The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy

Estrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response to endocrine therapy. Current endocrine therapies for ER-positive breast cancers target ER function at multiple levels. These include targeting the level of estrogen, blocking estrogen action at the ER, and decreasing ER levels. However, the ultimate effectiveness of therapy is limited by either intrinsic or acquired resistance. Identifying the factors and pathways responsible for sensitivity and resistance remains a challenge in improving the treatment of breast cancer. With a better understanding of coordinated action of ER, its coregulatory factors, and the influence of other intracellular signaling cascades, improvements in breast cancer therapy are emerging

Bacterial Flagella: Twist and Stick, or Dodge across the Kingdoms

The flagellum organelle is an intricate multiprotein assembly best known for its rotational propulsion of bacteria. However, recent studies have expanded our knowledge of other functions in pathogenic contexts, particularly adherence and immune modulation, e.g., for Salmonella enterica, Campylobacter jejuni, Pseudomonas aeruginosa, and Escherichia coli. Flagella-mediated adherence is important in host colonisation for several plant and animal pathogens, but the specific interactions that promote flagella binding to such diverse host tissues has remained elusive. Recent work has shown that the organelles act like probes that find favourable surface topologies to initiate binding. An emerging theme is that more general properties, such as ionic charge of repetitive binding epitopes and rotational force, allow interactions with plasma membrane components. At the same time, flagellin monomers are important inducers of plant and animal innate immunity: variation in their recognition impacts the course and outcome of infections in hosts from both kingdoms. Bacteria have evolved different strategies to evade or even promote this specific recognition, with some important differences shown for phytopathogens. These studies have provided a wider appreciation of the functions of bacterial flagella in the context of both plant and animal reservoirs

Dimension hopping and families of strictly positive definite zonal basis functions on spheres

Positive definite functions of compact support are widely used for radial basis function approximation as well as for estimation of spatial processes in geostatistics. Several constructions of such functions for Rd are based upon recurrence operators. These map functions of such type in a given space dimension onto similar ones in a space of lower or higher dimension. We provide analogs of these dimension hopping operators for positive definite, and strictly positive definite, zonal (radial) functions on the sphere. These operators are then used to provide new families of strictly positive definite functions with local support on the sphere

Remarks on Meshless Local Construction of Surfaces

This contribution deals with techniques for the construction of surfaces from N given data at irregularly distributed locations. Such methods should ideally have the properties computational eciency, smoothness of the resulting surface, if required, and quality of reproduction, but these goals turn out to be hard to meet by a single algorithm. Methods are split into a single construction or precalculation part and subsequent pointwise evaluations. Both parts are analyzed with respect to their complexity. It turns out that one has to expect the main workload on the side of geometric subproblems rather than within numerical techniques. Furthermore, if exact reconstruction at the data locations is required, and if the user wants to avoid solving non{local linear systems, there is no way around localized Langrange{type interpolation formulae. Thus two instances of such techniques are studied in some detail: interpolation by weighted local Lagrangians based on radial ..

Reconstructing multivariate functions from large data sets

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