Energetics and Mechanism of Drug Transport Mediated by the Lactococcal Multidrug Transporter LmrP

The gene encoding the secondary multidrug transporter LmrP of Lactococcus lactis was heterologously expressed in Escherichia coli. The energetics and mechanism of drug extrusion mediated by LmrP were studied in membrane vesicles of E. coli. LmrP-mediated extrusion of tetraphenyl phosphonium (TPP+) from right-side-out membrane vesicles and uptake of the fluorescent membrane probe 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH) into inside-out membrane vesicles are driven by the membrane potential (Δψ) and the transmembrane proton gradient (ΔpH), pointing to an electrogenic drug/proton antiport mechanism. Ethidium bromide, a substrate for LmrP, inhibited the LmrP-mediated TPP+ extrusion from right-sideout membrane vesicles, showing that LmrP is capable of transporting structurally unrelated drugs. Kinetic analysis of LmrP-mediated TMA-DPH transport revealed a direct relation between the transport rate and the amount of TMA-DPH associated with the cytoplasmic leaflet of the lipid bilayer. This observation indicates that drugs are extruded from the inner leaflet of the cytoplasmic membrane into the external medium. This is the first report that shows that drug extrusion by a secondary multidrug resistance (MDR) transporter occurs by a “hydrophobic vacuum cleaner” mechanism in a similar way as was proposed for the primary lactococcal MDR transporter, LmrA.

Financial problems and psychological distress: Investigating reciprocal effects among business owners

Abstract: Building on conservation of resources theory and the dynamic equilibrium model, this threewave longitudinal study among 302 Dutch agricultural business owners (one-year time intervals) investigated reciprocal relationships between the financial situation of the business and psychological distress. Results of structural equation modeling analyses revealed a negative spiral of farm decline, in which psychological variables played a key role. Experiencing financial problems predicted psychological distress, and acted as a self-fulfilling prophecy by strengthening intentions to quit the business, which predicted a deterioration of the objective financial situation of the business one year later. Moreover, farmers experiencing more psychological distress were more likely to get caught in this negative spiral than business owners with better mental health, because they experienced more financial problems, irrespective of their objective financial situation. Long-term psychological distress rather than temporary fluctuations in distress levels accounted for this effect

Prevention of retrogradation of starch

The invention provides an isolated or recombinant nucleic acid derived from a nucleic acid encoding a polypeptide essentially having alpha-glucanotransferase activity but having essentially no hydrolysing activity, said isolated or recombinant nucleic acid encoding a polypeptide with hydrolytic activity

Surface roughness over the northern half of the Greenland Ice Sheet from airborne laser altimetry

This is the published version, also available here: http://dx.doi.org/10.1029/2008JF001067.Surface roughness, defined as the standard deviation of small-scale elevation fluctuations from the linear trend over 0.5 km, can be estimated from high-resolution airborne laser altimetry. Here we present results for the northern half of the Greenland Ice Sheet using laser data collected in May 1995. Roughness is smallest in the central region straddling the ice divide, increases in amplitude toward the coast, and appears to be correlated with slope of the ice surface. For most of the study region surface roughness is 8 cm or less (<2.5 cm water equivalent). In smaller regions associated with fast flow, larger values are found. Comparison of the size of small-scale topographic disturbances with the spatial noise estimated from five closely spaced ice cores drilled in northwest Greenland shows good agreement. Similar correspondence was found earlier using nine ice cores from the Summit region. These results indicate that the airborne laser altimeter provides an efficient platform for characterizing the statistical nature of the snow surface over large areas of the polar ice sheets

Switching to nonhyperbolic cycles from codim 2 bifurcations of equilibria in ODEs

The paper provides full algorithmic details on switching to the continuation of all possible codim 1 cycle bifurcations from generic codim 2 equilibrium bifurcation points in n-dimensional ODEs. We discuss the implementation and the performance of the algorithm in several examples, including an extended Lorenz-84 model and a laser system.Comment: 17 pages, 7 figures, submitted to Physica

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution