966 research outputs found

    Angiotensinergic innervation of rat and human mesenteric resistant blood vessels

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    In contrast to the current believe that angiotensin II (Ang II) only interacts with the sympathetic nervous system (SNS) as a circulating hormone, we document here the existence of an endogenous renin-angiotensin system (RAS) in the sympathetic coeliac ganglion and the angiotensinergic innervation with mesenteric resistant blood vessels. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglion and may act as an endogenous neurotransmitter locally on the mesenteric resistant blood vessels

    Postpollination Changes in Floral Odor in Silene latifolia: Adaptive Mechanisms for Seed-Predator Avoidance?

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    Floral odor is a key trait for pollinator attraction in many plants, but may also direct antagonists like herbivores to flowers. In this study, we examined how floral scent changes after pollination in Silene latifolia, which has a specialized relationship with the seed predator Hadena bicruris. We found an overall decrease in total scent emission and considerable changes in relative amounts of scent compounds after pollination. Lilac aldehydes A and B as well as veratrole contributed most to the decrease in scent emission. These three compounds are known to be key signals for the attraction of H. bicruris to the flowers. A specific downregulation of these compounds may increase the reproductive success of the plant by reducing seed predation after pollinatio

    Splicing-dependent NMD does not require the EJC in Schizosaccharomyces pombe

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    Nonsense-mediated mRNA decay (NMD) is a translation-linked process that destroys mRNAs with premature translation termination codons (PTCs). In mammalian cells, NMD is also linked to pre-mRNA splicing, usually PTCs trigger strong NMD only when positioned upstream of at least one intron. The exon junction complex (EJC) is believed to mediate the link between splicing and NMD in these systems. Here, we report that in Schizosaccharomyces pombe splicing also enhances NMD, but against the EJC model prediction, an intron stimulated NMD regardless of whether it is positioned upstream or downstream of the PTC and EJC components are not required. Still the effect of splicing seems to be direct—we have found that the important NMD determinant is the proximity of an intron to the PTC, not just the occurrence of splicing. On the basis of these results, we propose a new model to explain how splicing could affect NMD

    Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay

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    The positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antiviral interventions. Here we present the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a mosquito-borne member of the alphaviruses, and host cell proteins. Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus' hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. In addition to observing a general inhibition of NMD about 4 hours post infection, we also demonstrate that transient expression of the SFV capsid protein is sufficient to inhibit NMD in cells, suggesting that the massive production of capsid protein during the SFV reproduction cycle is responsible for NMD inhibition. Author summary To take over control of the host cell and ensure its own replication, viral proteins do interact with a plethora of host cell proteins. Elucidating these viral-host cell protein interactions is therefore key for understanding the mechanisms that a virus applies to successfully hijack the host cell. This study provides the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a positive-strand, single-stranded RNA virus of the alphavirus family. While we previously discovered that the host cell recognizes and degrades the incoming viral genomic RNA by a cellular quality control system called Nonsense-Mediated mRNA Decay (NMD), our interactome study now led to uncovering of the other side of this arms race between SFV and the infected cells: We show in this study that the viral capsid protein has the capacity to inhibit NMD.Peer reviewe

    Arabidopsis thaliana computationally-generated next-state gene interaction models

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    The construction of gene interaction models must be a fully collaborative and intentional effort. All aspects of the research, such as growing the plants, extracting the measurements, refining the measured data, developing the statistical framework, and forming and applying the algorithmic techniques, must lend themselves to repeatable and sound practices. This paper holistically focuses on the process of producing gene interaction models based on transcript abundance data from Arabidopsis thaliana after stimulation by a plant hormone

    Determination of liposome/water partition coefficients of organic acids and bases by solid-phase microextraction

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    The extraction of two methylated anilines and three chlorinated phenols by solid-phase microextraction (SPME) fibers coated with polyacrylate was investigated as a function of pH. Only the neutral species of the acids and bases partitioned into the polymer. Extraction kinetics were accelerated for the hydrophobic phenols at pH values around their acidity constant. This is presumably due to a reconstitution of the neutral species in the unstirred aqueous layer adjacent to the polymer surface by the charged species through the fast acid-base equilibrium. Although the charged species is not taken up into the polymer. liposome/water distribution ratios could be measured up to a pH value, where 99% of the compounds were present as charged species. The partition coefficients of the neutral and charged species were extrapolated from the pH profiles of the liposome/water distribution ratios. The resulting values were slightly lower than those measured with equilibrium dialysis. The discrepancies are discussed with respect to differences in the experimental conditions and the possibility of matrix effects during SPME measurements

