Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity

“Heteroresistance” describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. Unfortunately, a lack of standard methods to determine heteroresistance has led to inappropriate use of this term. Heteroresistance has been recognized since at least 1947 and occurs in Gram-positive and Gram-negative bacteria. Its clinical relevance may be considerable, since more resistant subpopulations may be selected during antimicrobial therapy. However, the use of nonstandard methods to define heteroresistance, which are costly and involve considerable labor and resources, precludes evaluating the clinical magnitude and severity of this phenomenon. We review the available literature on antibiotic heteroresistance and propose recommendations for definitions and determination criteria for heteroresistant bacteria. This will help in assessing the global clinical impact of heteroresistance and developing uniform guidelines for improved therapeutic outcomes

Heat conduction and thermal stress analysis of laminated composites by a variable kinematic MITC9 shell element

The present paper considers the linear static thermal stress analysis of composite structures by means of a shell finite element with variable through-thethickness kinematic. The temperature profile along the thickness direction is calculated by solving the Fourier heat conduction equation. The refined models considered are both Equivalent Single Layer (ESL) and Layer Wise (LW) and are grouped in the Unified Formulation by Carrera (CUF). These permit the distribution of displacements, stresses along the thickness of the multilayered shell to be accurately described. The shell element has nine nodes, and the Mixed Interpolation of Tensorial Components (MITC) method is used to contrast the membrane and shear locking phenomenon. The governing equations are derived from the Principle of Virtual Displacement (PVD). Cross-ply plate, cylindrical and spherical shells with simply-supported edges and subjected to bi-sinusoidal thermal load are analyzed.Various thickness ratios and curvature ratios are considered. The results, obtained with different theories contained in the CUF, are compared with both the elasticity solutions given in the literature and the analytical solutions obtained using the CUF and the Navier’s method. Finally, plates and shells with different lamination and boundary conditions are analyzed using high-order theories in order to provide FEM benchmark solutions

Western diet-like culture conditions and oxidative stress on a cell model of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a major health burden in the Western world, as the Western diet (WD) appears to be the driving force of this disease. However, the individual contributions of the diet and the impacts of their individual metabolism are currently ill-defined. This study used HepG2 cells to understand the impact of the individual components of WD in early NAFLD development under basal insulin levels. Specifically, nutrient-induced changes in reactive oxygen species (ROS) and signaling pathways, such as sterol regulatory element binding proteins (SREBPs), were examined to identify the root cause of steatosis development. High-fat and WD-exposed cells were associated with triglyceride and lipid droplet accumulation, paired with changes in SREBPs and lipid processing genes. These cells displayed hallmarks of lipotoxicity, such as decreased cell number and increased ROS. Together, this work unravels the maladaptive phenotypes associated with WD consumption, as these events may be critical in the onset of NAFLD pathogenesis

Substrate specificity of bacterial oligosaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems

The PgIB oligosaccharyltransferase (OTase) of Campylobacter jejuni can be functionally expressed in Escherichia coli, and its relaxed oligosaccharide substrate specificity allows the transfer of different glycans from the lipid carrier undecaprenyl pyrophosphate to an acceptor protein. To investigate the substrate specificity of PgIB, we tested the transfer of a set of lipid-linked polysaccharides in E. coli and Salmonella enterica serovar Typhimurium. A hexose linked to the C-6 of the monosaccharide at the reducing end did not inhibit the transfer of the O antigen to the acceptor protein. However, PgIB required an acetamido group at the C-2. A model for the mechanism of PgIB involving this functional group was proposed. Previous experiments have shown that eukaryotic OTases have the same requirement, suggesting that eukaryotic and prokaryotic OTases catalyze the transfer of oligosaccharides by a conserved mechanism. Moreover, we demonstrated the functional transfer of the C. jejuni glycosylation system into S. enterica. The elucidation of the mechanism of action and the substrate specificity of PgIB represents the foundation for engineering glycoproteins that will have an impact on biotechnology