Stephanie D; Kessler, John D

    2014-09-01

    Marine hydrocarbon seeps are sources of methane and carbon dioxide to the ocean, and potentially to the atmosphere, though the magnitude of the fluxes and dynamics of these systems are poorly defined. To better constrain these variables in natural environments, we conducted the first high-resolution measurements of sea surface methane and carbon dioxide concentrations in the massive natural seep field near Coal Oil Point (COP), California. The corresponding high resolution fluxes were calculated, and the total dissolved phase air-sea fluxes over the surveyed plume area (∼363 km(2)) were 6.66 × 10(4) to 6.71 × 10(4) mol day(-1) with respect to CH4 and -6.01 × 10(5) to -5.99 × 10(5) mol day(-1) with respect to CO2. The mean and standard deviation of the dissolved phase air-sea fluxes of methane and carbon dioxide from the contour gridding analysis were estimated to be 0.18 ± 0.19 and -1.65 ± 1.23 mmol m(-2) day(-1), respectively. This methane flux is consistent with previous, lower-resolution estimates and was used, in part, to conservatively estimate the total area of the dissolved methane plume at 8400 km(2). The influx of carbon dioxide to the surface water refutes the hypothesis that COP seep methane appreciably influences carbon dioxide dynamics. Seeing that the COP seep field is one of the biggest natural seeps, a logical conclusion could be drawn that microbial oxidation of methane from natural seeps is of insufficient magnitude to change the resulting plume area from a sink of atmospheric carbon dioxide to a source.

  17. Evolution of GITRL Immune Function: Murine GITRL Exhibits Unique Structural and Biochemical Properties Within the TNF Superfamily

    SciTech Connect

    Chattopadhyay,K.; Ramagopal, U.; Brenowitz, M.; Nathenson, S.; Almo, S.

    2008-01-01

    Glucocorticoid-induced TNF receptor ligand (GITRL), a recently identified member of the TNF superfamily, binds to its receptor, GITR, on both effector and regulatory T cells and generates positive costimulatory signals implicated in a wide range of T cell functions. In contrast to all previously characterized homotrimeric TNF family members, the mouse GITRL crystal structure reveals a previously unrecognized dimeric assembly that is stabilized via a unique 'domain-swapping' interaction. Consistent with its crystal structure, mouse GITRL exists as a stable dimer in solution. Structure-guided mutagenesis studies confirmed the determinants responsible for dimerization and support a previously unrecognized receptor-recognition surface for mouse GITRL that has not been observed for any other TNF family members. Taken together, the unique structural and biochemical behavior of mouse GITRL, along with the unusual domain organization of murine GITR, support a previously unrecognized mechanism for signaling within the TNF superfamily.

  18. Some unique superconductive Properties of Cuprates

    NASA Astrophysics Data System (ADS)

    Müller, K. A.

    2013-04-01

    Copper oxides are the only materials that show transition temperatures, Tc, above the boiling point of liquid nitrogen, with a maximum Tmc of 162 K under pressure. Their structure is layered, with one to several CuO2 planes, and upon hole doping, their transition temperature follows a dome-shaped curve with a maximum at Tmc. In the underdoped regime, i.e., below Tmc, a pseudogap T* is found, with T* always being larger than Tc, a property unique to the copper oxides [1]. In the superconducting state, Cooper pairs (two holes with antiparallel spins) are formed that exhibit coherence lengths on the order of a lattice distance in the CuO2 plane and one order of magnitude less perpendicular to it. Their macroscopic wave function is parallel to the CuO2 plane near 100% d at their surface, but only 75% d and 25 % s in the bulk, and near 100% s perpendicular to the plane in YBCO. There are two gaps with the same Tc [2]. As function of doping, the oxygen isotope effect is novel and can be quantitatively accounted for by a two-band vibronic theory [3] near Tmc, and underdoped below it till Tc = 0 with by a formula valid for (bi)polarons [4]. These cuprates are intrinsically heterogeneous in a dynamic way. In terms of quasiparticles, Jahn-Teller bipolarons are present at low doping, and aggregate upon cooling [1], so that probably ramified clusters and/or stripes are formed, leading over to a more Fermi-liquid-type behavior at large carrier concentrations above Tmc.

  19. SMARTS revealed

    NASA Astrophysics Data System (ADS)

    Subasavage, John P.; Bailyn, Charles D.; Smith, R. Christopher; Henry, Todd J.; Walter, Frederick M.; Buxton, Michelle M.

    2010-07-01

    The Small and Moderate Aperture Research Telescope System (SMARTS)* consists of four telescopes atop Cerro Tololo Inter-American Observatory (CTIO): the 0.9m, 1.0m, 1.3m, and 1.5m. A consortium of twelve institutions and universities began funding operations in February 2003. Time allocation for these facilities is as follows: ~65% to consortium members, ~25% to the general community, and 10% to Chilean researchers. Thus, resources remain available to the community while providing a unique opportunity for consortium members; the possibility of high temporal cadence monitoring coupled with long time baseline monitoring. Indeed, a number of member programs have benefited from such a schema. Furthermore, two of the four telescopes are scheduled in a queue mode in which observations are collected by service observers. Queue mode investigators have access to spectroscopic observations (both RC and echelle) as well as direct imaging (both optical and near-IR simultaneously). Of the remaining two telescopes, the 1.0m is almost exclusively operated in user mode and contains a 20'×20' FOV optical imager, and the 0.9m is operated both in user and service mode in equal allotments and also has a dedicated optical imager. The latter facilities are frequently used for hands-on student training under the superb sky conditions afforded at CTIO. Currently, three of the partner universities are responsible for managing telescope scheduling and data handling, while one additional university is responsible for some of the instruments. In return, these universities receive additional telescope time. Operations are largely run by a handful of people, with six personnel from the four support universities and seven dedicated personnel in Chile (five observers, one observer support engineer, and one postdoctoral appointee). Thus far, this model has proven to be both an efficient and an effective method for operating the small telescopes at CTIO.

