Substrate Specificity within a Family of Outer Membrane Carboxylate Channels

Characterization of a large family of outer membrane channels from gram-negative bacteria suggest how they can thrive in nutrient-poor environments and how channel inactivation can contribute to antibiotic resistance

Unity through truth

Renewed worries about the unity of the proposition have been taken as a crucial stumbling block for any traditional conception of propositions. These worries are often framed in terms of how entities independent of mind and language can have truth conditions: why is the proposition that Desdemona loves Cassio true if and only if she loves him? I argue that the best understanding of these worries shows that they should be solved by our theory of truth and not our theory of content. Specifically, I propose a version of the redundancy theory according to which ‘it is true that Desdemona loves Cassio’ expresses the same proposition as ‘Desdemona loves Cassio’. Surprisingly, this variant of the redundancy theory treats ‘is true’ as an ordinary predicate of the language, thereby defusing many standard criticisms of the redundancy theory

Anthropogenic intensification of short-duration rainfall extremes

Short- duration (1-3 h) rainfall extremes can cause serious damage to societies through rapidly developing (flash) flooding and are determined by complex, multifaceted processes that are altering as Earth's climate warms. In this Review, we examine evidence from observational, theoretical and modelling studies for the intensification of these rainfall extremes, the drivers and the impact on flash flooding. Both short- duration and long- duration (\textgreater1 day) rainfall extremes are intensifying with warming at a rate consistent with the increase in atmospheric moisture (~7% K-1), while in some regions, increases in short- duration extreme rainfall intensities are stronger than expected from moisture increases alone. These stronger local increases are related to feedbacks in convective clouds, but their exact role is uncertain because of the very small scales involved. Future extreme rainfall intensification is also modulated by changes to temperature stratification and large- scale atmospheric circulation. The latter remains a major source of uncertainty. Intensification of short- duration extremes has likely increased the incidence of flash flooding at local scales and this can further compound with an increase in storm spatial footprint to considerably increase total event rainfall. These findings call for urgent climate change adaptation measures to manage increasing flood risks

Transmembrane passage of hydrophobic compounds through a protein channel wall

Membrane proteins that transport hydrophobic compounds have important roles in multi-drug resistance and can cause a number of diseases, underscoring the importance of protein-mediated transport of hydrophobic compounds. Hydrophobic compounds readily partition into regular membrane lipid bilayers, and their transport through an aqueous protein channel is energetically unfavourable. Alternative transport models involving acquisition from the lipid bilayer by lateral diffusion have been proposed for hydrophobic substrates. So far, all transport proteins for which a lateral diffusion mechanism has been proposed function as efflux pumps. Here we present the first example of a lateral diffusion mechanism for the uptake of hydrophobic substrates by the Escherichia coli outer membrane long-chain fatty acid transporter FadL. A FadL mutant in which a lateral opening in the barrel wall is constricted, but which is otherwise structurally identical to wild-type FadL, does not transport substrates. A crystal structure of FadL from Pseudomonas aeruginosa shows that the opening in the wall of the beta-barrel is conserved and delineates a long, hydrophobic tunnel that could mediate substrate passage from the extracellular environment, through the polar lipopolysaccharide layer and, by means of the lateral opening in the barrel wall, into the lipid bilayer from where the substrate can diffuse into the periplasm. Because FadL homologues are found in pathogenic and biodegrading bacteria, our results have implications for combating bacterial infections and bioremediating xenobiotics in the environment

Representative single-channel electrical recordings of the members of the OccD and OccK subfamilies with solved crystal structures.

<p>(A) OccD1; (B) OccD2; (C) OccD3; (D) OccK1; (E) OccK2; (F) OccK3; (G) OccK4; (H) OccK5; and (I) OccK6. The data were collected at an applied transmembrane potential of +80 mV. The buffer solution in the chamber contained 1 M KCl, 10 mM potassium phosphate, pH = 7.4. For the sake of clarity, the single-channel electrical traces were low-pass Bessel filtered at 2 kHz. The numbers located above the traces represent the single-channel conductance of the most probable substate of the channel. The averages were derived from at least three independent single-channel electrical recordings.</p

In vitro transport assays show a division of Occ channels into two subfamilies.

<p>Uptake of radiolabeled substrates in total membrane vesicles of <i>E. coli</i> Bl21 omp8 expressing empty plasmid (pB22), Occ channels, and <i>E. coli</i> OmpG or FadL. In addition, uptake mediated by the porin-containing strain C43 (DE3) is shown. Substrates are (A) arginine (0.25 µM, 15 min uptake), (B) benzoate (0.5 µM, 10 min), (C) glucuronate (0.5 µM, 10 min), (D) glucose (0.5 µM, 15 min), and (E) pyroglutamate (0.5 µM, 15 min). 100% specific activities correspond to 199.7±5.5 (A), 40.4±0.7 (B), 49.7±1.1 (C), 36.9±1.4 (D), and 20.7±0.5 (E) pmoles substrate/min/mg protein. Filter backgrounds are subtracted from all measurements.</p