Titratable residues that drive RND efflux: Insights from molecular simulations.

The resistance-nodulation-division efflux machinery confers antimicrobial resistance to Gram-negative bacteria by actively pumping antibiotics out of the cell. The protein complex is powered by proton motive force; however, the proton transfer mechanism itself and indeed even its stoichiometry is still unclear. Here we review computational studies from the last decade that focus on elucidating the number of protons transferred per conformational cycle of the pump.

Dual function of OmpM as outer membrane tether and nutrient uptake channel in diderm Firmicutes.

The outer membrane (OM) in diderm, or Gram-negative, bacteria must be tethered to peptidoglycan for mechanical stability and to maintain cell morphology. Most diderm phyla from the Terrabacteria group have recently been shown to lack well-characterised OM attachment systems, but instead have OmpM, which could represent an ancestral tethering system in bacteria. Here, we have determined the structure of the most abundant OmpM protein from Veillonella parvula (diderm Firmicutes) by single particle cryogenic electron microscopy.

Computational microbiology of bacteria: Advancements in molecular dynamics simulations.

Microbiology is traditionally considered within the context of wet laboratory methodologies. Computational techniques have a great potential to contribute to microbiology. Here, we describe our loose definition of "computational microbiology" and provide a short survey focused on molecular dynamics simulations of bacterial systems that fall within this definition.

Conformational dynamics and putative substrate extrusion pathways of the N-glycosylated outer membrane factor CmeC from Campylobacter jejuni.

The outer membrane factor CmeC of the efflux machinery CmeABC plays an important role in conferring antibiotic and bile resistance to Campylobacter jejuni. Curiously, the protein is N-glycosylated, with the glycans playing a key role in the effective function of this system. In this work we have employed atomistic equilibrium molecular dynamics simulations of CmeC in a representative model of the C.

A novel fold for acyltransferase-3 (AT3) proteins provides a framework for transmembrane acyl-group transfer.

Acylation of diverse carbohydrates occurs across all domains of life and can be catalysed by proteins with a membrane bound acyltransferase-3 (AT3) domain (PF01757). In bacteria, these proteins are essential in processes including symbiosis, resistance to viruses and antimicrobials, and biosynthesis of antibiotics, yet their structure and mechanism are largely unknown. In this study, evolutionary co-variance analysis was used to build a computational model of the structure of a bacterial O-antigen modifying acetyltransferase, OafB.

The role of polarizability in the interfacial thermal conductance at the gold-water interface.

We have studied the interfacial thermal conductance, G, of the flat Au(111)-water interface using non-equilibrium molecular dynamics simulations. We utilized two metal models, one based on the embedded atom method (EAM) and the other including metallic polarizability via a density readjusting EAM. These were combined with three popular water models, SPC/E, TIP4P, and TIP4P-FQ, to understand the role of polarizability in the thermal transport process.

Real space electrostatics for multipoles. III. Dielectric properties.

In Papers I and II, we developed new shifted potential, gradient shifted force, and Taylor shifted force real-space methods for multipole interactions in condensed phase simulations. Here, we discuss the dielectric properties of fluids that emerge from simulations using these methods. Most electrostatic methods (including the Ewald sum) require correction to the conducting boundary fluctuation formula for the static dielectric constants, and we discuss the derivation of these corrections for the new real space methods.

Real space electrostatics for multipoles. II. Comparisons with the Ewald sum.

We report on tests of the shifted potential (SP), gradient shifted force (GSF), and Taylor shifted force (TSF) real-space methods for multipole interactions developed in Paper I of this series, using the multipolar Ewald sum as a reference method. The tests were carried out in a variety of condensed-phase environments designed to test up to quadrupole-quadrupole interactions. Comparisons of the energy differences between configurations, molecular forces, and torques were used to analyze how well the real-space models perform relative to the more computationally expensive Ewald treatment.

Real space electrostatics for multipoles. I. Development of methods.

We have extended the original damped-shifted force (DSF) electrostatic kernel and have been able to derive three new electrostatic potentials for higher-order multipoles that are based on truncated Taylor expansions around the cutoff radius. These include a shifted potential (SP) that generalizes the Wolf method for point multipoles, and Taylor-shifted force (TSF) and gradient-shifted force (GSF) potentials that are both generalizations of DSF electrostatics for multipoles. We find that each of the distinct orientational contributions requires a separate radial function to ensure that pairwise energies, forces, and torques all vanish at the cutoff radius.

Injuries in elite and recreational snowboarders.

