Phenotypic and Genotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Related to Persistent Endovascular Infection.

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and genotypic profiles. For instance, PB strains exhibit less susceptibility to cationic host defense peptides and vancomycin (VAN) killing under in vivo-like conditions, greater damage to endothelial cells, thicker biofilm formation, altered growth rates, early activation of many global virulence regulons (e.g., sigB, sarA, sae and agr) and higher expression of purine biosynthesis genes (e.g., purF) than RB strains. Importantly, PB strains are significantly more resistant to VAN treatment in experimental infective endocarditis as compared to RB strains, despite similar VAN minimum inhibitory concentrations (MICs) in vitro. Here, we review relevant phenotypic and genotypic characteristics related to the PB outcome. These and future insights may improve our understanding of the specific mechanism(s) contributing to the PB outcome, and aid in the development of novel therapeutic and preventative measures against this life-threatening infection

KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation.

KDM2B (also known as FBXL10) controls stem cell self-renewal, somatic cell reprogramming and senescence, and tumorigenesis. KDM2B contains multiple functional domains, including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zinc-finger that recognizes CpG islands and recruits the polycomb repressive complex 1. Here, we report that KDM2B, via its F-box domain, functions as a subunit of the CUL1-RING ubiquitin ligase (CRL1/SCF(KDM2B)) complex. KDM2B targets c-Fos for polyubiquitylation and regulates c-Fos protein levels. Unlike the phosphorylation of other SCF (SKP1-CUL1-F-box)/CRL1 substrates that promotes substrates binding to F-box, epidermal growth factor (EGF)-induced c-Fos S374 phosphorylation dissociates c-Fos from KDM2B and stabilizes c-Fos protein. Non-phosphorylatable and phosphomimetic mutations at S374 result in c-Fos protein which cannot be induced by EGF or accumulates constitutively and lead to decreased or increased cell proliferation, respectively. Multiple tumor-derived KDM2B mutations impaired the function of KDM2B to target c-Fos degradation and to suppress cell proliferation. These results reveal a novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations

Monte Carlo Calculations for Liquid 4^4He at Negative Pressure

A Quadratic Diffusion Monte Carlo method has been used to obtain the equation of state of liquid $^4$He including the negative pressure region down to the spinodal point. The atomic interaction used is a renewed version (HFD-B(HE)) of the Aziz potential, which reproduces quite accurately the features of the experimental equation of state. The spinodal pressure has been calculated and the behavior of the sound velociy around the spinodal density has been analyzed.Comment: 10 pages, RevTex 3.0, with 4 PostScript figures include

Soil greenhouse gas fluxes and net global warming potential from intensively cultivated vegetable fields in southwestern China

Session 2: Nitrogen, Green House Gasses and Agricultur

Humanoid Balancing Behavior Featured by Underactuated Foot Motion

A novel control synthesis is proposed for humanoids to demonstrate unique foot-tilting behaviors that are comparable to humans in balance recovery. Our study of model-based behaviors explains the underlying mechanism and the significance of foot tilting well. Our main algorithms are composed of impedance control at the center of mass, virtual stoppers that prevent overtilting of the feet, and postural control for the torso. The proof of concept focuses on the sagittal scenario and the proposed control is effective to produce human-like balancing behaviors characterized by active foot tilting. The successful replication of this behavior on a real humanoid proves the feasibility of deliberately controlled underactuation. The experimental validation was rigorously performed, and the data from the submodules and the entire control were presented and analyzed

Early agr activation correlates with vancomycin treatment failure in multi-clonotype MRSA endovascular infections

Objectives Persistent MRSA infections are especially relevant to endovascular infections and correlate with suboptimal outcomes. However, the virulence signatures of Staphylococcus aureus that drive such persistence outcomes are not well defined. In the current study, we investigated correlations between accessory gene regulator (agr) activation and the outcome of vancomycin treatment in an experimental model of infective endocarditis (IE) due to MRSA strains with different agr and clonal complex (CC) types. Methods Twelve isolates with the four most common MRSA CC and agr types (CC5-agr II, CC8-agr I, CC30-agr III and CC45-agr I) were evaluated for heterogeneous vancomycin-intermediate S. aureus (hVISA), agr function, agrA and RNAIII transcription, agr locus sequences, virulence and response to vancomycin in the IE model. Results Early agr RNAIII activation (beginning at 2 h of growth) in parallel with strong δ-haemolysin production correlated with persistent outcomes in the IE model following vancomycin therapy. Importantly, such treatment failures occurred across the range of CC/agr types studied. In addition, these MRSA strains: (i) were vancomycin susceptible in vitro; (ii) were not hVISA or vancomycin tolerant; and (iii) did not evolve hVISA phenotypes or perturbed δ-haemolysin activity in vivo following vancomycin therapy. Moreover, agr locus sequence analyses revealed no common point mutations that correlated with either temporal RNAIII transcription or vancomycin treatment outcomes, encompassing different CC and agr types. Conclusions These data suggest that temporal agr RNAIII activation and agr functional profiles may be useful biomarkers to predict the in vivo persistence of endovascular MRSA infections despite vancomycin therap

Induced magnetization in La0.7_{0.7}Sr0.3_{0.3}MnO3_3/BiFeO3_3 superlattices

Using polarized neutron reflectometry (PNR), we observe an induced magnetization of 75$\pm$ 25 kA/m at 10 K in a La$_{0.7}$Sr$_{0.3}$MnO$_3$ (LSMO)/BiFeO$_3$ superlattice extending from the interface through several atomic layers of the BiFeO$_3$ (BFO). The induced magnetization in BFO is explained by density functional theory, where the size of bandgap of BFO plays an important role. Considering a classical exchange field between the LSMO and BFO layers, we further show that magnetization is expected to extend throughout the BFO, which provides a theoretical explanation for the results of the neutron scattering experiment.Comment: 5 pages, 4 figures, with Supplemental Materials. To appear in Physical Review Letter