Sample records for differentiation complex edc-encoded

  1. Identification and comparative analysis of the epidermal differentiation complex in snakes

    PubMed Central

    Brigit Holthaus, Karin; Mlitz, Veronika; Strasser, Bettina; Tschachler, Erwin; Alibardi, Lorenzo; Eckhart, Leopold

    2017-01-01

    The epidermis of snakes efficiently protects against dehydration and mechanical stress. However, only few proteins of the epidermal barrier to the environment have so far been identified in snakes. Here, we determined the organization of the Epidermal Differentiation Complex (EDC), a cluster of genes encoding protein constituents of cornified epidermal structures, in snakes and compared it to the EDCs of other squamates and non-squamate reptiles. The EDC of snakes displays shared synteny with that of the green anole lizard, including the presence of a cluster of corneous beta-protein (CBP)/beta-keratin genes. We found that a unique CBP comprising 4 putative beta-sheets and multiple cysteine-rich EDC proteins are conserved in all snakes and other squamates investigated. Comparative genomics of squamates suggests that the evolution of snakes was associated with a gene duplication generating two isoforms of the S100 fused-type protein, scaffoldin, the origin of distinct snake-specific EDC genes, and the loss of other genes that were present in the EDC of the last common ancestor of snakes and lizards. Taken together, our results provide new insights into the evolution of the skin in squamates and a basis for the characterization of the molecular composition of the epidermis in snakes. PMID:28345630

  2. EDCs Mixtures: A Stealthy Hazard for Human Health?

    PubMed

    Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

    2017-02-07

    Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed "body burden" of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex "body burden" of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce.

  3. EDCs Mixtures: A Stealthy Hazard for Human Health?

    PubMed Central

    Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

    2017-01-01

    Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed “body burden” of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex “body burden” of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce. PMID:29051438

  4. Effects of carbon-based nanoparticles (CNPs) on the fate of endocrine disrupting chemicals (EDCs) in different agricultural soils.

    NASA Astrophysics Data System (ADS)

    Stumpe, Britta; Wolski, Sabrina; Marschner, Bernd

    2013-04-01

    Nanotechnology is a major innovative scientific and economic growth area. To date there is a lack about possible adverse effects that may be associated with manufactured nanomaterial in terrestrial environments. Since it is known that on the one hand carbon-based nanoparticles (CNPs) and endocrine disrupting chemicals (EDCs) strongly interact in wastewater and that on the other hand CNPs and EDCs are released together via wastewater irrigation to agricultural soils, knowledge of CNP effects on the EDC fate in the soil environment is needed for further risk assessments. The overall goal of this project is to gain a better understanding of interaction of CNPs with EDCs within the soil system. Three different soil samples were applied with different CNPs, EDCs and CNP-EDC complexes and incubated over a period of 6 weeks. The EDC mineralization as well as their uptake by soil microorganisms was monitored to describe impacts of the nanomaterial on the EDC fate. As quality control for the biological soil activity soil respiration, enzyme activities and the soil microbial biomass were monitored in all incubated soil samples. Clearly, EDCs bound in CNP complexes showed a decrease in mineralization. While the free EDCs showed a total mineralization of 34 to 45 %, the nano complexed EDCs were only mineralized to 12 to 15 %. Since no effects of the nanomaterial on the biological soil activity were observed, we conclude that the reduced EDC mineralization is directly linked to their interaction with the CNPs. Since additionally the EDC adsorption to CNPs reduced the EDC uptake by soil microorganism, we assume that CNPs generally form more or less recalcitrant aggregates which likely protect the associated EDCs from degradation.

  5. Similar modes of interaction enable Trailer Hitch and EDC3 to associate with DCP1 and Me31B in distinct protein complexes.

    PubMed

    Tritschler, Felix; Eulalio, Ana; Helms, Sigrun; Schmidt, Steffen; Coles, Murray; Weichenrieder, Oliver; Izaurralde, Elisa; Truffault, Vincent

    2008-11-01

    Trailer Hitch (Tral or LSm15) and enhancer of decapping-3 (EDC3 or LSm16) are conserved eukaryotic members of the (L)Sm (Sm and Like-Sm) protein family. They have a similar domain organization, characterized by an N-terminal LSm domain and a central FDF motif; however, in Tral, the FDF motif is flanked by regions rich in charged residues, whereas in EDC3 the FDF motif is followed by a YjeF_N domain. We show that in Drosophila cells, Tral and EDC3 specifically interact with the decapping activator DCP1 and the DEAD-box helicase Me31B. Nevertheless, only Tral associates with the translational repressor CUP, whereas EDC3 associates with the decapping enzyme DCP2. Like EDC3, Tral interacts with DCP1 and localizes to mRNA processing bodies (P bodies) via the LSm domain. This domain remains monomeric in solution and adopts a divergent Sm fold that lacks the characteristic N-terminal alpha-helix, as determined by nuclear magnetic resonance analyses. Mutational analysis revealed that the structural integrity of the LSm domain is required for Tral both to interact with DCP1 and CUP and to localize to P-bodies. Furthermore, both Tral and EDC3 interact with the C-terminal RecA-like domain of Me31B through their FDF motifs. Together with previous studies, our results show that Tral and EDC3 are structurally related and use a similar mode to associate with common partners in distinct protein complexes.

  6. Differential gene expression patterns in developing sexually dimorphic rat brain regions exposed to antiandrogenic, estrogenic, or complex endocrine disruptor mixtures: glutamatergic synapses as target.

    PubMed

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver; Axelstad, Marta; Boberg, Julie; Christiansen, Sofie; Rehrauer, Hubert; Georgijevic, Jelena Kühn; Hass, Ulla; Kortenkamp, Andreas; Schlumpf, Margret

    2015-04-01

    The study addressed the question whether gene expression patterns induced by different mixtures of endocrine disrupting chemicals (EDCs) administered in a higher dose range, corresponding to 450×, 200×, and 100× high-end human exposure levels, could be characterized in developing brain with respect to endocrine activity of mixture components, and which developmental processes were preferentially targeted. Three EDC mixtures, A-Mix (anti-androgenic mixture) with 8 antiandrogenic chemicals (di-n-butylphthalate, diethylhexylphthalate, vinclozolin, prochloraz, procymidone, linuron, epoxiconazole, and DDE), E-Mix (estrogenic mixture) with 4 estrogenic chemicals (bisphenol A, 4-methylbenzylidene camphor, 2-ethylhexyl 4-methoxycinnamate, and butylparaben), a complex mixture, AEP-Mix, containing the components of A-Mix and E-Mix plus paracetamol, and paracetamol alone, were administered by oral gavage to rat dams from gestation day 7 until weaning. General developmental endpoints were not affected by EDC mixtures or paracetamol. Gene expression was analyzed on postnatal day 6, during sexual brain differentiation, by exon microarray in medial preoptic area in the high-dose group, and by real-time RT-PCR in medial preoptic area and ventromedial hypothalamus in all dose groups. Expression patterns were mixture, sex, and region specific. Effects of the analgesic drug paracetamol, which exhibits antiandrogenic activity in peripheral systems, differed from those of A-Mix. All mixtures had a strong, mixture-specific impact on genes encoding for components of excitatory glutamatergic synapses and genes controlling migration and pathfinding of glutamatergic and GABAergic neurons, as well as genes linked with increased risk of autism spectrum disorders. Because development of glutamatergic synapses is regulated by sex steroids also in hippocampus, this may represent a general target of ECD mixtures.

  7. Carbodiimide EDC induces cross-links that stabilize RNase A C-dimer against dissociation: EDC adducts can affect protein net charge, conformation, and activity.

    PubMed

    López-Alonso, Jorge P; Diez-García, Fernando; Font, Josep; Ribó, Marc; Vilanova, Maria; Scholtz, J Martin; González, Carlos; Vottariello, Francesca; Gotte, Giovanni; Libonati, Massimo; Laurents, Douglas V

    2009-08-19

    RNase A self-associates under certain conditions to form a series of domain-swapped oligomers. These oligomers show high catalytic activity against double-stranded RNA and striking antitumor actions that are lacking in the monomer. However, the dissociation of these metastable oligomers limits their therapeutic potential. Here, a widely used conjugating agent, 1-ethyl-3-(3-dimethylaminoisopropyl) carbodiimide (EDC), has been used to induce the formation of amide bonds between carboxylate and amine groups of different subunits of the RNase A C-dimer. A cross-linked C-dimer which does not dissociate was isolated and was found have augmented enzymatic activity toward double-stranded RNA relative to the unmodified C-dimer. Characterization using chromatography, electrophoresis, mass spectrometry, and NMR spectroscopy revealed that the EDC-treated C-dimer retains its structure and contains one to three novel amide bonds. Moreover, both the EDC-treated C-dimer and EDC-treated RNase A monomer were found to carry an increased number of positive charges (about 6 ± 2 charges per subunit). These additional positive charges are presumably due to adduct formation with EDC, which neutralizes a negatively charged carboxylate group and couples it to a positively charged tertiary amine. The increased net positive charge endowed by EDC adducts likely contributes to the heightened cleavage of double-stranded RNA of the EDC-treated monomer and EDC-treated C-dimer. Further evidence for EDC adduct formation is provided by the reaction of EDC with a dipeptide Ac-Asp-Ala-NH(2) monitored by NMR spectroscopy and mass spectrometry. To determine if EDC adduct formation with proteins is common and how this affects protein net charge, conformation, and activity, four well-characterized proteins, ribonuclease Sa, hen lysozyme, carbonic anhydrase, and hemoglobin, were incubated with EDC and the products were characterized. EDC formed adducts with all these proteins, as judged by mass

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

    PubMed Central

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

    2016-01-01

    The morphogenesis of feathers is a complex process that depends on a tight spatiotemporal regulation of gene expression and assembly of the protein components of mature feathers. Recent comparative genomics and gene transcription studies have indicated that genes within the epidermal differentiation complex (EDC) encode numerous structural proteins of cornifying skin cells in amniotes including birds. Here, we determined the localization of one of these proteins, termed EDMTFH (Epidermal Differentiation Protein starting with a MTF motif and rich in Histidine), which belongs to a group of EDC-encoded proteins rich in aromatic amino acid residues. We raised an antibody against an EDMTFH-specific epitope and performed immunohistochemical investigations by light microscopy and immunogold labeling by electron microscopy of chicken embryos at days 14–18 of development. EDMTFH was specifically present in the subperiderm, a transient layer of the embryonic epidermis, and in barbs and barbules of feathers. In the latter, it partially localized to bundles of so-called feather beta-keratins (corneous beta-proteins, CBPs). Cells of the embryonic periderm, the epidermis proper, and the feather sheath were immunonegative for EDMTFH. The results of this study indicate that EDMTFH may contribute to the unique mechanical properties of feathers and define EDMTFH as a common marker of the subperiderm and the feather barbules. This expression pattern of EDMTFH resembles that of epidermal differentiation cysteine-rich protein (EDCRP) and feather CBPs and is in accordance with the hypothesis that a major part of the cyclically regenerating feather follicle is topologically, developmentally and evolutionarily related to the embryonic subperiderm. PMID:27936131

  9. Differential expression of the nuclear-encoded mitochondrial transcriptome in pediatric septic shock.

    PubMed

    Weiss, Scott L; Cvijanovich, Natalie Z; Allen, Geoffrey L; Thomas, Neal J; Freishtat, Robert J; Anas, Nick; Meyer, Keith; Checchia, Paul A; Shanley, Thomas P; Bigham, Michael T; Fitzgerald, Julie; Banschbach, Sharon; Beckman, Eileen; Howard, Kelli; Frank, Erin; Harmon, Kelli; Wong, Hector R

    2014-11-19

    Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis. We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded mitochondrial genes using a false discovery rate of 1%. A series of bioinformatic approaches were applied to compare differentially expressed genes across previously validated gene expression-based subclasses (groups A, B, and C) of pediatric septic shock. In total, 118 genes were differentially regulated in subjects with septic shock compared to healthy controls, including 48 genes that were upregulated and 70 that were downregulated. The top scoring canonical pathway was oxidative phosphorylation, with general downregulation of the 51 genes corresponding to the electron transport system (ETS). The top two gene networks were composed primarily of mitochondrial ribosomal proteins highly connected to ETS complex I, and genes encoding for ETS complexes I, II, and IV that were highly connected to the peroxisome proliferator activated receptor (PPAR) family. There were 162 mitochondrial genes differentially regulated between groups A, B, and C. Group A, which had the highest maximum number of organ failures and mortality, exhibited a greater downregulation of mitochondrial genes compared to groups B and C. Based on a focused analysis of a pediatric septic shock transcriptomic database, nuclear-encoded mitochondrial genes were differentially regulated early in pediatric septic shock compared to healthy controls, as well

  10. EDC Cross-linking of Decellularized Tissue: A Promising Approach?

    PubMed

    Lehmann, Nadine; Christ, Torsten; Daugs, Aila; Bloch, Oliver; Holinski, Sebastian

    2017-07-01

    Decellularization of xenogenous cardiovascular structures is a promising approach to create scaffolds for tissue engineering. Unfortunately, handling and pliability of the unfixed tissue is challenging. N-(3-dimethylaminopropyl)-N9-ethylcarbodiimide (EDC) is an alternative cross-linking agent to glutaraldehyde (GA). Applied in native tissue, it provides biocompatibility and shows no potential for calcification. In addition, EDC can be used to link growth factors (GFs) to tissue scaffolds after decellularization. EDC cross-linking could thereby help to improve decellularized tissue without the toxicity of GA. Porcine aortic wall tissue specimens (TS) were decellularized, treated with EDC, and coated with fibroblast growth factor (FGF) or vascular endothelial growth factor (VEGF). Afterward, TS were subcutaneously implanted in 36 Lewis rats along with one decellularized TS without EDC treatment. After 2, 4, and 6 weeks TS were explanted from 12 rats, respectively. Vital cells were evaluated by RNA quantification, general cellular infiltration by hematoxylin and eosin staining (H&E), macrophage infiltration by CD68 staining, calcification by Von-Kossa staining, and tissue degradation by measurement of TS thickness. Quantification of vital cells showed reduced reseeding of EDC-treated TS compared to noncross-linked TS after 2 (p < 0.05) and 4 weeks (p < 0.05), while after 6 weeks only EDC+VEGF showed fewer viable cells (p < 0.01). Histological evaluation confirmed a reduced infiltration of EDC-treated TS. Macrophage infiltration decreased in all groups from 2 to 6 weeks, with the smallest population in EDC+VEGF-treated TS (p > 0.05). In EDC+FGF-treated TS, macrophages were reduced after 2 weeks compared to noncross-linked TS (p < 0.05), while after 4 and 6 weeks no significant difference was found (p > 0.05). Von-Kossa staining revealed no calcification in any of the specimens. Thickness of noncross-linked and EDC+FGF-treated TS was not

  11. EDC EXPOSURE METHODS

    EPA Science Inventory

    Endocrine disrupter compounds (EDCs) are exogenous agents that interfere with the production, release, transport, metabolism, binding action, or elimination of the natural hormones in the body responsible for the maintenance of homeostasis and regulation of developmental processe...

  12. Measurement of stress waves in EDC piles.

    DOT National Transportation Integrated Search

    2008-12-30

    "This project focused on instrumentation analysis of one Smart Structures Incorporated, EDC pile. In general, the EDC pile is a pre-stressed 18" x 18" concrete pile that has been outfitted with embedded strain gages and accelerometers at six location...

  13. Comparative Genomics Identifies Epidermal Proteins Associated with the Evolution of the Turtle Shell

    PubMed Central

    Holthaus, Karin Brigit; Strasser, Bettina; Sipos, Wolfgang; Schmidt, Heiko A.; Mlitz, Veronika; Sukseree, Supawadee; Weissenbacher, Anton; Tschachler, Erwin; Alibardi, Lorenzo; Eckhart, Leopold

    2016-01-01

    The evolution of reptiles, birds, and mammals was associated with the origin of unique integumentary structures. Studies on lizards, chicken, and humans have suggested that the evolution of major structural proteins of the outermost, cornified layers of the epidermis was driven by the diversification of a gene cluster called Epidermal Differentiation Complex (EDC). Turtles have evolved unique defense mechanisms that depend on mechanically resilient modifications of the epidermis. To investigate whether the evolution of the integument in these reptiles was associated with specific adaptations of the sequences and expression patterns of EDC-related genes, we utilized newly available genome sequences to determine the epidermal differentiation gene complement of turtles. The EDC of the western painted turtle (Chrysemys picta bellii) comprises more than 100 genes, including at least 48 genes that encode proteins referred to as beta-keratins or corneous beta-proteins. Several EDC proteins have evolved cysteine/proline contents beyond 50% of total amino acid residues. Comparative genomics suggests that distinct subfamilies of EDC genes have been expanded and partly translocated to loci outside of the EDC in turtles. Gene expression analysis in the European pond turtle (Emys orbicularis) showed that EDC genes are differentially expressed in the skin of the various body sites and that a subset of beta-keratin genes within the EDC as well as those located outside of the EDC are expressed predominantly in the shell. Our findings give strong support to the hypothesis that the evolutionary innovation of the turtle shell involved specific molecular adaptations of epidermal differentiation. PMID:26601937

  14. Endocrine Disrupting Chemicals (EDCs)

    MedlinePlus

    ... body’s hormones work. They have been linked to human health issues related to sperm quality, fertility, abnormalities in ... support a link between EDCs and harm to human health, but the cause-and-effect relationship is not ...

  15. DEVELOPMENT OF CHEMICAL METHODS TO CHARACTERIZE EXPOSURE TO EDCS IN THE NEUSE RIVER BASIN

    EPA Science Inventory

    To develop a quantitative health and environmental risk assessment of endocrine disrupting compounds (EDCs), information on exposures is essential. A full exposure assessment has complex requirements that require preliminary information to direct further research in this area....

  16. Effect of Transpiration on Plant Accumulation and Translocation of PPCP/EDCs

    PubMed Central

    Dodgen, Laurel K; Ueda, Aiko; Wu, Xiaoqin; Parker, David R; Gan, Jay

    2015-01-01

    The reuse of treated wastewater for agricultural irrigation in arid and hot climates where plant transpiration is high may affect plant accumulation of pharmaceutical and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs). In this study, carrot, lettuce, and tomato plants were grown in solution containing 16 PPCP/EDCs in either a cool-humid or a warm-dry environment. Leaf bioconcentration factors (BCF) were positively correlated with transpiration for chemical groups of different ionized states (p < 0.05). However, root BCFs were correlated with transpiration only for neutral PPCP/EDCs (p < 0.05). Neutral and cationic PPCP/EDCs showed similar accumulation, while anionic PPCP/EDCs had significantly higher accumulation in roots and significantly lower accumulation in leaves (p < 0.05). Results show that plant transpiration may play a significant role in the uptake and translocation of PPCP/EDCs, which may have a pronounced effect in arid and hot climates where irrigation with treated wastewater is common. PMID:25594843

  17. EDCs DataBank: 3D-Structure database of endocrine disrupting chemicals.

    PubMed

    Montes-Grajales, Diana; Olivero-Verbel, Jesus

    2015-01-02

    Endocrine disrupting chemicals (EDCs) are a group of compounds that affect the endocrine system, frequently found in everyday products and epidemiologically associated with several diseases. The purpose of this work was to develop EDCs DataBank, the only database of EDCs with three-dimensional structures. This database was built on MySQL using the EU list of potential endocrine disruptors and TEDX list. It contains the three-dimensional structures available on PubChem, as well as a wide variety of information from different databases and text mining tools, useful for almost any kind of research regarding EDCs. The web platform was developed employing HTML, CSS and PHP languages, with dynamic contents in a graphic environment, facilitating information analysis. Currently EDCs DataBank has 615 molecules, including pesticides, natural and industrial products, cosmetics, drugs and food additives, among other low molecular weight xenobiotics. Therefore, this database can be used to study the toxicological effects of these molecules, or to develop pharmaceuticals targeting hormone receptors, through docking studies, high-throughput virtual screening and ligand-protein interaction analysis. EDCs DataBank is totally user-friendly and the 3D-structures of the molecules can be downloaded in several formats. This database is freely available at http://edcs.unicartagena.edu.co. Copyright © 2014. Published by Elsevier Ireland Ltd.

  18. Comparative Genomics Identifies Epidermal Proteins Associated with the Evolution of the Turtle Shell.

    PubMed

    Holthaus, Karin Brigit; Strasser, Bettina; Sipos, Wolfgang; Schmidt, Heiko A; Mlitz, Veronika; Sukseree, Supawadee; Weissenbacher, Anton; Tschachler, Erwin; Alibardi, Lorenzo; Eckhart, Leopold

    2016-03-01

    The evolution of reptiles, birds, and mammals was associated with the origin of unique integumentary structures. Studies on lizards, chicken, and humans have suggested that the evolution of major structural proteins of the outermost, cornified layers of the epidermis was driven by the diversification of a gene cluster called Epidermal Differentiation Complex (EDC). Turtles have evolved unique defense mechanisms that depend on mechanically resilient modifications of the epidermis. To investigate whether the evolution of the integument in these reptiles was associated with specific adaptations of the sequences and expression patterns of EDC-related genes, we utilized newly available genome sequences to determine the epidermal differentiation gene complement of turtles. The EDC of the western painted turtle (Chrysemys picta bellii) comprises more than 100 genes, including at least 48 genes that encode proteins referred to as beta-keratins or corneous beta-proteins. Several EDC proteins have evolved cysteine/proline contents beyond 50% of total amino acid residues. Comparative genomics suggests that distinct subfamilies of EDC genes have been expanded and partly translocated to loci outside of the EDC in turtles. Gene expression analysis in the European pond turtle (Emys orbicularis) showed that EDC genes are differentially expressed in the skin of the various body sites and that a subset of beta-keratin genes within the EDC as well as those located outside of the EDC are expressed predominantly in the shell. Our findings give strong support to the hypothesis that the evolutionary innovation of the turtle shell involved specific molecular adaptations of epidermal differentiation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. 5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells

    PubMed Central

    Malashchuk, Igor; Lajoie, Brian R.; Mardaryev, Andrei N.; Gdula, Michal R.; Sharov, Andrey A.; Kohwi-Shigematsu, Terumi; Fessing, Michael Y.

    2017-01-01

    Mammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and

  20. Uptake and Accumulation of Four PPCP/EDCs in Two Leafy Vegetables

    PubMed Central

    Dodgen, LK; Li, J; Parker, D; Gan, JJ

    2013-01-01

    Many pharmaceutical and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs) are present in reclaimed water, leading to concerns of human health risks from the consumption of food crops irrigated with reclaimed water. This study evaluated the potential for plant uptake and accumulation of four commonly occurring PPCP/EDCs, i.e., bisphenol A (BPA), diclofenac sodium (DCL), naproxen (NPX), and 4-nonylphenol (NP), by lettuce (Lactuca sativa) and collards (Brassica oleracea) in hydroponic culture, using 14C-labeled compounds. In both plant species, plant accumulation followed the order of BPA > NP > DCL > NPX and accumulation in roots was much greater than in leaves and stems. Concentrations of 14C-PPCP/EDCs in plant tissues ranged from 0.22±0.03 to 927± 213 ng/g, but nearly all 14C-residue was non-extractable. PPCP/EDCs, particularly BPA and NP, were also extensively transformed in the nutrient solution. Dietary uptake of these PPCP/EDCs by humans was predicted to be negligible. PMID:23911624

  1. Uptake and accumulation of four PPCP/EDCs in two leafy vegetables.

    PubMed

    Dodgen, L K; Li, J; Parker, D; Gan, J J

    2013-11-01

    Many pharmaceutical and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs) are present in reclaimed water, leading to concerns of human health risks from the consumption of food crops irrigated with reclaimed water. This study evaluated the potential for plant uptake and accumulation of four commonly occurring PPCP/EDCs, i.e., bisphenol A (BPA), diclofenac sodium (DCL), naproxen (NPX), and 4-nonylphenol (NP), by lettuce (Lactuca sativa) and collards (Brassica oleracea) in hydroponic culture, using (14)C-labeled compounds. In both plant species, plant accumulation followed the order of BPA > NP > DCL > NPX and accumulation in roots was much greater than in leaves and stems. Concentrations of (14)C-PPCP/EDCs in plant tissues ranged from 0.22 ± 0.03 to 927 ± 213 ng/g, but nearly all (14)C-residue was non-extractable. PPCP/EDCs, particularly BPA and NP, were also extensively transformed in the nutrient solution. Dietary uptake of these PPCP/EDCs by humans was predicted to be negligible. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. EVALUATION OF DRINKING WATER TREATMENT TECHNOLOGIES FOR REMOVAL OF ENDOCRINE DISRUPTING CHEMICALS (EDCS)

    EPA Science Inventory

    A number of the chemicals identified as potential EDCs have been observed in surface and ground waters leading to concern over the possible presence of EDCs in finished drinking waters. Although there has not yet been a determination of risks posed by EDCs in finished waters, it ...

  3. A complexity-scalable software-based MPEG-2 video encoder.

    PubMed

    Chen, Guo-bin; Lu, Xin-ning; Wang, Xing-guo; Liu, Ji-lin

    2004-05-01

    With the development of general-purpose processors (GPP) and video signal processing algorithms, it is possible to implement a software-based real-time video encoder on GPP, and its low cost and easy upgrade attract developers' interests to transfer video encoding from specialized hardware to more flexible software. In this paper, the encoding structure is set up first to support complexity scalability; then a lot of high performance algorithms are used on the key time-consuming modules in coding process; finally, at programming level, processor characteristics are considered to improve data access efficiency and processing parallelism. Other programming methods such as lookup table are adopted to reduce the computational complexity. Simulation results showed that these ideas could not only improve the global performance of video coding, but also provide great flexibility in complexity regulation.

  4. DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis.

    PubMed

    MacConnell, Andrew B; McEnaney, Patrick J; Cavett, Valerie J; Paegel, Brian M

    2015-09-14

    The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the "structure elucidation problem": the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded solid-phase synthesis (DESPS), comprising parallel compound synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length <100 bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding positions. A series of isomers served as a testbed for DESPS's utility in split-and-pool diversification. Single-bead quantitative PCR detected 9 × 10(4) molecules/bead and sequencing allowed for elucidation of each compound's synthetic history. We applied DESPS to the combinatorial synthesis of a 75,645-member OBOC library containing scaffold, stereochemical and regiochemical diversity using mixed-scale resin (160-μm quality control beads and 10-μm screening beads). Tandem DNA sequencing/MALDI-TOF MS analysis of 19 quality control beads showed excellent agreement (<1 ppt) between DNA sequence-predicted mass and the observed mass. DESPS synergistically unites the advantages of solid-phase synthesis and DNA encoding, enabling single-bead structural elucidation of complex compounds and synthesis using reactions normally considered incompatible with unprotected DNA. The widespread availability of inexpensive oligonucleotide synthesis, enzymes, DNA sequencing, and PCR

  5. Exposure to bisphenol A affects GABAergic neuron differentiation in neurosphere cultures.

    PubMed

    Fukushima, Nobuyuki; Nagao, Tetsuji

    2018-06-13

    Endocrine-disrupting chemicals (EDCs) influence not only endocrine functions but also neuronal development and functions. In-vivo studies have suggested the relationship of EDC-induced neurobehavioral disorders with dysfunctions of neurotransmitter mechanisms including γ-aminobutyric acid (GABA)ergic mechanisms. However, whether EDCs affect GABAergic neuron differentiation remains unclear. In the present study, we show that a representative EDC, bisphenol A (BPA), affects GABAergic neuron differentiation. Cortical neurospheres prepared from embryonic mice were exposed to BPA for 7 days, and then neuronal differentiation was induced. We found that BPA exposure resulted in a decrease in the ratio of GABAergic neurons to total neurons. However, the same exposure stimulated the differentiation of neurons expressing calbindin, a calcium-binding protein observed in a subpopulation of GABAergic neurons. These findings suggested that BPA might influence the formation of an inhibitory neuronal network in developing cerebral cortex involved in the occurrence of neurobehavioral disorders.

  6. Performance of Electrostatic Dust Collectors (EDCs) for Endotoxin Assessment in Homes: Effect of Mailing, Placement, Heating and Electrostatic Charge

    PubMed Central

    Kilburg-Basnyat, Brita; Metwali, Nervana; Thorne, Peter S.

    2016-01-01

    Electrostatic Dust Collectors (EDCs) are in use for passive sampling of bioaerosols, but particular aspects of their performance have not yet been evaluated. This study investigated the effect of mailing EDCs on endotoxin loading and the effect of EDC deployment in front of and away from heated ventilation on endotoxin sampling. Endotoxin sampling efficiency of heated and unheated EDC cloths was also evaluated. Cross-country express mailing of dust-spiked EDCs yielded no significant changes in endotoxin concentrations compared to dust-only samples for both high spiked-EDCs (p=0.30) and low spiked-EDCs (p=0.36). EDCs were also deployed in 20 identical apartments with one EDC placed in front of the univent heater in each apartment and contemporaneous EDC placed on the built-in bookshelf in each apartment. The endotoxin concentrations were significantly different (p=0.049) indicating that the placement of EDC does impact endotoxin sampling. Heated and unheated EDCs were deployed for 7 days in pairs in farm homes. There was a significant difference between endotoxin concentrations (p=0.027) indicating that heating EDCs may diminish their electrostatic capabilities and impact endotoxin sampling. The last study investigated the electrostatic charge of 12 heated and 12 unheated EDC cloths. There was a significant difference in charge (p=0.009) which suggests that heating EDC cloths may make them less effective for sampling. In conclusion, EDCs can be mailed to and from deployment sites, EDC placement in relationship to ventilation is crucial, and heating EDCs reduces their electrostatic charge which may diminish their endotoxin sampling capabilities. PMID:26325020

  7. Performance of electrostatic dust collectors (EDCs) for endotoxin assessment in homes: Effect of mailing, placement, heating, and electrostatic charge.

    PubMed

    Kilburg-Basnyat, Brita; Metwali, Nervana; Thorne, Peter S

    2016-01-01

    Electrostatic Dust Collectors (EDCs) are in use for passive sampling of bioaerosols, but particular aspects of their performance have not yet been evaluated. This study investigated the effect of mailing EDCs on endotoxin loading and the effect of EDC deployment in front of, and away from, heated ventilation on endotoxin sampling. Endotoxin sampling efficiency of heated and unheated EDC cloths was also evaluated. Cross-country express mailing of dust-spiked EDCs yielded no significant changes in endotoxin concentrations compared to dust-only samples for both high-spiked EDCs (p = 0.30) and low-spiked EDCs (p = 0.36). EDCs were also deployed in 20 identical apartments with one EDC placed in front of the univent heater in each apartment and contemporaneous EDC placed on the built-in bookshelf in each apartment. The endotoxin concentrations were significantly different (p = 0.049) indicating that the placement of EDC does impact endotoxin sampling. Heated and unheated EDCs were deployed for 7 days in pairs in farm homes. There was a significant difference between endotoxin concentrations (p = 0.027) indicating that heating EDCs may diminish their electrostatic capabilities and impact endotoxin sampling. The last study investigated the electrostatic charge of 12 heated and 12 unheated EDC cloths. There was a significant difference in charge (p = 0.009) which suggests that heating EDC cloths may make them less effective for sampling. In conclusion, EDCs can be mailed to and from deployment sites, EDC placement in relationship to ventilation is crucial, and heating EDCs reduces their electrostatic charge which may diminish their endotoxin sampling capabilities.

  8. EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS (EDCS) ON FETAL TESTES HORMONE PRODUCTION

    EPA Science Inventory

    Effects of Endocrine Disrupting Chemicals (EDCs) on Fetal Testes Hormone Production
    CS Lambright, VS Wilson, JR Furr, CJ Wolf, N Noriega, LE Gray, Jr
    US EPA, ORD/NHEERL/RTD, RTP, NC 27711

    Exposure to EDCs during critical periods of fetal sexual development can have...

  9. Transformation and Removal Pathways of Four Common PPCP/EDCs in Soil

    PubMed Central

    Dodgen, LK; Li, J; Wu, X; Lu, Z; Gan, JJ

    2014-01-01

    Pharmaceutical and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) enter the soil environment via irrigation with treated wastewater, groundwater recharge, and land application of biosolids. The transformation and fate of PPCP/EDCs in soil affects their potential for plant uptake and groundwater pollution. This study examined four PPCP/EDCs (bisphenol A, diclofenac, naproxen, and 4-nonylphenol) in soil by using 14C-labeling and analyzing mineralization, extractable residue, bound residue, and formation of transformation products. At the end of 112 d of incubation, the majority of 14C-naproxen and 14C-diclofenac was mineralized to 14CO2, while a majority of 14C-bisphenol A and 14C-nonylphenol was converted to bound residue. After 112 d, the estimated half-lives of the parent compounds were only 1.4 – 5.4 d. However a variety of transformation products were found and several for bisphenol A and diclofenac were identified, suggesting the need to consider degradation intermediates in soils impacted by PPCP/EDCs. PMID:24997388

  10. DSD-Consistent JWL Equations of State for EDC35

    NASA Astrophysics Data System (ADS)

    Hodgson, Alexander

    2011-06-01

    The Detonation Shock Dynamics model (DSD) allows the calculation of curvature-dependent detonation propagation. It is of particular use when applied to insensitive high explosives, such as EDC35, since they have a greater non-ideal behaviour. The DSD model has been used in conjunction with an experimental cylinder test to obtain the JWL Equation of State (EoS) for EDC35. Adjustment of parameters in the JWL equation changes the expansion profile of the simulated wall expansion. The parameters are iterated until the best match can be made between simulation and experiment. Previous DSD models used at AWE have no energy release mechanism to adjust the release of chemical energy to match the detonation conditions. Two JWL calibrations are performed using the DSD model, with and without Hetherington's energy release model (these proceedings). Also in use is a newly-calibrated detonation speed-curvature relation that is much closer, compared to previous calibrations, to Bdzil's equivalent for PBX9502. This paper discusses the possible improvements that this approach makes to the EDC35 JWL EoS.

  11. Low-complexity video encoding method for wireless image transmission in capsule endoscope.

    PubMed

    Takizawa, Kenichi; Hamaguchi, Kiyoshi

    2010-01-01

    This paper presents a low-complexity video encoding method applicable for wireless image transmission in capsule endoscopes. This encoding method is based on Wyner-Ziv theory, in which side information available at a transmitter is treated as side information at its receiver. Therefore complex processes in video encoding, such as estimation of the motion vector, are moved to the receiver side, which has a larger-capacity battery. As a result, the encoding process is only to decimate coded original data through channel coding. We provide a performance evaluation for a low-density parity check (LDPC) coding method in the AWGN channel.

  12. Twenty-five years after "Wingspread"- Environmental endocrine disruptors (EDCs) and human health

    EPA Science Inventory

    The development of life-stage and tissue-specific AOPs for EDCs can reduce the uncertainty in extrapolating of the effects of EDCs from in vitro and in vivo studies in laboratory animals to humans. When the key events (KEs) and molecular initiating event (MIEs) in a pathway are...

  13. Similar Modes of Interaction Enable Trailer Hitch and EDC3 To Associate with DCP1 and Me31B in Distinct Protein Complexes▿ †

    PubMed Central

    Tritschler, Felix; Eulalio, Ana; Helms, Sigrun; Schmidt, Steffen; Coles, Murray; Weichenrieder, Oliver; Izaurralde, Elisa; Truffault, Vincent

    2008-01-01

    Trailer Hitch (Tral or LSm15) and enhancer of decapping-3 (EDC3 or LSm16) are conserved eukaryotic members of the (L)Sm (Sm and Like-Sm) protein family. They have a similar domain organization, characterized by an N-terminal LSm domain and a central FDF motif; however, in Tral, the FDF motif is flanked by regions rich in charged residues, whereas in EDC3 the FDF motif is followed by a YjeF_N domain. We show that in Drosophila cells, Tral and EDC3 specifically interact with the decapping activator DCP1 and the DEAD-box helicase Me31B. Nevertheless, only Tral associates with the translational repressor CUP, whereas EDC3 associates with the decapping enzyme DCP2. Like EDC3, Tral interacts with DCP1 and localizes to mRNA processing bodies (P bodies) via the LSm domain. This domain remains monomeric in solution and adopts a divergent Sm fold that lacks the characteristic N-terminal α-helix, as determined by nuclear magnetic resonance analyses. Mutational analysis revealed that the structural integrity of the LSm domain is required for Tral both to interact with DCP1 and CUP and to localize to P-bodies. Furthermore, both Tral and EDC3 interact with the C-terminal RecA-like domain of Me31B through their FDF motifs. Together with previous studies, our results show that Tral and EDC3 are structurally related and use a similar mode to associate with common partners in distinct protein complexes. PMID:18765641

  14. Intense THz pulses down-regulate genes associated with skin cancer and psoriasis: a new therapeutic avenue?

    PubMed Central

    Titova, Lyubov V.; Ayesheshim, Ayesheshim K.; Golubov, Andrey; Rodriguez-Juarez, Rocio; Woycicki, Rafal; Hegmann, Frank A.; Kovalchuk, Olga

    2013-01-01

    Terahertz (THz) radiation lies between the infrared and microwave regions of the electromagnetic spectrum and is non-ionizing. We show that exposure of artificial human skin tissue to intense, picosecond-duration THz pulses affects expression levels of numerous genes associated with non-melanoma skin cancers, psoriasis and atopic dermatitis. Genes affected by intense THz pulses include nearly half of the epidermal differentiation complex (EDC) members. EDC genes, which are mapped to the chromosomal human region 1q21, encode for proteins that partake in epidermal differentiation and are often overexpressed in conditions such as psoriasis and skin cancer. In nearly all the genes differentially expressed by exposure to intense THz pulses, the induced changes in transcription levels are opposite to disease-related changes. The ability of intense THz pulses to cause concerted favorable changes in the expression of multiple genes implicated in inflammatory skin diseases and skin cancers suggests potential therapeutic applications of intense THz pulses. PMID:23917523

  15. Comparative differential gene expression analysis of nucleus-encoded proteins for Rafflesia cantleyi against Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Ng, Siuk-Mun; Lee, Xin-Wei; Wan, Kiew-Lian; Firdaus-Raih, Mohd

    2015-09-01

    Regulation of functional nucleus-encoded proteins targeting the plastidial functions was comparatively studied for a plant parasite, Rafflesia cantleyi versus a photosynthetic plant, Arabidopsis thaliana. This study involved two species of different feeding modes and different developmental stages. A total of 30 nucleus-encoded proteins were found to be differentially-regulated during two stages in the parasite; whereas 17 nucleus-encoded proteins were differentially-expressed during two developmental stages in Arabidopsis thaliana. One notable finding observed for the two plants was the identification of genes involved in the regulation of photosynthesis-related processes where these processes, as expected, seem to be present only in the autotroph.

  16. Differential in Vitro Biological Action, Coregulator Interactions, and Molecular Dynamic Analysis of Bisphenol A (BPA), BPAF, and BPS Ligand-ERα Complexes.

    PubMed

    Li, Yin; Perera, Lalith; Coons, Laurel A; Burns, Katherine A; Tyler Ramsey, J; Pelch, Katherine E; Houtman, René; van Beuningen, Rinie; Teng, Christina T; Korach, Kenneth S

    2018-01-31

    Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that might be harmful to human health. Recently, there has been widespread usage of bisphenol chemicals (BPs), such as bisphenol AF (BPAF) and bisphenol S (BPS), as replacements for BPA. However, the potential biological actions, toxicity, and the molecular mechanism of these compounds are still poorly understood. Our objective was to examine the estrogenic effects of BPA, BPAF, and BPS and the molecular mechanisms of action in the estrogen receptor alpha (ERα) complex. In vitro cell models were used to compare the estrogenic effects of BPA, BPAF, and BPS to estrogen. Microarray Assay for Real-Time Coregulator-Nuclear receptor Interaction (MARCoNI) analysis was used to identify coregulators of BPA, BPAF, and BPS, and molecular dynamic (MD) simulations were used to determine the compounds binding in the ERα complex. We demonstrated that BPA and BPAF have agonistic activity for both ERα and ERβ, but BPS has ERα-selective specificity. We concluded that coregulators were differentially recruited in the presence of BPA, BPAF, or BPS. Interestingly, BPS recruited more corepressors when compared to BPA and BPAF. From a series of MD analysis, we concluded that BPA, BPAF, and BPS can bind to the ER-ligand-binding domain with differing energetics and conformations. In addition, the binding surface of coregulator interactions on ERα was characterized for the BPA, BPAF, and BPS complexes. These findings further our understanding of the molecular mechanisms of EDCs, such as BPs, in ER-mediated transcriptional activation, biological activity, and their effects on physiological functions in human health. https://doi.org/10.1289/EHP2505.

  17. Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation

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

    Ostlund, Cecilia; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Guan, Tinglu

    2009-11-13

    Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested. Because 4q35 has been linked to facioscapulohumeral muscular dystrophy (FSHD) and some adjacent genes are reportedly misregulated in the disorder, levels of p19A were analyzed in muscle samples from patients withmore » FSHD. Although p19A was increased in most cases, an absolute correlation was not observed. Nonetheless, p19A downregulation in normal muscle differentiation suggests that in the cases where its gene is inappropriately re-activated it could affect muscle differentiation and contribute to disease pathology.« less

  18. Twenty-five years after "Wingspread"- Environmental endocrine disruptors (EDCs) and human health.

    PubMed

    Gray, Leon Earl

    2017-04-01

    The aim of this paper is to provide the reader with a view of the Endocrine Disruptor Chemical (EDC) research field and its relevance to human health. My perspective is from working on the effects of EDCs that act via the androgen (A) or estrogen (E) signaling pathways in a regulatory agency for the last four decades with the objective of producing data that risk assessors could use to reduce the uncertainty in risk assessment. In vitro and in vivo data from our studies has contributed to regulatory agencies decision-making since the 1990s (https://www3.epa.gov/pesticides/chem_search/cleared_reviews/csr_PC-113201_7-Apr-98_238.pdf). From the start, we were evaluating the utility of in vitro and short-term in vivo effects to predict the adverse effects in developing animals [1; 2]. This approach has expanded greatly to include what is now known as Adverse Outcome Pathways (AOP) and networks (AOPn) [3; 4]. The AOP framework for the effects of chemicals that disrupt androgen signaling during sexual differentiation of the fetal male rat provides biological context for extrapolating mechanistic information from in vitro and in vivo assays in rodents to other species including humans. Such an approach has biological validity because the E and A pathways are highly conserved in vertebrates, including humans and laboratory animals.

  19. Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2

    PubMed Central

    Wurm, Stefanie; Zhang, Jisheng; Guinea-Viniegra, Juan; García, Fernando; Muñoz, Javier; Bakiri, Latifa; Ezhkova, Elena

    2015-01-01

    Altered epidermal differentiation characterizes numerous skin diseases affecting >25% of the human population. Here we identified Fra-2/AP-1 as a key regulator of terminal epidermal differentiation. Epithelial-restricted, ectopic expression of Fra-2 induced expression of epidermal differentiation genes located within the epidermal differentiation complex (EDC). Moreover, in a papilloma-prone background, a reduced tumor burden was observed due to precocious keratinocyte differentiation by Fra-2 expression. Importantly, loss of Fra-2 in suprabasal keratinocytes is sufficient to cause skin barrier defects due to reduced expression of differentiation genes. Mechanistically, Fra-2 binds and transcriptionally regulates EDC gene promoters, which are co-occupied by the transcriptional repressor Ezh2. Fra-2 remains transcriptionally inactive in nondifferentiated keratinocytes, where it was found monomethylated and dimethylated on Lys104 and interacted with Ezh2. Upon keratinocyte differentiation, Fra-2 is C-terminally phosphorylated on Ser320 and Thr322 by ERK1/2, leading to transcriptional activation. Thus, the induction of epidermal differentiation by Fra-2 is controlled by a dual mechanism involving Ezh2-dependent methylation and activation by ERK1/2-dependent phosphorylation. PMID:25547114

  20. Comparison of electronic data capture (EDC) with the standard data capture method for clinical trial data.

    PubMed

    Walther, Brigitte; Hossin, Safayet; Townend, John; Abernethy, Neil; Parker, David; Jeffries, David

    2011-01-01

    Traditionally, clinical research studies rely on collecting data with case report forms, which are subsequently entered into a database to create electronic records. Although well established, this method is time-consuming and error-prone. This study compares four electronic data capture (EDC) methods with the conventional approach with respect to duration of data capture and accuracy. It was performed in a West African setting, where clinical trials involve data collection from urban, rural and often remote locations. Three types of commonly available EDC tools were assessed in face-to-face interviews; netbook, PDA, and tablet PC. EDC performance during telephone interviews via mobile phone was evaluated as a fourth method. The Graeco Latin square study design allowed comparison of all four methods to standard paper-based recording followed by data double entry while controlling simultaneously for possible confounding factors such as interview order, interviewer and interviewee. Over a study period of three weeks the error rates decreased considerably for all EDC methods. In the last week of the study the data accuracy for the netbook (5.1%, CI95%: 3.5-7.2%) and the tablet PC (5.2%, CI95%: 3.7-7.4%) was not significantly different from the accuracy of the conventional paper-based method (3.6%, CI95%: 2.2-5.5%), but error rates for the PDA (7.9%, CI95%: 6.0-10.5%) and telephone (6.3%, CI95% 4.6-8.6%) remained significantly higher. While EDC-interviews take slightly longer, data become readily available after download, making EDC more time effective. Free text and date fields were associated with higher error rates than numerical, single select and skip fields. EDC solutions have the potential to produce similar data accuracy compared to paper-based methods. Given the considerable reduction in the time from data collection to database lock, EDC holds the promise to reduce research-associated costs. However, the successful implementation of EDC requires adjustment of

  1. Comparison of Electronic Data Capture (EDC) with the Standard Data Capture Method for Clinical Trial Data

    PubMed Central

    Walther, Brigitte; Hossin, Safayet; Townend, John; Abernethy, Neil; Parker, David; Jeffries, David

    2011-01-01

    Background Traditionally, clinical research studies rely on collecting data with case report forms, which are subsequently entered into a database to create electronic records. Although well established, this method is time-consuming and error-prone. This study compares four electronic data capture (EDC) methods with the conventional approach with respect to duration of data capture and accuracy. It was performed in a West African setting, where clinical trials involve data collection from urban, rural and often remote locations. Methodology/Principal Findings Three types of commonly available EDC tools were assessed in face-to-face interviews; netbook, PDA, and tablet PC. EDC performance during telephone interviews via mobile phone was evaluated as a fourth method. The Graeco Latin square study design allowed comparison of all four methods to standard paper-based recording followed by data double entry while controlling simultaneously for possible confounding factors such as interview order, interviewer and interviewee. Over a study period of three weeks the error rates decreased considerably for all EDC methods. In the last week of the study the data accuracy for the netbook (5.1%, CI95%: 3.5–7.2%) and the tablet PC (5.2%, CI95%: 3.7–7.4%) was not significantly different from the accuracy of the conventional paper-based method (3.6%, CI95%: 2.2–5.5%), but error rates for the PDA (7.9%, CI95%: 6.0–10.5%) and telephone (6.3%, CI95% 4.6–8.6%) remained significantly higher. While EDC-interviews take slightly longer, data become readily available after download, making EDC more time effective. Free text and date fields were associated with higher error rates than numerical, single select and skip fields. Conclusions EDC solutions have the potential to produce similar data accuracy compared to paper-based methods. Given the considerable reduction in the time from data collection to database lock, EDC holds the promise to reduce research-associated costs

  2. Polish Society of Endocrinology Position statement on endocrine disrupting chemicals (EDCs).

    PubMed

    Rutkowska, Aleksandra; Rachoń, Dominik; Milewicz, Andrzej; Ruchała, Marek; Bolanowski, Marek; Jędrzejuk, Diana; Bednarczuk, Tomasz; Górska, Maria; Hubalewska-Dydejczyk, Alicja; Kos-Kudła, Beata; Lewiński, Andrzej; Zgliczyński, Wojciech

    2015-01-01

    With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

  3. Method and system for efficient video compression with low-complexity encoder

    NASA Technical Reports Server (NTRS)

    Chen, Jun (Inventor); He, Dake (Inventor); Sheinin, Vadim (Inventor); Jagmohan, Ashish (Inventor); Lu, Ligang (Inventor)

    2012-01-01

    Disclosed are a method and system for video compression, wherein the video encoder has low computational complexity and high compression efficiency. The disclosed system comprises a video encoder and a video decoder, wherein the method for encoding includes the steps of converting a source frame into a space-frequency representation; estimating conditional statistics of at least one vector of space-frequency coefficients; estimating encoding rates based on the said conditional statistics; and applying Slepian-Wolf codes with the said computed encoding rates. The preferred method for decoding includes the steps of; generating a side-information vector of frequency coefficients based on previously decoded source data, encoder statistics, and previous reconstructions of the source frequency vector; and performing Slepian-Wolf decoding of at least one source frequency vector based on the generated side-information, the Slepian-Wolf code bits and the encoder statistics.

  4. ASSESSEMNT OF GONAD SIZE IN TAUTOGOLABRUS ADSPERSUS AS AN INDICATOR OF REPRODUCTION AND EDC EXPOSURE

    EPA Science Inventory

    Cunner habitat includes estuarine and marine areas where sewage treatment and other discharges containing estrogenic (EDCs) are likely.

    Endocrine-disrupting chemicals (EDCs) in the environment may disturb the population dynamics of wildlife by affecting their reproductive...

  5. Differential encoding of spatial information among retinal on cone bipolar cells

    PubMed Central

    Purgert, Robert J.

    2015-01-01

    The retina is the first stage of visual processing. It encodes elemental features of visual scenes. Distinct cone bipolar cells provide the substrate for this to occur. They encode visual information, such as color and luminance, a principle known as parallel processing. Few studies have directly examined whether different forms of spatial information are processed in parallel among cone bipolar cells. To address this issue, we examined the spatial information encoded by mouse ON cone bipolar cells, the subpopulation excited by increments in illumination. Two types of spatial processing were identified. We found that ON cone bipolar cells with axons ramifying in the central inner plexiform layer were tuned to preferentially encode small stimuli. By contrast, ON cone bipolar cells with axons ramifying in the proximal inner plexiform layer, nearest the ganglion cell layer, were tuned to encode both small and large stimuli. This dichotomy in spatial tuning is attributable to amacrine cells providing stronger inhibition to central ON cone bipolar cells compared with proximal ON cone bipolar cells. Furthermore, background illumination altered this difference in spatial tuning. It became less pronounced in bright light, as amacrine cell-driven inhibition became pervasive among all ON cone bipolar cells. These results suggest that differential amacrine cell input determined the distinct spatial encoding properties among ON cone bipolar cells. These findings enhance the known parallel processing capacity of the retina. PMID:26203104

  6. EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

    PubMed Central

    Chappell, V. A.; Fenton, S. E.; Flaws, J. A.; Nadal, A.; Prins, G. S.; Toppari, J.; Zoeller, R. T.

    2015-01-01

    The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans—especially during development—may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the

  7. Encoding techniques for complex information structures in connectionist systems

    NASA Technical Reports Server (NTRS)

    Barnden, John; Srinivas, Kankanahalli

    1990-01-01

    Two general information encoding techniques called relative position encoding and pattern similarity association are presented. They are claimed to be a convenient basis for the connectionist implementation of complex, short term information processing of the sort needed in common sense reasoning, semantic/pragmatic interpretation of natural language utterances, and other types of high level cognitive processing. The relationships of the techniques to other connectionist information-structuring methods, and also to methods used in computers, are discussed in detail. The rich inter-relationships of these other connectionist and computer methods are also clarified. The particular, simple forms are discussed that the relative position encoding and pattern similarity association techniques take in the author's own connectionist system, called Conposit, in order to clarify some issues and to provide evidence that the techniques are indeed useful in practice.

  8. Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health.

    PubMed

    Tapia-Orozco, Natalia; Santiago-Toledo, Gerardo; Barrón, Valeria; Espinosa-García, Ana María; García-García, José Antonio; García-Arrazola, Roeb

    2017-04-01

    Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Evaluation of different wastewater treatment techniques in three WWTPs in Istanbul for the removal of selected EDCs in liquid phase.

    PubMed

    Can, Zehra Semra; Fırlak, Melike; Kerç, Aslıhan; Evcimen, Serkan

    2014-01-01

    Endocrine-disrupting compounds (EDCs) are exogenous substances that cause adverse health effects in an intact organism, or its progeny, subsequent to the changes in endocrine function. Recent studies have shown that wastewater treatment plant effluents play an important role in the release of EDCs into aquatic environments. Therefore, in this study, influent and effluent samples from three different wastewater treatment plants (WWTPs) in Istanbul were analysed for the presence of the principal EDCs. These chemicals include steroids and synthetic organic chemicals. Thus, the occurrence and fate of EDCs of great health concern were monitored at three WWTPs in Istanbul. Furthermore, these WWTPs are employing different treatment processes. Therefore, the EDC removal performances of different treatment regimes were also evaluated. Phytosterol was the most abundant EDC in the influent samples. Second group of compounds at high influent levels were alkyl phenols. Pesticide levels of all three WWTP influent samples were low. Pasakoy Advanced WWTP is more effective at eliminating EDCs. Kadikoy Primary WWTP exhibits the lowest EDC elimination efficiencies. To the best of our knowledge, this work comprises the first detailed report on the occurrence and behaviour of both natural and synthetic EDCs in WWTPs of Istanbul and Turkey. The steroid estrogen levels of this study are higher than the previously documented values, except the levels given for Gaobeidian WWTP in Beijing, China. This is attributed to higher population densities of Beijing and Istanbul and as well as to lower individual water consumption rates in the two cities.

  10. Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis.

    PubMed

    Jeong, Hyeri; Kim, Jongwoon; Kim, Youngjun

    2017-09-30

    Approximately 1000 chemicals have been reported to possibly have endocrine disrupting effects, some of which are used in consumer products, such as personal care products (PCPs) and cosmetics. We conducted data integration combined with gene network analysis to: (i) identify causal molecular mechanisms between endocrine disrupting chemicals (EDCs) used in PCPs and breast cancer; and (ii) screen candidate EDCs associated with breast cancer. Among EDCs used in PCPs, four EDCs having correlation with breast cancer were selected, and we curated 27 common interacting genes between those EDCs and breast cancer to perform the gene network analysis. Based on the gene network analysis, ESR1, TP53, NCOA1, AKT1, and BCL6 were found to be key genes to demonstrate the molecular mechanisms of EDCs in the development of breast cancer. Using GeneMANIA, we additionally predicted 20 genes which could interact with the 27 common genes. In total, 47 genes combining the common and predicted genes were functionally grouped with the gene ontology and KEGG pathway terms. With those genes, we finally screened candidate EDCs for their potential to increase breast cancer risk. This study highlights that our approach can provide insights to understand mechanisms of breast cancer and identify potential EDCs which are in association with breast cancer.

  11. Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis

    PubMed Central

    Kim, Jongwoon

    2017-01-01

    Approximately 1000 chemicals have been reported to possibly have endocrine disrupting effects, some of which are used in consumer products, such as personal care products (PCPs) and cosmetics. We conducted data integration combined with gene network analysis to: (i) identify causal molecular mechanisms between endocrine disrupting chemicals (EDCs) used in PCPs and breast cancer; and (ii) screen candidate EDCs associated with breast cancer. Among EDCs used in PCPs, four EDCs having correlation with breast cancer were selected, and we curated 27 common interacting genes between those EDCs and breast cancer to perform the gene network analysis. Based on the gene network analysis, ESR1, TP53, NCOA1, AKT1, and BCL6 were found to be key genes to demonstrate the molecular mechanisms of EDCs in the development of breast cancer. Using GeneMANIA, we additionally predicted 20 genes which could interact with the 27 common genes. In total, 47 genes combining the common and predicted genes were functionally grouped with the gene ontology and KEGG pathway terms. With those genes, we finally screened candidate EDCs for their potential to increase breast cancer risk. This study highlights that our approach can provide insights to understand mechanisms of breast cancer and identify potential EDCs which are in association with breast cancer. PMID:28973975

  12. CCHCR1 interacts with EDC4, suggesting its localization in P-bodies

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

    Ling, Y.H.; Wong, C.C.; Li, K.W.

    2014-09-10

    Coiled‐coil alpha‐helical rod protein 1 (CCHCR1) is suggested as a candidate biomarker for psoriasis for more than a decade but its function remains poorly understood because of the inconsistent findings in the literature. CCHCR1 protein is suggested to be localized in the cytoplasm, nucleus, mitochondria, or centrosome and to regulate various cellular functions, including steroidogenesis, proliferation, differentiation, and cytoskeleton organization. In this study, we attempted to find a consensus between these findings by identifying the interaction partners of CCHCR1 using co-immunoprecipiation with a stable cell line expressing EGFP-tagged CCHCR1. Out of more than 100 co-immunoprecipitants identified by liquid chromatography-tandem massmore » spectrometry (LC-MS/MS), the enhancer of mRNA-decapping protein 4 (EDC4), which is a processing body (P-body) component, was particularly found to be the major interacting partner of CCHCR1. Confocal imaging confirmed the localization of CCHCR1 in P-bodies and its N-terminus is required for this subcellular localization, suggesting that CCHCR1 is a novel P-body component. As P-bodies are the site for mRNA metabolism, our findings provide a molecular basis for the function of CCHCR1, any disruption of which may affect the transcriptome of the cell, and causing abnormal cell functions. - Highlights: • We identified CCHCR1 as a novel P-body component. • We identified EDC4 as the major interacting partner of CCHCR1. • N-terminus of CCHCR1 protein is required for its P-bodies localization.« less

  13. The euryhaline yeast Debaryomyces hansenii has two catalase genes encoding enzymes with differential activity profile.

    PubMed

    Segal-Kischinevzky, Claudia; Rodarte-Murguía, Beatriz; Valdés-López, Victor; Mendoza-Hernández, Guillermo; González, Alicia; Alba-Lois, Luisa

    2011-03-01

    Debaryomyces hansenii is a spoilage yeast able to grow in a variety of ecological niches, from seawater to dairy products. Results presented in this article show that (i) D. hansenii has an inherent resistance to H2O2 which could be attributed to the fact that this yeast has a basal catalase activity which is several-fold higher than that observed in Saccharomyces cerevisiae under the same culture conditions, (ii) D. hansenii has two genes (DhCTA1 and DhCTT1) encoding two catalase isozymes with a differential enzymatic activity profile which is not strictly correlated with a differential expression profile of the encoding genes.

  14. Dopamine Is Differentially Encoded by D2 Receptors in Striatal Subregions.

    PubMed

    Engeln, Michel; Fox, Megan E; Lobo, Mary Kay

    2018-05-02

    Striatal dopamine signaling is differentially regulated along the dorso-ventral axis, but how these differences are encoded by dopamine receptors is unknown. In this issue of Neuron, Marcott et al. (2018) show that dopamine activates D2 receptors in regionally distinct ways and dissect the underlying mechanisms behind striatal D2 heterogeneity. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Stabilization of collagen with EDC/NHS in the presence of L-lysine: a comprehensive study.

    PubMed

    Usha, R; Sreeram, K J; Rajaram, A

    2012-02-01

    This paper reports the effect of L-lysine on the conformational, rheological, and thermal properties of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross linked collagen and investigates the influence of l-lysine on the self assembly processes of collagen. In the absence of L-lysine, the rheological characterization of collagen cross linked with EDC/NHS showed an increase in shearing stress with shearing speed indicating that the collagen chains become rigid and the molecules are reluctant to flow. On the other hand, the increase in shearing stress with shearing speed is comparatively much less in the presence of L-lysine indicating a greater flexibility of the collagen molecules. The self assembly processes of collagen treated with EDC/NHS in the absence and presence of L-lysine were characterized using powder XRD, FT-IR, polarizing optical microscopy and kinetic studies. XRD studies show an increase in peak intensity and sharpness in the presence of L-lysine indicating the enhancement of crystallinity of collagen nano-fibrils. FT-IR results suggest that the incorporation of L-lysine in the EDC/NHS cross linking favors the molecular stability of collagen. From the present study, it is possible to conclude that the pre-treatment of collagen with L-lysine enhances EDC/NHS cross linking and can be used for biomaterial applications. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Experiences in running a complex electronic data capture system using mobile phones in a large-scale population trial in southern Nepal.

    PubMed

    Style, Sarah; Beard, B James; Harris-Fry, Helen; Sengupta, Aman; Jha, Sonali; Shrestha, Bhim P; Rai, Anjana; Paudel, Vikas; Thondoo, Meelan; Pulkki-Brannstrom, Anni-Maria; Skordis-Worrall, Jolene; Manandhar, Dharma S; Costello, Anthony; Saville, Naomi M

    2017-01-01

    The increasing availability and capabilities of mobile phones make them a feasible means of data collection. Electronic Data Capture (EDC) systems have been used widely for public health monitoring and surveillance activities, but documentation of their use in complicated research studies requiring multiple systems is limited. This paper shares our experiences of designing and implementing a complex multi-component EDC system for a community-based four-armed cluster-Randomised Controlled Trial in the rural plains of Nepal, to help other researchers planning to use EDC for complex studies in low-income settings. We designed and implemented three interrelated mobile phone data collection systems to enrol and follow-up pregnant women (trial participants), and to support the implementation of trial interventions (women's groups, food and cash transfers). 720 field staff used basic phones to send simple coded text messages, 539 women's group facilitators used Android smartphones with Open Data Kit Collect, and 112 Interviewers, Coordinators and Supervisors used smartphones with CommCare. Barcoded photo ID cards encoded with participant information were generated for each enrolled woman. Automated systems were developed to download, recode and merge data for nearly real-time access by researchers. The systems were successfully rolled out and used by 1371 staff. A total of 25,089 pregnant women were enrolled, and 17,839 follow-up forms completed. Women's group facilitators recorded 5717 women's groups and the distribution of 14,647 food and 13,482 cash transfers. Using EDC sped up data collection and processing, although time needed for programming and set-up delayed the study inception. EDC using three interlinked mobile data management systems (FrontlineSMS, ODK and CommCare) was a feasible and effective method of data capture in a complex large-scale trial in the plains of Nepal. Despite challenges including prolonged set-up times, the systems met multiple data

  17. Experiences in running a complex electronic data capture system using mobile phones in a large-scale population trial in southern Nepal

    PubMed Central

    Style, Sarah; Beard, B. James; Harris-Fry, Helen; Sengupta, Aman; Jha, Sonali; Shrestha, Bhim P.; Rai, Anjana; Paudel, Vikas; Thondoo, Meelan; Pulkki-Brannstrom, Anni-Maria; Skordis-Worrall, Jolene; Manandhar, Dharma S.; Costello, Anthony; Saville, Naomi M.

    2017-01-01

    ABSTRACT The increasing availability and capabilities of mobile phones make them a feasible means of data collection. Electronic Data Capture (EDC) systems have been used widely for public health monitoring and surveillance activities, but documentation of their use in complicated research studies requiring multiple systems is limited. This paper shares our experiences of designing and implementing a complex multi-component EDC system for a community-based four-armed cluster-Randomised Controlled Trial in the rural plains of Nepal, to help other researchers planning to use EDC for complex studies in low-income settings. We designed and implemented three interrelated mobile phone data collection systems to enrol and follow-up pregnant women (trial participants), and to support the implementation of trial interventions (women’s groups, food and cash transfers). 720 field staff used basic phones to send simple coded text messages, 539 women’s group facilitators used Android smartphones with Open Data Kit Collect, and 112 Interviewers, Coordinators and Supervisors used smartphones with CommCare. Barcoded photo ID cards encoded with participant information were generated for each enrolled woman. Automated systems were developed to download, recode and merge data for nearly real-time access by researchers. The systems were successfully rolled out and used by 1371 staff. A total of 25,089 pregnant women were enrolled, and 17,839 follow-up forms completed. Women’s group facilitators recorded 5717 women’s groups and the distribution of 14,647 food and 13,482 cash transfers. Using EDC sped up data collection and processing, although time needed for programming and set-up delayed the study inception. EDC using three interlinked mobile data management systems (FrontlineSMS, ODK and CommCare) was a feasible and effective method of data capture in a complex large-scale trial in the plains of Nepal. Despite challenges including prolonged set-up times, the systems met

  18. Assessing EDCs in the Field: Challenges and New Approaches

    EPA Science Inventory

    Assessing the occurrence and effects of EDCs in the environment can be challenging from a number of perspectives. For example, conventional analytical approaches and/or toxicity tests may not be appropriate to detecting very potent chemicals that impact specific pathways, and oft...

  19. Minimized state complexity of quantum-encoded cryptic processes

    NASA Astrophysics Data System (ADS)

    Riechers, Paul M.; Mahoney, John R.; Aghamohammadi, Cina; Crutchfield, James P.

    2016-05-01

    The predictive information required for proper trajectory sampling of a stochastic process can be more efficiently transmitted via a quantum channel than a classical one. This recent discovery allows quantum information processing to drastically reduce the memory necessary to simulate complex classical stochastic processes. It also points to a new perspective on the intrinsic complexity that nature must employ in generating the processes we observe. The quantum advantage increases with codeword length: the length of process sequences used in constructing the quantum communication scheme. In analogy with the classical complexity measure, statistical complexity, we use this reduced communication cost as an entropic measure of state complexity in the quantum representation. Previously difficult to compute, the quantum advantage is expressed here in closed form using spectral decomposition. This allows for efficient numerical computation of the quantum-reduced state complexity at all encoding lengths, including infinite. Additionally, it makes clear how finite-codeword reduction in state complexity is controlled by the classical process's cryptic order, and it allows asymptotic analysis of infinite-cryptic-order processes.

  20. EVALUATION OF DRINKING WATER TREATMENT TECHNIQUES FOR EDC REMOVAL

    EPA Science Inventory

    Many of the chemicals identified as potential endocrine disrupting chemicals (EDCs) may be present in surface or ground waters used as drinking water sources, due to their disposal via domestic and industrial sewage treatment systems and wet-weather runoff. In order to decrease t...

  1. Nucleus Accumbens Core and Shell Differentially Encode Reward-Associated Cues after Reinforcer Devaluation

    PubMed Central

    West, Elizabeth A.

    2016-01-01

    Nucleus accumbens (NAc) neurons encode features of stimulus learning and action selection associated with rewards. The NAc is necessary for using information about expected outcome values to guide behavior after reinforcer devaluation. Evidence suggests that core and shell subregions may play dissociable roles in guiding motivated behavior. Here, we recorded neural activity in the NAc core and shell during training and performance of a reinforcer devaluation task. Long–Evans male rats were trained that presses on a lever under an illuminated cue light delivered a flavored sucrose reward. On subsequent test days, each rat was given free access to one of two distinctly flavored foods to consume to satiation and were then immediately tested on the lever pressing task under extinction conditions. Rats decreased pressing on the test day when the reinforcer earned during training was the sated flavor (devalued) compared with the test day when the reinforcer was not the sated flavor (nondevalued), demonstrating evidence of outcome-selective devaluation. Cue-selective encoding during training by NAc core (but not shell) neurons reliably predicted subsequent behavioral performance; that is, the greater the percentage of neurons that responded to the cue, the better the rats suppressed responding after devaluation. In contrast, NAc shell (but not core) neurons significantly decreased cue-selective encoding in the devalued condition compared with the nondevalued condition. These data reveal that NAc core and shell neurons encode information differentially about outcome-specific cues after reinforcer devaluation that are related to behavioral performance and outcome value, respectively. SIGNIFICANCE STATEMENT Many neuropsychiatric disorders are marked by impairments in behavioral flexibility. Although the nucleus accumbens (NAc) is required for behavioral flexibility, it is not known how NAc neurons encode this information. Here, we recorded NAc neurons during a training

  2. Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease

    PubMed Central

    2017-01-01

    The overwhelming increase in the global incidence of obesity and its associated complications such as insulin resistance, atherosclerosis, pulmonary disease, and degenerative disorders including dementia constitutes a serious public health problem. The Inhibitor of DNA Binding/Differentiation-3 (ID3), a member of the ID family of transcriptional regulators, has been shown to play a role in adipogenesis and therefore ID3 may influence obesity and metabolic health in response to environmental factors. This review will highlight the current understanding of how ID3 may contribute to complex chronic diseases via metabolic perturbations. Based on the increasing number of reports that suggest chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs) within the human body are associated with metabolic disorders, we will also consider the impact of these chemicals on ID3. Improved understanding of the ID3 pathways by which exposure to EDCs can potentiate complex chronic diseases in populations with metabolic disorders (obesity, metabolic syndrome, and glucose intolerance) will likely provide useful knowledge in the prevention and control of complex chronic diseases associated with exposure to environmental pollutants. PMID:28785583

  3. Temporal distribution of favourite books, movies, and records: differential encoding and re-sampling.

    PubMed

    Janssen, Steve M J; Chessa, Antonio G; Murre, Jaap M J

    2007-10-01

    The reminiscence bump is the effect that people recall more personal events from early adulthood than from childhood or adulthood. The bump has been examined extensively. However, the question of whether the bump is caused by differential encoding or re-sampling is still unanswered. To examine this issue, participants were asked to name their three favourite books, movies, and records. Furthermore,they were asked when they first encountered them. We compared the temporal distributions and found that they all showed recency effects and reminiscence bumps. The distribution of favourite books had the largest recency effect and the distribution of favourite records had the largest reminiscence bump. We can explain these results by the difference in rehearsal. Books are read two or three times, movies are watched more frequently, whereas records are listened to numerous times. The results suggest that differential encoding initially causes the reminiscence bump and that re-sampling increases the bump further.