Background: The relatively young sport of snowboarding exhibits high injury rates. The current efforts to characterise the injury pattern of snowboarders focus largely on the general snowboard population and upper extremity injuries, the most common injury site in snowboarders as a whole.

Methods: In an effort to describe the current published information available on snowboarding injuries in the elite-level population, a literature search was performed and the articles related to snowboarding injuries were analysed.

Heterogeneity of tibial plateau cartilage in response to a physiological compressive strain rate.

Knowledge of the extent to which tibial plateau cartilage displays non-uniform mechanical topography under physiologically relevant loading conditions is critical to evaluating the role of biomechanics in knee osteoarthritis. Cartilage explants from 21 tibial plateau sites of eight non-osteoarthritic female cadaveric knees (age: 41-54; BMI: 14-20) were tested in unconfined compression at 100% strain/s. The elastic tangent modulus at 10% strain (E(10%) ) was calculated for each site and averaged over four geographic regions: not covered by meniscus (I); covered by meniscus-anterior (II); covered by meniscus-exterior (III); and covered by meniscus-posterior (IV).

The absence of ABCD2 sensitizes mice to disruptions in lipid metabolism by dietary erucic acid.

ABCD2 (D2) is a peroxisomal transporter that is highly abundant in adipose tissue and promotes the oxidation of long-chain MUFA. Erucic acid (EA, 22:1ω9) reduces very long chain saturated fatty acids in patients with X-linked adrenoleukodystrophy but promotes dyslipidemia and dilated cardiomyopathy in rats. To determine the role of D2 in the metabolism of EA, we challenged wild-type and D2 deficient mice (D2 KO) with an enriched EA diet.

Bulk and Surface Properties of Rutile TiO2 from Self-Consistent-Charge Density Functional Tight Binding.

Bulk rutile TiO2 and its (110) surface have been investigated with a computationally efficient semiempirical tight binding method: self-consistent-charge density functional tight binding (SCC-DFTB). Comparisons of energetic, mechanical, and electronic properties are made to density functional theory (DFT) and to experiment to characterize the accuracy of SCC-DFTB for bulk rutile TiO2 and TiO2(110). Despite the fact that the SCC-DFTB parameters for Ti, Ti-Ti, and Ti-O were developed in the context of small biologically relevant Ti containing compounds, SCC-DFTB predicts many properties of bulk TiO2 and the TiO2(110) surface with accuracy similar to local and gradient-corrected DFT.

Invited review: the role of caterpillars in mare reproductive loss syndrome: a model for environmental causes of abortion.

A new abortigenic disease, now known as mare reproductive loss syndrome (MRLS), significantly affected the horse industry in the Ohio River Valley of the United States in late April and early May of 2001 and 2002. In 2001, approximately 25% of all pregnant mares aborted within several weeks (over 3,000 mares lost pregnancies), and abortion rates exceeded 60% on some farms. Mare reproductive loss syndrome struck hard and without warning, it was caused by something in the environment, it was not transmitted between animals, and it was not associated with any known abortigenic agent or disease.

Immune parameters of dry cows fed mannan oligosaccharide and subsequent transfer of immunity to calves.

The objective of this study was to evaluate the benefits of supplementation of mannan oligosaccharide (MOS) to cows during the last 3 wk of the dry period on immune function of the cows and subsequent transfer of passive immunity to their calves. Indicators of nonspecific and specific immunity were evaluated. Cows were vaccinated against rotavirus at 4 and 2 wk before expected parturition.

Effects of dietary mannan oligosaccharide, bacitracin methylene disalicylate, or both on the live performance and intestinal microbiology of turkeys.

Hybrid male turkeys were fed to 18 wk of age in a completely randomized design with 10 replicate pens (18 birds each) per treatment to compare growth promoters. Four dietary treatments were used: negative control (CON), bacitracin methylene disalicyate (BMD) at 55 mg/kg to 6 wk and 27.5 mg/kg thereafter, mannan oligosaccharide (MOS) at 0.

The effects of dietary mannaoligosaccharides on cecal parameters and the concentrations of enteric bacteria in the ceca of salmonella-challenged broiler chicks.

The ability of different enteric pathogens and coliforms to trigger agglutination of yeast cells (Saccharomyces cerevisiae, NCYC 1026) and a yeast cell wall preparation (MOS) was examined. Five of seven strains of Escherichia coli and 7 of 10 strains of Salmonella typhimurium and Salmonella enteritidis agglutinated MOS and Sac. cerevisiae cells.