60 research outputs found

    Mycobacteriumsmegmatis bio¢lm formationand slidingmotility are a¡ected by the serine/threonine protein kinase PknF

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    Eighteen ‘eukaryotic-like’ serine/threonine kinases are present in the Mycobacterium smegmatis genome. One of them encoded by the ORF 3677 demonstrates high similarity to the Mycobacterium tuberculosis protein kinase PknF. A merodiploid strain was generated, which showed reduced growth associated with irregular cell structure. The merodiploid strain displayed altered colony morphology, defective slidingmotility and biofilm formation. These data indicate a role for PknF in biofilm formation, possibly associated with alterations in glycopeptidolipid composition

    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

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    Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

    DIFFaX simulations of stacking faults in layered double hydroxides (LDHs)

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    Carbonate-intercalated layered double hydroxides of Co(II) and Ni(II) with Fe(III) and Al(III) were precipitated under different conditions(pH = 8-12; T = 25-80 degrees C). All the samples are replete with stacking faults which are not eliminated by post-precipitation hydrothermal treatment (80-180 degrees C, 18 h). DIFFaX simulations show that the layer stacking sequence of the disordered samples can be generated by a mixture of motifs corresponding to the 3R(1) and 2H(1)polytypes. These specific sequences are selected in preference to others because of the need for hydrogen bonding between the intercalated carbonates and hydroxide sheets. Thermodynamic considerations show that faulted crystals have greater stability than ordered crystals. Stacking faults arising from a mixture of 3R(1) and 2H(1) motifs, while having the same enthalpy as that of the ordered crystal, nevertheless contribute to thermodynamic stability by enhancing disorder

    Mechanism of the anion exchange reactions of the layered double hydroxides (LDHs) of Ca and Mg with Al

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    The nitrate containing layered double hydroxide (LDH) of Ca with Al on reaction with aqueous solutions of Na2CO3Na_{2}CO_{3} and Na3PO4Na_{3}PO_{4} yields CaCO3CaCO_{3} and Ca5(PO4)3OHCa_{5}(PO_{4})_{3}OH respectively rather than the carbonate/phosphate containing LDHs. The LDH of Mg with Al on reacting with dissolved phosphate ions also leads to the formation of unitary phosphates. This shows that the anion exchange reactions of layered double hydroxides take place by the dissolution-reprecipitation mechanism rather than by the topotactic mechanism

    Suppression of the Reversible Thermal Behavior of the Layered Double Hydroxide (LDH) of Mg with Al: Stabilization of Nanoparticulate Oxides

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    The layered double hydroxide of Mg with Al decomposes below 600°C with the loss of nearly 48% mass, resulting in the formation of an oxide residue having the rock salt structure and nanoparticulate morphology. However, this product reconstructs back into the parent LDH, owing to its compositional and morphological metastability. The oxide can be kinetically stabilized within an amorphous phosphate network built up through an ex situ reaction with a suitable phosphate source such as (NH4)H2PO4(NH_4)H_2PO_4. This oxide transforms into a thermodynamically more stable phase with a spinel structure on soaking in an aqueous medium. The oxide residue has a nanoparticulate morphology as revealed by the Scherrer broadening of the Bragg reflections as well as by electron microscopy. This work shows that the hydroxide reconstruction reaction and spinel formation are competing reactions. Suppression of the former catalyzes spinel formation as the excess free energy of the metastable oxide residue is unlocked to promote the diffusion of Mg2+Mg^{2+} ions from octahedral to tetrahedral sites, which is the essential precondition to the formation of a normal spinel. This reaction taking place as it does at ambient temperature and in solution helps in the retention of a nanostructured morphology for the spinel. Another way of stabilizing the oxide is by incorporating the thermally stable borate anion into the LDH. This paves the way for an in situ reaction between the cations of the host LDH and the borate guest. The in situ reaction directly leads to the formation of an oxide with a spinel structure

    Solution decomposition of the layered double hydroxide (LDH) of Zn with Al

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    The layered double hydroxides (LDH) of Zn with Al containing intercalated CO32CO_3 ^{2-} and NO3NO_3^- ions undergo solution decomposition to yield a highly crystalline oxide mixture comprising ZnO and ZnAl2O4ZnAl_2O_4 at temperatures as low as 150180oC150-180 ^oC under hydrothermal conditions. In contrast solid-state decomposition takes place at a much higher temperature (240315oC)(240-315 ^oC) in air. Solution decomposition is not only guided by the low octahedral crystal field stabilization energy of Zn2+Zn^{2+} ions, a factor that also affects solid-state decomposition, but also by solubility considerations. The LDHs of Mg and Ni with Al do not undergo solution decomposition

    The serine/threonine protein kinasePknI controls the growth of Mycobacterium tuberculosis upon infection

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    The protein kinase PknI is one of 11 functional serine/threonine protein kinases in Mycobacterium tuberculosis. Specialized transduction was performed to create a null mutant in the pknI gene. The resulting mutant was used to determine the role of PknI in M. tuberculosis growth and infectivity. The pknI mutant grows better under acidic pH and limited oxygen availability. We observed a modest increased growth of pknI mutant within macrophages during an in vitro infection and a hypervirulence phenotype in severe combined immunodeficiency mice. The internal signals used to activate PknI are most likely the host-associated signals such as low pH associated with limited oxygen availability. Thus, we have shown that PknI plays a role in sensing the host macrophage’s environment and translating it to slow the growth of M. tuberculosis within the infected host

    Stable prenucleation mineral clusters are liquid-like ionic polymers

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    Calcium carbonate is an abundant substance that can be created in several mineral forms by the reaction of dissolved carbon dioxide in water with calcium ions. Through biomineralization, organisms can harness and control this process to form various functional materials that can act as anything from shells through to lenses. The early stages of calcium carbonate formation have recently attracted attention as stable prenucleation clusters have been observed, contrary to classical models. Here we show, using computer simulations combined with the analysis of experimental data, that these mineral clusters are made of an ionic polymer, composed of alternating calcium and carbonate ions, with a dynamic topology consisting of chains, branches and rings. The existence of a disordered, flexible and strongly hydrated precursor provides a basis for explaining the formation of other liquid-like amorphous states of calcium carbonate, in addition to the non-classical behaviour during growth of amorphous calcium carbonate
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