  4. DSD/WBL-consistent JWL equations of state for EDC35

    NASA Astrophysics Data System (ADS)

    Hodgson, Alexander N.; Handley, Caroline Angela

    2012-03-01

    The Detonation Shock Dynamics (DSD) model allows the calculation of curvature-dependent detonation propagation. It is of particular use when applied to insensitive high explosives, such as EDC35, since they have a greater non-ideal behaviour. The DSD model is used in conjunction with experimental cylinder test data to obtain the JWL Equation of State (EOS) for EDC35. Adjustment of parameters in the JWL equation changes the expansion profile of the cylinder wall in hydrocode simulations. The parameters are iterated until the best match can be made between simulation and experiment. Previous DSD models used at AWE have no mechanism to adjust the chemical energy release to match the detonation conditions. Two JWL calibrations are performed using the DSD model, with and without Hetherington's energy release model (these proceedings). Also in use is a newly-calibrated detonation speed-curvature relation.

  5. Disruption of apoptosis pathways involved in zebrafish gonad differentiation by 17α-ethinylestradiol and fadrozole exposures.

    PubMed

    Luzio, Ana; Matos, Manuela; Santos, Dércia; Fontaínhas-Fernandes, António A; Monteiro, Sandra M; Coimbra, Ana M

    2016-08-01

    Zebrafish (Danio rerio) sex determination seems to involve genetic factors (GSD) but also environmental factors (ESD), such as endocrine disrupting chemicals (EDCs) that are known to mimic endogenous hormones and disrupt gonad differentiation. Apoptosis has also been proposed to play a crucial role in zebrafish gonad differentiation. Nevertheless, the interactions between EDCs and apoptosis have received little attention. Thus, this study aimed to assess if and which apoptotic pathways are involved in zebrafish gonad differentiation and how EDCs may interfere with this process. With these purposes, zebrafish were exposed to 17α-ethinylestradiol (EE2, 4ng/L) and fadrozole (Fad, 50μg/L) from 2h to 35days post-fertilization (dpf). Afterwards, a gene expression analysis by qRT-PCR and a stereological analysis, based on systematic sampling and protein immunohistochemistry, were performed. The death receptors (FAS; TRADD), anti-apoptotic (BCL-2; MDM2), pro-apoptotic (CASP-2 and -6) and cell proliferation (BIRC5/survivin; JUN) genes and proteins were evaluated. In general, apoptosis was inhibited in females through the involvement of anti-apoptotic pathways, while in males apoptosis seemed to be crucial to the failure of the "juvenile ovary" development and the induction of testes transformation. The JUN protein was shown to be necessary in juvenile ovaries, while the BIRC5 protein seemed to be involved in zebrafish spermatogenesis. Both EDCs, EE2 and Fad, increased the apoptosis stimulus in zebrafish gonad. It was noticed that the few females that were resistant to Fad-induced sex reversal had increased anti-apoptotic factor levels, while males exposed to EE2 showed increased pro-apoptotic genes/proteins and were more advanced in gonad differentiation. Overall, our findings show that apoptosis pathways are involved in zebrafish gonad differentiation and that EDCs can disrupt this process. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

    PubMed Central

    Chappell, V. A.; Fenton, S. E.; Flaws, J. A.; Nadal, A.; Prins, G. S.; Toppari, J.; Zoeller, R. T.

    2015-01-01

    This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health. PMID:26414233

  7. The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in immunity

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

    Buoso, Erica; Galasso, Marilisa; Ronfani, Melania

    We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p′DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p′DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity andmore » protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p′DDT and p,p′DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p′DDE exerting a stronger repressor effect than p,p′DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system. - Highlights: • RACK1 expression can be induced by AR agonists with a consequent enhancement of the response to LPS. • RACK1 can be negatively modulated by the AR antagonists DDT and its main metabolite p,p′DDE. • RACK1 can be a relevant target of EDCs, representing a bridge between the endocrine system and the immune system.« less

  8. Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries.

    PubMed

    Li, Yizhou; Gabriele, Elena; Samain, Florent; Favalli, Nicholas; Sladojevich, Filippo; Scheuermann, Jörg; Neri, Dario

    2016-08-08

    DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins of biological or pharmaceutical interest. In the majority of cases, synthetic procedures for the formation of DNA-encoded combinatorial libraries incorporate at least one step of amide bond formation between amino-modified DNA and a carboxylic acid. We investigated reaction conditions and established a methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole and N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% for 423/543 (78%) of the carboxylic acids tested. These reaction conditions were efficient with a variety of primary and secondary amines, as well as with various types of amino-modified oligonucleotides. The reaction conditions, which also worked efficiently over a broad range of DNA concentrations and reaction scales, should facilitate the synthesis of novel DNA-encoded combinatorial libraries.

  9. The classic EDCs, phthalate esters and organochlorines, in relation to abnormal sperm quality: a systematic review with meta-analysis.

    PubMed

    Wang, Chao; Yang, Lu; Wang, Shu; Zhang, Zhan; Yu, Yongquan; Wang, Meilin; Cromie, Meghan; Gao, Weimin; Wang, Shou-Lin

    2016-01-25

    The association between endocrine disrupting chemicals (EDCs) and human sperm quality is controversial due to the inconsistent literature findings, therefore, a systematic review with meta-analysis was performed. Through the literature search and selection based on inclusion criteria, a total of 9 studies (7 cross-sectional, 1 case-control, and 1 pilot study) were analyzed for classic EDCs (5 studies for phthalate esters and 4 studies for organochlorines). Funnel plots revealed a symmetrical distribution with no evidence of publication bias (Begg's test: intercept = 0.40; p = 0.692). The summary odds ratios (OR) of human sperm quality associated with the classic EDCs was 1.67 (95% CI: 1.31-2.02). After stratification by specific chemical class, consistent increases in the risk of abnormal sperm quality were found in phthalate ester group (OR = 1.52; 95% CI: 1.09-1.95) and organochlorine group (OR = 1.98; 95% CI: 1.34-2.62). Additionally, identification of official data, and a comprehensive review of the mechanisms were performed, and better elucidated the increased risk of these classic EDCs on abnormal sperm quality. The present systematic review and meta-analysis helps to identify the impact of classic EDCs on human sperm quality. However, it still highlights the need for additional epidemiological studies in a larger variety of geographic locations.

  10. The classic EDCs, phthalate esters and organochlorines, in relation to abnormal sperm quality: a systematic review with meta-analysis

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Yang, Lu; Wang, Shu; Zhang, Zhan; Yu, Yongquan; Wang, Meilin; Cromie, Meghan; Gao, Weimin; Wang, Shou-Lin

    2016-01-01

    The association between endocrine disrupting chemicals (EDCs) and human sperm quality is controversial due to the inconsistent literature findings, therefore, a systematic review with meta-analysis was performed. Through the literature search and selection based on inclusion criteria, a total of 9 studies (7 cross-sectional, 1 case-control, and 1 pilot study) were analyzed for classic EDCs (5 studies for phthalate esters and 4 studies for organochlorines). Funnel plots revealed a symmetrical distribution with no evidence of publication bias (Begg’s test: intercept = 0.40 p = 0.692). The summary odds ratios (OR) of human sperm quality associated with the classic EDCs was 1.67 (95% CI: 1.31-2.02). After stratification by specific chemical class, consistent increases in the risk of abnormal sperm quality were found in phthalate ester group (OR = 1.52 95% CI: 1.09-1.95) and organochlorine group (OR = 1.98 95% CI: 1.34-2.62). Additionally, identification of official data, and a comprehensive review of the mechanisms were performed, and better elucidated the increased risk of these classic EDCs on abnormal sperm quality. The present systematic review and meta-analysis helps to identify the impact of classic EDCs on human sperm quality. However, it still highlights the need for additional epidemiological studies in a larger variety of geographic locations.

  11. Degradation of the endocrine disrupting chemicals (EDCs) carbamazepine, clofibric acid, and iopromide by corona discharge over water.

    PubMed

    Krause, Holger; Schweiger, Bianca; Schuhmacher, Jörg; Scholl, Saskia; Steinfeld, Ute

    2009-04-01

    Common wastewater treatment plants often do not eliminate endocrine disrupting chemicals (EDCs). Aqueous solutions of three EDCs were treated with an enhanced corona discharge technology. The three EDCs were clofibric acid, a blood lipid regulator, carbamazepine, an antiepileptic drug, and iopromide, a contrast media. To simulate real conditions, EDC solutions containing landfill leachate were also used. In our setup, two barrier electrodes provided an atmospheric pressure corona discharge over a thin water film, in which the counter-electrode was submerged. Clofibric acid, carbamazepine, and iopromide were effectively removed from a single solution. After a treatment of 15min, there were no traces of iopromide estrogen activity either as a single substance or as degradation products when using an E-Screen Assay. Continuous treatment was compared with pulsed treatment using carbamazepine solutions mixed with pretreated landfill leachate. Best degradation results were achieved with a 500 W continuous duty cycle treatment. Counter-electrodes from materials such as boron doped diamond (BDD), titanium iridium oxide, and iron were investigated for their influences on the process effectivity. Significant improvements were achieved by using an enclosed reactor, BDD electrodes, and circulating only a fresh air or argon/air mixture as cooling gas through the barrier electrodes.

  12. Embedded data collector (EDC) phase II load and resistance factor design (LRFD).

    DOT National Transportation Integrated Search

    2015-09-01

    A total of 16 static load test results was collected in Florida and Louisiana. New static load tests on five test piles : in Florida (four of which were voided) were monitored with Embedded Data Collector (EDC) instrumentation and : contributed to th...

  13. Tissue factor pathway inhibitor 2 is found in skin and its C-terminal region encodes for antibacterial activity.

    PubMed

    Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E; Lundqvist, Katarina; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

    2012-01-01

    Tissue factor pathway inhibitor 2 (TFPI-2) is a matrix-associated serine protease inhibitor with an enigmatic function in vivo. Here, we describe that TFPI-2 is present in fibrin of wounds and also expressed in skin, where it is up-regulated upon wounding. Neutrophil elastase cleaved TFPI-2, and a C-terminal fragment was found to bind to bacteria. Similarly, a prototypic peptide representing this C-terminal part, EDC34, bound to bacteria and bacterial lipopolysaccharide, and induced bacterial permeabilization. The peptide also induced leakage in artificial liposomes, and displayed a random coil conformation upon interactions with liposomes as well as lipopolysaccharide. EDC34 was antibacterial against both Gram-negative and Gram-positive bacteria in physiological buffer conditions. The results demonstrate that the C-terminus of TFPI-2 encodes for antimicrobial activity, and may be released during wounding.

  14. The Text Encoding Initiative: Flexible and Extensible Document Encoding.

    ERIC Educational Resources Information Center

    Barnard, David T.; Ide, Nancy M.

    1997-01-01

    The Text Encoding Initiative (TEI), an international collaboration aimed at producing a common encoding scheme for complex texts, examines the requirement for generality versus the requirement to handle specialized text types. Discusses how documents and users tax the limits of fixed schemes requiring flexible extensible encoding to support…

  15. TITLE: Twenty-five years after “Wingspread” – Environmental endocrine disruptors (EDCs) and human health: EDSP, HTS, AOPs, and TSCA

    EPA Science Inventory

    The aim of this paper is to provide the reader with a view of the Endocrine Disruptor Chemical (EDC) research field and its relevance to human health. My perspective is from working on the effects of EDCs that act via the androgen (A) or estrogen (E) signaling pathways in a regul...

  16. Global Phosphoproteomics Identifies a Major Role for AKT and 14-3-3 in Regulating EDC3*

    PubMed Central

    Larance, Mark; Rowland, Alexander F.; Hoehn, Kyle L.; Humphreys, David T.; Preiss, Thomas; Guilhaus, Michael; James, David E.

    2010-01-01

    Insulin plays an essential role in metabolic homeostasis in mammals, and many of the underlying biochemical pathways are regulated via the canonical phosphatidylinositol 3-kinase/AKT pathway. To identify novel metabolic actions of insulin, we conducted a quantitative proteomics analysis of insulin-regulated 14-3-3-binding proteins in muscle cells. These studies revealed a novel role for insulin in the post-transcriptional regulation of mRNA expression. EDC3, a component of the mRNA decay and translation repression pathway associated with mRNA processing bodies, was shown to be phosphorylated by AKT downstream of insulin signaling. The major insulin-regulated site was mapped to Ser-161, and phosphorylation at this site led to increased 14-3-3 binding. Functional studies indicated that induction of 14-3-3 binding to EDC3 causes morphological changes in processing body structures, inhibition of microRNA-mediated mRNA post-transcriptional regulation, and alterations in the protein- protein interactions of EDC3. These data highlight an important new arm of the insulin signaling cascade in the regulation of mRNA utilization. PMID:20051463

  17. Transcriptional Modulation of Genes Encoding Structural Characteristics of Differentiating Enterocytes During Development of a Polarized Epithelium In Vitro

    PubMed Central

    Halbleib, Jennifer M.; Sääf, Annika M.

    2007-01-01

    Although there is considerable evidence implicating posttranslational mechanisms in the development of epithelial cell polarity, little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized the temporal program of gene expression during cell–cell adhesion–initiated polarization of human Caco-2 cells in tissue culture, which develop structural and functional polarity similar to that of enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts between neighboring cells. Expression of genes involved in cell proliferation was down-regulated concomitant with induction of genes necessary for functional specialization of polarized epithelial cells. Transcriptional up-regulation of these latter genes correlated with formation of important structural and functional features in enterocyte differentiation and establishment of structural and functional cell polarity; components of the apical microvilli were induced as the brush border formed during polarization; as barrier function was established, expression of tight junction transmembrane proteins peaked; transcripts encoding components of the apical, but not the basal-lateral trafficking machinery were increased during polarization. Coordinated expression of genes encoding components of functional cell structures were often observed indicating temporal control of expression and assembly of multiprotein complexes. PMID:17699590

  18. BIODEGRADABILITY OF SELECTED EDCS UNDER REDOX CONDITIONS TYPICAL OF WASTEWATER TREATMENT AND SEDIMENTS

    EPA Science Inventory

    A number of emerging chemicals being detected in the environment are now gaining attention for having possible endocrine disrupting capabilities. These endocrine disrupting chemicals (EDCs) have been shown to have adverse affects on the endocrine system of fish and wildlife. But ...

  19. IDENTIFICATION OF NEURAL BIOMARKERS OF ALTERED SEXUAL DIFFERENTIATION FOLLOWING GESTATIONAL EXPOSURE***

    EPA Science Inventory

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

  20. Identification of neural biomarkers of altered sexual differentiation following gestational exposure

    EPA Science Inventory

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) during...

  1. Identification of neural biomarkers of altered sexual differentiation following gestational exposure###

    EPA Science Inventory

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

  2. INFLUENCE OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ON MAMMARY GLAND DEVELOPMENT AND TUMOR SUSCEPTIBILITY

    EPA Science Inventory

    Influence of Endocrine Disrupting Compounds (EDCs) on Mammary Gland Development and Tumor Susceptibility.

    Suzanne E. Fenton1, and Jennifer Rayner1,2

    1 Reproductive Toxicology Division, NHEERL/ORD, U.S. EPA, Research Triangle Park, NC, and 2 Department of Environmen...

  3. Embedded data collector (EDC) evaluation, phase II - comparison with instrumented static load tests.

    DOT National Transportation Integrated Search

    2013-12-01

    A total of 139 piles and 213,000 hammer blows were compared between the Embedded Data Collector : (EDC), the Pile Driving Analyzer (PDA), and the CAse Pile Wave Analysis Program (CAPWAP) along with : SmartPile Review versions (3.6, 3.72, 3.73, 3.76 a...

  4. The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

    PubMed

    Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-01-01

    Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

  5. The TFPI-2 Derived Peptide EDC34 Improves Outcome of Gram-Negative Sepsis

    PubMed Central

    Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E.; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-01-01

    Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections. PMID:24339780

  6. Circuit variability interacts with excitatory-inhibitory diversity of interneurons to regulate network encoding capacity.

    PubMed

    Tsai, Kuo-Ting; Hu, Chin-Kun; Li, Kuan-Wei; Hwang, Wen-Liang; Chou, Ya-Hui

    2018-05-23

    Local interneurons (LNs) in the Drosophila olfactory system exhibit neuronal diversity and variability, yet it is still unknown how these features impact information encoding capacity and reliability in a complex LN network. We employed two strategies to construct a diverse excitatory-inhibitory neural network beginning with a ring network structure and then introduced distinct types of inhibitory interneurons and circuit variability to the simulated network. The continuity of activity within the node ensemble (oscillation pattern) was used as a readout to describe the temporal dynamics of network activity. We found that inhibitory interneurons enhance the encoding capacity by protecting the network from extremely short activation periods when the network wiring complexity is very high. In addition, distinct types of interneurons have differential effects on encoding capacity and reliability. Circuit variability may enhance the encoding reliability, with or without compromising encoding capacity. Therefore, we have described how circuit variability of interneurons may interact with excitatory-inhibitory diversity to enhance the encoding capacity and distinguishability of neural networks. In this work, we evaluate the effects of different types and degrees of connection diversity on a ring model, which may simulate interneuron networks in the Drosophila olfactory system or other biological systems.

  7. A pituitary gene encodes a protein that produces differentiation of breast and prostate cancer cells.

    PubMed

    Platica, Micsunica; Ivan, Elena; Holland, James F; Ionescu, Alin; Chen, Sheryl; Mandeli, John; Unger, Pamela D; Platica, Ovidiu

    2004-02-10

    A cDNA clone of 1.1 kb encoding a 108-aa polypeptide was isolated from a human pituitary cDNA library by expression cloning. This protein was named tumor differentiation factor (TDF). The recombinant TDF protein and a 20-aa peptide, P1, selected from the ORF of the gene, induced morphological and biochemical changes consistent with differentiation of human breast and prostate cancer cells. Fibroblast, kidney, hepatoma, and leukemic lymphocytic cell lines were unaffected. Breast and prostate cancer cells aggregated in spheroid-like structures within 24 h of exposure to TDF. This effect was abrogated by a specific affinity-purified rabbit polyclonal anti-P1 Ab. E-cadherin expression was increased in a dose-dependent manner by TDF. Treatment of MCF7 cells with TDF led to production of a lactalbumin-related protein. Peptide P1 significantly decreased the growth of androgen-independent DU145 prostate cancer in severe combined immunodeficient mice. The presence of TDF protein in human sera was detected by the anti-P1 Ab, suggesting a role of TDF in endocrine metabolism. The fact that all activities of TDF can be mimicked by a peptide derived from the encoding TDF sequence opens the possibility of therapeutic applications.

  8. Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity

    PubMed Central

    Zhang, Jin; Ruhlman, Tracey A.; Sabir, Jamal S. M.; Blazier, John Chris; Weng, Mao-Lun; Park, Seongjun; Jansen, Robert K.

    2016-01-01

    Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear–plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. PMID:26893456

  9. Integrator complex plays an essential role in adipose differentiation

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

    Otani, Yuichiro; Nakatsu, Yusuke; Sakoda, Hideyuki

    2013-05-03

    Highlights: •IntS6 and IntS11 are subunits of the Integrator complex. •Expression levels of IntS6 and IntS11 were very low in 3T3-L1 fibroblast. •IntS6 and IntS11 were upregulated during adipose differentiation. •Suppression of IntS6 or IntS11 expression inhibited adipose differentiation. -- Abstract: The dynamic process of adipose differentiation involves stepwise expressions of transcription factors and proteins specific to the mature fat cell phenotype. In this study, it was revealed that expression levels of IntS6 and IntS11, subunits of the Integrator complex, were increased in 3T3-L1 cells in the period when the cells reached confluence and differentiated into adipocytes, while being reducedmore » to basal levels after the completion of differentiation. Suppression of IntS6 or IntS11 expression using siRNAs in 3T3-L1 preadipocytes markedly inhibited differentiation into mature adipocytes, based on morphological findings as well as mRNA analysis of adipocyte-specific genes such as Glut4, perilipin and Fabp4. Although Pparγ2 protein expression was suppressed in IntS6 or IntS11-siRNA treated cells, adenoviral forced expression of Pparγ2 failed to restore the capacity for differentiation into mature adipocytes. Taken together, these findings demonstrate that increased expression of Integrator complex subunits is an indispensable event in adipose differentiation. Although further study is necessary to elucidate the underlying mechanism, the processing of U1, U2 small nuclear RNAs may be involved in cell differentiation steps.« less

  10. Control of information in working memory: Encoding and removal of distractors in the complex-span paradigm.

    PubMed

    Oberauer, Klaus; Lewandowsky, Stephan

    2016-11-01

    The article reports four experiments with complex-span tasks in which encoding of memory items alternates with processing of distractors. The experiments test two assumptions of a computational model of complex span, SOB-CS: (1) distractor processing impairs memory because distractors are encoded into working memory, thereby interfering with memoranda; and (2) free time following distractors is used to remove them from working memory by unbinding their representations from list context. Experiment 1 shows that distractors are erroneously chosen for recall more often than not-presented stimuli, demonstrating that distractors are encoded into memory. Distractor intrusions declined with longer free time, as predicted by distractor removal. Experiment 2 shows these effects even when distractors precede the memory list, ruling out an account based on selective rehearsal of memoranda during free time. Experiments 3 and 4 test the notion that distractors decay over time. Both experiments show that, contrary to the notion of distractor decay, the chance of a distractor intruding at test does not decline with increasing time since encoding of that distractor. Experiment 4 provides additional evidence against the prediction from distractor decay that distractor intrusions decline over an unfilled retention interval. Taken together, the results support SOB-CS and rule out alternative explanations. Data and simulation code are available on Open Science Framework: osf.io/3ewh7. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing

    PubMed Central

    Wongpalee, Somsakul Pop; Vashisht, Ajay; Sharma, Shalini; Chui, Darryl; Wohlschlegel, James A; Black, Douglas L

    2016-01-01

    Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition. The active early complex formed in the absence of PTBP1 proceeded to assemble an EDC with the eviction of hnRNP proteins, the late recruitment of SR proteins, and binding of the U2 snRNP. These results demonstrate that during early stages of splicing, exon RNP complexes are highly dynamic with many proteins failing to bind during PTBP1 arrest. DOI: http://dx.doi.org/10.7554/eLife.19743.001 PMID:27882870

  12. Artificial neural networks using complex numbers and phase encoded weights.

    PubMed

    Michel, Howard E; Awwal, Abdul Ahad S

    2010-04-01

    The model of a simple perceptron using phase-encoded inputs and complex-valued weights is proposed. The aggregation function, activation function, and learning rule for the proposed neuron are derived and applied to Boolean logic functions and simple computer vision tasks. The complex-valued neuron (CVN) is shown to be superior to traditional perceptrons. An improvement of 135% over the theoretical maximum of 104 linearly separable problems (of three variables) solvable by conventional perceptrons is achieved without additional logic, neuron stages, or higher order terms such as those required in polynomial logic gates. The application of CVN in distortion invariant character recognition and image segmentation is demonstrated. Implementation details are discussed, and the CVN is shown to be very attractive for optical implementation since optical computations are naturally complex. The cost of the CVN is less in all cases than the traditional neuron when implemented optically. Therefore, all the benefits of the CVN can be obtained without additional cost. However, on those implementations dependent on standard serial computers, CVN will be more cost effective only in those applications where its increased power can offset the requirement for additional neurons.

  13. NMR-based Metabolomics for Studying Toxicity, Compensation, and Recovery in Small Fish Exposed to EDCs

    EPA Science Inventory

    Determining the impact(s) on fish and other aquatic organisms of exposure to endocrine disrupting compounds (EDCs) is critical for determining the risks that these chemicals pose. However, to accurately evaluate these risks, beyond simply measuring a “before and after exposure” ...

  14. Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity.

    PubMed

    Zhang, Jin; Ruhlman, Tracey A; Sabir, Jamal S M; Blazier, John Chris; Weng, Mao-Lun; Park, Seongjun; Jansen, Robert K

    2016-02-17

    Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear-plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. Encoding, rehearsal, and recall in signers and speakers: shared network but differential engagement.

    PubMed

    Bavelier, D; Newman, A J; Mukherjee, M; Hauser, P; Kemeny, S; Braun, A; Boutla, M

    2008-10-01

    Short-term memory (STM), or the ability to hold verbal information in mind for a few seconds, is known to rely on the integrity of a frontoparietal network of areas. Here, we used functional magnetic resonance imaging to ask whether a similar network is engaged when verbal information is conveyed through a visuospatial language, American Sign Language, rather than speech. Deaf native signers and hearing native English speakers performed a verbal recall task, where they had to first encode a list of letters in memory, maintain it for a few seconds, and finally recall it in the order presented. The frontoparietal network described to mediate STM in speakers was also observed in signers, with its recruitment appearing independent of the modality of the language. This finding supports the view that signed and spoken STM rely on similar mechanisms. However, deaf signers and hearing speakers differentially engaged key structures of the frontoparietal network as the stages of STM unfold. In particular, deaf signers relied to a greater extent than hearing speakers on passive memory storage areas during encoding and maintenance, but on executive process areas during recall. This work opens new avenues for understanding similarities and differences in STM performance in signers and speakers.

  16. Encoding, Rehearsal, and Recall in Signers and Speakers: Shared Network but Differential Engagement

    PubMed Central

    Newman, A. J.; Mukherjee, M.; Hauser, P.; Kemeny, S.; Braun, A.; Boutla, M.

    2008-01-01

    Short-term memory (STM), or the ability to hold verbal information in mind for a few seconds, is known to rely on the integrity of a frontoparietal network of areas. Here, we used functional magnetic resonance imaging to ask whether a similar network is engaged when verbal information is conveyed through a visuospatial language, American Sign Language, rather than speech. Deaf native signers and hearing native English speakers performed a verbal recall task, where they had to first encode a list of letters in memory, maintain it for a few seconds, and finally recall it in the order presented. The frontoparietal network described to mediate STM in speakers was also observed in signers, with its recruitment appearing independent of the modality of the language. This finding supports the view that signed and spoken STM rely on similar mechanisms. However, deaf signers and hearing speakers differentially engaged key structures of the frontoparietal network as the stages of STM unfold. In particular, deaf signers relied to a greater extent than hearing speakers on passive memory storage areas during encoding and maintenance, but on executive process areas during recall. This work opens new avenues for understanding similarities and differences in STM performance in signers and speakers. PMID:18245041

  17. Tributyltin Differentially Promotes Development of a Phenotypically Distinct Adipocyte

    PubMed Central

    Regnier, Shane M.; El-Hashani, Essam; Kamau, Wakanene; Zhang, Xiaojie; Massad, Nicole L.; Sargis, Robert M.

    2015-01-01

    Objective Environmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being pro-adipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known. Methods The co-stimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose. Results TBT enhanced expression of the adipocyte marker C/EBPα with co-exposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of co-treatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake. Conclusions TBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis. PMID:26243053

  18. Tributyltin differentially promotes development of a phenotypically distinct adipocyte.

    PubMed

    Regnier, Shane M; El-Hashani, Essam; Kamau, Wakanene; Zhang, Xiaojie; Massad, Nicole L; Sargis, Robert M

    2015-09-01

    Environmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being proadipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known. The costimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose. TBT enhanced expression of the adipocyte marker C/EBPα with coexposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of cotreatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake. TBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis. © 2015 The Obesity Society.

  19. Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

    PubMed Central

    van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

    1992-01-01

    Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

  20. The decapping activator Edc3 and the Q/N-rich domain of Lsm4 function together to enhance mRNA stability and alter mRNA decay pathway dependence in Saccharomyces cerevisiae.

    PubMed

    Huch, Susanne; Müller, Maren; Muppavarapu, Mridula; Gommlich, Jessie; Balagopal, Vidya; Nissan, Tracy

    2016-10-15

    The rate and regulation of mRNA decay are major elements in the proper control of gene expression. Edc3 and Lsm4 are two decapping activator proteins that have previously been shown to function in the assembly of RNA granules termed P bodies. Here, we show that deletion of edc3, when combined with a removal of the glutamine/asparagine rich region of Lsm4 (edc3Δ lsm4ΔC) reduces mRNA stability and alters pathways of mRNA degradation. Multiple tested mRNAs exhibited reduced stability in the edc3Δ lsm4ΔC mutant. The destabilization was linked to an increased dependence on Ccr4-mediated deadenylation and mRNA decapping. Unlike characterized mutations in decapping factors that either are neutral or are able to stabilize mRNA, the combined edc3Δ lsm4ΔC mutant reduced mRNA stability. We characterized the growth and activity of the major mRNA decay systems and translation in double mutant and wild-type yeast. In the edc3Δ lsm4ΔC mutant, we observed alterations in the levels of specific mRNA decay factors as well as nuclear accumulation of the catalytic subunit of the decapping enzyme Dcp2. Hence, we suggest that the effects on mRNA stability in the edc3Δ lsm4ΔC mutant may originate from mRNA decay protein abundance or changes in mRNPs, or alternatively may imply a role for P bodies in mRNA stabilization. © 2016. Published by The Company of Biologists Ltd.

  1. The decapping activator Edc3 and the Q/N-rich domain of Lsm4 function together to enhance mRNA stability and alter mRNA decay pathway dependence in Saccharomyces cerevisiae

    PubMed Central

    Huch, Susanne; Müller, Maren; Muppavarapu, Mridula; Gommlich, Jessie; Balagopal, Vidya; Nissan, Tracy

    2016-01-01

    ABSTRACT The rate and regulation of mRNA decay are major elements in the proper control of gene expression. Edc3 and Lsm4 are two decapping activator proteins that have previously been shown to function in the assembly of RNA granules termed P bodies. Here, we show that deletion of edc3, when combined with a removal of the glutamine/asparagine rich region of Lsm4 (edc3Δ lsm4ΔC) reduces mRNA stability and alters pathways of mRNA degradation. Multiple tested mRNAs exhibited reduced stability in the edc3Δ lsm4ΔC mutant. The destabilization was linked to an increased dependence on Ccr4-mediated deadenylation and mRNA decapping. Unlike characterized mutations in decapping factors that either are neutral or are able to stabilize mRNA, the combined edc3Δ lsm4ΔC mutant reduced mRNA stability. We characterized the growth and activity of the major mRNA decay systems and translation in double mutant and wild-type yeast. In the edc3Δ lsm4ΔC mutant, we observed alterations in the levels of specific mRNA decay factors as well as nuclear accumulation of the catalytic subunit of the decapping enzyme Dcp2. Hence, we suggest that the effects on mRNA stability in the edc3Δ lsm4ΔC mutant may originate from mRNA decay protein abundance or changes in mRNPs, or alternatively may imply a role for P bodies in mRNA stabilization. PMID:27543059

  2. Artificial Intelligence Techniques to Optimize the EDC/NHS-Mediated Immobilization of Cellulase on Eudragit L-100

    PubMed Central

    Zhang, Yu; Xu, Jing-Liang; Yuan, Zhen-Hong; Qi, Wei; Liu, Yun-Yun; He, Min-Chao

    2012-01-01

    Two artificial intelligence techniques, namely artificial neural network (ANN) and genetic algorithm (GA) were combined to be used as a tool for optimizing the covalent immobilization of cellulase on a smart polymer, Eudragit L-100. 1-Ethyl-3-(3-dimethyllaminopropyl) carbodiimide (EDC) concentration, N-hydroxysuccinimide (NHS) concentration and coupling time were taken as independent variables, and immobilization efficiency was taken as the response. The data of the central composite design were used to train ANN by back-propagation algorithm, and the result showed that the trained ANN fitted the data accurately (correlation coefficient R2 = 0.99). Then a maximum immobilization efficiency of 88.76% was searched by genetic algorithm at a EDC concentration of 0.44%, NHS concentration of 0.37% and a coupling time of 2.22 h, where the experimental value was 87.97 ± 6.45%. The application of ANN based optimization by GA is quite successful. PMID:22942683

  3. Neural Repetition Effects in the Medial Temporal Lobe Complex are Modulated by Previous Encoding Experience

    PubMed Central

    Greene, Ciara M.; Soto, David

    2012-01-01

    It remains an intriguing question why the medial temporal lobe (MTL) can display either attenuation or enhancement of neural activity following repetition of previously studied items. To isolate the role of encoding experience itself, we assessed neural repetition effects in the absence of any ongoing task demand or intentional orientation to retrieve. Experiment 1 showed that the hippocampus and surrounding MTL regions displayed neural repetition suppression (RS) upon repetition of past items that were merely attended during an earlier study phase but this was not the case following re-occurrence of items that had been encoded into working memory (WM). In this latter case a trend toward neural repetition enhancement (RE) was observed, though this was highly variable across individuals. Interestingly, participants with a higher degree of neural RE in the MTL complex displayed higher memory sensitivity in a later, surprise recognition test. Experiment 2 showed that massive exposure at encoding effected a change in the neural architecture supporting incidental repetition effects, with regions of the posterior parietal and ventral-frontal cortex in addition to the hippocampus displaying neural RE, while no neural RS was observed. The nature of encoding experience therefore modulates the expression of neural repetition effects in the MTL and the neocortex in the absence of memory goals. PMID:22829892

  4. Differentiation of Mycobacterium tuberculosis complex from non-tubercular mycobacteria by nested multiplex PCR targeting IS6110, MTP40 and 32kD alpha antigen encoding gene fragments.

    PubMed

    Sinha, Pallavi; Gupta, Anamika; Prakash, Pradyot; Anupurba, Shampa; Tripathi, Rajneesh; Srivastava, G N

    2016-03-12

    Control of the global burden of tuberculosis is obstructed due to lack of simple, rapid and cost effective diagnostic techniques that can be used in resource poor-settings. To facilitate the early diagnosis of TB directly from clinical specimens, we have standardized and validated the use of nested multiplex PCR, targeting gene fragments IS6110, MTP40 and 32kD α-antigen encoding genes specific for Mycobacterium tuberculosis complex and non-tubercular mycobacteria (NTM), in comparison to smear microscopy, solid culture and single step multiplex PCR. The results were evaluated in comparison to a composite reference standard (CRS) comprising of microbiological results (smear and culture), clinical, radiological and cytopathological findings, clinical treatment and response to anti-tubercular therapy. The nested multiplex PCR (nMPCR) assay was evaluated to test its utility in 600 (535 pulmonary and 65 extra-pulmonary specimens) clinically suspected TB cases. All specimens were processed for smear, culture, single step multiplex PCR and nested multiplex PCR testing. Out of 535 screened pulmonary and 65 extra-pulmonary specimens, 329 (61.5%) and 19 (29.2%) cases were culture positive for M. tuberculosis. Based on CRS, 450 patients had "clinical TB" (definitive-TB, probable-TB and possible-TB). Remaining 150 were confirmed "non-TB" cases. For culture, the sensitivity was low, 79.3% for pulmonary and 54.3% for extra-pulmonary cases. The sensitivity and specificity results for nMPCR test were evaluated taken composite reference standard as a gold standard. The sensitivity of the nMPCR assay was 97.1% for pulmonary and 91.4% for extra-pulmonary TB cases with specificity of 100% and 93.3% respectively. Nested multiplex PCR using three gene primers is a rapid, reliable and highly sensitive and specific diagnostic technique for the detection and differentiation of M. tuberculosis complex from NTM genome and will be useful in diagnosing paucibacillary samples. Nested multiplex

  5. Ectromelia virus encodes a novel family of F-box proteins that interact with the SCF complex.

    PubMed

    van Buuren, Nick; Couturier, Brianne; Xiong, Yue; Barry, Michele

    2008-10-01

    Poxviruses are notorious for encoding multiple proteins that regulate cellular signaling pathways, including the ubiquitin-proteasome system. Bioinformatics indicated that ectromelia virus, the causative agent of lethal mousepox, encoded four proteins, EVM002, EVM005, EVM154, and EVM165, containing putative F-box domains. In contrast to cellular F-box proteins, the ectromelia virus proteins contain C-terminal F-box domains in conjunction with N-terminal ankyrin repeats, a combination that has not been previously reported for cellular proteins. These observations suggested that the ectromelia virus F-box proteins interact with SCF (Skp1, cullin-1, and F-box) ubiquitin ligases. We focused our studies on EVM005, since this protein had only one ortholog in cowpox virus. Using mass spectrometry, we identified cullin-1 as a binding partner for EVM005, and this interaction was confirmed by overexpression of hemagglutinin (HA)-cullin-1. During infection, Flag-EVM005 and HA-cullin-1 colocalized to distinct cellular bodies. Significantly, EVM005 coprecipitated with endogenous Skp1, cullin-1, and Roc1 and associated with conjugated ubiquitin, suggesting that EVM005 interacted with the components of a functional ubiquitin ligase. Interaction of EVM005 with cullin-1 and Skp1 was abolished upon deletion of the F-box, indicating that the F-box played a crucial role in interaction with the SCF complex. Additionally, EVM002 and EVM154 interacted with Skp1 and conjugated ubiquitin, suggesting that ectromelia virus encodes multiple F-box-containing proteins that regulate the SCF complex. Our results indicate that ectromelia virus has evolved multiple proteins that interact with the SCF complex.

  6. TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

    EPA Science Inventory

    This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

  7. The list-composition effect in memory for emotional and neutral pictures: Differential contribution of ventral and dorsal attention networks to successful encoding.

    PubMed

    Barnacle, Gemma E; Montaldi, Daniela; Talmi, Deborah; Sommer, Tobias

    2016-09-01

    The Emotional enhancement of memory (EEM) is observed in immediate free-recall memory tests when emotional and neutral stimuli are encoded and tested together ("mixed lists"), but surprisingly, not when they are encoded and tested separately ("pure lists"). Here our aim was to investigate whether the effect of list-composition (mixed versus pure lists) on the EEM is due to differential allocation of attention. We scanned participants with fMRI during encoding of semantically-related emotional (negative valence only) and neutral pictures. Analysis of memory performance data replicated previous work, demonstrating an interaction between list composition and emotional valence. In mixed lists, neural subsequent memory effects in the dorsal attention network were greater for neutral stimulus encoding, while neural subsequent memory effects for emotional stimuli were found in a region associated with the ventral attention network. These results imply that when life experiences include both emotional and neutral elements, memory for the latter is more highly correlated with neural activity representing goal-directed attention processing at encoding. Copyright © 2016. Published by Elsevier Ltd.

  8. Dynamic and differential expression of the gonadal aromatase during the process of sexual differentiation in a novel transgenic cyp19a1a-eGFP zebrafish line.

    PubMed

    Hinfray, Nathalie; Sohm, Frédéric; Caulier, Morgane; Chadili, Edith; Piccini, Benjamin; Torchy, Camille; Porcher, Jean-Marc; Guiguen, Yann; Brion, François

    2018-05-15

    sexual differentiation, its expression persists whatever the sex suggesting that estradiol synthesis is important for gonadal development of both sexes. Monitoring the expression of GFP in control and exposed-fish will help determine the sensitivity of this transgenic line to EDCs and to refine mechanistic based-assays for the study of EDCs. In fine, this transgenic zebrafish line will be a useful tool to study physiological processes such as reproduction and sexual differentiation, and their perturbations by EDCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells

    PubMed Central

    Watanabe, Yukiko; Onodera, Atsushi; Kanai, Urara; Ichikawa, Tomomi; Obata-Ninomiya, Kazushige; Wada, Tomoko; Kiuchi, Masahiro; Iwamura, Chiaki; Tumes, Damon J.; Shinoda, Kenta; Yagi, Ryoji; Motohashi, Shinichiro; Hirahara, Kiyoshi; Nakayama, Toshinori

    2014-01-01

    Epigenetic modifications, such as posttranslational modifications of histones, play an important role in gene expression and regulation. These modifications are in part mediated by the Trithorax group (TrxG) complex and the Polycomb group (PcG) complex, which activate and repress transcription, respectively. We herein investigate the role of Menin, a component of the TrxG complex in T helper (Th) cell differentiation and show a critical role for Menin in differentiation and maintenance of Th17 cells. Menin−/− T cells do not efficiently differentiate into Th17 cells, leaving Th1 and Th2 cell differentiation intact in in vitro cultures. Menin deficiency resulted in the attenuation of Th17-induced airway inflammation. In differentiating Th17 cells, Menin directly bound to the Il17a gene locus and was required for the deposition of permissive histone modifications and recruitment of the RNA polymerase II transcriptional complex. Interestingly, although Menin bound to the Rorc locus, Menin was dispensable for the induction of Rorc expression and permissive histone modifications in differentiating Th17 cells. In contrast, Menin was required to maintain expression of Rorc in differentiated Th17 cells, indicating that Menin is essential to stabilize expression of the Rorc gene. Thus, Menin orchestrates Th17 cell differentiation and function by regulating both the induction and maintenance of target gene expression. PMID:25136117

  10. Differential Encoding of Time by Prefrontal and Striatal Network Dynamics.

    PubMed

    Bakhurin, Konstantin I; Goudar, Vishwa; Shobe, Justin L; Claar, Leslie D; Buonomano, Dean V; Masmanidis, Sotiris C

    2017-01-25

    Telling time is fundamental to many forms of learning and behavior, including the anticipation of rewarding events. Although the neural mechanisms underlying timing remain unknown, computational models have proposed that the brain represents time in the dynamics of neural networks. Consistent with this hypothesis, changing patterns of neural activity dynamically in a number of brain areas-including the striatum and cortex-has been shown to encode elapsed time. To date, however, no studies have explicitly quantified and contrasted how well different areas encode time by recording large numbers of units simultaneously from more than one area. Here, we performed large-scale extracellular recordings in the striatum and orbitofrontal cortex of mice that learned the temporal relationship between a stimulus and a reward and reported their response with anticipatory licking. We used a machine-learning algorithm to quantify how well populations of neurons encoded elapsed time from stimulus onset. Both the striatal and cortical networks encoded time, but the striatal network outperformed the orbitofrontal cortex, a finding replicated both in simultaneously and nonsimultaneously recorded corticostriatal datasets. The striatal network was also more reliable in predicting when the animals would lick up to ∼1 s before the actual lick occurred. Our results are consistent with the hypothesis that temporal information is encoded in a widely distributed manner throughout multiple brain areas, but that the striatum may have a privileged role in timing because it has a more accurate "clock" as it integrates information across multiple cortical areas. The neural representation of time is thought to be distributed across multiple functionally specialized brain structures, including the striatum and cortex. However, until now, the neural code for time has not been compared quantitatively between these areas. Here, we performed large-scale recordings in the striatum and orbitofrontal

  11. Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting.

    PubMed

    Street, Maria Elisabeth; Angelini, Sabrina; Bernasconi, Sergio; Burgio, Ernesto; Cassio, Alessandra; Catellani, Cecilia; Cirillo, Francesca; Deodati, Annalisa; Fabbrizi, Enrica; Fanos, Vassilios; Gargano, Giancarlo; Grossi, Enzo; Iughetti, Lorenzo; Lazzeroni, Pietro; Mantovani, Alberto; Migliore, Lucia; Palanza, Paola; Panzica, Giancarlo; Papini, Anna Maria; Parmigiani, Stefano; Predieri, Barbara; Sartori, Chiara; Tridenti, Gabriele; Amarri, Sergio

    2018-06-02

    Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

  12. Emotional Complexity and the Neural Representation of Emotion in Motion

    PubMed Central

    Barnard, Philip J.; Lawrence, Andrew D.

    2011-01-01

    According to theories of emotional complexity, individuals low in emotional complexity encode and represent emotions in visceral or action-oriented terms, whereas individuals high in emotional complexity encode and represent emotions in a differentiated way, using multiple emotion concepts. During functional magnetic resonance imaging, participants viewed valenced animated scenarios of simple ball-like figures attending either to social or spatial aspects of the interactions. Participant’s emotional complexity was assessed using the Levels of Emotional Awareness Scale. We found a distributed set of brain regions previously implicated in processing emotion from facial, vocal and bodily cues, in processing social intentions, and in emotional response, were sensitive to emotion conveyed by motion alone. Attention to social meaning amplified the influence of emotion in a subset of these regions. Critically, increased emotional complexity correlated with enhanced processing in a left temporal polar region implicated in detailed semantic knowledge; with a diminished effect of social attention; and with increased differentiation of brain activity between films of differing valence. Decreased emotional complexity was associated with increased activity in regions of pre-motor cortex. Thus, neural coding of emotion in semantic vs action systems varies as a function of emotional complexity, helping reconcile puzzling inconsistencies in neuropsychological investigations of emotion recognition. PMID:20207691

  13. Heterozygous variants in ACTL6A, encoding a component of the BAF complex, are associated with intellectual disability.

    PubMed

    Marom, Ronit; Jain, Mahim; Burrage, Lindsay C; Song, I-Wen; Graham, Brett H; Brown, Chester W; Stevens, Servi J C; Stegmann, Alexander P A; Gunter, Andrew T; Kaplan, Julie D; Gavrilova, Ralitza H; Shinawi, Marwan; Rosenfeld, Jill A; Bae, Yangjin; Tran, Alyssa A; Chen, Yuqing; Lu, James T; Gibbs, Richard A; Eng, Christine; Yang, Yaping; Rousseau, Justine; de Vries, Bert B A; Campeau, Philippe M; Lee, Brendan

    2017-10-01

    Pathogenic variants in genes encoding components of the BRG1-associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel variants in ACTL6A, a gene encoding a component of the BAF complex, in three subjects with varying degrees of intellectual disability. Two subjects have missense variants affecting highly conserved amino acid residues within the actin-like domain. Missense mutations in the homologous region in yeast actin were previously reported to be dominant lethal and were associated with impaired binding of the human ACTL6A to β-actin and BRG1. A third subject has a splicing variant that creates an in-frame deletion. Our findings suggest that the variants identified in our subjects may have a deleterious effect on the function of the protein by disturbing the integrity of the BAF complex. Thus, ACTL6A gene mutation analysis should be considered in patients with intellectual disability, learning disabilities, or developmental language disorder. © 2017 Wiley Periodicals, Inc.

  14. The value of electrocardiography for differential diagnosis in wide QRS complex tachycardia.

    PubMed

    Sousa, Pedro A; Pereira, Salomé; Candeias, Rui; de Jesus, Ilídio

    2014-03-01

    Correct diagnosis in wide QRS complex tachycardia remains a challenge. Differential diagnosis between ventricular and supraventricular tachycardia has important therapeutic and prognostic implications, and although data from clinical history and physical examination may suggest a particular origin, it is the 12-lead surface electrocardiogram that usually enables this differentiation. Since 1978, various electrocardiographic criteria have been proposed for the differential diagnosis of wide complex tachycardias, particularly the presence of atrioventricular dissociation, and the axis, duration and morphology of QRS complexes. Despite the wide variety of criteria, diagnosis is still often difficult, and errors can have serious consequences. To reduce such errors, several differential diagnosis algorithms have been proposed since 1991. However, in a small percentage of wide QRS tachycardias the diagnosis remains uncertain and in these the wisest decision is to treat them as ventricular tachycardias. The authors' objective was to review the main electrocardiographic criteria and differential diagnosis algorithms of wide QRS tachycardia. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  15. Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings.

    PubMed Central

    Tulving, E; Kapur, S; Craik, F I; Moscovitch, M; Houle, S

    1994-01-01

    Data are reviewed from positron emission tomography studies of encoding and retrieval processes in episodic memory. These data suggest a hemispheric encoding/retrieval asymmetry model of prefrontal involvement in encoding and retrieval of episodic memory. According to this model, the left and right prefrontal lobes are part of an extensive neuronal network that subserves episodic remembering, but the two prefrontal hemispheres play different roles. Left prefrontal cortical regions are differentially more involved in retrieval of information from semantic memory and in simultaneously encoding novel aspects of the retrieved information into episodic memory. Right prefrontal cortical regions, on the other hand, are differentially more involved in episodic memory retrieval. PMID:8134342

  16. Global genetic differentiation of complex traits shaped by natural selection in humans.

    PubMed

    Guo, Jing; Wu, Yang; Zhu, Zhihong; Zheng, Zhili; Trzaskowski, Maciej; Zeng, Jian; Robinson, Matthew R; Visscher, Peter M; Yang, Jian

    2018-05-14

    There are mean differences in complex traits among global human populations. We hypothesize that part of the phenotypic differentiation is due to natural selection. To address this hypothesis, we assess the differentiation in allele frequencies of trait-associated SNPs among African, Eastern Asian, and European populations for ten complex traits using data of large sample size (up to ~405,000). We show that SNPs associated with height ([Formula: see text]), waist-to-hip ratio ([Formula: see text]), and schizophrenia ([Formula: see text]) are significantly more differentiated among populations than matched "control" SNPs, suggesting that these trait-associated SNPs have undergone natural selection. We further find that SNPs associated with height ([Formula: see text]) and schizophrenia ([Formula: see text]) show significantly higher variance in linkage disequilibrium (LD) scores across populations than control SNPs. Our results support the hypothesis that natural selection has shaped the genetic differentiation of complex traits, such as height and schizophrenia, among worldwide populations.

  17. The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals

    PubMed Central

    Rich, Alisa L.; Phipps, Laura M.; Tiwari, Sweta; Rudraraju, Hemanth; Dokpesi, Philip O.

    2016-01-01

    An increasing number of children are born with intersex variation (IV; ambiguous genitalia/hermaphrodite, pseudohermaphroditism, etc.). Evidence shows that endocrine-disrupting chemicals (EDCs) in the environment can cause reproductive variation through dysregulation of normal reproductive tissue differentiation, growth, and maturation if the fetus is exposed to EDCs during critical developmental times in utero. Animal studies support fish and reptile embryos exhibited IV and sex reversal when exposed to EDCs. Occupational studies verified higher prevalence of offspring with IV in chemically exposed workers (male and female). Chemicals associated with endocrine-disrupting ability in humans include organochlorine pesticides, poly-chlorinated biphenyls, bisphenol A, phthalates, dioxins, and furans. Intersex individuals may have concurrent physical disorders requiring lifelong medical intervention and experience gender dysphoria. An urgent need exists to determine which chemicals possess the greatest risk for IV and the mechanisms by which these chemicals are capable of interfering with normal physiological development in children. PMID:27660460

  18. CHANGES IN GENE AND PROTEIN EXPRESSION IN ZEBRAFISH (DANIO RERIO) FOLLOWING EXPOSURE TO ENVIRONMENTALLY-RELEVANT ENDOCRINE DISRUPTING COMPOUNDS (EDCS)

    EPA Science Inventory

    Endocrine-disrupting chemicals (EDCs) are increasingly being reported in waterways worldwide and have been shown to affect fish species by disrupting numerous aspects of development, behavior, reproduction, and survival. Furthermore, new data have suggested that the reduced repr...

  19. EDC-mediated DNA attachment to nanocrystalline CVD diamond films.

    PubMed

    Christiaens, P; Vermeeren, V; Wenmackers, S; Daenen, M; Haenen, K; Nesládek, M; vandeVen, M; Ameloot, M; Michiels, L; Wagner, P

    2006-08-15

    Chemical vapour deposited (CVD) diamond is a very promising material for biosensor fabrication owing both to its chemical inertness and the ability to make it electrical semiconducting that allows for connection with integrated circuits. For biosensor construction, a biochemical method to immobilize nucleic acids to a diamond surface has been developed. Nanocrystalline diamond is grown using microwave plasma-enhanced chemical vapour deposition (MPECVD). After hydrogenation of the surface, 10-undecenoic acid, an omega-unsaturated fatty acid, is tethered by 254 nm photochemical attachment. This is followed by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC)-mediated attachment of amino (NH(2))-modified dsDNA. The functionality of the covalently bound dsDNA molecules is confirmed by fluorescence measurements, PCR and gel electrophoresis during 35 denaturation and rehybridisation steps. The linking method after the fatty acid attachment can easily be applied to other biomolecules like antibodies and enzymes.

  20. METABOLOMICS AS A TOOL FOR DISCRIMINATING AMONG ADAPTIVE, COMPENSATORY, AND TOXIC RESPONSES UPON EXPOSURE OF SMALL FISH TO EDCS

    EPA Science Inventory

    Determining the impact(s) of exposure on aquatic organisms by endocrine disrupting compounds (EDCs) is essential for determining the risks that these chemicals pose. However, to accurately evaluate these risks, beyond simply measuring a before and after exposure snapshot, resear...

  1. Method for data compression by associating complex numbers with files of data values

    DOEpatents

    Feo, J.T.; Hanks, D.C.; Kraay, T.A.

    1998-02-10

    A method for compressing data for storage or transmission is disclosed. Given a complex polynomial and a value assigned to each root, a root generated data file (RGDF) is created, one entry at a time. Each entry is mapped to a point in a complex plane. An iterative root finding technique is used to map the coordinates of the point to the coordinates of one of the roots of the polynomial. The value associated with that root is assigned to the entry. An equational data compression (EDC) method reverses this procedure. Given a target data file, the EDC method uses a search algorithm to calculate a set of m complex numbers and a value map that will generate the target data file. The error between a simple target data file and generated data file is typically less than 10%. Data files can be transmitted or stored without loss by transmitting the m complex numbers, their associated values, and an error file whose size is at most one-tenth of the size of the input data file. 4 figs.

  2. Method for data compression by associating complex numbers with files of data values

    DOEpatents

    Feo, John Thomas; Hanks, David Carlton; Kraay, Thomas Arthur

    1998-02-10

    A method for compressing data for storage or transmission. Given a complex polynomial and a value assigned to each root, a root generated data file (RGDF) is created, one entry at a time. Each entry is mapped to a point in a complex plane. An iterative root finding technique is used to map the coordinates of the point to the coordinates of one of the roots of the polynomial. The value associated with that root is assigned to the entry. An equational data compression (EDC) method reverses this procedure. Given a target data file, the EDC method uses a search algorithm to calculate a set of m complex numbers and a value map that will generate the target data file. The error between a simple target data file and generated data file is typically less than 10%. Data files can be transmitted or stored without loss by transmitting the m complex numbers, their associated values, and an error file whose size is at most one-tenth of the size of the input data file.

  3. Silver complexation and tandem mass spectrometry for differentiation of isomeric flavonoid diglycosides.

    PubMed

    Zhang, Junmei; Brodbelt, Jennifer S

    2005-03-15

    For detection and differentiation of isomeric flavonoids, electrospray ionization mass spectrometry is used to generate silver complexes of the type (Ag + flavonoid)+. Collisionally activated dissociation (CAD) of the resulting 1:1 silver/flavonoid complexes allows isomer differentiation of flavonoids. Eighteen flavonoid diglycosides constituting seven isomeric series are distinguishable from each other based on the CAD patterns of their silver complexes. Characteristic dissociation pathways allow identification of the site of glycosylation, the type of disaccharide (rutinose versus neohesperidose), and the type of aglycon (flavonol versus flavone versus flavanone). This silver complexation method is more universal than previous metal complexation methods, as intense silver complexes are observed even for flavonoids that lack the typical metal chelation sites. To demonstrate the feasibility of using silver complexation and tandem mass spectrometry to characterize flavonoids in complex mixtures, flavonoids extracted from grapefruit juice are separated by high-performance liquid chromatography and analyzed via a postcolumn complexation ESI-MS/MS strategy. Diagnostic fragmentation pathways of the silver complexes of the individual eluting flavonoids allow successful identification of the six flavonoids in the extract.

  4. Diagnostic Assessment of the Ecological Risk of EDCs in Complex Mixtures

    EPA Science Inventory

    Although it is important to be able to forecast the potential endocrine toxicity of chemical mixtures that could enter aquatic environments, in many instances there is a need to determine possible effects of endocrine-active chemicals already present in complex environmental mixt...

  5. Simultaneous determination of PPCPs, EDCs, and artificial sweeteners in environmental water samples using a single-step SPE coupled with HPLC-MS/MS and isotope dilution.

    PubMed

    Tran, Ngoc Han; Hu, Jiangyong; Ong, Say Leong

    2013-09-15

    A high-throughput method for the simultaneous determination of 24 pharmaceuticals and personal care products (PPCPs), endocrine disrupting chemicals (EDCs) and artificial sweeteners (ASs) was developed. The method was based on a single-step solid phase extraction (SPE) coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and isotope dilution. In this study, a single-step SPE procedure was optimized for simultaneous extraction of all target analytes. Good recoveries (≥ 70%) were observed for all target analytes when extraction was performed using Chromabond(®) HR-X (500 mg, 6 mL) cartridges under acidic condition (pH 2). HPLC-MS/MS parameters were optimized for the simultaneous analysis of 24 PPCPs, EDCs and ASs in a single injection. Quantification was performed by using 13 isotopically labeled internal standards (ILIS), which allows correcting efficiently the loss of the analytes during SPE procedure, matrix effects during HPLC-MS/MS and fluctuation in MS/MS signal intensity due to instrument. Method quantification limit (MQL) for most of the target analytes was below 10 ng/L in all water samples. The method was successfully applied for the simultaneous determination of PPCPs, EDCs and ASs in raw wastewater, surface water and groundwater samples collected in a local catchment area in Singapore. In conclusion, the developed method provided a valuable tool for investigating the occurrence, behavior, transport, and the fate of PPCPs, EDCs and ASs in the aquatic environment. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. An edge preserving differential image coding scheme

    NASA Technical Reports Server (NTRS)

    Rost, Martin C.; Sayood, Khalid

    1992-01-01

    Differential encoding techniques are fast and easy to implement. However, a major problem with the use of differential encoding for images is the rapid edge degradation encountered when using such systems. This makes differential encoding techniques of limited utility, especially when coding medical or scientific images, where edge preservation is of utmost importance. A simple, easy to implement differential image coding system with excellent edge preservation properties is presented. The coding system can be used over variable rate channels, which makes it especially attractive for use in the packet network environment.

  7. Bacillus subtilis 168 Contains Two Differentially Regulated Genes Encoding l-Asparaginase

    PubMed Central

    Fisher, Susan H.; Wray, Lewis V.

    2002-01-01

    Expression of the two Bacillus subtilis genes encoding l-asparaginase is controlled by independent regulatory factors. The ansZ gene (formerly yccC) was shown by mutational analysis to encode a functional l-asparaginase, the expression of which is activated during nitrogen-limited growth by the TnrA transcription factor. Gel mobility shift and DNase I footprinting experiments indicate that TnrA regulates ansZ expression by binding to a DNA site located upstream of the ansZ promoter. The expression of the ansA gene, which encodes the second l-asparaginase, was found to be induced by asparagine. The ansA repressor, AnsR, was shown to negatively regulate its own expression. PMID:11914346

  8. Bacillus subtilis 168 contains two differentially regulated genes encoding L-asparaginase.

    PubMed

    Fisher, Susan H; Wray, Lewis V

    2002-04-01

    Expression of the two Bacillus subtilis genes encoding L-asparaginase is controlled by independent regulatory factors. The ansZ gene (formerly yccC) was shown by mutational analysis to encode a functional L-asparaginase, the expression of which is activated during nitrogen-limited growth by the TnrA transcription factor. Gel mobility shift and DNase I footprinting experiments indicate that TnrA regulates ansZ expression by binding to a DNA site located upstream of the ansZ promoter. The expression of the ansA gene, which encodes the second L-asparaginase, was found to be induced by asparagine. The ansA repressor, AnsR, was shown to negatively regulate its own expression.

  9. Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology

    PubMed Central

    Kotlikoff, Michael I

    2007-01-01

    This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed. PMID:17038427

  10. EDCs, estrogenicity and genotoxicity reduction in a mixed (domestic + textile) secondary effluent by means of ozonation: a full-scale experience.

    PubMed

    Bertanza, G; Papa, M; Pedrazzani, R; Repice, C; Mazzoleni, G; Steimberg, N; Feretti, D; Ceretti, E; Zerbini, I

    2013-08-01

    WWTP (wastewater treatment plant) effluents are considered to be a major source for the release in the aquatic environment of EDCs (Endocrine-Disrupting Compounds), a group of anthropogenic substances able to alter the normal function of the endocrine system. The application of conventional processes (e.g. activated sludge with biological nitrogen removal) does not provide complete elimination of all these micropollutants and, consequently, an advanced treatment should be implemented. This experimental work was conducted on the tertiary ozonation stage of a 140,000 p.e. activated sludge WWTP, treating a mixed domestic and textile wastewater: an integrated monitoring, including both chemical (nonylphenol, together with the parent compounds mono- and di-ethoxylated, and bisphenol A were chosen as model EDCs) and biological (estrogenic and genotoxic activities) analyses, was carried out. Removal efficiencies of measured EDCs varied from 20% to 70%, depending on flow conditions (ozone dosage being 0.5 gO3/gTOC). Biological tests, furthermore, displayed that the oxidation stage did not significantly reduce (only by 20%) the estrogenicity of the effluent and revealed the presence and/or formation of genotoxic compounds. These results highlight the importance of the application of an integrated (biological+chemical) analytical procedure for a global evaluation of treatment suitability; poor performances recorded in this study have been attributed to the presence of a significant industrial component in the influent wastewater. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Peroxisome Proliferator-Activated Receptor γ Target Gene Encoding a Novel Angiopoietin-Related Protein Associated with Adipose Differentiation

    PubMed Central

    Yoon, J. Cliff; Chickering, Troy W.; Rosen, Evan D.; Dussault, Barry; Qin, Yubin; Soukas, Alexander; Friedman, Jeffrey M.; Holmes, William E.; Spiegelman, Bruce M.

    2000-01-01

    The nuclear receptor peroxisome proliferator-activated receptor γ regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. However, the identities of the biologically relevant target genes are largely unknown. Here we describe the isolation and characterization of a novel target gene induced by PPARγ ligands, termed PGAR (for PPARγ angiopoietin related), which encodes a novel member of the angiopoietin family of secreted proteins. The transcriptional induction of PGAR follows a rapid time course typical of immediate-early genes and occurs in the absence of protein synthesis. The expression of PGAR is predominantly localized to adipose tissues and placenta and is consistently elevated in genetic models of obesity. Hormone-dependent adipocyte differentiation coincides with a dramatic early induction of the PGAR transcript. Alterations in nutrition and leptin administration are found to modulate the PGAR expression in vivo. Taken together, these data suggest a possible role for PGAR in the regulation of systemic lipid metabolism or glucose homeostasis. PMID:10866690

  12. Random technique to encode complex valued holograms with on axis reconstruction onto phase-only displays.

    PubMed

    Luis Martínez Fuentes, Jose; Moreno, Ignacio

    2018-03-05

    A new technique for encoding the amplitude and phase of diffracted fields in digital holography is proposed. It is based on a random spatial multiplexing of two phase-only diffractive patterns. The first one is the phase information of the intended pattern, while the second one is a diverging optical element whose purpose is the control of the amplitude. A random number determines the choice between these two diffractive patterns at each pixel, and the amplitude information of the desired field governs its discrimination threshold. This proposed technique is computationally fast and does not require iterative methods, and the complex field reconstruction appears on axis. We experimentally demonstrate this new encoding technique with holograms implemented onto a flicker-free phase-only spatial light modulator (SLM), which allows the axial generation of such holograms. The experimental verification includes the phase measurement of generated patterns with a phase-shifting polarization interferometer implemented in the same experimental setup.

  13. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

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

    Biemann, Ronald, E-mail: ronald.biemann@medizin.uni-halle.de; Navarrete Santos, Anne; Navarrete Santos, Alexander

    Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study,more » we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.« less

  14. 1H-NMR METABOLOMICS ANALYIS OF ZEBRAFISH (DANIO RERIO) EXPOSED TO THE ENVIRONMENTALLY-RELEVANT EDC 17 ALPHA-ETHINYLESTRADIOL (EE2)

    EPA Science Inventory

    Elevated levels of endocrine-disrupting chemicals (EDCs) have been reported in waterways worldwide and have been shown to affect numerous aspects of development, behavior, reproduction, and survival in various fish species. We have examined the effects of the synthetic steroid 1...

  15. Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

    PubMed Central

    Martin, Carol-Anne; Murray, Jennie E.; Carroll, Paula; Leitch, Andrea; Mackenzie, Karen J.; Halachev, Mihail; Fetit, Ahmed E.; Keith, Charlotte; Bicknell, Louise S.; Fluteau, Adeline; Gautier, Philippe; Hall, Emma A.; Joss, Shelagh; Soares, Gabriela; Silva, João; Bober, Michael B.; Duker, Angela; Wise, Carol A.; Quigley, Alan J.; Phadke, Shubha R.; Wood, Andrew J.; Vagnarelli, Paola; Jackson, Andrew P.

    2016-01-01

    Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. PMID:27737959

  16. Possible strategies for EDC testing in the future: exploring roles of pathway-based in silico, in vitro and in vivo methods

    EPA Science Inventory

    Current methods for screening, testing and monitoring endocrine-disrupting chemicals (EDCs) rely relatively substantially upon moderate- to long-term assays that can, in some instances, require significant numbers of animals. Recent developments in the areas of in vitro testing...

  17. Influence of EDC/NHS coupling chemistry on stability and cytotoxicity of ZnO nanoparticles modified with proteins

    NASA Astrophysics Data System (ADS)

    Keleştemur, Seda; Altunbek, Mine; Culha, Mustafa

    2017-05-01

    The toxicity of ZnO nanoparticles (NPs) is a growing concern due to its increasing use in several products including sunscreens, paints, pigments and ceramics for its antibacterial, antifungal, anti-corrosive and UV filtering properties. The toxicity of ZnO NPs is mostly attributed to the Zn2+ release causing an increase in the intracellular reactive oxygen species (ROS) level. The surface modification with a biocompatible ligand or a polymer can be a good strategy to reduce dissolution based toxicity. In two previous studies, the conflicting results with EDC/NHS coupling chemistry for ZnO NPs were reported. In this study, the same surface modification strategy with an emphasis on the stability of ZnO NPs is clarified. First, the density of -OH groups on the ZnO NPs is increased with hydrogen peroxide (H2O2) treatment, and then a silica coating on the ZnO NPs (Si-ZnO) surface is performed. Finally, a covalent attachment of bovine serum albumin (BSA) on three different concentrations of ZnO-Si is carried out by EDC/NHS coupling chemistry. ZnO NPs have a very high dissolution rate under acidic conditions of EDC/NHS coupling chemistry as determined from the ICP-MS analysis. In addition, the amount of ZnO NPs in coupling reaction has an important effect on the dissolution rate of Zn2+ and dependently BSA attached on the ZnO NP surfaces. Finally, the cytotoxicity of the BSA modified Si-ZnO NPs on human lung cancer (A549) and human skin fibroblast (HSF) is evaluated. Although an increased association of BSA modified ZnO NPs with cells was observed, the modification significantly decreased their cytotoxicity. This can be explained with the decreased active surface area of ZnO NPs with the surface modification. However, an increase in the mitochondrial depolarization and ROS production was observed depending on the amount of BSA coverage.

  18. Endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) in the aquatic environment: implications for the drinking water industry and global environmental health.

    PubMed

    Rahman, M F; Yanful, E K; Jasim, S Y

    2009-06-01

    Endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) are a group of chemical compounds with diverse physical and chemical properties. Recent studies have indicated undesired effects of EDCs and PPCPs at their reported trace concentrations (ng l(-1) to microg l(-1)). This paper reviews the current knowledge on the sources, properties, occurrence and health impacts of EDCs and PPCPs, and their removal from drinking water using ozonation and ozone/hydrogen peroxide-based advanced oxidation. The paper also examines the potential threats posed by these chemicals to drinking water and public health. While these compounds are known to have adverse effects on ecosystem health, notably in the fish population, a similar link is yet to be established between ingestion of these compounds through drinking water and human health. In addition, data on the effectiveness of existing methods for the removal of these compounds are not conclusive. Further studies are required to characterize risks, and also to evaluate and optimize existing removal processes. Also concerted international effort is urgent to cut down the risk of exposure and restrain the production and marketing of toxic chemicals.

  19. Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.

