Role of PknB Kinase in Antibiotic Resistance and Virulence in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain USA300

The regulation of cellular processes by eukaryote-like serine/threonine kinases is widespread in bacteria. In the last 2 years, several studies have examined the role of serine/threonine kinases in Staphylococcus aureus on cell wall metabolism, autolysis, and virulence, mostly in S. aureus laboratory isolates in the 8325-4 lineage. In this study, we showed that the pknB gene (also called stk1) of methicillin-resistant S. aureus (MRSA) strain COL and the community-acquired MRSA (CA-MRSA) strain USA300 is involved in cell wall metabolism, with the pknB mutant exhibiting enhanced sensitivity to β-lactam antibiotics but not to other classes of antibiotics, including aminoglycosides, ciprofloxacin, bactrim, and other types of cell wall-active agents (e.g., vancomycin and bacitracin). Additionally, the pknB mutant of USA300 was found to be more resistant to Triton X-100-induced autolysis and also to lysis by lysostaphin. We also showed that pknB is a positive regulator of sigB activity, resulting in compromise in its response to heat and oxidative stresses. In association with reduced sigB activity, the expression levels of RNAII and RNAIII of agr and the downstream effector hla are upregulated while spa expression is downmodulated in the pknB mutant compared to the level in the parent. Consistent with an enhanced agr response in vitro, virulence studies of the pknB mutant of USA300 in a murine cutaneous model of infection showed that the mutant was more virulent than the parental strain. Collectively, our results have linked the pknB gene in CA-MRSA to antibiotic resistance, sigB activity, and virulence and have highlighted important differences in pknB phenotypes (virulence and sigB activity) between laboratory isolates and the prototypic CA-MRSA strain USA300

Sensitivity of a VIRGO pair to stochastic GW backgrounds

The sensitivity of a pair of VIRGO interferometers to gravitational waves backgrounds (GW) of cosmological origin is analyzed for the cases of maximal and minimal overlap of the two detectors. The improvements in the detectability prospects of scale-invariant and non-scale-invariant logarithmic energy spectra of relic GW are discussed.Comment: 25 pages in RevTex style with 6 figure

Response of VIRGO detectors to pre-big-bang gravitons

The sensitivity achievable by a pair of VIRGO detectors to stochastic and isotropic gravitational wave backgrounds produced in pre-big-bang models is discussed in view of the development of a second VIRGO interferometer. We describe a semi-analytical technique allowing to compute the signal-to-noise ratio for (monotonic or non-monotonic) logarithmic energy spectra of relic gravitons of arbitrary slope. We apply our results to the case of two correlated and coaligned VIRGO detectors and we compute their achievable sensitivities. We perform our calculations both for the usual case of minimal string cosmological scenario and in the case of a non-minimal scenario where a long dilaton dominated phase is present prior to the onset of the ordinary radiation dominated phase. In this framework, we investigate possible improvements of the achievable sensitivities by selective reduction of the thermal contributions (pendulum and pendulum's internal modes) to the noise power spectra of the detectors. Since a reduction of the shot noise does not increase significantly the expected sensitivity of a VIRGO pair (in spite of the relative spatial location of the two detectors) our findings support the experimental efforts directed towards a substantial reduction of thermal noise.Comment: 23 pages in Latex styl

Fully automated convolutional neural network-based affine algorithm improves liver registration and lesion co-localization on hepatobiliary phase T1-weighted MR images.

BackgroundLiver alignment between series/exams is challenged by dynamic morphology or variability in patient positioning or motion. Image registration can improve image interpretation and lesion co-localization. We assessed the performance of a convolutional neural network algorithm to register cross-sectional liver imaging series and compared its performance to manual image registration.MethodsThree hundred fourteen patients, including internal and external datasets, who underwent gadoxetate disodium-enhanced magnetic resonance imaging for clinical care from 2011 to 2018, were retrospectively selected. Automated registration was applied to all 2,663 within-patient series pairs derived from these datasets. Additionally, 100 within-patient series pairs from the internal dataset were independently manually registered by expert readers. Liver overlap, image correlation, and intra-observation distances for manual versus automated registrations were compared using paired t tests. Influence of patient demographics, imaging characteristics, and liver uptake function was evaluated using univariate and multivariate mixed models.ResultsCompared to the manual, automated registration produced significantly lower intra-observation distance (p < 0.001) and higher liver overlap and image correlation (p < 0.001). Intra-exam automated registration achieved 0.88 mean liver overlap and 0.44 mean image correlation for the internal dataset and 0.91 and 0.41, respectively, for the external dataset. For inter-exam registration, mean overlap was 0.81 and image correlation 0.41. Older age, female sex, greater inter-series time interval, differing uptake, and greater voxel size differences independently reduced automated registration performance (p ≤ 0.020).ConclusionA fully automated algorithm accurately registered the liver within and between examinations, yielding better liver and focal observation co-localization compared to manual registration

Are heterotrophic and silica-rich eukaryotic microbes an important part of the lichen symbiosis?