  20. Cryptosporidiosis in Haiti: surprisingly low level of species diversity revealed by molecular characterization of Cryptosporidium oocysts from surface water and groundwater

    PubMed Central

    Damiani, Céline; Balthazard-Accou, Ketty; Clervil, Elmyre; Diallo, Aïssata; Da Costa, Cécilia; Emmanuel, Evens; Totet, Anne; Agnamey, Patrice

    2013-01-01

    The protozoan parasite Cryptosporidium sp. has emerged as one of the most important water contaminants, causing waterborne outbreaks of diarrhoeal diseases worldwide. In Haiti, cryptosporidiosis is a frequent cause of diarrhoea in children under the age of five years, HIV-infected individuals, and people living in low socioeconomic conditions, mainly due to the consumption of water or food polluted by Cryptosporidium oocysts. The aim of this study was to detect and identify Cryptosporidium oocysts present in 12 water samples collected in Port-au-Prince and 4 water samples collected in Cap Haïtien. Initial detection consisted of immunomagnetic separation – immunofluorescence assay (IMS-IFA), which was confirmed by nested PCR, targeting the most polymorphic region of the 18S rRNA gene in 15/16 samples. Genotyping was performed by PCR-restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. Under our working conditions, neither nested PCR-RFLP nor direct DNA sequencing revealed the expected species diversity, as only Cryptosporidium parvum was identified in the water samples studied. This study highlights the difficulty of detecting mixed populations of Cryptosporidium species in environmental samples. PMID:24252814

  1. Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target

    PubMed Central

    Town, Jennifer; Pais, Helio; Harrison, Sally; Bataille, Carole; Bunjobpol, Wilawan; Zhang, Jing; Rabbitts, Terence H.

    2016-01-01

    The cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers for that tumor type and potential proteins that can be the target of antibody-mediated therapy. We have used next-generation deep RNA sequencing (RNA-seq) coupled to an in-house database of genes encoding cell surface proteins (herein referred to as the surfaceome) as a tool to define a cell surface proteome of Ewing sarcoma compared with progenitor mesenchymal stem cells. This subtractive RNA-seq analysis revealed a specific surfaceome of Ewing and showed unexpectedly that the leucine-rich repeat and Ig domain protein 1 (LINGO1) is expressed in over 90% of Ewing sarcoma tumors, but not expressed in any other somatic tissue apart from the brain. We found that the LINGO1 protein acts as a gateway protein internalizing into the tumor cells when engaged by antibody and can carry antibody conjugated with drugs to kill Ewing sarcoma cells. Therefore, LINGO1 is a new, unique, and specific biomarker and drug target for the treatment of Ewing sarcoma. PMID:26979953

  2. Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target.

    PubMed

    Town, Jennifer; Pais, Helio; Harrison, Sally; Stead, Lucy F; Bataille, Carole; Bunjobpol, Wilawan; Zhang, Jing; Rabbitts, Terence H

    2016-03-29

    The cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers for that tumor type and potential proteins that can be the target of antibody-mediated therapy. We have used next-generation deep RNA sequencing (RNA-seq) coupled to an in-house database of genes encoding cell surface proteins (herein referred to as the surfaceome) as a tool to define a cell surface proteome of Ewing sarcoma compared with progenitor mesenchymal stem cells. This subtractive RNA-seq analysis revealed a specific surfaceome of Ewing and showed unexpectedly that the leucine-rich repeat and Ig domain protein 1 (LINGO1) is expressed in over 90% of Ewing sarcoma tumors, but not expressed in any other somatic tissue apart from the brain. We found that the LINGO1 protein acts as a gateway protein internalizing into the tumor cells when engaged by antibody and can carry antibody conjugated with drugs to kill Ewing sarcoma cells. Therefore, LINGO1 is a new, unique, and specific biomarker and drug target for the treatment of Ewing sarcoma. PMID:26979953

  3. Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target.

    PubMed

    Town, Jennifer; Pais, Helio; Harrison, Sally; Stead, Lucy F; Bataille, Carole; Bunjobpol, Wilawan; Zhang, Jing; Rabbitts, Terence H

    2016-03-29

    The cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers for that tumor type and potential proteins that can be the target of antibody-mediated therapy. We have used next-generation deep RNA sequencing (RNA-seq) coupled to an in-house database of genes encoding cell surface proteins (herein referred to as the surfaceome) as a tool to define a cell surface proteome of Ewing sarcoma compared with progenitor mesenchymal stem cells. This subtractive RNA-seq analysis revealed a specific surfaceome of Ewing and showed unexpectedly that the leucine-rich repeat and Ig domain protein 1 (LINGO1) is expressed in over 90% of Ewing sarcoma tumors, but not expressed in any other somatic tissue apart from the brain. We found that the LINGO1 protein acts as a gateway protein internalizing into the tumor cells when engaged by antibody and can carry antibody conjugated with drugs to kill Ewing sarcoma cells. Therefore, LINGO1 is a new, unique, and specific biomarker and drug target for the treatment of Ewing sarcoma.