    PubMed

    Martin, Carol-Anne; Murray, Jennie E; Carroll, Paula; Leitch, Andrea; Mackenzie, Karen J; Halachev, Mihail; Fetit, Ahmed E; Keith, Charlotte; Bicknell, Louise S; Fluteau, Adeline; Gautier, Philippe; Hall, Emma A; Joss, Shelagh; Soares, Gabriela; Silva, João; Bober, Michael B; Duker, Angela; Wise, Carol A; Quigley, Alan J; Phadke, Shubha R; Wood, Andrew J; Vagnarelli, Paola; Jackson, Andrew P

    2016-10-01

    Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. © 2016 Martin et al.; Published by Cold Spring Harbor Laboratory Press.

  20. PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex.

    PubMed

    Schrader, Laura A; Anderson, Anne E; Mayne, Amber; Pfaffinger, Paul J; Sweatt, John David

    2002-12-01

    A-type channels, encoded by the pore-forming alpha-subunits of the Kv4.x family, are particularly important in regulating membrane excitability in the CNS and the heart. Given the key role of modulation of A currents by kinases, we sought to investigate the protein structure-function relationships underlying the regulation of these currents by PKA. We have previously shown the existence of two PKA phosphorylation sites in the Kv4.2 sequence; therefore, we focused this study on the Kv4.2 primary subunit. In the present studies we made the surprising finding that PKA phosphorylation of the Kv4.2 alpha-subunit is necessary but not sufficient for channel modulation; channel modulation by PKA required the presence of an ancillary subunit, the K+ channel interacting protein (KChIP3). Therefore, these findings indicate a surprising complexity to kinase regulation of A currents, in that an interaction of two separate molecular events, alpha-subunit phosphorylation and the association of an ancillary subunit (KChIP3), are necessary for phosphorylation-dependent regulation of Kv4.2-encoded A channels by PKA. Overall, our studies indicate that PKA must of necessity act on a supramolecular complex of pore-forming alpha-subunits plus ancillary subunits to alter channel properties.

  1. Characterization of HKE2: an ancient antigen encoded in the major histocompatibility complex.

    PubMed

    Ostrov, D A; Barnes, C L; Smith, L E; Binns, S; Brusko, T M; Brown, A C; Quint, P S; Litherland, S A; Roopenian, D C; Iczkowski, K A

    2007-02-01

    Genes at the centromeric end of the human leukocyte antigen region influence adaptive autoimmune diseases and cancer. In this study, we characterized protein expression of HKE2, a gene located in the centromeric portion of the class II region of the major histocompatibility complex encoding subunit 6 of prefoldin. Immunohistochemical analysis using an anti-HKE2 antibody indicated that HKE2 protein expression is dramatically upregulated as a consequence of activation. In a tissue microarray and in several tumors, HKE2 was overexpressed in certain cancers compared with normal counterparts. The localization of the HKE2 gene to the class II region, its cytoplasmic expression and putative protein-binding domain suggest that HKE2 may function in adaptive immunity and cancer.

  2. The Impact of Mitochondrial Complex Inhibition on mESC Differentiation

    EPA Science Inventory

    The Impact of Mitochondrial Complex Inhibition on mESC Differentiation JE Royland, SH Warren, S Jeffay, MR Hoopes, HP Nichols, ES Hunter U.S. Environmental Protection Agency, Integrated Systems Toxicology Division, Research Triangle Park, NC The importance of mitochondrial funct...

  3. Area, speed and power measurements of FPGA-based complex orthogonal space-time block code channel encoders

    NASA Astrophysics Data System (ADS)

    Passas, Georgios; Freear, Steven; Fawcett, Darren

    2010-01-01

    Space-time coding (STC) is an important milestone in modern wireless communications. In this technique, more copies of the same signal are transmitted through different antennas (space) and different symbol periods (time), to improve the robustness of a wireless system by increasing its diversity gain. STCs are channel coding algorithms that can be readily implemented on a field programmable gate array (FPGA) device. This work provides some figures for the amount of required FPGA hardware resources, the speed that the algorithms can operate and the power consumption requirements of a space-time block code (STBC) encoder. Seven encoder very high-speed integrated circuit hardware description language (VHDL) designs have been coded, synthesised and tested. Each design realises a complex orthogonal space-time block code with a different transmission matrix. All VHDL designs are parameterisable in terms of sample precision. Precisions ranging from 4 bits to 32 bits have been synthesised. Alamouti's STBC encoder design [Alamouti, S.M. (1998), 'A Simple Transmit Diversity Technique for Wireless Communications', IEEE Journal on Selected Areas in Communications, 16:55-108.] proved to be the best trade-off, since it is on average 3.2 times smaller, 1.5 times faster and requires slightly less power than the next best trade-off in the comparison, which is a 3/4-rate full-diversity 3Tx-antenna STBC.

  4. Identification and Characterization of Three Differentially Expressed Genes, Encoding S-Adenosylhomocysteine Hydrolase, Methionine Aminopeptidase, and a Histone-Like Protein, in the Toxic Dinoflagellate Alexandrium fundyense†

    PubMed Central

    Taroncher-Oldenburg, Gaspar; Anderson, Donald M.

    2000-01-01

    Genes showing differential expression related to the early G1 phase of the cell cycle during synchronized circadian growth of the toxic dinoflagellate Alexandrium fundyense were identified and characterized by differential display (DD). The determination in our previous work that toxin production in Alexandrium is relegated to a narrow time frame in early G1 led to the hypothesis that transcriptionally up- or downregulated genes during this subphase of the cell cycle might be related to toxin biosynthesis. Three genes, encoding S-adenosylhomocysteine hydrolase (Sahh), methionine aminopeptidase (Map), and a histone-like protein (HAf), were isolated. Sahh was downregulated, while Map and HAf were upregulated, during the early G1 phase of the cell cycle. Sahh and Map encoded amino acid sequences with about 90 and 70% similarity to those encoded by several eukaryotic and prokaryotic Sahh and Map genes, respectively. The partial Map sequence also contained three cobalt binding motifs characteristic of all Map genes. HAf encoded an amino acid sequence with 60% similarity to those of two histone-like proteins from the dinoflagellate Crypthecodinium cohnii Biecheler. This study documents the potential of applying DD to the identification of genes that are related to physiological processes or cell cycle events in phytoplankton under conditions where small sample volumes represent an experimental constraint. The identification of an additional 21 genes with various cell cycle-related DD patterns also provides evidence for the importance of pretranslational or transcriptional regulation in dinoflagellates, contrary to previous reports suggesting the possibility that translational mechanisms are the primary means of circadian regulation in this group of organisms. PMID:10788388

  5. Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex

    PubMed Central

    Li, Ya-tang; Liu, Bao-hua; Chou, Xiao-lin; Zhang, Li I.

    2015-01-01

    In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels. Voltage-clamp recordings further revealed that although excitatory inputs to complex and simple cells exhibited a similar degree of OS, inhibition in complex cells was more narrowly tuned than excitation, whereas in simple cells inhibition was more broadly tuned than excitation. The differential inhibitory tuning can primarily account for the difference in OS between complex and simple cells. Interestingly, the differential synaptic tuning correlated well with the spatial organization of synaptic input: the inhibitory visual RF in complex cells was more elongated in shape than its excitatory counterpart and also was more elongated than that in simple cells. Together, our results demonstrate that OS of complex and simple cells is differentially shaped by cortical inhibition based on its orientation tuning profile relative to excitation, which is contributed at least partially by the spatial organization of RFs of presynaptic inhibitory neurons. SIGNIFICANCE STATEMENT Simple and complex cells, two classes of principal neurons in the primary visual cortex (V1), are generally thought to be equally selective for orientation. In mouse V1, we report that complex cells, identified by their overlapping on/off subfields, has significantly weaker orientation selectivity (OS) than simple cells. This can be primarily attributed to the

  6. Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex.

    PubMed

    Li, Ya-tang; Liu, Bao-hua; Chou, Xiao-lin; Zhang, Li I; Tao, Huizhong W

    2015-08-05

    In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels. Voltage-clamp recordings further revealed that although excitatory inputs to complex and simple cells exhibited a similar degree of OS, inhibition in complex cells was more narrowly tuned than excitation, whereas in simple cells inhibition was more broadly tuned than excitation. The differential inhibitory tuning can primarily account for the difference in OS between complex and simple cells. Interestingly, the differential synaptic tuning correlated well with the spatial organization of synaptic input: the inhibitory visual RF in complex cells was more elongated in shape than its excitatory counterpart and also was more elongated than that in simple cells. Together, our results demonstrate that OS of complex and simple cells is differentially shaped by cortical inhibition based on its orientation tuning profile relative to excitation, which is contributed at least partially by the spatial organization of RFs of presynaptic inhibitory neurons. Simple and complex cells, two classes of principal neurons in the primary visual cortex (V1), are generally thought to be equally selective for orientation. In mouse V1, we report that complex cells, identified by their overlapping on/off subfields, has significantly weaker orientation selectivity (OS) than simple cells. This can be primarily attributed to the differential tuning selectivity

  7. mTOR complexes differentially orchestrates eosinophil development in allergy.

    PubMed

    Zhu, Chen; Xia, Lixia; Li, Fei; Zhou, Lingren; Weng, Qingyu; Li, Zhouyang; Wu, Yinfang; Mao, Yuanyuan; Zhang, Chao; Wu, Yanping; Li, Miao; Ying, Songmin; Chen, Zhihua; Shen, Huahao; Li, Wen

    2018-05-02

    Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.

  8. Investigation of Different Constituent Encoders in a Turbo-code Scheme for Reduced Decoder Complexity

    NASA Technical Reports Server (NTRS)

    Kwatra, S. C.

    1998-01-01

    A large number of papers have been published attempting to give some analytical basis for the performance of Turbo-codes. It has been shown that performance improves with increased interleaver length. Also procedures have been given to pick the best constituent recursive systematic convolutional codes (RSCC's). However testing by computer simulation is still required to verify these results. This thesis begins by describing the encoding and decoding schemes used. Next simulation results on several memory 4 RSCC's are shown. It is found that the best BER performance at low E(sub b)/N(sub o) is not given by the RSCC's that were found using the analytic techniques given so far. Next the results are given from simulations using a smaller memory RSCC for one of the constituent encoders. Significant reduction in decoding complexity is obtained with minimal loss in performance. Simulation results are then given for a rate 1/3 Turbo-code with the result that this code performed as well as a rate 1/2 Turbo-code as measured by the distance from their respective Shannon limits. Finally the results of simulations where an inaccurate noise variance measurement was used are given. From this it was observed that Turbo-decoding is fairly stable with regard to noise variance measurement.

  9. Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation.

    PubMed

    Fukasawa, Rikiya; Iida, Satoshi; Tsutsui, Taiki; Hirose, Yutaka; Ohkuma, Yoshiaki

    2015-11-01

    The Mediator complex (Mediator) plays key roles in transcription and functions as the nexus for integration of various transcriptional signals. Previously, we screened for Mediator cyclin-dependent kinase (CDK)-interacting factors and identified three proteins related to chromatin regulation. One of them, SUZ12 is required for both stability and activity of Polycomb Repressive Complex 2 (PRC2). PRC2 primarily suppresses gene expression through histone H3 lysine 27 trimethylation, resulting in stem cell maintenance and differentiation; perturbation of this process leads to oncogenesis. Recent work showed that Mediator contributes to the embryonic stem cell state through DNA loop formation, which is strongly associated with chromatin architecture; however, it remains unclear how Mediator regulates gene expression in cooperation with chromatin regulators (i.e. writers, readers and remodelers). We found that Mediator CDKs interact directly with the PRC2 subunit EZH2, as well as SUZ12. Known PRC2 target genes were deregulated by Mediator CDK knockdown during neuronal differentiation, and both Mediator and PRC2 complexes co-occupied the promoters of developmental genes regulated by retinoic acid. Our results provide a mechanistic link between Mediator and PRC2 during neuronal differentiation. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  10. Prenatal Alcohol Exposure and Cellular Differentiation

    PubMed Central

    Veazey, Kylee J.; Muller, Daria; Golding, Michael C.

    2013-01-01

    Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell–cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell’s identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes—the Polycomb and Trithorax proteins—are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder. PMID:24313167

  11. Obesity and Metabolic Comorbidities: Environmental Diseases?

    PubMed Central

    Lubrano, Carla; Genovesi, Giuseppe; Specchia, Palma; Costantini, Daniela; Mariani, Stefania; Petrangeli, Elisa; Lenzi, Andrea; Gnessi, Lucio

    2013-01-01

    Obesity and metabolic comorbidities represent increasing health problems. Endocrine disrupting compounds (EDCs) are exogenous agents that change endocrine function and cause adverse health effects. Most EDCs are synthetic chemicals; some are natural food components as phytoestrogens. People are exposed to complex mixtures of chemicals throughout their lives. EDCs impact hormone-dependent metabolic systems and brain function. Laboratory and human studies provide compelling evidence that human chemical contamination can play a role in obesity epidemic. Chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes. EDCs can alter methylation patterns and normal epigenetic programming in cells. Oxidative stress may be induced by many of these chemicals, and accumulating evidence indicates that it plays important roles in the etiology of chronic diseases. The individual sensitivity to chemicals is variable, depending on environment and ability to metabolize hazardous chemicals. A number of genes, especially those representing antioxidant and detoxification pathways, have potential application as biomarkers of risk assessment. The potential health effects of combined exposures make the risk assessment process more complex compared to the assessment of single chemicals. Techniques and methods need to be further developed to fill data gaps and increase the knowledge on harmful exposure combinations. PMID:23577225

  12. Costs and benefits in item-method directed forgetting: differential effects of encoding and retrieval.

    PubMed

    Lee, Yuh-Shiow

    2013-01-01

    This study examined how encoding and retrieval factors affected directed forgetting costs and benefits in an item-method procedure. Experiment 1 used a typical item-method procedure and revealed a levels-of-processing effect in overall recall. However, the deep encoding condition showed a smaller directed forgetting effect than the shallow encoding conditions. More importantly, "remember" (R) words were selectively rehearsed as indicated by greater recall from the primacy portion of the list and more apt to be recalled before "forget" (F) words. Experiment 2 showed that a deep encoding operation reduced directed forgetting costs and that directed forgetting benefits occurred only when R words were recalled before F words. These findings supported the hypotheses that encoding manipulation affected directed forgetting costs and that directed forgetting benefits were associated with output order bias. Results were discussed in terms of mechanisms that produce item-method directed forgetting.

  13. A CU-Level Rate and Distortion Estimation Scheme for RDO of Hardware-Friendly HEVC Encoders Using Low-Complexity Integer DCTs.

    PubMed

    Lee, Bumshik; Kim, Munchurl

    2016-08-01

    In this paper, a low complexity coding unit (CU)-level rate and distortion estimation scheme is proposed for High Efficiency Video Coding (HEVC) hardware-friendly implementation where a Walsh-Hadamard transform (WHT)-based low-complexity integer discrete cosine transform (DCT) is employed for distortion estimation. Since HEVC adopts quadtree structures of coding blocks with hierarchical coding depths, it becomes more difficult to estimate accurate rate and distortion values without actually performing transform, quantization, inverse transform, de-quantization, and entropy coding. Furthermore, DCT for rate-distortion optimization (RDO) is computationally high, because it requires a number of multiplication and addition operations for various transform block sizes of 4-, 8-, 16-, and 32-orders and requires recursive computations to decide the optimal depths of CU or transform unit. Therefore, full RDO-based encoding is highly complex, especially for low-power implementation of HEVC encoders. In this paper, a rate and distortion estimation scheme is proposed in CU levels based on a low-complexity integer DCT that can be computed in terms of WHT whose coefficients are produced in prediction stages. For rate and distortion estimation in CU levels, two orthogonal matrices of 4×4 and 8×8 , which are applied to WHT that are newly designed in a butterfly structure only with addition and shift operations. By applying the integer DCT based on the WHT and newly designed transforms in each CU block, the texture rate can precisely be estimated after quantization using the number of non-zero quantized coefficients and the distortion can also be precisely estimated in transform domain without de-quantization and inverse transform required. In addition, a non-texture rate estimation is proposed by using a pseudoentropy code to obtain accurate total rate estimates. The proposed rate and the distortion estimation scheme can effectively be used for HW-friendly implementation of

  14. Is the encoding of Reward Prediction Error reliable during development?

    PubMed

    Keren, Hanna; Chen, Gang; Benson, Brenda; Ernst, Monique; Leibenluft, Ellen; Fox, Nathan A; Pine, Daniel S; Stringaris, Argyris

    2018-05-16

    Reward Prediction Errors (RPEs), defined as the difference between the expected and received outcomes, are integral to reinforcement learning models and play an important role in development and psychopathology. In humans, RPE encoding can be estimated using fMRI recordings, however, a basic measurement property of RPE signals, their test-retest reliability across different time scales, remains an open question. In this paper, we examine the 3-month and 3-year reliability of RPE encoding in youth (mean age at baseline = 10.6 ± 0.3 years), a period of developmental transitions in reward processing. We show that RPE encoding is differentially distributed between the positive values being encoded predominantly in the striatum and negative RPEs primarily encoded in the insula. The encoding of negative RPE values is highly reliable in the right insula, across both the long and the short time intervals. Insula reliability for RPE encoding is the most robust finding, while other regions, such as the striatum, are less consistent. Striatal reliability appeared significant as well once covarying for factors, which were possibly confounding the signal to noise ratio. By contrast, task activation during feedback in the striatum is highly reliable across both time intervals. These results demonstrate the valence-dependent differential encoding of RPE signals between the insula and striatum, and the consistency of RPE signals or lack thereof, during childhood and into adolescence. Characterizing the regions where the RPE signal in BOLD fMRI is a reliable marker is key for estimating reward-processing alterations in longitudinal designs, such as developmental or treatment studies. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Functional differentiation and spatial-temporal co-expression networks of the NBS-encoding gene family in Jilin ginseng, Panax ginseng C.A. Meyer.

    PubMed

    Yin, Rui; Zhao, Mingzhu; Wang, Kangyu; Lin, Yanping; Wang, Yanfang; Sun, Chunyu; Wang, Yi; Zhang, Meiping

    2017-01-01

    Ginseng, Panax ginseng C.A. Meyer, is one of the most important medicinal plants for human health and medicine. It has been documented that over 80% of genes conferring resistance to bacteria, viruses, fungi and nematodes are contributed by the nucleotide binding site (NBS)-encoding gene family. Therefore, identification and characterization of NBS genes expressed in ginseng are paramount to its genetic improvement and breeding. However, little is known about the NBS-encoding genes in ginseng. Here we report genome-wide identification and systems analysis of the NBS genes actively expressed in ginseng (PgNBS genes). Four hundred twelve PgNBS gene transcripts, derived from 284 gene models, were identified from the transcriptomes of 14 ginseng tissues. These genes were classified into eight types, including TNL, TN, CNL, CN, NL, N, RPW8-NL and RPW8-N. Seven conserved motifs were identified in both the Toll/interleukine-1 receptor (TIR) and coiled-coil (CC) typed genes whereas six were identified in the RPW8 typed genes. Phylogenetic analysis showed that the PgNBS gene family is an ancient family, with a vast majority of its genes originated before ginseng originated. In spite of their belonging to a family, the PgNBS genes have functionally dramatically differentiated and been categorized into numerous functional categories. The expressions of the across tissues, different aged roots and the roots of different genotypes. However, they are coordinating in expression, forming a single co-expression network. These results provide a deeper understanding of the origin, evolution and functional differentiation and expression dynamics of the NBS-encoding gene family in plants in general and in ginseng particularly, and a NBS gene toolkit useful for isolation and characterization of disease resistance genes and for enhanced disease resistance breeding in ginseng and related species.

  16. Functional differentiation and spatial-temporal co-expression networks of the NBS-encoding gene family in Jilin ginseng, Panax ginseng C.A. Meyer

    PubMed Central

    Wang, Kangyu; Lin, Yanping; Wang, Yanfang; Sun, Chunyu; Wang, Yi

    2017-01-01

    Ginseng, Panax ginseng C.A. Meyer, is one of the most important medicinal plants for human health and medicine. It has been documented that over 80% of genes conferring resistance to bacteria, viruses, fungi and nematodes are contributed by the nucleotide binding site (NBS)-encoding gene family. Therefore, identification and characterization of NBS genes expressed in ginseng are paramount to its genetic improvement and breeding. However, little is known about the NBS-encoding genes in ginseng. Here we report genome-wide identification and systems analysis of the NBS genes actively expressed in ginseng (PgNBS genes). Four hundred twelve PgNBS gene transcripts, derived from 284 gene models, were identified from the transcriptomes of 14 ginseng tissues. These genes were classified into eight types, including TNL, TN, CNL, CN, NL, N, RPW8-NL and RPW8-N. Seven conserved motifs were identified in both the Toll/interleukine-1 receptor (TIR) and coiled-coil (CC) typed genes whereas six were identified in the RPW8 typed genes. Phylogenetic analysis showed that the PgNBS gene family is an ancient family, with a vast majority of its genes originated before ginseng originated. In spite of their belonging to a family, the PgNBS genes have functionally dramatically differentiated and been categorized into numerous functional categories. The expressions of the across tissues, different aged roots and the roots of different genotypes. However, they are coordinating in expression, forming a single co-expression network. These results provide a deeper understanding of the origin, evolution and functional differentiation and expression dynamics of the NBS-encoding gene family in plants in general and in ginseng particularly, and a NBS gene toolkit useful for isolation and characterization of disease resistance genes and for enhanced disease resistance breeding in ginseng and related species. PMID:28727829

  17. The measured temperature and pressure of EDC37 detonation products

    NASA Astrophysics Data System (ADS)

    Ferguson, J. W.; Richley, J. C.; Sutton, B. D.; Price, E.; Ota, T. A.

    2017-01-01

    We present the experimentally determined temperature and pressure of the detonation products of EDC37; a HMX based conventional high explosive. These measurements were performed on a series of cylinder tests. The temperature measurements were undertaken at the end of the cylinder with optical fibres observing the bare explosive through a LiF window. The temperature of the products was measured for approximately 2 µs using single colour pyrometry, multicolour pyrometry and also using time integrated optical emission spectroscopy with the results from all three methods being broadly consistent. The peak temperature was found to be ≈ 3600 K dropping to ≈ 2400 K at the end of the measurement window. The spectroscopy was time integrated and showed that the emission spectra can be approximated using a grey body curve between 520 - 800 nm with no emission or absorption lines being observed. The pressure was obtained using an analytical method which requires the velocity of the expanding cylinder wall and the velocity of detonation. The pressure drops from an initial CJ value of ≈ 38 GPa to ≈ 4 GPa after 2 µs.

  18. Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation.

    PubMed

    Tarpey, Patrick S; Stevens, Claire; Teague, Jon; Edkins, Sarah; O'Meara, Sarah; Avis, Tim; Barthorpe, Syd; Buck, Gemma; Butler, Adam; Cole, Jennifer; Dicks, Ed; Gray, Kristian; Halliday, Kelly; Harrison, Rachel; Hills, Katy; Hinton, Jonathon; Jones, David; Menzies, Andrew; Mironenko, Tatiana; Perry, Janet; Raine, Keiran; Richardson, David; Shepherd, Rebecca; Small, Alexandra; Tofts, Calli; Varian, Jennifer; West, Sofie; Widaa, Sara; Yates, Andy; Catford, Rachael; Butler, Julia; Mallya, Uma; Moon, Jenny; Luo, Ying; Dorkins, Huw; Thompson, Deborah; Easton, Douglas F; Wooster, Richard; Bobrow, Martin; Carpenter, Nancy; Simensen, Richard J; Schwartz, Charles E; Stevenson, Roger E; Turner, Gillian; Partington, Michael; Gecz, Jozef; Stratton, Michael R; Futreal, P Andrew; Raymond, F Lucy

    2006-12-01

    In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found at the cytoplasmic face of coated vesicles located at the Golgi complex. The complex mediates the recruitment of clathrin to the vesicle membrane. Aberrant endocytic processing through disruption of adaptor protein complexes is likely to result from the AP1S2 mutations identified in the three XLMR-affected families, and such defects may plausibly cause abnormal synaptic development and function. AP1S2 is the first reported XLMR gene that encodes a protein directly involved in the assembly of endocytic vesicles.

  19. Competing risks and the development of adaptive management plans for water resources: Field reconnaissance investigation of risks to fishes and other aquatic biota exposed to endocrine disrupting chemicals (edcs) in lake mead, Nevada USA

    USGS Publications Warehouse

    Linder, G.; Little, E.E.

    2009-01-01

    The analysis and characterization of competing risks for water resources rely on a wide spectrum of tools to evaluate hazards and risks associated with their management. For example, waters of the lower Colorado River stored in reservoirs such as Lake Mead present a wide range of competing risks related to water quantity and water quality. These risks are often interdependent and complicated by competing uses of source waters for sustaining biological resources and for supporting a range of agricultural, municipal, recreational, and industrial uses. USGS is currently conducting a series of interdisciplinary case-studies on water quality of Lake Mead and its source waters. In this case-study we examine selected constituents potentially entering the Lake Mead system, particularly endocrine disrupting chemicals (EDCs). Worldwide, a number of environmental EDCs have been identified that affect reproduction, development, and adaptive behaviors in a wide range of organisms. Many EDCs are minimally affected by current treatment technologies and occur in treated sewage effluents. Several EDCs have been detected in Lake Mead, and several substances have been identified that are of concern because of potential impacts to the aquatic biota, including the sport fishery of Lake Mead and endangered razorback suckers (Xyrauchen texanus) that occur in the Colorado River system. For example, altered biomarkers relevant to reproduction and thyroid function in fishes have been observed and may be predictive of impaired metabolism and development. Few studies, however, have addressed whether such EDC-induced responses observed in the field have an ecologically significant effect on the reproductive success of fishes. To identify potential linkages between EDCs and species of management concern, the risk analysis and characterization in this reconnaissance study focused on effects (and attendant uncertainties) that might be expressed by exposed populations. In addition, risk reduction

  20. 6.0 K microarray reveals differential transcriptomic responses in the dinoflagellate Prorocentrum minimum exposed to polychlorinated biphenyl (PCB).

    PubMed

    Wang, Hui; Guo, Ruoyu; Ki, Jang-Seu

    2018-03-01

    Endocrine disrupting chemicals (EDCs) have toxic effects on algae; however, their molecular genomic responses have not been sufficiently elucidated. Here, we evaluated genome-scaled responses of the dinoflagellate alga Prorocentrum minimum exposed to an EDC, polychlorinated biphenyl (PCB), using a 6.0 K microarray. Based on two-fold change cut-off, we identified that 609 genes (∼10.2%) responded to the PCB treatment. KEGG pathway analysis showed that differentially expressed genes (DEGs) were related to ribosomes, biosynthesis of amino acids, spliceosomes, and cellular processes. Many DEGs were involved in cell cycle progression, apoptosis, signal transduction, ion binding, and cellular transportation. In contrast, only a few genes related to photosynthesis and oxidative stress were expressed in response to PCB exposure. This was supported by that fact that there were no obvious changes in the photosynthetic efficiency and reactive oxygen species (ROS) production. These results suggest that PCB might not cause chloroplast and oxidative damage, but could lead to cell cycle arrest and apoptosis. In addition, various signal transduction and transport pathways might be disrupted in the cells, which could further contribute to cell death. These results expand the genomic understanding of the effects of EDCs on this dinoflagellate protist. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Charlotte - EDC Evaluation and Demonstration (CEED) Human-in-the-Loop Results Briefing to ATD-2 FAA Partners

    NASA Technical Reports Server (NTRS)

    Chevalley, Eric

    2016-01-01

    The Charlotte EDC Evaluation and Demonstration (CEED) was the first Human-In-The-Loop experiment under the Air Traffic Management Technology Demonstration-2 (ATD-2) project. The purpose of the study was fourfold: 1) to establish a simulation environment (Charlotte) for airspace operations for ATD-2 technology, 2) to simulate current-day departures and arrival operations, 3) to assess the impact of current Traffic Management Initiatives (TMI) on Charlotte (CLT) departure flows and en route operations in Washington (ZDC) and Atlanta Centers (ZTL), and 4) to assess the impact of departure takeoff time compliance on airspace operations. The experimental design compared 3 TMIs and 2 compliance levels. Fourteen FAA retired controllers participated in the simulation. In addition, two Traffic Management Coordinators from ZTL and ZDC managed traffic flows. Surface and airborne delays, control efficiency, throughput, realism, workload, and acceptability were assessed and will be compared across the experimental conditions. Participants rated the simulation as very realistic. Results indicate that different TMIs have different impacts on surface and airspace delay. Departure compliance indicates partial benefits to sector complexity and controller workload. This simulation will provide an initial assessment of the tactical scheduling problems that the ATD-2 technology will address in the near term.

  2. Dissecting the Calcium-Induced Differentiation of Human Primary Keratinocytes Stem Cells by Integrative and Structural Network Analyses

    PubMed Central

    Toufighi, Kiana; Yang, Jae-Seong; Luis, Nuno Miguel; Aznar Benitah, Salvador; Lehner, Ben; Serrano, Luis; Kiel, Christina

    2015-01-01

    The molecular details underlying the time-dependent assembly of protein complexes in cellular networks, such as those that occur during differentiation, are largely unexplored. Focusing on the calcium-induced differentiation of primary human keratinocytes as a model system for a major cellular reorganization process, we look at the expression of genes whose products are involved in manually-annotated protein complexes. Clustering analyses revealed only moderate co-expression of functionally related proteins during differentiation. However, when we looked at protein complexes, we found that the majority (55%) are composed of non-dynamic and dynamic gene products (‘di-chromatic’), 19% are non-dynamic, and 26% only dynamic. Considering three-dimensional protein structures to predict steric interactions, we found that proteins encoded by dynamic genes frequently interact with a common non-dynamic protein in a mutually exclusive fashion. This suggests that during differentiation, complex assemblies may also change through variation in the abundance of proteins that compete for binding to common proteins as found in some cases for paralogous proteins. Considering the example of the TNF-α/NFκB signaling complex, we suggest that the same core complex can guide signals into diverse context-specific outputs by addition of time specific expressed subunits, while keeping other cellular functions constant. Thus, our analysis provides evidence that complex assembly with stable core components and competition could contribute to cell differentiation. PMID:25946651

  3. Gametophyte differentiation and imprinting control in plants: Crosstalk between RBR and chromatin.

    PubMed

    Johnston, Amal J; Gruissem, Wilhelm

    2009-01-01

    The Retinoblastoma (pRb) pathway has been implicated as a convergent regulatory unit in the control of cell cycle and disease. We have shown that a crosstalk between RETINOBLASTOMA RELATED (RBR), the Arabidopsis homologue of pRb, and the genes encoding proteins of the chromatin complexes involved in DNA or histone methylation, controls gametophytic and post-fertilization differentiation events and a subset of imprinting effects. We describe here a plausible model that incorporates several components of the plant Retinoblastoma pathway, thus offering a novel paradigm that merges the traditional cell cycle and the chromatin components in the control of cell differentiation and imprinting.

  4. IQCJ-SCHIP1, a novel fusion transcript encoding a calmodulin-binding IQ motif protein

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

    Kwasnicka-Crawford, Dorota A.; Carson, Andrew R.; Scherer, Stephen W.

    The existence of transcripts that span two adjacent, independent genes is considered rare in the human genome. This study characterizes a novel human fusion gene named IQCJ-SCHIP1. IQCJ-SCHIP1 is the longest isoform of a complex transcriptional unit that bridges two separate genes that encode distinct proteins, IQCJ, a novel IQ motif containing protein and SCHIP1, a schwannomin interacting protein that has been previously shown to interact with the Neurofibromatosis type 2 (NF2) protein. IQCJ-SCHIP1 is located on the chromosome 3q25 and comprises a 1692-bp transcript encompassing 11 exons spanning 828 kb of the genomic DNA. We show that IQCJ-SCHIP1 mRNAmore » is highly expressed in the brain. Protein encoded by the IQCJ-SCHIP1 gene was localized to cytoplasm and actin-rich regions and in differentiated PC12 cells was also seen in neurite extensions.« less

  5. The feature-weighted receptive field: an interpretable encoding model for complex feature spaces.

    PubMed

    St-Yves, Ghislain; Naselaris, Thomas

    2017-06-20

    We introduce the feature-weighted receptive field (fwRF), an encoding model designed to balance expressiveness, interpretability and scalability. The fwRF is organized around the notion of a feature map-a transformation of visual stimuli into visual features that preserves the topology of visual space (but not necessarily the native resolution of the stimulus). The key assumption of the fwRF model is that activity in each voxel encodes variation in a spatially localized region across multiple feature maps. This region is fixed for all feature maps; however, the contribution of each feature map to voxel activity is weighted. Thus, the model has two separable sets of parameters: "where" parameters that characterize the location and extent of pooling over visual features, and "what" parameters that characterize tuning to visual features. The "where" parameters are analogous to classical receptive fields, while "what" parameters are analogous to classical tuning functions. By treating these as separable parameters, the fwRF model complexity is independent of the resolution of the underlying feature maps. This makes it possible to estimate models with thousands of high-resolution feature maps from relatively small amounts of data. Once a fwRF model has been estimated from data, spatial pooling and feature tuning can be read-off directly with no (or very little) additional post-processing or in-silico experimentation. We describe an optimization algorithm for estimating fwRF models from data acquired during standard visual neuroimaging experiments. We then demonstrate the model's application to two distinct sets of features: Gabor wavelets and features supplied by a deep convolutional neural network. We show that when Gabor feature maps are used, the fwRF model recovers receptive fields and spatial frequency tuning functions consistent with known organizational principles of the visual cortex. We also show that a fwRF model can be used to regress entire deep

  6. A strategy for isolation of cDNAs encoding proteins affecting human intestinal epithelial cell growth and differentiation: characterization of a novel gut-specific N-myristoylated annexin.

    PubMed

    Wice, B M; Gordon, J I

    1992-01-01

    The human intestinal epithelium is rapidly and perpetually renewed as the descendants of multipotent stem cells located in crypts undergo proliferation, differentiation, and eventual exfoliation during a very well organized migration along the crypt to villus axis. The mechanisms that establish and maintain this balance between proliferation and differentiation are largely unknown. We have utilized HT-29 cells, derived from a human colon adenocarcinoma, as a model system for identifying gene products that may regulate these processes. Proliferating HT-29 cells cultured in the absence of glucose (e.g., using inosine as the carbon source) have some of the characteristics of undifferentiated but committed crypt epithelial cells while postconfluent cells cultured in the absence of glucose resemble terminally differentiated enterocytes or goblet cells. A cDNA library, constructed from exponentially growing HT-29 cells maintained in inosine-containing media, was sequentially screened with a series of probes depleted of sequences encoding housekeeping functions and enriched for intestine-specific sequences that are expressed in proliferating committed, but not differentiated, epithelial cells. Of 100,000 recombinant phage surveyed, one was found whose cDNA was derived from an apparently gut-specific mRNA. It encodes a 316 residue, 35,463-D protein that is a new member of the annexin/lipocortin family. Other family members have been implicated in regulation of cellular growth and in signal transduction pathways. RNA blot and in situ hybridization studies indicate that the gene encoding this new annexin exhibits region-specific expression along both axes of the human gut: (a) highest levels of mRNA are present in the jejunum with marked and progressive reductions occurring distally; (b) its mRNA appears in crypt-associated epithelial cells and increases in concentration as they exit the crypt. Villus-associated epithelial cells continue to transcribe this gene during their

  7. Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination.

    PubMed

    Wu, Lai Man Natalie; Wang, Jincheng; Conidi, Andrea; Zhao, Chuntao; Wang, Haibo; Ford, Zachary; Zhang, Liguo; Zweier, Christiane; Ayee, Brian G; Maurel, Patrice; Zwijsen, An; Chan, Jonah R; Jankowski, Michael P; Huylebroeck, Danny; Lu, Q Richard

    2016-08-01

    The mechanisms that coordinate and balance a complex network of opposing regulators to control Schwann cell (SC) differentiation remain elusive. Here we demonstrate that zinc-finger E-box-binding homeobox 2 (Zeb2, also called Sip1) transcription factor is a critical intrinsic timer that controls the onset of SC differentiation by recruiting histone deacetylases HDAC 1 and 2 (HDAC1/2) and nucleosome remodeling and deacetylase complex (NuRD) co-repressor complexes in mice. Zeb2 deletion arrests SCs at an undifferentiated state during peripheral nerve development and inhibits remyelination after injury. Zeb2 antagonizes inhibitory effectors including Notch and Sox2. Importantly, genome-wide transcriptome analysis reveals a Zeb2 target gene encoding the Notch effector Hey2 as a potent inhibitor for Schwann cell differentiation. Strikingly, a genetic Zeb2 variant associated with Mowat-Wilson syndrome disrupts the interaction with HDAC1/2-NuRD and abolishes Zeb2 activity for SC differentiation. Therefore, Zeb2 controls SC maturation by recruiting HDAC1/2-NuRD complexes and inhibiting a Notch-Hey2 signaling axis, pointing to the critical role of HDAC1/2-NuRD activity in peripheral neuropathies caused by ZEB2 mutations.

  8. Value Differentiation in Adolescence: The Role of Age and Cultural Complexity

    ERIC Educational Resources Information Center

    Daniel, Ella; Schiefer, David; Mollering, Anna; Benish-Weisman, Maya; Boehnke, Klaus; Knafo, Ariel

    2012-01-01

    Living in complex social worlds, individuals encounter discordant values across life contexts, potentially resulting in different importance of values across contexts. Value differentiation is defined here as the degree to which values receive different importance depending on the context in which they are considered. Early and mid-adolescents (N…

  9. Identification and Differential Abundance of Mitochondrial Genome Encoding Small RNAs (mitosRNA) in Breast Muscles of Modern Broilers and Unselected Chicken Breed

    PubMed Central

    Bottje, Walter G.; Khatri, Bhuwan; Shouse, Stephanie A.; Seo, Dongwon; Mallmann, Barbara; Orlowski, Sara K.; Pan, Jeonghoon; Kong, Seongbae; Owens, Casey M.; Anthony, Nicholas B.; Kim, Jae K.; Kong, Byungwhi C.

    2017-01-01

    Background: Although small non-coding RNAs are mostly encoded by the nuclear genome, thousands of small non-coding RNAs encoded by the mitochondrial genome, termed as mitosRNAs were recently reported in human, mouse and trout. In this study, we first identified chicken mitosRNAs in breast muscle using small RNA sequencing method and the differential abundance was analyzed between modern pedigree male (PeM) broilers (characterized by rapid growth and large muscle mass) and the foundational Barred Plymouth Rock (BPR) chickens (characterized by slow growth and small muscle mass). Methods: Small RNA sequencing was performed with total RNAs extracted from breast muscles of PeM and BPR (n = 6 per group) using the 1 × 50 bp single end read method of Illumina sequencing. Raw reads were processed by quality assessment, adapter trimming, and alignment to the chicken mitochondrial genome (GenBank Accession: X52392.1) using the NGen program. Further statistical analyses were performed using the JMP Genomics 8. Differentially expressed (DE) mitosRNAs between PeM and BPR were confirmed by quantitative PCR. Results: Totals of 183,416 unique small RNA sequences were identified as potential chicken mitosRNAs. After stringent filtering processes, 117 mitosRNAs showing >100 raw read counts were abundantly produced from all 37 mitochondrial genes (except D-loop region) and the length of mitosRNAs ranged from 22 to 46 nucleotides. Of those, abundance of 44 mitosRNAs were significantly altered in breast muscles of PeM compared to those of BPR: all mitosRNAs were higher in PeM breast except those produced from 16S-rRNA gene. Possibly, the higher mitosRNAs abundance in PeM breast may be due to a higher mitochondrial content compared to BPR. Our data demonstrate that in addition to 37 known mitochondrial genes, the mitochondrial genome also encodes abundant mitosRNAs, that may play an important regulatory role in muscle growth via mitochondrial gene expression control. PMID:29104541

  10. Encoding vs. retention: differential effects of cue manipulation on working memory performance in schizophrenia.

    PubMed

    Javitt, Daniel C; Rabinowicz, Esther; Silipo, Gail; Dias, Elisa C

    2007-03-01

    Deficits in working memory performance are among the most widely replicated findings in schizophrenia. Roles of encoding vs. memory retention in working memory remain unresolved. The present study evaluated working memory performance in schizophrenia using an AX-type continuous performance test (AX-CPT) paradigm. Participants included 48 subjects with schizophrenia and 27 comparison subjects. Behavior was obtained in 3 versions of the task, which differed based upon ease of cue interoperability. In a simple cue version of the task, cue letters were replaced with red or green circles. In the complex cue version, letter/color conjunctions served as cues. In the base version of the task, patients showed increased rates of false alarms to invalidly cued targets, similar to prior reports. However, when the cue stimuli were replaced with green or red circles to ease interpretation, patients showed similar false alarm rates to controls. When feature conjunction cues were used, patients were also disproportionately affected relative to controls. No significant group by interstimulus interval interaction effects were observed in either the simple or complex cue conditions, suggesting normal retention of information even in the presence of overall performance decrements. These findings suggest first, that cue manipulation disproportionately affects AX-CPT performance in schizophrenia and, second, that substantial behavioral deficits may be observed on working memory tasks even in the absence of disturbances in mnemonic retention.

  11. Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells

    PubMed Central

    Pomeroy, Jordan E.; Nguyen, Hung X.; Hoffman, Brenton D.; Bursac, Nenad

    2017-01-01

    Our knowledge of pluripotent stem cell biology has advanced considerably in the past four decades, but it has yet to deliver on the great promise of regenerative medicine. The slow progress can be mainly attributed to our incomplete understanding of the complex biologic processes regulating the dynamic developmental pathways from pluripotency to fully-differentiated states of functional somatic cells. Much of the difficulty arises from our lack of specific tools to query, or manipulate, the molecular scale circuitry on both single-cell and organismal levels. Fortunately, the last two decades of progress in the field of optogenetics have produced a variety of genetically encoded, light-mediated tools that enable visualization and control of the spatiotemporal regulation of cellular function. The merging of optogenetics and pluripotent stem cell biology could thus be an important step toward realization of the clinical potential of pluripotent stem cells. In this review, we have surveyed available genetically encoded photoactuators and photosensors, a rapidly expanding toolbox, with particular attention to those with utility for studying pluripotent stem cells. PMID:28912894

  12. A novel encoding Lempel-Ziv complexity algorithm for quantifying the irregularity of physiological time series.

    PubMed

    Zhang, Yatao; Wei, Shoushui; Liu, Hai; Zhao, Lina; Liu, Chengyu

    2016-09-01

    The Lempel-Ziv (LZ) complexity and its variants have been extensively used to analyze the irregularity of physiological time series. To date, these measures cannot explicitly discern between the irregularity and the chaotic characteristics of physiological time series. Our study compared the performance of an encoding LZ (ELZ) complexity algorithm, a novel variant of the LZ complexity algorithm, with those of the classic LZ (CLZ) and multistate LZ (MLZ) complexity algorithms. Simulation experiments on Gaussian noise, logistic chaotic, and periodic time series showed that only the ELZ algorithm monotonically declined with the reduction in irregularity in time series, whereas the CLZ and MLZ approaches yielded overlapped values for chaotic time series and time series mixed with Gaussian noise, demonstrating the accuracy of the proposed ELZ algorithm in capturing the irregularity, rather than the complexity, of physiological time series. In addition, the effect of sequence length on the ELZ algorithm was more stable compared with those on CLZ and MLZ, especially when the sequence length was longer than 300. A sensitivity analysis for all three LZ algorithms revealed that both the MLZ and the ELZ algorithms could respond to the change in time sequences, whereas the CLZ approach could not. Cardiac interbeat (RR) interval time series from the MIT-BIH database were also evaluated, and the results showed that the ELZ algorithm could accurately measure the inherent irregularity of the RR interval time series, as indicated by lower LZ values yielded from a congestive heart failure group versus those yielded from a normal sinus rhythm group (p < 0.01). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Efficient biprediction decision scheme for fast high efficiency video coding encoding

    NASA Astrophysics Data System (ADS)

    Park, Sang-hyo; Lee, Seung-ho; Jang, Euee S.; Jun, Dongsan; Kang, Jung-Won

    2016-11-01

    An efficient biprediction decision scheme of high efficiency video coding (HEVC) is proposed for fast-encoding applications. For low-delay video applications, bidirectional prediction can be used to increase compression performance efficiently with previous reference frames. However, at the same time, the computational complexity of the HEVC encoder is significantly increased due to the additional biprediction search. Although a some research has attempted to reduce this complexity, whether the prediction is strongly related to both motion complexity and prediction modes in a coding unit has not yet been investigated. A method that avoids most compression-inefficient search points is proposed so that the computational complexity of the motion estimation process can be dramatically decreased. To determine if biprediction is critical, the proposed method exploits the stochastic correlation of the context of prediction units (PUs): the direction of a PU and the accuracy of a motion vector. Through experimental results, the proposed method showed that the time complexity of biprediction can be reduced to 30% on average, outperforming existing methods in view of encoding time, number of function calls, and memory access.

  14. The Effects of Differential Goal Weights on the Performance of a Complex Financial Task.

    ERIC Educational Resources Information Center

    Edmister, Robert O.; Locke, Edwin A.

    1987-01-01

    Determined whether people could obtain outcomes on a complex task that would be in line with differential goal weights corresponding to different aspects of the task. Bank lending officers were run through lender-simulation exercises. Five performance goals were weighted. Demonstrated effectiveness of goal setting with complex tasks, using group…

  15. Disentangling the Trichoderma viridescens complex.

    PubMed

    Jaklitsch, W M; Samuels, G J; Ismaiel, A; Voglmayr, H

    2013-12-01

    Trichoderma viridescens is recognised as a species complex. Multigene analyses based on the translation elongation factor 1-alpha encoding gene (tef1), a part of the rpb2 gene, encoding the second largest RNA polymerase subunit and the larger subunit of ATP citrate lyase (acl1) reveals 13 phylogenetic species with little or no phenotypic differentiation. This is the first use of acl1 in Trichoderma phylogenetics. The typification of T. viridescens s.str. is clarified and Hypocrea viridescens is replaced by the new name T. paraviridescens. Besides these two species, eleven are phylogenetically recognised and T. olivascens, T. viridarium, T. virilente, T. trixiae, T. viridialbum, T. appalachiense, T. neosinense, T. composticola, T. nothescens and T. sempervirentis are formally described and illustrated. Several species produce yellow diffusing pigment on cornmeal dextrose agar, particularly after storage at 15 °C, while T. olivascens is characterised by the formation of an olivaceous pigment. The results are compared with earlier publications on this group of species.

  16. Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) in stormwater canals and Bayou St. John in New Orleans, Louisiana, USA.

    PubMed

    Boyd, Glen R; Palmeri, Jordan M; Zhang, Shaoyuan; Grimm, Deborah A

    2004-10-15

    Samples were collected from two stormwater canals and a recreational urban waterway known as Bayou St. John in New Orleans, Louisiana, USA and analyzed for a range of pharmaceuticals and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs). Concentrations of 7 PPCPs and EDCs were measured by a method that provides for simultaneous extraction and quantification of the following compounds: clofibric acid, naproxen, ibuprofen, fluoxetine, clorophene, triclosan, bisphenol A. The method also was used as an indicator of the occurrence of estrogenic compounds by targeting estrone and 17beta-estradiol. The two canals (Orleans and London) are used to drain a portion of the city's stormwater directly into the Mississippi River or Lake Pontchartrain. Bayou St. John is located between the two canals and supplied with water from Lake Pontchartrain. Results from the 6-month sampling period indicated the following concentration ranges for the two stormwater canals: naproxen (ND - 145 ng/l), ibuprofen (ND - 674 ng/l), triclosan (ND - 29 ng/l) and bisphenol A (1.9-158 ng/l). Concentrations of these target analytes increased with cumulative rainfall. For bayou waters, only naproxen (2.1-4.8 ng/l) and bisphenol A (0.9-44 ng/l) were detected. Estrone was detected but determined non-quantifiable for multiple sampling events at the 3 sites. None of the other target analytes (clofibric acid, fluoxetine, clorophene, and 17beta-estradiol) were detected above their method detection levels. Results of this study demonstrate the occurrence of PPCPs and EDCs in New Orleans stormwater canals and Bayou St. John. Results also demonstrate the use of this analytical technique as an indicator of non-point source sewage contamination in New Orleans stormwater canals.

  17. DNA–PKcs–SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation

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

    Xu, Yong; Fang, Shi-ji; Zhu, Li-juan

    Highlights: • LDI increases ALP activity, promotes type I collagen (Col I)/Runx2 mRNA expression. • LDI induces DNA–PKcs activation, which is required for osteoblast differentiation. • Akt activation mediates LDI-induced ALP activity and Col I/Runx2 mRNA increase. • DNA–PKcs–SIN1 complexation mediates LDI-induced Akt Ser-473 phosphorylation. • DNA–PKcs–SIN1 complexation is important for osteoblast differentiation. - Abstract: Low-dose irradiation (LDI) induces osteoblast differentiation, however the underlying mechanisms are not fully understood. In this study, we explored the potential role of DNA-dependent protein kinase catalytic subunit (DNA–PKcs)–Akt signaling in LDI-induced osteoblast differentiation. We confirmed that LDI promoted mouse calvarial osteoblast differentiation, which wasmore » detected by increased alkaline phosphatase (ALP) activity as well as mRNA expression of type I collagen (Col I) and runt-related transcription factor 2 (Runx2). In mouse osteoblasts, LDI (1 Gy) induced phosphorylation of DNA–PKcs and Akt (mainly at Ser-473). The kinase inhibitors against DNA–PKcs (NU-7026 and NU-7441) or Akt (LY294002, perifosine and MK-2206), as well as partial depletion of DNA–PKcs or Akt1 by targeted-shRNA, dramatically inhibited LDI-induced Akt activation and mouse osteoblast differentiation. Further, siRNA-knockdown of SIN1, a key component of mTOR complex 2 (mTORC2), also inhibited LDI-induced Akt Ser-473 phosphorylation as well as ALP activity increase and Col I/Runx2 expression in mouse osteoblasts. Co-immunoprecipitation (Co-IP) assay results demonstrated that LDI-induced DNA–PKcs–SIN1 complexation, which was inhibited by NU-7441 or SIN1 siRNA-knockdown in mouse osteoblasts. In summary, our data suggest that DNA–PKcs–SIN1 complexation-mediated Akt activation (Ser-473 phosphorylation) is required for mouse osteoblast differentiation.« less

  18. USING 1H-NMR METABOLOMICS TO CHARACTERIZE ALTERED METABOLIC PROFILES IN ZEBRAFISH (DANIO RERIO) EXPOSED TO THE MODEL EDCS 17 ALPHA-ETHINYLESTRADIOL (EE2) AND FADROZOLE

    EPA Science Inventory

    Elevated levels of endocrine-disrupting chemicals (EDCs) have been reported in waterways worldwide and have been shown to affect numerous aspects of development, behavior, reproduction, and survival in various fish species. We have examined the effects of the synthetic steroid 17...

  19. Androgen Receptor Involvement in Rat Amelogenesis: An Additional Way for Endocrine-Disrupting Chemicals to Affect Enamel Synthesis.

    PubMed

    Jedeon, Katia; Loiodice, Sophia; Salhi, Khaled; Le Normand, Manon; Houari, Sophia; Chaloyard, Jessica; Berdal, Ariane; Babajko, Sylvie

    2016-11-01

    Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-α, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERβ remained undetectable. AR was the only receptor selectively expressed in ameloblasts involved in final enamel mineralization. AR nuclear translocation and induction of androgen-responsive element-containing promoter activity upon T treatment, demonstrated ameloblast responsiveness to androgens. T regulated the expression of genes involved in enamel mineralization such as KLK4, amelotin, SLC26A4, and SLC5A8 but not the expression of genes encoding matrix proteins, which determine enamel thickness. Vinclozolin and to a lesser extent bisphenol A, two antiandrogenic EDCs that cause enamel defects, counteracted the actions of T. In conclusion, we show, for the first time, the following: 1) ameloblasts express AR; 2) the androgen signaling pathway is involved in the enamel mineralization process; and 3) EDCs with antiandrogenic effects inhibit AR activity and preferentially affect amelogenesis in male rats. Their action, through the AR pathway, may specifically and irreversibly affect enamel, potentially leading to the use of dental defects as a biomarker of exposure to environmental pollutants. These results are consistent with the steroid hormones affecting ameloblasts, raising the issue of the hormonal influence on amelogenesis and possible sexual dimorphism in enamel quality.

  20. The decoy Fcγ receptor encoded by the cytomegalovirus UL119-UL118 gene has differential affinity to IgG proteins expressing different GM allotypes.

    PubMed

    Pandey, Janardan P; Namboodiri, Aryan M; Radwan, Faisal F; Nietert, Paul J

    2015-08-01

    Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been implicated in many diseases. However, there is significant divergence between HCMV seroprevalence and the prevalence of HCMV-associated diseases, implying the presence of host genetic factors that might modulate immunity to this virus. HCMV deploys many sophisticated strategies to evade host immunosurveillance. One strategy involves encoding for proteins that have functional properties of the Fcγ receptor (FcγR). The aim of the present investigation was to determine whether the UL119-UL118-encoded recombinant FcγR ectodomain binds differentially to genetically disparate IgG1 proteins. Results show that mean absorbance values for binding of HCMV UL119-UL118-encoded Fcγ receptor to the immunoglobulin GM (γ marker) 1,17-expressing IgG1 were significantly higher than to the IgG1 expressing the allelic GM 3 allotype (0.225 vs. 0.151; p=0.039). These findings suggest possible mechanisms underlying the maintenance of immunoglobulin GM gene polymorphism and its putative role in the etiology of HCMV-associated diseases. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. Cloning, sequencing and expression in MEL cells of a cDNA encoding the mouse ribosomal protein S5.

    PubMed

    Vanegas, N; Castañeda, V; Santamaría, D; Hernández, P; Schvartzman, J B; Krimer, D B

    1997-06-05

    We describe the isolation and characterization of a cDNA encoding the mouse S5 ribosomal protein. It was isolated from a MEL (murine erythroleukemia) cell cDNA library by differential hybridization as a down regulated sequence during HMBA-induced differentiation. Northern series analysis showed that S5 mRNA expression is reduced 5-fold throughout the differentiation process. The mouse S5 mRNA is 760 bp long and encodes for a 204 amino acid protein with 94% homology with the human and rat S5.

  2. The Chlamydomonas Dhc1 gene encodes a dynein heavy chain subunit required for assembly of the I1 inner arm complex.

    PubMed Central

    Myster, S H; Knott, J A; O'Toole, E; Porter, M E

    1997-01-01

    Multiple members of the dynein heavy chain (Dhc) gene family have been recovered in several organisms, but the relationships between these sequences and the Dhc isoforms that they encode are largely unknown. To identify Dhc loci and determine the specific functions of the individual Dhc isoforms, we have screened a collection of motility mutants generated by insertional mutagenesis in Chlamydomonas. In this report, we characterize one strain, pf9-3, in which the insertion event was accompanied by a deletion of approximately 13 kb of genomic DNA within the transcription unit of the Dhc1 gene. Northern blot analysis confirms that pf9-3 is a null mutation. Biochemical and structural studies of isolated axonemes demonstrate that the pf9-3 mutant fails to assemble the I1 inner arm complex, a two-headed dynein isoform composed of two Dhcs (1 alpha and 1 beta) and three intermediate chains. To determine if the Dhc1 gene product corresponds to one of the Dhcs of the I1 complex, antibodies were generated against a Dhc1-specific peptide sequence. Immunoblot analysis reveals that the Dhc1 gene encodes the 1 alpha Dhc subunit. These studies thus, identify the first inner arm Dhc locus to be described in any organism and further demonstrate that the 1 alpha Dhc subunit plays an essential role in the assembly of the I1 inner arm complex. Images PMID:9247642

  3. Cloning and characterization of Sdga gene encoding alpha-subunit of heterotrimeric guanosine 5'-triphosphate-binding protein complex in Scoparia dulcis.

    PubMed

    Shite, Masato; Yamamura, Yoshimi; Hayashi, Toshimitsu; Kurosaki, Fumiya

    2008-11-01

    A homology-based cloning strategy yielded Sdga, a cDNA clone presumably encoding alpha-subunit of heterotrimeric guanosine 5'-triphosphate-binding protein complex, from leaf tissues of Scoparia dulcis. Phylogenetic tree analysis of G-protein alpha-subunits from various biological sources suggested that, unlike in animal cells, classification of Galpha-proteins into specific subfamilies could not be applicable to the proteins from higher plants. Restriction digests of genomic DNA of S. dulcis showed a single hybridized signal in Southern blot analysis, suggesting that Sdga is a sole gene encoding Galpha-subunit in this plant. The expression level of Sdga appeared to be maintained at almost constant level after exposure of the leaves to methyl jasmonate as analyzed by reverse-transcription polymerase chain reaction. These results suggest that Sdga plays roles in methyl jasmonate-induced responses of S. dulcis without a notable change in the transcriptional level.

  4. Encoding and choice in the task span paradigm.

    PubMed

    Reiman, Kaitlin M; Weaver, Starla M; Arrington, Catherine M

    2015-03-01

    Cognitive control during sequences of planned behaviors requires both plan-level processes such as generating, maintaining, and monitoring the plan, as well as task-level processes such as selecting, establishing and implementing specific task sets. The task span paradigm (Logan in J Exp Psychol Gen 133:218-236, 2004) combines two common cognitive control paradigms, task switching and working memory span, to investigate the integration of plan-level and task-level processes during control of sequential behavior. The current study expands past task span research to include measures of encoding processes and choice behavior with volitional sequence generation, using the standard task span as well as a novel voluntary task span paradigm. In two experiments, we consider how sequence complexity, defined separately for plan-level and task-level complexity, influences sequence encoding (Experiment 1), sequence choice (Experiment 2), sequence memory, and task performance of planned sequences of action. Results indicate that participants were sensitive to sequence complexity, but that different aspects of behavior are most strongly influenced by different types of complexity. Hierarchical complexity at the plan level best predicts voluntary sequence generation and memory; while switch frequency at the task level best predicts encoding of externally defined sequences and task performance. Furthermore, performance RTs were similar for externally and internally defined plans, whereas memory was improved for internally defined sequences. Finally, participants demonstrated a significant sequence choice bias in the voluntary task span. Consistent with past research on choice behavior, volitional selection of plans was markedly influenced by both the ease of memory and performance.

  5. Saccharomyces cerevisiae ribosomal protein L37 is encoded by duplicate genes that are differentially expressed.

    PubMed

    Tornow, J; Santangelo, G M

    1994-06-01

    A duplicate copy of the RPL37A gene (encoding ribosomal protein L37) was cloned and sequenced. The coding region of RPL37B is very similar to that of RPL37A, with only one conservative amino-acid difference. However, the intron and flanking sequences of the two genes are extremely dissimilar. Disruption experiments indicate that the two loci are not functionally equivalent: disruption of RPL37B was insignificant, but disruption of RPL37A severely impaired the growth rate of the cell. When both RPL37 loci are disrupted, the cell is unable to grow at all, indicating that rpL37 is an essential protein. The functional disparity between the two RPL37 loci could be explained by differential gene expression. The results of two experiments support this idea: gene fusion of RPL37A to a reporter gene resulted in six-fold higher mRNA levels than was generated by the same reporter gene fused to RPL37B, and a modest increase in gene dosage of RPL37B overcame the lack of a functional RPL37A gene.

  6. Epigenetic impacts of endocrine disruptors in the brain☆

    PubMed Central

    Walker, Deena M.; Gore, Andrea C.

    2017-01-01

    The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner. PMID:27663243

  7. Effects of TCDD on the Expression of Nuclear Encoded Mitochondrial Genes

    PubMed Central

    Forgacs, Agnes L.; Burgoon, Lyle D.; Lynn, Scott G.; LaPres, John J.; Zacharewski, Timothy

    2014-01-01

    Generation of mitochondrial reactive oxygen species (ROS) can be perturbed following exposure to environmental chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Reports indicate that the aryl hydrocarbon receptor (AhR) mediates TCDD-induced sustained hepatic oxidative stress by decreasing hepatic ATP levels and through hyperpolarization of the inner mitochondrial membrane. To further elucidate the effects of TCDD on the mitochondria, high-throughput quantitative real-time PCR (HTP-QRTPCR) was used to evaluate the expression of 90 genes encoding mitochondrial proteins involved in electron transport, oxidative phosphorylation, uncoupling, and associated chaperones. HTP-QRTPCR analysis of time course (30 μg/kg TCDD at 2, 4, 8, 12, 18, 24, 72, and 168 hrs) liver samples obtained from orally gavaged immature, ovariectomized C57BL/6 mice identified 54 differentially expressed genes (|fold change|>1.5 and P-value <0.1). Of these, 8 exhibited a dose response (0.03 to 300 μg/kg TCDD) at 4, 24 or 72 hrs. Dose responsive genes encoded proteins associated with electron transport chain (ETC) complex I (NADH dehydrogenase), III (cytochrome c reductase), IV (cytochrome c oxidase), and V (ATP synthase) and could be generally categorized as having proton gradient, ATP synthesis, and chaperone activities. In contrast, transcript levels of ETC complex II, succinate dehydrogenase, remained unchanged. Putative dioxin response elements were computationally found in the promoter regions of the 8 dose-responsive genes. This high-throughput approach suggests that TCDD alters the expression of genes associated with mitochondrial function which may contribute to TCDD-elicited mitochondrial toxicity. PMID:20399798

  8. Vector Adaptive/Predictive Encoding Of Speech

    NASA Technical Reports Server (NTRS)

    Chen, Juin-Hwey; Gersho, Allen

    1989-01-01

    Vector adaptive/predictive technique for digital encoding of speech signals yields decoded speech of very good quality after transmission at coding rate of 9.6 kb/s and of reasonably good quality at 4.8 kb/s. Requires 3 to 4 million multiplications and additions per second. Combines advantages of adaptive/predictive coding, and code-excited linear prediction, yielding speech of high quality but requires 600 million multiplications and additions per second at encoding rate of 4.8 kb/s. Vector adaptive/predictive coding technique bridges gaps in performance and complexity between adaptive/predictive coding and code-excited linear prediction.

  9. Is junk DNA bunk? A critique of ENCODE.

    PubMed

    Doolittle, W Ford

    2013-04-02

    Do data from the Encyclopedia Of DNA Elements (ENCODE) project render the notion of junk DNA obsolete? Here, I review older arguments for junk grounded in the C-value paradox and propose a thought experiment to challenge ENCODE's ontology. Specifically, what would we expect for the number of functional elements (as ENCODE defines them) in genomes much larger than our own genome? If the number were to stay more or less constant, it would seem sensible to consider the rest of the DNA of larger genomes to be junk or, at least, assign it a different sort of role (structural rather than informational). If, however, the number of functional elements were to rise significantly with C-value then, (i) organisms with genomes larger than our genome are more complex phenotypically than we are, (ii) ENCODE's definition of functional element identifies many sites that would not be considered functional or phenotype-determining by standard uses in biology, or (iii) the same phenotypic functions are often determined in a more diffuse fashion in larger-genomed organisms. Good cases can be made for propositions ii and iii. A larger theoretical framework, embracing informational and structural roles for DNA, neutral as well as adaptive causes of complexity, and selection as a multilevel phenomenon, is needed.

  10. Monoamines differentially modulate neuropeptide release from distinct sites within a single neuron pair.

    PubMed

    Clark, Tobias; Hapiak, Vera; Oakes, Mitchell; Mills, Holly; Komuniecki, Richard

    2018-01-01

    Monoamines and neuropeptides often modulate the same behavior, but monoaminergic-peptidergic crosstalk remains poorly understood. In Caenorhabditis elegans, the adrenergic-like ligands, tyramine (TA) and octopamine (OA) require distinct subsets of neuropeptides in the two ASI sensory neurons to inhibit nociception. TA selectively increases the release of ASI neuropeptides encoded by nlp-14 or nlp-18 from either synaptic/perisynaptic regions of ASI axons or the ASI soma, respectively, and OA selectively increases the release of ASI neuropeptides encoded by nlp-9 asymmetrically, from only the synaptic/perisynaptic region of the right ASI axon. The predicted amino acid preprosequences of genes encoding either TA- or OA-dependent neuropeptides differed markedly. However, these distinct preprosequences were not sufficient to confer monoamine-specificity and additional N-terminal peptide-encoding sequence was required. Collectively, our results demonstrate that TA and OA specifically and differentially modulate the release of distinct subsets of neuropeptides from different subcellular sites within the ASIs, highlighting the complexity of monoaminergic/peptidergic modulation, even in animals with a relatively simple nervous system.

  11. Monoamines differentially modulate neuropeptide release from distinct sites within a single neuron pair

    PubMed Central

    Oakes, Mitchell; Mills, Holly; Komuniecki, Richard

    2018-01-01

    Monoamines and neuropeptides often modulate the same behavior, but monoaminergic-peptidergic crosstalk remains poorly understood. In Caenorhabditis elegans, the adrenergic-like ligands, tyramine (TA) and octopamine (OA) require distinct subsets of neuropeptides in the two ASI sensory neurons to inhibit nociception. TA selectively increases the release of ASI neuropeptides encoded by nlp-14 or nlp-18 from either synaptic/perisynaptic regions of ASI axons or the ASI soma, respectively, and OA selectively increases the release of ASI neuropeptides encoded by nlp-9 asymmetrically, from only the synaptic/perisynaptic region of the right ASI axon. The predicted amino acid preprosequences of genes encoding either TA- or OA-dependent neuropeptides differed markedly. However, these distinct preprosequences were not sufficient to confer monoamine-specificity and additional N-terminal peptide-encoding sequence was required. Collectively, our results demonstrate that TA and OA specifically and differentially modulate the release of distinct subsets of neuropeptides from different subcellular sites within the ASIs, highlighting the complexity of monoaminergic/peptidergic modulation, even in animals with a relatively simple nervous system. PMID:29723289

  12. Performance study of large area encoding readout MRPC

    NASA Astrophysics Data System (ADS)

    Chen, X. L.; Wang, Y.; Chen, G.; Han, D.; Wang, X.; Zeng, M.; Zeng, Z.; Zhao, Z.; Guo, B.

    2018-02-01

    Muon tomography system built by the 2-D readout high spatial resolution Multi-gap Resistive Plate Chamber (MRPC) detector is a project of Tsinghua University. An encoding readout method based on the fine-fine configuration has been used to minimize the number of the readout electronic channels resulting in reducing the complexity and the cost of the system. In this paper, we provide a systematic comparison of the MRPC detector performance with and without fine-fine encoding readout. Our results suggest that the application of the fine-fine encoding readout leads us to achieve a detecting system with slightly worse spatial resolution but dramatically reduce the number of electronic channels.

  13. Concurrent encoding of frequency and amplitude modulation in human auditory cortex: encoding transition.

    PubMed

    Luo, Huan; Wang, Yadong; Poeppel, David; Simon, Jonathan Z

    2007-12-01

    Complex natural sounds (e.g., animal vocalizations or speech) can be characterized by specific spectrotemporal patterns the components of which change in both frequency (FM) and amplitude (AM). The neural coding of AM and FM has been widely studied in humans and animals but typically with either pure AM or pure FM stimuli. The neural mechanisms employed to perceptually unify AM and FM acoustic features remain unclear. Using stimuli with simultaneous sinusoidal AM (at rate f(AM) = 37 Hz) and FM (with varying rates f(FM)), magnetoencephalography (MEG) is used to investigate the elicited auditory steady-state response (aSSR) at relevant frequencies (f(AM), f(FM), f(AM) + f(FM)). Previous work demonstrated that for sounds with slower FM dynamics (f(FM) < 5 Hz), the phase of the aSSR at f(AM) tracked the FM; in other words, AM and FM features were co-tracked and co-represented by "phase modulation" encoding. This study explores the neural coding mechanism for stimuli with faster FM dynamics (< or =30 Hz), demonstrating that at faster rates (f(FM) > 5 Hz), there is a transition from pure phase modulation encoding to a single-upper-sideband (SSB) response (at frequency f(AM) + f(FM)) pattern. We propose that this unexpected SSB response can be explained by the additional involvement of subsidiary AM encoding responses simultaneously to, and in quadrature with, the ongoing phase modulation. These results, using MEG to reveal a possible neural encoding of specific acoustic properties, demonstrate more generally that physiological tests of encoding hypotheses can be performed noninvasively on human subjects, complementing invasive, single-unit recordings in animals.

  14. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

    PubMed

    Glass, Donald A; Bialek, Peter; Ahn, Jong Deok; Starbuck, Michael; Patel, Millan S; Clevers, Hans; Taketo, Mark M; Long, Fanxin; McMahon, Andrew P; Lang, Richard A; Karsenty, Gerard

    2005-05-01

    Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of beta-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis.

