Mecanismes de control negatiu de la inflamació vehiculats per receptors nuclears

Els receptors nuclears són una família de factors de transcripció dependents de lligand que regulen la reproducció, el desenvolupament, el metabolisme i la resposta immunitària. Diversos membres de la família dels receptors nuclears tenen un paper important en el control negatiu de la inflamació. Centrarem aquesta revisió en alguns dels receptors nuclears que presenten una activitat repressora de la inflamació ben caracteritzada i revisarem els mecanismes moleculars involucrats en aquestes accions antiinflamatòries.Nuclear receptors are a superfamily of ligand-dependent transcription factors that regulate reproduction, development, metabolism and immune responses. Several nuclear receptors play an important role in the negative control of inflammation. In this review we will focus on those nuclear receptors with better characterised anti-inflammatory roles and the molecular mechanisms underlying their actions

Carbon Sequestration Capacities of Different Land Cover Types and Climate Change

Human-caused climate change creates a positive feedback loop that emits more carbon dioxide into the atmosphere instead of being sequestered in the Earth or its oceans. A major contributor to this feedback loop is deforestation in order to use land for agriculture and livestock. This study aims to investigate differences in carbon sequestration capabilities of forests, pastures, and cropland through soil and tree sampling in Gettysburg, Pennsylvania. The main hypothesis of this study is that forested land will be the most effective at carbon sequestration. The loss on ignition method (LOI) was used to determine the percent organic material in the soil for each land type. The soil in the forest sequestered the most CO2 per unit area at 0.012 tons/m2, followed by the pasture at 0.010 tons/m2, and finally the cropland at 0.009 tons/m2. When including the trees in the total carbon sequestered per unit area the carbon sequestered per unit area was 0.109 tons/m2 with average carbon sequestered per tree being 43644.4 pounds (21.8 tons). These results have implications for land management practices being used to mitigate climate change, as the different land covers sequestered significantly different amounts of CO2

Experimental and Numerical Investigations of High Strength Cold-formed Lapped Z Purlins under Combined Bending and Shear

Plain C or Z- sections are two of the most common cold-formed steel purlins in use for roof systems throughout the world. Especially for Z- sections, their lapping ability provides continuity and double thickness material at the support regions results in greater performance and more economical designs. At the region just outside the end of the lap, the purlin may fail under a combination of high bending and shear. Design methods for these sections are normally specified in the Australian/New Zealand Standard for Cold-Formed Steel Structures (AS/NZS 4600:2005) or the North American Specification for Cold- Formed Steel Structural Members (2007). Both Effective Width Method (EWM) and the newly developed Direct Strength Method (DSM) can be used for the design. The DSM presented [Chapter 7 of AS/NZS 4600:2005, Appendix 1 of (AISI 2007)] is developed for columns and beams and is limited to pure compression and pure bending. The situation of combined bending and shear as occurs in a continuous purlin system is not considered. This paper presents a testing program performed at the University of Sydney to determine the ultimate strength of high strength cold-formed lapped Z purlins with two different lap lengths. Tests were also conducted both with and without straps screwed on the top flanges. These straps provide torsion/distortion restraints which may enhance the capacity of the purlins. Numerical simulations using the Finite Element Method (FEM) were also performed. The simulations are compared with and calibrated against tests. The accurate results from FEM allowed extension of the test data by varying the lap lengths. The results of both the experimental tests and FEM were used and plotted on the design interaction curves. The proposals for an extension to the DSM in combined bending and shear are given in the paper

Effect of random and hub gene disruptions on environmental and mutational robustness in Escherichia coli

BACKGROUND: Genome-wide profiling has allowed the regulatory interaction networks of many organisms to be visualised and the pattern of connections between genes to be studied. These networks are non-random, following a power-law distribution with a small number of well-connected 'hubs' and many genes with only one or a few connections. Theoretical work predicts that power-law networks display several unique properties. One of the most biologically interesting of these is an intrinsic robustness to disturbance such that removal of a random gene will have little effect on network function. Conversely, targeted removal of a hub gene is expected to have a large effect. RESULTS: We compared the response of Escherichia coli to environmental and mutational stress following disruption of random or hub genes. We found that disruption of random genes had less effect on robustness to environmental stress than did the targeted disruption of hub genes. In contrast, random disruption strains were slightly less robust to the effect of mutational stress than were hub disruption strains. When we compared the effect of each disruption on environmental and mutational stress, we found a negative relationship, such that strains that were more environmentally robust tended to be less robust to mutational stress. CONCLUSION: Our results demonstrate that mutant strains of E. coli respond differently to stress, depending on whether random or hub genes are disrupted. This difference indicates that the power-law distribution of regulatory interactions has biological significance, making random disruptions less deleterious to organisms facing environmental stress. That E. coli can reduce the effect of environmental stress without reducing the phenotypic effect of additional mutations, indicates that robustness and evolvability need not be antagonistic

Broadening substrate specificity of a chain-extending ketosynthase through a single active-site mutation.

An in vitro model system based on a ketosynthase domain of the erythromycin polyketide synthase was used to probe the apparent substrate tolerance of ketosynthase domains of the mycolactone polyketide synthase. A specific residue change was identified that led to an emphatic increase in turnover of a range of substrates.BBSRC (BB/J007250/1)This is the final version of the article. It first appeared from Royal Society of Chemistry] via https://doi.org/10.1039/C6CC03501A

Iterative Mechanism of Macrodiolide Formation in the Anticancer Compound Conglobatin.

Conglobatin is an unusual C2-symmetrical macrodiolide from the bacterium Streptomyces conglobatus with promising antitumor activity. Insights into the genes and enzymes that govern both the assembly-line production of the conglobatin polyketide and its dimerization are essential to allow rational alterations to be made to the conglobatin structure. We have used a rapid, direct in vitro cloning method to obtain the entire cluster on a 41-kbp fragment, encoding a modular polyketide synthase assembly line. The cloned cluster directs conglobatin biosynthesis in a heterologous host strain. Using a model substrate to mimic the conglobatin monomer, we also show that the conglobatin cyclase/thioesterase acts iteratively, ligating two monomers head-to-tail then re-binding the dimer product and cyclizing it. Incubation of two different monomers with the cyclase produces hybrid dimers and trimers, providing the first evidence that conglobatin analogs may in future become accessible through engineering of the polyketide synthase.We gratefully acknowledge BBSRC (project grant BB/J007250/1 to P.F.L.), the European Commission (Marie Curie Fellowship to Y.Z.), and the University of Cambridge (Herchel Smith Research Fellowship to A.C.M.), and Ms. Asha Boodhun (Department of Chemistry, University of Cambridge) for help in HR-MS analysis. L.C.D. acknowledges the support of Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Proc. 2012/04616-3 and 2012/02230-0). P.F.L. is an International Research Awardee of the Alexander von Humboldt Foundation.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.chembiol.2015.05.01

Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro

Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treat-ment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains un-known, but recent studies suggested the possibilities of the presence of antibiotic resistant Borreliapersister cells and biofilms.In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferispirochetes, persisters, and bio-film forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to differ-ent microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combina-tions. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Sub-culture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics weretested against attached biofilms, Stevia significantly reduced B. burgdorferiforms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi