Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways

The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice. Cav-3 deficiency fully abrogated serotonin-induced constriction of extrapulmonary airways in organ baths while leaving intrapulmonary airways unaffected, as assessed in precision cut lung slices. The selective expression of cav-3 in tracheal, but not intrapulmonary bronchial epithelial cells, revealed by immunohistochemistry, might explain the differential effects of cav-3 deficiency on serotonergic ASM constriction. The cholinergic response of extrapulmonary airways was not altered, whereas a considerable increase was observed in cav-3â -/- intrapulmonary bronchi. Thus, cav-3 differentially organizes serotonergic and cholinergic signaling in ASM through mechanisms that are specific for airways of certain caliber and anatomical position. This may allow for selective and site-specific intervention in hyperreactive states

Thermalized Displaced and Squeezed Number States in Coordinate Representation

Within the framework of thermofield dynamics, the wavefunctions of the thermalized displaced number and squeezed number states are given in the coordinate representation. Furthermore, the time evolution of these wavefunctions is considered by introducing a thermal coordinate representation, and we also calculate the corresponding probability densities, average values and variances of position coordinate, which are consistent with results in the literature.Comment: 12 pages, no figures, Revtex. v3: substantially revise

Entangling macroscopic oscillators exploiting radiation pressure

It is shown that radiation pressure can be profitably used to entangle {\it macroscopic} oscillators like movable mirrors, using present technology. We prove a new sufficient criterion for entanglement and show that the achievable entanglement is robust against thermal noise. Its signature can be revealed using common optomechanical readout apparatus.Comment: 4 pages, 2 eps figures, new separability criterion added, new figure 2, authors list change

Generalized Husimi Functions: Analyticity and Information Content

The analytic properties of a class of generalized Husimi functions are discussed, with particular reference to the problem of state reconstruction. The class consists of the subset of Wodkiewicz's operational probability distributions for which the filter reference state is a squeezed vacuum state. The fact that the function is analytic means that perfectly precise knowledge of its values over any small region of phase space provides enough information to reconstruct the density matrix. If, however, one only has imprecise knowledge of its values, then the amplification of statistical errors which occurs when one attempts to carry out the continuation seriously limits the amount of information which can be extracted. To take account of this fact a distinction is made between explicate, or experimentally accessible information, and information which is only present in implicate, experimentally inaccessible form. It is shown that an explicate description of various aspects of the system can be found localised on various 2 real dimensional surfaces in complexified phase space. In particular, the continuation of the function to the purely imaginary part of complexified phase space provides an explicate description of the Wigner function.Comment: 16 pages, 2 figures, AMS-latex. Replaced with published versio

Questioning policy, youth participation and lifestyle sports

Young people have been identified as a key target group for whom participation in sport and physical activity could have important benefits to health and wellbeing and consequently have been the focus of several government policies to increase participation in the UK. Lifestyle sports represent one such strategy for encouraging and sustaining new engagements in sport and physical activity in youth groups, however, there is at present a lack of understanding of the use of these activities within policy contexts. This paper presents findings from a government initiative which sought to increase participation in sport for young people through provision of facilities for mountain biking in a forest in south-east England. Findings from qualitative research with 40 young people who participated in mountain biking at the case study location highlight the importance of non-traditional sports as a means to experience the natural environments through forms of consumption which are healthy, active and appeal to their identities. In addition, however, the paper raises questions over the accessibility of schemes for some individuals and social groups, and the ability to incorporate sports which are inherently participant-led into state-managed schemes. Lifestyle sports such as mountain biking involve distinct forms of participation which present a challenge for policy-makers who seek to create and maintain sustainable communities of youth participants