  15. Neutron-Encoded Protein Quantification by Peptide Carbamylation

    NASA Astrophysics Data System (ADS)

    Ulbrich, Arne; Merrill, Anna E.; Hebert, Alexander S.; Westphall, Michael S.; Keller, Mark P.; Attie, Alan D.; Coon, Joshua J.

    2014-01-01

    We describe a chemical tag for duplex proteome quantification using neutron encoding (NeuCode). The method utilizes the straightforward, efficient, and inexpensive carbamylation reaction. We demonstrate the utility of NeuCode carbamylation by accurately measuring quantitative ratios from tagged yeast lysates mixed in known ratios and by applying this method to quantify differential protein expression in mice fed a either control or high-fat diet.

  16. Distributed encoding of spatial and object categories in primate hippocampal microcircuits

    PubMed Central

    Opris, Ioan; Santos, Lucas M.; Gerhardt, Greg A.; Song, Dong; Berger, Theodore W.; Hampson, Robert E.; Deadwyler, Sam A.

    2015-01-01

    The primate hippocampus plays critical roles in the encoding, representation, categorization and retrieval of cognitive information. Such cognitive abilities may use the transformational input-output properties of hippocampal laminar microcircuitry to generate spatial representations and to categorize features of objects, images, and their numeric characteristics. Four nonhuman primates were trained in a delayed-match-to-sample (DMS) task while multi-neuron activity was simultaneously recorded from the CA1 and CA3 hippocampal cell fields. The results show differential encoding of spatial location and categorization of images presented as relevant stimuli in the task. Individual hippocampal cells encoded visual stimuli only on specific types of trials in which retention of either, the Sample image, or the spatial position of the Sample image indicated at the beginning of the trial, was required. Consistent with such encoding, it was shown that patterned microstimulation applied during Sample image presentation facilitated selection of either Sample image spatial locations or types of images, during the Match phase of the task. These findings support the existence of specific codes for spatial and numeric object representations in primate hippocampus which can be applied on differentially signaled trials. Moreover, the transformational properties of hippocampal microcircuitry, together with the patterned microstimulation are supporting the practical importance of this approach for cognitive enhancement and rehabilitation, needed for memory neuroprosthetics. PMID:26500473

  17. SNPing at the Epidermal Barrier.

    PubMed

    Kelsell, David P; Byrne, Carolyn

    2011-08-01

    Filaggrin variants are well-established risk factors for atopic eczema (AE). Recent studies suggest additional epidermal differentiation complex (EDC) gene associations with AE. In this issue, Marenholz and colleagues confirm this prediction and show that a small proline-rich protein 3 (SPRR3) variant confers susceptibility to AE. This finding suggests that further genetic and functional characterization of SPRR3 should be performed in patients with AE.

  18. Differential regulation of mnp2, a new manganese peroxidase-encoding gene from the ligninolytic fungus Trametes versicolor PRL 572.

    PubMed

    Johansson, Tomas; Nyman, Per Olof; Cullen, Daniel

    2002-04-01

    A peroxidase-encoding gene, mnp2, and its corresponding cDNA were characterized from the white-rot basidiomycete Trametes versicolor PRL 572. We used quantitative reverse transcriptase-mediated PCR to identify mnp2 transcripts in nutrient-limited stationary cultures. Although mnp2 lacks upstream metal response elements (MREs), addition of MnSO(4) to cultures increased mnp2 transcript levels 250-fold. In contrast, transcript levels of an MRE-containing gene of T. versicolor, mnp1, increased only eightfold under the same conditions. Thus, the manganese peroxidase genes in T. versicolor are differentially regulated, and upstream MREs are not necessarily involved. Our results support the hypothesis that fungal and plant peroxidases arose through an ancient duplication and folding of two structural domains, since we found the mnp1 and mnp2 polypeptides to have internal homology.

  19. Differential Regulation of mnp2, a New Manganese Peroxidase-Encoding Gene from the Ligninolytic Fungus Trametes versicolor PRL 572

    PubMed Central

    Johansson, Tomas; Nyman, Per Olof; Cullen, Daniel

    2002-01-01

    A peroxidase-encoding gene, mnp2, and its corresponding cDNA were characterized from the white-rot basidiomycete Trametes versicolor PRL 572. We used quantitative reverse transcriptase-mediated PCR to identify mnp2 transcripts in nutrient-limited stationary cultures. Although mnp2 lacks upstream metal response elements (MREs), addition of MnSO4 to cultures increased mnp2 transcript levels 250-fold. In contrast, transcript levels of an MRE-containing gene of T. versicolor, mnp1, increased only eightfold under the same conditions. Thus, the manganese peroxidase genes in T. versicolor are differentially regulated, and upstream MREs are not necessarily involved. Our results support the hypothesis that fungal and plant peroxidases arose through an ancient duplication and folding of two structural domains, since we found the mnp1 and mnp2 polypeptides to have internal homology. PMID:11916737

  20. Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues.

    PubMed

    Homan, Erica P; Lietman, Caressa; Grafe, Ingo; Lennington, Jennifer; Morello, Roy; Napierala, Dobrawa; Jiang, Ming-Ming; Munivez, Elda M; Dawson, Brian; Bertin, Terry K; Chen, Yuqing; Lua, Rhonald; Lichtarge, Olivier; Hicks, John; Weis, Mary Ann; Eyre, David; Lee, Brendan H L

    2014-01-01

    Mutations in the genes encoding cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1) were the first identified causes of recessive Osteogenesis Imperfecta (OI). These proteins, together with cyclophilin B (encoded by PPIB), form a complex that 3-hydroxylates a single proline residue on the α1(I) chain (Pro986) and has cis/trans isomerase (PPIase) activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1(H662A) ). This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I) and α1(II) collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase activity

  1. Cerebellar re-encoding of self-generated head movements

    PubMed Central

    Dugué, Guillaume P; Tihy, Matthieu; Gourévitch, Boris; Léna, Clément

    2017-01-01

    Head movements are primarily sensed in a reference frame tied to the head, yet they are used to calculate self-orientation relative to the world. This requires to re-encode head kinematic signals into a reference frame anchored to earth-centered landmarks such as gravity, through computations whose neuronal substrate remains to be determined. Here, we studied the encoding of self-generated head movements in the rat caudal cerebellar vermis, an area essential for graviceptive functions. We found that, contrarily to peripheral vestibular inputs, most Purkinje cells exhibited a mixed sensitivity to head rotational and gravitational information and were differentially modulated by active and passive movements. In a subpopulation of cells, this mixed sensitivity underlay a tuning to rotations about an axis defined relative to gravity. Therefore, we show that the caudal vermis hosts a re-encoded, gravitationally polarized representation of self-generated head kinematics in freely moving rats. DOI: http://dx.doi.org/10.7554/eLife.26179.001 PMID:28608779

  2. Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society

    PubMed Central

    Brown, T. R.; Doan, L. L.; Gore, A. C.; Skakkebaek, N. E.; Soto, A. M.; Woodruff, T. J.; Vom Saal, F. S.

    2012-01-01

    An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures. PMID:22733974

  3. From simplicial Lie algebras and hypercrossed complexes to differential graded Lie algebras via 1-jets

    NASA Astrophysics Data System (ADS)

    Jurčo, Branislav

    2012-12-01

    Let g be a simplicial Lie algebra with Moore complex Ng of length k. Let G be the simplicial Lie group integrating g, such that each Gn is simply connected. We use the 1-jet of the classifying space W¯ G to construct, starting from g, a Lie k-algebra L. The so constructed Lie k-algebra L is actually a differential graded Lie algebra. The differential and the brackets are explicitly described in terms (of a part) of the corresponding k-hypercrossed complex structure of Ng. The result can be seen as a geometric interpretation of Quillen's (purely algebraic) construction of the adjunction between simplicial Lie algebras and dg-Lie algebras.

  4. Outlier Resistant Predictive Source Encoding for a Gaussian Stationary Nominal Source.

    DTIC Science & Technology

    1987-09-18

    breakdown point and influence function . The proposed sequence of predictive encoders attains strictly positive breakdown point and uniformly bounded... influence function , at the expense of increased mean difference-squared distortion and differential entropy, at the Gaussian nominal source.

  5. Mutations in CTC1, Encoding the CTS Telomere Maintenance Complex Component 1, Cause Cerebroretinal Microangiopathy with Calcifications and Cysts

    PubMed Central

    Polvi, Anne; Linnankivi, Tarja; Kivelä, Tero; Herva, Riitta; Keating, James P.; Mäkitie, Outi; Pareyson, Davide; Vainionpää, Leena; Lahtinen, Jenni; Hovatta, Iiris; Pihko, Helena; Lehesjoki, Anna-Elina

    2012-01-01

    Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is a rare multisystem disorder characterized by extensive intracranial calcifications and cysts, leukoencephalopathy, and retinal vascular abnormalities. Additional features include poor growth, skeletal and hematological abnormalities, and recurrent gastrointestinal bleedings. Autosomal-recessive inheritance has been postulated. The pathogenesis of CRMCC is unknown, but its phenotype has key similarities with Revesz syndrome, which is caused by mutations in TINF2, a gene encoding a member of the telomere protecting shelterin complex. After a whole-exome sequencing approach in four unrelated individuals with CRMCC, we observed four recessively inherited compound heterozygous mutations in CTC1, which encodes the CTS telomere maintenance complex component 1. Sanger sequencing revealed seven more compound heterozygous mutations in eight more unrelated affected individuals. Two individuals who displayed late-onset cerebral findings, a normal fundus appearance, and no systemic findings did not have CTC1 mutations, implying that systemic findings are an important indication for CTC1 sequencing. Of the 11 mutations identified, four were missense, one was nonsense, two resulted in in-frame amino acid deletions, and four were short frameshift-creating deletions. All but two affected individuals were compound heterozygous for a missense mutation and a frameshift or nonsense mutation. No individuals with two frameshift or nonsense mutations were identified, which implies that severe disturbance of CTC1 function from both alleles might not be compatible with survival. Our preliminary functional experiments did not show evidence of severely affected telomere integrity in the affected individuals. Therefore, determining the underlying pathomechanisms associated with deficient CTC1 function will require further studies. PMID:22387016

  6. Encoding of contextual fear memory requires de novo proteins in the prelimbic cortex

    PubMed Central

    Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu L.; Swarnkar, Supriya; Lora, Joan; Kadakkuzha, Beena M.; Liu, Xin-An; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.

    2016-01-01

    Background Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory. Methods Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex manipulation (n = 56) of Homer 3, a candidate identified from polyribosome profiling. Results We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA enriched in polyribosomes following CFC, in the PL constrained encoding of contextual fear memory. Conclusions Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC. PMID:28503670

  7. Research on Optimization of Encoding Algorithm of PDF417 Barcodes

    NASA Astrophysics Data System (ADS)

    Sun, Ming; Fu, Longsheng; Han, Shuqing

    The purpose of this research is to develop software to optimize the data compression of a PDF417 barcode using VC++6.0. According to the different compression mode and the particularities of Chinese, the relevant approaches which optimize the encoding algorithm of data compression such as spillage and the Chinese characters encoding are proposed, a simple approach to compute complex polynomial is introduced. After the whole data compression is finished, the number of the codeword is reduced and then the encoding algorithm is optimized. The developed encoding system of PDF 417 barcodes will be applied in the logistics management of fruits, therefore also will promote the fast development of the two-dimensional bar codes.

  8. Minimal-memory realization of pearl-necklace encoders of general quantum convolutional codes

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

    Houshmand, Monireh; Hosseini-Khayat, Saied

    2011-02-15

    Quantum convolutional codes, like their classical counterparts, promise to offer higher error correction performance than block codes of equivalent encoding complexity, and are expected to find important applications in reliable quantum communication where a continuous stream of qubits is transmitted. Grassl and Roetteler devised an algorithm to encode a quantum convolutional code with a ''pearl-necklace'' encoder. Despite their algorithm's theoretical significance as a neat way of representing quantum convolutional codes, it is not well suited to practical realization. In fact, there is no straightforward way to implement any given pearl-necklace structure. This paper closes the gap between theoretical representation andmore » practical implementation. In our previous work, we presented an efficient algorithm to find a minimal-memory realization of a pearl-necklace encoder for Calderbank-Shor-Steane (CSS) convolutional codes. This work is an extension of our previous work and presents an algorithm for turning a pearl-necklace encoder for a general (non-CSS) quantum convolutional code into a realizable quantum convolutional encoder. We show that a minimal-memory realization depends on the commutativity relations between the gate strings in the pearl-necklace encoder. We find a realization by means of a weighted graph which details the noncommutative paths through the pearl necklace. The weight of the longest path in this graph is equal to the minimal amount of memory needed to implement the encoder. The algorithm has a polynomial-time complexity in the number of gate strings in the pearl-necklace encoder.« less

  9. TDP-43 regulates the microprocessor complex activity during in vitro neuronal differentiation.

    PubMed

    Di Carlo, Valerio; Grossi, Elena; Laneve, Pietro; Morlando, Mariangela; Dini Modigliani, Stefano; Ballarino, Monica; Bozzoni, Irene; Caffarelli, Elisa

    2013-12-01

    TDP-43 (TAR DNA-binding protein 43) is an RNA-binding protein implicated in RNA metabolism at several levels. Even if ubiquitously expressed, it is considered as a neuronal activity-responsive factor and a major signature for neurological pathologies, making the comprehension of its activity in the nervous system a very challenging issue. TDP-43 has also been described as an accessory component of the Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) microprocessor complex, which is crucially involved in basal and tissue-specific RNA processing events. In the present study, we exploited in vitro neuronal differentiation systems to investigate the TDP-43 demand for the microprocessor function, focusing on both its canonical microRNA biosynthetic activity and its alternative role as a post-transcriptional regulator of gene expression. Our findings reveal a novel role for TDP-43 as an essential factor that controls the stability of Drosha protein during neuronal differentiation, thus globally affecting the production of microRNAs. We also demonstrate that TDP-43 is required for the Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha target, resulted to be TDP-43-independent. These results implicate a previously uncovered contribution of TDP-43 in regulating the abundance and the substrate specificity of the microprocessor complex and provide new insights into TDP-43 as a key player in neuronal differentiation.

  10. The process of EDC-NHS cross-linking of reconstituted collagen fibres increases collagen fibrillar order and alignment

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

    Shepherd, D. V., E-mail: dvs23@cam.ac.uk; Shepherd, J. H.; Cameron, R. E.

    We describe the production of collagen fibre bundles through a multi-strand, semi-continuous extrusion process. Cross-linking using an EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N-hydroxysuccinimide) combination was considered. Atomic Force Microscopy and Raman spectroscopy focused on how cross-linking affected the collagen fibrillar structure. In the cross-linked fibres, a clear fibrillar structure comparable to native collagen was observed which was not observed in the non-cross-linked fibre. The amide III doublet in the Raman spectra provided additional evidence of alignment in the cross-linked fibres. Raman spectroscopy also indicated no residual polyethylene glycol (from the fibre forming buffer) or water in any of the fibres.

  11. Word Associated Arousal as an Encoding Dimension in Short Term Memory.

    ERIC Educational Resources Information Center

    Hayduk, Allan W.; Osborne, John W.

    1981-01-01

    The fact that a significant amount of release from proactive interference was obtained with subjects in this study by shifting between differentially arousing categories of words suggested that rated word arousal is an encoding dimension in short-term memory. (CM)

  12. Neural encoding of competitive effort in the anterior cingulate cortex.

    PubMed

    Hillman, Kristin L; Bilkey, David K

    2012-09-01

    In social environments, animals often compete to obtain limited resources. Strategically electing to work against another animal represents a cost-benefit decision. Is the resource worth an investment of competitive effort? The anterior cingulate cortex (ACC) has been implicated in cost-benefit decision-making, but its role in competitive effort has not been examined. We recorded ACC neurons in freely moving rats as they performed a competitive foraging choice task. When at least one of the two choice options demanded competitive effort, the majority of ACC neurons exhibited heightened and differential firing between the goal trajectories. Inter- and intrasession manipulations revealed that differential firing was not attributable to effort or reward in isolation; instead ACC encoding patterns appeared to indicate net utility assessments of available choice options. Our findings suggest that the ACC is important for encoding competitive effort, a cost-benefit domain that has received little neural-level investigation despite its predominance in nature.

  13. New composite materials prepared by calcium phosphate precipitation in chitosan/collagen/hyaluronic acid sponge cross-linked by EDC/NHS.

    PubMed

    Kaczmarek, B; Sionkowska, A; Kozlowska, J; Osyczka, A M

    2018-02-01

    Nowadays, fabrication of composite materials based on biopolymers is a rising field due to potential for bone repair and tissue engineering application. Blending of different biopolymers and incorporation of inorganic particles in the blend can lead to new materials with improved physicochemical properties and biocompatibility. In this work 3D porous structures called scaffolds based on chitosan, collagen and hyaluronic acid were obtained through the lyophilization process. Scaffolds were cross-linked by EDC/NHS. Infrared spectra for the materials were made, the percentage of swelling, scaffolds porosity and density, mechanical parameters, thermal stability were studied. Moreover, the scaffolds were used as matrixes for the calcium phosphate in situ precipitation. SEM images were taken and EDX analysis was carried out for calcium and phosphorous content determination in the scaffold. In addition, the adhesion and proliferation of human osteosarcoma SaOS-2 cells was examined on obtained scaffolds. The results showed that the properties of 3D composites cross-linked by EDC/NHS were altered after the addition of 1, 2 and 5% hyaluronic acid. Mechanical parameters, thermal stability and porosity of scaffolds were improved. Moreover, calcium and phosphorous were found in each kind of scaffold. SEM images showed that the precipitation was homogeneously carried in the whole volume of samples. Attachment of SaOS-2 cells to all modified materials was better compared to unmodified control and proliferation of these cells was markedly increased on scaffolds with precipitated calcium phosphate. Obtained materials can provide the support useful in tissue engineering and regenerative medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Environmental Factors, Epigenetics, and Developmental Origin of Reproductive Disorders

    PubMed Central

    Ho, Shuk-Mei; Cheong, Ana; Adgent, Margaret A.; Veevers, Jennifer; Suen, Alisa A.; Tam, Neville N.C.; Leung, Yuet-Kin; Jefferson, Wendy N.; Williams, Carmen J.

    2016-01-01

    Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure to estrogenic and anti-androgenic endocrine disrupting chemicals (EDCs) is associated with reproductive dysfunction in adulthood. Human data in support of “Developmental Origins of Health and Disease” (DOHaD) comes from multigenerational studies on offspring of diethylstilbestrol-exposed mothers/grandmothers. Animal data indicate that ovarian reserve, female cycling, adult uterine abnormalities, sperm quality, prostate disease, and mating behavior are susceptible to DOHaD effects induced by EDCs such as bisphenol A, genistein, diethylstilbestrol, p,p′-dichlorodiphenyl-dichloroethylene, phthalates, and polyaromatic hydrocarbons. Mechanisms underlying these EDC effects include direct mimicry of sex steroids or morphogens and interference with epigenomic sculpting during cell and tissue differentiation. Exposure to EDCs is associated with abnormal DNA methylation and other epigenetic modifications, as well as altered expression of genes important for development and function of reproductive tissues. Here we review the literature exploring the connections between developmental exposure to EDCs and adult reproductive dysfunction, and the mechanisms underlying these effects. PMID:27421580

  15. The effects of age on the neural correlates of episodic encoding.

    PubMed

    Grady, C L; McIntosh, A R; Rajah, M N; Beig, S; Craik, F I

    1999-12-01

    Young and old adults underwent positron emission tomographic scans while encoding pictures of objects and words using three encoding strategies: deep processing (a semantic living/nonliving judgement), shallow processing (size judgement) and intentional learning. Picture memory exceeded word memory in both young and old groups, and there was an age-related decrement only in word recognition. During the encoding tasks three brain activity patterns were found that differentiated stimulus type and the different encoding strategies. The stimulus-specific pattern was characterized by greater activity in extrastriate and medial temporal cortices during picture encoding, and greater activity in left prefrontal and temporal cortices during encoding of words. The older adults showed this pattern to a significantly lesser degree. A pattern distinguishing deep processing from intentional learning of words and pictures was identified, characterized mainly by differences in prefrontal cortex, and this pattern also was of significantly lesser magnitude in the old group. A final pattern identified areas with increased activity during deep processing and intentional learning of pictures, including left prefrontal and bilateral medial temporal regions. There was no group difference in this pattern. These results indicate age-related dysfunction in several encoding networks, with sparing of one specifically involved in more elaborate encoding of pictures. These age-related changes appear to affect verbal memory more than picture memory.

  16. Dissociations within human hippocampal subregions during encoding and retrieval of spatial information.

    PubMed

    Suthana, Nanthia; Ekstrom, Arne; Moshirvaziri, Saba; Knowlton, Barbara; Bookheimer, Susan

    2011-07-01

    Although the hippocampus is critical for the formation and retrieval of spatial memories, it is unclear how subregions are differentially involved in these processes. Previous high-resolution functional magnetic resonance imaging (fMRI) studies have shown that CA2, CA3, and dentate gyrus (CA23DG) regions support the encoding of novel associations, whereas the subicular cortices support the retrieval of these learned associations. Whether these subregions are used in humans during encoding and retrieval of spatial information has yet to be explored. Using high-resolution fMRI (1.6 mm × 1.6-mm in-plane), we found that activity within the right CA23DG increased during encoding compared to retrieval. Conversely, right subicular activity increased during retrieval compared to encoding of spatial associations. These results are consistent with the previous studies illustrating dissociations within human hippocampal subregions and further suggest that these regions are similarly involved during the encoding and retrieval of spatial information. Copyright © 2010 Wiley-Liss, Inc.

  17. Differential Regulation of Endosomal GPCR/β-Arrestin Complexes and Trafficking by MAPK*

    PubMed Central

    Khoury, Etienne; Nikolajev, Ljiljana; Simaan, May; Namkung, Yoon; Laporte, Stéphane A.

    2014-01-01

    β-Arrestins are signaling adaptors that bind to agonist-occupied G protein-coupled receptors (GPCRs) and target them for endocytosis; however, the mechanisms regulating receptor/β-arrestin complexes and trafficking in endosomes, remain ill defined. Here we show, in live cells, differential dynamic regulation of endosomal bradykinin B2 receptor (B2R) complexes with either β-arrestin-1 or -2. We find a novel role for MAPK in the B2R/β-arrestin-2 complex formation, receptor trafficking and signaling mediated by an ERK1/2 regulatory motif in the hinge domain of the rat β-arrestin-2 (PET178P), but not rat β-arrestin-1 (PER177P). While the ERK1/2 regulatory motif is conserved between rat and mouse β-arrestin-2, it is surprisingly not conserved in human β-arrestin-2 (PEK178P). However, mutation of lysine 178 to threonine is sufficient to confer MAPK sensitivity to the human β-arrestin-2. Furthermore, substitution for a phosphomimetic residue in both the rat and the human β-arrestin-2 (T/K178D) significantly stabilizes B2R/β-arrestin complexes in endosomes, delays receptor recycling to the plasma membrane and maintains intracellular MAPK signaling. Similarly, the endosomal trafficking of β2-adrenergic, angiotensin II type 1 and vasopressin V2 receptors was altered by the β-arrestin-2 T178D mutant. Our findings unveil a novel subtype specific mode of MAPK-dependent regulation of β-arrestins in intracellular trafficking and signaling of GPCRs, and suggest differential endosomal receptor/β-arrestin-2 signaling roles among species. PMID:25016018

  18. Pronounced fixation, strong population differentiation and complex population history in the Canary Islands blue tit subspecies complex.

    PubMed

    Hansson, Bengt; Ljungqvist, Marcus; Illera, Juan-Carlos; Kvist, Laura

    2014-01-01

    Evolutionary molecular studies of island radiations may lead to insights in the role of vicariance, founder events, population size and drift in the processes of population differentiation. We evaluate the degree of population genetic differentiation and fixation of the Canary Islands blue tit subspecies complex using microsatellite markers and aim to get insights in the population history using coalescence based methods. The Canary Island populations were strongly genetically differentiated and had reduced diversity with pronounced fixation including many private alleles. In population structure models, the relationship between the central island populations (La Gomera, Tenerife and Gran Canaria) and El Hierro was difficult to disentangle whereas the two European populations showed consistent clustering, the two eastern islands (Fuerteventura and Lanzarote) and Morocco weak clustering, and La Palma a consistent unique lineage. Coalescence based models suggested that the European mainland forms an outgroup to the Afrocanarian population, a split between the western island group (La Palma and El Hierro) and the central island group, and recent splits between the three central islands, and between the two eastern islands and Morocco, respectively. It is clear that strong genetic drift and low level of concurrent gene flow among populations have shaped complex allelic patterns of fixation and skewed frequencies over the archipelago. However, understanding the population history remains challenging; in particular, the pattern of extreme divergence with low genetic diversity and yet unique genetic material in the Canary Island system requires an explanation. A potential scenario is population contractions of a historically large and genetically variable Afrocanarian population, with vicariance and drift following in the wake. The suggestion from sequence-based analyses of a Pleistocene extinction of a substantial part of North Africa and a Pleistocene/Holocene eastward

  19. Pronounced Fixation, Strong Population Differentiation and Complex Population History in the Canary Islands Blue Tit Subspecies Complex

    PubMed Central

    Hansson, Bengt; Ljungqvist, Marcus; Illera, Juan-Carlos; Kvist, Laura

    2014-01-01

    Evolutionary molecular studies of island radiations may lead to insights in the role of vicariance, founder events, population size and drift in the processes of population differentiation. We evaluate the degree of population genetic differentiation and fixation of the Canary Islands blue tit subspecies complex using microsatellite markers and aim to get insights in the population history using coalescence based methods. The Canary Island populations were strongly genetically differentiated and had reduced diversity with pronounced fixation including many private alleles. In population structure models, the relationship between the central island populations (La Gomera, Tenerife and Gran Canaria) and El Hierro was difficult to disentangle whereas the two European populations showed consistent clustering, the two eastern islands (Fuerteventura and Lanzarote) and Morocco weak clustering, and La Palma a consistent unique lineage. Coalescence based models suggested that the European mainland forms an outgroup to the Afrocanarian population, a split between the western island group (La Palma and El Hierro) and the central island group, and recent splits between the three central islands, and between the two eastern islands and Morocco, respectively. It is clear that strong genetic drift and low level of concurrent gene flow among populations have shaped complex allelic patterns of fixation and skewed frequencies over the archipelago. However, understanding the population history remains challenging; in particular, the pattern of extreme divergence with low genetic diversity and yet unique genetic material in the Canary Island system requires an explanation. A potential scenario is population contractions of a historically large and genetically variable Afrocanarian population, with vicariance and drift following in the wake. The suggestion from sequence-based analyses of a Pleistocene extinction of a substantial part of North Africa and a Pleistocene/Holocene eastward

  20. CRISPR screen identifies the NCOR/HDAC3 complex as a major suppressor of differentiation in rhabdomyosarcoma

    PubMed Central

    Phelps, Michael P.; Bailey, Jenna N.; Vleeshouwer-Neumann, Terra

    2016-01-01

    Dysregulated gene expression resulting from abnormal epigenetic alterations including histone acetylation and deacetylation has been demonstrated to play an important role in driving tumor growth and progression. However, the mechanisms by which specific histone deacetylases (HDACs) regulate differentiation in solid tumors remains unclear. Using pediatric rhabdomyosarcoma (RMS) as a paradigm to elucidate the mechanism blocking differentiation in solid tumors, we identified HDAC3 as a major suppressor of myogenic differentiation from a high-efficiency Clustered regularly interspaced short palindromic repeats (CRISPR)-based phenotypic screen of class I and II HDAC genes. Detailed characterization of the HDAC3-knockout phenotype in vitro and in vivo using a tamoxifen-inducible CRISPR targeting strategy demonstrated that HDAC3 deacetylase activity and the formation of a functional complex with nuclear receptor corepressors (NCORs) were critical in restricting differentiation in RMS. The NCOR/HDAC3 complex specifically functions by blocking myoblast determination protein 1 (MYOD1)-mediated activation of myogenic differentiation. Interestingly, there was also a transient up-regulation of growth-promoting genes upon initial HDAC3 targeting, revealing a unique cancer-specific response to the forced transition from a neoplastic state to terminal differentiation. Our study applied modifications of CRISPR/CRISPR-associated endonuclease 9 (Cas9) technology to interrogate the function of essential cancer genes and pathways and has provided insights into cancer cell adaptation in response to altered differentiation status. Because current pan-HDAC inhibitors have shown disappointing results in clinical trials of solid tumors, therapeutic targets specific to HDAC3 function represent a promising option for differentiation therapy in malignant tumors with dysregulated HDAC3 activity. PMID:27956629

  1. CRISPR screen identifies the NCOR/HDAC3 complex as a major suppressor of differentiation in rhabdomyosarcoma.

    PubMed

    Phelps, Michael P; Bailey, Jenna N; Vleeshouwer-Neumann, Terra; Chen, Eleanor Y

    2016-12-27

    Dysregulated gene expression resulting from abnormal epigenetic alterations including histone acetylation and deacetylation has been demonstrated to play an important role in driving tumor growth and progression. However, the mechanisms by which specific histone deacetylases (HDACs) regulate differentiation in solid tumors remains unclear. Using pediatric rhabdomyosarcoma (RMS) as a paradigm to elucidate the mechanism blocking differentiation in solid tumors, we identified HDAC3 as a major suppressor of myogenic differentiation from a high-efficiency Clustered regularly interspaced short palindromic repeats (CRISPR)-based phenotypic screen of class I and II HDAC genes. Detailed characterization of the HDAC3-knockout phenotype in vitro and in vivo using a tamoxifen-inducible CRISPR targeting strategy demonstrated that HDAC3 deacetylase activity and the formation of a functional complex with nuclear receptor corepressors (NCORs) were critical in restricting differentiation in RMS. The NCOR/HDAC3 complex specifically functions by blocking myoblast determination protein 1 (MYOD1)-mediated activation of myogenic differentiation. Interestingly, there was also a transient up-regulation of growth-promoting genes upon initial HDAC3 targeting, revealing a unique cancer-specific response to the forced transition from a neoplastic state to terminal differentiation. Our study applied modifications of CRISPR/CRISPR-associated endonuclease 9 (Cas9) technology to interrogate the function of essential cancer genes and pathways and has provided insights into cancer cell adaptation in response to altered differentiation status. Because current pan-HDAC inhibitors have shown disappointing results in clinical trials of solid tumors, therapeutic targets specific to HDAC3 function represent a promising option for differentiation therapy in malignant tumors with dysregulated HDAC3 activity.

  2. Prmt7 is dispensable in tissue culture models for adipogenic differentiation.

    PubMed

    Hu, Yu-Jie; Sif, Saïd; Imbalzano, Anthony N

    2013-01-01

    Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts) that catalyze monomethylation, asymmetric dimethylation, and symmetric dimethylation on arginine residues. Protein arginine methyltransferase 7 (Prmt7) is categorized as a type II and type III enzyme that produces symmetric dimethylated arginine and monomethylated arginine, respectively. However, the biological role of Prmt7 is not well characterized. We previously showed that Prmt5, a type II Prmt that associates with Brg1-based SWI/SNF chromatin remodeling complex, is required for adipocyte differentiation. Since Prmt7 also associates with Brg1-based SWI/SNF complex and modifies core histones, we hypothesized that Prmt7 might play a role in transcriptional regulation of adipogenesis. In the present study, we determined that the expression of Prmt7 did not change throughout adipogenic differentiation of C3H10T1/2 mesenchymal cells. Knockdown or over-expression of Prmt7 had no effect on lipid accumulation or adipogenic gene expression in differentiating C3H10T1/2 cells or in C/EBPα-reprogrammed NIH3T3 fibroblasts. Based on these results, we conclude that Prmt7, unlike Prmt5, is dispensable for adipogenic differentiation in tissue culture models.

  3. Prmt7 is dispensable in tissue culture models for adipogenic differentiation

    PubMed Central

    Imbalzano, Anthony N.

    2013-01-01

    Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts) that catalyze monomethylation, asymmetric dimethylation, and symmetric dimethylation on arginine residues. Protein arginine methyltransferase 7 (Prmt7) is categorized as a type II and type III enzyme that produces symmetric dimethylated arginine and monomethylated arginine, respectively. However, the biological role of Prmt7 is not well characterized. We previously showed that Prmt5, a type II Prmt that associates with Brg1-based SWI/SNF chromatin remodeling complex, is required for adipocyte differentiation. Since Prmt7 also associates with Brg1-based SWI/SNF complex and modifies core histones, we hypothesized that Prmt7 might play a role in transcriptional regulation of adipogenesis. In the present study, we determined that the expression of Prmt7 did not change throughout adipogenic differentiation of C3H10T1/2 mesenchymal cells. Knockdown or over-expression of Prmt7 had no effect on lipid accumulation or adipogenic gene expression in differentiating C3H10T1/2 cells or in C/EBPα-reprogrammed NIH3T3 fibroblasts. Based on these results, we conclude that Prmt7, unlike Prmt5, is dispensable for adipogenic differentiation in tissue culture models. PMID:24715966

  4. An Investigation of Differential Encoding and Retrieval in Older Adult College Students.

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.; Reif, Laurie

    Three experiments were conducted in order to clarify the encoding/retrieval dilemma in older adult students; and the recognition/recall test issue was also explored. First, a mnemonic technique based on the "key word" method of Funk and Tarshis was used; secondly, a semantic processing task was tried; and lastly, a repetition task, based…

  5. Transgenerational neuroendocrine disruption of reproduction

    PubMed Central

    Walker, Deena M.; Gore, Andrea C.

    2014-01-01

    Exposure to endocrine disrupting chemicals (EDCs) is associated with dysfunctions of metabolism, energy balance, thyroid function and reproduction, and an increased risk of endocrine cancers. These multifactorial disorders can be ‘programmed’ through molecular epigenetic changes induced by exposure to EDCs early in life, the expression of which may not manifest until adulthood. In some cases, EDCs have detrimental effects on subsequent generations, which indicates that traits for disease predisposition may be passed to future generations by nongenomic inheritance. This Review discusses current understanding of the epigenetic mechanisms that underlie sexual differentiation of reproductive neuroendocrine systems in mammals and summarizes the literature on transgenerational epigenetic effects of representative EDCs: vinclozolin, diethylstilbesterol, bisphenol A and polychlorinated biphenyls. The article differentiates between context-dependent epigenetic transgenerational changes—namely, those that require environmental exposure, either via the EDC itself or through behavioral or physiological differences in parents—and germline-dependent epigenetic mechanisms. These processes, albeit discrete, are not mutually exclusive and can involve similar molecular mechanisms including DNA methylation and histone modifications and may predispose exposed individuals to transgenerational disruption of reproductive processes. New insights stress the crucial need to develop a clear understanding of how EDCs may program the epigenome of exposed individuals and their descendants. PMID:21263448

  6. Genetic differentiation and phylogeographical structure of the Brachionus calyciflorus complex in eastern China.

    PubMed

    Xiang, Xian-Ling; Xi, Yi-Long; Wen, Xin-Li; Zhang, Gen; Wang, Jin-Xia; Hu, Ke

    2011-07-01

    Spatio-temporal patterns and processes of genetic differentiation in passively dispersing zooplankton are drawing much attention from both ecologists and evolutionary biologists. Two opposite phylogeographical scenarios have already been demonstrated in rotifers, which consist of high levels of genetic differentiation among populations even on small geographical scales on the one hand and the traditionally known cosmopolitanism that is associated with high levels of gene flow and long-distance dispersal via diapausing stages on the other hand. Here, we analysed the population genetic structure and the phylogeography of the Brachionus calyciflorus species complex in eastern China. By screening a total of 318 individuals from ten locations along a 2320-km gradient and analysing samples from two growing seasons, we aimed at focusing on both small- and large-scale patterns. We identified eight cryptic species and verified species status of two of these by sexual reproduction tests. Samples in summer and winter yielded different cryptic species. The distribution patterns of these genetically distinct cryptic species were diverse across eastern China, from full cosmopolitanism to local endemism. The two most abundant cryptic species BcWIII and BcSW showed a pattern of strong genetic differentiation among populations and no significant isolation by distance. Long-distance colonization, secondary contact and recent range expansion are probably responsible for the indistinct pattern of isolation by distance. Our results suggest that geographical distance is more important than temporal segregation across seasons in explaining population differentiation and the occurrence of cryptic species. We explain the current phylogeographical structure in the B. calyciflorus species complex by a combination of recent population expansion, restricted gene flow, priority effects and long-distance colonization. © 2011 Blackwell Publishing Ltd.

  7. SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

    PubMed

    Hitz, Benjamin C; Rowe, Laurence D; Podduturi, Nikhil R; Glick, David I; Baymuradov, Ulugbek K; Malladi, Venkat S; Chan, Esther T; Davidson, Jean M; Gabdank, Idan; Narayana, Aditi K; Onate, Kathrina C; Hilton, Jason; Ho, Marcus C; Lee, Brian T; Miyasato, Stuart R; Dreszer, Timothy R; Sloan, Cricket A; Strattan, J Seth; Tanaka, Forrest Y; Hong, Eurie L; Cherry, J Michael

    2017-01-01

    The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package.

  8. SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata

    PubMed Central

    Podduturi, Nikhil R.; Glick, David I.; Baymuradov, Ulugbek K.; Malladi, Venkat S.; Chan, Esther T.; Davidson, Jean M.; Gabdank, Idan; Narayana, Aditi K.; Onate, Kathrina C.; Hilton, Jason; Ho, Marcus C.; Lee, Brian T.; Miyasato, Stuart R.; Dreszer, Timothy R.; Sloan, Cricket A.; Strattan, J. Seth; Tanaka, Forrest Y.; Hong, Eurie L.; Cherry, J. Michael

    2017-01-01

    The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package. PMID:28403240

  9. Climatic differentiation in polyploid apomictic Ranunculus auricomus complex in Europe.

    PubMed

    Paule, Juraj; Dunkel, Franz G; Schmidt, Marco; Gregor, Thomas

    2018-05-21

    Polyploidy and apomixis are important factors influencing plant distributions often resulting in range shifts, expansions and geographical parthenogenesis. We used the Ranunculus auricomus complex as a model to asses if the past and present distribution and climatic preferences were determined by these phenomena. Ecological differentiation among diploids and polyploids was tested by comparing the sets of climatic variables and distribution modelling using 191 novel ploidy estimations and 561 literature data. Significant differences in relative genome size on the diploid level were recorded between the "auricomus" and "cassubicus" groups and several new diploid occurrences were found in Slovenia and Hungary. The current distribution of diploids overlapped with the modelled paleodistribution (22 kyr BP), except Austria and the Carpathians, which are proposed to be colonized later on from refugia in the Balkans. Current and historical presence of diploids from the R. auricomus complex is suggested also for the foothills of the Caucasus. Based on comparisons of the climatic preferences polyploids from the R. auricomus complex occupy slightly drier and colder habitats than the diploids. The change of reproductive mode and selection due to competition with the diploid ancestors may have facilitated the establishment of polyploids within the R. auricomus complex in environments slightly cooler and drier, than those tolerated by diploid ancestors. Much broader distribution of polyploid apomicts may have been achieved due to faster colonization mediated by uniparental reproductive system.

  10. Reduction of nuclear encoded enzymes of mitochondrial energy metabolism in cells devoid of mitochondrial DNA

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

    Mueller, Edith E., E-mail: ed.mueller@salk.at; Mayr, Johannes A., E-mail: h.mayr@salk.at; Zimmermann, Franz A., E-mail: f.zimmermann@salk.at

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We examined OXPHOS and citrate synthase enzyme activities in HEK293 cells devoid of mtDNA. Black-Right-Pointing-Pointer Enzymes partially encoded by mtDNA show reduced activities. Black-Right-Pointing-Pointer Also the entirely nuclear encoded complex II and citrate synthase exhibit reduced activities. Black-Right-Pointing-Pointer Loss of mtDNA induces a feedback mechanism that downregulates complex II and citrate synthase. -- Abstract: Mitochondrial DNA (mtDNA) depletion syndromes are generally associated with reduced activities of oxidative phosphorylation (OXPHOS) enzymes that contain subunits encoded by mtDNA. Conversely, entirely nuclear encoded mitochondrial enzymes in these syndromes, such as the tricarboxylic acid cycle enzyme citrate synthase (CS) and OXPHOS complexmore » II, usually exhibit normal or compensatory enhanced activities. Here we report that a human cell line devoid of mtDNA (HEK293 {rho}{sup 0} cells) has diminished activities of both complex II and CS. This finding indicates the existence of a feedback mechanism in {rho}{sup 0} cells that downregulates the expression of entirely nuclear encoded components of mitochondrial energy metabolism.« less

  11. A-type Lamins Form Distinct Filamentous Networks with Differential Nuclear Pore Complex Associations.

    PubMed

    Xie, Wei; Chojnowski, Alexandre; Boudier, Thomas; Lim, John S Y; Ahmed, Sohail; Ser, Zheng; Stewart, Colin; Burke, Brian

    2016-10-10

    The nuclear lamina is a universal feature of metazoan nuclear envelopes (NEs) [1]. In mammalian cells, it appears as a 10-30 nm filamentous layer at the nuclear face of the inner nuclear membrane (INM) and is composed primarily of A- and B-type lamins, members of the intermediate filament family [2]. While providing structural integrity to the NE, the lamina also represents an important signaling and regulatory platform [3]. Two A-type lamin isoforms, lamins A and C (LaA and LaC), are expressed in most adult human cells. Encoded by a single gene, these proteins are largely identical, diverging only in their C-terminal tail domains. By contrast with that of LaC, the unique LaA tail undergoes extensive processing, including farnesylation and endo-proteolysis [4, 5]. However, functional differences between LaA and LaC are still unclear. Compounding this uncertainty, the structure of the lamina remains ill defined. In this study, we used BioID, an in vivo proximity-labeling method to identify differential interactors of A-type lamins [6]. One of these, Tpr, a nuclear pore complex (NPC) protein, is highlighted by its selective association with LaC. By employing superresolution microscopy, we demonstrate that this Tpr association is mirrored in enhanced interaction of LaC with NPCs. Further superresolution studies visualizing both endogenous A- and B-type lamins have allowed us to construct a nanometer-scale model of the mammalian nuclear lamina. Our data indicate that different A- and B-type lamin species assemble into separate filament networks that together form an extended composite structure at the nuclear periphery providing attachment sites for NPCs, thereby regulating their distribution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Differentiation of Constriction and Restriction: Complex Cardiovascular Hemodynamics.

    PubMed

    Geske, Jeffrey B; Anavekar, Nandan S; Nishimura, Rick A; Oh, Jae K; Gersh, Bernard J

    2016-11-29

    Differentiation of constrictive pericarditis (CP) from restrictive cardiomyopathy (RCM) is a complex and often challenging process. Because CP is a potentially curable cause of heart failure and therapeutic options for RCM are limited, distinction of these 2 conditions is critical. Although different in regard to etiology, prognosis, and treatment, CP and RCM share a common clinical presentation of predominantly right-sided heart failure, in the absence of significant left ventricular systolic dysfunction or valve disease, due to impaired ventricular diastolic filling. Fundamental to the diagnosis of either condition is a clear understanding of the underlying hemodynamic principles and pathophysiology. We present a contemporary review of the pathophysiology, hemodynamics, diagnostic assessment, and therapeutic approach to patients presenting with CP and RCM. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Diffusive gradients in thin-films (DGT) for in situ sampling of selected endocrine disrupting chemicals (EDCs) in waters.

    PubMed

    Chen, Wei; Pan, Suhong; Cheng, Hao; Sweetman, Andrew J; Zhang, Hao; Jones, Kevin C

    2018-06-15

    A passive water sampler based on the diffusive gradients in thin-films (DGT) technique was developed and tested for 3 groups of endocrine disrupting chemicals (EDCs, including oestrogens, alkyl-phenols and bisphenols). Three different resins (hydrophilic-lipophilic-balanced (HLB), XAD18 and Strata-XL-A (SXLA)) were investigated for their suitability as the binding phase for DGT devices. Laboratory tests across a range of pH (3.5-9.5), ionic strength (0.001-0.5 M) and dissolved organic matter concentration (0-20 mg L -1 ) showed HLB and XAD18-DGT devices were more stable compared to SXLA-DGT. HLB-DGT and XAD18-DGT accumulated test chemicals with time consistent with theoretical predictions, while SXLA-DGT accumulated reduced amounts of chemical. DGT performance was also compared in field deployments up to 28 days, alongside conventional active sampling at a wastewater treatment plant. Uptake was linear to the samplers over 18 days, and then began to plateau/decline, indicating the maximum deployment time in those conditions. Concentrations provided by the DGT samplers compared well with those provided by auto-samplers. DGT integrated concentrations over the deployment period in a way that grab-sampling cannot. The advantages of the DGT sampler over active sampling include: low cost, ease of simultaneous multi-site deployment, in situ analyte pre-concentration and reduction of matrix interferences compared with conventional methods. Compared to other passive sampler designs, DGT uptake is independent of flow rate and therefore allows direct derivation of field concentrations from measured compound diffusion coefficients. This passive DGT sampler therefore constitutes a viable and attractive alternative to conventional grab and active water sampling for routine monitoring of selected EDCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy

    PubMed Central

    Shamseldin, Hanan E.; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S.; Gleeson, Joseph G.; Alkuraya, Fowzan S.

    2016-01-01

    Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. PMID:26708753

  15. Spatial encoding using the nonlinear field perturbations from magnetic materials.

    PubMed

    Karimi, Hirad; Dominguez-Viqueira, William; Cunningham, Charles H

    2014-08-01

    A proof-of-concept study was performed to assess the technical feasibility of using magnetic materials to generate spatial encoding fields. Spatially varying magnetic fields were generated by the placement of markers with different volume susceptibilities within the imaging volume. No linear gradients were used for spatial encoding during the signal acquisition. A signal-encoding model is described for reconstructing the images encoded with these field perturbations. Simulation and proof-of-concept experimental results are presented. Experiments were performed using field perturbations from a cylindrical marker as an example of the new encoding fields. Based on this experimental setup, annular rings were reconstructed from signals encoded with the new fields. Simulation results were presented for different acquisition parameters. Proof-of-concept was supported by the correspondence of regions in an image reconstructed from experimental data compared to those in a conventional gradient-echo image. Experimental results showed that inclusions of dimensions 1.5 mm in size could be resolved with the experimental setup. This study shows the technical feasibility of using magnetic markers to produce encoding fields. Magnetic materials will allow generating spatial encoding fields, which can be tailored to an imaging application with less complexity and at lower cost compared to the use of gradient inserts. Copyright © 2013 Wiley Periodicals, Inc.

  16. Enhanced Right Amygdala Activity in Adolescents during Encoding of Positively-Valenced Pictures

    PubMed Central

    Vasa, Roma A.; Pine, Daniel S.; Thorn, Julia M.; Nelson, Tess E.; Spinelli, Simona; Nelson, Eric; Maheu, Francoise S.; Ernst, Monique; Bruck, Maggie; Mostofsky, Stewart H.

    2010-01-01

    While studies among adults implicate the amygdala and interconnecting brain regions in encoding emotional stimuli, few studies have examined whether developmental changes occur within this emotional-memory network during adolescence. The present study examined whether adolescents and adults differentially engaged the amygdala and hippocampus during successful encoding of emotional pictures, with either positive or negative valence. Eighteen adults and twelve adolescents underwent event-related fMRI while encoding emotional pictures. Approximately 30 minutes later, outside the scanner, subjects were asked to recall the pictures seen during the scan. Age group differences in brain activity in the amygdala and hippocampus during encoding of the pictures that were later successfully and unsuccessfully recalled were separately compared for the positive and negative pictures. Adolescents, relative to adults, demonstrated enhanced activity in the right amygdala during encoding of positive pictures that were later recalled compared to not recalled. There were no age group differences in amygdala or hippocampal activity during successful encoding of negative pictures. The findings of preferential activity within the adolescent right amygdala during successful encoding of positive pictures may have implications for the increased reward and novelty seeking behavior, as well as elevated rates of psychopathology, observed during this distinct developmental period. PMID:21127721

  17. A novel application of three phase hollow fiber based liquid phase microextraction (HF-LPME) for the HPLC determination of two endocrine disrupting compounds (EDCs), n-octylphenol and n-nonylphenol, in environmental waters.

    PubMed

    Villar-Navarro, Mercedes; Ramos-Payán, María; Fernández-Torres, Rut; Callejón-Mochón, Manuel; Bello-López, Miguel Ángel

    2013-01-15

    This work proposes for the first time the use of a three phase hollow fiber liquid phase microextraction (HF-LPME) procedure for the extraction, and the later HPLC determination using fluorescence detection, of two much known endocrine disrupting compounds (EDCs): n-octylphenol (OP) and n-nonylphenol (NP). The extraction was carried out through a dihexyl ether liquid membrane supported on an Accurel® Q3/2 polypropylene hollow fiber. Optimum pH for donor and acceptor phases and extraction time were established. Enrichment (preconcentration) factors of 50 were obtained that allows detection limits of 0.54 and 0.52 ng mL(-1) for OP and NP, respectively. The method was successfully applied to the determination of these EDCs in environmental water samples, including urban wastewaters. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Nuclear Involvement in the Appearance of a Chloroplast-Encoded 32,000 Dalton Thylakoid Membrane Polypeptide Integral to the Photosystem II Complex 1

    PubMed Central

    Leto, Kenneth J.; Keresztes, Aron; Arntzen, Charles J.

    1982-01-01

    The genetic locus for the high chlorophyll fluorescent photosystem II-deficient maize mutant hcf*-3 has been definitively located to the nuclear genome. Fluorography of lamellar polypeptides labeled with [35S]methionine in vivo revealed the specific loss of a heavily labeled 32,000 dalton thylakoid membrane polypeptide as well as its chloroplast encoded precursor species at 34,000 daltons. Examination of freeze-fractured mesophyll and bundle sheath thylakoids from hcf*-3 revealed that both plastid types lacked the large EFs particles believed to consist of the photosystem II reaction center-core complex and associated light harvesting chlorophyll-proteins. The present evidence suggests that the synthesis or turnover/integration of the chloroplast-encoded 34,000 to 32,000 dalton polypeptide is under nuclear control, and that these polyipeptides are integral components of photosystem II which may be required for the assembly or structural stabilization of newly formed photosystem II reaction centers in both mesophyll and bundle sheath chloroplasts. Images PMID:16662421

  19. Differential effects of habitat complexity, predators and competitors on abundance of juvenile and adult coral reef fishes.

    PubMed

    Almany, Glenn R

    2004-09-01

    Greater structural complexity is often associated with greater abundance and diversity, perhaps because high complexity habitats reduce predation and competition. Using 16 spatially isolated live-coral reefs in the Bahamas, I examined how abundance of juvenile (recruit) and adult (non-recruit) fishes was affected by two factors: (1) structural habitat complexity and (2) the presence of predators and interference competitors. Manipulating the abundance of low and high complexity corals created two levels of habitat complexity, which was cross-factored with the presence or absence of resident predators (sea basses and moray eels) plus interference competitors (territorial damselfishes). Over 60 days, predators and competitors greatly reduced recruit abundance regardless of habitat complexity, but did not affect adult abundance. In contrast, increased habitat complexity had a strong positive effect on adult abundance and a weak positive effect on recruit abundance. Differential responses of recruits and adults may be related to the differential effects of habitat complexity on their primary predators. Sedentary recruits are likely most preyed upon by small resident predators that ambush prey, while larger adult fishes that forage widely and use reefs primarily for shelter are likely most preyed upon by large transient predators that chase prey. Increased habitat complexity may have inhibited foraging by transient predators but not resident predators. Results demonstrate the importance of habitat complexity to community dynamics, which is of concern given the accelerated degradation of habitats worldwide.

  20. Machining of Molybdenum by EDM-EP and EDC Processes

    NASA Astrophysics Data System (ADS)

    Wu, K. L.; Chen, H. J.; Lee, H. M.; Lo, J. S.

    2017-12-01

    Molybdenum metal (Mo) can be machined with conventional tools and equipment, however, its refractory propertytends to chip when being machined. In this study, the nonconventional processes of electrical discharge machining (EDM) and electro-polishing (EP) have been conducted to investigate the machining of Mo metal and fabrication of Mo grid. Satisfactory surface quality was obtained using appropriate EDM parameters of Ip ≦ 3A and Ton < 80μs at a constant pulse interval of 100μs. The finished Mometal has accomplished by selecting appropriate EP parameters such as electrolyte flow rate of 0.42m/s under EP voltage of 50V and flush time of 20 sec to remove the recast layer and craters on the surface of Mo metal. The surface roughness of machined Mo metal can be improved from Ra of 0.93μm (Rmax = 8.51μm) to 0.23μm (Rmax = 1.48μm). Machined Mo metal surface, when used as grid component in electron gun, needs to be modified by coating materials with high work function, such as silicon carbide (SiC). The main purpose of this study is to explore the electrical discharge coating (EDC) process for coating the SiC layer on EDMed Mo metal. Experimental results proved that the appropriate parameters of Ip = 5A and Ton = 50μs at Toff = 10μs can obtain the deposit with about 60μm thickness. The major phase of deposit on machined Mo surface was SiC ceramic, while the minor phases included MoSi2 and/or SiO2 with the presence of free Si due to improper discharging parameters and the use of silicone oil as the dielectric fluid.

  1. Sex Differentiation as a Target of Endocrine Disrupting Compounds in Early Life Stage Fathead Minnows (Pimephales promelas)

    EPA Science Inventory

    The occurrence of endocrine disrupting chemicals (EDCs) in concentrated animal feed operation (CAFO) waste, and the potential effects of these chemicals on aquatic ecosystems have been of recent concern. There is evidence that exposure to EDCs during enhanced windows of sensitiv...

  2. Environmental factors, epigenetics, and developmental origin of reproductive disorders.

    PubMed

    Ho, Shuk-Mei; Cheong, Ana; Adgent, Margaret A; Veevers, Jennifer; Suen, Alisa A; Tam, Neville N C; Leung, Yuet-Kin; Jefferson, Wendy N; Williams, Carmen J

    2017-03-01

    Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure to estrogenic and anti-androgenic endocrine disrupting chemicals (EDCs) is associated with reproductive dysfunction in adulthood. Human data in support of "Developmental Origins of Health and Disease" (DOHaD) comes from multigenerational studies on offspring of diethylstilbestrol-exposed mothers/grandmothers. Animal data indicate that ovarian reserve, female cycling, adult uterine abnormalities, sperm quality, prostate disease, and mating behavior are susceptible to DOHaD effects induced by EDCs such as bisphenol A, genistein, diethylstilbestrol, p,p'-dichlorodiphenyl-dichloroethylene, phthalates, and polyaromatic hydrocarbons. Mechanisms underlying these EDC effects include direct mimicry of sex steroids or morphogens and interference with epigenomic sculpting during cell and tissue differentiation. Exposure to EDCs is associated with abnormal DNA methylation and other epigenetic modifications, as well as altered expression of genes important for development and function of reproductive tissues. Here we review the literature exploring the connections between developmental exposure to EDCs and adult reproductive dysfunction, and the mechanisms underlying these effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Experimental measurement-device-independent quantum key distribution with uncharacterized encoding.

    PubMed

    Wang, Chao; Wang, Shuang; Yin, Zhen-Qiang; Chen, Wei; Li, Hong-Wei; Zhang, Chun-Mei; Ding, Yu-Yang; Guo, Guang-Can; Han, Zheng-Fu

    2016-12-01

    Measurement-device-independent quantum key distribution (MDI QKD) is an efficient way to share secrets using untrusted measurement devices. However, the assumption on the characterizations of encoding states is still necessary in this promising protocol, which may lead to unnecessary complexity and potential loopholes in realistic implementations. Here, by using the mismatched-basis statistics, we present the first proof-of-principle experiment of MDI QKD with uncharacterized encoding sources. In this demonstration, the encoded states are only required to be constrained in a two-dimensional Hilbert space, and two distant parties (Alice and Bob) are resistant to state preparation flaws even if they have no idea about the detailed information of their encoding states. The positive final secure key rates of our system exhibit the feasibility of this novel protocol, and demonstrate its value for the application of secure communication with uncharacterized devices.

  4. Adipogenic Effects of a Combination of the Endocrine-Disrupting Compounds Bisphenol A, Diethylhexylphthalate, and Tributyltin

    PubMed Central

    Biemann, Ronald; Fischer, Bernd; Navarrete Santos, Anne

    2014-01-01

    Objective The food contaminants bisphenol A (BPA), diethylhexylphthalate (DEHP), and tributyltin (TBT) are potent endocrine-disrupting compounds (EDC) known to interfere with adipogenesis. EDC usually act in mixtures and not as single compounds. The aim of this study was to investigate the effects of a simultaneous exposure of BPA, DEHP, and TBT on mesenchymal stem cell differentiation into adipocytes. Methods Multipotent murine mesenchymal stem cells (C3H10T1/2) were exposed to EDC mixtures in high concentrations, i.e. MIX-high (10 µmol/l BPA, 100 µmol/l DEHP, 100 nmol/l TBT), and in environmentally relevant concentrations, i.e. MIX-low (10 nmol/l BPA, 100 nmol/l DEHP, 1 nmol/l TBT). The exposure was performed either for the entire culture time (0-12 days) or at distinct stages of adipogenic differentiation. At day 12 of cell culture, the amount of adipocytes, triglyceride content (TG), and adipogenic marker gene expression were analyzed. Results MIX-high increased the development of adipocytes and the expression of adipogenic marker genes independently of the exposure window. The total TG amount was not increased. The low-concentrated EDC mixture had no obvious impact on adipogenesis. Conclusion In EDC mixtures, the adipogenic effect of TBT and DEHP predominates single effects of BPA. Mixture effects of EDC are not deducible from single compound experiments. PMID:24503497

  5. Fluorescent nanocolloids for differential labeling of the endocytic pathway and drug delivery applications

    NASA Astrophysics Data System (ADS)

    Delehanty, James B.; Spillmann, Christopher M.; Naciri, Jawad; Algar, W. Russ; Ratna, Banahalli R.; Medintz, Igor L.

    2013-02-01

    The demonstration of fine control over nanomaterials within biological systems, particularly in live cells, is integral for the successful implementation of nanoparticles (NPs) in biomedical applications. Here, we show the ability to differentially label the endocytic pathway of mammalian cells in a spatiotemporal manner utilizing fluorescent nanocolloids (NCs) doped with a perylene-based dye. EDC-based conjugation of green- and red-emitting NCs to the iron transport protein transferrin resulted in stable bioconjugates that were efficiently endocytosed by HEK 293T/17 cells. The staggered delivery of the bioconjugates allowed for the time-resolved, differential labeling of distinct vesicular compartments along the endocytic pathway in a nontoxic manner. We further demonstrated the ability of the NCs to be impregnated with the anticancer therapeutic, doxorubicin. Delivery of the drug-doped nanoconjugates resulted in the intracellular release and nuclear accumulation of doxorubicin in a time- and dose-dependent manner. We discuss our results in the context of the utility of such materials for NP-mediated drug delivery applications.

  6. Temporal texture of associative encoding modulates recall processes.

    PubMed

    Tibon, Roni; Levy, Daniel A

    2014-02-01

    Binding aspects of an experience that are distributed over time is an important element of episodic memory. In the current study, we examined how the temporal complexity of an experience may govern the processes required for its retrieval. We recorded event-related potentials during episodic cued recall following pair associate learning of concurrently and sequentially presented object-picture pairs. Cued recall success effects over anterior and posterior areas were apparent in several time windows. In anterior locations, these recall success effects were similar for concurrently and sequentially encoded pairs. However, in posterior sites clustered over parietal scalp the effect was larger for the retrieval of sequentially encoded pairs. We suggest that anterior aspects of the mid-latency recall success effects may reflect working-with-memory operations or direct access recall processes, while more posterior aspects reflect recollective processes which are required for retrieval of episodes of greater temporal complexity. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Dissociative detachment and memory impairment: reversible amnesia or encoding failure?

    PubMed

    Allen, J G; Console, D A; Lewis, L

    1999-01-01

    The authors propose that clinicians endeavor to differentiate between reversible and irreversible memory failures in patients with dissociative symptoms who report "memory gaps" and "lost time." The classic dissociative disorders, such as dissociative amnesia and dissociative identity disorder, entail reversible memory failures associated with encoding experience in altered states. The authors propose another realm of memory failures associated with severe dissociative detachment that may preclude the level of encoding of ongoing experience needed to support durable autobiographical memories. They describe how dissociative detachment may be intertwined with neurobiological factors that impair memory, and they spell out the significance of distinguishing reversible and irreversible memory impairment for diagnosis, patient education, psychotherapy, and research.

  8. Distinct Reward Properties are Encoded via Corticostriatal Interactions

    PubMed Central

    Smith, David V.; Rigney, Anastasia E.; Delgado, Mauricio R.

    2016-01-01

    The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior. PMID:26831208

  9. Distinct Reward Properties are Encoded via Corticostriatal Interactions.

    PubMed

    Smith, David V; Rigney, Anastasia E; Delgado, Mauricio R

    2016-02-02

    The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior.

  10. Quantum dot SOA input power dynamic range improvement for differential-phase encoded signals.

    PubMed

    Vallaitis, T; Bonk, R; Guetlein, J; Hillerkuss, D; Li, J; Brenot, R; Lelarge, F; Duan, G H; Freude, W; Leuthold, J

    2010-03-15

    Experimentally we find a 10 dB input power dynamic range advantage for amplification of phase encoded signals with quantum dot SOA as compared to low-confinement bulk SOA. An analysis of amplitude and phase effects shows that this improvement can be attributed to the lower alpha-factor found in QD SOA.

  11. Deep Marginalized Sparse Denoising Auto-Encoder for Image Denoising

    NASA Astrophysics Data System (ADS)

    Ma, Hongqiang; Ma, Shiping; Xu, Yuelei; Zhu, Mingming

    2018-01-01

    Stacked Sparse Denoising Auto-Encoder (SSDA) has been successfully applied to image denoising. As a deep network, the SSDA network with powerful data feature learning ability is superior to the traditional image denoising algorithms. However, the algorithm has high computational complexity and slow convergence rate in the training. To address this limitation, we present a method of image denoising based on Deep Marginalized Sparse Denoising Auto-Encoder (DMSDA). The loss function of Sparse Denoising Auto-Encoder is marginalized so that it satisfies both sparseness and marginality. The experimental results show that the proposed algorithm can not only outperform SSDA in the convergence speed and training time, but also has better denoising performance than the current excellent denoising algorithms, including both the subjective and objective evaluation of image denoising.

  12. The effect of encoding strategy on the neural correlates of memory for faces.

    PubMed

    Bernstein, Lori J; Beig, Sania; Siegenthaler, Amy L; Grady, Cheryl L

    2002-01-01

    Encoding and recognition of unfamiliar faces in young adults were examined using positron emission tomography to determine whether different encoding strategies would lead to encoding/retrieval differences in brain activity. Three types of encoding were compared: a 'deep' task (judging pleasantness/unpleasantness), a 'shallow' task (judging right/left orientation), and an intentional learning task in which subjects were instructed to learn the faces for a subsequent memory test but were not provided with a specific strategy. Memory for all faces was tested with an old/new recognition test. A modest behavioral effect was obtained, with deeply-encoded faces being recognized more accurately than shallowly-encoded or intentionally-learned faces. Regardless of encoding strategy, encoding activated a primarily ventral system including bilateral temporal and fusiform regions and left prefrontal cortices, whereas recognition activated a primarily dorsal set of regions including right prefrontal and parietal areas. Within encoding, the type of strategy produced different brain activity patterns, with deep encoding being characterized by left amygdala and left anterior cingulate activation. There was no effect of encoding strategy on brain activity during the recognition conditions. Posterior fusiform gyrus activation was related to better recognition accuracy in those conditions encouraging perceptual strategies, whereas activity in left frontal and temporal areas correlated with better performance during the 'deep' condition. Results highlight three important aspects of face memory: (1) the effect of encoding strategy was seen only at encoding and not at recognition; (2) left inferior prefrontal cortex was engaged during encoding of faces regardless of strategy; and (3) differential activity in fusiform gyrus was found, suggesting that activity in this area is not only a result of automatic face processing but is modulated by controlled processes.

  13. ATP6V1H regulates the growth and differentiation of bone marrow stromal cells.

    PubMed

    Li, Lin; Yang, Shaoqing; Zhang, Yanli; Ji, Dongrui; Jin, Zuolin; Duan, Xiaohong

    2018-05-18

    ATP6V1H encodes subunit H of vacuolar ATPase (V-ATPase) and may regulate osteoclastic function. The deficiency of ATP6V1H caused bone loss in human, mouse and zebrafish. In this report, we identified the mechanisms by which ATP6V1H regulates proliferation and differentiation of bone marrow stromal cells (BMSCs). We found that ATP6V1H was expressed in BMSCs, andAtp6v1h +/- BMSCs exhibited the lower proliferation rate, cell cycle arrest and reduced osteogenic differentiation capacity, as well as the increased adipogenic potentials. Histologic analysis confirmed less bone formation and more fatty degeneration in Atp6v1h +/- mice in the different age groups. Q-PCR analysis revealed that loss of ATP6V1H function downregulated the mRNA level of TGF-β1 receptor, and its binding molecule, subunit β of adaptor protein complex 2 (AP-2), suggesting ATP6V1H regulates the proliferation and differentiation of BMSCs by interacting with TGF-β receptor I and AP-2 complex. Copyright © 2018. Published by Elsevier Inc.

  14. Fundamental mode of ultra-low frequency electrostatic dust-cyclotron surface waves in a magnetized complex plasma with drifting ions

    NASA Astrophysics Data System (ADS)

    Lee, Seungjun; Lee, Myoung-Jae

    2012-10-01

    The electrostatic dust-cyclotron (EDC) waves in a magnetized dusty plasma was reported that they could be excited by gravity in a collisional plasma [1]. Rosenberg suggested that EDC waves could be excited by ions drifting along the magnetic field in a collisional plasma containing dust grains with large thermal speeds [2]. The existing investigations, however, focus on EDC volume waves in which the boundary effects are not considered. In this work, we attempt to obtain some physical results concerning the fundamental mode of EDC surface wave and the stability of wave by utilizing a kinetic method. The EDC surface wave is assumed to propagate along an external magnetic field at the interface between the plasma and the vacuum. The plasma is comprised of drifting ions flowing along an external magnetic field. To derive the growth rate of surface waves, we employ the specular reflection boundary conditions. The EDC surface wave is found to be unstable when the ion drift velocity is larger than the phase velocity of the wave. In addition, the wave becomes to be more unstable if dust particles carry more negative charges.[4pt] [1] N. D'Angelo, Phys. Lett. A 323, 445 (2004).[0pt] [2] M. Rosenberg, Phys. Scr. 82, 035505 (2010).

  15. Encoding-related brain activity during deep processing of verbal materials: a PET study.

    PubMed

    Fujii, Toshikatsu; Okuda, Jiro; Tsukiura, Takashi; Ohtake, Hiroya; Suzuki, Maki; Kawashima, Ryuta; Itoh, Masatoshi; Fukuda, Hiroshi; Yamadori, Atsushi

    2002-12-01

    The recent advent of neuroimaging techniques provides an opportunity to examine brain regions related to a specific memory process such as episodic memory encoding. There is, however, a possibility that areas active during an assumed episodic memory encoding task, compared with a control task, involve not only areas directly relevant to episodic memory encoding processes but also areas associated with other cognitive processes for on-line information. We used positron emission tomography (PET) to differentiate these two kinds of regions. Normal volunteers were engaged in deep (semantic) or shallow (phonological) processing of new or repeated words during PET. Results showed that deep processing, compared with shallow processing, resulted in significantly better recognition performance and that this effect was associated with activation of various brain areas. Further analyses revealed that there were regions directly relevant to episodic memory encoding in the anterior part of the parahippocampal gyrus, inferior frontal gyrus, supramarginal gyrus, anterior cingulate gyrus, and medial frontal lobe in the left hemisphere. Our results demonstrated that several regions, including the medial temporal lobe, play a role in episodic memory encoding.

  16. Prenatal alcohol exposure and cellular differentiation: a role for Polycomb and Trithorax group proteins in FAS phenotypes?

    PubMed

    Veazey, Kylee J; Muller, Daria; Golding, Michael C

    2013-01-01

    Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell-cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell's identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes--the Polycomb and Trithorax proteins--are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder.

  17. Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy.

