440 research outputs found

    A multinuclear NMR and quantum chemical study of solid trimethylammonium chloride

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    The solid salt, trimethylammonium chloride (TMAC), is investigated by a combination of NMR spectroscopic techniques and quantum chemical calculations. Chemical shift and nuclear quadrupolar interaction parameters have been measured for 35Cl, 1H/2H, and 15N/14N. These parameters have also been calculated as a function of the hydrogen position in the N\u2022\u2022\u2022H\u2022\u2022\u2022Cl fragment. Overall, the measured parameters are consistent with a structure in which the hydrogen is completely transferred to the nitrogen (i.e., N\u2013H\u2022\u2022\u2022Cl). The high hydrogen chemical shift (10.9 ppm by 2H CP/MAS) and relatively small deuterium quadrupolar coupling constant (127 kHz) indicate a moderately strong N\u2013H\u2022\u2022\u2022Cl hydrogen bond. A pronounced deuterium isotope effect on the 35Cl quadrupolar coupling constant is observed.Peer reviewed: YesNRC publication: Ye

    Ferredoxin containing bacteriocins suggest a novel mechanism of iron uptake in <i>Pectobacterium spp</i>

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    In order to kill competing strains of the same or closely related bacterial species, many bacteria produce potent narrow-spectrum protein antibiotics known as bacteriocins. Two sequenced strains of the phytopathogenic bacterium &lt;i&gt;Pectobacterium carotovorum&lt;/i&gt; carry genes encoding putative bacteriocins which have seemingly evolved through a recombination event to encode proteins containing an N-terminal domain with extensive similarity to a [2Fe-2S] plant ferredoxin and a C-terminal colicin M-like catalytic domain. In this work, we show that these genes encode active bacteriocins, pectocin M1 and M2, which target strains of &lt;i&gt;Pectobacterium carotovorum&lt;/i&gt; and &lt;i&gt;Pectobacterium atrosepticum&lt;/i&gt; with increased potency under iron limiting conditions. The activity of pectocin M1 and M2 can be inhibited by the addition of spinach ferredoxin, indicating that the ferredoxin domain of these proteins acts as a receptor binding domain. This effect is not observed with the mammalian ferredoxin protein adrenodoxin, indicating that &lt;i&gt;Pectobacterium spp.&lt;/i&gt; carries a specific receptor for plant ferredoxins and that these plant pathogens may acquire iron from the host through the uptake of ferredoxin. In further support of this hypothesis we show that the growth of strains of &lt;i&gt;Pectobacterium carotovorum&lt;/i&gt; and &lt;i&gt;atrosepticum&lt;/i&gt; that are not sensitive to the cytotoxic effects of pectocin M1 is enhanced in the presence of pectocin M1 and M2 under iron limiting conditions. A similar growth enhancement under iron limiting conditions is observed with spinach ferrodoxin, but not with adrenodoxin. Our data indicate that pectocin M1 and M2 have evolved to parasitise an existing iron uptake pathway by using a ferredoxin-containing receptor binding domain as a Trojan horse to gain entry into susceptible cells

    MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

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    MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

    Effect of surfactants on the deformation and break-up of an aqueous drop in oils under high electric field strengths

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    Understanding the deformation and break-up of drops is of great significance in various applications such as emulsification and phase separation. Most practical systems contain surface-active agents that are present as impurities affecting the properties of the system, e.g. modifying the rigidity of the film that affects emulsion stability. In this paper, the effect of surfactants on the deformation and break-up of an aqueous drop in an immiscible dielectric oil under the action of an electric field is addressed. The experiments were carried out on a single drop in a microscopic cell under an applied external electric field. A nonionic surfactant, polyethylene glycol sorbitan monolaurate (Tween 20), and an ionic surfactant, sodium dodecyl sulfate (SDS), were used at different concentrations. The drop adopted in most cases a prolate shape. However, the presence of the surfactant affected both the extent of deformation and the modes of break-up. The drop deformation extent increased rapidly with the surfactant concentration, while smaller drops deformed less under the same external electric field strength. When the surfactant concentration was high, the position of break-up could be from both poles along the main axis of the drops in the direction of the electric field

    The Structure and Regulation of Human Muscle α-Actinin

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    SummaryThe spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton in various cell types, crosslinks actin filaments, and acts as scaffolds for the assembly of large protein complexes involved in structural integrity and mechanosensation, as well as cell signaling. α-actinins in particular are the major actin crosslinkers in muscle Z-disks, focal adhesions, and actin stress fibers. We report a complete high-resolution structure of the 200 kDa α-actinin-2 dimer from striated muscle and explore its functional implications on the biochemical and cellular level. The structure provides insight into the phosphoinositide-based mechanism controlling its interaction with sarcomeric proteins such as titin, lays a foundation for studying the impact of pathogenic mutations at molecular resolution, and is likely to be broadly relevant for the regulation of spectrin-like proteins
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