  4. Surface deformation associated with the March 1996 earthquake swarm at Akutan Island, Alaska, revealed by C-band ERS and L-band JERS radar interferometry

    USGS Publications Warehouse

    Lu, Zhiming; Wicks, C.; Kwoun, O.; Power, J.A.; Dzurisin, D.

    2005-01-01

    In March 1996, an intense earthquake swarm beneath Akutan Island, Alaska, was accompanied by extensive ground cracking but no eruption of Akutan volcano. Radar interferograms produced from L-band JERS-1 and C-band ERS-1/2 images show uplift associated with the swarm by as much as 60 cm on the western part of the island. The JERS-1 interferogram has greater coherence, especially in areas with loose surface material or thick vegetation. It also shows subsidence of similar magnitude on the eastern part of the island and displacements along faults reactivated during the swarm. The axis of uplift and subsidence strikes about N70??W, which is roughly parallel to a zone of fresh cracks on the northwest flank of the volcano, to normal faults that cut the island and to the inferred maximum compressive stress direction. A common feature of models that fit the deformation is the emplacement of a shallow dike along this trend beneath the northwest flank of the volcano. Both before and after the swarm, the northwest flank was uplifted 5-20 mm/year relative to the southwest flank, probably by magma intrusion. The zone of fresh cracks subsided about 20 mm during 1996-1997 and at lesser rates thereafter, possibly because of cooling and degassing of the intrusion. ?? 2005 CASI.

  5. Surface- vs Diffusion-Limited Mechanisms of Anion Exchange in CsPbBr3 Nanocrystal Cubes Revealed through Kinetic Studies.

    PubMed

    Koscher, Brent A; Bronstein, Noah D; Olshansky, Jacob H; Bekenstein, Yehonadav; Alivisatos, A Paul

    2016-09-21

    Ion-exchange transformations allow access to nanocrystalline materials with compositions that are inaccessible via direct synthetic routes. However, additional mechanistic insight into the processes that govern these reactions is needed. We present evidence for the presence of two distinct mechanisms of exchange during anion exchange in CsPbX3 nanocrystals (NCs), ranging in size from 6.5 to 11.5 nm, for transformations from CsPbBr3 to CsPbCl3 or CsPbI3. These NCs exhibit bright luminescence throughout the exchange, allowing their optical properties to be observed in real time, in situ. The iodine exchange presents surface-reaction-limited exchanges allowing all anionic sites within the NC to appear chemically identical, whereas the chlorine exchange presents diffusion-limited exchanges proceeding through a more complicated exchange mechanism. Our results represent the first steps toward developing a microkinetic description of the anion exchange, with implications not only for understanding the lead halide perovskites but also for nanoscale ion exchange in general. PMID:27606934

  6. Different emissive states in the bulk and at the surface of methylammonium lead bromide perovskite revealed by two-photon micro-spectroscopy and lifetime measurements

    NASA Astrophysics Data System (ADS)

    Karki, Khadga Jung; Abdellah, Mohamed; Zhang, Wei; Pullerits, Tõnu

    2016-07-01

    Two photon photoluminescence (2PPL) from single crystals of methyl ammonium lead bromide (CH3NH3PbBr3, MAPbBr3) is studied. We observe two components in the 2PPL spectra, which we assign to the photoluminescence (PL) from the carrier recombination at the band edge and the recombination due to self-trapping of excitons. The PL Stokes shift of self-trapped excitons is about 100 meV from the band-gap energy. Our measurements show that about 15% of the total PL from regions about 40 μm deep inside the crystal is due to the emission from self-trapped exciton. This contribution increases to about 20% in the PL from the regions close to the surface. Time resolved measurements of 2PPL show that the PL due to band-edge recombination has a life time of about 8 ns while the PL lifetime of self-trapped excitons is in the order of 100 ns. Quantification of self-trapped excitons in the materials used in photovoltaics is important as such excitons hinder charge separation. As our results also show that an appreciable fraction of photo-generated carriers get trapped, the results are important in rational design of photovoltaics. On the other hand, our results also show that the self-trapped excitons broaden the emission spectrum, which may be useful in designing broadband light emitting devices.

  7. Forage fish of the Pacific Rim as revealed by diet of a piscivorous seabird: Synchrony and relationships with sea surface temperature

    USGS Publications Warehouse

    Thayer, J.A.; Bertram, D.F.; Hatch, Shyla A.; Hipfner, M.J.; Slater, L.; Sydeman, W.J.; Watanuki, Y.