    PubMed

    Shamseldin, Hanan E; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S; Gleeson, Joseph G; Alkuraya, Fowzan S

    2016-01-07

    Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. A linear-encoding model explains the variability of the target morphology in regeneration

    PubMed Central

    Lobo, Daniel; Solano, Mauricio; Bubenik, George A.; Levin, Michael

    2014-01-01

    A fundamental assumption of today's molecular genetics paradigm is that complex morphology emerges from the combined activity of low-level processes involving proteins and nucleic acids. An inherent characteristic of such nonlinear encodings is the difficulty of creating the genetic and epigenetic information that will produce a given self-assembling complex morphology. This ‘inverse problem’ is vital not only for understanding the evolution, development and regeneration of bodyplans, but also for synthetic biology efforts that seek to engineer biological shapes. Importantly, the regenerative mechanisms in deer antlers, planarian worms and fiddler crabs can solve an inverse problem: their target morphology can be altered specifically and stably by injuries in particular locations. Here, we discuss the class of models that use pre-specified morphological goal states and propose the existence of a linear encoding of the target morphology, making the inverse problem easy for these organisms to solve. Indeed, many model organisms such as Drosophila, hydra and Xenopus also develop according to nonlinear encodings producing linear encodings of their final morphologies. We propose the development of testable models of regeneration regulation that combine emergence with a top-down specification of shape by linear encodings of target morphology, driving transformative applications in biomedicine and synthetic bioengineering. PMID:24402915

  19. Differentiation and Response Bias in Episodic Memory: Evidence from Reaction Time Distributions

    ERIC Educational Resources Information Center

    Criss, Amy H.

    2010-01-01

    In differentiation models, the processes of encoding and retrieval produce an increase in the distribution of memory strength for targets and a decrease in the distribution of memory strength for foils as the amount of encoding increases. This produces an increase in the hit rate and decrease in the false-alarm rate for a strongly encoded compared…

  20. Compression of surface myoelectric signals using MP3 encoding.

    PubMed

    Chan, Adrian D C

    2011-01-01

    The potential of MP3 compression of surface myoelectric signals is explored in this paper. MP3 compression is a perceptual-based encoder scheme, used traditionally to compress audio signals. The ubiquity of MP3 compression (e.g., portable consumer electronics and internet applications) makes it an attractive option for remote monitoring and telemedicine applications. The effects of muscle site and contraction type are examined at different MP3 encoding bitrates. Results demonstrate that MP3 compression is sensitive to the myoelectric signal bandwidth, with larger signal distortion associated with myoelectric signals that have higher bandwidths. Compared to other myoelectric signal compression techniques reported previously (embedded zero-tree wavelet compression and adaptive differential pulse code modulation), MP3 compression demonstrates superior performance (i.e., lower percent residual differences for the same compression ratios).

  1. The contributions of non-numeric dimensions to number encoding, representations, and decision-making factors.

    PubMed

    Odic, Darko

    2017-01-01

    Leibovich et al. suggest that congruency effects in number perception (biases towards smaller, denser, etc., dots) are evidence for the number's dependence on these dimensions. I argue that they fail to differentiate between effects at three distinct levels of number perception - encoding, representations, and decision making - and that differentiating between these allows the number to be independent from, but correlated with, non-numeric dimensions.

  2. Time dependent effects of stress prior to encoding on event-related potentials and 24 h delayed retrieval.

    PubMed

    Quaedflieg, Conny W E M; Schwabe, Lars; Meyer, Thomas; Smeets, Tom

    2013-12-01

    Stress can exert profound effects on memory encoding. Here, we investigated whether (sub)cortical information processing during encoding and memory retrieval at a 24 h delayed test are affected by the temporal proximity between stress and memory encoding. Sixty-four participants engaged in the Maastricht Acute Stress Test (MAST) or a no-stress control condition either immediately before (i.e., proximate condition) or 30 min before (i.e., distant condition) a picture encoding task. In general, stress decreased the number of freely recalled and recognized pictures and increased the number of false alarms. However, timing of stress exposure did not differentially affect picture recall, recognition or selective attention processes (i.e., LPP). Nevertheless, stress-induced cortisol responses and correctly recognized neutral pictures were positively associated within the proximate stress condition but negatively associated within the distant stress condition. These findings suggest that the time at which a stressor is applied might differentially impact the association between stress-induced cortisol elevations and memory formation and indicate the need for a finer delineation of the time window during which glucocorticoids affect memory formation processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Iterative deep convolutional encoder-decoder network for medical image segmentation.

    PubMed

    Jung Uk Kim; Hak Gu Kim; Yong Man Ro

    2017-07-01

    In this paper, we propose a novel medical image segmentation using iterative deep learning framework. We have combined an iterative learning approach and an encoder-decoder network to improve segmentation results, which enables to precisely localize the regions of interest (ROIs) including complex shapes or detailed textures of medical images in an iterative manner. The proposed iterative deep convolutional encoder-decoder network consists of two main paths: convolutional encoder path and convolutional decoder path with iterative learning. Experimental results show that the proposed iterative deep learning framework is able to yield excellent medical image segmentation performances for various medical images. The effectiveness of the proposed method has been proved by comparing with other state-of-the-art medical image segmentation methods.

  4. Complex formation between the protein components of methane monooxygenase from Methylosinus trichosporium OB3b. Identification of sites of component interaction.

    PubMed

    Fox, B G; Liu, Y; Dege, J E; Lipscomb, J D

    1991-01-05

    Kinetic, spectroscopic, and chemical evidence for the formation of specific catalytically essential complexes between the three protein components of the soluble form of methane monooxygenase from Methylosinus trichosporium OB3b is reported. The effects of the concentrations of the reductase and component B on the hydroxylation activity of the reconstituted enzyme system has been numerically simulated based on a kinetic model which assumes formation of multiple high affinity complexes with the hydroxylase component during catalysis. The formation of several of these complexes has been directly demonstrated. By using EPR spectroscopy, the binding of approximately 2 mol of component B/mol of hydroxylase (subunit structure (alpha beta gamma)2) is shown to significantly change the electronic environment of the mu-(H/R)-oxo-bridged binuclear iron cluster of the hydroxylase in both the mixed valent (Fe(II).Fe(III)) and fully reduced (Fe(II).Fe(II)) states. Protein-protein complexes between the reductase and component B as well as between the reductase and hydroxylase have been shown to form by monitoring quenching of the tryptophan fluorescence spectrum of either the component B (KD approximately 0.4 microM) or hydroxylase (two binding sites, KDa approximately 10 nM, KDb approximately 8 microM). The observed KD values are in agreement with the best fit values from the kinetic simulation. Through the use of the covalent zero length cross-linking reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), the binding sites of the component B and reductase were shown to be on the hydroxylase alpha and beta subunits, respectively. The alpha and beta subunits of the hydroxylase are cross-linked by EDC suggesting that they are juxtaposed. EDC also caused the rapid loss of the ability of the monomeric component B to stimulate the hydroxylation reaction suggesting that cross-linking of reactive groups on the protein surface had occurred. This effect was inhibited by the

  5. Effects of the plasmid-encoded toxin of enteroaggregative Escherichia coli on focal adhesion complexes

    PubMed Central

    Cappello, Renato E; Estrada-Gutierrez, Guadalupe; Irles, Claudine; Giono-Cerezo, Silvia; Bloch, Robert J; Nataro, James P

    2011-01-01

    Enteroaggregative Escherichia coli (EAEC) is an emerging diarrheal pathogen. Many EAEC strains produce the plasmid encoded toxin (Pet), which elicits cytotoxic effects on human intestinal tissue. Pet-intoxicated HEp-2 cells exhibit rounding and detachment from the substratum, accompanied by loss of F-actin stress fibers and condensation of the spectrin-containing membrane cytoskeleton. Although studies suggest that Pet directly cleaves spectrin, it is not known if this is the essential mode of action of the toxin. In addition, the effects of Pet on cytoskeletal elements other than actin and spectrin have not been reported. Here, we demonstrate by immunofluorescence that upon Pet intoxication, HEp-2 and HT29 cells lose focal adhesion complexes (FAC), a process that includes redistribution of focal adhesion kinase (FAK), α-actinin, paxillin, vinculin, F-actin, and spectrin itself. This redistribution was coupled with depletion of phosphotyrosine labeling at FACs. Immunoblotting and immunoprecipitation experiments revealed that FAK was tyrosine dephosphorylated, prior to the redistribution of FAK and spectrin. Moreover, phosphatase inhibition blocked cell retraction, suggesting that tyrosine dephosphorylation is an event that precedes FAK cleavage. Finally, we show that in vitro tyrosine-dephophorylated FAK was susceptible to Pet cleavage. These data suggest that mechanisms other than spectrin redistribution occur during Pet intoxication. PMID:21205005

  6. QSAR-like models: a potential tool for the selection of PhACs and EDCs for monitoring purposes in drinking water treatment systems--a review.

    PubMed

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-12-01

    Recent studies have demonstrated the presence of trace-level pharmaceutically active compounds (PhACs) and endocrine disrupting compounds (EDCs) in a number of finished drinking waters (DWs). Since there is sparse knowledge currently available on the potential effects on human health associated with the chronic exposure to trace levels of these Emerging Contaminants (ECs) through routes such as DW, it is suggested that the most appropriate criterion is a treatment criterion in order to prioritize ECs to be monitored during DW preparation. Hence, only the few ECs showing the lowest removals towards a given DW Treatment (DWT) process would serve as indicators of the overall efficiency of this process and would be relevant for DW quality monitoring. In addition, models should be developed for estimating the removal of ECs in DWT processes, thereby overcoming the practical difficulties of experimentally assessing each compound. Therefore, the present review has two objectives: (1) to provide an overview of the recent scientific surveys on the occurrence of PhACs and EDCs in finished DWs; and (2) to propose the potential of Quantitative-Structure-Activity-Relationship-(QSAR)-like models to rank ECs found in environmental waters, including parent compounds, metabolites and transformation products, in order to select the most relevant compounds to be considered as indicators for monitoring purposes in DWT systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Differential gene expression in ripening banana fruit.

    PubMed Central

    Clendennen, S K; May, G D

    1997-01-01

    During banana (Musa acuminata L.) fruit ripening ethylene production triggers a developmental cascade that is accompanied by a massive conversion of starch to sugars, an associated burst of respiratory activity, and an increase in protein synthesis. Differential screening of cDNA libraries representing banana pulp at ripening stages 1 and 3 has led to the isolation of 11 nonredundant groups of differentially expressed mRNAs. Identification of these transcripts by partial sequence analysis indicates that two of the mRNAs encode proteins involved in carbohydrate metabolism, whereas others encode proteins thought to be associated with pathogenesis, senescence, or stress responses in plants. Their relative abundance in the pulp and tissue-specific distribution in greenhouse-grown banana plants were determined by northern-blot analyses. The relative abundance of transcripts encoding starch synthase, granule-bound starch synthase, chitinase, lectin, and a type-2 metallothionein decreased in pulp during ripening. Transcripts encoding endochitinase, beta-1,3-glucanase, a thaumatin-like protein, ascorbate peroxidase, metallothionein, and a putative senescence-related protein increased early in ripening. The elucidation of the molecular events associated with banana ripening will facilitate a better understanding and control of these processes, and will allow us to attain our long-term goal of producing candidate oral vaccines in transgenic banana plants. PMID:9342866

  8. PROVIDING A BETTER UNDERSTANDING OF THE SCIENCE UNDERLYING THE EFFECTS, EXPOSURE, ASSESSMENT, AND MANAGEMENT OF EDCS: DOES MILD HYPOTHYROIDISM INDUCED BY ENVIRONMENTAL CONTAMINANTS IRREVERSIBLY ALTER CNS FUNCTION IN THE JUVENILE AND ADULT ANIMAL?

    EPA Science Inventory

    SUMMARY: The NTD research project on Endocrine-Disrupting Chemicals (EDC) is focused on the effects of thyroid hormone (TH) deficiencies on the developing brain and is one component of a larger NHEERL research program evaluating androgen, estrogen, and thyroid-disrupting chemical...

  9. Patterns and processes in the genetic differentiation of the Brachionus calyciflorus complex, a passively dispersing freshwater zooplankton.

    PubMed

    Xiang, Xian-ling; Xi, Yi-long; Wen, Xin-li; Zhang, Gen; Wang, Jin-xia; Hu, Ke

    2011-05-01

    Elucidating the evolutionary patterns and processes of extant species is an important objective of any research program that seeks to understand population divergence and, ultimately, speciation. The island-like nature and temporal fluctuation of limnetic habitats create opportunities for genetic differentiation in rotifers through space and time. To gain further understanding of spatio-temporal patterns of genetic differentiation in rotifers other than the well-studied Brachionus plicatilis complex in brackish water, a total of 318 nrDNA ITS sequences from the B. calyciflorus complex in freshwater were analysed using phylogenetic and phylogeographic methods. DNA taxonomy conducted by both the sequence divergence and the GMYC model suggested the occurrence of six potential cryptic species, supported also by reproductive isolation among the tested lineages. The significant genetic differentiation and non-significant correlation between geographic and genetic distances existed in the most abundant cryptic species, BcI-W and Bc-SW. The large proportion of genetic variability for cryptic species Bc-SW was due to differences between sampling localities within seasons, rather than between different seasons. Nested Clade Analysis suggested allopatric or past fragmentation, contiguous range expansion and long-distance colonization possibly coupled with subsequent fragmentation as the probable main forces shaping the present-day phylogeographic structure of the B. calyciflorus species complex. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. A SSVEP Stimuli Encoding Method Using Trinary Frequency-Shift Keying Encoded SSVEP (TFSK-SSVEP).

    PubMed

    Zhao, Xing; Zhao, Dechun; Wang, Xia; Hou, Xiaorong

    2017-01-01

    SSVEP is a kind of BCI technology with advantage of high information transfer rate. However, due to its nature, frequencies could be used as stimuli are scarce. To solve such problem, a stimuli encoding method which encodes SSVEP signal using Frequency Shift-Keying (FSK) method is developed. In this method, each stimulus is controlled by a FSK signal which contains three different frequencies that represent "Bit 0," "Bit 1" and "Bit 2" respectively. Different to common BFSK in digital communication, "Bit 0" and "Bit 1" composited the unique identifier of stimuli in binary bit stream form, while "Bit 2" indicates the ending of a stimuli encoding. EEG signal is acquired on channel Oz, O1, O2, Pz, P3, and P4, using ADS1299 at the sample rate of 250 SPS. Before original EEG signal is quadrature demodulated, it is detrended and then band-pass filtered using FFT-based FIR filtering to remove interference. Valid peak of the processed signal is acquired by calculating its derivative and converted into bit stream using window method. Theoretically, this coding method could implement at least 2 n -1 ( n is the length of bit command) stimulus while keeping the ITR the same. This method is suitable to implement stimuli on a monitor and where the frequency and phase could be used to code stimuli is limited as well as implementing portable BCI devices which is not capable of performing complex calculations.

  11. Distribution and Phylogeny of EFL and EF-1α in Euglenozoa Suggest Ancestral Co-Occurrence Followed by Differential Loss

    PubMed Central

    Gile, Gillian H.; Faktorová, Drahomíra; Castlejohn, Christina A.; Burger, Gertraud; Lang, B. Franz; Farmer, Mark A.; Lukeš, Julius; Keeling, Patrick J.

    2009-01-01

    Background The eukaryotic elongation factor EF-1α (also known as EF1A) catalyzes aminoacyl-tRNA binding by the ribosome during translation. Homologs of this essential protein occur in all domains of life, and it was previously thought to be ubiquitous in eukaryotes. Recently, however, a number of eukaryotes were found to lack EF-1α and instead encode a related protein called EFL (for EF-Like). EFL-encoding organisms are scattered widely across the tree of eukaryotes, and all have close relatives that encode EF-1α. This intriguingly complex distribution has been attributed to multiple lateral transfers because EFL's near mutual exclusivity with EF-1α makes an extended period of co-occurrence seem unlikely. However, differential loss may play a role in EFL evolution, and this possibility has been less widely discussed. Methodology/Principal Findings We have undertaken an EST- and PCR-based survey to determine the distribution of these two proteins in a previously under-sampled group, the Euglenozoa. EF-1α was found to be widespread and monophyletic, suggesting it is ancestral in this group. EFL was found in some species belonging to each of the three euglenozoan lineages, diplonemids, kinetoplastids, and euglenids. Conclusions/Significance Interestingly, the kinetoplastid EFL sequences are specifically related despite the fact that the lineages in which they are found are not sisters to one another, suggesting that EFL and EF-1α co-occurred in an early ancestor of kinetoplastids. This represents the strongest phylogenetic evidence to date that differential loss has contributed to the complex distribution of EFL and EF-1α. PMID:19357788

  12. ERP Correlates of Encoding Success and Encoding Selectivity in Attention Switching

    PubMed Central

    Yeung, Nick

    2016-01-01

    Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures—memory selectivity and global memory—to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm—in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials—with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable. PMID:27907075

  13. Translation and Assembly of Radiolabeled Mitochondrial DNA-Encoded Protein Subunits from Cultured Cells and Isolated Mitochondria.

    PubMed

    Formosa, Luke E; Hofer, Annette; Tischner, Christin; Wenz, Tina; Ryan, Michael T

    2016-01-01

    In higher eukaryotes, the mitochondrial electron transport chain consists of five multi-subunit membrane complexes responsible for the generation of cellular ATP. Of these, four complexes are under dual genetic control as they contain subunits encoded by both the mitochondrial and nuclear genomes, thereby adding another layer of complexity to the puzzle of respiratory complex biogenesis. These subunits must be synthesized and assembled in a coordinated manner in order to ensure correct biogenesis of different respiratory complexes. Here, we describe techniques to (1) specifically radiolabel proteins encoded by mtDNA to monitor the rate of synthesis using pulse labeling methods, and (2) analyze the stability, assembly, and turnover of subunits using pulse-chase methods in cultured cells and isolated mitochondria.

  14. Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation

    PubMed Central

    Cesar, Beatriz; Abud, Ana Paula R.; de Oliveira, Carolina C.; Cardoso, Francolino; Bernardi, Raffaello Popa Di; Guimarães, Fernando S. F.; Gabardo, Juarez; de Freitas Buchi, Dorly

    2011-01-01

    A homeopathic complex medication (HCM), with immunomodulatory properties, is recommended for patients with depressed immune systems. Previous studies demonstrated that the medication induces an increase in leukocyte number. The bone marrow microenvironment is composed of growth factors, stromal cells, an extracellular matrix and progenitor cells that differentiate into mature blood cells. Mice were our biological model used in this research. We now report in vivo immunophenotyping of total bone marrow cells and ex vivo effects of the medication on mononuclear cell differentiation at different times. Cells were examined by light microscopy and cytokine levels were measured in vitro. After in vivo treatment with HCM, a pool of cells from the new marrow microenvironment was analyzed by flow cytometry to detect any trend in cell alteration. The results showed decreases, mainly, in CD11b and TER-119 markers compared with controls. Mononuclear cells were used to analyze the effects of ex vivo HCM treatment and the number of cells showing ring nuclei, niche cells and activated macrophages increased in culture, even in the absence of macrophage colony-stimulating factor. Cytokines favoring stromal cell survival and differentiation in culture were induced in vitro. Thus, we observe that HCM is immunomodulatory, either alone or in association with other products. PMID:19736221

  15. Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome.

    PubMed

    Bicknell, Louise S; Walker, Sarah; Klingseisen, Anna; Stiff, Tom; Leitch, Andrea; Kerzendorfer, Claudia; Martin, Carol-Anne; Yeyati, Patricia; Al Sanna, Nouriya; Bober, Michael; Johnson, Diana; Wise, Carol; Jackson, Andrew P; O'Driscoll, Mark; Jeggo, Penny A

    2011-02-27

    Studies into disorders of extreme growth failure (for example, Seckel syndrome and Majewski osteodysplastic primordial dwarfism type II) have implicated fundamental cellular processes of DNA damage response signaling and centrosome function in the regulation of human growth. Here we report that mutations in ORC1, encoding a subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. We establish that these mutations disrupt known ORC1 functions including pre-replicative complex formation and origin activation. ORC1 deficiency perturbs S-phase entry and S-phase progression. Additionally, we show that Orc1 depletion in zebrafish is sufficient to markedly reduce body size during rapid embryonic growth. Our data suggest a model in which ORC1 mutations impair replication licensing, slowing cell cycle progression and consequently impeding growth during development, particularly at times of rapid proliferation. These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing.

  16. DNA-Encoded Dynamic Combinatorial Chemical Libraries.

    PubMed

    Reddavide, Francesco V; Lin, Weilin; Lehnert, Sarah; Zhang, Yixin

    2015-06-26

    Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus

    PubMed Central

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S.

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites. PMID:27588023

  18. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

    PubMed

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

  19. The NuRD complex component p66 suppresses photoreceptor neuron regeneration in planarians.

    PubMed

    Vásquez-Doorman, Constanza; Petersen, Christian P

    2016-06-01

    Regeneration involves precise control of cell fate to produce an appropriate complement of tissues formed within a blastema. Several chromatin-modifying complexes have been identified as required for regeneration in planarians, but it is unclear whether this class of molecules uniformly promotes the production of differentiated cells. We identify a function for p66, encoding a DNA-binding protein component of the NuRD (nucleosome remodeling and deacetylase) complex, as well as the chromodomain helicase chd4, in suppressing production of photoreceptor neurons (PRNs) in planarians. This suppressive effect appeared restricted to PRNs because p66 inhibition did not influence numbers of eye pigment cup cells (PCCs) and decreased numbers of brain neurons and epidermal progenitors. PRNs from p66(RNAi) animals differentiated with some abnormalities but nonetheless produced arrestin+ projections to the brain. p66 inhibition produced excess ovo+otxA+ PRN progenitors without affecting numbers of ovo+otxA- PCC progenitors, and ovo and otxA were each required for the p66(RNAi) excess PRN phenotype. Together these results suggest that p66 acts through the NuRD complex to suppress PRN production by limiting expression of lineage-specific transcription factors.

  20. Global gene expression during stringent response in Corynebacterium glutamicum in presence and absence of the rel gene encoding (p)ppGpp synthase

    PubMed Central

    Brockmann-Gretza, Olaf; Kalinowski, Jörn

    2006-01-01

    Background The stringent response is the initial reaction of microorganisms to nutritional stress. During stringent response the small nucleotides (p)ppGpp act as global regulators and reprogram bacterial transcription. In this work, the genetic network controlled by the stringent response was characterized in the amino acid-producing Corynebacterium glutamicum. Results The transcriptome of a C. glutamicum rel gene deletion mutant, unable to synthesize (p)ppGpp and to induce the stringent response, was compared with that of its rel-proficient parent strain by microarray analysis. A total of 357 genes were found to be transcribed differentially in the rel-deficient mutant strain. In a second experiment, the stringent response was induced by addition of DL-serine hydroxamate (SHX) in early exponential growth phase. The time point of the maximal effect on transcription was determined by real-time RT-PCR using the histidine and serine biosynthetic genes. Transcription of all of these genes reached a maximum at 10 minutes after SHX addition. Microarray experiments were performed comparing the transcriptomes of SHX-induced cultures of the rel-proficient strain and the rel mutant. The differentially expressed genes were grouped into three classes. Class A comprises genes which are differentially regulated only in the presence of an intact rel gene. This class includes the non-essential sigma factor gene sigB which was upregulated and a large number of genes involved in nitrogen metabolism which were downregulated. Class B comprises genes which were differentially regulated in response to SHX in both strains, independent of the rel gene. A large number of genes encoding ribosomal proteins fall into this class, all being downregulated. Class C comprises genes which were differentially regulated in response to SHX only in the rel mutant. This class includes genes encoding putative stress proteins and global transcriptional regulators that might be responsible for the complex

  1. Differential Binary Encoding Method for Calibrating Image Sensors Based on IOFBs

    PubMed Central

    Fernández, Pedro R.; Lázaro-Galilea, José Luis; Gardel, Alfredo; Espinosa, Felipe; Bravo, Ignacio; Cano, Ángel

    2012-01-01

    Image transmission using incoherent optical fiber bundles (IOFBs) requires prior calibration to obtain the spatial in-out fiber correspondence necessary to reconstruct the image captured by the pseudo-sensor. This information is recorded in a Look-Up Table called the Reconstruction Table (RT), used later for reordering the fiber positions and reconstructing the original image. This paper presents a very fast method based on image-scanning using spaces encoded by a weighted binary code to obtain the in-out correspondence. The results demonstrate that this technique yields a remarkable reduction in processing time and the image reconstruction quality is very good compared to previous techniques based on spot or line scanning, for example. PMID:22666023

  2. Inactivation of Genes Encoding Subunits of the Peripheral and Membrane Arms of Neurospora Mitochondrial Complex I and Effects on Enzyme Assembly

    PubMed Central

    Duarte, M.; Sousa, R.; Videira, A.

    1995-01-01

    We have isolated and characterized the nuclear genes encoding the 12.3-kD subunit of the membrane arm and the 29.9-kD subunit of the peripheral arm of complex I from Neurospora crassa. The former gene was known to be located in linkage group I and the latter is now assigned to linkage group IV of the fungal genome. The genes were separately transformed into different N. crassa strains and transformants with duplicated DNA sequences were isolated. Selected transformants were then mated with other strains to generate repeat-induced point mutations in both copies of the genes present in the nucleus of the parental transformant. From the progeny of the crosses, we were then able to recover two individual mutants lacking the 12.3- and 29.9-kD proteins in their mitochondria, mutants nuo12.3 and nuo29.9, respectively. Several other subunits of complex I are present in the mutant organelles, although with altered stoichiometries as compared with those in the wild-type strain. Based on the analysis of Triton-solubilized mitochondrial complexes in sucrose gradients, neither mutant is able to fully assemble complex I. Our results indicate that mutant nuo12.3 separately assembles the peripheral arm and most of the membrane arm of the enzyme. Mutant nuo29.9 seems to accumulate the membrane arm of complex I and being devoid of the peripheral part. This implicates the 29.9-kD protein in an early step of complex I assembly. PMID:7768434

  3. A Novel Nonparametric Approach for Neural Encoding and Decoding Models of Multimodal Receptive Fields.

    PubMed

    Agarwal, Rahul; Chen, Zhe; Kloosterman, Fabian; Wilson, Matthew A; Sarma, Sridevi V

    2016-07-01

    Pyramidal neurons recorded from the rat hippocampus and entorhinal cortex, such as place and grid cells, have diverse receptive fields, which are either unimodal or multimodal. Spiking activity from these cells encodes information about the spatial position of a freely foraging rat. At fine timescales, a neuron's spike activity also depends significantly on its own spike history. However, due to limitations of current parametric modeling approaches, it remains a challenge to estimate complex, multimodal neuronal receptive fields while incorporating spike history dependence. Furthermore, efforts to decode the rat's trajectory in one- or two-dimensional space from hippocampal ensemble spiking activity have mainly focused on spike history-independent neuronal encoding models. In this letter, we address these two important issues by extending a recently introduced nonparametric neural encoding framework that allows modeling both complex spatial receptive fields and spike history dependencies. Using this extended nonparametric approach, we develop novel algorithms for decoding a rat's trajectory based on recordings of hippocampal place cells and entorhinal grid cells. Results show that both encoding and decoding models derived from our new method performed significantly better than state-of-the-art encoding and decoding models on 6 minutes of test data. In addition, our model's performance remains invariant to the apparent modality of the neuron's receptive field.

  4. Nuclear-encoded mitochondrial complex I gene expression is restored to normal levels by inhibition of unedited ATP9 transgene expression in Arabidopsis thaliana.

    PubMed

    Busi, María V; Gómez-Casati, Diego F; Perales, Mariano; Araya, Alejandro; Zabaleta, Eduardo

    2006-01-01

    Mitochondria play an important role during sporogenesis in plants. The steady state levels of the nuclear-encoded mitochondrial complex I (nCI), PSST, TYKY and NADHBP transcripts increase in flowers of male-sterile plants with impairment of mitochondrial function generated by the expression of the unedited version of ATP9 (u-ATP9). This suggests a nuclear control of nCI genes in response to the mitochondrial flaw. To evaluate this hypothesis, transgenic plants carrying the GUS reporter gene, under the control of the PSST, TYKY and NADHBP promoters, were constructed. We present evidence that suppression by antisense strategy of the expression of u-ATP9 restores the normal levels of three nCI transcripts, indicating that the increase in PSST, TYKY and NADHBP in plants with a mitochondrial flaw occurs at the transcriptional level. The data presented here support the hypothesis that a mitochondrial dysfunction triggers a retrograde signaling which induce some nuclear-encoded mitochondrial genes. Moreover, these results demonstrate that this is a valuable experimental model for studying nucleus-mitochondria cross-talk events.

  5. The differential effect of trigeminal vs. peripheral pain stimulation on visual processing and memory encoding is influenced by pain-related fear.

    PubMed

    Schmidt, K; Forkmann, K; Sinke, C; Gratz, M; Bitz, A; Bingel, U

    2016-07-01

    Compared to peripheral pain, trigeminal pain elicits higher levels of fear, which is assumed to enhance the interruptive effects of pain on concomitant cognitive processes. In this fMRI study we examined the behavioral and neural effects of trigeminal (forehead) and peripheral (hand) pain on visual processing and memory encoding. Cerebral activity was measured in 23 healthy subjects performing a visual categorization task that was immediately followed by a surprise recognition task. During the categorization task subjects received concomitant noxious electrical stimulation on the forehead or hand. Our data show that fear ratings were significantly higher for trigeminal pain. Categorization and recognition performance did not differ between pictures that were presented with trigeminal and peripheral pain. However, object categorization in the presence of trigeminal pain was associated with stronger activity in task-relevant visual areas (lateral occipital complex, LOC), memory encoding areas (hippocampus and parahippocampus) and areas implicated in emotional processing (amygdala) compared to peripheral pain. Further, individual differences in neural activation between the trigeminal and the peripheral condition were positively related to differences in fear ratings between both conditions. Functional connectivity between amygdala and LOC was increased during trigeminal compared to peripheral painful stimulation. Fear-driven compensatory resource activation seems to be enhanced for trigeminal stimuli, presumably due to their exceptional biological relevance. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Expression of c-Fes protein isoforms correlates with differentiation in myeloid leukemias.

    PubMed

    Carlson, Anne; Berkowitz, Jeanne McAdara; Browning, Damaris; Slamon, Dennis J; Gasson, Judith C; Yates, Karen E

    2005-05-01

    The cellular fes gene encodes a 93-kilodalton protein-tyrosine kinase (p93) that is expressed in both normal and neoplastic myeloid cells. Increased c-Fes expression is associated with differentiation in normal myeloid cells and cell lines. Our hypothesis was that primary leukemia cells would show a similar pattern of increased expression in more differentiated cells. Therefore, we compared c-Fes expression in cells with an undifferentiated, blast phenotype (acute myelogenous leukemia--AML) to cells with a differentiated phenotype (chronic myelogenous leukemia--CML). Instead of differences in p93 expression levels, we found complex patterns of c-Fes immunoreactive proteins that corresponded with differentiation in normal and leukemic myeloid cells. The "blast" pattern consisted of c-Fes immunoreactive proteins p93, p74, and p70; the "differentiated" pattern showed two additional c-Fes immunoreactive proteins, p67 and p62. Using mRNA from mouse and human cell lines, we found deletion of one or more exons in the c-fes mRNA. Those deletions predicted truncation of conserved domains (CDC15/FCH and SH2) involved in protein-protein interactions. No deletions were found, however, within the kinase domain. We infer that alternative splicing generates a family of c-Fes proteins. This may be a mechanism to direct the c-Fes kinase domain to different subcellular locations and/or substrates at specific stages of myeloid cell differentiation.

  7. Context dependent prediction and category encoding for DPCM image compression

    NASA Technical Reports Server (NTRS)

    Beaudet, Paul R.

    1989-01-01

    Efficient compression of image data requires the understanding of the noise characteristics of sensors as well as the redundancy expected in imagery. Herein, the techniques of Differential Pulse Code Modulation (DPCM) are reviewed and modified for information-preserving data compression. The modifications include: mapping from intensity to an equal variance space; context dependent one and two dimensional predictors; rationale for nonlinear DPCM encoding based upon an image quality model; context dependent variable length encoding of 2x2 data blocks; and feedback control for constant output rate systems. Examples are presented at compression rates between 1.3 and 2.8 bits per pixel. The need for larger block sizes, 2D context dependent predictors, and the hope for sub-bits-per-pixel compression which maintains spacial resolution (information preserving) are discussed.

  8. A SSVEP Stimuli Encoding Method Using Trinary Frequency-Shift Keying Encoded SSVEP (TFSK-SSVEP)

    PubMed Central

    Zhao, Xing; Zhao, Dechun; Wang, Xia; Hou, Xiaorong

    2017-01-01

    SSVEP is a kind of BCI technology with advantage of high information transfer rate. However, due to its nature, frequencies could be used as stimuli are scarce. To solve such problem, a stimuli encoding method which encodes SSVEP signal using Frequency Shift–Keying (FSK) method is developed. In this method, each stimulus is controlled by a FSK signal which contains three different frequencies that represent “Bit 0,” “Bit 1” and “Bit 2” respectively. Different to common BFSK in digital communication, “Bit 0” and “Bit 1” composited the unique identifier of stimuli in binary bit stream form, while “Bit 2” indicates the ending of a stimuli encoding. EEG signal is acquired on channel Oz, O1, O2, Pz, P3, and P4, using ADS1299 at the sample rate of 250 SPS. Before original EEG signal is quadrature demodulated, it is detrended and then band-pass filtered using FFT-based FIR filtering to remove interference. Valid peak of the processed signal is acquired by calculating its derivative and converted into bit stream using window method. Theoretically, this coding method could implement at least 2n−1 (n is the length of bit command) stimulus while keeping the ITR the same. This method is suitable to implement stimuli on a monitor and where the frequency and phase could be used to code stimuli is limited as well as implementing portable BCI devices which is not capable of performing complex calculations. PMID:28626393

  9. Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

    PubMed Central

    Ravens, Sarina; Fournier, Marjorie; Ye, Tao; Stierle, Matthieu; Dembele, Doulaye; Chavant, Virginie; Tora, Làszlò

    2014-01-01

    The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation. DOI: http://dx.doi.org/10.7554/eLife.02104.001 PMID:24898753

  10. Rhizobial peptidase HrrP cleaves host-encoded signaling peptides and mediates symbiotic compatibility

    PubMed Central

    Price, Paul A.; Tanner, Houston R.; Dillon, Brett A.; Shabab, Mohammed; Walker, Graham C.; Griffitts, Joel S.

    2015-01-01

    Legume–rhizobium pairs are often observed that produce symbiotic root nodules but fail to fix nitrogen. Using the Sinorhizobium meliloti and Medicago truncatula symbiotic system, we previously described several naturally occurring accessory plasmids capable of disrupting the late stages of nodule development while enhancing bacterial proliferation within the nodule. We report here that host range restriction peptidase (hrrP), a gene found on one of these plasmids, is capable of conferring both these properties. hrrP encodes an M16A family metallopeptidase whose catalytic activity is required for these symbiotic effects. The ability of hrrP to suppress nitrogen fixation is conditioned upon the genotypes of both the host plant and the hrrP-expressing rhizobial strain, suggesting its involvement in symbiotic communication. Purified HrrP protein is capable of degrading a range of nodule-specific cysteine-rich (NCR) peptides encoded by M. truncatula. NCR peptides are crucial signals used by M. truncatula for inducing and maintaining rhizobial differentiation within nodules, as demonstrated in the accompanying article [Horváth B, et al. (2015) Proc Natl Acad Sci USA, 10.1073/pnas.1500777112]. The expression pattern of hrrP and its effects on rhizobial morphology are consistent with the NCR peptide cleavage model. This work points to a symbiotic dialogue involving a complex ensemble of host-derived signaling peptides and bacterial modifier enzymes capable of adjusting signal strength, sometimes with exploitative outcomes. PMID:26401024

  11. Rhizobial peptidase HrrP cleaves host-encoded signaling peptides and mediates symbiotic compatibility.

    PubMed

    Price, Paul A; Tanner, Houston R; Dillon, Brett A; Shabab, Mohammed; Walker, Graham C; Griffitts, Joel S

    2015-12-08

    Legume-rhizobium pairs are often observed that produce symbiotic root nodules but fail to fix nitrogen. Using the Sinorhizobium meliloti and Medicago truncatula symbiotic system, we previously described several naturally occurring accessory plasmids capable of disrupting the late stages of nodule development while enhancing bacterial proliferation within the nodule. We report here that host range restriction peptidase (hrrP), a gene found on one of these plasmids, is capable of conferring both these properties. hrrP encodes an M16A family metallopeptidase whose catalytic activity is required for these symbiotic effects. The ability of hrrP to suppress nitrogen fixation is conditioned upon the genotypes of both the host plant and the hrrP-expressing rhizobial strain, suggesting its involvement in symbiotic communication. Purified HrrP protein is capable of degrading a range of nodule-specific cysteine-rich (NCR) peptides encoded by M. truncatula. NCR peptides are crucial signals used by M. truncatula for inducing and maintaining rhizobial differentiation within nodules, as demonstrated in the accompanying article [Horváth B, et al. (2015) Proc Natl Acad Sci USA, 10.1073/pnas.1500777112]. The expression pattern of hrrP and its effects on rhizobial morphology are consistent with the NCR peptide cleavage model. This work points to a symbiotic dialogue involving a complex ensemble of host-derived signaling peptides and bacterial modifier enzymes capable of adjusting signal strength, sometimes with exploitative outcomes.

  12. Visual short-term memory: activity supporting encoding and maintenance in retinotopic visual cortex.

    PubMed

    Sneve, Markus H; Alnæs, Dag; Endestad, Tor; Greenlee, Mark W; Magnussen, Svein

    2012-10-15

    Recent studies have demonstrated that retinotopic cortex maintains information about visual stimuli during retention intervals. However, the process by which transient stimulus-evoked sensory responses are transformed into enduring memory representations is unknown. Here, using fMRI and short-term visual memory tasks optimized for univariate and multivariate analysis approaches, we report differential involvement of human retinotopic areas during memory encoding of the low-level visual feature orientation. All visual areas show weaker responses when memory encoding processes are interrupted, possibly due to effects in orientation-sensitive primary visual cortex (V1) propagating across extrastriate areas. Furthermore, intermediate areas in both dorsal (V3a/b) and ventral (LO1/2) streams are significantly more active during memory encoding compared with non-memory (active and passive) processing of the same stimulus material. These effects in intermediate visual cortex are also observed during memory encoding of a different stimulus feature (spatial frequency), suggesting that these areas are involved in encoding processes on a higher level of representation. Using pattern-classification techniques to probe the representational content in visual cortex during delay periods, we further demonstrate that simply initiating memory encoding is not sufficient to produce long-lasting memory traces. Rather, active maintenance appears to underlie the observed memory-specific patterns of information in retinotopic cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. A Developmental Study of Conceptual, Semantic Differential, and Acoustical Dimensions as Encoding Categories in Short-Term Memory. Final Report.

    ERIC Educational Resources Information Center

    Pender, Nola J.

    The purpose of this research was to investigate developmental changes in encoding processes. It attempted to determine the extent to which children of varying ages utilize semantic (denotative or connotative) and acoustical encoding categories in a short-term memory task. It appears to be a reasonable assumption that as associational hierarchies…

  14. Hippocampal place cell encoding of sloping terrain.

    PubMed

    Porter, Blake S; Schmidt, Robert; Bilkey, David K

    2018-05-21

    Effective navigation relies on knowledge of one's environment. A challenge to effective navigation is accounting for the time and energy costs of routes. Irregular terrain in ecological environments poses a difficult navigational problem as organisms ought to avoid effortful slopes to minimize travel costs. Route planning and navigation have previously been shown to involve hippocampal place cells and their ability to encode and store information about an organism's environment. However, little is known about how place cells may encode the slope of space and associated energy costs as experiments are traditionally carried out in flat, horizontal environments. We set out to investigate how dorsal-CA1 place cells in rats encode systematic changes to the slope of an environment by tilting a shuttle box from flat to 15° and 25° while minimizing external cue change. Overall, place cell encoding of tilted space was as robust as their encoding of flat ground as measured by traditional place cell metrics such as firing rates, spatial information, coherence, and field size. A large majority of place cells did, however, respond to slope by undergoing partial, complex remapping when the environment was shifted from one tilt angle to another. The propensity for place cells to remap did not, however, depend on the vertical distance the field shifted. Changes in slope also altered the temporal coding of information as measured by the rate of theta phase precession of place cell spikes, which decreased with increasing tilt angles. Together these observations indicate that place cells are sensitive to relatively small changes in terrain slope and that terrain slope may be an important source of information for organizing place cell ensembles. The terrain slope information encoded by place cells could be utilized by efferent regions to determine energetically advantageous routes to goal locations. This article is protected by copyright. All rights reserved. © 2018 Wiley

  15. Metadata Analysis of Phanerochaete chrysosporium Gene Expression Data Identified Common CAZymes Encoding Gene Expression Profiles Involved in Cellulose and Hemicellulose Degradation.

    PubMed

    Kameshwar, Ayyappa Kumar Sista; Qin, Wensheng

    2017-01-01

    In literature, extensive studies have been conducted on popular wood degrading white rot fungus, Phanerochaete chrysosporium about its lignin degrading mechanisms compared to the cellulose and hemicellulose degrading abilities. This study delineates cellulose and hemicellulose degrading mechanisms through large scale metadata analysis of P. chrysosporium gene expression data (retrieved from NCBI GEO) to understand the common expression patterns of differentially expressed genes when cultured on different growth substrates. Genes encoding glycoside hydrolase classes commonly expressed during breakdown of cellulose such as GH-5,6,7,9,44,45,48 and hemicellulose are GH-2,8,10,11,26,30,43,47 were found to be highly expressed among varied growth conditions including simple customized and complex natural plant biomass growth mediums. Genes encoding carbohydrate esterase class enzymes CE (1,4,8,9,15,16) polysaccharide lyase class enzymes PL-8 and PL-14, and glycosyl transferases classes GT (1,2,4,8,15,20,35,39,48) were differentially expressed in natural plant biomass growth mediums. Based on these results, P. chrysosporium, on natural plant biomass substrates was found to express lignin and hemicellulose degrading enzymes more than cellulolytic enzymes except GH-61 (LPMO) class enzymes, in early stages. It was observed that the fate of P. chrysosporium transcriptome is significantly affected by the wood substrate provided. We believe, the gene expression findings in this study plays crucial role in developing genetically efficient microbe with effective cellulose and hemicellulose degradation abilities.

  16. Parametric fMRI analysis of visual encoding in the human medial temporal lobe.

    PubMed

    Rombouts, S A; Scheltens, P; Machielson, W C; Barkhof, F; Hoogenraad, F G; Veltman, D J; Valk, J; Witter, M P

    1999-01-01

    A number of functional brain imaging studies indicate that the medial temporal lobe system is crucially involved in encoding new information into memory. However, most studies were based on differences in brain activity between encoding of familiar vs. novel stimuli. To further study the underlying cognitive processes, we applied a parametric design of encoding. Seven healthy subjects were instructed to encode complex color pictures into memory. Stimuli were presented in a parametric fashion at different rates, thus representing different loads of encoding. Functional magnetic resonance imaging (fMRI) was used to assess changes in brain activation. To determine the number of pictures successfully stored into memory, recognition scores were determined afterwards. During encoding, brain activation occurred in the medial temporal lobe, comparable to the results obtained by others. Increasing the encoding load resulted in an increase in the number of successfully stored items. This was reflected in a significant increase in brain activation in the left lingual gyrus, in the left and right parahippocampal gyrus, and in the right inferior frontal gyrus. This study shows that fMRI can detect changes in brain activation during variation of one aspect of higher cognitive tasks. Further, it strongly supports the notion that the human medial temporal lobe is involved in encoding novel visual information into memory.

  17. The BAF (BRG1/BRM-Associated Factor) chromatin-remodeling complex exhibits ethanol sensitivity in fetal neural progenitor cells and regulates transcription at the miR-9-2 encoding gene locus.

    PubMed

    Burrowes, Sasha G; Salem, Nihal A; Tseng, Alexander M; Balaraman, Sridevi; Pinson, Marisa R; Garcia, Cadianna; Miranda, Rajesh C

    2017-05-01

    Fetal alcohol spectrum disorders are a leading cause of intellectual disability worldwide. Previous studies have shown that developmental ethanol exposure results in loss of microRNAs (miRNAs), including miR-9, and loss of these miRNAs, in turn, mediates some of ethanol's teratogenic effects in the developing brain. We previously found that ethanol increased methylation at the miR-9-2 encoding gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for epigenetic silencing of this locus and consequently, miR-9 loss in NSCs. Therefore, we assessed the role of the BAF (BRG1/BRM-Associated Factor) complex, which disassembles nucleosomes to facilitate access to chromatin, as an epigenetic mediator of ethanol's effects on miR-9. Chromatin immunoprecipitation and DNAse I-hypersensitivity analyses showed that the BAF complex was associated with both transcriptionally accessible and heterochromatic regions of the miR-9-2 locus, and that disintegration of the BAF complex by combined knockdown of BAF170 and BAF155 resulted in a significant decrease in miR-9. We hypothesized that ethanol exposure would result in loss of BAF-complex function at the miR-9-2 locus. However, ethanol exposure significantly increased mRNA transcripts for maturation-associated BAF-complex members BAF170, SS18, ARID2, BAF60a, BRM/BAF190b, and BAF53b. Ethanol also significantly increased BAF-complex binding within an intron containing a CpG island and in the terminal exon encoding precursor (pre)-miR-9-2. These data suggest that the BAF complex may adaptively respond to ethanol exposure to protect against a complete loss of miR-9-2 in fetal NSCs. Chromatin remodeling factors may adapt to the presence of a teratogen, to maintain transcription of critical miRNA regulatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Unusual chromosomal organization of telomeric sequences and expeditious karyotypic differentiation in the recently evolved Mus terricolor complex.

    PubMed

    Sharma, G G; Sharma, T

    1998-01-01

    The Mus terricolor complex displays a stable homozygous arrangement of autosomal heterochromatin variations in the form of accretion of definitive autosomal short arms among three nonoverlapping populations, in concert with an expeditious evolutionary differentiation into three chromosomal species: M. terricolor I, II, and III. In contrast to the highly conservative M. musculus-like chromosomes in the coexisting sibling species, M. booduga, reshuffling and differentiation of centric heterochromatin has occurred in harmony with a revision of centric configurations, resulting in acrocentric and submetacentric autosomes. The chromosomal distribution of the prevalent vertebrate telomeric sequence (TTAGGG)n was examined by fluorescence in situ hybridization to metaphase cells of M. terricolor I, II, and III. An unusual centric organization of internal telomeric sequences was detected in all the submetacentric and acrocentric autosomes. An auxiliary role of these presumably fragile, recombinogenic telomeric sequences in the evolutionary revision of centric configurations in the terricolor complex is hypothesized.

  19. Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins.

    PubMed

    Kasai, Masataka; Ishida, Reiko; Nakahara, Kazuhiko; Okumura, Ko; Aoki, Katsunori

    2018-05-08

    Translin and translin-associated factor X (translin/TRAX) proteins have been implicated in a variety of cellular activities central to nucleic acid metabolism. Accumulating evidence indicates that translin/TRAX complexes participate in processes ensuring the replication of DNA, as well as cell division. Significant progress has been made in understanding the roles of translin/TRAX complexes in RNA metabolism, such as through RNA-induced silencing complex activation or the microRNA depletion that occurs in Dicer deficiency. At the cellular level, translin-deficient (Tsn -/- ) mice display delayed endochondral ossification or progressive bone marrow failure with ectopic osteogenesis and adipogenesis, suggesting involvement in mesenchymal cell differentiation. In this review, we summarize the molecular and cellular functions of translin homo-octamer and translin/TRAX hetero-octamer. Finally, we discuss the multifaceted roles of translin, TRAX, and associated proteins in the healthy and disease states. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of The New York Academy of Sciences.

  20. Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways.

    PubMed

    Manteiga, Sara; Lee, Kyongbum

    2017-04-01

    A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals' effects on adult adipose tissue. Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor's activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ.

  1. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation.

    PubMed

    Wang, Fang; Travins, Jeremy; DeLaBarre, Byron; Penard-Lacronique, Virginie; Schalm, Stefanie; Hansen, Erica; Straley, Kimberly; Kernytsky, Andrew; Liu, Wei; Gliser, Camelia; Yang, Hua; Gross, Stefan; Artin, Erin; Saada, Veronique; Mylonas, Elena; Quivoron, Cyril; Popovici-Muller, Janeta; Saunders, Jeffrey O; Salituro, Francesco G; Yan, Shunqi; Murray, Stuart; Wei, Wentao; Gao, Yi; Dang, Lenny; Dorsch, Marion; Agresta, Sam; Schenkein, David P; Biller, Scott A; Su, Shinsan M; de Botton, Stephane; Yen, Katharine E

    2013-05-03

    A number of human cancers harbor somatic point mutations in the genes encoding isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). These mutations alter residues in the enzyme active sites and confer a gain-of-function in cancer cells, resulting in the accumulation and secretion of the oncometabolite (R)-2-hydroxyglutarate (2HG). We developed a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q. A crystal structure of AGI-6780 complexed with IDH2/R140Q revealed that the inhibitor binds in an allosteric manner at the dimer interface. The results of steady-state enzymology analysis were consistent with allostery and slow-tight binding by AGI-6780. Treatment with AGI-6780 induced differentiation of TF-1 erythroleukemia and primary human acute myelogenous leukemia cells in vitro. These data provide proof-of-concept that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer.

  2. Binding Affinity prediction with Property Encoded Shape Distribution signatures

    PubMed Central

    Das, Sourav; Krein, Michael P.

    2010-01-01

    We report the use of the molecular signatures known as “Property-Encoded Shape Distributions” (PESD) together with standard Support Vector Machine (SVM) techniques to produce validated models that can predict the binding affinity of a large number of protein ligand complexes. This “PESD-SVM” method uses PESD signatures that encode molecular shapes and property distributions on protein and ligand surfaces as features to build SVM models that require no subjective feature selection. A simple protocol was employed for tuning the SVM models during their development, and the results were compared to SFCscore – a regression-based method that was previously shown to perform better than 14 other scoring functions. Although the PESD-SVM method is based on only two surface property maps, the overall results were comparable. For most complexes with a dominant enthalpic contribution to binding (ΔH/-TΔS > 3), a good correlation between true and predicted affinities was observed. Entropy and solvent were not considered in the present approach and further improvement in accuracy would require accounting for these components rigorously. PMID:20095526

  3. Matrix differentiation formulas

    NASA Technical Reports Server (NTRS)

    Usikov, D. A.; Tkhabisimov, D. K.

    1983-01-01

    A compact differentiation technique (without using indexes) is developed for scalar functions that depend on complex matrix arguments which are combined by operations of complex conjugation, transposition, addition, multiplication, matrix inversion and taking the direct product. The differentiation apparatus is developed in order to simplify the solution of extremum problems of scalar functions of matrix arguments.

  4. Developmental programming: Impact of fetal exposure to endocrine disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus

    PubMed Central

    Mahoney, Megan M.; Padmanabhan, Vasantha

    2010-01-01

    Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine disrupting chemicals (EDCs) with estrogenic and anti-androgenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude and MXC on LH surge timing in sheep. The neural mechanisms involved in differential disruption of the LH surge by these two EDCs remains to be elucidated. We tested the hypothesis that differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2 mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC or BPA (5 mg/kg/day) from day 30 to 90 of gestation (term 147 d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F2α, just prior to the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female. PMID:20621667

  5. A channel differential EZW coding scheme for EEG data compression.

    PubMed

    Dehkordi, Vahid R; Daou, Hoda; Labeau, Fabrice

    2011-11-01

    In this paper, a method is proposed to compress multichannel electroencephalographic (EEG) signals in a scalable fashion. Correlation between EEG channels is exploited through clustering using a k-means method. Representative channels for each of the clusters are encoded individually while other channels are encoded differentially, i.e., with respect to their respective cluster representatives. The compression is performed using the embedded zero-tree wavelet encoding adapted to 1-D signals. Simulations show that the scalable features of the scheme lead to a flexible quality/rate tradeoff, without requiring detailed EEG signal modeling.

  6. Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE.

    PubMed

    Trinh, Quang M; Jen, Fei-Yang Arthur; Zhou, Ziru; Chu, Kar Ming; Perry, Marc D; Kephart, Ellen T; Contrino, Sergio; Ruzanov, Peter; Stein, Lincoln D

    2013-07-22

    Funded by the National Institutes of Health (NIH), the aim of the Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the biological research community with a comprehensive encyclopedia of functional genomic elements for both model organisms C. elegans (worm) and D. melanogaster (fly). With a total size of just under 10 terabytes of data collected and released to the public, one of the challenges faced by researchers is to extract biologically meaningful knowledge from this large data set. While the basic quality control, pre-processing, and analysis of the data has already been performed by members of the modENCODE consortium, many researchers will wish to reinterpret the data set using modifications and enhancements of the original protocols, or combine modENCODE data with other data sets. Unfortunately this can be a time consuming and logistically challenging proposition. In recognition of this challenge, the modENCODE DCC has released uniform computing resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE-DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In particular, we have released Galaxy workflows for interpreting ChIP-seq data which use the same quality control (QC) and peak calling standards adopted by the modENCODE and ENCODE communities. For convenience of use, we have created Amazon and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE data, software and other dependencies. Using these resources provides a framework for running consistent and reproducible analyses on modENCODE data, ultimately allowing researchers to use more of their time using modENCODE data, and less time moving it around.

  7. Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE

    PubMed Central

    2013-01-01

    Background Funded by the National Institutes of Health (NIH), the aim of the Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the biological research community with a comprehensive encyclopedia of functional genomic elements for both model organisms C. elegans (worm) and D. melanogaster (fly). With a total size of just under 10 terabytes of data collected and released to the public, one of the challenges faced by researchers is to extract biologically meaningful knowledge from this large data set. While the basic quality control, pre-processing, and analysis of the data has already been performed by members of the modENCODE consortium, many researchers will wish to reinterpret the data set using modifications and enhancements of the original protocols, or combine modENCODE data with other data sets. Unfortunately this can be a time consuming and logistically challenging proposition. Results In recognition of this challenge, the modENCODE DCC has released uniform computing resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE-DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In particular, we have released Galaxy workflows for interpreting ChIP-seq data which use the same quality control (QC) and peak calling standards adopted by the modENCODE and ENCODE communities. For convenience of use, we have created Amazon and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE data, software and other dependencies. Conclusions Using these resources provides a framework for running consistent and reproducible analyses on modENCODE data, ultimately allowing researchers to use more of their time using modENCODE data, and less time moving it around. PMID:23875683

  8. The BOS1 gene encodes an essential 27-kD putative membrane protein that is required for vesicular transport from the ER to the Golgi complex in yeast

    PubMed Central

    1991-01-01

    We recently described the identification of BOS1 (Newman, A., J. Shim, and S. Ferro-Novick. 1990. Mol. Cell. Biol. 10:3405-3414.). BOS1 is a gene that in multiple copy suppresses the growth and secretion defect of bet1 and sec22, two mutants that disrupt transport from the ER to the Golgi complex in yeast. The ability of BOS1 to specifically suppress mutants blocked at a particular stage of the secretory pathway suggested that this gene encodes a protein that functions in this process. The experiments presented in this study support this hypothesis. Specifically, the BOS1 gene was found to be essential for cellular growth. Furthermore, cells depleted of the Bos1 protein fail to transport pro-alpha-factor and carboxypeptidase Y (CPY) to the Golgi apparatus. This defect in export leads to the accumulation of an extensive network of ER and small vesicles. DNA sequence analysis predicts that Bos1 is a 27-kD protein containing a putative membrane- spanning domain. This prediction is supported by differential centrifugation experiments. Thus, Bos1 appears to be a membrane protein that functions in conjunction with Bet1 and Sec22 to facilitate the transport of proteins at a step subsequent to translocation into the ER but before entry into the Golgi apparatus. PMID:2007627

  9. Information encoder/decoder using chaotic systems

    DOEpatents

    Miller, Samuel Lee; Miller, William Michael; McWhorter, Paul Jackson

    1997-01-01

    The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals.

  10. Deviance detection based on regularity encoding along the auditory hierarchy: electrophysiological evidence in humans.

    PubMed

    Escera, Carles; Leung, Sumie; Grimm, Sabine

    2014-07-01

    Detection of changes in the acoustic environment is critical for survival, as it prevents missing potentially relevant events outside the focus of attention. In humans, deviance detection based on acoustic regularity encoding has been associated with a brain response derived from the human EEG, the mismatch negativity (MMN) auditory evoked potential, peaking at about 100-200 ms from deviance onset. By its long latency and cerebral generators, the cortical nature of both the processes of regularity encoding and deviance detection has been assumed. Yet, intracellular, extracellular, single-unit and local-field potential recordings in rats and cats have shown much earlier (circa 20-30 ms) and hierarchically lower (primary auditory cortex, medial geniculate body, inferior colliculus) deviance-related responses. Here, we review the recent evidence obtained with the complex auditory brainstem response (cABR), the middle latency response (MLR) and magnetoencephalography (MEG) demonstrating that human auditory deviance detection based on regularity encoding-rather than on refractoriness-occurs at latencies and in neural networks comparable to those revealed in animals. Specifically, encoding of simple acoustic-feature regularities and detection of corresponding deviance, such as an infrequent change in frequency or location, occur in the latency range of the MLR, in separate auditory cortical regions from those generating the MMN, and even at the level of human auditory brainstem. In contrast, violations of more complex regularities, such as those defined by the alternation of two different tones or by feature conjunctions (i.e., frequency and location) fail to elicit MLR correlates but elicit sizable MMNs. Altogether, these findings support the emerging view that deviance detection is a basic principle of the functional organization of the auditory system, and that regularity encoding and deviance detection is organized in ascending levels of complexity along the auditory

  11. Acute Effects of Alcohol on Encoding and Consolidation of Memory for Emotional Stimuli

    PubMed Central

    Weafer, Jessica; Gallo, David A.; De Wit, Harriet

    2016-01-01

    Objective: Acute doses of alcohol impair memory when administered before encoding of emotionally neutral stimuli but enhance memory when administered immediately after encoding, potentially by affecting memory consolidation. Here, we examined whether alcohol produces similar biphasic effects on memory for positive or negative emotional stimuli. Method: The current study examined memory for emotional stimuli after alcohol (0.8 g/kg) was administered either before stimulus viewing (encoding group; n = 20) or immediately following stimulus viewing (consolidation group; n = 20). A third group received placebo both before and after stimulus viewing (control group; n = 19). Participants viewed the stimuli on one day, and their retrieval was assessed exactly 48 hours later, when they performed a surprise cued recollection and recognition test of the stimuli in a drug-free state. Results: As in previous studies, alcohol administered before encoding impaired memory accuracy, whereas alcohol administered after encoding enhanced memory accuracy. Critically, alcohol effects on cued recollection depended on the valence of the emotional stimuli: Its memory-impairing effects during encoding were greatest for emotional stimuli, whereas its memory-enhancing effects during consolidation were greatest for emotionally neutral stimuli. Effects of alcohol on recognition were not related to stimulus valence. Conclusions: This study extends previous findings with memory for neutral stimuli, showing that alcohol differentially affects the encoding and consolidation of memory for emotional stimuli. These effects of alcohol on memory for emotionally salient material may contribute to the development of alcohol-related problems, perhaps by dampening memory for adverse consequences of alcohol consumption. PMID:26751358

  12. Similarity, not complexity, determines visual working memory performance.

    PubMed

    Jackson, Margaret C; Linden, David E J; Roberts, Mark V; Kriegeskorte, Nikolaus; Haenschel, Corinna

    2015-11-01

    A number of studies have shown that visual working memory (WM) is poorer for complex versus simple items, traditionally accounted for by higher information load placing greater demands on encoding and storage capacity limits. Other research suggests that it may not be complexity that determines WM performance per se, but rather increased perceptual similarity between complex items as a result of a large amount of overlapping information. Increased similarity is thought to lead to greater comparison errors between items encoded into WM and the test item(s) presented at retrieval. However, previous studies have used different object categories to manipulate complexity and similarity, raising questions as to whether these effects are simply due to cross-category differences. For the first time, here the relationship between complexity and similarity in WM using the same stimulus category (abstract polygons) are investigated. The authors used a delayed discrimination task to measure WM for 1-4 complex versus simple simultaneously presented items and manipulated the similarity between the single test item at retrieval and the sample items at encoding. WM was poorer for complex than simple items only when the test item was similar to 1 of the encoding items, and not when it was dissimilar or identical. The results provide clear support for reinterpretation of the complexity effect in WM as a similarity effect and highlight the importance of the retrieval stage in governing WM performance. The authors discuss how these findings can be reconciled with current models of WM capacity limits. (c) 2015 APA, all rights reserved).

  13. Fast MPEG-CDVS Encoder With GPU-CPU Hybrid Computing.

    PubMed

    Duan, Ling-Yu; Sun, Wei; Zhang, Xinfeng; Wang, Shiqi; Chen, Jie; Yin, Jianxiong; See, Simon; Huang, Tiejun; Kot, Alex C; Gao, Wen

    2018-05-01

    The compact descriptors for visual search (CDVS) standard from ISO/IEC moving pictures experts group has succeeded in enabling the interoperability for efficient and effective image retrieval by standardizing the bitstream syntax of compact feature descriptors. However, the intensive computation of a CDVS encoder unfortunately hinders its widely deployment in industry for large-scale visual search. In this paper, we revisit the merits of low complexity design of CDVS core techniques and present a very fast CDVS encoder by leveraging the massive parallel execution resources of graphics processing unit (GPU). We elegantly shift the computation-intensive and parallel-friendly modules to the state-of-the-arts GPU platforms, in which the thread block allocation as well as the memory access mechanism are jointly optimized to eliminate performance loss. In addition, those operations with heavy data dependence are allocated to CPU for resolving the extra but non-necessary computation burden for GPU. Furthermore, we have demonstrated the proposed fast CDVS encoder can work well with those convolution neural network approaches which enables to leverage the advantages of GPU platforms harmoniously, and yield significant performance improvements. Comprehensive experimental results over benchmarks are evaluated, which has shown that the fast CDVS encoder using GPU-CPU hybrid computing is promising for scalable visual search.

  14. Fast MPEG-CDVS Encoder With GPU-CPU Hybrid Computing

    NASA Astrophysics Data System (ADS)

    Duan, Ling-Yu; Sun, Wei; Zhang, Xinfeng; Wang, Shiqi; Chen, Jie; Yin, Jianxiong; See, Simon; Huang, Tiejun; Kot, Alex C.; Gao, Wen

    2018-05-01

    The compact descriptors for visual search (CDVS) standard from ISO/IEC moving pictures experts group (MPEG) has succeeded in enabling the interoperability for efficient and effective image retrieval by standardizing the bitstream syntax of compact feature descriptors. However, the intensive computation of CDVS encoder unfortunately hinders its widely deployment in industry for large-scale visual search. In this paper, we revisit the merits of low complexity design of CDVS core techniques and present a very fast CDVS encoder by leveraging the massive parallel execution resources of GPU. We elegantly shift the computation-intensive and parallel-friendly modules to the state-of-the-arts GPU platforms, in which the thread block allocation and the memory access are jointly optimized to eliminate performance loss. In addition, those operations with heavy data dependence are allocated to CPU to resolve the extra but non-necessary computation burden for GPU. Furthermore, we have demonstrated the proposed fast CDVS encoder can work well with those convolution neural network approaches which has harmoniously leveraged the advantages of GPU platforms, and yielded significant performance improvements. Comprehensive experimental results over benchmarks are evaluated, which has shown that the fast CDVS encoder using GPU-CPU hybrid computing is promising for scalable visual search.

  15. What–where–when memory and encoding strategies in healthy aging

    PubMed Central

    2016-01-01

    Older adults exhibit disproportionate impairments in memory for item-associations. These impairments may stem from an inability to self-initiate deep encoding strategies. The present study investigates this using the “treasure-hunt task”; a what–where–when style episodic memory test that requires individuals to “hide” items around complex scenes. This task separately assesses memory for item, location, and temporal order, as well as bound what–where–when information. The results suggest that older adults are able to ameliorate integration memory deficits by using self-initiated encoding strategies when these are externally located and therefore place reduced demands on working memory and attentional resources. PMID:26884230

  16. Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail

    USGS Publications Warehouse

    Ottinger, M.A.; Abdelnabi, M.A.; Henry, P.; McGary, S.; Thompson, N.; Wu, J.M.

    2001-01-01

    Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in

  17. The Anaerobe-Specific Orange Protein Complex of Desulfovibrio vulgaris Hildenborough Is Encoded by Two Divergent Operons Coregulated by σ54 and a Cognate Transcriptional Regulator▿†

    PubMed Central

    Fiévet, Anouchka; My, Laetitia; Cascales, Eric; Ansaldi, Mireille; Pauleta, Sofia R.; Moura, Isabel; Dermoun, Zorah; Bernard, Christophe S.; Dolla, Alain; Aubert, Corinne

    2011-01-01

    Analysis of sequenced bacterial genomes revealed that the genomes encode more than 30% hypothetical and conserved hypothetical proteins of unknown function. Among proteins of unknown function that are conserved in anaerobes, some might be determinants of the anaerobic way of life. This study focuses on two divergent clusters specifically found in anaerobic microorganisms and mainly composed of genes encoding conserved hypothetical proteins. We show that the two gene clusters DVU2103-DVU2104-DVU2105 (orp2) and DVU2107-DVU2108-DVU2109 (orp1) form two divergent operons transcribed by the σ54-RNA polymerase. We further demonstrate that the σ54-dependent transcriptional regulator DVU2106, located between orp1 and orp2, collaborates with σ54-RNA polymerase to orchestrate the simultaneous expression of the divergent orp operons. DVU2106, whose structural gene is transcribed by the σ70-RNA polymerase, negatively retrocontrols its own expression. By using an endogenous pulldown strategy, we identify a physiological complex composed of DVU2103, DVU2104, DVU2105, DVU2108, and DVU2109. Interestingly, inactivation of DVU2106, which is required for orp operon transcription, induces morphological defects that are likely linked to the absence of the ORP complex. A putative role of the ORP proteins in positioning the septum during cell division is discussed. PMID:21531797

  18. Musicians Show General Enhancement of Complex Sound Encoding and Better Inhibition of Irrelevant Auditory Change in Music: An ERP Study

    PubMed Central

    Kaganovich, Natalya; Kim, Jihyun; Herring, Caryn; Schumaker, Jennifer; MacPherson, Megan; Weber-Fox, Christine

    2012-01-01

    Using electrophysiology, we have examined two questions in relation to musical training – namely, whether it enhances sensory encoding of the human voice and whether it improves the ability to ignore irrelevant auditory change. Participants performed an auditory distraction task, in which they identified each sound as either short (350 ms) or long (550 ms) and ignored a change in sounds’ timbre. Sounds consisted of a male and a female voice saying a neutral sound [a], and of a cello and a French Horn playing an F3 note. In some blocks, musical sounds occurred on 80% of trials, while voice sounds on 20% of trials. In other blocks, the reverse was true. Participants heard naturally recorded sounds in half of experimental blocks and their spectrally-rotated versions in the other half. Regarding voice perception, we found that musicians had a larger N1 ERP component not only to vocal sounds but also to their never before heard spectrally-rotated versions. We, therefore, conclude that musical training is associated with a general improvement in the early neural encoding of complex sounds. Regarding the ability to ignore irrelevant auditory change, musicians’ accuracy tended to suffer less from the change in sounds’ timbre, especially when deviants were musical notes. This behavioral finding was accompanied by a marginally larger re-orienting negativity in musicians, suggesting that their advantage may lie in a more efficient disengagement of attention from the distracting auditory dimension. PMID:23301775

  19. Information encoder/decoder using chaotic systems

    DOEpatents

    Miller, S.L.; Miller, W.M.; McWhorter, P.J.

    1997-10-21

    The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals. 32 figs.

  20. Complexity of parallel implementation of domain decomposition techniques for elliptic partial differential equations

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

    Gropp, W.D.; Keyes, D.E.

    1988-03-01

    The authors discuss the parallel implementation of preconditioned conjugate gradient (PCG)-based domain decomposition techniques for self-adjoint elliptic partial differential equations in two dimensions on several architectures. The complexity of these methods is described on a variety of message-passing parallel computers as a function of the size of the problem, number of processors and relative communication speeds of the processors. They show that communication startups are very important, and that even the small amount of global communication in these methods can significantly reduce the performance of many message-passing architectures.

