152 research outputs found

    INFLUENCE OF THE SEA-SIDE RESORT FACTORS UPON FIBRINOLYTIC ACTIVITY OF PATIENTS WITH HYPERTENSION

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    Magnesium Limitation Is an Environmental Trigger of the Pseudomonas aeruginosa Biofilm Lifestyle

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    Biofilm formation is a conserved strategy for long-term bacterial survival in nature and during infections. Biofilms are multicellular aggregates of cells enmeshed in an extracellular matrix. The RetS, GacS and LadS sensors control the switch from a planktonic to a biofilm mode of growth in Pseudomonas aeruginosa. Here we detail our approach to identify environmental triggers of biofilm formation by investigating environmental conditions that repress expression of the biofilm repressor RetS. Mg2+ limitation repressed the expression of retS leading to increased aggregation, exopolysaccharide (EPS) production and biofilm formation. Repression of retS expression under Mg2+ limitation corresponded with induced expression of the GacA-controlled small regulatory RNAs rsmZ and rsmY and the EPS biosynthesis operons pel and psl. We recently demonstrated that extracellular DNA sequesters Mg2+ cations and activates the cation-sensing PhoPQ two-component system, which leads to increased antimicrobial peptide resistance in biofilms. Here we show that exogenous DNA and EDTA, through their ability to chelate Mg2+, promoted biofilm formation. The repression of retS in low Mg2+ was directly controlled by PhoPQ. PhoP also directly controlled expression of rsmZ but not rsmY suggesting that PhoPQ controls the equilibrium of the small regulatory RNAs and thus fine-tunes the expression of genes in the RetS pathway. In summary, Mg2+ limitation is a biologically relevant environmental condition and the first bonafide environmental signal identified that results in transcriptional repression of retS and promotes P. aeruginosa biofilm formation

    Experimental signatures of emergent quantum electrodynamics in Pr2_2Hf2_2O7_7

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    In a quantum spin liquid, the magnetic moments of the constituent electron spins evade classical long-range order to form an exotic state that is quantum entangled and coherent over macroscopic length scales [1-2]. Such phases offer promising perspectives for device applications in quantum information technologies, and their study can reveal fundamentally novel physics in quantum matter. Quantum spin ice is an appealing proposal of one such state, in which the fundamental ground state properties and excitations are described by an emergent U(1) lattice gauge theory [3-7]. This quantum-coherent regime has quasiparticles that are predicted to behave like magnetic and electric monopoles, along with a gauge boson playing the role of an artificial photon. However, this emergent lattice quantum electrodynamics has proved elusive in experiments. Here we report neutron scattering measurements of the rare-earth pyrochlore magnet Pr2_2Hf2_2O7_7 that provide evidence for a quantum spin ice ground state. We find a quasi-elastic structure factor with pinch points - a signature of a classical spin ice - that are partially suppressed, as expected in the quantum-coherent regime of the lattice field theory at finite temperature. Our result allows an estimate for the speed of light associated with magnetic photon excitations. We also reveal a continuum of inelastic spin excitations, which resemble predictions for the fractionalized, topological excitations of a quantum spin ice. Taken together, these two signatures suggest that the low-energy physics of Pr2_2Hf2_2O7_7 can be described by emergent quantum electrodynamics. If confirmed, the observation of a quantum spin ice ground state would constitute a concrete example of a three-dimensional quantum spin liquid - a topical state of matter which has so far mostly been explored in lower dimensionalities.Comment: 15 pages, 3 figure

    Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies

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    Abstract\ud \ud Background\ud Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere. Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments. While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform “community-level” metabolism of lignocellulose. Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.\ud \ud \ud Results\ud Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost. Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks. Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment. Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera. The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance. A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant. This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation. The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.\ud \ud \ud Conclusions\ud A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks. In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.This work was funded by Biotechnology and Biological Sciences Research\ud Council (BBSRC) Grants BB/1018492/1, BB/K020358/1 and BB/P027717/1, the\ud BBSRC Network in Biotechnology and Bioenergy BIOCATNET and São Paulo\ud Research Foundation (FAPESP) Grant 10/52362-5. ERdA thanks EMBRAPA\ud Instrumentation São Carlos and Dr. Luiz Alberto Colnago for providing the\ud NMR facility and CNPq Grant 312852/2014-2. The authors would like to thank\ud Deborah Rathbone and Susan Heywood from the Biorenewables Develop‑\ud ment Centre for technical assistance in rRNA amplicon sequencing

    The NuRD nucleosome remodelling complex and NHK-1 kinase are required for chromosome condensation in oocytes

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    Chromosome condensation during cell division is one of the most dramatic events in the cell cycle. Condensin and topoisomerase II are the most studied factors in chromosome condensation. However, their inactivation leads to only mild defects and little is known about the roles of other factors. Here, we took advantage of Drosophila oocytes to elucidate the roles of potential condensation factors by performing RNA interference (RNAi). Consistent with previous studies, depletion of condensin I subunits or topoisomerase II in oocytes only mildly affected chromosome condensation. In contrast, we found severe undercondensation of chromosomes after depletion of the Mi-2-containing NuRD nucleosome remodelling complex or the protein kinase NHK-1 (also known as Ballchen in Drosophila). The further phenotypic analysis suggests that Mi-2 and NHK-1 are involved in different pathways of chromosome condensation. We show that the main role of NHK-1 in chromosome condensation is to phosphorylate Barrier-to-autointegration factor (BAF) and suppress its activity in linking chromosomes to nuclear envelope proteins. We further show that NHK-1 is important for chromosome condensation during mitosis as well as in oocytes

    Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU)

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    The disruption of proteostasis in neurodegenerative diseases

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    Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

    Consensus guidelines for the use and interpretation of angiogenesis assays

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    The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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