Signal integration between IFN gamma and TLR signalling pathways in macrophages

Macrophages are major effector cells of the innate immune system, and appropriate regulation of macrophage function requires the integration of multiple signalling inputs derived from the recognition of host factors (e.g. interferon-gamma/IFN gamma) and pathogen products (e.g. toll-like receptor/TLR agonists). The profound effects of IFN gamma pre-treatment (priming) on TLR-induced macrophage activation have long been recognised, but many of the mechanisms underlying the priming phenotype have only recently been identified. This review summarises the known mechanisms of integration between the IFN gamma and TLR signalling pathways. Synergy occurs at multiple levels, ranging from signal recognition to convergence of signals at the promoters of target genes. In particular, the cross-talk between the IFN gamma and LPS and CpG DNA signalling pathways is discussed. (c) 2006 Elsevier GmbH. All rights reserved.

Binocular summation at contrast threshold:a new look

Contrast sensitivity is better with two eyes than one. The standard view is that thresholds are about 1.4 (v2) times better with two eyes, and that this arises from monocular responses that, near threshold, are proportional to the square of contrast, followed by binocular summation of the two monocular signals. However, estimates of the threshold ratio in the literature vary from about 1.2 to 1.9, and many early studies had methodological weaknesses. We collected extensive new data, and applied a general model of binocular summation to interpret the threshold ratio. We used horizontal gratings (0.25 - 4 cycles deg-1) flickering sinusoidally (1 - 16 Hz), presented to one or both eyes through frame-alternating ferroelectric goggles with negligible cross-talk, and used a 2AFC staircase method to estimate contrast thresholds and psychometric slopes. Four naive observers completed 20 000 trials each, and their mean threshold ratios were 1.63, 1.69, 1.71, 1.81 - grand mean 1.71 - well above the classical v2. Mean ratios tended to be slightly lower (~1.60) at low spatial or high temporal frequencies. We modelled contrast detection very simply by assuming a single binocular mechanism whose response is proportional to (Lm + Rm) p, followed by fixed additive noise, where L,R are contrasts in the left and right eyes, and m, p are constants. Contrast-gain-control effects were assumed to be negligible near threshold. On this model the threshold ratio is 2(?1/m), implying that m=1.3 on average, while the Weibull psychometric slope (median 3.28) equals 1.247mp, yielding p=2.0. Together, the model and data suggest that, at low contrasts across a wide spatiotemporal frequency range, monocular pathways are nearly linear in their contrast response (m close to 1), while a strongly accelerating nonlinearity (p=2, a 'soft threshold') occurs after binocular summation. [Supported by EPSRC project grant GR/S74515/01]

The interrogation and multiplexing of long period grating curvature sensors using a Bragg grating based, derivative spectroscopy technique

A long period grating is interrogated with a fibre Bragg grating using a derivative spectroscopy technique. A quasi-linear relationship between the output of the sensing scheme and the curvature experienced by the long period grating is demonstrated, with a sensitivity of 5.05 m and with an average curvature resolution of 2.9 × 10-2 m-1. In addition, the feasibility of multiplexing an in-line series of long period gratings with this interrogation scheme is demonstrated with two pairs of fibre Bragg gratings and long period gratings. With this arrangement the cross-talk error between channels was less than ± 2.4 × 10-3 m-1.

Novel glucose sensor based on enzymeimmobilized 81° tilted fiber grating

We demonstrate a novel glucose sensor based on an optical fiber grating with an excessively tilted index fringe structure and its surface modified by glucose oxidase (GOD). The aminopropyltriethoxysilane (APTES) was utilized as binding site for the subsequent GOD immobilization. Confocal microscopy and fluorescence microscope were used to provide the assessment of the effectiveness in modifying the fiber surface. The resonance wavelength of the sensor exhibited red-shift after the binding of the APTES and GOD to the fiber surface and also in the glucose detection process. The red-shift of the resonance wavelength showed a good linear response to the glucose concentration with a sensitivity of 0.298nm(mg/ml)-1 in the very low concentration range of 0.0∼3.0mg/ml. Compared to the previously reported glucose sensor based on the GOD-immobilized long period grating (LPG), the 81° tilted fiber grating (81°-TFG) based sensor has shown a lower thermal cross-talk effect, better linearity and higher Q-factor in sensing response. In addition, its sensitivity for glucose concentration can be further improved by increasing the grating length and/or choosing a higher-order cladding mode for detection. Potentially, the proposed techniques based on 81°-TFG can be developed as sensitive, label free and micro-structural sensors for applications in food safety, disease diagnosis, clinical analysis and environmental monitoring.

1-Tb/s DWDM amplification in a fiber optical parametric amplifier

We report less than 1-dB cross-talk penalty for 26 DWDM channels modulated at 43.7 Gb/s RZ-DPSK when amplified by a fiber optical parametric amplifier showing compatibility with high-capacity (> 1 Tb/s) communication systems. © 2010 Optical Society of America.

1-Tb/s DWDM amplification in a fiber optical parametric amplifier

We report less than 1-dB cross-talk penalty for 26 DWDM channels modulated at 43.7 Gb/s RZ-DPSK when amplified by a fiber optical parametric amplifier showing compatibility with high-capacity (> 1 Tb/s) communication systems. © 2010 Optical Society of America.