  1. Linear phase encoding for holographic data storage with a single phase-only spatial light modulator.

    PubMed

    Nobukawa, Teruyoshi; Nomura, Takanori

    2016-04-01

    A linear phase encoding is presented for realizing a compact and simple holographic data storage system with a single spatial light modulator (SLM). This encoding method makes it possible to modulate a complex amplitude distribution with a single phase-only SLM in a holographic storage system. In addition, an undesired light due to the imperfection of an SLM can be removed by spatial frequency filtering with a Nyquist aperture. The linear phase encoding is introduced to coaxial holographic data storage. The generation of a signal beam using linear phase encoding is experimentally verified in an interferometer. In a coaxial holographic data storage system, single data recording, shift selectivity, and shift multiplexed recording are experimentally demonstrated.

  2. Stochastic Differential Games with Complexity Constrained Strategies.

    DTIC Science & Technology

    1982-03-01

    Stochastic Differential Game ..... . 39 2.-1 A b.mp.C mcamp e ..... .... ................ . ..... qu CHAPTER 3 - PROBLEM OF STATE ESTDAATION IN TWO...similar to that used vith the differential game , e vould find that the optimal K has the form K T[T* + ( 2.58) This is not a surprising ansver in viev...Examle Example: Discrete-time, one-stage scalar game Transition equation: Y X + U - V P-offtfuntinl: J E + {5 2 CV Cc~ c>a> 0 Observation equations: Z x

  3. An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.

    PubMed

    Tasseff, Ryan; Jensen, Holly A; Congleton, Johanna; Dai, David; Rogers, Katharine V; Sagar, Adithya; Bunaciu, Rodica P; Yen, Andrew; Varner, Jeffrey D

    2017-10-30

    In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.

  4. Semantic attributes are encoded in human electrocorticographic signals during visual object recognition.

    PubMed

    Rupp, Kyle; Roos, Matthew; Milsap, Griffin; Caceres, Carlos; Ratto, Christopher; Chevillet, Mark; Crone, Nathan E; Wolmetz, Michael

    2017-03-01

    Non-invasive neuroimaging studies have shown that semantic category and attribute information are encoded in neural population activity. Electrocorticography (ECoG) offers several advantages over non-invasive approaches, but the degree to which semantic attribute information is encoded in ECoG responses is not known. We recorded ECoG while patients named objects from 12 semantic categories and then trained high-dimensional encoding models to map semantic attributes to spectral-temporal features of the task-related neural responses. Using these semantic attribute encoding models, untrained objects were decoded with accuracies comparable to whole-brain functional Magnetic Resonance Imaging (fMRI), and we observed that high-gamma activity (70-110Hz) at basal occipitotemporal electrodes was associated with specific semantic dimensions (manmade-animate, canonically large-small, and places-tools). Individual patient results were in close agreement with reports from other imaging modalities on the time course and functional organization of semantic processing along the ventral visual pathway during object recognition. The semantic attribute encoding model approach is critical for decoding objects absent from a training set, as well as for studying complex semantic encodings without artificially restricting stimuli to a small number of semantic categories. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Quantification of residual EDU (N-ethyl-N'-(dimethylaminopropyl) carbodiimide (EDC) hydrolyzed urea derivative) and other residual by LC-MS/MS.

    PubMed

    Lei, Q Paula; Lamb, David H; Shannon, Anthony G; Cai, Xinxing; Heller, Ronald K; Huang, Michael; Zablackis, Earl; Ryall, Robert; Cash, Patricia

    2004-12-25

    An LC-MS/MS method for determination of the break down product of N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) urea derivative, EDU, has been developed and validated for monitoring the residual coupling reagents. Results indicate that the method exhibits suitable specificity, sensitivity, precision, linearity and accuracy for quantification of residual EDU in the presence of meningococcal polysaccharide-diphtheria toxoid conjugate vaccine and other vaccine matrix compounds. The assay has been validated for a detection range of 10-100 ng/mL and then successfully transferred to quality control (QC) lab. This same method has also been applied to the determination of residual diaminohexane (DAH) in the presence of EDU. LC-MS/MS has proven to be useful as a quick and sensitive approach for simultaneous determination of multiple residual compounds in glycoconjugate vaccine samples.

  6. Heterocellular interaction enhances recruitment of {alpha} and {beta}-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

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

    Talhouk, Rabih S.; Mroue, Rana; Mokalled, Mayssa

    2008-11-01

    Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation ({beta}-casein expression) was evaluated. Heterocellular interaction is critical for {beta}-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complexmore » components ({alpha}-catenin, {beta}-catenin and ZO-2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although {beta}-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and {beta}-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear {beta}-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of {beta}-catenin in GJ complexes.« less

  7. The CCR4-NOT complex mediates deadenylation and degradation of stem cell mRNAs and promotes planarian stem cell differentiation.

    PubMed

    Solana, Jordi; Gamberi, Chiara; Mihaylova, Yuliana; Grosswendt, Stefanie; Chen, Chen; Lasko, Paul; Rajewsky, Nikolaus; Aboobaker, A Aziz

    2013-01-01

    Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A) tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A) tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology.

  8. The CCR4-NOT Complex Mediates Deadenylation and Degradation of Stem Cell mRNAs and Promotes Planarian Stem Cell Differentiation

    PubMed Central

    Solana, Jordi; Gamberi, Chiara; Mihaylova, Yuliana; Grosswendt, Stefanie; Chen, Chen; Lasko, Paul; Rajewsky, Nikolaus; Aboobaker, A. Aziz

    2013-01-01

    Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A) tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A) tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology. PMID:24367277

  9. Differentiating subgroups of children with special health care needs by health status and complexity of health care needs.

    PubMed

    Bramlett, Matthew D; Read, Debra; Bethell, Christina; Blumberg, Stephen J

    2009-03-01

    Our objective is to use the Children with Special Health Care Needs (CSHCN) Screener to identify subgroups of CSHCN differentiated by health status and complexity of need. Data are from the National Survey of Children with Special Health Care Needs, 2001 and the National Survey of Children's Health, 2003 (conducted by the Maternal and Child Health Bureau and the National Center for Health Statistics); and the 2001 and 2002 Medical Expenditure Panel Survey, conducted by the Agency for Healthcare Research and Quality. A broad array of variables measuring health status, complexity of need, and related issues are examined by subgroupings of CSHCN. Relative to other CSHCN, CSHCN with functional limitations or who qualify on more CSHCN Screener items have poorer health status and more complex health care needs. They more often experience a variety of health issues; their insurance is more often inadequate; the impact of their conditions on their families is higher; and their medical costs are higher. In the absence of information on specific conditions, health status, or complexity of need, the CSHCN Screener alone can be used to create useful analytic subgroups that differ on these dimensions. The proposed subgroups, based on the type or number of CSHCN screening criteria, differentiate CSHCN by health status and complexity of health care needs, and also show differences in the impact of their conditions on their families, costs of their medical care, and prevalence of various health problems.

  10. Human jagged polypeptide, encoding nucleic acids and methods of use

    DOEpatents

    Li, Linheng; Hood, Leroy

    2000-01-01

    The present invention provides an isolated polypeptide exhibiting substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the polypeptide does not have the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. The invention further provides an isolated nucleic acid molecule containing a nucleotide sequence encoding substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the nucleotide sequence does not encode the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. Also provided herein is a method of inhibiting differentiation of hematopoietic progenitor cells by contacting the progenitor cells with an isolated JAGGED polypeptide, or active fragment thereof. The invention additionally provides a method of diagnosing Alagille Syndrome in an individual. The method consists of detecting an Alagille Syndrome disease-associated mutation linked to a JAGGED locus.

  11. Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers.

    PubMed

    Dogan, Selen; Simsek, Tayup

    2016-07-01

    The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose-response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless. Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Fragments of a larger whole: retrieval cues constrain observed neural correlates of memory encoding.

    PubMed

    Otten, Leun J

    2007-09-01

    Laying down a new memory involves activity in a number of brain regions. Here, it is shown that the particular regions associated with successful encoding depend on the way in which memory is probed. Event-related functional magnetic resonance imaging signals were acquired while subjects performed an incidental encoding task on a series of visually presented words denoting objects. A recognition memory test using the Remember/Know procedure to separate responses based on recollection and familiarity followed 1 day later. Critically, half of the studied objects were cued with a corresponding spoken word, and half with a corresponding picture. Regardless of cue, activity in prefrontal and hippocampal regions predicted subsequent recollection of a word. Type of retrieval cue modulated activity in prefrontal, temporal, and parietal cortices. Words subsequently recognized on the basis of a sense of familiarity were at study also associated with differential activity in a number of brain regions, some of which were probe dependent. Thus, observed neural correlates of successful encoding are constrained by type of retrieval cue, and are only fragments of all encoding-related neural activity. Regions exhibiting cue-specific effects may be sites that support memory through the degree of overlap between the processes engaged during encoding and those engaged during retrieval.

  13. Plasmonic Encoding

    DTIC Science & Technology

    2014-10-06

    The nanosheets, like many SERS platforms, are ideally suited for encoding schemes based on the SERS signal from a variety of thiolated small...counterfeiting purposes. The nanosheets, like many SERS platforms, are ideally suited for encoding schemes based on the SERS signal from a variety of...environments ( like the surface of human hair). 2. Nanoflares In 2007, we first introduced the concept of nanoflares. Nanoflares are a new class of

  14. Dissection of affinity captured LINE-1 macromolecular complexes

    PubMed Central

    Mita, Paolo; Jiang, Hua; Adney, Emily M; Wudzinska, Aleksandra; Badri, Sana; Ischenko, Dmitry; Eng, George; Burns, Kathleen H; Fenyö, David; Chait, Brian T; Alexeev, Dmitry; Rout, Michael P; Boeke, Jef D

    2018-01-01

    Long Interspersed Nuclear Element-1 (LINE-1, L1) is a mobile genetic element active in human genomes. L1-encoded ORF1 and ORF2 proteins bind L1 RNAs, forming ribonucleoproteins (RNPs). These RNPs interact with diverse host proteins, some repressive and others required for the L1 lifecycle. Using differential affinity purifications, quantitative mass spectrometry, and next generation RNA sequencing, we have characterized the proteins and nucleic acids associated with distinctive, enzymatically active L1 macromolecular complexes. Among them, we describe a cytoplasmic intermediate that we hypothesize to be the canonical ORF1p/ORF2p/L1-RNA-containing RNP, and we describe a nuclear population containing ORF2p, but lacking ORF1p, which likely contains host factors participating in target-primed reverse transcription. PMID:29309035

  15. Is junk DNA bunk? A critique of ENCODE

    PubMed Central

    Doolittle, W. Ford

    2013-01-01

    Do data from the Encyclopedia Of DNA Elements (ENCODE) project render the notion of junk DNA obsolete? Here, I review older arguments for junk grounded in the C-value paradox and propose a thought experiment to challenge ENCODE’s ontology. Specifically, what would we expect for the number of functional elements (as ENCODE defines them) in genomes much larger than our own genome? If the number were to stay more or less constant, it would seem sensible to consider the rest of the DNA of larger genomes to be junk or, at least, assign it a different sort of role (structural rather than informational). If, however, the number of functional elements were to rise significantly with C-value then, (i) organisms with genomes larger than our genome are more complex phenotypically than we are, (ii) ENCODE’s definition of functional element identifies many sites that would not be considered functional or phenotype-determining by standard uses in biology, or (iii) the same phenotypic functions are often determined in a more diffuse fashion in larger-genomed organisms. Good cases can be made for propositions ii and iii. A larger theoretical framework, embracing informational and structural roles for DNA, neutral as well as adaptive causes of complexity, and selection as a multilevel phenomenon, is needed. PMID:23479647

  16. Encoding processes during retrieval tasks.

    PubMed

    Buckner, R L; Wheeler, M E; Sheridan, M A

    2001-04-01

    Episodic memory encoding is pervasive across many kinds of task and often arises as a secondary processing effect in tasks that do not require intentional memorization. To illustrate the pervasive nature of information processing that leads to episodic encoding, a form of incidental encoding was explored based on the "Testing" phenomenon: The incidental-encoding task was an episodic memory retrieval task. Behavioral data showed that performing a memory retrieval task was as effective as intentional instructions at promoting episodic encoding. During fMRI imaging, subjects viewed old and new words and indicated whether they remembered them. Relevant to encoding, the fate of the new words was examined using a second, surprise test of recognition after the imaging session. fMRI analysis of those new words that were later remembered revealed greater activity in left frontal regions than those that were later forgotten - the same pattern of results as previously observed for traditional incidental and intentional episodic encoding tasks. This finding may offer a partial explanation for why repeated testing improves memory performance. Furthermore, the observation of correlates of episodic memory encoding during retrieval tasks challenges some interpretations that arise from direct comparisons between "encoding tasks" and "retrieval tasks" in imaging data. Encoding processes and their neural correlates may arise in many tasks, even those nominally labeled as retrieval tasks by the experimenter.

  17. Molecular cloning of Foxl2 gene and the effects of endocrine-disrupting chemicals on its mRNA level in rare minnow, Gobiocypris rarus.

    PubMed

    Wang, Houpeng; Wu, Tingting; Qin, Fang; Wang, Lihong; Wang, Zaizhao

    2012-06-01

    Endocrine-disrupting chemicals (EDCs) can affect normal sexual differentiation in fish. Foxl2, one forkhead transcription factor, plays an important role in ovarian differentiation in the early development of the female gonad in mammals and fish. How EDCs affect Foxl2 expression is little known. In this study, we isolated a Foxl2 cDNA from the ovary of rare minnow Gobiocypris rarus and examined its expression during early development stages and in different adult tissues. Then, we analyzed Foxl2 expression in G. rarus juvenile following 3-day exposure to 17α- ethinylestradiol (EE2), 4-n-nonylphenol (NP), and bisphenol A (BPA). Alignment of known Foxl2 sequences among vertebrates showed high identity in forkhead domain and C-terminal region with other vertebrate proteins. Quantitative RT-PCR analysis showed that Foxl2 expression was linear decrease and cyp19a1a, the downstream target gene of Foxl2, had no correlation with Foxl2 from 18 to 50 days post fertilization (dpf). Among different adult tissues, Foxl2 is mainly expressed in ovary, brain, gill, eye, and male spleen. In the 3-day exposure, the juvenile fish to EDCs, 0.1 nM EE2, and 1 nM BPA significantly up-regulated the expression of Foxl2 gene, while NP had no effect on Foxl2 expression. Altogether, these results provide basic data for further study on how Foxl2 mediates EDCs impact on the sexual differentiation in G. rarus.

  18. Optical delay encoding for fast timing and detector signal multiplexing in PET

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

    Grant, Alexander M.; Levin, Craig S., E-mail: cslevin@stanford.edu; Molecular Imaging Program at Stanford

    2015-08-15

    Purpose: The large number of detector channels in modern positron emission tomography (PET) scanners poses a challenge in terms of readout electronics complexity. Multiplexing schemes are typically implemented to reduce the number of physical readout channels, but often result in performance degradation. Novel methods of multiplexing in PET must be developed to avoid this data degradation. The preservation of fast timing information is especially important for time-of-flight PET. Methods: A new multiplexing scheme based on encoding detector interaction events with a series of extremely fast overlapping optical pulses with precise delays is demonstrated in this work. Encoding events in thismore » way potentially allows many detector channels to be simultaneously encoded onto a single optical fiber that is then read out by a single digitizer. A two channel silicon photomultiplier-based prototype utilizing this optical delay encoding technique along with dual threshold time-over-threshold is demonstrated. Results: The optical encoding and multiplexing prototype achieves a coincidence time resolution of 160 ps full width at half maximum (FWHM) and an energy resolution of 13.1% FWHM at 511 keV with 3 × 3 × 5 mm{sup 3} LYSO crystals. All interaction information for both detectors, including timing, energy, and channel identification, is encoded onto a single optical fiber with little degradation. Conclusions: Optical delay encoding and multiplexing technology could lead to time-of-flight PET scanners with fewer readout channels and simplified data acquisition systems.« less

  19. Recent advances on the encoding and selection methods of DNA-encoded chemical library.

    PubMed

    Shi, Bingbing; Zhou, Yu; Huang, Yiran; Zhang, Jianfu; Li, Xiaoyu

    2017-02-01

    DNA-encoded chemical library (DEL) has emerged as a powerful and versatile tool for ligand discovery in chemical biology research and in drug discovery. Encoding and selection methods are two of the most important technological aspects of DEL that can dictate the performance and utilities of DELs. In this digest, we have summarized recent advances on the encoding and selection strategies of DEL and also discussed the latest developments on DNA-encoded dynamic library, a new frontier in DEL research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. N-Consecutive-Phase Encoder

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Lee, Ho-Kyoung; Weber, Charles

    1995-01-01

    N-consecutive-phase encoder (NCPE) is conceptual encoder for generating alphabet of N consecutive full-response continuous-phase-modulation (CPM) signals. Enables use of binary preencoder of higher rate than used with simple continuous-phase encoder (CPE). NCPE makes possible to achieve power efficiencies and bandwidth efficiencies greater than conventional trellis coders with continuous-phase frequency-shift keying (CPFSK).

  1. Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodiumfalciparum plastid.

    PubMed

    Biswas, Subir; Lim, Erin E; Gupta, Ankit; Saqib, Uzma; Mir, Snober S; Siddiqi, Mohammad Imran; Ralph, Stuart A; Habib, Saman

    2011-03-01

    Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader sequence targeted GFP to the apicoplast, confirming that PfEF-Ts functions in this organelle. Recombinant PfEF-Ts mediated nucleotide exchange on PfEF-Tu and homology modeling of the PfEF-Tu:PfEF-Ts complex revealed PfEF-Ts-induced structural alterations that would expedite GDP release from PfEF-Tu. Our results establish functional interaction between two apicoplast translation factors encoded by genes residing in different cellular compartments and highlight the significance of their sequence/structural differences from bacterial elongation factors in relation to inhibitor activity. These data provide an experimental system to study the effects of novel inhibitors targeting PfEF-Tu and PfEF-Tu.PfEF-Ts interaction. Our finding that apicoplast EF-Tu possesses chaperone-related disulphide reductase activity also provides a rationale for retention of the tufA gene on the plastid genome. Copyright © 2010 Australian Society for Parasitology Inc. All rights reserved.

  2. Developmental programming: Impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus

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

    Mahoney, Megan M.; Padmanabhan, Vasantha, E-mail: vasantha@umich.ed

    Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseedmore » oil (controls), MXC, or BPA (5 mg/kg/day) from day 30 to 90 of gestation (term 147 d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F{sub 2{alpha}}, just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female.« less

  3. Developmental programming: impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus.

    PubMed

    Mahoney, Megan M; Padmanabhan, Vasantha

    2010-09-01

    Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5mg/kg/day) from day 30 to 90 of gestation (term 147d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F(2alpha), just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female. 2010 Elsevier Inc. All rights reserved.

  4. Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases

    PubMed Central

    Watters, Kelly; Inankur, Bahar; Gardiner, Jaye C.; Warrick, Jay; Sherer, Nathan M.; Yin, John

    2017-01-01

    ABSTRACT The RNA rhinoviruses (RV) encode 2A proteases (2Apro) that contribute essential polyprotein processing and host cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2Apro sequences that act differentially on specific Nups. Since only subsets of Phe/Gly motifs, particularly those within Nup62, Nup98, and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2Apro predict RV genotype-specific targeting of NPC pathways and cargos. To test this idea, transformed HeLa cell lines were created with fluorescent cargos (mCherry) for the importin α/β, transportin 1, and transportin 3 import pathways and the Crm1-mediated export pathway. Live-cell imaging of single cells expressing recombinant RV 2Apro (A16, A45, B04, B14, B52, C02, and C15) showed disruption of each pathway with measurably different efficiencies and reaction rates. The B04 and B52 proteases preferentially targeted Nups in the import pathways, while B04 and C15 proteases were more effective against the export pathway. Virus-type-specific trends were also observed during infection of cells with A16, B04, B14, and B52 viruses or their chimeras, as measured by NF-κB (p65/Rel) translocation into the nucleus and the rates of virus-associated cytopathic effects. This study provides new tools for evaluating the host cell response to RV infections in real time and suggests that differential 2Apro activities explain, in part, strain-dependent host responses and diverse RV disease phenotypes. IMPORTANCE Genetic variation among human rhinovirus types includes unexpected diversity in the genes encoding viral proteases (2Apro) that help these viruses achieve antihost responses. When the enzyme activities of 7 different 2Apro were measured

  5. Encoding model of temporal processing in human visual cortex.

    PubMed

    Stigliani, Anthony; Jeska, Brianna; Grill-Spector, Kalanit

    2017-12-19

    How is temporal information processed in human visual cortex? Visual input is relayed to V1 through segregated transient and sustained channels in the retina and lateral geniculate nucleus (LGN). However, there is intense debate as to how sustained and transient temporal channels contribute to visual processing beyond V1. The prevailing view associates transient processing predominately with motion-sensitive regions and sustained processing with ventral stream regions, while the opposing view suggests that both temporal channels contribute to neural processing beyond V1. Using fMRI, we measured cortical responses to time-varying stimuli and then implemented a two temporal channel-encoding model to evaluate the contributions of each channel. Different from the general linear model of fMRI that predicts responses directly from the stimulus, the encoding approach first models neural responses to the stimulus from which fMRI responses are derived. This encoding approach not only predicts cortical responses to time-varying stimuli from milliseconds to seconds but also, reveals differential contributions of temporal channels across visual cortex. Consistent with the prevailing view, motion-sensitive regions and adjacent lateral occipitotemporal regions are dominated by transient responses. However, ventral occipitotemporal regions are driven by both sustained and transient channels, with transient responses exceeding the sustained. These findings propose a rethinking of temporal processing in the ventral stream and suggest that transient processing may contribute to rapid extraction of the content of the visual input. Importantly, our encoding approach has vast implications, because it can be applied with fMRI to decipher neural computations in millisecond resolution in any part of the brain. Copyright © 2017 the Author(s). Published by PNAS.

  6. Inferior colliculus contributions to phase encoding of stop consonants in an animal model

    PubMed Central

    Warrier, Catherine M; Abrams, Daniel A; Nicol, Trent G; Kraus, Nina

    2011-01-01

    The human auditory brainstem is known to be exquisitely sensitive to fine-grained spectro-temporal differences between speech sound contrasts, and the ability of the brainstem to discriminate between these contrasts is important for speech perception. Recent work has described a novel method for translating brainstem timing differences in response to speech contrasts into frequency-specific phase differentials. Results from this method have shown that the human brainstem response is surprisingly sensitive to phase-differences inherent to the stimuli across a wide extent of the spectrum. Here we use an animal model of the auditory brainstem to examine whether the stimulus-specific phase signatures measured in human brainstem responses represent an epiphenomenon associated with far field (i.e., scalp-recorded) measurement of neural activity, or alternatively whether these specific activity patterns are also evident in auditory nuclei that contribute to the scalp-recorded response, thereby representing a more fundamental temporal processing phenomenon. Responses in anaesthetized guinea pigs to three minimally-contrasting consonant-vowel stimuli were collected simultaneously from the cortical surface vertex and directly from central nucleus of the inferior colliculus (ICc), measuring volume conducted neural activity and multiunit, near-field activity, respectively. Guinea pig surface responses were similar to human scalp-recorded responses to identical stimuli in gross morphology as well as phase characteristics. Moreover, surface recorded potentials shared many phase characteristics with near-field ICc activity. Response phase differences were prominent during formant transition periods, reflecting spectro-temporal differences between syllables, and showed more subtle differences during the identical steady-state periods. ICc encoded stimulus distinctions over a broader frequency range, with differences apparent in the highest frequency ranges analyzed, up to 3000 Hz

  7. Musicians show general enhancement of complex sound encoding and better inhibition of irrelevant auditory change in music: an ERP study.

    PubMed

    Kaganovich, Natalya; Kim, Jihyun; Herring, Caryn; Schumaker, Jennifer; Macpherson, Megan; Weber-Fox, Christine

    2013-04-01

    Using electrophysiology, we have examined two questions in relation to musical training - namely, whether it enhances sensory encoding of the human voice and whether it improves the ability to ignore irrelevant auditory change. Participants performed an auditory distraction task, in which they identified each sound as either short (350 ms) or long (550 ms) and ignored a change in timbre of the sounds. Sounds consisted of a male and a female voice saying a neutral sound [a], and of a cello and a French Horn playing an F3 note. In some blocks, musical sounds occurred on 80% of trials, while voice sounds on 20% of trials. In other blocks, the reverse was true. Participants heard naturally recorded sounds in half of experimental blocks and their spectrally-rotated versions in the other half. Regarding voice perception, we found that musicians had a larger N1 event-related potential component not only to vocal sounds but also to their never before heard spectrally-rotated versions. We therefore conclude that musical training is associated with a general improvement in the early neural encoding of complex sounds. Regarding the ability to ignore irrelevant auditory change, musicians' accuracy tended to suffer less from the change in timbre of the sounds, especially when deviants were musical notes. This behavioral finding was accompanied by a marginally larger re-orienting negativity in musicians, suggesting that their advantage may lie in a more efficient disengagement of attention from the distracting auditory dimension. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Common capacity-limited neural mechanisms of selective attention and spatial working memory encoding

    PubMed Central

    Fusser, Fabian; Linden, David E J; Rahm, Benjamin; Hampel, Harald; Haenschel, Corinna; Mayer, Jutta S

    2011-01-01

    One characteristic feature of visual working memory (WM) is its limited capacity, and selective attention has been implicated as limiting factor. A possible reason why attention constrains the number of items that can be encoded into WM is that the two processes share limited neural resources. Functional magnetic resonance imaging (fMRI) studies have indeed demonstrated commonalities between the neural substrates of WM and attention. Here we investigated whether such overlapping activations reflect interacting neural mechanisms that could result in capacity limitations. To independently manipulate the demands on attention and WM encoding within one single task, we combined visual search and delayed discrimination of spatial locations. Participants were presented with a search array and performed easy or difficult visual search in order to encode one, three or five positions of target items into WM. Our fMRI data revealed colocalised activation for attention-demanding visual search and WM encoding in distributed posterior and frontal regions. However, further analysis yielded two patterns of results. Activity in prefrontal regions increased additively with increased demands on WM and attention, indicating regional overlap without functional interaction. Conversely, the WM load-dependent activation in visual, parietal and premotor regions was severely reduced during high attentional demand. We interpret this interaction as indicating the sites of shared capacity-limited neural resources. Our findings point to differential contributions of prefrontal and posterior regions to the common neural mechanisms that support spatial WM encoding and attention, providing new imaging evidence for attention-based models of WM encoding. PMID:21781193

  9. Multi-output differential technologies

    NASA Astrophysics Data System (ADS)

    Bidare, Srinivas R.

    1997-01-01

    A differential is a very old and proven mechanical device that allows a single input to be split into two outputs having equal torque irrespective of the output speeds. A standard differential is capable of providing only two outputs from a single input. A recently patented multi-output differential technology known as `Plural-Output Differential' allows a single input to be split into many outputs. This new technology is the outcome of a systematic study of complex gear trains (Bidare 1992). The unique feature of a differential (equal torque at different speeds) can be applied to simplify the construction and operation of many complex mechanical devices that require equal torque's or forces at multiple outputs. It is now possible to design a mechanical hand with three or more fingers with equal torque. Since these finger are powered via a differential they are `mechanically intelligent'. A prototype device is operational and has been used to demonstrate the utility and flexibility of the design. In this paper we shall review two devices that utilize the new technology resulting in increased performance, robustness with reduced complexity and cost.

  10. 3D Chemical Patterning of Micromaterials for Encoded Functionality.

    PubMed

    Ceylan, Hakan; Yasa, Immihan Ceren; Sitti, Metin

    2017-03-01

    Programming local chemical properties of microscale soft materials with 3D complex shapes is indispensable for creating sophisticated functionalities, which has not yet been possible with existing methods. Precise spatiotemporal control of two-photon crosslinking is employed as an enabling tool for 3D patterning of microprinted structures for encoding versatile chemical moieties. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false EAS Encoder. 11.32 Section 11.32....32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described... must additionally provide the following minimum specifications: (1) Encoder programming. Access to...

  12. Accelerated Slice Encoding for Metal Artifact Correction

    PubMed Central

    Hargreaves, Brian A.; Chen, Weitian; Lu, Wenmiao; Alley, Marcus T.; Gold, Garry E.; Brau, Anja C. S.; Pauly, John M.; Pauly, Kim Butts

    2010-01-01

    Purpose To demonstrate accelerated imaging with artifact reduction near metallic implants and different contrast mechanisms. Materials and Methods Slice-encoding for metal artifact correction (SEMAC) is a modified spin echo sequence that uses view-angle tilting and slice-direction phase encoding to correct both in-plane and through-plane artifacts. Standard spin echo trains and short-TI inversion recovery (STIR) allow efficient PD-weighted imaging with optional fat suppression. A completely linear reconstruction allows incorporation of parallel imaging and partial Fourier imaging. The SNR effects of all reconstructions were quantified in one subject. 10 subjects with different metallic implants were scanned using SEMAC protocols, all with scan times below 11 minutes, as well as with standard spin echo methods. Results The SNR using standard acceleration techniques is unaffected by the linear SEMAC reconstruction. In all cases with implants, accelerated SEMAC significantly reduced artifacts compared with standard imaging techniques, with no additional artifacts from acceleration techniques. The use of different contrast mechanisms allowed differentiation of fluid from other structures in several subjects. Conclusion SEMAC imaging can be combined with standard echo-train imaging, parallel imaging, partial-Fourier imaging and inversion recovery techniques to offer flexible image contrast with a dramatic reduction of metal-induced artifacts in scan times under 11 minutes. PMID:20373445

  13. Accelerated slice encoding for metal artifact correction.

    PubMed

    Hargreaves, Brian A; Chen, Weitian; Lu, Wenmiao; Alley, Marcus T; Gold, Garry E; Brau, Anja C S; Pauly, John M; Pauly, Kim Butts

    2010-04-01

    To demonstrate accelerated imaging with both artifact reduction and different contrast mechanisms near metallic implants. Slice-encoding for metal artifact correction (SEMAC) is a modified spin echo sequence that uses view-angle tilting and slice-direction phase encoding to correct both in-plane and through-plane artifacts. Standard spin echo trains and short-TI inversion recovery (STIR) allow efficient PD-weighted imaging with optional fat suppression. A completely linear reconstruction allows incorporation of parallel imaging and partial Fourier imaging. The signal-to-noise ratio (SNR) effects of all reconstructions were quantified in one subject. Ten subjects with different metallic implants were scanned using SEMAC protocols, all with scan times below 11 minutes, as well as with standard spin echo methods. The SNR using standard acceleration techniques is unaffected by the linear SEMAC reconstruction. In all cases with implants, accelerated SEMAC significantly reduced artifacts compared with standard imaging techniques, with no additional artifacts from acceleration techniques. The use of different contrast mechanisms allowed differentiation of fluid from other structures in several subjects. SEMAC imaging can be combined with standard echo-train imaging, parallel imaging, partial-Fourier imaging, and inversion recovery techniques to offer flexible image contrast with a dramatic reduction of metal-induced artifacts in scan times under 11 minutes. (c) 2010 Wiley-Liss, Inc.

  14. Genome-wide comparative analysis of NBS-encoding genes between Brassica species and Arabidopsis thaliana.

    PubMed

    Yu, Jingyin; Tehrim, Sadia; Zhang, Fengqi; Tong, Chaobo; Huang, Junyan; Cheng, Xiaohui; Dong, Caihua; Zhou, Yanqiu; Qin, Rui; Hua, Wei; Liu, Shengyi

    2014-01-03

    Plant disease resistance (R) genes with the nucleotide binding site (NBS) play an important role in offering resistance to pathogens. The availability of complete genome sequences of Brassica oleracea and Brassica rapa provides an important opportunity for researchers to identify and characterize NBS-encoding R genes in Brassica species and to compare with analogues in Arabidopsis thaliana based on a comparative genomics approach. However, little is known about the evolutionary fate of NBS-encoding genes in the Brassica lineage after split from A. thaliana. Here we present genome-wide analysis of NBS-encoding genes in B. oleracea, B. rapa and A. thaliana. Through the employment of HMM search and manual curation, we identified 157, 206 and 167 NBS-encoding genes in B. oleracea, B. rapa and A. thaliana genomes, respectively. Phylogenetic analysis among 3 species classified NBS-encoding genes into 6 subgroups. Tandem duplication and whole genome triplication (WGT) analyses revealed that after WGT of the Brassica ancestor, NBS-encoding homologous gene pairs on triplicated regions in Brassica ancestor were deleted or lost quickly, but NBS-encoding genes in Brassica species experienced species-specific gene amplification by tandem duplication after divergence of B. rapa and B. oleracea. Expression profiling of NBS-encoding orthologous gene pairs indicated the differential expression pattern of retained orthologous gene copies in B. oleracea and B. rapa. Furthermore, evolutionary analysis of CNL type NBS-encoding orthologous gene pairs among 3 species suggested that orthologous genes in B. rapa species have undergone stronger negative selection than those in B .oleracea species. But for TNL type, there are no significant differences in the orthologous gene pairs between the two species. This study is first identification and characterization of NBS-encoding genes in B. rapa and B. oleracea based on whole genome sequences. Through tandem duplication and whole genome

  15. Space vehicle onboard command encoder

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A flexible onboard encoder system was designed for the space shuttle. The following areas were covered: (1) implementation of the encoder design into hardware to demonstrate the various encoding algorithms/code formats, (2) modulation techniques in a single hardware package to maintain comparable reliability and link integrity of the existing link systems and to integrate the various techniques into a single design using current technology. The primary function of the command encoder is to accept input commands, generated either locally onboard the space shuttle or remotely from the ground, format and encode the commands in accordance with the payload input requirements and appropriately modulate a subcarrier for transmission by the baseband RF modulator. The following information was provided: command encoder system design, brassboard hardware design, test set hardware and system packaging, and software.

  16. Decapping activators in Saccharomyces cerevisiae act by multiple mechanisms.

    PubMed

    Nissan, Tracy; Rajyaguru, Purusharth; She, Meipei; Song, Haiwei; Parker, Roy

    2010-09-10

    Eukaryotic mRNA degradation often occurs in a process whereby translation initiation is inhibited and the mRNA is targeted for decapping. In yeast cells, Pat1, Scd6, Edc3, and Dhh1 all function to promote decapping by an unknown mechanism(s). We demonstrate that purified Scd6 and a region of Pat1 directly repress translation in vitro by limiting the formation of a stable 48S preinitiation complex. Moreover, while Pat1, Edc3, Dhh1, and Scd6 all bind the decapping enzyme, only Pat1 and Edc3 enhance its activity. We also identify numerous direct interactions between Pat1, Dcp1, Dcp2, Dhh1, Scd6, Edc3, Xrn1, and the Lsm1-7 complex. These observations identify three classes of decapping activators that function to directly repress translation initiation and/or stimulate Dcp1/2. Moreover, Pat1 is identified as critical in mRNA decay by first inhibiting translation initiation, then serving as a scaffold to recruit components of the decapping complex, and finally activating Dcp2. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Encoding electric signals by Gymnotus omarorum: heuristic modeling of tuberous electroreceptor organs.

    PubMed

    Cilleruelo, Esteban R; Caputi, Angel Ariel

    2012-01-24

    The role of different substructures of electroreceptor organs in signal encoding was explored using a heuristic computational model. This model consists of four modules representing the pre-receptor structures, the transducer cells, the synapses and the afferent fiber, respectively. Simulations reproduced previously obtained experimental data. We showed that different electroreceptor types described in the literature can be qualitative modeled with the same set of equations by changing only two parameters, one affecting the filtering properties of the pre-receptor, and the other affecting the transducer module. We studied the responses of different electroreceptor types to natural stimuli using simulations derived from an experimentally-obtained database in which the fish were exposed to resistive or capacitive objects. Our results indicate that phase and frequency spectra are differentially encoded by different subpopulations of tuberous electroreceptors. A different type of receptor responses to the same input is a necessary condition for encoding a multidimensional space of stimuli as in the waveform of the EOD. Our simulation analysis suggested that the electroreceptive mosaic may perform a waveform analysis of electrosensory signals. As in color vision or tactile texture perception, a secondary attribute, "electric color" may be encoded as a parallel activity of various electroreceptor types. This article is part of a Special Issue entitled Neural Coding. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. On the adaptivity and complexity embedded into differential evolution

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

    Senkerik, Roman; Pluhacek, Michal; Jasek, Roman

    2016-06-08

    This research deals with the comparison of the two modern approaches for evolutionary algorithms, which are the adaptivity and complex chaotic dynamics. This paper aims on the investigations on the chaos-driven Differential Evolution (DE) concept. This paper is aimed at the embedding of discrete dissipative chaotic systems in the form of chaotic pseudo random number generators for the DE and comparing the influence to the performance with the state of the art adaptive representative jDE. This research is focused mainly on the possible disadvantages and advantages of both compared approaches. Repeated simulations for Lozi map driving chaotic systems were performedmore » on the simple benchmark functions set, which are more close to the real optimization problems. Obtained results are compared with the canonical not-chaotic and not adaptive DE. Results show that with used simple test functions, the performance of ChaosDE is better in the most cases than jDE and Canonical DE, furthermore due to the unique sequencing in CPRNG given by the hidden chaotic dynamics, thus better and faster selection of unique individuals from population, ChaosDE is faster.« less

  19. Software package for performing experiments about the convolutionally encoded Voyager 1 link

    NASA Technical Reports Server (NTRS)

    Cheng, U.

    1989-01-01

    A software package enabling engineers to conduct experiments to determine the actual performance of long constraint-length convolutional codes over the Voyager 1 communication link directly from the Jet Propulsion Laboratory (JPL) has been developed. Using this software, engineers are able to enter test data from the Laboratory in Pasadena, California. The software encodes the data and then sends the encoded data to a personal computer (PC) at the Goldstone Deep Space Complex (GDSC) over telephone lines. The encoded data are sent to the transmitter by the PC at GDSC. The received data, after being echoed back by Voyager 1, are first sent to the PC at GDSC, and then are sent back to the PC at the Laboratory over telephone lines for decoding and further analysis. All of these operations are fully integrated and are completely automatic. Engineers can control the entire software system from the Laboratory. The software encoder and the hardware decoder interface were developed for other applications, and have been modified appropriately for integration into the system so that their existence is transparent to the users. This software provides: (1) data entry facilities, (2) communication protocol for telephone links, (3) data displaying facilities, (4) integration with the software encoder and the hardware decoder, and (5) control functions.

  20. Decoding spike timing: the differential reverse correlation method

    PubMed Central

    Tkačik, Gašper; Magnasco, Marcelo O.

    2009-01-01

    It is widely acknowledged that detailed timing of action potentials is used to encode information, for example in auditory pathways; however the computational tools required to analyze encoding through timing are still in their infancy. We present a simple example of encoding, based on a recent model of time-frequency analysis, in which units fire action potentials when a certain condition is met, but the timing of the action potential depends also on other features of the stimulus. We show that, as a result, spike-triggered averages are smoothed so much they do not represent the true features of the encoding. Inspired by this example, we present a simple method, differential reverse correlations, that can separate an analysis of what causes a neuron to spike, and what controls its timing. We analyze with this method the leaky integrate-and-fire neuron and show the method accurately reconstructs the model's kernel. PMID:18597928

  1. Epigenetics, chromatin and genome organization: recent advances from the ENCODE project.

    PubMed

    Siggens, L; Ekwall, K

    2014-09-01

    The organization of the genome into functional units, such as enhancers and active or repressed promoters, is associated with distinct patterns of DNA and histone modifications. The Encyclopedia of DNA Elements (ENCODE) project has advanced our understanding of the principles of genome, epigenome and chromatin organization, identifying hundreds of thousands of potential regulatory regions and transcription factor binding sites. Part of the ENCODE consortium, GENCODE, has annotated the human genome with novel transcripts including new noncoding RNAs and pseudogenes, highlighting transcriptional complexity. Many disease variants identified in genome-wide association studies are located within putative enhancer regions defined by the ENCODE project. Understanding the principles of chromatin and epigenome organization will help to identify new disease mechanisms, biomarkers and drug targets, particularly as ongoing epigenome mapping projects generate data for primary human cell types that play important roles in disease. © 2014 The Association for the Publication of the Journal of Internal Medicine.

  2. The hippocampal formation participates in novel picture encoding: evidence from functional magnetic resonance imaging.

    PubMed Central

    Stern, C E; Corkin, S; González, R G; Guimaraes, A R; Baker, J R; Jennings, P J; Carr, C A; Sugiura, R M; Vedantham, V; Rosen, B R

    1996-01-01

    Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however, have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task. High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of novel, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory. Images Fig. 1 Fig. 3 PMID:8710927

  3. Regulated expression of the MRP8 and MRP14 genes during terminal differentiation of human promyelocytic leukemic HL-60 cells

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

    Warner-Bartnicki, A.L.; Murao, S.; Collart, F.R.

    1992-02-14

    The calcium-binding proteins MRP8 and MRP14 are induced during monomyelocytic cell maturation and may mediate the growth arrest in differentiating HL-60 cells. We determined the levels of a protein complex (PC) containing MRP8 and MRP14 and investigated the mechanism by which the genes encoding these proteins are regulated in HL-60 cells treated with the differentiation-inducing agent mycophenolic acid. Elevated levels of the PC were found to directly parallel gains in the steady-state levels of MRP8 and MRP14 mRNA. Transcription studies with the use of nuclear run-on experiments revealed increased transcription initiation at the MRP8 and MRP14 promoters after MPA treatment.more » 1{alpha},25-Dihydroxyvitamin D{sub 3}, which induces HL-60 cell differentiation by another mechanism, was also found to increase transcription initiation at the MRP8 and MRP14 promoters, suggesting that this initiation is the major control of MRP8 and MRP14 gene expression during terminal differentiation of human promyelocytic cells.« less

  4. Epidermal differentiation during ontogeny and after hatching in the snake Liasis fuscus (Pythonidae, Serpentes, Reptilia), with emphasis on the formation of the shedding complex.

    PubMed

    Alibardi, L; Thompson, M B

    2003-04-01

    Differentiation and localization of keratin in the epidermis during embryonic development and up to 3 months posthatching in the Australian water python, Liasis fuscus, was studied by ultrastructural and immunocytochemical methods. Scales arise from dome-like folds in the skin that produce tightly imbricating scales. The dermis of these scales is completely differentiated before any epidermal differentiation begins, with a loose dermis made of mesenchymal cells beneath the differentiating outer scale surface. At this stage (33) the embryo is still unpigmented and two layers of suprabasal cells contain abundant glycogen. At Stage 34 (beginning of pigmentation) the first layers of cells beneath the bilayered periderm (presumptive clear and oberhautchen layers) have not yet formed a shedding complex, within which prehatching shedding takes place. At Stage 35 the shedding complex, consisting of the clear and oberhautchen layers, is discernible. The clear layer contains a fine fibrous network that faces the underlying oberhautchen, where the spinulae initially contain a core of fibrous material and small beta-keratin packets. Differentiation continues at Stage 36 when the beta-layer forms and beta-keratin packets are deposited both on the fibrous core of the oberhautchen and within beta-cells. Mesos cells are produced from the germinal layer but remain undifferentiated. At Stage 37, before hatching, the beta-layer is compact, the mesos layer contains mesos granules, and cells of the alpha-layer are present but are not yet keratinized. They are still only partially differentiated a few hours after hatching, when a new shedding complex is forming underneath. Using antibodies against chick scale beta-keratin resolved at high magnification with immunofluorescent or immunogold conjugates, we offer the first molecular confirmation that in snakes only the oberhautchen component of the shedding complex and the underlying beta cells contain beta-keratin. Initially, there is

  5. Tissue-Specific 5′ Heterogeneity of PPARα Transcripts and Their Differential Regulation by Leptin

    PubMed Central

    Garratt, Emma S.; Vickers, Mark H.; Gluckman, Peter D.; Hanson, Mark A.

    2013-01-01

    The genes encoding nuclear receptors comprise multiple 5′untranslated exons, which give rise to several transcripts encoding the same protein, allowing tissue-specific regulation of expression. Both human and mouse peroxisome proliferator activated receptor (PPAR) α genes have multiple promoters, although their function is unknown. Here we have characterised the rat PPARα promoter region and have identified three alternative PPARα transcripts, which have different transcription start sites owing to the utilisation of distinct first exons. Moreover these alternative PPARα transcripts were differentially expressed between adipose tissue and liver. We show that while the major adipose (P1) and liver (P2) transcripts were both induced by dexamethasone, they were differentially regulated by the PPARα agonist, clofibric acid, and leptin. Leptin had no effect on the adipose-specific P1 transcript, but induced liver-specific P2 promoter activity via a STAT3/Sp1 mechanism. Moreover in Wistar rats, leptin treatment between postnatal day 3–13 led to an increase in P2 but not P1 transcription in adipose tissue which was sustained into adulthood. This suggests that the expression of the alternative PPARα transcripts are in part programmed by early life exposure to leptin leading to persistent change in adipose tissue fatty acid metabolism through specific activation of a quiescent PPARα promoter. Such complexity in the regulation of PPARα may allow the expression of PPARα to be finely regulated in response to environmental factors. PMID:23825665

  6. Sumoylation Dynamics During Keratinocyte Differentiation

    PubMed Central

    Deyrieux, Adeline F.; Rosas-Acosta, Germán; Ozbun, Michelle A.; Wilson, Van G.

    2012-01-01

    Summary SUMO modification regulates the activity of numerous transcription factors that have a direct role in cell cycle progression, apoptosis, cellular proliferation, and development, but its role in differentiation processes is less clear. Keratinocyte differentiation requires the coordinated activation of a series of transcription factors, and as several critical keratinocyte transcription factors are known to be SUMO substrates, we investigated the role of sumoylation in keratinocyte differentiation. In a human keratinocyte cell line model (HaCaT cells), calcium-induced differentiation led to the transient and coordinated transcriptional activation of the genes encoding critical sumoylation system components, including SAE1, SAE2, Ubc9, SENP1, Miz-1 (PIASxβ), SUMO2, and SUMO3. The increased gene expression resulted in higher levels of the respective proteins and changes in the pattern of sumoylated substrate proteins during the differentiation process. Similar to the HaCaT results, stratified human foreskin keratinocytes showed an upregulation of Ubc9 in the suprabasal layers. Lastly, abrogation of sumoylation by Gam1 expression severely disrupted normal HaCaT differentiation, consistent with an important role for sumoylation in the proper progression of this biological process. PMID:17164289

  7. Neural correlates of the encoding of multimodal contextual features

    PubMed Central

    Gottlieb, Lauren J.; Wong, Jenny; de Chastelaine, Marianne; Rugg, Michael D.

    2012-01-01

    Functional magnetic resonance imaging (fMRI) was employed to identify neural regions engaged during the encoding of contextual features belonging to different modalities. Subjects studied objects that were presented to the left or right of fixation. Each object was paired with its name, spoken in either a male or a female voice. The test requirement was to discriminate studied from unstudied pictures and, for each picture judged old, to retrieve its study location and the gender of the voice that spoke its name. Study trials associated with accurate rather than inaccurate location memory demonstrated enhanced activity in the fusiform and parahippocampal cortex and the hippocampus and reduced activity (a negative subsequent memory effect) in the medial occipital cortex. Successful encoding of voice information was associated with enhanced study activity in the right middle superior temporal sulcus and activity reduction in the right superior frontal cortex. These findings support the proposal that encoding of a contextual feature is associated with enhanced activity in regions engaged during its online processing. In addition, they indicate that negative subsequent memory effects can also demonstrate feature-selectivity. Relative to other classes of study trials, trials for which both contextual features were later retrieved demonstrated enhanced activity in the lateral occipital complex and reduced activity in the temporo-parietal junction. These findings suggest that multifeatural encoding was facilitated when the study item was processed efficiently and study processing was not interrupted by redirection of attention toward extraneous events. PMID:23166292

  8. Modulating the focus of attention for spoken words at encoding affects frontoparietal activation for incidental verbal memory.

    PubMed

    Christensen, Thomas A; Almryde, Kyle R; Fidler, Lesley J; Lockwood, Julie L; Antonucci, Sharon M; Plante, Elena

    2012-01-01

    Attention is crucial for encoding information into memory, and current dual-process models seek to explain the roles of attention in both recollection memory and incidental-perceptual memory processes. The present study combined an incidental memory paradigm with event-related functional MRI to examine the effect of attention at encoding on the subsequent neural activation associated with unintended perceptual memory for spoken words. At encoding, we systematically varied attention levels as listeners heard a list of single English nouns. We then presented these words again in the context of a recognition task and assessed the effect of modulating attention at encoding on the BOLD responses to words that were either attended strongly, weakly, or not heard previously. MRI revealed activity in right-lateralized inferior parietal and prefrontal regions, and positive BOLD signals varied with the relative level of attention present at encoding. Temporal analysis of hemodynamic responses further showed that the time course of BOLD activity was modulated differentially by unintentionally encoded words compared to novel items. Our findings largely support current models of memory consolidation and retrieval, but they also provide fresh evidence for hemispheric differences and functional subdivisions in right frontoparietal attention networks that help shape auditory episodic recall.

  9. Modulating the Focus of Attention for Spoken Words at Encoding Affects Frontoparietal Activation for Incidental Verbal Memory

    PubMed Central

    Christensen, Thomas A.; Almryde, Kyle R.; Fidler, Lesley J.; Lockwood, Julie L.; Antonucci, Sharon M.; Plante, Elena

    2012-01-01

    Attention is crucial for encoding information into memory, and current dual-process models seek to explain the roles of attention in both recollection memory and incidental-perceptual memory processes. The present study combined an incidental memory paradigm with event-related functional MRI to examine the effect of attention at encoding on the subsequent neural activation associated with unintended perceptual memory for spoken words. At encoding, we systematically varied attention levels as listeners heard a list of single English nouns. We then presented these words again in the context of a recognition task and assessed the effect of modulating attention at encoding on the BOLD responses to words that were either attended strongly, weakly, or not heard previously. MRI revealed activity in right-lateralized inferior parietal and prefrontal regions, and positive BOLD signals varied with the relative level of attention present at encoding. Temporal analysis of hemodynamic responses further showed that the time course of BOLD activity was modulated differentially by unintentionally encoded words compared to novel items. Our findings largely support current models of memory consolidation and retrieval, but they also provide fresh evidence for hemispheric differences and functional subdivisions in right frontoparietal attention networks that help shape auditory episodic recall. PMID:22144982

  10. Characterization of the complex locus of bean encoding polygalacturonase-inhibiting proteins reveals subfunctionalization for defense against fungi and insects.

    PubMed

    D'Ovidio, Renato; Raiola, Alessandro; Capodicasa, Cristina; Devoto, Alessandra; Pontiggia, Daniela; Roberti, Serena; Galletti, Roberta; Conti, Eric; O'Sullivan, Donal; De Lorenzo, Giulia

    2004-08-01

    Polygalacturonase-inhibiting proteins (PGIPs) are extracellular plant inhibitors of fungal endopolygalacturonases (PGs) that belong to the superfamily of Leu-rich repeat proteins. We have characterized the full complement of pgip genes in the bean (Phaseolus vulgaris) genotype BAT93. This comprises four clustered members that span a 50-kb region and, based on their similarity, form two pairs (Pvpgip1/Pvpgip2 and Pvpgip3/Pvpgip4). Characterization of the encoded products revealed both partial redundancy and subfunctionalization against fungal-derived PGs. Notably, the pair PvPGIP3/PvPGIP4 also inhibited PGs of two mirid bugs (Lygus rugulipennis and Adelphocoris lineolatus). Characterization of Pvpgip genes of Pinto bean showed variations limited to single synonymous substitutions or small deletions. A three-amino acid deletion encompassing a residue previously identified as crucial for recognition of PG of Fusarium moniliforme was responsible for the inability of BAT93 PvPGIP2 to inhibit this enzyme. Consistent with the large variations observed in the promoter sequences, reverse transcription-PCR expression analysis revealed that the different family members differentially respond to elicitors, wounding, and salicylic acid. We conclude that both biochemical and regulatory redundancy and subfunctionalization of pgip genes are important for the adaptation of plants to pathogenic fungi and phytophagous insects.

  11. Transfection of gene regulation nanoparticles complexed with pDNA and shRNA controls multilineage differentiation of hMSCs.

    PubMed

    Kim, Hye Jin; Yi, Se Won; Oh, Hyun Jyung; Lee, Jung Sun; Park, Ji Sun; Park, Keun-Hong

    2018-05-29

    Overexpression and knockdown of specific proteins can control stem cell differentiation for therapeutic purposes. In this study, we fabricated RUNX2, SOX9, and C/EBPα plasmid DNAs (pDNAs) and ATF4-targeting shRNA (shATF4) to induce osteogenesis, chondrogenesis, and adipogenesis of human mesenchymal stem cells (hMSCs). The pDNAs and shATF4 were complexed with TRITC-gene regulation nanoparticles (GRN). Osteogenesis-related gene expression was reduced at early (12 h) and late (36 h) time points after co-delivery of shATF4 and SOX9 or C/EBPα pDNA, respectively, and osteogenesis was inhibited in these hMSCs. By contrast, osteogenesis-related genes were highly expressed upon co-delivery of RUNX2 and ATF4 pDNAs. DEX in GRN enhanced chondrogenic differentiation. Expression of osteogenesis-, chondrogenesis-, and adipogenesis-related genes was higher in hMSCs transfected with NPs complexed with RUNX2 and ATF4 pDNAs, shATF4 and SOX9 pDNA, and shATF4 and C/EBPα pDNA for 72 h than in control hMSCs, respectively. Moreover, delivery of these NPs also increased expression of osteogenesis-, chondrogenesis-, and adipogenesis-related proteins. These alterations in expression led to morphological changes, indicating that hMSCs differentiated into osteoblasts, chondrocytes, and adipose cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Real-time optical laboratory solution of parabolic differential equations

    NASA Technical Reports Server (NTRS)

    Casasent, David; Jackson, James

    1988-01-01

    An optical laboratory matrix-vector processor is used to solve parabolic differential equations (the transient diffusion equation with two space variables and time) by an explicit algorithm. This includes optical matrix-vector nonbase-2 encoded laboratory data, the combination of nonbase-2 and frequency-multiplexed data on such processors, a high-accuracy optical laboratory solution of a partial differential equation, new data partitioning techniques, and a discussion of a multiprocessor optical matrix-vector architecture.

  13. fMRI differences in encoding and retrieval of pictures due to encoding strategy in the elderly.

    PubMed

    Mandzia, Jennifer L; Black, Sandra E; McAndrews, Mary Pat; Grady, Cheryl; Graham, Simon

    2004-01-01

    Functional MRI (fMRI) was used to examine the neural correlates of depth of processing during encoding and retrieval of photographs in older normal volunteers (n = 12). Separate scans were run during deep (natural vs. man-made decision) and shallow (color vs. black-and-white decision) encoding and during old/new recognition of pictures initially presented in one of the two encoding conditions. A baseline condition consisting of a scrambled, color photograph was used as a contrast in each scan. Recognition accuracy was greater for the pictures on which semantic decisions were made at encoding, consistent with the expected levels of processing effect. A mixed-effects model was used to compare fMRI differences between conditions (deep-baseline vs. shallow-baseline) in both encoding and retrieval. For encoding, this contrast revealed greater activation associated with deep encoding in several areas, including the left parahippocampal gyrus (PHG), left middle temporal gyrus, and left anterior thalamus. Increased left hippocampal, right dorsolateral, and inferior frontal activations were found for recognition of items that had been presented in the deep relative to the shallow encoding condition. We speculate that the modulation of activity in these regions by the depth of processing manipulation shows that these regions support effective encoding and successful retrieval. A direct comparison between encoding and retrieval revealed greater activation during retrieval in the medial temporal (right hippocampus and bilateral PHG), anterior cingulate, and bilateral prefrontal (inferior and dorsolateral). Most notably, greater right posterior PHG was found during encoding compared to recognition. Focusing on the medial temporal lobe (MTL) region, our results suggest a greater involvement of both anterior MTL and prefrontal regions in retrieval compared to encoding. Copyright 2003 Wiley-Liss, Inc.

  14. Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

    PubMed

    Fenwick, Aimee L; Kliszczak, Maciej; Cooper, Fay; Murray, Jennie; Sanchez-Pulido, Luis; Twigg, Stephen R F; Goriely, Anne; McGowan, Simon J; Miller, Kerry A; Taylor, Indira B; Logan, Clare; Bozdogan, Sevcan; Danda, Sumita; Dixon, Joanne; Elsayed, Solaf M; Elsobky, Ezzat; Gardham, Alice; Hoffer, Mariette J V; Koopmans, Marije; McDonald-McGinn, Donna M; Santen, Gijs W E; Savarirayan, Ravi; de Silva, Deepthi; Vanakker, Olivier; Wall, Steven A; Wilson, Louise C; Yuregir, Ozge Ozalp; Zackai, Elaine H; Ponting, Chris P; Jackson, Andrew P; Wilkie, Andrew O M; Niedzwiedz, Wojciech; Bicknell, Louise S

    2016-07-07

    DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?

    PubMed

    Moosa, Amer; Shu, Henry; Sarachana, Tewarit; Hu, Valerie W

    2018-05-01

    Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Evidence for a differential contribution of early perceptual and late cognitive processes during encoding to episodic memory impairment in schizophrenia.

    PubMed

    Green, Amity E; Fitzgerald, Paul B; Johnston, Patrick J; Nathan, Pradeep J; Kulkarni, Jayashri; Croft, Rodney J

    2017-08-01

    Schizophrenia is characterised by significant episodic memory impairment that is thought to be related to problems with encoding, however the neuro-functional mechanisms underlying these deficits are not well understood. The present study used a subsequent recognition memory paradigm and event-related potentials (ERPs) to investigate temporal aspects of episodic memory encoding deficits in schizophrenia. Electroencephalographic data was recorded in 24 patients and 19 healthy controls whilst participants categorised single words as pleasant/unpleasant. ERPs were generated to subsequently recognised versus unrecognised words on the basis of a forced-choice recognition memory task. Subsequent memory effects were examined with the late positive component (LPP). Group differences in N1, P2, N400 and LPP were examined for words correctly recognised. Patients performed more poorly than controls on the recognition task. During encoding patients had significantly reduced N400 and LPP amplitudes than controls. LPP amplitude correlated with task performance however amplitudes did not differ between patients and controls as a function of subsequent memory. No significant differences in N1 or P2 amplitude or latency were observed. The present results indicate that early sensory processes are intact and dysfunctional higher order cognitive processes during encoding are contributing to episodic memory impairments in schizophrenia.

  17. Non-Interfering Effects of Active Post-Encoding Tasks on Episodic Memory Consolidation in Humans.

    PubMed

    Varma, Samarth; Takashima, Atsuko; Krewinkel, Sander; van Kooten, Maaike; Fu, Lily; Medendorp, W Pieter; Kessels, Roy P C; Daselaar, Sander M

    2017-01-01

    So far, studies that investigated interference effects of post-learning processes on episodic memory consolidation in humans have used tasks involving only complex and meaningful information. Such tasks require reallocation of general or encoding-specific resources away from consolidation-relevant activities. The possibility that interference can be elicited using a task that heavily taxes our limited brain resources, but has low semantic and hippocampal related long-term memory processing demands, has never been tested. We address this question by investigating whether consolidation could persist in parallel with an active, encoding-irrelevant, minimally semantic task, regardless of its high resource demands for cognitive processing. We distinguish the impact of such a task on consolidation based on whether it engages resources that are: (1) general/executive, or (2) specific/overlapping with the encoding modality. Our experiments compared subsequent memory performance across two post-encoding consolidation periods: quiet wakeful rest and a cognitively demanding n-Back task. Across six different experiments (total N = 176), we carefully manipulated the design of the n-Back task to target general or specific resources engaged in the ongoing consolidation process. In contrast to previous studies that employed interference tasks involving conceptual stimuli and complex processing demands, we did not find any differences between n-Back and rest conditions on memory performance at delayed test, using both recall and recognition tests. Our results indicate that: (1) quiet, wakeful rest is not a necessary prerequisite for episodic memory consolidation; and (2) post-encoding cognitive engagement does not interfere with memory consolidation when task-performance has minimal semantic and hippocampally-based episodic memory processing demands. We discuss our findings with reference to resource and reactivation-led interference theories.

  18. Opiates Modulate Noxious Chemical Nociception through a Complex Monoaminergic/Peptidergic Cascade

    PubMed Central

    Mills, Holly; Ortega, Amanda; Law, Wenjing; Hapiak, Vera; Summers, Philip; Clark, Tobias

    2016-01-01

    The ability to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral response is essential for survival. In Caenorhabditis elegans, opioid receptor agonists, such as morphine, mimic serotonin, and suppress the overall withdrawal from noxious stimuli through a pathway requiring the opioid-like receptor, NPR-17. This serotonin- or morphine-dependent modulation can be rescued in npr-17-null animals by the expression of npr-17 or a human κ opioid receptor in the two ASI sensory neurons, with ASI opioid signaling selectively inhibiting ASI neuropeptide release. Serotonergic modulation requires peptides encoded by both nlp-3 and nlp-24, and either nlp-3 or nlp-24 overexpression mimics morphine and suppresses withdrawal. Peptides encoded by nlp-3 act differentially, with only NLP-3.3 mimicking morphine, whereas other nlp-3 peptides antagonize NLP-3.3 modulation. Together, these results demonstrate that opiates modulate nociception in Caenorhabditis elegans through a complex monoaminergic/peptidergic cascade, and suggest that this model may be useful for dissecting opiate signaling in mammals. SIGNIFICANCE STATEMENT Opiates are used extensively to treat chronic pain. In Caenorhabditis elegans, opioid receptor agonists suppress the overall withdrawal from noxious chemical stimuli through a pathway requiring an opioid-like receptor and two distinct neuropeptide-encoding genes, with individual peptides from the same gene functioning antagonistically to modulate nociception. Endogenous opioid signaling functions as part of a complex, monoaminergic/peptidergic signaling cascade and appears to selectively inhibit neuropeptide release, mediated by a α-adrenergic-like receptor, from two sensory neurons. Importantly, receptor null animals can be rescued by the expression of the human κ opioid receptor, and injection of human opioid receptor ligands mimics exogenous opiates, highlighting the utility of this model for dissecting opiate

  19. Complex Conjugated certificateless-based signcryption with differential integrated factor for secured message communication in mobile network

    PubMed Central

    Rajagopalan, S. P.

    2017-01-01

    Certificateless-based signcryption overcomes inherent shortcomings in traditional Public Key Infrastructure (PKI) and Key Escrow problem. It imparts efficient methods to design PKIs with public verifiability and cipher text authenticity with minimum dependency. As a classic primitive in public key cryptography, signcryption performs validity of cipher text without decryption by combining authentication, confidentiality, public verifiability and cipher text authenticity much more efficiently than the traditional approach. In this paper, we first define a security model for certificateless-based signcryption called, Complex Conjugate Differential Integrated Factor (CC-DIF) scheme by introducing complex conjugates through introduction of the security parameter and improving secured message distribution rate. However, both partial private key and secret value changes with respect to time. To overcome this weakness, a new certificateless-based signcryption scheme is proposed by setting the private key through Differential (Diff) Equation using an Integration Factor (DiffEIF), minimizing computational cost and communication overhead. The scheme is therefore said to be proven secure (i.e. improving the secured message distributing rate) against certificateless access control and signcryption-based scheme. In addition, compared with the three other existing schemes, the CC-DIF scheme has the least computational cost and communication overhead for secured message communication in mobile network. PMID:29040290

  20. Complex Conjugated certificateless-based signcryption with differential integrated factor for secured message communication in mobile network.

    PubMed

    Alagarsamy, Sumithra; Rajagopalan, S P

    2017-01-01

    Certificateless-based signcryption overcomes inherent shortcomings in traditional Public Key Infrastructure (PKI) and Key Escrow problem. It imparts efficient methods to design PKIs with public verifiability and cipher text authenticity with minimum dependency. As a classic primitive in public key cryptography, signcryption performs validity of cipher text without decryption by combining authentication, confidentiality, public verifiability and cipher text authenticity much more efficiently than the traditional approach. In this paper, we first define a security model for certificateless-based signcryption called, Complex Conjugate Differential Integrated Factor (CC-DIF) scheme by introducing complex conjugates through introduction of the security parameter and improving secured message distribution rate. However, both partial private key and secret value changes with respect to time. To overcome this weakness, a new certificateless-based signcryption scheme is proposed by setting the private key through Differential (Diff) Equation using an Integration Factor (DiffEIF), minimizing computational cost and communication overhead. The scheme is therefore said to be proven secure (i.e. improving the secured message distributing rate) against certificateless access control and signcryption-based scheme. In addition, compared with the three other existing schemes, the CC-DIF scheme has the least computational cost and communication overhead for secured message communication in mobile network.

  1. Ribosomes slide on lysine-encoding homopolymeric A stretches

    PubMed Central

    Koutmou, Kristin S; Schuller, Anthony P; Brunelle, Julie L; Radhakrishnan, Aditya; Djuranovic, Sergej; Green, Rachel

    2015-01-01

    Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertion of synonymous AAG codons. Kinetic studies in E. coli reveal that differential protein production results from pausing on consecutive AAA-lysines followed by ribosome sliding on homopolymeric A sequence. Translation in a cell-free expression system demonstrates that diminished output from AAA-codon-containing reporters results from premature translation termination on out of frame stop codons following ribosome sliding. In eukaryotes, these premature termination events target the mRNAs for Nonsense-Mediated-Decay (NMD). The finding that ribosomes slide on homopolymeric A sequences explains bioinformatic analyses indicating that consecutive AAA codons are under-represented in gene-coding sequences. Ribosome ‘sliding’ represents an unexpected type of ribosome movement possible during translation. DOI: http://dx.doi.org/10.7554/eLife.05534.001 PMID:25695637

  2. Polynucleotides encoding TRF1 binding proteins

    DOEpatents

    Campisi, Judith; Kim, Sahn-Ho

    2002-01-01

    The present invention provides a novel telomere associated protein (Trf1-interacting nuclear protein 2 "Tin2") that hinders the binding of Trf1 to its specific telomere repeat sequence and mediates the formation of a Tin2-Trf1-telomeric DNA complex that limits telomerase access to the telomere. Also included are the corresponding nucleic acids that encode the Tin2 of the present invention, as well as mutants of Tin2. Methods of making, purifying and using Tin2 of the present invention are described. In addition, drug screening assays to identify drugs that mimic and/or complement the effect of Tin2 are presented.

  3. Multimodal ophthalmic imaging using swept source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Malone, Joseph D.; El-Haddad, Mohamed T.; Tye, Logan A.; Majeau, Lucas; Godbout, Nicolas; Rollins, Andrew M.; Boudoux, Caroline; Tao, Yuankai K.

    2016-03-01

    Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) benefit clinical diagnostic imaging in ophthalmology by enabling in vivo noninvasive en face and volumetric visualization of retinal structures, respectively. Spectrally encoding methods enable confocal imaging through fiber optics and reduces system complexity. Previous applications in ophthalmic imaging include spectrally encoded confocal scanning laser ophthalmoscopy (SECSLO) and a combined SECSLO-OCT system for image guidance, tracking, and registration. However, spectrally encoded imaging suffers from speckle noise because each spectrally encoded channel is effectively monochromatic. Here, we demonstrate in vivo human retinal imaging using a swept source spectrally encoded scanning laser ophthalmoscope and OCT (SSSESLO- OCT) at 1060 nm. SS-SESLO-OCT uses a shared 100 kHz Axsun swept source, shared scanner and imaging optics, and are detected simultaneously on a shared, dual channel high-speed digitizer. SESLO illumination and detection was performed using the single mode core and multimode inner cladding of a double clad fiber coupler, respectively, to preserve lateral resolution while improving collection efficiency and reducing speckle contrast at the expense of confocality. Concurrent en face SESLO and cross-sectional OCT images were acquired with 1376 x 500 pixels at 200 frames-per-second. Our system design is compact and uses a shared light source, imaging optics, and digitizer, which reduces overall system complexity and ensures inherent co-registration between SESLO and OCT FOVs. En face SESLO images acquired concurrent with OCT cross-sections enables lateral motion tracking and three-dimensional volume registration with broad applications in multivolume OCT averaging, image mosaicking, and intraoperative instrument tracking.