    2008-01-01

    We tested the hypothesis of synchronous interannual changes in forage fish dynamics around the North Pacific Rim. To do this, we sampled forage fish communities using a seabird predator, the rhinoceros auklet (Cerorhinca monocerata), at six coastal study sites from Japan to California. We investigated whether take of forage fishes was related to local marine conditions as indexed by sea surface temperature (SST). SST was concordant across sites in the eastern Pacific, but inversely correlated between east and west. Forage fish communities consisted of anchovy (Engraulis spp.), sandlance (Ammodytes spp.), capelin (Mallotus spp.), and juvenile rockfish (Sebastes spp.), among others, and take of forage fish varied in response to interannual and possibly lower-frequency oceanographic variability. Take of primary forage species were significantly related to changes in SST only at the eastern sites. We found synchrony in interannual variation of primary forage fishes across several regions in the eastern Pacific, but no significant east-west correlations. Specifically in the Japan Sea, factors other than local SST or interannual variability may more strongly influence forage fishes. Predator diet sampling offers a fishery-independent, large-scale perspective on forage fish dynamics that may be difficult to obtain using conventional means of study. ?? 2008 NRC.

  8. Change of the Topography of Ventral Cell Surface during Spreading of Fibroblasts as Revealed by Evanescent Wave-Excited Fluorescence Microscopy: Effect of Contractility and Microtubule Integrity

    NASA Astrophysics Data System (ADS)

    Hirata, Hiroaki; Ohki, Kazuo; Miyata, Hidetake

    Evanescent wave-excited fluorescence microscopy, which selectively probes the ventral membranes of cells adhered to glass substrate, was utilized to observe the change in the topography of the ventral plasma membranes of Swiss 3T3 fibroblasts during spreading. In the initial stage of the spreading (up to 2 hours after seeding), the ventral membrane was close (<100nm) to the substrate in the peripheral and the central regions. About 4 hrs after seeding, the ventral surface assumed a flat topography for a short period and then gradually became uneven, displaying streak pattern of cell-to-substrate contact (6-8 hours after seeding). By 24 hours after seeding, cells gained polygonal shape and most regions except for the focal adhesions were separated from the substrate. Within these well-spread cells actin stress fibers were found to emanate obliquely from the focal adhesions, as previously reported. When cells were grown in the presence of 2, 3-butanedione monoxime (BDM), an inhibitor of actomyosin-based contraction of stress fibers and the cell, the ventral membranes in majority of the cells displayed flat topography, and the tilt of the stress fibers decreased. Cells grown in the presence of colchicine, a microtubule-depolymerizing agent also possessed flat ventral membrane and less tilted stress fibers. These results suggest that the contraction of stress fibers and integrity of microtubules are important in the formation of the uneven topography of ventral membrane and the tilt of stress fibers.

  9. Atmospheric boundary layer structures associated with the Ora del Garda wind in the Alps as revealed from airborne and surface measurements

    NASA Astrophysics Data System (ADS)

    Laiti, Lavinia; Zardi, Dino; de Franceschi, Massimiliano; Rampanelli, Gabriele

    2013-10-01

    The paper investigates a coupled lake-breeze and valley-wind system, known as Ora del Garda. The latter typically originates on clear-sky days over the northern shore of Lake Garda in the Alps. After channelling into the nearby Sarca Valley and Lakes Valley, this airflow finally breaks out, through an elevated saddle, into the adjacent Adige Valley, where it strongly interacts with the local valley wind. Two flights of an instrumented motorglider explored, under different synoptic conditions, the thermal structure of the atmospheric boundary layer (ABL) associated with this wind at selected vertical sections-namely over the lake shore, at mid-valley, and at the junction with the Adige Valley. Data from airborne measurements, as well as from weather stations disseminated along the valley floor, provided the basis for mapping 3D fields of potential temperature over high-resolution grids by means of a Residual Kriging (RK) technique. This representation allowed the identification of site-specific ABL features associated with the Ora del Garda. In particular, a typical daytime coastal-breeze structure is detected in the lake shore region, where the advection of colder air tends to stabilize the atmosphere throughout the ABL depth. Mid-valley vertical profiles from both flights display shallow convective mixed layers, surmounted by deeper weakly stable layers. On the other hand, RK-gridded temperature maps show cross-valley thermal asymmetries, amenable to the complex topography and to the inhomogeneous surface coverage, as well as to a curvature of the valley axis. Finally, in the area where the upper Lakes Valley joins the Adige Valley, specific features associated with the complex interaction between the Ora del Garda and the local up-valley wind are found.

  10. Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

    PubMed

    Garnett, James P; Braun, Daniela; McCarthy, Alex J; Farrant, Matthew R; Baker, Emma H; Lindsay, Jodi A; Baines, Deborah L

    2014-12-01

    Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection.

  11. Identification of the lambda integrase surface that interacts with Xis reveals a residue that is also critical for Int dimer formation.

