125 research outputs found

    A dynamic zinc redox switch

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    Structure of the unphosphorylated STAT5a dimer

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    STAT proteins have the function of signaling from the cell membrane into the nucleus, where they regulate gene transcription. Latent mammalian STAT proteins can form dimers in the cytoplasm even before receptor-mediated activation by specific tyrosine phosphorylation. Here we describe the 3.21-angstrom crystal structure of an unphosphorylated STAT5a homodimer lacking the N-terminal domain as well as the C-terminal transactivation domain. The overall structure of this fragment is very similar to phosphorylated STATs. However, important differences exist in the dimerization mode. Although the interface between phosphorylated STATs is mediated by their Src-homology 2 domains, the unphosphorylated STAT5a fragment dimerizes in a completely different manner via interactions between their beta-barrel and four-helix bundle domains. The STAT4 N-terminal domain dimer can be docked onto this STAT5a core fragment dimer based on shape and charge complementarities. The separation of the dimeric arrangement, taking place upon activation and nuclear translocation of STAT5a, is demonstrated by fluorescence resonance energy transfer experiments in living cells

    Priming of NLRP3 inflammasome activation 1 by Msn Kinase MINK1 in Macrophages

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    The nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome is essential in inflammation and inflammatory disorders. Phosphorylation at various sites on NLRP3 differentially regulates inflammasome activation. The Ser725 phosphorylation site on NLRP3 is depicted in multiple inflammasome activation scenarios, but the importance and regulation of this site has not been clarified. The present study revealed that the phosphorylation of Ser725 was an essential step for the priming of the NLRP3 inflammasome in macrophages. We also showed that Ser725 was directly phosphorylated by misshapen (Msn)/NIK-related kinase 1 (MINK1), depending on the direct interaction between MINK1 and the NLRP3 LRR domain. MINK1 deficiency reduced NLRP3 activation and suppressed inflammatory responses in mouse models of acute sepsis and peritonitis. Reactive oxygen species (ROS) upregulated the kinase activity of MINK1 and subsequently promoted inflammasome priming via NLRP3 Ser725 phosphorylation. Eliminating ROS suppressed NLRP3 activation and reduced sepsis and peritonitis symptoms in a MINK1-dependent manner. Altogether, our study reveals a direct regulation of the NLRP3 inflammasome by Msn family kinase MINK1 and suggests that modulation of MINK1 activity is a potential intervention strategy for inflammasome-related diseases

    Country Perspectives on Hay-Making Landscapes as Part of the European Agricultural Heritage

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    This paper provides an overview of traditional hay-making structures and the related agricultural landscapes in Europe. The information was collected using a standardised questionnaire that was completed by experts from different countries. What all countries had in common was that hay production with its corresponding structures was widespread. However, the scope and importance differed among the countries today. We found differences in type and extent, in degree of awareness, and in the cultural meaning of hay-making structures. The differences were connected with built structures, as well as with other tangible and intangible aspects of cultural heritage. The distribution of the broad variety of hay-making-related structures, especially semipermanent ones, has changed throughout history, as well as the hay-making techniques, as a result of agrarian specialisation, land reclamation, and consolidation. Today, in some countries, the relevance of hay-making was mainly connected to horse keeping and landscape management (like in Germany and Hungary), while in others (like Slovakia and Slovenia), it was still predominantly used for cattle and sheep

    Influenţa fertilizării diferențiate la o cultură de rucola perenă în câmp deschis

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    Perennial wall-rocket (Diplotaxis tenuifolia L.) is a less studied species in Romania. It belongs to the Brassicaceae family, being cultivated for its fresh leaves used in the preparation of salads. In this context, the objective of this study was to evaluate the effects of different type of fertilizers application on productivity indicators of perennial wall-rocket, cultivated in open field. The monofactorial experience was located in the didactic and experimental field of the Vegetables Discipline within the Faculty of Horticulture, U.S.V. Iasi. The experimental variants were represented by the application of different types of fertilizers, as follows: V1= organic (fertilization with vermicompost), V2= chemical (fertilization with Complex 16:16:16), V3= organic (fertilization with Orgevit), V4= microorganisms (Micoseeds MB) and V5= unfertilized. The best results for all the investigated parameters were obtained in the case of the variant treated with chemical fertilizers, followed, in descending order, by the variants fertilized with vermicompost, Orgevit and Micoseeds MB

    The effect of myco‐biocontrol based formulates on yield, physiology and secondary products of organically grown basil

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    The development of organic farming as a result of increasing consumer preference for organic food has led to the development and registration of new pest‐control products for certified organic production. In this study, the effects of three biocontrol products containing spores and mycelium of Arthrobotrys oligospora—Artis®, Beauveria bassiana—Bora®, and Coniothyrium minitans— Öko‐ni® were tested on four basil (Ocimum basilicum L.) cultivars: ‘Aromat de Buzau’, ‘Serafim’, ‘Macedon’ and ‘Cuisoare’. The application of Öko‐ni® increased basil yields by 8% relative to Control. The application of Bora® increased chlorophyll content of basil leaves by 2% and the activity of photosynthesis by 66% relative to the Control. Basil essential oil (EO) content was increased by 18% with the application of Artis® and by 34% with the application of Bora® and Öko‐ni®, respectively. The content of phenolic compounds analyzed by HPLC varied; caffeic acid concentration was higher in the plants treated with Öko‐ni®, hyperoside, isoquercitrin and rutin concentrations were higher in those treated with Artis®, while the quercitrin content was higher in Bora®‐treated plants. The two main EO constituents that were identified were linalool and methyl chavicol in ‘Aromat de Buzau’, linalool and eugenol in ‘Serafim’, neral and geranial in ‘Macedon’, also linalool and eugenol in ‘Cuisoare’. The investigated myco‐biocontrol products had positive effects on basil fresh biomass and EO content and also influenced the content of phenolic compounds
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