We speculate that heterotrophic and/or silica-rich eukaryotic microorganisms maybe an important part of the lichen symbiosis. None of the very few studies of heterotrophic protists associated with lichens have considered the possibility that they may be of functional significance in the lichen symbiosis. Here we start to develop, currently speculative, theoretical ideas about their potential significance. For example, all the protist taxa identified in lichens we sampled in Ohio USA depend on silica for growth and construction of their cell walls, this could suggest that silica-rich lichen symbionts may be significant in the biogeochemistry of the lichen symbiosis. We also present arguments suggesting a role for protists in nitrogen cycling within lichen thalli and a potential role in controlling bacterial populations associated with lichens. In this necessarily speculative paper we highlight areas for future research and how newer technologies may be useful for understanding the full suite of organisms involved in the lichen symbiosis. Keywords: lichens; protists; symbiosis; testate amoebae; diatom; chrysophyt

Chemistry-induced Intrinsic Stress Variations During the Chemical Vapor Deposition of Polycrystalline Diamond

Intrinsic tensile stresses in polycrystalline films are often attributed to the coalescence of neighboring grains during the early stages of film growth, where the energy decrease associated with converting two free surfaces into a grain boundary provides the driving force for creating tensile stress. Several recent models have analyzed this energy trade off to establish relationships between the stress and the surface∕interfacial energy driving force, the elastic properties of the film, and the grain size. To investigate these predictions, experiments were conducted with diamond films produced by chemical vapor deposition. A multistep processing procedure was used to produce films with significant variations in the tensile stress, but with essentially identical grain sizes. The experimental results demonstrate that modest changes in the deposition chemistry can lead to significant changes in the resultant tensile stresses. Two general approaches were considered to reconcile this data with existing models of stress evolution. Geometric effects associated with the shape of the growing crystal were evaluated with a finite element model of stress evolution, and variations in the surface∕interfacial energy driving force were assessed in terms of both chemical changes in the deposition atmosphere and differences in the crystal growth morphology. These attempts to explain the experimental results were only partially successful, which suggests that other factors probably affect intrinsic tensile stress evolution due to grain boundary formation

Weak Liouville-Arnold Theorems & Their Implications

This paper studies the existence of invariant smooth Lagrangian graphs for Tonelli Hamiltonian systems with symmetries. In particular, we consider Tonelli Hamiltonians with n independent but not necessarily involutive constants of motion and obtain two theorems reminiscent of the Liouville-Arnold theorem. Moreover, we also obtain results on the structure of the configuration spaces of such systems that are reminiscent of results on the configuration space of completely integrable Tonelli Hamiltonians.Comment: 24 pages, 1 figure; v2 corrects typo in online abstract; v3 includes new title (was: A Weak Liouville-Arnold Theorem), re-arrangement of introduction, re-numbering of main theorems; v4 updates the authors' email and physical addresses, clarifies notation in section 4. Final versio

Harmonizing Lipidomics: NIST Interlaboratory Comparison Exercise for Lipidomics Using SRM 1950-metabolites in Frozen Human Plasma

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement

Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

Abstract 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed [1] -hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20- HETE on mesenchymal stem cell (MSC)-derived adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1–1 M) increased adipogenesis in a dose dependent manner in these cells ( P \u3c 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE 2 , enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE 2 resulted in the increased expression of the adipogenic regulators PPAR and -catenin in MSC-derived adipocytes. Taken together we show for the fi rst time that 20-HETE-derived COX-2-dependent 20-OH-PGE 2 enhances mature infl amed adipocyte hypertrophy in MSC undergoing adipogenic differentiation. — Kim, D. H., N. Puri, K. Sodhi, J. R. Falck, N. G. Abraham, J. Shapiro, and M. L. Schwartzman. Cyclooxygenase-2 dependent metabolism of 20-HETE increasesadiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

An Extended Grid of Nova Models: II. The Parameter Space of Nova Outbursts

This paper is a sequel to an earlier paper devoted to multiple, multicycle nova evolution models (Prialnik & Kovetz 1995, first paper of the series), which showed that the different characteristics of nova outbursts can be reproduced by varying the values of three basic and independent parameters: the white dwarf mass-M_{WD}, the temperature of its isothermal core-T_{WD} and the mass transfer rate-Mdot. Apart from being the largest computational classical novae parameter-space survey, we show here that the parameter space is constrained by several analytical considerations and find its limiting surfaces. Consequently, we extend the grid of multicycle nova evolution models presented in Paper I almost to its limits, adding multicycle nova outburst calculations for a considerable number of new parameter combinations. In particular, the extended parameter pace that produces nova eruptions includes low mass transfer rates down to 5e-13 Msun/yr, and more models for low T_{WD}. Resulting characteristics of these runs are added to the former parameter combination results, to provide a full grid spanning the entire parameter space for Carbon-Oxygen white dwarfs. The full grid covers the entire range of observed nova characteristics, even those of peculiar objects, which have not been numerically reproduced until now. Most remarkably, runs for very low Mdot lead to very high values for some characteristics, such as outburst amplitude A>~20, high super-Eddington luminosities at maximum, heavy element abundance of the ejecta Z_{ej}~0.63 and high ejected masses m_{ej}~7e-4 Msun.Comment: Accepted for publication in ApJ - 04/2005. Complete grid results (Tables 2+3) data available at: http://geophysics.tau.ac.il/personal/oferya/ under "Publications