    PubMed

    Warren, David; Sam, My D; Manley, Kate; Sarkar, Dibyendu; Lee, Sang Yeol; Abbani, Mohamad; Wojciak, Jonathan M; Clubb, Robert T; Landy, Arthur

    2003-07-01

    Lambda integrase (Int) is a heterobivalent DNA-binding protein that together with the accessory DNA-bending proteins IHF, Fis, and Xis, forms the higher-order protein-DNA complexes that execute integrative and excisive recombination at specific loci on the chromosomes of phage lambda and its Escherichia coli host. The large carboxyl-terminal domain of Int is responsible for binding to core-type DNA sites and catalysis of DNA cleavage and ligation reactions. The small amino-terminal domain (residues 1-70), which specifies binding to arm-type DNA sites distant from the regions of strand exchange, consists of a three-stranded beta-sheet, proposed to recognize the cognate DNA site, and an alpha-helix. We report here that a site on this alpha-helix is critical for both homomeric interactions between Int protomers and heteromeric interactions with Xis. The mutant E47A, which was identified by alanine-scanning mutagenesis, abolishes interactions between Int and Xis bound at adjacent binding sites and reduces interactions between Int protomers bound at adjacent arm-type sites. Concomitantly, this residue is essential for excisive recombination and contributes to the efficiency of the integrative reaction. NMR titration data with a peptide corresponding to Xis residues 57-69 strongly suggest that the carboxyl-terminal tail of Xis and the alpha-helix of the aminoterminal domain of Int comprise the primary interaction surface for these two proteins. The use of a common site on lambda Int for both homotypic and heterotypic interactions fits well with the complex regulatory patterns associated with this site-specific recombination reaction.

  12. Topological analysis of HIV-1 glycoproteins expressed in situ on virus surfaces reveals tighter packing but greater conformational flexibility than for soluble gp120.

    PubMed

    Tong, Tommy; Osawa, Keiko; Robinson, James E; Crooks, Ema T; Binley, James M

    2013-08-01

    In natural infection, antibodies interact with HIV-1 primarily through nonfunctional forms of envelope glycoproteins (Env), including uncleaved (UNC) gp160 and gp41 stumps. These antigens are important to fully characterize, as they may be decoys that promote nonneutralizing responses and may also be targets for nonneutralizing effector responses. In this study, we compared the antigenic properties of Env expressed in situ on pseudovirion virus-like particle (VLP) surfaces and soluble gp120 using harmonized enzyme-linked immunosorbent assays (ELISAs) and a panel of 51 monoclonal antibodies (MAbs). Only 32 of 46 soluble gp120-reactive MAbs recognized the primary UNC gp160 antigen of VLPs. Indeed, many epitopes were poorly exposed (C1, V2, C1-C4, C4, C4-V3, CD4 induced [CD4i], and PGT group 3) or obscured (C2, C5, and C1-C5) on VLPs. In further studies, VLP Env exhibited an increased degree of inter-MAb competition, the epicenter of which was the base of the V3 loop, where PGT, 2G12, V3, and CD4 binding site specificities competed. UNC gp160 also underwent more drastic soluble CD4 (sCD4)-induced conformational changes than soluble gp120, exposing CD4i, C1-C4, and V2 epitopes. A greater propensity of UNC gp160 to undergo conformational changes was also suggested by the induction of CD4i MAb binding to VLPs by a V3 MAb as well as by soluble CD4. The same effect was not observed for soluble gp120. Taken together, our data suggest that membrane-expressed UNC gp160 exists in a less "triggered" conformational state than soluble gp120 and that MAb binding to UNC gp160 tends to have greater conformational consequences.

  13. Patterns of the loop current system and regions of sea surface height variability in the eastern Gulf of Mexico revealed by the self-organizing maps

    NASA Astrophysics Data System (ADS)

    Liu, Yonggang; Weisberg, Robert H.; Vignudelli, Stefano; Mitchum, Gary T.

    2016-04-01

    The Self-Organizing Map (SOM), an unsupervised learning neural network, is employed to extract patterns evinced by the Loop Current (LC) system and to identify regions of sea surface height (SSH) variability in the eastern Gulf of Mexico (GoM) from 23 years (1993-2015) of altimetry data. Spatial patterns are characterized as different LC extensions and different stages in the process of LC eddy shedding. The temporal evolutions and the frequency of occurrences of these patterns are obtained, and the typical trajectories of the LC system progression on the SOM grid are investigated. For an elongated, northwest-extended, or west-positioned LC, it is common for the LC anticyclonic eddy (LCE) to separate and propagate into the western GoM, while an initially separated LCE in close proximity to the west Florida continental slope often reattaches to the LC and develops into an elongated LC, or reduces intensity locally before moving westward as a smaller eddy. Regions of differing SSH variations are also identified using the joint SOM-wavelet analysis. Along the general axis of the LC, SSH exhibits strong variability on time scales of 3 months to 2 years, also with energetic intraseasonal variations, which is consistent with the joint Empirical Orthogonal Function (EOF)-wavelet analysis. In the more peripheral regions, the SSH has a dominant seasonal variation that also projects across the coastal ocean. The SOM, when applied to both space and time domains of the same data, provides a powerful tool for diagnosing ocean processes from such different perspectives.

  14. Transcriptome Dynamics of Developing Photoreceptors in Three-Dimensional Retina Cultures Recapitulates Temporal Sequence of Human Cone and Rod Differentiation Revealing Cell Surface Markers and Gene Networks.