    Adsorption of Streptococcus mutans on Chemically Treated Hydroxyapatite

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    Adsorption of Streptococcus mutans on hydroxyapatite and chemically treated hydroxyapatite was studied. Zeta potentials of the surfaces were measured. Chemically treated hydroxyapatite gave higher ζ potentials and lower S mutans adsorption.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67845/2/10.1177_00220345780570091601.pd

    Identification and characterization of an inhibitory fibroblast growth factor receptor 2 (FGFR2) molecule, up-regulated in an Apert Syndrome mouse model

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    AS (Apert syndrome) is a congenital disease composed of skeletal, visceral and neural abnormalities, caused by dominant-acting mutations in FGFR2 [FGF (fibroblast growth factor) receptor 2]. Multiple FGFR2 splice variants are generated through alternative splicing, including PTC (premature termination codon)-containing transcripts that are normally eliminated via the NMD (nonsense-mediated decay) pathway. We have discovered that a soluble truncated FGFR2 molecule encoded by a PTC-containing transcript is up-regulated and persists in tissues of an AS mouse model. We have termed this IIIa–TM as it arises from aberrant splicing of FGFR2 exon 7 (IIIa) into exon 10 [TM (transmembrane domain)]. IIIa–TM is glycosylated and can modulate the binding of FGF1 to FGFR2 molecules in BIAcore-binding assays. We also show that IIIa–TM can negatively regulate FGF signalling in vitro and in vivo. AS phenotypes are thought to result from gain-of-FGFR2 signalling, but our findings suggest that IIIa–TM can contribute to these through a loss-of-FGFR2 function mechanism. Moreover, our findings raise the interesting possibility that FGFR2 signalling may be a regulator of the NMD pathway

    Developmental Changes in the Metabolic Network of Snapdragon Flowers

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    Evolutionary and reproductive success of angiosperms, the most diverse group of land plants, relies on visual and olfactory cues for pollinator attraction. Previous work has focused on elucidating the developmental regulation of pathways leading to the formation of pollinator-attracting secondary metabolites such as scent compounds and flower pigments. However, to date little is known about how flowers control their entire metabolic network to achieve the highly regulated production of metabolites attracting pollinators. Integrative analysis of transcripts and metabolites in snapdragon sepals and petals over flower development performed in this study revealed a profound developmental remodeling of gene expression and metabolite profiles in petals, but not in sepals. Genes up-regulated during petal development were enriched in functions related to secondary metabolism, fatty acid catabolism, and amino acid transport, whereas down-regulated genes were enriched in processes involved in cell growth, cell wall formation, and fatty acid biosynthesis. The levels of transcripts and metabolites in pathways leading to scent formation were coordinately up-regulated during petal development, implying transcriptional induction of metabolic pathways preceding scent formation. Developmental gene expression patterns in the pathways involved in scent production were different from those of glycolysis and the pentose phosphate pathway, highlighting distinct developmental regulation of secondary metabolism and primary metabolic pathways feeding into it

    GTP-dependent structural rearrangement of the eRF1:eRF3 complex and eRF3 sequence motifs essential for PABP binding

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    Translation termination in eukaryotes is governed by the concerted action of eRF1 and eRF3 factors. eRF1 recognizes the stop codon in the A site of the ribosome and promotes nascent peptide chain release, and the GTPase eRF3 facilitates this peptide release via its interaction with eRF1. In addition to its role in termination, eRF3 is involved in normal and nonsense-mediated mRNA decay through its association with cytoplasmic poly(A)-binding protein (PABP) via PAM2-1 and PAM2-2 motifs in the N-terminal domain of eRF3. We have studied complex formation between full-length eRF3 and its ligands (GDP, GTP, eRF1 and PABP) using isothermal titration calorimetry, demonstrating formation of the eRF1:eRF3:PABP:GTP complex. Analysis of the temperature dependence of eRF3 interactions with G nucleotides reveals major structural rearrangements accompanying formation of the eRF1:eRF3:GTP complex. This is in contrast to eRF1:eRF3:GDP complex formation, where no such rearrangements were detected. Thus, our results agree with the established active role of GTP in promoting translation termination. Through point mutagenesis of PAM2-1 and PAM2-2 motifs in eRF3, we demonstrate that PAM2-2, but not PAM2-1 is indispensible for eRF3:PABP complex formation
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