Coordinated Regulation by AgrA, SarA, and SarR To Control agr Expression in Staphylococcus aureus

The agr locus of Staphylococcus aureus is composed of two divergent transcripts (RNAII and RNAIII) driven by the P2 and P3 promoters. The P2-P3 intergenic region comprises the SarA/SarR binding sites and the four AgrA boxes to which AgrA binds. We reported here the role of AgrA, SarA, and SarR on agr P2 and P3 transcription. Using real-time reverse transcription (RT)-PCR and promoter fusion studies with selected single, double, triple, and complemented mutants, we showed that AgrA is indispensable to agr P2 and P3 transcription, whereas SarA activates and SarR represses P2 transcription. In vitro runoff transcription assays revealed that AgrA alone promoted transcription from the agr P2 promoter, with SarA enhancing it and SarR inhibiting agr P2 transcription in the presence of AgrA or with SarA and AgrA. Electrophoretic mobility shift assay (EMSA) analysis disclosed that SarR binds more avidly to the agr promoter than SarA and displaces SarA from the agr promoter. Additionally, SarA and AgrA bend the agr P2 promoter, whereas SarR does not. Collectively, these data indicated that AgrA activates agr P2 and P3 promoters while SarA activates the P2 promoter, presumably via bending of promoter DNA to bring together AgrA dimers to facilitate engagement of RNA polymerase (RNAP) to initiate transcription

Production of Fusaric Acid by Fusarium spp. in Pure Culture and in Solid Medium Co-Cultures.

The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species in co-culture revealed de novo induction of fusaric acid based on HRMS. Structure confirmation of this toxin, using sensitive microflow NMR, required only three 9-cm Petri dishes of fungal culture. A targeted metabolomics study based on UHPLC-HRMS confirmed that the production of fusaric acid was strain-dependent. Furthermore, the detected toxin levels suggested that onychomycosis-associated fungal strains of the F. oxysporum and F. fujikuroi species complexes are much more frequently producing fusaric acid, and in higher amount, than strains of the F. solani species complex. Fusarium strains producing no significant amounts of this compound in pure culture, were shown to de novo produce that compound when grown in co-culture. The role of fusaric acid in fungal virulence and defense is discussed

Terbinafine Resistance of Trichophyton Clinical Isolates Caused by Specific Point Mutations in the Squalene Epoxidase Gene.

Terbinafine is one of the allylamine antifungal agents whose target is squalene epoxidase (SQLE). This agent has been extensively used in the therapy of dermatophyte infections. The incidence of patients with tinea pedis or unguium tolerant to terbinafine treatment prompted us to screen the terbinafine resistance of all javax.xml.bind.JAXBElement@dc06fb4 clinical isolates from the laboratory of the Centre Hospitalier Universitaire Vaudois collected over a 3-year period and to identify their mechanism of resistance. Among 2,056 tested isolates, 17 (≈1%) showed reduced terbinafine susceptibility, and all of these were found to harbor javax.xml.bind.JAXBElement@374d721c gene alleles with different single point mutations, leading to single amino acid substitutions at one of four positions (Leu javax.xml.bind.JAXBElement@4655f570 , Phe javax.xml.bind.JAXBElement@112b804a , Phe javax.xml.bind.JAXBElement@1f18e014 , and His javax.xml.bind.JAXBElement@4319ac79 ) of the SQLE protein. Point mutations leading to the corresponding amino acid substitutions were introduced into the endogenous javax.xml.bind.JAXBElement@2a0e3f1f gene of a terbinafine-sensitive javax.xml.bind.JAXBElement@67eac3c4 (formerly javax.xml.bind.JAXBElement@3f2a876d ) strain. All of the generated javax.xml.bind.JAXBElement@315e9e95 transformants expressing mutated SQLE proteins exhibited obvious terbinafine-resistant phenotypes compared to the phenotypes of the parent strain and of transformants expressing wild-type SQLE proteins. Nearly identical phenotypes were also observed in javax.xml.bind.JAXBElement@6af3a966 transformants expressing mutant forms of javax.xml.bind.JAXBElement@5bb6b31f SQLE proteins. Considering that the genome size of dermatophytes is about 22 Mb, the frequency of terbinafine-resistant clinical isolates was strikingly high. Increased exposure to antifungal drugs could favor the generation of resistant strains