    PubMed

    Kaewkhaw, Rossukon; Kaya, Koray Dogan; Brooks, Matthew; Homma, Kohei; Zou, Jizhong; Chaitankar, Vijender; Rao, Mahendra; Swaroop, Anand

    2015-12-01

    The derivation of three-dimensional (3D) stratified neural retina from pluripotent stem cells has permitted investigations of human photoreceptors. We have generated a H9 human embryonic stem cell subclone that carries a green fluorescent protein (GFP) reporter under the control of the promoter of cone-rod homeobox (CRX), an established marker of postmitotic photoreceptor precursors. The CRXp-GFP reporter replicates endogenous CRX expression in vitro when the H9 subclone is induced to form self-organizing 3D retina-like tissue. At day 37, CRX+ photoreceptors appear in the basal or middle part of neural retina and migrate to apical side by day 67. Temporal and spatial patterns of retinal cell type markers recapitulate the predicted sequence of development. Cone gene expression is concomitant with CRX, whereas rod differentiation factor neural retina leucine zipper protein (NRL) is first observed at day 67. At day 90, robust expression of NRL and its target nuclear receptor NR2E3 is evident in many CRX+ cells, while minimal S-opsin and no rhodopsin or L/M-opsin is present. The transcriptome profile, by RNA-seq, of developing human photoreceptors is remarkably concordant with mRNA and immunohistochemistry data available for human fetal retina although many targets of CRX, including phototransduction genes, exhibit a significant delay in expression. We report on temporal changes in gene signatures, including expression of cell surface markers and transcription factors; these expression changes should assist in isolation of photoreceptors at distinct stages of differentiation and in delineating coexpression networks. Our studies establish the first global expression database of developing human photoreceptors, providing a reference map for functional studies in retinal cultures. PMID:26235913

  15. Comparative Analysis of Antibody Responses against HSP60, Invariant Surface Glycoprotein 70, and Variant Surface Glycoprotein Reveals a Complex Antigen-Specific Pattern of Immunoglobulin Isotype Switching during Infection by Trypanosoma brucei

    PubMed Central

    Radwanska, Magdalena; Magez, Stefan; Michel, Alain; Stijlemans, Benoît; Geuskens, Maurice; Pays, Etienne

    2000-01-01

    During Trypanosoma brucei infections, the response against the variant surface glycoprotein (VSG) of the parasite represents a major interaction between the mammalian host immune system and the parasite surface. Since immune recognition of other parasite derived factors also occurs, we examined the humoral host response against trypanosome heat shock protein 60 (HSP60), a conserved antigen with an autoimmune character. During experimental T. brucei infection in BALB/c mice, the anti-HSP60 response was induced when parasites differentiated into stumpy forms. This response was characterized by a stage-specific immunoglobulin isotype switching as well as by the induction of an autoimmune response. Specific recognition of trypanosome HSP60 was found to occur during the entire course of infection. Immunoglobulin G2a (IgG2a) and IgG2b antibodies, induced mainly in a T-cell-independent manner, were observed during the first peak of parasitemia, whereas IgG1 and IgG3 antibodies were found at the end of the infection, due to a specific T-cell-mediated response. Comparative analysis of the kinetics of anti-HSP60, anti-invariant surface glycoprotein 70 (ISG70), and anti-VSG antibody responses indicated that the three trypanosome antigens give rise to specific and independent patterns of immunoglobulin isotype switching. PMID:10639455

  16. Clusters, surfaces, and catalysis

    PubMed Central

    Somorjai, Gabor A.; Contreras, Anthony M.; Montano, Max; Rioux, Robert M.

    2006-01-01

    The surface science of heterogeneous metal catalysis uses model systems ranging from single crystals to monodispersed nanoparticles in the 1–10 nm range. Molecular studies reveal that bond activation (C–H, H–H, C–C, CO) occurs at 300 K or below as the active metal sites simultaneously restructure. The strongly adsorbed molecules must be mobile to free up these sites for continued turnover of reaction. Oxide–metal interfaces are also active for catalytic turnover. Examples using C–H and CO activation are described to demonstrate these properties. Future directions include synthesis, characterization, and reaction studies with 2D and 3D monodispersed metal nanoclusters to obtain 100% selectivity in multipath reactions. Investigations of the unique structural, dynamic, and electronic properties of nanoparticles are likely to have major impact in surface technologies. The fields of heterogeneous, enzyme, and homogeneous catalysis are likely to merge for the benefit of all three. PMID:16740668

  17. Deep Sequencing of the Trypanosoma cruzi GP63 Surface Proteases Reveals Diversity and Diversifying Selection among Chronic and Congenital Chagas Disease Patients

    PubMed Central

    Llewellyn, Martin S.; Messenger, Louisa A.; Luquetti, Alejandro O.; Garcia, Lineth; Torrico, Faustino; Tavares, Suelene B. N.; Cheaib, Bachar; Derome, Nicolas; Delepine, Marc; Baulard, Céline; Deleuze, Jean-Francois; Sauer, Sascha; Miles, Michael A.

    2015-01-01

    Background Chagas disease results from infection with the diploid protozoan parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and multiclonal infections in individual hosts are common, but little studied. In this study, we explore T. cruzi infection multiclonality in the context of age, sex and clinical profile among a cohort of chronic patients, as well as paired congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep sequencing technology. Methodology/ Principal Findings A 450bp fragment of the trypomastigote TcGP63I surface protease gene was amplified and sequenced across 70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a second, mitochondrial target—ND5—was sequenced across the same cohort of cases. Several million reads were generated, and sequencing read depths were normalized within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of variance indicated no clear correlation between intra-host sequence diversity and age, sex or symptoms, while principal coordinate analyses showed no clustering by symptoms between patients. Between congenital pairs, we found evidence for the transmission of multiple sequence types from mother to infant, as well as widespread instances of novel genotypes in infants. Finally, non-synonymous to synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and TcGP63Ib subfamilies within each cohort provided powerful evidence of strong diversifying selection at this locus. Conclusions/Significance Our results shed light on the diversity of parasite DTUs within each patient, as well as the extent to which parasite strains pass between mother and foetus in congenital cases. Although we were unable to find any evidence that parasite diversity accumulates with age in our study cohorts, putative diversifying selection within members of the TcGP63I

  18. Falls Prevention: Unique to Older Adults

    MedlinePlus

    ... Prevention Sleep Problems Stroke Join our e-newsletter! Aging & Health A to Z Falls Prevention Unique to ... difficulties. Optimizing Management of Congestive Heart Failure and COPD Congestive Heart Failure (CHF) Many older people develop ...