An integrated ChIP-seq analysis platform with customizable workflows

<p>Abstract</p> <p>Background</p> <p>Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq), enables unbiased and genome-wide mapping of protein-DNA interactions and epigenetic marks. The first step in ChIP-seq data analysis involves the identification of peaks (i.e., genomic locations with high density of mapped sequence reads). The next step consists of interpreting the biological meaning of the peaks through their association with known genes, pathways, regulatory elements, and integration with other experiments. Although several programs have been published for the analysis of ChIP-seq data, they often focus on the peak detection step and are usually not well suited for thorough, integrative analysis of the detected peaks.</p> <p>Results</p> <p>To address the peak interpretation challenge, we have developed ChIPseeqer, an integrative, comprehensive, fast and user-friendly computational framework for in-depth analysis of ChIP-seq datasets. The novelty of our approach is the capability to combine several computational tools in order to create easily customized workflows that can be adapted to the user's needs and objectives. In this paper, we describe the main components of the ChIPseeqer framework, and also demonstrate the utility and diversity of the analyses offered, by analyzing a published ChIP-seq dataset.</p> <p>Conclusions</p> <p>ChIPseeqer facilitates ChIP-seq data analysis by offering a flexible and powerful set of computational tools that can be used in combination with one another. The framework is freely available as a user-friendly GUI application, but all programs are also executable from the command line, thus providing flexibility and automatability for advanced users.</p

Preparation of nonclassical states in cavities with a moving mirror

Published versio

Subcycle Quantum Electrodynamics

Besides their stunning physical properties which are unmatched in a classical world, squeezed states of electromagnetic radiation bear advanced application potentials in quantum information systems and precision metrology, including gravitational wave detectors with unprecedented sensitivity. Since the first experiments on such nonclassical light, quantum analysis has been based on homodyning techniques and photon correlation measurements. These methods require a well-defined carrier frequency and photons contained in a quantum state need to be absorbed or amplified. They currently function in the visible to near-infrared and microwave spectral ranges. Quantum nondemolition experiments may be performed at the expense of excess fluctuations in another quadrature. Here we generate mid-infrared time-locked patterns of squeezed vacuum noise. After propagation through free space, the quantum fluctuations of the electric field are studied in the time domain by electro-optic sampling with few-femtosecond laser pulses. We directly compare the local noise amplitude to the level of bare vacuum fluctuations. This nonlinear approach operates off resonance without absorption or amplification of the field that is investigated. Subcycle intervals with noise level significantly below the pure quantum vacuum are found. Enhanced fluctuations in adjacent time segments manifest generation of highly correlated quantum radiation as a consequence of the uncertainty principle. Together with efforts in the far infrared, this work opens a window to the elementary quantum dynamics of light and matter in an energy range at the boundary between vacuum and thermal background conditions.Comment: 19 pages, 4 figure

Cell cycle-independent phospho-regulation of Fkh2 during hyphal growth regulates Candida albicans pathogenesis.

The opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Although previous gene-knockout studies have identified many factors involved in this transformation, it remains unclear how these factors are regulated to coordinate the switch. Investigating morphogenetic control by post-translational phosphorylation has generated important regulatory insights into this process, especially focusing on coordinated control by the cyclin-dependent kinase Cdc28. Here we have identified the Fkh2 transcription factor as a regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a role distinct from its conserved function in cell cycle progression. In stationary phase yeast cells 2D gel electrophoresis shows that there is a diverse pool of Fkh2 phospho-isoforms. For a short window on hyphal induction, far before START in the cell cycle, the phosphorylation profile is transformed before reverting to the yeast profile. This transformation does not occur when stationary phase cells are reinoculated into fresh medium supporting yeast growth. Mass spectrometry and mutational analyses identified residues phosphorylated by Cdc28 and Cbk1. Substitution of these residues with non-phosphorylatable alanine altered the yeast phosphorylation profile and abrogated the characteristic transformation to the hyphal profile. Transcript profiling of the phosphorylation site mutant revealed that the hyphal phosphorylation profile is required for the expression of genes involved in pathogenesis, host interaction and biofilm formation. We confirmed that these changes in gene expression resulted in corresponding defects in pathogenic processes. Furthermore, we identified that Fkh2 interacts with the chromatin modifier Pob3 in a phosphorylation-dependent manner, thereby providing a possible mechanism by which the phosphorylation of Fkh2 regulates its specificity. Thus, we have discovered a novel cell cycle-independent phospho-regulatory event that subverts a key component of the cell cycle machinery to a role in the switch from commensalism to pathogenicity