  4. Robust Encoding of Spatial Information in Orbitofrontal Cortex and Striatum.

    PubMed

    Yoo, Seng Bum Michael; Sleezer, Brianna J; Hayden, Benjamin Y

    2018-06-01

    Knowing whether core reward regions carry information about the positions of relevant objects is crucial for adjudicating between choice models. One limitation of previous studies, including our own, is that spatial positions can be consistently differentially associated with rewards, and thus position can be confounded with attention, motor plans, or target identity. We circumvented these problems by using a task in which value-and thus choices-was determined solely by a frequently changing rule, which was randomized relative to spatial position on each trial. We presented offers asynchronously, which allowed us to control for reward expectation, spatial attention, and motor plans in our analyses. We find robust encoding of the spatial position of both offers and choices in two core reward regions, orbitofrontal Area 13 and ventral striatum, as well as in dorsal striatum of macaques. The trial-by-trial correlation in noise in encoding of position was associated with variation in choice, an effect known as choice probability correlation, suggesting that the spatial encoding is associated with choice and is not incidental to it. Spatial information and reward information are not carried by separate sets of neurons, although the two forms of information are temporally dissociable. These results highlight the ubiquity of multiplexed information in association cortex and argue against the idea that these ostensible reward regions serve as part of a pure value domain.

  5. Increased mitochondrial-encoded gene transcription in immortal DF-1 cells.

    PubMed

    Kim, H; You, S; Kim, I J; Farris, J; Foster, L K; Foster, D N

    2001-05-01

    We have established, in continuous cell culture, a spontaneously immortalized chicken embryo fibroblast (CEF) cell line (DF-1) as well as several other immortal CEF cell lines. The immortal DF-1 cells divided more rapidly than primary and other immortal CEF cells. To identify the genes involved in rapidly dividing DF-1 cells, we have used differential display RT-PCR. Of the numerous genes analyzed, three mitochondrial-encoded genes (ATPase 8/6, 16S rRNA, and cytochrome b) were shown to express at higher levels in DF-1 cells compared to primary and other immortal CEF cells. The inhibition of mitochondrial translation by treatment with chloramphenicol markedly decreased ATP production and cell proliferation in DF-1 cells, while not affecting growth in either primary or other immortal CEF cells. This result suggests a correlation between rapid cell proliferation and the increased mitochondrial respiratory functions. We also determined that the increased transcription of mitochondrial-encoded genes in DF-1 cells is due to increased de novo transcript synthesis as shown by mitochondrial run-on assays, and not the result of either increased mitochondrial biogenesis or mitochondrial transcript half-lives. Together, the present studies suggest that the transcriptional activation of mitochondrial-encoded genes and the elevated respiratory function should be one of the characteristics of rapidly dividing immortal cells. Copyright 2001 Academic Press.

  6. Drosophila variable nurse cells encodes Arrest defective 1 (ARD1), the catalytic subunit of the major N-terminal acetyltransferase complex

    PubMed Central

    Wang, Ying; Mijares, Michelle; Gall, Megan D.; Turan, Tolga; Javier, Anna; Bornemann, Douglas J; Manage, Kevin; Warrior, Rahul

    2010-01-01

    Mutations in the Drosophila variable nurse cells (vnc) gene result in female sterility and oogenesis defects, including egg chambers with too many or too few nurse cells. We show that vnc corresponds to Arrest Defective1 (Ard1) and encodes the catalytic subunit of NatA, the major N-terminal acetyl-transferase complex. While N-terminal acetylation is one of the most prevalent covalent protein modifications in eukaryotes, analysis of its role in development has been challenging since mutants that compromise NatA activity have not been described in any multicellular animal. Our data show that reduced ARD1 levels result in pleiotropic oogenesis defects including abnormal cyst encapsulation, desynchronized cystocyte division, disrupted nurse cell chromosome dispersion and abnormal chorion patterning, consistent with the wide range of predicted NatA substrates. Further we find that loss of Ard1 affects cell survival/proliferation and is lethal for the animal, providing the first demonstration that this modification is essential in higher eukaryotes. PMID:20882681

  7. Recognition memory strength is predicted by pupillary responses at encoding while fixation patterns distinguish recollection from familiarity.

    PubMed

    Kafkas, Alexandros; Montaldi, Daniela

    2011-10-01

    Thirty-five healthy participants incidentally encoded a set of man-made and natural object pictures, while their pupil response and eye movements were recorded. At retrieval, studied and new stimuli were rated as novel, familiar (strong, moderate, or weak), or recollected. We found that both pupil response and fixation patterns at encoding predict later recognition memory strength. The extent of pupillary response accompanying incidental encoding was found to be predictive of subsequent memory. In addition, the number of fixations was also predictive of later recognition memory strength, suggesting that the accumulation of greater visual detail, even for single objects, is critical for the creation of a strong memory. Moreover, fixation patterns at encoding distinguished between recollection and familiarity at retrieval, with more dispersed fixations predicting familiarity and more clustered fixations predicting recollection. These data reveal close links between the autonomic control of pupil responses and eye movement patterns on the one hand and memory encoding on the other. Moreover, the data illustrate quantitative as well as qualitative differences in the incidental visual processing of stimuli, which are differentially predictive of the strength and the kind of memory experienced at recognition.

  8. Nonlinear inversion of potential-field data using a hybrid-encoding genetic algorithm

    USGS Publications Warehouse

    Chen, C.; Xia, J.; Liu, J.; Feng, G.

    2006-01-01

    Using a genetic algorithm to solve an inverse problem of complex nonlinear geophysical equations is advantageous because it does not require computer gradients of models or "good" initial models. The multi-point search of a genetic algorithm makes it easier to find the globally optimal solution while avoiding falling into a local extremum. As is the case in other optimization approaches, the search efficiency for a genetic algorithm is vital in finding desired solutions successfully in a multi-dimensional model space. A binary-encoding genetic algorithm is hardly ever used to resolve an optimization problem such as a simple geophysical inversion with only three unknowns. The encoding mechanism, genetic operators, and population size of the genetic algorithm greatly affect search processes in the evolution. It is clear that improved operators and proper population size promote the convergence. Nevertheless, not all genetic operations perform perfectly while searching under either a uniform binary or a decimal encoding system. With the binary encoding mechanism, the crossover scheme may produce more new individuals than with the decimal encoding. On the other hand, the mutation scheme in a decimal encoding system will create new genes larger in scope than those in the binary encoding. This paper discusses approaches of exploiting the search potential of genetic operations in the two encoding systems and presents an approach with a hybrid-encoding mechanism, multi-point crossover, and dynamic population size for geophysical inversion. We present a method that is based on the routine in which the mutation operation is conducted in the decimal code and multi-point crossover operation in the binary code. The mix-encoding algorithm is called the hybrid-encoding genetic algorithm (HEGA). HEGA provides better genes with a higher probability by a mutation operator and improves genetic algorithms in resolving complicated geophysical inverse problems. Another significant

  9. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.

    PubMed

    Landt, Stephen G; Marinov, Georgi K; Kundaje, Anshul; Kheradpour, Pouya; Pauli, Florencia; Batzoglou, Serafim; Bernstein, Bradley E; Bickel, Peter; Brown, James B; Cayting, Philip; Chen, Yiwen; DeSalvo, Gilberto; Epstein, Charles; Fisher-Aylor, Katherine I; Euskirchen, Ghia; Gerstein, Mark; Gertz, Jason; Hartemink, Alexander J; Hoffman, Michael M; Iyer, Vishwanath R; Jung, Youngsook L; Karmakar, Subhradip; Kellis, Manolis; Kharchenko, Peter V; Li, Qunhua; Liu, Tao; Liu, X Shirley; Ma, Lijia; Milosavljevic, Aleksandar; Myers, Richard M; Park, Peter J; Pazin, Michael J; Perry, Marc D; Raha, Debasish; Reddy, Timothy E; Rozowsky, Joel; Shoresh, Noam; Sidow, Arend; Slattery, Matthew; Stamatoyannopoulos, John A; Tolstorukov, Michael Y; White, Kevin P; Xi, Simon; Farnham, Peggy J; Lieb, Jason D; Wold, Barbara J; Snyder, Michael

    2012-09-01

    Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals.

  10. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia

    PubMed Central

    Landt, Stephen G.; Marinov, Georgi K.; Kundaje, Anshul; Kheradpour, Pouya; Pauli, Florencia; Batzoglou, Serafim; Bernstein, Bradley E.; Bickel, Peter; Brown, James B.; Cayting, Philip; Chen, Yiwen; DeSalvo, Gilberto; Epstein, Charles; Fisher-Aylor, Katherine I.; Euskirchen, Ghia; Gerstein, Mark; Gertz, Jason; Hartemink, Alexander J.; Hoffman, Michael M.; Iyer, Vishwanath R.; Jung, Youngsook L.; Karmakar, Subhradip; Kellis, Manolis; Kharchenko, Peter V.; Li, Qunhua; Liu, Tao; Liu, X. Shirley; Ma, Lijia; Milosavljevic, Aleksandar; Myers, Richard M.; Park, Peter J.; Pazin, Michael J.; Perry, Marc D.; Raha, Debasish; Reddy, Timothy E.; Rozowsky, Joel; Shoresh, Noam; Sidow, Arend; Slattery, Matthew; Stamatoyannopoulos, John A.; Tolstorukov, Michael Y.; White, Kevin P.; Xi, Simon; Farnham, Peggy J.; Lieb, Jason D.; Wold, Barbara J.; Snyder, Michael

    2012-01-01

    Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals. PMID:22955991

  11. Unconscious relational encoding depends on hippocampus

    PubMed Central

    Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens

    2014-01-01

    Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

  12. Influence of controlled encoding and retrieval facilitation on memory performance in patients with different profiles of mild cognitive impairment.

    PubMed

    Perri, Roberta; Monaco, Marco; Fadda, Lucia; Serra, Laura; Marra, Camillo; Caltagirone, Carlo; Bruni, Amalia C; Curcio, Sabrina; Bozzali, M; Carlesimo, Giovanni A

    2015-01-01

    Memory tests able to differentiate encoding and retrieval processes from the memoranda storing ones should be used to differentiate patients in a very early phase of AD. In fact, individuals with mild cognitive impairment (MCI) can be characterized by two different memory profiles: a pure amnestic one (with poor learning and retrieval and poor improvement when encoding is assisted and retrieval is facilitated) and a dysexecutive one (with inefficient encoding and/or poor retrieval strategies and improvement with assisted encoding and retrieval). The amnestic profile characterizes subjects affected by medio-temporal atrophy typical of AD. In this study, a Grober-Buschke memory procedure was used to evaluate normal controls and MCI patients with different cognitive profiles: pure amnestic (aMCIsd), amnestic plus other cognitive impairments (aMCImd) and non-amnestic (naMCI). An index of sensitivity of cueing (ISC) measured the advantage passing from free to cued recall. Results showed that both strategic and consolidation abilities were impaired in the aMCIsd and aMCImd groups and were preserved in the naMCI group. aMCImd, however, compensated the memory deficit with assisted encoding and retrieval, but aMCIsd performed very poorly. When MCI subjects were defined according to the ISC value, subjects with poor ISC were primarily in the aMCIsd group and, to a lesser extent, in the aMCImd group and the naMCI group. Finally, patients with a poor ISC showed cerebral atrophy documented in the precocious phase of AD and the retrosplenial cerebral areas seemed to be the most useful areas for identifying patients in the early phase of AD.

  13. Stress as a mnemonic filter: Interactions between medial temporal lobe encoding processes and post-encoding stress

    PubMed Central

    Ritchey, Maureen; McCullough, Andrew M.; Ranganath, Charan; Yonelinas, Andrew P.

    2016-01-01

    Acute stress has been shown to modulate memory for recently learned information, an effect attributed to the influence of stress hormones on medial temporal lobe (MTL) consolidation processes. However, little is known about which memories will be affected when stress follows encoding. One possibility is that stress interacts with encoding processes to selectively protect memories that had elicited responses in the hippocampus and amygdala, two MTL structures important for memory formation. There is limited evidence for interactions between encoding processes and consolidation effects in humans, but recent studies of consolidation in rodents have emphasized the importance of encoding “tags” for determining the impact of consolidation manipulations on memory. Here, we used fMRI in humans to test the hypothesis that the effects of post-encoding stress depend on MTL processes observed during encoding. We found that changes in stress hormone levels were associated with an increase in the contingency of memory outcomes on hippocampal and amygdala encoding responses. That is, for participants showing high cortisol reactivity, memories became more dependent on MTL activity observed during encoding, thereby shifting the distribution of recollected events toward those that had elicited relatively high activation. Surprisingly, this effect was generally larger for neutral, compared to emotionally negative, memories. The results suggest that stress does not uniformly enhance memory, but instead selectively preserves memories tagged during encoding, effectively acting as mnemonic filter. PMID:27774683

  14. Narrative organisation at encoding facilitated children's long-term episodic memory.

    PubMed

    Wang, Qi; Bui, Van-Kim; Song, Qingfang

    2015-01-01

    This study examined the effect of narrative organisation at encoding on long-term episodic memory in a sample of five- to seven-year-old children (N = 113). At an initial interview, children were asked to narrate a story from a picture book. Six months later, they were interviewed again and asked to recall the story and answer a series of direct questions about the story. Children who initially encoded more information in narrative and produced more complete, complex, cohesive and coherent narratives remembered the story in greater detail and accuracy following the six-month interval, independent of age and verbal skills. The relation between narrative organisation and memory was consistent across culture and gender. These findings provide new insight into the critical role of narrative in episodic memory.

  15. The neural correlates of self-referential memory encoding and retrieval in schizophrenia.

    PubMed

    Jimenez, Amy M; Lee, Junghee; Wynn, Jonathan K; Green, Michael F

    2018-01-31

    Enhanced memory for self-oriented information is known as the self-referential memory (SRM) effect. fMRI studies of the SRM effect have focused almost exclusively on encoding, revealing selective engagement of the medial prefrontal cortex (mPFC) during "self" relative to other processing conditions. Other critical areas for self-processing include ventrolateral prefrontal cortex (vlPFC), temporo-parietal junction (TPJ) and posterior cingulate/precuneus (PCC/PC). Previous behavioral studies show that individuals with schizophrenia fail to benefit from this memory boost. However, the neural correlates of this deficit, at either encoding or retrieval, are unknown. Twenty individuals with schizophrenia and 16 healthy controls completed an event-related fMRI SRM paradigm. During encoding, trait adjectives were judged in terms of structural features ("case" condition), social desirability ("other" condition), or as self-referential ("self" condition). Participants then completed an unexpected recognition test (retrieval phase). We examined BOLD activation during both encoding and retrieval within mPFC, vlPFC, TPJ, and PCC/PC regions-of-interest (ROIs). During encoding, fMRI data indicated both groups had greater activation during the "self" relative to the "other" condition across ROIs. Controls showed this primarily in mPFC whereas patients showed this in PCC/PC. During retrieval, fMRI data indicated controls showed differentiation across ROIs between "self" and "other" conditions, but patients did not. Results suggest regional differences in the neural processing of self-referential information in individuals with schizophrenia, perhaps because representation of the self is not as well established in patients relative to controls. The current study presents novel findings that add to the literature implicating impaired self-oriented processing in schizophrenia. Published by Elsevier Ltd.

  16. Distinct encoding of risk and value in economic choice between multiple risky options☆

    PubMed Central

    Wright, Nicholas D.; Symmonds, Mkael; Dolan, Raymond J.

    2013-01-01

    Neural encoding of value-based stimuli is suggested to involve representations of summary statistics, including risk and expected value (EV). A more complex, but ecologically more common, context is when multiple risky options are evaluated together. However, it is unknown whether encoding related to option evaluation in these situations involves similar principles. Here we employed fMRI during a task that parametrically manipulated EV and risk in two simultaneously presented lotteries, both of which contained either gains or losses. We found representations of EV in medial prefrontal cortex and anterior insula, an encoding that was dependent on which option was chosen (i.e. chosen and unchosen EV) and whether the choice was over gains or losses. Parietal activity reflected whether the riskier or surer option was selected, whilst activity in a network of regions that also included parietal cortex reflected both combined risk and difference in risk for the two options. Our findings provide support for the idea that summary statistics underpin a representation of value-based stimuli, and further that these summary statistics undergo distinct forms of encoding. PMID:23684860

  17. Optical image encryption method based on incoherent imaging and polarized light encoding

    NASA Astrophysics Data System (ADS)

    Wang, Q.; Xiong, D.; Alfalou, A.; Brosseau, C.

    2018-05-01

    We propose an incoherent encoding system for image encryption based on a polarized encoding method combined with an incoherent imaging. Incoherent imaging is the core component of this proposal, in which the incoherent point-spread function (PSF) of the imaging system serves as the main key to encode the input intensity distribution thanks to a convolution operation. An array of retarders and polarizers is placed on the input plane of the imaging structure to encrypt the polarized state of light based on Mueller polarization calculus. The proposal makes full use of randomness of polarization parameters and incoherent PSF so that a multidimensional key space is generated to deal with illegal attacks. Mueller polarization calculus and incoherent illumination of imaging structure ensure that only intensity information is manipulated. Another key advantage is that complicated processing and recording related to a complex-valued signal are avoided. The encoded information is just an intensity distribution, which is advantageous for data storage and transition because information expansion accompanying conventional encryption methods is also avoided. The decryption procedure can be performed digitally or using optoelectronic devices. Numerical simulation tests demonstrate the validity of the proposed scheme.

  18. Complex effect of hydroxyapatite nanoparticles on the differentiation and functional activity of human pre-osteoclastic cells.

    PubMed

    Costa-Rodrigues, João; Silva, Ana; Santos, Catarina; Almeida, Maria Margarida; Costa, Maria Elisabete; Fernandes, Maria Helena

    2014-12-01

    Nanosized hydroxyapatite (HA) is a promising material in clinical applications targeting the bone tissue. NanoHA is able to modulate bone cellular events, which accounts for its potential utility, but also raises safety concerns regarding the maintenance of the bone homeostasis. This work analyses the effects of HA nanoparticles (HAnp) on osteoclastic differentiation and activity, an issue that has been barely addressed. Rod-like HAnp, produced by a hydrothermal precipitation method, were tested on peripheral blood mononuclear cells (PBMC), which contains the CD14+ osteoclastic precursors, in unstimulated or osteoclastogenic-induced conditions. HAnp were added at three time-points during the osteoclastic differentiation pathway, and cell response was evaluated for osteoclastic related parameters. Results showed that HAnp modulated the differentiation and function of osteoclastic cells in a dose- and time-dependent manner. In addition, the effects were dependent on the stage of osteoclastic differentiation. In unstimulated PBMC, HAnp significantly increased osteoclastogenesis, leading to the formation of mature osteoclasts, as evident by the significant increase of TRAP activity, number of TRAP-positive multinucleated cells, osteoclastic gene expression and resorbing ability. However, in a population of mature osteoclasts (formed in osteoclastogenic-induced PBMC cultures), HAnp caused a dose-dependent decrease on the osteoclastic-related parameters. These results highlight the complex effects of HAnp in osteoclastic differentiation and activity, and suggest the possibility of HAnp to modulate/disrupt osteoclastic behavior, with eventual imbalances in the bone metabolism. This should be carefully considered in bone-related and other established and prospective biomedical applications of HAnp.

  19. Neural Encoding and Integration of Learned Probabilistic Sequences in Avian Sensory-Motor Circuitry

    PubMed Central

    Brainard, Michael S.

    2013-01-01

    Many complex behaviors, such as human speech and birdsong, reflect a set of categorical actions that can be flexibly organized into variable sequences. However, little is known about how the brain encodes the probabilities of such sequences. Behavioral sequences are typically characterized by the probability of transitioning from a given action to any subsequent action (which we term “divergence probability”). In contrast, we hypothesized that neural circuits might encode the probability of transitioning to a given action from any preceding action (which we term “convergence probability”). The convergence probability of repeatedly experienced sequences could naturally become encoded by Hebbian plasticity operating on the patterns of neural activity associated with those sequences. To determine whether convergence probability is encoded in the nervous system, we investigated how auditory-motor neurons in vocal premotor nucleus HVC of songbirds encode different probabilistic characterizations of produced syllable sequences. We recorded responses to auditory playback of pseudorandomly sequenced syllables from the bird's repertoire, and found that variations in responses to a given syllable could be explained by a positive linear dependence on the convergence probability of preceding sequences. Furthermore, convergence probability accounted for more response variation than other probabilistic characterizations, including divergence probability. Finally, we found that responses integrated over >7–10 syllables (∼700–1000 ms) with the sign, gain, and temporal extent of integration depending on convergence probability. Our results demonstrate that convergence probability is encoded in sensory-motor circuitry of the song-system, and suggest that encoding of convergence probability is a general feature of sensory-motor circuits. PMID:24198363

  20. Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation

    PubMed Central

    Singh, Ajeet Pratap; Archer, Trevor K.

    2014-01-01

    The regulatory networks of differentiation programs and the molecular mechanisms of lineage-specific gene regulation in mammalian embryos remain only partially defined. We document differential expression and temporal switching of BRG1-associated factor (BAF) subunits, core pluripotency factors and cardiac-specific genes during post-implantation development and subsequent early organogenesis. Using affinity purification of BRG1 ATPase coupled to mass spectrometry, we characterized the cardiac-enriched remodeling complexes present in E8.5 mouse embryos. The relative abundance and combinatorial assembly of the BAF subunits provides functional specificity to Switch/Sucrose NonFermentable (SWI/SNF) complexes resulting in a unique gene expression profile in the developing heart. Remarkably, the specific depletion of the BAF250a subunit demonstrated differential effects on cardiac-specific gene expression and resulted in arrhythmic contracting cardiomyocytes in vitro. Indeed, the BAF250a physically interacts and functionally cooperates with Nucleosome Remodeling and Histone Deacetylase (NURD) complex subunits to repressively regulate chromatin structure of the cardiac genes by switching open and poised chromatin marks associated with active and repressed gene expression. Finally, BAF250a expression modulates BRG1 occupancy at the loci of cardiac genes regulatory regions in P19 cell differentiation. These findings reveal specialized and novel cardiac-enriched SWI/SNF chromatin-remodeling complexes, which are required for heart formation and critical for cardiac gene expression regulation at the early stages of heart development. PMID:24335282

  1. Landscape Encodings Enhance Optimization

    PubMed Central

    Klemm, Konstantin; Mehta, Anita; Stadler, Peter F.

    2012-01-01

    Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states) of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state. PMID:22496860

  2. PNA-encoded chemical libraries.

    PubMed

    Zambaldo, Claudio; Barluenga, Sofia; Winssinger, Nicolas

    2015-06-01

    Peptide nucleic acid (PNA)-encoded chemical libraries along with DNA-encoded libraries have provided a powerful new paradigm for library synthesis and ligand discovery. PNA-encoding stands out for its compatibility with standard solid phase synthesis and the technology has been used to prepare libraries of peptides, heterocycles and glycoconjugates. Different screening formats have now been reported including selection-based and microarray-based methods that have yielded specific ligands against diverse target classes including membrane receptors, lectins and challenging targets such as Hsp70. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Association of Rpn10 with high molecular weight complex is enhanced during retinoic acid-induced differentiation of neuroblastoma cells.

    PubMed

    Tayama, Yoko; Kawahara, Hiroyuki; Minami, Ryosuke; Shimada, Masumi; Yokosawa, Hideyoshi

    2007-12-01

    The ubiquitin-binding Rpn10 protein serves as an ubiquitin receptor that delivers client proteins to the 26S proteasome, the protein degradation complex. It has been suggested that the ubiquitin-dependent protein degradation is critical for neuronal differentiation and for preventing neurodegenerative diseases. Our previous study indicated the importance of Rpn10 in control of cellular differentiation (Shimada et al., Mol Biol Cell 17:5356-5371, 2006), though the functional relevance of Rpn10 in neuronal cell differentiation remains a mystery to be uncovered. In the present study, we have examined the level of Rpn10 in a proteasome-containing high molecular weight (HMW) protein fraction prepared from the mouse neuroblastoma cell line Neuro2a. We here report that the protein level of Rpn10 in HMW fraction from un-differentiated Neuro2a cells was significantly lower than that of other cultured cell lines. We have found that retinoic acid-induced neural differentiation of Neuro2a cells significantly stimulates the incorporation of Rpn10 into HMW fractions, although the amounts of 26S proteasome subunits were not changed. Our findings provide the first evidence that the modulation of Rpn10 is linked to the control of retinoic acid-induced differentiation of neuroblastoma cells.

  4. Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

    PubMed Central

    Midic, Uros; Vincent, Kailey A.; VandeVoort, Catherine A; Latham, Keith E.

    2016-01-01

    Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28 days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed. PMID:27614199

  5. Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells.

    PubMed

    Midic, Uros; Vincent, Kailey A; VandeVoort, Catherine A; Latham, Keith E

    2016-10-01

    Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Ultrastructure of the embryonic snake skin and putative role of histidine in the differentiation of the shedding complex.

    PubMed

    Alibardi, Lorenzo

    2002-02-01

    The morphogenesis and ultrastructure of the epidermis of snake embryos were studied at progressive stages of development through hatching to determine the time and modality of differentiation of the shedding complex. Scales form as symmetric epidermal bumps that become slanted and eventually very overlapped. During the asymmetrization of the bumps, the basal cells of the forming outer surface of the scale become columnar, as in an epidermal placode, and accumulate glycogen. Small dermal condensations are sometimes seen and probably represent primordia of the axial dense dermis of the growing tip of scales. Deep, dense, and superficial loose dermal regions are formed when the epidermis is bilayered (periderm and basal epidermis) and undifferentiated. Glycogen and lipids decrease from basal cells to differentiating suprabasal cells. On the outer scale surface, beneath the peridermis, a layer containing dense granules and sparse 25-30-nm thick coarse filaments is formed. The underlying clear layer does not contain keratohyalin-like granules but has a rich cytoskeleton of intermediate filaments. Small denticles are formed and they interdigitate with the oberhautchen spinulae formed underneath. On the inner scale surface the clear layer contains dense granules, coarse filaments, and does not form denticles with the aspinulated oberhautchen. On the inner side surface the oberhautchen only forms occasional spinulae. The sloughing of the periderm and embryonic epidermis takes place in ovo 5-6 days before hatching. There follow beta-, mesos-, and alpha-layers, not yet mature before hatching. No resting period is present but a new generation is immediately produced so that at 6-10 h posthatching an inner generation and a new shedding complex are forming beneath the outer generation. The first shedding complex differentiates 10-11 days before hatching. In hatchlings 6-10 h old, tritiated histidine is taken up in the epidermis 4 h after injection and is found mainly in the

  7. Phylogenetic analysis of fungal heterotrimeric G protein-encoding genes and their expression during dimorphism in Mucor circinelloides.

    PubMed

    Valle-Maldonado, Marco Iván; Jácome-Galarza, Irvin Eduardo; Díaz-Pérez, Alma Laura; Martínez-Cadena, Guadalupe; Campos-García, Jesús; Ramírez-Díaz, Martha Isela; Reyes-De la Cruz, Homero; Riveros-Rosas, Héctor; Díaz-Pérez, César; Meza-Carmen, Víctor

    2015-12-01

    In fungi, heterotrimeric G proteins are key regulators of biological processes such as mating, virulence, morphology, among others. Mucor circinelloides is a model organism for many biological processes, and its genome contains the largest known repertoire of genes that encode putative heterotrimeric G protein subunits in the fungal kingdom: twelve Gα (McGpa1-12), three Gβ (McGpb1-3), and three Gγ (McGpg1-3). Phylogenetic analysis of fungal Gα showed that they are divided into four distinct groups as reported previously. Fungal Gβ and Gγ are also divided into four phylogenetic groups, and to our understanding this is the first report of a phylogenetic classification for fungal Gβ and Gγ subunits. Almost all genes that encode putative heterotrimeric G subunits in M. circinelloides are differentially expressed during dimorphic growth, except for McGpg1 (Gγ) that showed very low mRNA levels at all developmental stages. Moreover, several of the subunits are expressed in a similar pattern and at the same level, suggesting that they constitute discrete complexes. For example, McGpb3 (Gβ), and McGpg2 (Gγ), are co-expressed during mycelium growth, and McGpa1, McGpb2, and McGpg2, are co-expressed during yeast development. These findings provide the conceptual framework to study the biological role of these genes during M. circinelloides morphogenesis. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  8. Multiplex PCR for rapid detection of genes encoding class A carbapenemases.

    PubMed

    Hong, Sang Sook; Kim, Kyeongmi; Huh, Ji Young; Jung, Bochan; Kang, Myung Seo; Hong, Seong Geun

    2012-09-01

    In recent years, there have been increasing reports of KPC-producing Klebsiella pneumoniae in Korea. The modified Hodge test can be used as a phenotypic screening test for class A carbapenamase (CAC)-producing clinical isolates; however, it does not distinguish between carbapenemase types. The confirmation of type of CAC is important to ensure optimal therapy and to prevent transmission. This study applied a novel multiplex PCR assay to detect and differentiate CAC genes in a single reaction. Four primer pairs were designed to amplify fragments encoding 4 CAC families (SME, IMI/NMC-A, KPC, and GES). The multiplex PCR detected all genes tested for 4 CAC families that could be differentiated by fragment size according to gene type. This multiplex PCR offers a simple and useful approach for detecting and distinguishing CAC genes in carbapenem-resistant strains that are metallo-β-lactamase nonproducers.

  9. Non-Interfering Effects of Active Post-Encoding Tasks on Episodic Memory Consolidation in Humans

    PubMed Central

    Varma, Samarth; Takashima, Atsuko; Krewinkel, Sander; van Kooten, Maaike; Fu, Lily; Medendorp, W. Pieter; Kessels, Roy P. C.; Daselaar, Sander M.

    2017-01-01

    So far, studies that investigated interference effects of post-learning processes on episodic memory consolidation in humans have used tasks involving only complex and meaningful information. Such tasks require reallocation of general or encoding-specific resources away from consolidation-relevant activities. The possibility that interference can be elicited using a task that heavily taxes our limited brain resources, but has low semantic and hippocampal related long-term memory processing demands, has never been tested. We address this question by investigating whether consolidation could persist in parallel with an active, encoding-irrelevant, minimally semantic task, regardless of its high resource demands for cognitive processing. We distinguish the impact of such a task on consolidation based on whether it engages resources that are: (1) general/executive, or (2) specific/overlapping with the encoding modality. Our experiments compared subsequent memory performance across two post-encoding consolidation periods: quiet wakeful rest and a cognitively demanding n-Back task. Across six different experiments (total N = 176), we carefully manipulated the design of the n-Back task to target general or specific resources engaged in the ongoing consolidation process. In contrast to previous studies that employed interference tasks involving conceptual stimuli and complex processing demands, we did not find any differences between n-Back and rest conditions on memory performance at delayed test, using both recall and recognition tests. Our results indicate that: (1) quiet, wakeful rest is not a necessary prerequisite for episodic memory consolidation; and (2) post-encoding cognitive engagement does not interfere with memory consolidation when task-performance has minimal semantic and hippocampally-based episodic memory processing demands. We discuss our findings with reference to resource and reactivation-led interference theories. PMID:28424596

  10. The effect of interference on delta modulation encoded video signals

    NASA Technical Reports Server (NTRS)

    Schilling, D. L.

    1979-01-01

    The results of a study on the use of the delta modulator as a digital encoder of television signals are presented. The computer simulation was studied of different delta modulators in order to find a satisfactory delta modulator. After finding a suitable delta modulator algorithm via computer simulation, the results are analyzed and then implemented in hardware to study the ability to encode real time motion pictures from an NTSC format television camera. The effects were investigated of channel errors on the delta modulated video signal and several error correction algorithms were tested via computer simulation. A very high speed delta modulator was built (out of ECL logic), incorporating the most promising of the correction schemes, so that it could be tested on real time motion pictures. The final area of investigation concerned itself with finding delta modulators which could achieve significant bandwidth reduction without regard to complexity or speed. The first such scheme to be investigated was a real time frame to frame encoding scheme which required the assembly of fourteen, 131,000 bit long shift registers as well as a high speed delta modulator. The other schemes involved two dimensional delta modulator algorithms.

  11. Describing the complexity of systems: multivariable "set complexity" and the information basis of systems biology.

    PubMed

    Galas, David J; Sakhanenko, Nikita A; Skupin, Alexander; Ignac, Tomasz

    2014-02-01

    Context dependence is central to the description of complexity. Keying on the pairwise definition of "set complexity," we use an information theory approach to formulate general measures of systems complexity. We examine the properties of multivariable dependency starting with the concept of interaction information. We then present a new measure for unbiased detection of multivariable dependency, "differential interaction information." This quantity for two variables reduces to the pairwise "set complexity" previously proposed as a context-dependent measure of information in biological systems. We generalize it here to an arbitrary number of variables. Critical limiting properties of the "differential interaction information" are key to the generalization. This measure extends previous ideas about biological information and provides a more sophisticated basis for the study of complexity. The properties of "differential interaction information" also suggest new approaches to data analysis. Given a data set of system measurements, differential interaction information can provide a measure of collective dependence, which can be represented in hypergraphs describing complex system interaction patterns. We investigate this kind of analysis using simulated data sets. The conjoining of a generalized set complexity measure, multivariable dependency analysis, and hypergraphs is our central result. While our focus is on complex biological systems, our results are applicable to any complex system.

  12. Encoding sensory and motor patterns as time-invariant trajectories in recurrent neural networks.

    PubMed

    Goudar, Vishwa; Buonomano, Dean V

    2018-03-14

    Much of the information the brain processes and stores is temporal in nature-a spoken word or a handwritten signature, for example, is defined by how it unfolds in time. However, it remains unclear how neural circuits encode complex time-varying patterns. We show that by tuning the weights of a recurrent neural network (RNN), it can recognize and then transcribe spoken digits. The model elucidates how neural dynamics in cortical networks may resolve three fundamental challenges: first, encode multiple time-varying sensory and motor patterns as stable neural trajectories; second, generalize across relevant spatial features; third, identify the same stimuli played at different speeds-we show that this temporal invariance emerges because the recurrent dynamics generate neural trajectories with appropriately modulated angular velocities. Together our results generate testable predictions as to how recurrent networks may use different mechanisms to generalize across the relevant spatial and temporal features of complex time-varying stimuli. © 2018, Goudar et al.

  13. Encoding sensory and motor patterns as time-invariant trajectories in recurrent neural networks

    PubMed Central

    2018-01-01

    Much of the information the brain processes and stores is temporal in nature—a spoken word or a handwritten signature, for example, is defined by how it unfolds in time. However, it remains unclear how neural circuits encode complex time-varying patterns. We show that by tuning the weights of a recurrent neural network (RNN), it can recognize and then transcribe spoken digits. The model elucidates how neural dynamics in cortical networks may resolve three fundamental challenges: first, encode multiple time-varying sensory and motor patterns as stable neural trajectories; second, generalize across relevant spatial features; third, identify the same stimuli played at different speeds—we show that this temporal invariance emerges because the recurrent dynamics generate neural trajectories with appropriately modulated angular velocities. Together our results generate testable predictions as to how recurrent networks may use different mechanisms to generalize across the relevant spatial and temporal features of complex time-varying stimuli. PMID:29537963

  14. Event-related Potentials Reveal Age Differences in the Encoding and Recognition of Scenes

    PubMed Central

    Gutchess, Angela H.; Ieuji, Yoko; Federmeier, Kara D.

    2009-01-01

    The present study used event-related potentials (ERPs) to investigate how the encoding and recognition of complex scenes change with normal aging. Although functional magnetic resonance imaging (fMRI) studies have identified more drastic age impairments at encoding than at recognition, ERP studies accumulate more evidence for age differences at retrieval. However, stimulus type and paradigm differences across the two literatures have made direct comparisons difficult. Here, we collected young and elderly adults’ encoding- and recognition-phase ERPs using the same materials and paradigm as a previous fMRI study. Twenty young and 20 elderly adults incidentally encoded and then recognized photographs of outdoor scenes. During encoding, young adults showed a frontocentral subsequent memory effect, with high-confidence hits exhibiting greater positivity than misses. Elderly adults showed a similar subsequent memory effect, which, however, did not differ as a function of confidence. During recognition, young adults elicited a widespread old/new effect, and high-confidence hits were distinct from both low-confidence hits and false alarms. Elderly adults elicited a smaller and later old/new effect, which was unaffected by confidence, and hits and false alarms were indistinguishable in the waveforms. Consistent with prior ERP work, these results point to important age-related changes in recognition-phase brain activity, even when behavioral measures of memory and confidence pattern similarly across groups. We speculate that memory processes with different time signatures contribute to the apparent differences across encoding and retrieval stages, and across methods. PMID:17583986

  15. An encoding readout method used for Multi-gap Resistive Plate Chambers (MRPCs) for muon tomography

    NASA Astrophysics Data System (ADS)

    Yue, X.; Zeng, M.; Wang, Y.; Wang, X.; Zeng, Z.; Zhao, Z.; Cheng, J.

    2014-09-01

    A muon tomography facility has been built in Tsinghua University. Because of the low flux of cosmic muon, an encoding readout method, based on the fine-fine configuration, was implemented for the 2880 channels induced signals from the Multi-gap Resistive Plate Chamber (MRPC) detectors. With the encoding method, the number of the readout electronics was dramatically reduced and thus the complexity and the cost of the facility was reduced, too. In this paper, the details of the encoding method, and the overall readout system setup in the muon tomography facility are described. With the commissioning of the facility, the readout method works well. The spatial resolution of all MRPC detectors are measured with cosmic muon and the preliminary imaging result are also given.

  16. Simple low cost differentiation of Candida auris from Candida haemulonii complex using CHROMagar Candida medium supplemented with Pal's medium.

    PubMed

    Kumar, Anil; Sachu, Arun; Mohan, Karthika; Vinod, Vivek; Dinesh, Kavitha; Karim, Shamsul

    Candida auris is unique due to its multidrug resistance and misidentification as Candida haemulonii by commercial systems. Its correct identification is important to avoid inappropriate treatments. To develop a cheap method for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Fifteen C. auris isolates, six isolates each of C. haemulonii and Candida duobushaemulonii, and one isolate of Candida haemulonii var. vulnera were tested using CHROMagar Candida medium supplemented with Pal's agar for better differentiation. On CHROMagar Candida medium supplemented with Pal's agar all C. auris strains showed confluent growth of white to cream colored smooth colonies at 37°C and 42°C after 24 and 48h incubation and did not produce pseudohyphae. The isolates of the C. haemulonii complex, on the contrary, showed poor growth of smooth, light-pink colonies at 24h while at 48h the growth was semiconfluent with the production of pseudohyphae. C. haemulonii complex failed to grow at 42°C. We report a rapid and cheap method using CHROMagar Candida medium supplemented with Pal's agar for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5).

    PubMed

    Falcón-Pérez, Juan M; Romero-Calderón, Rafael; Brooks, Elizabeth S; Krantz, David E; Dell'Angelica, Esteban C

    2007-02-01

    Lysosome-related organelles comprise a group of specialized intracellular compartments that include melanosomes and platelet dense granules (in mammals) and eye pigment granules (in insects). In humans, the biogenesis of these organelles is defective in genetic disorders collectively known as Hermansky-Pudlak syndrome (HPS). Patients with HPS-2, and two murine HPS models, carry mutations in genes encoding subunits of adaptor protein (AP)-3. Other genes mutated in rodent models include those encoding VPS33A and Rab38. Orthologs of all of these genes in Drosophila melanogaster belong to the 'granule group' of eye pigmentation genes. Other genes associated with HPS encode subunits of three complexes of unknown function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2 and -3, for which the Drosophila counterparts had not been characterized. Here, we report that the gene encoding the Drosophila ortholog of the HPS5 subunit of BLOC-2 is identical to the granule group gene pink (p), which was first studied in 1910 but had not been identified at the molecular level. The phenotype of pink mutants was exacerbated by mutations in AP-3 subunits or in the orthologs of VPS33A and Rab38. These results validate D. melanogaster as a genetic model to study the function of the BLOCs.

  18. Complexity control algorithm based on adaptive mode selection for interframe coding in high efficiency video coding

    NASA Astrophysics Data System (ADS)

    Chen, Gang; Yang, Bing; Zhang, Xiaoyun; Gao, Zhiyong

    2017-07-01

    The latest high efficiency video coding (HEVC) standard significantly increases the encoding complexity for improving its coding efficiency. Due to the limited computational capability of handheld devices, complexity constrained video coding has drawn great attention in recent years. A complexity control algorithm based on adaptive mode selection is proposed for interframe coding in HEVC. Considering the direct proportionality between encoding time and computational complexity, the computational complexity is measured in terms of encoding time. First, complexity is mapped to a target in terms of prediction modes. Then, an adaptive mode selection algorithm is proposed for the mode decision process. Specifically, the optimal mode combination scheme that is chosen through offline statistics is developed at low complexity. If the complexity budget has not been used up, an adaptive mode sorting method is employed to further improve coding efficiency. The experimental results show that the proposed algorithm achieves a very large complexity control range (as low as 10%) for the HEVC encoder while maintaining good rate-distortion performance. For the lowdelayP condition, compared with the direct resource allocation method and the state-of-the-art method, an average gain of 0.63 and 0.17 dB in BDPSNR is observed for 18 sequences when the target complexity is around 40%.

  19. Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy

    PubMed Central

    Schmidts, Miriam; Vodopiutz, Julia; Christou-Savina, Sonia; Cortés, Claudio R.; McInerney-Leo, Aideen M.; Emes, Richard D.; Arts, Heleen H.; Tüysüz, Beyhan; D’Silva, Jason; Leo, Paul J.; Giles, Tom C.; Oud, Machteld M.; Harris, Jessica A.; Koopmans, Marije; Marshall, Mhairi; Elçioglu, Nursel; Kuechler, Alma; Bockenhauer, Detlef; Moore, Anthony T.; Wilson, Louise C.; Janecke, Andreas R.; Hurles, Matthew E.; Emmet, Warren; Gardiner, Brooke; Streubel, Berthold; Dopita, Belinda; Zankl, Andreas; Kayserili, Hülya; Scambler, Peter J.; Brown, Matthew A.; Beales, Philip L.; Wicking, Carol; Duncan, Emma L.; Mitchison, Hannah M.

    2013-01-01

    Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery. PMID:24183451

  20. Characterization of the Complex Locus of Bean Encoding Polygalacturonase-Inhibiting Proteins Reveals Subfunctionalization for Defense against Fungi and Insects1

    PubMed Central

    D'Ovidio, Renato; Raiola, Alessandro; Capodicasa, Cristina; Devoto, Alessandra; Pontiggia, Daniela; Roberti, Serena; Galletti, Roberta; Conti, Eric; O'Sullivan, Donal; De Lorenzo, Giulia

    2004-01-01

    Polygalacturonase-inhibiting proteins (PGIPs) are extracellular plant inhibitors of fungal endopolygalacturonases (PGs) that belong to the superfamily of Leu-rich repeat proteins. We have characterized the full complement of pgip genes in the bean (Phaseolus vulgaris) genotype BAT93. This comprises four clustered members that span a 50-kb region and, based on their similarity, form two pairs (Pvpgip1/Pvpgip2 and Pvpgip3/Pvpgip4). Characterization of the encoded products revealed both partial redundancy and subfunctionalization against fungal-derived PGs. Notably, the pair PvPGIP3/PvPGIP4 also inhibited PGs of two mirid bugs (Lygus rugulipennis and Adelphocoris lineolatus). Characterization of Pvpgip genes of Pinto bean showed variations limited to single synonymous substitutions or small deletions. A three-amino acid deletion encompassing a residue previously identified as crucial for recognition of PG of Fusarium moniliforme was responsible for the inability of BAT93 PvPGIP2 to inhibit this enzyme. Consistent with the large variations observed in the promoter sequences, reverse transcription-PCR expression analysis revealed that the different family members differentially respond to elicitors, wounding, and salicylic acid. We conclude that both biochemical and regulatory redundancy and subfunctionalization of pgip genes are important for the adaptation of plants to pathogenic fungi and phytophagous insects. PMID:15299124

  1. PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation[S

    PubMed Central

    Hallenborg, Philip; Petersen, Rasmus Koefoed; Feddersen, Søren; Sundekilde, Ulrik; Hansen, Jacob B.; Blagoev, Blagoy; Madsen, Lise; Kristiansen, Karsten

    2014-01-01

    Adipocyte differentiation is orchestrated by the ligand-activated nuclear receptor PPARγ. Endogenous ligands comprise oxidized derivatives of arachidonic acid and structurally similar PUFAs. Although expression of PPARγ peaks in mature adipocytes, ligands are produced primarily at the onset of differentiation. Concomitant with agonist production, murine fibroblasts undergo two rounds of mitosis referred to as mitotic clonal expansion. Here we show that mouse embryonic fibroblasts deficient in either of two cell cycle inhibitors, the transcription factor p53 or its target gene encoding the cyclin-dependent kinase inhibitor p21, exhibit increased adipogenic potential. The antiadipogenic effect of p53 relied on its transcriptional activity and p21 expression but was circumvented by administration of an exogenous PPARγ agonist suggesting a linkage between cell cycling and PPARγ ligand production. Indeed, cell cycle inhibitory compounds decreased PPARγ ligand production in differentiating 3T3-L1 preadipocytes. Furthermore, these inhibitors abolished the release of arachidonic acid induced by the hormonal cocktail initiating adipogenesis. Collectively, our results suggest that murine fibroblasts require clonal expansion for PPARγ ligand production at the onset of adipocyte differentiation. PMID:25312885

  2. Pea chloroplast DNA encodes homologues of Escherichia coli ribosomal subunit S2 and the beta'-subunit of RNA polymerase.

    PubMed Central

    Cozens, A L; Walker, J E

    1986-01-01

    The nucleotide sequence has been determined of a segment of 4680 bases of the pea chloroplast genome. It adjoins a sequence described elsewhere that encodes subunits of the F0 membrane domain of the ATP-synthase complex. The sequence contains a potential gene encoding a protein which is strongly related to the S2 polypeptide of Escherichia coli ribosomes. It also encodes an incomplete protein which contains segments that are homologous to the beta'-subunit of E. coli RNA polymerase and to yeast RNA polymerases II and III. PMID:3530249

  3. Video time encoding machines.

    PubMed

    Lazar, Aurel A; Pnevmatikakis, Eftychios A

    2011-03-01

    We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value.

  4. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K [Idaho Falls, ID

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  5. A MPEG-4 encoder based on TMS320C6416

    NASA Astrophysics Data System (ADS)

    Li, Gui-ju; Liu, Wei-ning

    2013-08-01

    Engineering and products need to achieve real-time video encoding by DSP, but the high computational complexity and huge amount of data requires that system has high data throughput. In this paper, a real-time MPEG-4 video encoder is designed based on TMS320C6416 platform. The kernel is the DSP of TMS320C6416T and FPGA chip f as the organization and management of video data. In order to control the flow of input and output data. Encoded stream is output using the synchronous serial port. The system has the clock frequency of 1GHz and has up to 8000 MIPS speed processing capacity when running at full speed. Due to the low coding efficiency of MPEG-4 video encoder transferred directly to DSP platform, it is needed to improve the program structure, data structures and algorithms combined with TMS320C6416T characteristics. First: Design the image storage architecture by balancing the calculation spending, storage space cost and EDMA read time factors. Open up a more buffer in memory, each buffer cache 16 lines of video data to be encoded, reconstruction image and reference image including search range. By using the variable alignment mode of the DSP, modifying the definition of structure variables and change the look-up table which occupy larger space with a direct calculation array to save memory space. After the program structure optimization, the program code, all variables, buffering buffers and the interpolation image including the search range can be placed in memory. Then, as to the time-consuming process modules and some functions which are called many times, the corresponding modules are written in parallel assembly language of TMS320C6416T which can increase the running speed. Besides, the motion estimation algorithm is improved by using a cross-hexagon search algorithm, The search speed can be increased obviously. Finally, the execution time, signal-to-noise ratio and compression ratio of a real-time image acquisition sequence is given. The experimental

  6. Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide

    NASA Astrophysics Data System (ADS)

    Ermakova, Yulia G.; Bilan, Dmitry S.; Matlashov, Mikhail E.; Mishina, Natalia M.; Markvicheva, Ksenia N.; Subach, Oksana M.; Subach, Fedor V.; Bogeski, Ivan; Hoth, Markus; Enikolopov, Grigori; Belousov, Vsevolod V.

    2014-10-01

    Reactive oxygen species (ROS) are conserved regulators of numerous cellular functions, and overproduction of ROS is a hallmark of various pathological processes. Genetically encoded fluorescent probes are unique tools to study ROS production in living systems of different scale and complexity. However, the currently available recombinant redox sensors have green emission, which overlaps with the spectra of many other probes. Expanding the spectral range of recombinant in vivo ROS probes would enable multiparametric in vivo ROS detection. Here we present the first genetically encoded red fluorescent sensor for hydrogen peroxide detection, HyPerRed. The performance of this sensor is similar to its green analogues. We demonstrate the utility of the sensor by tracing low concentrations of H2O2 produced in the cytoplasm of cultured cells upon growth factor stimulation. Moreover, using HyPerRed we detect local and transient H2O2 production in the mitochondrial matrix upon inhibition of the endoplasmic reticulum Ca2+ uptake.

  7. Memory for emotional words: The role of semantic relatedness, encoding task and affective valence.

    PubMed

    Ferré, Pilar; Fraga, Isabel; Comesaña, Montserrat; Sánchez-Casas, Rosa

    2015-01-01

    Emotional stimuli have been repeatedly demonstrated to be better remembered than neutral ones. The aim of the present study was to test whether this advantage in memory is mainly produced by the affective content of the stimuli or it can be rather accounted for by factors such as semantic relatedness or type of encoding task. The valence of the stimuli (positive, negative and neutral words that could be either semantically related or unrelated) as well as the type of encoding task (focused on either familiarity or emotionality) was manipulated. The results revealed an advantage in memory for emotional words (either positive or negative) regardless of semantic relatedness. Importantly, this advantage was modulated by the encoding task, as it was reliable only in the task which focused on emotionality. These findings suggest that congruity with the dimension attended at encoding might contribute to the superiority in memory for emotional words, thus offering us a more complex picture of the underlying mechanisms behind the advantage for emotional information in memory.

  8. Encoding of Reward and Space During a Working Memory Task in the Orbitofrontal Cortex and Anterior Cingulate Sulcus

    PubMed Central

    Kennerley, Steven W.

    2009-01-01

    Several lines of research indicate that emotional and motivational information may be useful in guiding the allocation of attentional resources. Two areas of the frontal lobe that are particularly implicated in the encoding of motivational information are the orbital prefrontal cortex (PFo) and the dorsomedial region of prefrontal cortex, specifically the anterior cingulate sulcus (PFcs). However, it remains unclear whether these areas use this information to influence spatial attention. We used single-unit neurophysiology to examine whether, at the level of individual neurons, there was evidence for integration between reward information and spatial attention. We trained two subjects to perform a task that required them to attend to a spatial location across a delay under different expectancies of reward for correct performance. We balanced the order of presentation of spatial and reward information so we could assess the neuronal encoding of the two pieces of information independently and conjointly. We found little evidence for encoding of the spatial location in either PFo or PFcs. In contrast, both areas encoded the expected reward. Furthermore, PFo consistently encoded reward more quickly than PFcs, although reward encoding was subsequently more prevalent and stronger in PFcs. These results suggest a differential contribution of PFo and PFcs to reward encoding, with PFo potentially more important for initially determining the value of rewards predicted by sensory stimuli. They also suggest that neither PFo nor PFcs play a direct role in the control of spatial attention. PMID:19776363

  9. PCR-based Methodologies Used to Detect and Differentiate the Burkholderia pseudomallei complex: B. pseudomallei, B. mallei, and B. thailandensis.

    PubMed

    Lowe, Woan; March, Jordon K; Bunnell, Annette J; O'Neill, Kim L; Robison, Richard A

    2014-01-01

    Methods for the rapid detection and differentiation of the Burkholderia pseudomallei complex comprising B. pseudomallei, B. mallei, and B. thailandensis, have been the topic of recent research due to the high degree of phenotypic and genotypic similarities of these species. B. pseudomallei and B. mallei are recognized by the CDC as tier 1 select agents. The high mortality rates of glanders and melioidosis, their potential use as bioweapons, and their low infectious dose, necessitate the need for rapid and accurate detection methods. Although B. thailandensis is generally avirulent in mammals, this species displays very similar phenotypic characteristics to that of B. pseudomallei. Optimal identification of these species remains problematic, due to the difficulty in developing a sensitive, selective, and accurate assay. The development of PCR technologies has revolutionized diagnostic testing and these detection methods have become popular due to their speed, sensitivity, and accuracy. The purpose of this review is to provide a comprehensive overview and evaluation of the advancements in PCR-based detection and differentiation methodologies for the B. pseudomallei complex, and examine their potential uses in diagnostic and environmental testing.

  10. DNA-encoded libraries - an efficient small molecule discovery technology for the biomedical sciences.

    PubMed

    Kunig, Verena; Potowski, Marco; Gohla, Anne; Brunschweiger, Andreas

    2018-06-27

    DNA-encoded compound libraries are a highly attractive technology for the discovery of small molecule protein ligands. These compound collections consist of small molecules covalently connected to individual DNA sequences carrying readable information about the compound structure. DNA-tagging allows for efficient synthesis, handling and interrogation of vast numbers of chemically synthesized, drug-like compounds. They are screened on proteins by an efficient, generic assay based on Darwinian principles of selection. To date, selection of DNA-encoded libraries allowed for the identification of numerous bioactive compounds. Some of these compounds uncovered hitherto unknown allosteric binding sites on target proteins; several compounds proved their value as chemical biology probes unraveling complex biology; and the first examples of clinical candidates that trace their ancestry to a DNA-encoded library were reported. Thus, DNA-encoded libraries proved their value for the biomedical sciences as a generic technology for the identification of bioactive drug-like molecules numerous times. However, large scale experiments showed that even the selection of billions of compounds failed to deliver bioactive compounds for the majority of proteins in an unbiased panel of target proteins. This raises the question of compound library design.

  11. Genomic profiling of dedifferentiated liposarcoma compared to matched well-differentiated liposarcoma reveals higher genomic complexity and a common origin

    PubMed Central

    Beird, Hannah C.; Wu, Chia-Chin; Ingram, Davis R.; Wang, Wei-Lien; Alimohamed, Asrar; Gumbs, Curtis; Little, Latasha; Song, Xingzhi; Feig, Barry W.; Roland, Christina L.; Zhang, Jianhua; Benjamin, Robert S.; Hwu, Patrick; Lazar, Alexander J.; Futreal, P. Andrew; Somaiah, Neeta

    2018-01-01

    Well-differentiated (WD) liposarcoma is a low-grade mesenchymal tumor with features of mature adipocytes and high propensity for local recurrence. Often, WD patients present with or later progress to a higher-grade nonlipogenic form known as dedifferentiated (DD) liposarcoma. These DD tumors behave more aggressively and can metastasize. Both WD and DD liposarcomas harbor neochromosomes formed from amplifications and rearrangements of Chr 12q that encode oncogenes (MDM2, CDK4, and YEATS2) and adipocytic differentiation factors (HMGA2 and CPM). However, genomic changes associated with progression from WD to DD have not been well-defined. Therefore, we selected patients with matched WD and DD tumors for extensive genomic profiling in order to understand their clonal relationships and to delineate any defining alterations for each entity. Exome and transcriptomic sequencing was performed for 17 patients with both WD and DD diagnoses. Somatic point and copy-number alterations were integrated with transcriptional analyses to determine subtype-associated genomic features and pathways. The results were, on average, that only 8.3% of somatic mutations in WD liposarcoma were shared with their cognate DD component. DD tumors had higher numbers of somatic copy-number losses, amplifications involving Chr 12q, and fusion transcripts than WD tumors. HMGA2 and CPM rearrangements occur more frequently in DD components. The shared somatic mutations indicate a clonal origin for matched WD and DD tumors and show early divergence with ongoing genomic instability due to continual generation and selection of neochromosomes. Stochastic generation and subsequent expression of fusion transcripts from the neochromosome that involve adipogenesis genes such as HMGA2 and CPM may influence the differentiation state of the subsequent tumor. PMID:29610390

  12. Multiplex PCR for Rapid Detection of Genes Encoding Class A Carbapenemases

    PubMed Central

    Hong, Sang Sook; Kim, Kyeongmi; Huh, Ji Young; Jung, Bochan; Kang, Myung Seo

    2012-01-01

    In recent years, there have been increasing reports of KPC-producing Klebsiella pneumoniae in Korea. The modified Hodge test can be used as a phenotypic screening test for class A carbapenamase (CAC)-producing clinical isolates; however, it does not distinguish between carbapenemase types. The confirmation of type of CAC is important to ensure optimal therapy and to prevent transmission. This study applied a novel multiplex PCR assay to detect and differentiate CAC genes in a single reaction. Four primer pairs were designed to amplify fragments encoding 4 CAC families (SME, IMI/NMC-A, KPC, and GES). The multiplex PCR detected all genes tested for 4 CAC families that could be differentiated by fragment size according to gene type. This multiplex PCR offers a simple and useful approach for detecting and distinguishing CAC genes in carbapenem-resistant strains that are metallo-β-lactamase nonproducers. PMID:22950072

  13. Prospective memory function in late adulthood: affect at encoding and resource allocation costs.

    PubMed

    Henry, Julie D; Joeffry, Sebastian; Terrett, Gill; Ballhausen, Nicola; Kliegel, Matthias; Rendell, Peter G

    2015-01-01

    Some studies have found that prospective memory (PM) cues which are emotionally valenced influence age effects in prospective remembering, but it remains unclear whether this effect reflects the operation of processes implemented at encoding or retrieval. In addition, none of the prior ageing studies of valence on PM function have examined potential costs of engaging in different valence conditions, or resource allocation trade-offs between the PM and the ongoing task. In the present study, younger, young-old and old-old adults completed a PM task in which the valence of the cues varied systematically (positive, negative or neutral) at encoding, but was kept constant (neutral) at retrieval. The results indicated that PM accuracy did not vary as a function of affect at encoding, and that this effect did not interact with age group. There was also no main or interaction effect of valence on PM reaction time in PM cue trials, indicating that valence costs across the three encoding conditions were equivalent. Old-old adults' PM accuracy was reduced relative to both young-old and younger adults. Prospective remembering incurred dual-task costs for all three groups. Analyses of reaction time data suggested that for both young-old and old-old, these costs were greater, implying differential resource allocation cost trade-offs. However, when reaction time data were expressed as a proportional change that adjusted for the general slowing of the older adults, costs did not differ as a function of group.

  14. Prospective Memory Function in Late Adulthood: Affect at Encoding and Resource Allocation Costs

    PubMed Central

    Henry, Julie D.; Joeffry, Sebastian; Terrett, Gill; Ballhausen, Nicola; Kliegel, Matthias; Rendell, Peter G.

    2015-01-01

    Some studies have found that prospective memory (PM) cues which are emotionally valenced influence age effects in prospective remembering, but it remains unclear whether this effect reflects the operation of processes implemented at encoding or retrieval. In addition, none of the prior ageing studies of valence on PM function have examined potential costs of engaging in different valence conditions, or resource allocation trade-offs between the PM and the ongoing task. In the present study, younger, young-old and old-old adults completed a PM task in which the valence of the cues varied systematically (positive, negative or neutral) at encoding, but was kept constant (neutral) at retrieval. The results indicated that PM accuracy did not vary as a function of affect at encoding, and that this effect did not interact with age group. There was also no main or interaction effect of valence on PM reaction time in PM cue trials, indicating that valence costs across the three encoding conditions were equivalent. Old-old adults’ PM accuracy was reduced relative to both young-old and younger adults. Prospective remembering incurred dual-task costs for all three groups. Analyses of reaction time data suggested that for both young-old and old-old, these costs were greater, implying differential resource allocation cost trade-offs. However, when reaction time data were expressed as a proportional change that adjusted for the general slowing of the older adults, costs did not differ as a function of group. PMID:25893540

  15. Encoder: A Connectionist Model of How Learning to Visually Encode Fixated Text Images Improves Reading Fluency

    ERIC Educational Resources Information Center

    Martin, Gale L.

    2004-01-01

    This article proposes that visual encoding learning improves reading fluency by widening the span over which letters are recognized from a fixated text image so that fewer fixations are needed to cover a text line. Encoder is a connectionist model that learns to convert images like the fixated text images human readers encode into the…

  16. Cyclic Di-GMP modulates the disease progression of Erwinia amylovora.

    PubMed

    Edmunds, Adam C; Castiblanco, Luisa F; Sundin, George W; Waters, Christopher M

    2013-05-01

    The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis.

  17. Cyclic Di-GMP Modulates the Disease Progression of Erwinia amylovora

    PubMed Central

    Edmunds, Adam C.; Castiblanco, Luisa F.; Sundin, George W.

    2013-01-01

    The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis. PMID:23475975

  18. Epstein-Barr virus (EBV)-encoded dUTPase and chronic restraint induce impaired learning and memory and sickness responses.

    PubMed

    Aubrecht, Taryn G; Weil, Zachary M; Ariza, Maria Eugenia; Williams, Marshall; Reader, Brenda F; Glaser, Ronald; Sheridan, John F; Nelson, Randy J

    2014-10-01

    Most adult humans have been infected with Epstein-Barr virus (EBV) and carry the latent virus. The EBV genome codes for several proteins that form an early antigen complex important for viral replication; one of these proteins is deoxyuridine triphosphate nucleotidohydrolase (dUTPase). The EBV-encoded dUTPase can induce sickness responses in mice. Because stress can increase latent virus reactivation, we hypothesized that chronic restraint would exacerbate sickness behaviors elicited by EBV-encoded dUTPase. Male Swiss-Webster mice were injected daily for 15 days with either saline or EBV-encoded dUTPase. Additionally, half of the mice from each condition were either restrained for 3h daily or left undisturbed. Restraint stress impaired learning and memory in the passive avoidance chamber; impaired learning and memory was due to EBV-encoded dUTPase injected into restrained mice. EBV-encoded dUTPase induced sickness responses and restraint stress interacts with EBV-encoded dUTPase to exacerbate the sickness response. These data support a role for EBV-encoded dUTPase and restraint stress in altering the pathophysiology of EBV independent of viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Multiplexed fluorescent microarray for human salivary protein analysis using polymer microspheres and fiber-optic bundles.

    PubMed

    Nie, Shuai; Benito-Peña, Elena; Zhang, Huaibin; Wu, Yue; Walt, David R

    2013-10-10

    Herein, we describe a protocol for simultaneously measuring six proteins in saliva using a fiber-optic microsphere-based antibody array. The immuno-array technology employed combines the advantages of microsphere-based suspension array fabrication with the use of fluorescence microscopy. As described in the video protocol, commercially available 4.5 μm polymer microspheres were encoded into seven different types, differentiated by the concentration of two fluorescent dyes physically trapped inside the microspheres. The encoded microspheres containing surface carboxyl groups were modified with monoclonal capture antibodies through EDC/NHS coupling chemistry. To assemble the protein microarray, the different types of encoded and functionalized microspheres were mixed and randomly deposited in 4.5 μm microwells, which were chemically etched at the proximal end of a fiber-optic bundle. The fiber-optic bundle was used as both a carrier and for imaging the microspheres. Once assembled, the microarray was used to capture proteins in the saliva supernatant collected from the clinic. The detection was based on a sandwich immunoassay using a mixture of biotinylated detection antibodies for different analytes with a streptavidin-conjugated fluorescent probe, R-phycoerythrin. The microarray was imaged by fluorescence microscopy in three different channels, two for microsphere registration and one for the assay signal. The fluorescence micrographs were then decoded and analyzed using a homemade algorithm in MATLAB.

  20. Differential encoding of factors influencing predicted reward value in monkey rostral anterior cingulate cortex.

    PubMed

    Toda, Koji; Sugase-Miyamoto, Yasuko; Mizuhiki, Takashi; Inaba, Kiyonori; Richmond, Barry J; Shidara, Munetaka

    2012-01-01

    The value of a predicted reward can be estimated based on the conjunction of both the intrinsic reward value and the length of time to obtain it. The question we addressed is how the two aspects, reward size and proximity to reward, influence the responses of neurons in rostral anterior cingulate cortex (rACC), a brain region thought to play an important role in reward processing. We recorded from single neurons while two monkeys performed a multi-trial reward schedule task. The monkeys performed 1-4 sequential color discrimination trials to obtain a reward of 1-3 liquid drops. There were two task conditions, a valid cue condition, where the number of trials and reward amount were associated with visual cues, and a random cue condition, where the cue was picked from the cue set at random. In the valid cue condition, the neuronal firing is strongly modulated by the predicted reward proximity during the trials. Information about the predicted reward amount is almost absent at those times. In substantial subpopulations, the neuronal responses decreased or increased gradually through schedule progress to the predicted outcome. These two gradually modulating signals could be used to calculate the effect of time on the perception of reward value. In the random cue condition, little information about the reward proximity or reward amount is encoded during the course of the trial before reward delivery, but when the reward is actually delivered the responses reflect both the reward proximity and reward amount. Our results suggest that the rACC neurons encode information about reward proximity and amount in a manner that is dependent on utility of reward information. The manner in which the information is represented could be used in the moment-to-moment calculation of the effect of time and amount on predicted outcome value.

  1. Video Time Encoding Machines

    PubMed Central

    Lazar, Aurel A.; Pnevmatikakis, Eftychios A.

    2013-01-01

    We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value. PMID:21296708

  2. Spectrally-encoded color imaging

    PubMed Central

    Kang, DongKyun; Yelin, Dvir; Bouma, Brett E.; Tearney, Guillermo J.

    2010-01-01

    Spectrally-encoded endoscopy (SEE) is a technique for ultraminiature endoscopy that encodes each spatial location on the sample with a different wavelength. One limitation of previous incarnations of SEE is that it inherently creates monochromatic images, since the spectral bandwidth is expended in the spatial encoding process. Here we present a spectrally-encoded imaging system that has color imaging capability. The new imaging system utilizes three distinct red, green, and blue spectral bands that are configured to illuminate the grating at different incident angles. By careful selection of the incident angles, the three spectral bands can be made to overlap on the sample. To demonstrate the method, a bench-top system was built, comprising a 2400-lpmm grating illuminated by three 525-μm-diameter beams with three different spectral bands. Each spectral band had a bandwidth of 75 nm, producing 189 resolvable points. A resolution target, color phantoms, and excised swine small intestine were imaged to validate the system's performance. The color SEE system showed qualitatively and quantitatively similar color imaging performance to that of a conventional digital camera. PMID:19688002

  3. Mapping gene expression patterns during myeloid differentiation using the EML hematopoietic progenitor cell line.

    PubMed

    Du, Yang; Campbell, Janee L; Nalbant, Demet; Youn, Hyewon; Bass, Ann C Hughes; Cobos, Everardo; Tsai, Schickwann; Keller, Jonathan R; Williams, Simon C

    2002-07-01

    The detailed examination of the molecular events that control the early stages of myeloid differentiation has been hampered by the relative scarcity of hematopoietic stem cells and the lack of suitable cell line models. In this study, we examined the expression of several myeloid and nonmyeloid genes in the murine EML hematopoietic stem cell line. Expression patterns for 19 different genes were examined by Northern blotting and RT-PCR in RNA samples from EML, a variety of other immortalized cell lines, and purified murine hematopoietic stem cells. Representational difference analysis (RDA) was performed to identify differentially expressed genes in EML. Expression patterns of genes encoding transcription factors (four members of the C/EBP family, GATA-1, GATA-2, PU.1, CBFbeta, SCL, and c-myb) in EML were examined and were consistent with the proposed functions of these proteins in hematopoietic differentiation. Expression levels of three markers of terminal myeloid differentiation (neutrophil elastase, proteinase 3, and Mac-1) were highest in EML cells at the later stages of differentiation. In a search for genes that were differentially expressed in EML cells during myeloid differentiation, six cDNAs were isolated. These included three known genes (lysozyme, histidine decarboxylase, and tryptophan hydroxylase) and three novel genes. Expression patterns of known genes in differentiating EML cells accurately reflected their expected expression patterns based on previous studies. The identification of three novel genes, two of which encode proteins that may act as regulators of hematopoietic differentiation, suggests that EML is a useful model system for the molecular analysis of hematopoietic differentiation.