  19. Unique Ideas in a New Facility

    ERIC Educational Resources Information Center

    Hamby, G. W.

    1977-01-01

    Unique features of a new vocational agriculture department facility in Diamond, Missouri, are described, which include an overhead hoist system, arc welders, storage areas, paint room, and greenhouse. (TA)

  20. Modularity, comparative cognition and human uniqueness

    PubMed Central

    Shettleworth, Sara J.

    2012-01-01

    Darwin's claim ‘that the difference in mind between man and the higher animals … is certainly one of degree and not of kind’ is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the ‘core knowledge’ account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research. PMID:22927578

  1. Modularity, comparative cognition and human uniqueness.

    PubMed

    Shettleworth, Sara J

    2012-10-01

    Darwin's claim 'that the difference in mind between man and the higher animals … is certainly one of degree and not of kind' is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the 'core knowledge' account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research. PMID:22927578

  2. Unique Gold Nanoparticle Aggregates as a Highly Active SERS Substrate

    SciTech Connect

    Schwartzberg, A M; Grant, C D; Wolcott, A; Talley, C E; Huser, T R; Bogomolni, R; Zhang, J Z

    2004-04-06

    A unique gold nanoparticle aggregate (GNA) system has been shown to be an excellent substrate for surface-enhanced Raman scattering (SERS) applications. Rhodamine 6G (R6G), a common molecule used for testing SERS activity on silver, but generally difficult to detect on gold substrates, has been found to readily bind to the GNA and exhibit strong SERS activity due to the unique surface chemistry afforded by sulfur species on the surface. This GNA system has yielded a large SERS enhancement of 10{sup 7}-10{sup 9} in bulk solution for R6G, on par with or greater than any previously reported gold SERS substrate. SERS activity has also been successfully demonstrated for several biological molecules including adenine, L-cysteine, L-lysine, and L-histidine for the first time on a gold SERS substrate, showing the potential of this GNA as a convenient and powerful SERS substrate for biomolecular detection. In addition, SERS spectrum of R6G on single aggregates has been measured. We have shown that the special surface properties of the GNA, in conjunction with strong near IR absorption, make it useful for SERS analysis of a wide variety of molecules.

  3. A Unique Case of Allogeneic Fat Grafting Between Brothers

    PubMed Central

    Kim, Samuel; Edelson, Richard L.; Sumpio, Brandon; Kwei, Stephanie

    2016-01-01

    Summary: We present a case of a 65-year-old man with cutaneous T-cell lymphoma treated with radiation therapy and an allogeneic hematopoietic stem cell transplant from his human leukocyte antigen-matched brother. Engraftment was successful, but the patient went on to develop painful, radiation-induced ulcers. The ulcers were fat-allografted using liposuctioned fat from his brother because of the patient’s unique chimeric state. Postprocedure follow-up revealed epithelialization of the ulcer sites and significant improvement in neuropathic pain. Our unique case study supports the use of fat grafting for its restorative purposes and for its ability to alleviate chronic neuropathic pain. Additionally, it appears that our case provides a basis of a general approach to the treatment of radiation-induced ulcers in chimeric patients with lymphoid malignancies. PMID:27757347

  4. The Role of Visual Working Memory in Attentive Tracking of Unique Objects

    ERIC Educational Resources Information Center

    Makovski, Tal; Jiang, Yuhong V.

    2009-01-01

    When tracking moving objects in space humans usually attend to the objects' spatial locations and update this information over time. To what extent do surface features assist attentive tracking? In this study we asked participants to track identical or uniquely colored objects. Tracking was enhanced when objects were unique in color. The benefit…

  5. Suomi satellite brings to light a unique frontier of nighttime environmental sensing capabilities

    PubMed Central

    Miller, Steven D.; Mills, Stephen P.; Elvidge, Christopher D.; Lindsey, Daniel T.; Lee, Thomas F.; Hawkins, Jeffrey D.

    2012-01-01

    Most environmental satellite radiometers use solar reflectance information when it is available during the day but must resort at night to emission signals from infrared bands, which offer poor sensitivity to low-level clouds and surface features. A few sensors can take advantage of moonlight, but the inconsistent availability of the lunar source limits measurement utility. Here we show that the Day/Night Band (DNB) low-light visible sensor on the recently launched Suomi National Polar-orbiting Partnership (NPP) satellite has the unique ability to image cloud and surface features by way of reflected airglow, starlight, and zodiacal light illumination. Examples collected during new moon reveal not only meteorological and surface features, but also the direct emission of airglow structures in the mesosphere, including expansive regions of diffuse glow and wave patterns forced by tropospheric convection. The ability to leverage diffuse illumination sources for nocturnal environmental sensing applications extends the advantages of visible-light information to moonless nights. PMID:22984179

  6. Experimental investigation of a unique airbreathing pulsed laser propulsion concept

    NASA Technical Reports Server (NTRS)

    Myrabo, L. N.; Nagamatsu, H. T.; Manka, C.; Lyons, P. W.; Jones, R. A.