Spectroscopy, Interactions and Level Splittings in Au Nanoparticles

We have measured the electronic energy spectra of nm-scale Au particles using a new tunneling spectroscopy configuration. The particle diameters ranged from 5nm to 9nm, and at low energies the spectrum is discrete, as expected by the electron-in-a-box model. The density of tunneling resonances increases rapidly with energy, and at higher energies the resonances overlap forming broad resonances. Near the Thouless energy, the broad resonances merge into a continuum. The tunneling resonances display Zeeman splitting in a magnetic field. Surprisingly, the g-factors (~0.3) of energy levels in Au nano-particles are much smaller than the g-factor (2.1) in bulk gold

A lattice in more than two Kac--Moody groups is arithmetic

Let $\Gamma$ be an irreducible lattice in a product of n infinite irreducible complete Kac-Moody groups of simply laced type over finite fields. We show that if n is at least 3, then each Kac-Moody groups is in fact a simple algebraic group over a local field and $\Gamma$ is an arithmetic lattice. This relies on the following alternative which is satisfied by any irreducible lattice provided n is at least 2: either $\Gamma$ is an S-arithmetic (hence linear) group, or it is not residually finite. In that case, it is even virtually simple when the ground field is large enough. More general CAT(0) groups are also considered throughout.Comment: Subsection 2.B was modified and an example was added ther

Near surface nutrient and phytoplankton distribution in the Drake Passage during early December

Nutrient concentrations and phytoplankton species composition in near surface samples were studied along a S-N gradient in the Drake Passage, in early December 1984. Nitrate concentrations were much lower than usually previously reported from circum-Antarctic waters. Comparison of dissolved nutrient concentrations with growth requirements of Antarctic plankton algae suggests potential limitation of at least some species by nitrate or silicate. The taxonomic composition of the phytoplankton in our samples seemed to be partially controlled by competition for limiting nutrients

Superconducting gap node spectroscopy using nonlinear electrodynamics

We present a method to determine the nodal structure of the energy gap of unconventional superconductors such as high $T_c$ materials. We show how nonlinear electrodynamics phenomena in the Meissner regime, arising from the presence of lines on the Fermi surface where the superconducting energy gap is very small or zero, can be used to perform ``node spectroscopy'', that is, as a sensitive bulk probe to locate the angular position of those lines. In calculating the nonlinear supercurrent response, we include the effects of orthorhombic distortion and $a-b$ plane anisotropy. Analytic results presented demonstrate a systematic way to experimentally distinguish order parameters of different symmetries, including cases with mixed symmetry (for example, $d+s$ and $s+id$). We consider, as suggested by various experiments, order parameters with predominantly $d$-wave character, and describe how to determine the possible presence of other symmetries. The nonlinear magnetic moment displays a distinct behavior if nodes in the gap are absent but regions with small, finite, values of the energy gap exist.Comment: 18 pages, Revtex, 9 postscript figures. Submitted to Phys. Rev

Strongly coupled quantum criticality with a Fermi surface in two dimensions: fractionalization of spin and charge collective modes

We describe two dimensional models with a metallic Fermi surface which display quantum phase transitions controlled by strongly interacting critical field theories below their upper critical dimension. The primary examples involve transitions with a topological order parameter associated with dislocations in collinear spin density wave ("stripe") correlations: the gapping of the order parameter fluctuations leads to a fractionalization of spin and charge collective modes, and this transition has been proposed as a candidate for the cuprates near optimal doping. The coupling between the order parameter and long-wavelength volume and shape deformations of the Fermi surface is analyzed by the renormalization group, and a runaway flow to a non-perturbative regime is found in most cases. A phenomenological scaling analysis of simple observable properties of possible second order quantum critical points is presented, with results quite similar to those near quantum spin glass transitions and to phenomenological forms proposed by Schroeder et al. (cond-mat/0011002).Comment: 16 pages, 4 figures; (v2) additional clarifying remark

Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

Midgap edge states and pairing symmetry of quasi-one-dimensional organic superconductors

The singlet s-, d- and triplet p-wave pairing symmetries in quasi-one-dimensional organic superconductors can be experimentally discriminated by probing the Andreev bound states at the sample edges. These states have the energy in the middle of the superconducting gap and manifest themselves as a zero-bias peak in tunneling conductance into the corresponding edge. Their existence is related to the sign change of the pairing potential around the Fermi surface. We present an exact self-consistent solution of the edge problem showing the presence of the midgap states for p_x-wave superconductivity. The spins of the edge state respond paramagnetically to a magnetic field parallel to the vector d that characterizes triplet pairing.Comment: 6 pages, 4 figures. V.2: New section on spin response is added and references are updated. V.3: Final version accepted to PRB. Typos are corrected and important note is added in proof