  4. Evaluating standard terminologies for encoding allergy information.

    PubMed

    Goss, Foster R; Zhou, Li; Plasek, Joseph M; Broverman, Carol; Robinson, George; Middleton, Blackford; Rocha, Roberto A

    2013-01-01

    Allergy documentation and exchange are vital to ensuring patient safety. This study aims to analyze and compare various existing standard terminologies for representing allergy information. Five terminologies were identified, including the Systemized Nomenclature of Medical Clinical Terms (SNOMED CT), National Drug File-Reference Terminology (NDF-RT), Medication Dictionary for Regulatory Activities (MedDRA), Unique Ingredient Identifier (UNII), and RxNorm. A qualitative analysis was conducted to compare desirable characteristics of each terminology, including content coverage, concept orientation, formal definitions, multiple granularities, vocabulary structure, subset capability, and maintainability. A quantitative analysis was also performed to compare the content coverage of each terminology for (1) common food, drug, and environmental allergens and (2) descriptive concepts for common drug allergies, adverse reactions (AR), and no known allergies. Our qualitative results show that SNOMED CT fulfilled the greatest number of desirable characteristics, followed by NDF-RT, RxNorm, UNII, and MedDRA. Our quantitative results demonstrate that RxNorm had the highest concept coverage for representing drug allergens, followed by UNII, SNOMED CT, NDF-RT, and MedDRA. For food and environmental allergens, UNII demonstrated the highest concept coverage, followed by SNOMED CT. For representing descriptive allergy concepts and adverse reactions, SNOMED CT and NDF-RT showed the highest coverage. Only SNOMED CT was capable of representing unique concepts for encoding no known allergies. The proper terminology for encoding a patient's allergy is complex, as multiple elements need to be captured to form a fully structured clinical finding. Our results suggest that while gaps still exist, a combination of SNOMED CT and RxNorm can satisfy most criteria for encoding common allergies and provide sufficient content coverage.

  5. Evaluating standard terminologies for encoding allergy information

    PubMed Central

    Goss, Foster R; Zhou, Li; Plasek, Joseph M; Broverman, Carol; Robinson, George; Middleton, Blackford; Rocha, Roberto A

    2013-01-01

    Objective Allergy documentation and exchange are vital to ensuring patient safety. This study aims to analyze and compare various existing standard terminologies for representing allergy information. Methods Five terminologies were identified, including the Systemized Nomenclature of Medical Clinical Terms (SNOMED CT), National Drug File–Reference Terminology (NDF-RT), Medication Dictionary for Regulatory Activities (MedDRA), Unique Ingredient Identifier (UNII), and RxNorm. A qualitative analysis was conducted to compare desirable characteristics of each terminology, including content coverage, concept orientation, formal definitions, multiple granularities, vocabulary structure, subset capability, and maintainability. A quantitative analysis was also performed to compare the content coverage of each terminology for (1) common food, drug, and environmental allergens and (2) descriptive concepts for common drug allergies, adverse reactions (AR), and no known allergies. Results Our qualitative results show that SNOMED CT fulfilled the greatest number of desirable characteristics, followed by NDF-RT, RxNorm, UNII, and MedDRA. Our quantitative results demonstrate that RxNorm had the highest concept coverage for representing drug allergens, followed by UNII, SNOMED CT, NDF-RT, and MedDRA. For food and environmental allergens, UNII demonstrated the highest concept coverage, followed by SNOMED CT. For representing descriptive allergy concepts and adverse reactions, SNOMED CT and NDF-RT showed the highest coverage. Only SNOMED CT was capable of representing unique concepts for encoding no known allergies. Conclusions The proper terminology for encoding a patient's allergy is complex, as multiple elements need to be captured to form a fully structured clinical finding. Our results suggest that while gaps still exist, a combination of SNOMED CT and RxNorm can satisfy most criteria for encoding common allergies and provide sufficient content coverage. PMID:23396542

  6. Encoders for block-circulant LDPC codes

    NASA Technical Reports Server (NTRS)

    Andrews, Kenneth; Dolinar, Sam; Thorpe, Jeremy

    2005-01-01

    In this paper, we present two encoding methods for block-circulant LDPC codes. The first is an iterative encoding method based on the erasure decoding algorithm, and the computations required are well organized due to the block-circulant structure of the parity check matrix. The second method uses block-circulant generator matrices, and the encoders are very similar to those for recursive convolutional codes. Some encoders of the second type have been implemented in a small Field Programmable Gate Array (FPGA) and operate at 100 Msymbols/second.

  7. Emotional arousal and memory after deep encoding.

    PubMed

    Leventon, Jacqueline S; Camacho, Gabriela L; Ramos Rojas, Maria D; Ruedas, Angelica

    2018-05-22

    Emotion often enhances long-term memory. One mechanism for this enhancement is heightened arousal during encoding. However, reducing arousal, via emotion regulation (ER) instructions, has not been associated with reduced memory. In fact, the opposite pattern has been observed: stronger memory for emotional stimuli encoded with an ER instruction to reduce arousal. This pattern may be due to deeper encoding required by ER instructions. In the current research, we examine the effects of emotional arousal and deep-encoding on memory across three studies. In Study 1, adult participants completed a writing task (deep-encoding) for encoding negative, neutral, and positive picture stimuli, whereby half the emotion stimuli had the ER instruction to reduce the emotion. Memory was strong across conditions, and no memory enhancement was observed for any condition. In Study 2, adult participants completed the same writing task as Study 1, as well as a shallow-encoding task for one-third of negative, neutral, and positive trials. Memory was strongest for deep vs. shallow encoding trials, with no effects of emotion or ER instruction. In Study 3, adult participants completed a shallow-encoding task for negative, neutral, and positive stimuli, with findings indicating enhanced memory for negative emotional stimuli. Findings suggest that deep encoding must be acknowledged as a source of memory enhancement when examining manipulations of emotion-related arousal. Copyright © 2018. Published by Elsevier B.V.

  8. Pulse Vector-Excitation Speech Encoder

    NASA Technical Reports Server (NTRS)

    Davidson, Grant; Gersho, Allen

    1989-01-01

    Proposed pulse vector-excitation speech encoder (PVXC) encodes analog speech signals into digital representation for transmission or storage at rates below 5 kilobits per second. Produces high quality of reconstructed speech, but with less computation than required by comparable speech-encoding systems. Has some characteristics of multipulse linear predictive coding (MPLPC) and of code-excited linear prediction (CELP). System uses mathematical model of vocal tract in conjunction with set of excitation vectors and perceptually-based error criterion to synthesize natural-sounding speech.

  9. Pneumatic binary encoder replaces multiple solenoid system

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Pneumatic binary encoder replaces solenoid system in the pilot stage of a digital actuator. The encoder operates in flip-flop manner to valve gas at either high or low pressures. By rotating the disk in a pinion-to-encoding gear ratio, six to eight adder circuits may be operated from single encoder.

  10. Novel Multiplex Real-Time PCR Diagnostic Assay for Identification and Differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis Complex Strains▿†

    PubMed Central

    Reddington, Kate; O'Grady, Justin; Dorai-Raj, Siobhan; Maher, Majella; van Soolingen, Dick; Barry, Thomas

    2011-01-01

    Tuberculosis (TB) in humans is caused by members of the Mycobacterium tuberculosis complex (MTC). Rapid detection of the MTC is necessary for the timely initiation of antibiotic treatment, while differentiation between members of the complex may be important to guide the appropriate antibiotic treatment and provide epidemiological information. In this study, a multiplex real-time PCR diagnostics assay using novel molecular targets was designed to identify the MTC while simultaneously differentiating between M. tuberculosis and M. canettii. The lepA gene was targeted for the detection of members of the MTC, the wbbl1 gene was used for the differentiation of M. tuberculosis and M. canettii from the remainder of the complex, and a unique region of the M. canettii genome, a possible novel region of difference (RD), was targeted for the specific identification of M. canettii. The multiplex real-time PCR assay was tested using 125 bacterial strains (64 MTC isolates, 44 nontuberculosis mycobacteria [NTM], and 17 other bacteria). The assay was determined to be 100% specific for the mycobacteria tested. Limits of detection of 2.2, 2.17, and 0.73 cell equivalents were determined for M. tuberculosis/M. canettii, the MTC, and M. canettii, respectively, using probit regression analysis. Further validation of this diagnostics assay, using clinical samples, should demonstrate its potential for the rapid, accurate, and sensitive diagnosis of TB caused by M. tuberculosis, M. canettii, and the other members of the MTC. PMID:21123525

  11. The importance of situation-specific encodings: analysis of a simple connectionist model of letter transposition effects

    NASA Astrophysics Data System (ADS)

    Fang, Shin-Yi; Smith, Garrett; Tabor, Whitney

    2018-04-01

    This paper analyses a three-layer connectionist network that solves a translation-invariance problem, offering a novel explanation for transposed letter effects in word reading. Analysis of the hidden unit encodings provides insight into two central issues in cognitive science: (1) What is the novelty of claims of "modality-specific" encodings? and (2) How can a learning system establish a complex internal structure needed to solve a problem? Although these topics (embodied cognition and learnability) are often treated separately, we find a close relationship between them: modality-specific features help the network discover an abstract encoding by causing it to break the initial symmetries of the hidden units in an effective way. While this neural model is extremely simple compared to the human brain, our results suggest that neural networks need not be black boxes and that carefully examining their encoding behaviours may reveal how they differ from classical ideas about the mind-world relationship.

  12. Experiments in encoding multilevel images as quadtrees

    NASA Technical Reports Server (NTRS)

    Lansing, Donald L.

    1987-01-01

    Image storage requirements for several encoding methods are investigated and the use of quadtrees with multigray level or multicolor images are explored. The results of encoding a variety of images having up to 256 gray levels using three schemes (full raster, runlength and quadtree) are presented. Although there is considerable literature on the use of quadtrees to store and manipulate binary images, their application to multilevel images is relatively undeveloped. The potential advantage of quadtree encoding is that an entire area with a uniform gray level may be encoded as a unit. A pointerless quadtree encoding scheme is described. Data are presented on the size of the quadtree required to encode selected images and on the relative storage requirements of the three encoding schemes. A segmentation scheme based on the statistical variation of gray levels within a quadtree quadrant is described. This parametric scheme may be used to control the storage required by an encoded image and to preprocess a scene for feature identification. Several sets of black and white and pseudocolor images obtained by varying the segmentation parameter are shown.

  13. Quantitative Chemical Shift-Encoded MRI Is an Accurate Method to Quantify Hepatic Steatosis

    PubMed Central

    Kühn, Jens-Peter; Hernando, Diego; Mensel, Birger; Krüger, Paul C.; Ittermann, Till; Mayerle, Julia; Hosten, Norbert; Reeder, Scott B.

    2014-01-01

    Purpose To compare the accuracy of liver fat quantification using a three-echo chemical shift-encoded magnetic resonance imaging (MRI) technique without and with correction for confounders with spectroscopy (MRS) as the reference standard. Materials and Methods Fifty patients (23 women, mean age 56.6 ± 13.2 years) with fatty liver disease were enrolled. Patients underwent T2-corrected single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE) sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and T1 correction and multispectral modeling of fat and compared with MRS-FF using linear regression. Results The spectroscopic range of liver fat was 0.11%–38.7%. Excellent correlation between MRS-FF and MRI-FF was observed when using T2* correction (R2=0.96). With use of T2* correction alone, the slope was significantly different from 1 (1.16 ± 0.03, P < 0.001) and the intercept was different from 0 (1.14% ± 0.50%, P < 0.023). This slope was significantly different than 1.0 when no T1 correction was used (P=0.001). When T2*, T1, and spectral complexity of fat were addressed, the results showed equivalence between fat quantification using MRI and MRS (slope: 1.02 ± 0.03, P=0.528; intercept: 0.26% ± 0.46%, P=0.572). Conclusion Complex three-echo chemical shift-encoded MRI is equivalent to MRS for quantifying liver fat, but only with correction for T2* decay and T1 recovery and use of spectral modeling of fat. This is necessary because T2* decay, T1 recovery, and multispectral complexity of fat are processes which may otherwise bias the measurements. PMID:24123655

  14. Quantitative chemical shift-encoded MRI is an accurate method to quantify hepatic steatosis.

    PubMed

    Kühn, Jens-Peter; Hernando, Diego; Mensel, Birger; Krüger, Paul C; Ittermann, Till; Mayerle, Julia; Hosten, Norbert; Reeder, Scott B

    2014-06-01

    To compare the accuracy of liver fat quantification using a three-echo chemical shift-encoded magnetic resonance imaging (MRI) technique without and with correction for confounders with spectroscopy (MRS) as the reference standard. Fifty patients (23 women, mean age 56.6 ± 13.2 years) with fatty liver disease were enrolled. Patients underwent T2-corrected single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE) sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and T1 correction and multispectral modeling of fat and compared with MRS-FF using linear regression. The spectroscopic range of liver fat was 0.11%-38.7%. Excellent correlation between MRS-FF and MRI-FF was observed when using T2* correction (R(2)  = 0.96). With use of T2* correction alone, the slope was significantly different from 1 (1.16 ± 0.03, P < 0.001) and the intercept was different from 0 (1.14% ± 0.50%, P < 0.023). This slope was significantly different than 1.0 when no T1 correction was used (P = 0.001). When T2*, T1, and spectral complexity of fat were addressed, the results showed equivalence between fat quantification using MRI and MRS (slope: 1.02 ± 0.03, P = 0.528; intercept: 0.26% ± 0.46%, P = 0.572). Complex three-echo chemical shift-encoded MRI is equivalent to MRS for quantifying liver fat, but only with correction for T2* decay and T1 recovery and use of spectral modeling of fat. This is necessary because T2* decay, T1 recovery, and multispectral complexity of fat are processes which may otherwise bias the measurements. Copyright © 2013 Wiley Periodicals, Inc.

  15. Evolution of tuf genes: ancient duplication, differential loss and gene conversion.

    PubMed

    Lathe, W C; Bork, P

    2001-08-03

    The tuf gene of eubacteria, encoding the EF-tu elongation factor, was duplicated early in the evolution of the taxon. Phylogenetic and genomic location analysis of 20 complete eubacterial genomes suggests that this ancient duplication has been differentially lost and maintained in eubacteria.

  16. Comparison of H.265/HEVC encoders

    NASA Astrophysics Data System (ADS)

    Trochimiuk, Maciej

    2016-09-01

    The H.265/HEVC is the state-of-the-art video compression standard, which allows the bitrate reduction up to 50% compared with its predecessor, H.264/AVC, maintaining equal perceptual video quality. The growth in coding efficiency was achieved by increasing the number of available intra- and inter-frame prediction features and improvements in existing ones, such as entropy encoding and filtering. Nevertheless, to achieve real-time performance of the encoder, simplifications in algorithm are inevitable. Some features and coding modes shall be skipped, to reduce time needed to evaluate modes forwarded to rate-distortion optimisation. Thus, the potential acceleration of the encoding process comes at the expense of coding efficiency. In this paper, a trade-off between video quality and encoding speed of various H.265/HEVC encoders is discussed.

  17. Differential Gene Expression of Longan Under Simulated Acid Rain Stress.

    PubMed

    Zheng, Shan; Pan, Tengfei; Ma, Cuilan; Qiu, Dongliang

    2017-05-01

    Differential gene expression profile was studied in Dimocarpus longan Lour. in response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH 5.6) using differential display reverse transcription polymerase chain reaction (DDRT-PCR). Results showed that mRNA differential display conditions were optimized to find an expressed sequence tag (EST) related with acid rain stress. The potential encoding products had 80% similarity with a transcription initiation factor IIF of Gossypium raimondii and 81% similarity with a protein product of Theobroma cacao. This fragment is the transcription factor activated by second messenger substances in longan leaves after signal perception of acid rain.

  18. Aroclor1254 interferes with estrogen receptor-mediated neuroprotection against beta-amyloid toxicity in cholinergic SN56 cells.

    PubMed

    Bang, Yeojin; Lim, Juhee; Kim, Sa Suk; Jeong, Hyung Min; Jung, Ki-Kyung; Kang, Il-Hyun; Lee, Kwang-Youl; Choi, Hyun Jin

    2011-10-01

    Because estrogen plays important neurotrophic and neuroprotective roles in the brain by activating estrogen receptors (ERs), disruption of normal estrogen signaling can leave neurons vulnerable to a variety of insults, including β-amyloid peptide (Aβ). Aroclor1254 (A1254) belongs to the endocrine-disrupting chemical (EDC) polychlorinated biphenyls and has anti-estrogenic properties. In the present study, we evaluated the effect of A1254 on the protective activity of estrogen against Aβ toxicity in differentiated cholinergic SN56 cells. Aged Aβ25-35 causes apoptotic cell death in differentiated SN56 cells, and the cytotoxic evidences are effectively rescued by estrogen. We found that A1254 abolishes the neuroprotective activity of estrogen against Aβ toxicity, and attenuates the suppressive effect of estrogen on Aβ-induced tau phosphorylation and JNK activation. The effects of A1254 on the neuroprotective effects of estrogen in Aβ toxicity are very similar to the effects of the estrogen receptor antagonist ICI182,780. Thus, exposure to EDCs that have anti-estrogenic activity might interfere with normal estrogen-activated neuroprotective signaling events and leave neurons more vulnerable to dangerous stimuli. Our present results provide new understanding of the mechanisms contributing to the harmful effects of EDCs on the function and viability of neurons, and the possible relevance of EDCs in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Visual feature binding in younger and older adults: encoding and suffix interference effects.

    PubMed

    Brown, Louise A; Niven, Elaine H; Logie, Robert H; Rhodes, Stephen; Allen, Richard J

    2017-02-01

    Three experiments investigated younger (18-25 yrs) and older (70-88 yrs) adults' temporary memory for colour-shape combinations (binding). We focused upon estimating the magnitude of the binding cost for each age group across encoding time (Experiment 1; 900/1500 ms), presentation format (Experiment 2; simultaneous/sequential), and interference (Experiment 3; control/suffix) conditions. In Experiment 1, encoding time did not differentially influence binding in the two age groups. In Experiment 2, younger adults exhibited poorer binding performance with sequential relative to simultaneous presentation, and serial position analyses highlighted a particular age-related difficulty remembering the middle item of a series (for all memory conditions). Experiments 1-3 demonstrated small to medium binding effect sizes in older adults across all encoding conditions, with binding less accurate than shape memory. However, younger adults also displayed negative effects of binding (small to large) in two of the experiments. Even when older adults exhibited a greater suffix interference effect in Experiment 3, this was for all memory types, not just binding. We therefore conclude that there is no consistent evidence for a visual binding deficit in healthy older adults. This relative preservation contrasts with the specific and substantial deficits in visual feature binding found in several recent studies of Alzheimer's disease.

  20. Ecological characterization and molecular differentiation of Culex pipiens complex taxa and Culex torrentium in eastern Austria.

    PubMed

    Zittra, Carina; Flechl, Eva; Kothmayer, Michael; Vitecek, Simon; Rossiter, Heidemarie; Zechmeister, Thomas; Fuehrer, Hans-Peter

    2016-04-11

    Culex pipiens complex taxa differ in behaviour, ecophysiology and epidemiologic importance. Despite their epidemiologic significance, information on genetic diversity, occurrence and seasonal and spatial distribution patterns of the Cx. pipiens complex is still insufficient. Assessment of seasonal and spatial distribution patterns of Culex pipiens forms and their congener Cx. torrentium is crucial for the understanding of their vector-pathogen dynamics. Female mosquitoes were trapped from April-October 2014 twice a month for a 24-h time period with BG-sentinel traps at 24 sampling sites in eastern Austria, using carbon dioxide as attractant. Ecological forms of Cx. pipiens s.l. and their hybrids were differentiated using the CQ11 locus, and Cx. pipiens forms and their congener Cx. torrentium using the ACE-2 gene. Differential exploitation of ecological niches by Cx. pipiens forms and Cx. torrentium was analysed using likelihood ratio tests. Possible effects of environmental parameters on these taxa were tested using PERMANOVA based on distance matrices and, if significant, were modelled in nMDS ordination space to estimate non-linear relationships. For this study, 1476 Culex spp. were sampled. Culex pipiens f. pipiens representing 87.33 % of the total catch was most abundant, followed by hybrids of both forms (5.62 %), Cx. torrentium (3.79 %) and Cx. pipiens f. molestus (3.25 %). Differences in proportional abundances were found between land cover classes. Ecological parameters affecting seasonal and spatial distribution of these taxa in eastern Austria are precipitation duration, air temperature, sunlight and the interaction term of precipitation amount and the Danube water level, which can be interpreted as a proxy for breeding habitat availability. The Cx. pipiens complex of eastern Austria comprises both ecologically different forms, the mainly ornithophilic form pipiens and the mainly mammalophilic and anthropophilic form molestus. Heterogeneous agricultural

  1. Positive Selection in Rapidly Evolving Plastid–Nuclear Enzyme Complexes

    PubMed Central

    Rockenbach, Kate; Havird, Justin C.; Monroe, J. Grey; Triant, Deborah A.; Taylor, Douglas R.; Sloan, Daniel B.

    2016-01-01

    Rates of sequence evolution in plastid genomes are generally low, but numerous angiosperm lineages exhibit accelerated evolutionary rates in similar subsets of plastid genes. These genes include clpP1 and accD, which encode components of the caseinolytic protease (CLP) and acetyl-coA carboxylase (ACCase) complexes, respectively. Whether these extreme and repeated accelerations in rates of plastid genome evolution result from adaptive change in proteins (i.e., positive selection) or simply a loss of functional constraint (i.e., relaxed purifying selection) is a source of ongoing controversy. To address this, we have taken advantage of the multiple independent accelerations that have occurred within the genus Silene (Caryophyllaceae) by examining phylogenetic and population genetic variation in the nuclear genes that encode subunits of the CLP and ACCase complexes. We found that, in species with accelerated plastid genome evolution, the nuclear-encoded subunits in the CLP and ACCase complexes are also evolving rapidly, especially those involved in direct physical interactions with plastid-encoded proteins. A massive excess of nonsynonymous substitutions between species relative to levels of intraspecific polymorphism indicated a history of strong positive selection (particularly in CLP genes). Interestingly, however, some species are likely undergoing loss of the native (heteromeric) plastid ACCase and putative functional replacement by a duplicated cytosolic (homomeric) ACCase. Overall, the patterns of molecular evolution in these plastid–nuclear complexes are unusual for anciently conserved enzymes. They instead resemble cases of antagonistic coevolution between pathogens and host immune genes. We discuss a possible role of plastid–nuclear conflict as a novel cause of accelerated evolution. PMID:27707788

  2. A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors.

    PubMed

    Evangelisti, Cecilia; de Biase, Dario; Kurelac, Ivana; Ceccarelli, Claudio; Prokisch, Holger; Meitinger, Thomas; Caria, Paola; Vanni, Roberta; Romeo, Giovanni; Tallini, Giovanni; Gasparre, Giuseppe; Bonora, Elena

    2015-03-21

    Thyroid neoplasias with oncocytic features represent a specific phenotype in non-medullary thyroid cancer, reflecting the unique biological phenomenon of mitochondrial hyperplasia in the cytoplasm. Oncocytic thyroid cells are characterized by a prominent eosinophilia (or oxyphilia) caused by mitochondrial abundance. Although disruptive mutations in the mitochondrial DNA (mtDNA) are the most significant hallmark of such tumors, oncocytomas may be envisioned as heterogeneous neoplasms, characterized by multiple nuclear and mitochondrial gene lesions. We investigated the nuclear mutational profile of oncocytic tumors to pinpoint the mutations that may trigger the early oncogenic hit. Total DNA was extracted from paraffin-embedded tissues from 45 biopsies of oncocytic tumors. High-resolution melting was used for mutation screening of mitochondrial complex I subunits genes. Specific nuclear rearrangements were investigated by RT-PCR (RET/PTC) or on isolated nuclei by interphase FISH (PAX8/PPARγ). Recurrent point mutations were analyzed by direct sequencing. In our oncocytic tumor samples, we identified rare TP53 mutations. The series of analyzed cases did not include poorly- or undifferentiated thyroid carcinomas, and none of the TP53 mutated cases had significant mitotic activity or high-grade features. Thus, the presence of disruptive TP53 mutations was completely unexpected. In addition, novel mutations in nuclear-encoded complex I genes were identified. These findings suggest that nuclear genetic lesions altering the bioenergetics competence of thyroid cells may give rise to an aberrant mitochondria-centered compensatory mechanism and ultimately to the oncocytic phenotype.

  3. Multidimensionally encoded magnetic resonance imaging.

    PubMed

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. Copyright © 2012 Wiley Periodicals, Inc.

  4. Evolution of the eukaryotic dynactin complex, the activator of cytoplasmic dynein

    PubMed Central

    2012-01-01

    Background Dynactin is a large multisubunit protein complex that enhances the processivity of cytoplasmic dynein and acts as an adapter between dynein and the cargo. It is composed of eleven different polypeptides of which eight are unique to this complex, namely dynactin1 (p150Glued), dynactin2 (p50 or dynamitin), dynactin3 (p24), dynactin4 (p62), dynactin5 (p25), dynactin6 (p27), and the actin-related proteins Arp1 and Arp10 (Arp11). Results To reveal the evolution of dynactin across the eukaryotic tree the presence or absence of all dynactin subunits was determined in most of the available eukaryotic genome assemblies. Altogether, 3061 dynactin sequences from 478 organisms have been annotated. Phylogenetic trees of the various subunit sequences were used to reveal sub-family relationships and to reconstruct gene duplication events. Especially in the metazoan lineage, several of the dynactin subunits were duplicated independently in different branches. The largest subunit repertoire is found in vertebrates. Dynactin diversity in vertebrates is further increased by alternative splicing of several subunits. The most prominent example is the dynactin1 gene, which may code for up to 36 different isoforms due to three different transcription start sites and four exons that are spliced as differentially included exons. Conclusions The dynactin complex is a very ancient complex that most likely included all subunits in the last common ancestor of extant eukaryotes. The absence of dynactin in certain species coincides with that of the cytoplasmic dynein heavy chain: Organisms that do not encode cytoplasmic dynein like plants and diplomonads also do not encode the unique dynactin subunits. The conserved core of dynactin consists of dynactin1, dynactin2, dynactin4, dynactin5, Arp1, and the heterodimeric actin capping protein. The evolution of the remaining subunits dynactin3, dynactin6, and Arp10 is characterized by many branch- and species-specific gene loss events. PMID

  5. Identification of protein features encoded by alternative exons using Exon Ontology.

    PubMed

    Tranchevent, Léon-Charles; Aubé, Fabien; Dulaurier, Louis; Benoit-Pilven, Clara; Rey, Amandine; Poret, Arnaud; Chautard, Emilie; Mortada, Hussein; Desmet, François-Olivier; Chakrama, Fatima Zahra; Moreno-Garcia, Maira Alejandra; Goillot, Evelyne; Janczarski, Stéphane; Mortreux, Franck; Bourgeois, Cyril F; Auboeuf, Didier

    2017-06-01

    Transcriptomic genome-wide analyses demonstrate massive variation of alternative splicing in many physiological and pathological situations. One major challenge is now to establish the biological contribution of alternative splicing variation in physiological- or pathological-associated cellular phenotypes. Toward this end, we developed a computational approach, named "Exon Ontology," based on terms corresponding to well-characterized protein features organized in an ontology tree. Exon Ontology is conceptually similar to Gene Ontology-based approaches but focuses on exon-encoded protein features instead of gene level functional annotations. Exon Ontology describes the protein features encoded by a selected list of exons and looks for potential Exon Ontology term enrichment. By applying this strategy to exons that are differentially spliced between epithelial and mesenchymal cells and after extensive experimental validation, we demonstrate that Exon Ontology provides support to discover specific protein features regulated by alternative splicing. We also show that Exon Ontology helps to unravel biological processes that depend on suites of coregulated alternative exons, as we uncovered a role of epithelial cell-enriched splicing factors in the AKT signaling pathway and of mesenchymal cell-enriched splicing factors in driving splicing events impacting on autophagy. Freely available on the web, Exon Ontology is the first computational resource that allows getting a quick insight into the protein features encoded by alternative exons and investigating whether coregulated exons contain the same biological information. © 2017 Tranchevent et al.; Published by Cold Spring Harbor Laboratory Press.

  6. Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways

    PubMed Central

    Manteiga, Sara; Lee, Kyongbum

    2016-01-01

    Background: A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals’ effects on adult adipose tissue. Objectives: Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. Methods: We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Results: Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor’s activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Conclusions: Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ. Citation: Manteiga S, Lee K. 2017. Monoethylhexyl phthalate elicits an inflammatory response in adipocytes characterized by alterations in lipid and cytokine pathways. Environ Health Perspect 125:615–622; http://dx.doi.org/10.1289/EHP464 PMID:27384973

  7. A pseudo differential Gm—C complex filter with frequency tuning for IEEE802.15.4 applications

    NASA Astrophysics Data System (ADS)

    Xin, Cheng; Lungui, Zhong; Haigang, Yang; Fei, Liu; Tongqiang, Gao

    2011-07-01

    This paper presents a CMOS Gm—C complex filter for a low-IF receiver of the IEEE 802.15.4 standard. A pseudo differential OTA with reconfigurable common mode feedback and common mode feed-forward is proposed as well as the frequency tuning method based on a relaxation oscillator. A detailed analysis of non-ideality of the OTA and the frequency tuning method is elaborated. The analysis and measurement results have shown that the center frequency of the complex filter could be tuned accurately. The chip was fabricated in a standard 0.35 μm CMOS process, with a single 3.3 V power supply. The filter consumes 2.1mA current, has a measured in-band group delay ripple of less than 0.16 μs and an IRR larger than 28 dB at 2 MHz apart, which could meet the requirements oftheIEEE802.15.4 standard.

  8. Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

    PubMed Central

    Naganathan, Saranga; Grunbeck, Amy; Tian, He; Huber, Thomas; Sakmar, Thomas P.

    2013-01-01

    To facilitate structural and dynamic studies of G protein-coupled receptor (GPCR) signaling complexes, new approaches are required to introduce informative probes or labels into expressed receptors that do not perturb receptor function. We used amber codon suppression technology to genetically-encode the unnatural amino acid, p-azido-L-phenylalanine (azF) at various targeted positions in GPCRs heterologously expressed in mammalian cells. The versatility of the azido group is illustrated here in different applications to study GPCRs in their native cellular environment or under detergent solubilized conditions. First, we demonstrate a cell-based targeted photocrosslinking technology to identify the residues in the ligand-binding pocket of GPCR where a tritium-labeled small-molecule ligand is crosslinked to a genetically-encoded azido amino acid. We then demonstrate site-specific modification of GPCRs by the bioorthogonal Staudinger-Bertozzi ligation reaction that targets the azido group using phosphine derivatives. We discuss a general strategy for targeted peptide-epitope tagging of expressed membrane proteins in-culture and its detection using a whole-cell-based ELISA approach. Finally, we show that azF-GPCRs can be selectively tagged with fluorescent probes. The methodologies discussed are general, in that they can in principle be applied to any amino acid position in any expressed GPCR to interrogate active signaling complexes. PMID:24056801

  9. Genes encoded within 8q24 on the amplicon of a large extrachromosomal element are selectively repressed during the terminal differentiation of HL-60 cells.

    PubMed

    Hirano, Tetsuo; Ike, Fumio; Murata, Takehide; Obata, Yuichi; Utiyama, Hiroyasu; Yokoyama, Kazunari K

    2008-04-02

    Human acute myeloblastic leukemia HL-60 cells become resistant to differentiation during long-term cultivation. After 150 passages, double minute chromosomes (dmins) found in early-passaged cells are replaced by large extrachromosomal elements (LEEs). In a DNA library derived from a purified fraction of LEEs, 12.6% (23/183) of clones were assigned to 8q24 and 9.2% (17/183) were assigned to 14q11 in the human genome. Fluorescence in situ hybridization (FISH) revealed a small aberrant chromosome, which had not been found in early-passaged cells, in addition to the purified LEEs. We determined that each LEE consisted of six discontinuous segments in a region that extended for 4.4Mb over the 8q24 locus. Five genes, namely, Myc (a proto-oncogene), NSMCE2 (for a SUMO ligase), CCDC26 (for a retinoic acid-dependent modulator of myeloid differentiation), TRIB1 (for a regulator of MAPK kinase) and LOC389637 (for a protein of unknown function), were encoded by the amplicon. Breaks in the chromosomal DNA within the amplicon were found in the NSMCE2 and CCDC26 genes. The discontinuous structure of the amplicon unit of the LEEs was identical with that of dmins in HL-60 early-passaged cells. The difference between them seemed, predominantly, to be the number (10-15 copies per LEE versus 2 or 3 copies per dmin) of constituent units. Expression of the Myc, NSMCE2, CCDC26 and LOC389637 and TRIB1 genes was constitutive in all lines of HL-60 cells and that of the first four genes was repressed during the terminal differentiation of early-passaged HL-60 cells. We also detected abnormal transcripts of CCDC26. Our results suggest that these genes were selected during the development of amplicons. They might be amplified and, sometimes, truncated to contribute to the maintenance of HL-60 cells in an undifferentiated state.

  10. hCG and Its Disruption by Environmental Contaminants during Human Pregnancy.

    PubMed

    Paulesu, Luana; Rao, Ch V; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

    2018-03-20

    Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para -Nonylphenol ( p -NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances.

  11. hCG and Its Disruption by Environmental Contaminants during Human Pregnancy

    PubMed Central

    Paulesu, Luana; Rao, Ch.V.; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

    2018-01-01

    Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances. PMID:29558393

  12. Endocrine Disrupting Chemical Induced "Pollution of Metabolic Pathways": A Case of Shifting Paradigms With Implications for Vascular Diseases.

    PubMed

    Janardhanan, Rajiv

    2018-05-14

    The latter half of the twentieth century has witnessed a humongous spurt in the use of synthetic chemicals in a wide variety of industrial and agricultural applications are leading to niche specific perturbations affecting every trophic level of the ecosystems due to unmitigated environmental contamination. Despite the incremental usefulness of endocrine disrupting chemicals (EDCs) such as pesticides and plasticizers, their statutory impact on environmental health is assuming worrisome proportions. The EDCs can disrupt physiological homeostasis resulting in developmental and reproductive abnormalities. Both preclinical animal experiments, as well as epidemiological studies, have correlated EDC exposure with metabolic disorders such as metabolic syndrome, type 2 diabetes as well as cardiovascular health. Here we briefly review the statutory impact of EDCs on metabolic disruption as well as their impact on environmental health. Finally, difficulties pertaining to the categorization of EDC induced metabolic diseases as risk factors for global disease burden have been addressed taking into account the complexity of such interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Field programmable gate array based fuzzy neural signal processing system for differential diagnosis of QRS complex tachycardia and tachyarrhythmia in noisy ECG signals.

    PubMed

    Chowdhury, Shubhajit Roy

    2012-04-01

    The paper reports of a Field Programmable Gate Array (FPGA) based embedded system for detection of QRS complex in a noisy electrocardiogram (ECG) signal and thereafter differential diagnosis of tachycardia and tachyarrhythmia. The QRS complex has been detected after application of entropy measure of fuzziness to build a detection function of ECG signal, which has been previously filtered to remove power line interference and base line wander. Using the detected QRS complexes, differential diagnosis of tachycardia and tachyarrhythmia has been performed. The entire algorithm has been realized in hardware on an FPGA. Using the standard CSE ECG database, the algorithm performed highly effectively. The performance of the algorithm in respect of QRS detection with sensitivity (Se) of 99.74% and accuracy of 99.5% is achieved when tested using single channel ECG with entropy criteria. The performance of the QRS detection system has been compared and found to be better than most of the QRS detection systems available in literature. Using the system, 200 patients have been diagnosed with an accuracy of 98.5%.

  14. Sample Complexity Bounds for Differentially Private Learning

    PubMed Central

    Chaudhuri, Kamalika; Hsu, Daniel

    2013-01-01

    This work studies the problem of privacy-preserving classification – namely, learning a classifier from sensitive data while preserving the privacy of individuals in the training set. In particular, the learning algorithm is required in this problem to guarantee differential privacy, a very strong notion of privacy that has gained significant attention in recent years. A natural question to ask is: what is the sample requirement of a learning algorithm that guarantees a certain level of privacy and accuracy? We address this question in the context of learning with infinite hypothesis classes when the data is drawn from a continuous distribution. We first show that even for very simple hypothesis classes, any algorithm that uses a finite number of examples and guarantees differential privacy must fail to return an accurate classifier for at least some unlabeled data distributions. This result is unlike the case with either finite hypothesis classes or discrete data domains, in which distribution-free private learning is possible, as previously shown by Kasiviswanathan et al. (2008). We then consider two approaches to differentially private learning that get around this lower bound. The first approach is to use prior knowledge about the unlabeled data distribution in the form of a reference distribution chosen independently of the sensitive data. Given such a reference , we provide an upper bound on the sample requirement that depends (among other things) on a measure of closeness between and the unlabeled data distribution. Our upper bound applies to the non-realizable as well as the realizable case. The second approach is to relax the privacy requirement, by requiring only label-privacy – namely, that the only labels (and not the unlabeled parts of the examples) be considered sensitive information. An upper bound on the sample requirement of learning with label privacy was shown by Chaudhuri et al. (2006); in this work, we show a lower bound. PMID:25285183

  15. Loss of aPKCλ in Differentiated Neurons Disrupts the Polarity Complex but Does Not Induce Obvious Neuronal Loss or Disorientation in Mouse Brains

    PubMed Central

    Yamanaka, Tomoyuki; Tosaki, Asako; Kurosawa, Masaru; Akimoto, Kazunori; Hirose, Tomonori; Ohno, Shigeo; Hattori, Nobutaka; Nukina, Nobuyuki

    2013-01-01

    Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS). Recent studies have established the significance of atypical protein kinase C (aPKC) and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation. PMID:24391875

  16. The impact of path crossing on visuo-spatial serial memory: encoding or rehearsal effect?

    PubMed

    Parmentier, Fabrice B R; Andrés, Pilar

    2006-11-01

    The determinants of visuo-spatial serial memory have been the object of little research, despite early evidence that not all sequences are equally remembered. Recently, empirical evidence was reported indicating that the complexity of the path formed by the to-be-remembered locations impacted on recall performance, defined for example by the presence of crossings in the path formed by successive locations (Parmentier, Elford, & Maybery, 2005). In this study, we examined whether this effect reflects rehearsal or encoding processes. We examined the effect of a retention interval and spatial interference on the ordered recall of spatial sequences with and without path crossings. Path crossings decreased recall performance, as did a retention interval. In line with the encoding hypothesis, but in contrast with the rehearsal hypothesis, the effect of crossing was not affected by the retention interval nor by tapping. The possible nature of the impact of path crossing on encoding mechanisms is discussed.

  17. Structural Mechanism behind Distinct Efficiency of Oct4/Sox2 Proteins in Differentially Spaced DNA Complexes

    PubMed Central

    Yesudhas, Dhanusha; Anwar, Muhammad Ayaz; Panneerselvam, Suresh; Durai, Prasannavenkatesh; Shah, Masaud; Choi, Sangdun

    2016-01-01

    The octamer-binding transcription factor 4 (Oct4) and sex-determining region Y (SRY)-box 2 (Sox2) proteins induce various transcriptional regulators to maintain cellular pluripotency. Most Oct4/Sox2 complexes have either 0 base pairs (Oct4/Sox20bp) or 3 base pairs (Oct4/Sox23bp) separation between their DNA-binding sites. Results from previous biochemical studies have shown that the complexes separated by 0 base pairs are associated with a higher pluripotency rate than those separated by 3 base pairs. Here, we performed molecular dynamics (MD) simulations and calculations to determine the binding free energy and per-residue free energy for the Oct4/Sox20bp and Oct4/Sox23bp complexes to identify structural differences that contribute to differences in induction rate. Our MD simulation results showed substantial differences in Oct4/Sox2 domain movements, as well as secondary-structure changes in the Oct4 linker region, suggesting a potential reason underlying the distinct efficiencies of these complexes during reprogramming. Moreover, we identified key residues and hydrogen bonds that potentially facilitate protein-protein and protein-DNA interactions, in agreement with previous experimental findings. Consequently, our results confess that differential spacing of the Oct4/Sox2 DNA binding sites can determine the magnitude of transcription of the targeted genes during reprogramming. PMID:26790000

  18. Architecture for VLSI design of Reed-Solomon encoders

    NASA Technical Reports Server (NTRS)

    Liu, K. Y.

    1981-01-01

    The logic structure of a universal VLSI chip called the symbol-slice Reed-Solomon (RS) encoder chip is discussed. An RS encoder can be constructed by cascading and properly interconnecting a group of such VLSI chips. As a design example, it is shown that a (255,223) RD encoder requiring around 40 discrete CMOS ICs may be replaced by an RS encoder consisting of four identical interconnected VLSI RS encoder chips. Besides the size advantage, the VLSI RS encoder also has the potential advantages of requiring less power and having a higher reliability.

  19. Optimization of complex slater-type functions with analytic derivative methods for describing photoionization differential cross sections.

    PubMed

    Matsuzaki, Rei; Yabushita, Satoshi

    2017-05-05

    The complex basis function (CBF) method applied to various atomic and molecular photoionization problems can be interpreted as an L2 method to solve the driven-type (inhomogeneous) Schrödinger equation, whose driven term being dipole operator times the initial state wave function. However, efficient basis functions for representing the solution have not fully been studied. Moreover, the relation between their solution and that of the ordinary Schrödinger equation has been unclear. For these reasons, most previous applications have been limited to total cross sections. To examine the applicability of the CBF method to differential cross sections and asymmetry parameters, we show that the complex valued solution to the driven-type Schrödinger equation can be variationally obtained by optimizing the complex trial functions for the frequency dependent polarizability. In the test calculations made for the hydrogen photoionization problem with five or six complex Slater-type orbitals (cSTOs), their complex valued expansion coefficients and the orbital exponents have been optimized with the analytic derivative method. Both the real and imaginary parts of the solution have been obtained accurately in a wide region covering typical molecular regions. Their phase shifts and asymmetry parameters are successfully obtained by extrapolating the CBF solution from the inner matching region to the asymptotic region using WKB method. The distribution of the optimized orbital exponents in the complex plane is explained based on the close connection between the CBF method and the driven-type equation method. The obtained information is essential to constructing the appropriate basis sets in future molecular applications. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing

    PubMed Central

    Crain, D. Andrew; Janssen, Sarah J.; Edwards, Thea M.; Heindel, Jerrold; Ho, Shuk-mei; Hunt, Patricia; Iguchi, Taisen; Juul, Anders; McLachlan, John A.; Schwartz, Jackie; Skakkebaek, Niels; Soto, Ana M.; Swan, Shanna; Walker, Cheryl; Woodruff, Teresa K.; Woodruff, Tracey J.; Giudice, Linda C.; Guillette, Louis J.

    2014-01-01

    Objective To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. Design Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. Conclusion(s) The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which women’s health can be improved. PMID:18929049

  1. Centriole, differentiation, and senescence.

    PubMed

    Tkemaladze, J; Chichinadze, K

    2010-01-01

    Irreversible differentiation (change of morphogenetic status) and programmed death (apoptosis) are observed only in somatic cells, and cell division is the only way by which the morphogenetic status of the offspring cells may be modified. It is known that there is a fixed limit to the number of possible cell divisions, the so-called Hayflick limit. Existing links between cell division, differentiation, and apoptosis make it possible to conclude that all of these processes could be controlled by a single self-reproducing structure. Potential candidates for this replicable structure in a somatic cell are the chromosomes, mitochondria (both contain DNA), and centrioles. Centrioles (a diplosome, or pair of centrioles) are the most likely unit that can fully regulate the processes of irreversible differentiation, determination, and modification of the morphogenetic status. Centrioles may contain differently encoded RNA molecules stacked in a definite order, and during mitosis, these RNA molecules are released one by one into the cytoplasm. In the presence of reverse transcriptase and endonuclease, processing of this RNA presumably changes the status of repressed and potentially active genes and, subsequently, the morphogenetic status of a cell.

  2. Systematic Identification and Characterization of Novel Human Skin-Associated Genes Encoding Membrane and Secreted Proteins

    PubMed Central

    Buhren, Bettina Alexandra; Martinez, Cynthia; Schrumpf, Holger; Gasis, Marcia; Grether-Beck, Susanne; Krutmann, Jean

    2013-01-01

    Through bioinformatics analyses of a human gene expression database representing 105 different tissues and cell types, we identified 687 skin-associated genes that are selectively and highly expressed in human skin. Over 50 of these represent uncharacterized genes not previously associated with skin and include a subset that encode novel secreted and plasma membrane proteins. The high levels of skin-associated expression for eight of these novel therapeutic target genes were confirmed by semi-quantitative real time PCR, western blot and immunohistochemical analyses of normal skin and skin-derived cell lines. Four of these are expressed specifically by epidermal keratinocytes; two that encode G-protein-coupled receptors (GPR87 and GPR115), and two that encode secreted proteins (WFDC5 and SERPINB7). Further analyses using cytokine-activated and terminally differentiated human primary keratinocytes or a panel of common inflammatory, autoimmune or malignant skin diseases revealed distinct patterns of regulation as well as disease associations that point to important roles in cutaneous homeostasis and disease. Some of these novel uncharacterized skin genes may represent potential biomarkers or drug targets for the development of future diagnostics or therapeutics. PMID:23840300

  3. Construction of type-II QC-LDPC codes with fast encoding based on perfect cyclic difference sets

    NASA Astrophysics Data System (ADS)

    Li, Ling-xiang; Li, Hai-bing; Li, Ji-bi; Jiang, Hua

    2017-09-01

    In view of the problems that the encoding complexity of quasi-cyclic low-density parity-check (QC-LDPC) codes is high and the minimum distance is not large enough which leads to the degradation of the error-correction performance, the new irregular type-II QC-LDPC codes based on perfect cyclic difference sets (CDSs) are constructed. The parity check matrices of these type-II QC-LDPC codes consist of the zero matrices with weight of 0, the circulant permutation matrices (CPMs) with weight of 1 and the circulant matrices with weight of 2 (W2CMs). The introduction of W2CMs in parity check matrices makes it possible to achieve the larger minimum distance which can improve the error- correction performance of the codes. The Tanner graphs of these codes have no girth-4, thus they have the excellent decoding convergence characteristics. In addition, because the parity check matrices have the quasi-dual diagonal structure, the fast encoding algorithm can reduce the encoding complexity effectively. Simulation results show that the new type-II QC-LDPC codes can achieve a more excellent error-correction performance and have no error floor phenomenon over the additive white Gaussian noise (AWGN) channel with sum-product algorithm (SPA) iterative decoding.

  4. Subjective memory complaints are associated with brain activation supporting successful memory encoding.

    PubMed

    Hayes, Jessica M; Tang, Lingfei; Viviano, Raymond P; van Rooden, Sanneke; Ofen, Noa; Damoiseaux, Jessica S

    2017-12-01

    Subjective memory complaints, the perceived decline in cognitive abilities in the absence of clinical deficits, may precede Alzheimer's disease. Individuals with subjective memory complaints show differential brain activation during memory encoding; however, whether such differences contribute to successful memory formation remains unclear. Here, we investigated how subsequent memory effects, activation which is greater for hits than misses during an encoding task, differed between healthy older adults aged 50 to 85 years with (n = 23) and without (n = 41) memory complaints. Older adults with memory complaints, compared to those without, showed lower subsequent memory effects in the occipital lobe, superior parietal lobe, and posterior cingulate cortex. In addition, older adults with more memory complaints showed a more negative subsequent memory effects in areas of the default mode network, including the posterior cingulate cortex, precuneus, and ventromedial prefrontal cortex. Our findings suggest that for successful memory formation, older adults with subjective memory complaints rely on distinct neural mechanisms which may reflect an overall decreased task-directed attention. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. RNA-Seq Analysis of the Expression of Genes Encoding Cell Wall Degrading Enzymes during Infection of Lupin (Lupinus angustifolius) by Phytophthora parasitica

    PubMed Central

    Blackman, Leila M.; Cullerne, Darren P.; Torreña, Pernelyn; Taylor, Jen; Hardham, Adrienne R.

    2015-01-01

    RNA-Seq analysis has shown that over 60% (12,962) of the predicted transcripts in the Phytophthora parasitica genome are expressed during the first 60 h of lupin root infection. The infection transcriptomes included 278 of the 431 genes encoding P. parasitica cell wall degrading enzymes. The transcriptome data provide strong evidence of global transcriptional cascades of genes whose encoded proteins target the main categories of plant cell wall components. A major cohort of pectinases is predominantly expressed early but as infection progresses, the transcriptome becomes increasingly dominated by transcripts encoding cellulases, hemicellulases, β-1,3-glucanases and glycoproteins. The most highly expressed P. parasitica carbohydrate active enzyme gene contains two CBM1 cellulose binding modules and no catalytic domains. The top 200 differentially expressed genes include β-1,4-glucosidases, β-1,4-glucanases, β-1,4-galactanases, a β-1,3-glucanase, an α-1,4-polygalacturonase, a pectin deacetylase and a pectin methylesterase. Detailed analysis of gene expression profiles provides clues as to the order in which linkages within the complex carbohydrates may come under attack. The gene expression profiles suggest that (i) demethylation of pectic homogalacturonan occurs before its deacetylation; (ii) cleavage of the backbone of pectic rhamnogalacturonan I precedes digestion of its side chains; (iii) early attack on cellulose microfibrils by non-catalytic cellulose-binding proteins and enzymes with auxiliary activities may facilitate subsequent attack by glycosyl hydrolases and enzymes containing CBM1 cellulose-binding modules; (iv) terminal hemicellulose backbone residues are targeted after extensive internal backbone cleavage has occurred; and (v) the carbohydrate chains on glycoproteins are degraded late in infection. A notable feature of the P. parasitica infection transcriptome is the high level of transcription of genes encoding enzymes that degrade β-1

  6. RNA-Seq Analysis of the Expression of Genes Encoding Cell Wall Degrading Enzymes during Infection of Lupin (Lupinus angustifolius) by Phytophthora parasitica.

    PubMed

    Blackman, Leila M; Cullerne, Darren P; Torreña, Pernelyn; Taylor, Jen; Hardham, Adrienne R

    2015-01-01

    RNA-Seq analysis has shown that over 60% (12,962) of the predicted transcripts in the Phytophthora parasitica genome are expressed during the first 60 h of lupin root infection. The infection transcriptomes included 278 of the 431 genes encoding P. parasitica cell wall degrading enzymes. The transcriptome data provide strong evidence of global transcriptional cascades of genes whose encoded proteins target the main categories of plant cell wall components. A major cohort of pectinases is predominantly expressed early but as infection progresses, the transcriptome becomes increasingly dominated by transcripts encoding cellulases, hemicellulases, β-1,3-glucanases and glycoproteins. The most highly expressed P. parasitica carbohydrate active enzyme gene contains two CBM1 cellulose binding modules and no catalytic domains. The top 200 differentially expressed genes include β-1,4-glucosidases, β-1,4-glucanases, β-1,4-galactanases, a β-1,3-glucanase, an α-1,4-polygalacturonase, a pectin deacetylase and a pectin methylesterase. Detailed analysis of gene expression profiles provides clues as to the order in which linkages within the complex carbohydrates may come under attack. The gene expression profiles suggest that (i) demethylation of pectic homogalacturonan occurs before its deacetylation; (ii) cleavage of the backbone of pectic rhamnogalacturonan I precedes digestion of its side chains; (iii) early attack on cellulose microfibrils by non-catalytic cellulose-binding proteins and enzymes with auxiliary activities may facilitate subsequent attack by glycosyl hydrolases and enzymes containing CBM1 cellulose-binding modules; (iv) terminal hemicellulose backbone residues are targeted after extensive internal backbone cleavage has occurred; and (v) the carbohydrate chains on glycoproteins are degraded late in infection. A notable feature of the P. parasitica infection transcriptome is the high level of transcription of genes encoding enzymes that degrade β-1

  7. Influence of Layer-by-Layer Polyelectrolyte Deposition and EDC/NHS Activated Heparin Immobilization onto Silk Fibroin Fabric

    PubMed Central

    Elahi, M. Fazley; Guan, Guoping; Wang, Lu; King, Martin W.

    2014-01-01

    To enhance the hemocompatibility of silk fibroin fabric as biomedical material, polyelectrolytes architectures have been assembled through the layer-by-layer (LbL) technique on silk fibroin fabric (SFF). In particular, 1.5 and 2.5 bilayer of oppositely charged polyelectrolytes were assembled onto SFF using poly(allylamine hydrochloride) (PAH) as polycationic polymer and poly(acrylic acid) (PAA) as polyanionic polymer with PAH topmost. Low molecular weight heparin (LMWH) activated with 1-ethyl-3-(dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) was then immobilized on its surface. Alcian Blue staining, toluidine blue assay and X-ray photoelectron spectroscopy (XPS) confirmed the presence of heparin on modified SFF surfaces. The surface morphology of the modified silk fibroin fabric surfaces was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and obtained increased roughness. Negligible hemolytic effect and a higher concentration of free hemoglobin by a kinetic clotting time test ensured the improved biological performance of the modified fibroin fabric. Overall, the deposition of 2.5 bilayer was found effective in terms of biological and surface properties of the modified fibroin fabric compared to 1.5 bilayer self-assembly technique. Therefore, this novel approach to surface modification may demonstrate long term patency in future in vivo animal trials of small diameter silk fibroin vascular grafts. PMID:28788601

  8. Spatial differentiation of gene expression in Aspergillus niger colony grown for sugar beet pulp utilization

    PubMed Central

    Benoit, Isabelle; Zhou, Miaomiao; Vivas Duarte, Alexandra; Downes, Damien J.; Todd, Richard B.; Kloezen, Wendy; Post, Harm; Heck, Albert J. R.; Maarten Altelaar, A. F.; de Vries, Ronald P.

    2015-01-01

    Degradation of plant biomass to fermentable sugars is of critical importance for the use of plant materials for biofuels. Filamentous fungi are ubiquitous organisms and major plant biomass degraders. Single colonies of some fungal species can colonize massive areas as large as five soccer stadia. During growth, the mycelium encounters heterogeneous carbon sources. Here we assessed whether substrate heterogeneity is a major determinant of spatial gene expression in colonies of Aspergillus niger. We analyzed whole-genome gene expression in five concentric zones of 5-day-old colonies utilizing sugar beet pulp as a complex carbon source. Growth, protein production and secretion occurred throughout the colony. Genes involved in carbon catabolism were expressed uniformly from the centre to the periphery whereas genes encoding plant biomass degrading enzymes and nitrate utilization were expressed differentially across the colony. A combined adaptive response of carbon-catabolism and enzyme production to locally available monosaccharides was observed. Finally, our results demonstrate that A. niger employs different enzymatic tools to adapt its metabolism as it colonizes complex environments. PMID:26314379

  9. Spatial differentiation of gene expression in Aspergillus niger colony grown for sugar beet pulp utilization.

    PubMed

    Benoit, Isabelle; Zhou, Miaomiao; Vivas Duarte, Alexandra; Downes, Damien J; Todd, Richard B; Kloezen, Wendy; Post, Harm; Heck, Albert J R; Maarten Altelaar, A F; de Vries, Ronald P

    2015-08-28

    Degradation of plant biomass to fermentable sugars is of critical importance for the use of plant materials for biofuels. Filamentous fungi are ubiquitous organisms and major plant biomass degraders. Single colonies of some fungal species can colonize massive areas as large as five soccer stadia. During growth, the mycelium encounters heterogeneous carbon sources. Here we assessed whether substrate heterogeneity is a major determinant of spatial gene expression in colonies of Aspergillus niger. We analyzed whole-genome gene expression in five concentric zones of 5-day-old colonies utilizing sugar beet pulp as a complex carbon source. Growth, protein production and secretion occurred throughout the colony. Genes involved in carbon catabolism were expressed uniformly from the centre to the periphery whereas genes encoding plant biomass degrading enzymes and nitrate utilization were expressed differentially across the colony. A combined adaptive response of carbon-catabolism and enzyme production to locally available monosaccharides was observed. Finally, our results demonstrate that A. niger employs different enzymatic tools to adapt its metabolism as it colonizes complex environments.

  10. A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.

    PubMed

    Annibali, Daniela; Gioia, Ubaldo; Savino, Mauro; Laneve, Pietro; Caffarelli, Elisa; Nasi, Sergio

    2012-01-01

    The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs) are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.

  11. Persistent Organic Pollutants and Early Menopause in U.S. Women

    PubMed Central

    Grindler, Natalia M.; Allsworth, Jenifer E.; Macones, George A.; Kannan, Kurunthachalam; Roehl, Kimberly A.; Cooper, Amber R.

    2015-01-01

    Objective Endocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause. Methods Cross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45–55 years. Findings This analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of β-hexachlorocyclohexane, mirex, p,p’-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners −70, −99, −105, −118, −138, −153, −156, −170, and −183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women. Conclusions This study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and

  12. Performance of DPSK with convolutional encoding on time-varying fading channels

    NASA Technical Reports Server (NTRS)

    Mui, S. Y.; Modestino, J. W.

    1977-01-01

    The bit error probability performance of a differentially-coherent phase-shift keyed (DPSK) modem with convolutional encoding and Viterbi decoding on time-varying fading channels is examined. Both the Rician and the lognormal channels are considered. Bit error probability upper bounds on fully-interleaved (zero-memory) fading channels are derived and substantiated by computer simulation. It is shown that the resulting coded system performance is a relatively insensitive function of the choice of channel model provided that the channel parameters are related according to the correspondence developed as part of this paper. Finally, a comparison of DPSK with a number of other modulation strategies is provided.

  13. Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors.

    PubMed

    Klümper, Niklas; Syring, Isabella; Offermann, Anne; Shaikhibrahim, Zaki; Vogel, Wenzel; Müller, Stefan C; Ellinger, Jörg; Strauß, Arne; Radzun, Heinz Joachim; Ströbel, Philipp; Brägelmann, Johannes; Perner, Sven; Bremmer, Felix

    2015-09-17

    Testicular germ cell tumors (TGCT) are the most common cancer entities in young men with increasing incidence observed in the last decades. For therapeutic management it is important, that TGCT are divided into several histological subtypes. MED15 is part of the multiprotein Mediator complex which presents an integrative hub for transcriptional regulation and is known to be deregulated in several malignancies, such as prostate cancer and bladder cancer role, whereas the role of the Mediator complex in TGCT has not been investigated so far. Aim of the study was to investigate the implication of MED15 in TGCT development and its stratification into histological subtypes. Immunohistochemical staining (IHC) against Mediator complex subunit MED15 was conducted on a TGCT cohort containing tumor-free testis (n = 35), intratubular germ cell neoplasia unclassified (IGCNU, n = 14), seminomas (SEM, n = 107) and non-seminomatous germ cell tumors (NSGCT, n = 42), further subdivided into embryonic carcinomas (EC, n = 30), yolk sac tumors (YST, n = 5), chorionic carcinomas (CC, n = 5) and teratomas (TER, n = 2). Quantification of MED15 protein expression was performed through IHC followed by semi-quantitative image analysis using the Definiens software. In tumor-free seminiferous tubules, MED15 protein expression was absent or only low expressed in spermatogonia. Interestingly, the precursor lesions IGCNU exhibited heterogeneous but partly very strong MED15 expression. SEM weakly express the Mediator complex subunit MED15, whereas NSGCT and especially EC show significantly enhanced expression compared to tumor-free testis. In conclusion, MED15 is differentially expressed in tumor-free testis and TGCT. While MED15 is absent or low in tumor-free testis and SEM, NSGCT highly express MED15, hinting at the diagnostic potential of this marker to distinguish between SEM and NSGCT. Further, the precursor lesion IGCNU showed increased nuclear MED15

  14. Variation in functional responses to water stress and differentiation between natural allopolyploid populations in the Brachypodium distachyon species complex.

    PubMed

    Martínez, Luisa M; Fernández-Ocaña, Ana; Rey, Pedro J; Salido, Teresa; Amil-Ruiz, Francisco; Manzaneda, Antonio J

    2018-06-08

    Some polyploid species show enhanced physiological tolerance to drought compared with their progenitors. However, very few studies have examined the consistency of physiological drought response between genetically differentiated natural polyploid populations, which is key to evaluation of the importance of adaptive evolution after polyploidization in those systems where drought exerts a selective pressure. A comparative functional approach was used to investigate differentiation of drought-tolerance-related traits in the Brachypodium species complex, a model system for grass polyploid adaptive speciation and functional genomics that comprises three closely related annual species: the two diploid parents, B. distachyon and B. stacei, and the allotetraploid derived from them, B. hybridum. Differentiation of drought-tolerance-related traits between ten genetically distinct B. hybridum populations and its ecological correlates was further analysed. The functional drought response is overall well differentiated between Brachypodium species. Brachypodium hybridum allotetraploids showed a transgressive expression pattern in leaf phytohormone content in response to drought. In contrast, other B. hybridum physiological traits correlated to B. stacei ones. Particularly, proline and water content were the traits that best discriminated these species from B. distachyon under drought. After polyploid formation and/or colonization, B. hybridum populations have adaptively diverged physiologically and genetically in response to variations in aridity.

  15. A tumor-promoting mechanism mediated by retrotransposon-encoded reverse transcriptase is active in human transformed cell lines

    PubMed Central

    Sciamanna, Ilaria; Gualtieri, Alberto; Cossetti, Cristina; Osimo, Emanuele Felice; Ferracin, Manuela; Macchia, Gianfranco; Aricò, Eleonora; Prosseda, Gianni; Vitullo, Patrizia; Misteli, Tom; Spadafora, Corrado

    2013-01-01

    LINE-1 elements make up the most abundant retrotransposon family in the human genome. Full-length LINE-1 elements encode a reverse transcriptase (RT) activity required for their own retrotranpsosition as well as that of non-autonomous Alu elements. LINE-1 are poorly expressed in normal cells and abundantly in cancer cells. Decreasing RT activity in cancer cells, by either LINE-1-specific RNA interference, or by RT inhibitory drugs, was previously found to reduce proliferation and promote differentiation and to antagonize tumor growth in animal models. Here we have investigated how RT exerts these global regulatory functions. We report that the RT inhibitor efavirenz (EFV) selectively downregulates proliferation of transformed cell lines, while exerting only mild effects on non-transformed cells; this differential sensitivity matches a differential RT abundance, which is high in the former and undetectable in the latter. Using CsCl density gradients, we selectively identify Alu and LINE-1 containing DNA:RNA hybrid molecules in cancer but not in normal cells. Remarkably, hybrid molecules fail to form in tumor cells treated with EFV under the same conditions that repress proliferation and induce the reprogramming of expression profiles of coding genes, microRNAs (miRNAs) and ultraconserved regions (UCRs). The RT-sensitive miRNAs and UCRs are significantly associated with Alu sequences. The results suggest that LINE-1-encoded RT governs the balance between single-stranded and double-stranded RNA production. In cancer cells the abundant RT reverse-transcribes retroelement-derived mRNAs forming RNA:DNA hybrids. We propose that this impairs the formation of double-stranded RNAs and the ensuing production of small regulatory RNAs, with a direct impact on gene expression. RT inhibition restores the ‘normal’ small RNA profile and the regulatory networks that depend on them. Thus, the retrotransposon-encoded RT drives a previously unrecognized mechanism crucial to the

  16. Genetically Encoded Catalytic Hairpin Assembly for Sensitive RNA Imaging in Live Cells.

    PubMed

    Mudiyanselage, Aruni P K K Karunanayake; Yu, Qikun; Leon-Duque, Mark A; Zhao, Bin; Wu, Rigumula; You, Mingxu

    2018-06-26

    DNA and RNA nanotechnology has been used for the development of dynamic molecular devices. In particular, programmable enzyme-free nucleic acid circuits, such as catalytic hairpin assembly, have been demonstrated as useful tools for bioanalysis and to scale up system complexity to an extent beyond current cellular genetic circuits. However, the intracellular functions of most synthetic nucleic acid circuits have been hindered by challenges in the biological delivery and degradation. On the other hand, genetically encoded and transcribed RNA circuits emerge as alternative powerful tools for long-term embedded cellular analysis and regulation. Herein, we reported a genetically encoded RNA-based catalytic hairpin assembly circuit for sensitive RNA imaging inside living cells. The split version of Broccoli, a fluorogenic RNA aptamer, was used as the reporter. One target RNA can catalytically trigger the fluorescence from tens-to-hundreds of Broccoli. As a result, target RNAs can be sensitively detected. We have further engineered our circuit to allow easy programming to image various target RNA sequences. This design principle opens the arena for developing a large variety of genetically encoded RNA circuits for cellular applications.

  17. Silver Nanoparticles: Two-Faced Neuronal Differentiation-Inducing Material in Neuroblastoma (SH-SY5Y) Cells.

    PubMed

    Abdal Dayem, Ahmed; Lee, Soo Bin; Choi, Hye Yeon; Cho, Ssang-Goo

    2018-05-15

    We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated SH-SY5Y cells showed significantly higher reactive oxygen species (ROS) generation, stronger mitochondrial membrane depolarization, lower dual-specificity phosphatase expression, higher extracellular-signal-regulated kinase (ERK) phosphorylation, lower AKT phosphorylation, and lower expression of the genes encoding the antioxidant enzymes than RA-treated cells. Notably, pretreatment with N -acetyl-l-cysteine significantly abolished AgNP-induced neuronal differentiation, but not in that induced by RA. ERK inhibition, but not AKT inhibition, suppresses neurite growth that is induced by AgNP. Taken together, our results uncover the pivotal contribution of ROS in the AgNP-induced neuronal differentiation mechanism, which is different from that of RA. However, the negative consequence of AgNP-induced neurite growth may be high ROS generation and the downregulation of the expression of the genes encoding the antioxidant enzymes, which prompts the future consideration and an in-depth study of the application of AgNP-differentiated cells in neurodegenerative disease therapy.

  18. Scalable boson sampling with time-bin encoding using a loop-based architecture.

    PubMed

    Motes, Keith R; Gilchrist, Alexei; Dowling, Jonathan P; Rohde, Peter P

    2014-09-19

    We present an architecture for arbitrarily scalable boson sampling using two nested fiber loops. The architecture has fixed experimental complexity, irrespective of the size of the desired interferometer, whose scale is limited only by fiber and switch loss rates. The architecture employs time-bin encoding, whereby the incident photons form a pulse train, which enters the loops. Dynamically controlled loop coupling ratios allow the construction of the arbitrary linear optics interferometers required for boson sampling. The architecture employs only a single point of interference and may thus be easier to stabilize than other approaches. The scheme has polynomial complexity and could be realized using demonstrated present-day technologies.

  19. A functional TOC complex contributes to gravity signal transduction in Arabidopsis

    PubMed Central

    Strohm, Allison K.; Barrett-Wilt, Greg A.; Masson, Patrick H.

    2014-01-01

    Although plastid sedimentation has long been recognized as important for a plant's perception of gravity, it was recently shown that plastids play an additional function in gravitropism. The Translocon at the Outer envelope membrane of Chloroplasts (TOC) complex transports nuclear-encoded proteins into plastids, and a receptor of this complex, Toc132, was previously hypothesized to contribute to gravitropism either by directly functioning as a gravity signal transducer or by indirectly mediating the plastid localization of a gravity signal transducer. Here we show that mutations in multiple genes encoding TOC complex components affect gravitropism in a genetically sensitized background and that the cytoplasmic acidic domain of Toc132 is not required for its involvement in this process. Furthermore, mutations in TOC132 enhance the gravitropic defect of a mutant whose amyloplasts lack starch. Finally, we show that the levels of several nuclear-encoded root proteins are altered in toc132 mutants. These data suggest that the TOC complex indirectly mediates gravity signal transduction in Arabidopsis and support the idea that plastids are involved in gravitropism not only through their ability to sediment but also as part of the signal transduction mechanism. PMID:24795735

  20. A functional TOC complex contributes to gravity signal transduction in Arabidopsis.

    PubMed

    Strohm, Allison K; Barrett-Wilt, Greg A; Masson, Patrick H

    2014-01-01

    Although plastid sedimentation has long been recognized as important for a plant's perception of gravity, it was recently shown that plastids play an additional function in gravitropism. The Translocon at the Outer envelope membrane of Chloroplasts (TOC) complex transports nuclear-encoded proteins into plastids, and a receptor of this complex, Toc132, was previously hypothesized to contribute to gravitropism either by directly functioning as a gravity signal transducer or by indirectly mediating the plastid localization of a gravity signal transducer. Here we show that mutations in multiple genes encoding TOC complex components affect gravitropism in a genetically sensitized background and that the cytoplasmic acidic domain of Toc132 is not required for its involvement in this process. Furthermore, mutations in TOC132 enhance the gravitropic defect of a mutant whose amyloplasts lack starch. Finally, we show that the levels of several nuclear-encoded root proteins are altered in toc132 mutants. These data suggest that the TOC complex indirectly mediates gravity signal transduction in Arabidopsis and support the idea that plastids are involved in gravitropism not only through their ability to sediment but also as part of the signal transduction mechanism.