    1991-01-01

    Investigations were conducted into unique methods of converting pulsed laser energy into propulsive thrust across a flat impulse surface under atmospheric conditions. The propulsion experiments were performed with a 1-micron neodymium-glass laser at the Space Plasma Branch of the Naval Research Laboratory. Laser-induced impulse was measured dynamically by ballistic pendulums and statically using piezoelectric pressure transducers on a stationary impulse surface. The principal goal was to explore methods for increasing the impulse coupling performance of airbreathing laser-propulsion engines. A magnetohydrodynamic thrust augmentation effect was discovered when a tesla-level magnetic field was applied perpendicular to the impulse surface. The impulse coupling coefficient performance doubled and continued to improve with increasing laser-pulse energies. The resultant performance of 180 to 200 N-s/MJ was found to be comparable to that of the earliest afterburning turbojets.

  7. Uniquely designed nuclear structures of lower eukaryotes.

    PubMed

    Iwamoto, Masaaki; Hiraoka, Yasushi; Haraguchi, Tokuko

    2016-06-01

    The nuclear structures of lower eukaryotes, specifically protists, often vary from those of yeasts and metazoans. Several studies have demonstrated the unique and fascinating features of these nuclear structures, such as a histone-independent condensed chromatin in dinoflagellates and two structurally distinct nuclear pore complexes in ciliates. Despite their unique molecular/structural features, functions required for formation of their cognate molecules/structures are highly conserved. This provides important information about the structure-function relationship of the nuclear structures. In this review, we highlight characteristic nuclear structures found in lower eukaryotes, and discuss their attractiveness as potential biological systems for studying nuclear structures.

  8. Uniqueness of Nash equilibrium in vaccination games.

    PubMed

    Bai, Fan

    2016-12-01

    One crucial condition for the uniqueness of Nash equilibrium set in vaccination games is that the attack ratio monotonically decreases as the vaccine coverage level increasing. We consider several deterministic vaccination models in homogeneous mixing population and in heterogeneous mixing population. Based on the final size relations obtained from the deterministic epidemic models, we prove that the attack ratios can be expressed in terms of the vaccine coverage levels, and also prove that the attack ratios are decreasing functions of vaccine coverage levels. Some thresholds are presented, which depend on the vaccine efficacy. It is proved that for vaccination games in homogeneous mixing population, there is a unique Nash equilibrium for each game.

  9. Transcriptomics exposes the uniqueness of parasitic plants.

    PubMed

    Ichihashi, Yasunori; Mutuku, J Musembi; Yoshida, Satoko; Shirasu, Ken

    2015-07-01

    Parasitic plants have the ability to obtain nutrients directly from other plants, and several species are serious biological threats to agriculture by parasitizing crops of high economic importance. The uniqueness of parasitic plants is characterized by the presence of a multicellular organ called a haustorium, which facilitates plant-plant interactions, and shutting down or reducing their own photosynthesis. Current technical advances in next-generation sequencing and bioinformatics have allowed us to dissect the molecular mechanisms behind the uniqueness of parasitic plants at the genome-wide level. In this review, we summarize recent key findings mainly in transcriptomics that will give us insights into the future direction of parasitic plant research.

  10. Unique Phase Recovery for Nonperiodic Objects

    NASA Astrophysics Data System (ADS)

    Nugent, K. A.; Peele, A. G.; Chapman, H. N.; Mancuso, A. P.

    2003-11-01

    It is well known that the loss of phase information at detection means that a diffraction pattern may be consistent with a multitude of physically different structures. This Letter shows that it is possible to perform unique structural determination in the absence of a priori information using x-ray fields with phase curvature. We argue that significant phase curvature is already available using modern x-ray optics and we demonstrate an algorithm that allows the phase to be recovered uniquely and reliably.

  11. Unique forbidden beta decays and neutrino mass

    SciTech Connect

    Dvornický, Rastislav; Šimkovic, Fedor

    2015-10-28

    The measurement of the electron energy spectrum in single β decays close to the endpoint provides a direct determination of the neutrino masses. The most sensitive experiments use β decays with low Q value, e.g. KATRIN (tritium) and MARE (rhenium). We present the theoretical spectral shape of electrons emitted in the first, second, and fourth unique forbidden β decays. Our findings show that the Kurie functions for these unique forbidden β transitions are linear in the limit of massless neutrinos like the Kurie function of the allowed β decay of tritium.

  12. (-)-Botryodiplodin, A Unique Ribose Analog Toxin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many toxins owe their mechanisms of action to being structural analogs of essential metabolites, messengers or structural components. Examples range from tubo-curare to penicillin. Ribose plays a unique role in the metabolism of living organisms, whether prokaryotes or eukaryotes. It and its deri...

  13. LCA – Unique and Controversial Case Studies

    EPA Science Inventory</