The interrogation and multiplexing of long period grating curvature sensors using a Bragg grating based, derivative spectroscopy technique

A long period grating is interrogated with a fibre Bragg grating using a derivative spectroscopy technique. A quasi-linear relationship between the output of the sensing scheme and the curvature experienced by the long period grating is demonstrated, with a sensitivity of 5.05 m and with an average curvature resolution of 2.9 × 10-2 m-1. In addition, the feasibility of multiplexing an in-line series of long period gratings with this interrogation scheme is demonstrated with two pairs of fibre Bragg gratings and long period gratings. With this arrangement the cross-talk error between channels was less than ± 2.4 × 10-3 m-1.

Nonlinear inverse synthesis and eigenvalue division multiplexing in optical fiber channels

We scrutinize the concept of integrable nonlinear communication channels, resurrecting and extending the idea of eigenvalue communications in a novel context of nonsoliton coherent optical communications. Using the integrable nonlinear Schrödinger equation as a channel model, we introduce a new approach - the nonlinear inverse synthesis method - for digital signal processing based on encoding the information directly onto the nonlinear signal spectrum. The latter evolves trivially and linearly along the transmission line, thus, providing an effective eigenvalue division multiplexing with no nonlinear channel cross talk. The general approach is illustrated with a coherent optical orthogonal frequency division multiplexing transmission format. We show how the strategy based upon the inverse scattering transform method can be geared for the creation of new efficient coding and modulation standards for the nonlinear channel. © Published by the American Physical Society.

The use of erythrocytic and animal models in the study of protein phosphorylation

Phosphorylation processes are common post-transductional mechanisms, by which it is possible to modulate a number of metabolic pathways. Proteins are highly sensitive to phosphorylation, which governs many protein-protein interactions. The enzymatic activity of some protein tyrosine-kinases is under tyrosine-phosphorylation control, as well as several transmembrane anion-fluxes and cation exchanges. In addition, phosphorylation reactions are involved in intra and extra-cellular 'cross-talk' processes. Early studies adopted laboratory animals to study these little known phosphorylation processes. The main difficulty encountered with these animal techniques was obtaining sufficient kinase or phosphatase activity suitable for studying the enzymatic process. Large amounts of biological material from organs, such as the liver and spleen were necessary to conduct such work with protein kinases. Subsequent studies revealed the ubiquity and complexity of phosphorylation processes and techniques evolved from early rat studies to the adaptation of more rewarding in vitro models. These involved human erythrocytes, which are a convenient source both for the enzymes, we investigated and for their substrates. This preliminary work facilitated the development of more advanced phosphorylative models that are based on cell lines. © 2005 Elsevier B.V. All rights reserved.

Experimental full duplex simultaneous transmission of LTE over a DWDM directly modulated RoF system

In this paper, we experimentally demonstrate the seamless integration of full duplex system frequency division duplex (FDD) long-term evolution (LTE) technology with radio over fiber (RoF) for eNodeB (eNB) coverage extension. LTE is composed of quadrature phase-shift keying (QPSK), 16-quadrature amplitude modulation (16-QAM) and 64-QAM, modulated onto orthogonal frequency division multiplexing (OFDM) and single-carrier-frequency division multiplexing for downlink (DL) and uplink (UL) transmissions, respectively. The RoF system is composed of dedicated directly modulated lasers for DL and UL with dense wavelength division multiplexing (DWDM) for instantaneous connections and for Rayleigh backscattering and nonlinear interference mitigation. DL and UL signals have varying carrier frequencies and are categorized as broad frequency spacing (BFS), intermediate frequency spacing (IFS), and narrow frequency spacing (NFS). The adjacent channel leakage ratio (ACLR) for DL and UL with 64-QAM are similar for all frequency spacings while cross talk is observed for NFS. For the best case scenario for DL and UL transmissions we achieve error vector magnitude (EVM) values of ~2.30%, ~2.33%, and ~2.39% for QPSK, 16-QAM, and 64-QAM, respectively, while for the worst case scenario with a NFS EVM is increased by 0.40% for all schemes. © 2009-2012 OSA.

Nonlinear inverse synthesis for high spectral efficiency transmission in optical fibers

In linear communication channels, spectral components (modes) defined by the Fourier transform of the signal propagate without interactions with each other. In certain nonlinear channels, such as the one modelled by the classical nonlinear Schrödinger equation, there are nonlinear modes (nonlinear signal spectrum) that also propagate without interacting with each other and without corresponding nonlinear cross talk, effectively, in a linear manner. Here, we describe in a constructive way how to introduce such nonlinear modes for a given input signal. We investigate the performance of the nonlinear inverse synthesis (NIS) method, in which the information is encoded directly onto the continuous part of the nonlinear signal spectrum. This transmission technique, combined with the appropriate distributed Raman amplification, can provide an effective eigenvalue division multiplexing with high spectral efficiency, thanks to highly suppressed channel cross talk. The proposed NIS approach can be integrated with any modulation formats. Here, we demonstrate numerically the feasibility of merging the NIS technique in a burst mode with high spectral efficiency methods, such as orthogonal frequency division multiplexing and Nyquist pulse shaping with advanced modulation formats (e.g., QPSK, 16QAM, and 64QAM), showing a performance improvement up to 4.5 dB, which is comparable to results achievable with multi-step per span digital back propagation.

Reflectionless potentials for slow whispering gallery modes in surface nanoscale axial photonic fiber resonators

We consider an optical fiber with a nanoscale variation of the effective fiber radius that supports whispering gallery modes slowly propagating along the fiber, and reveal that the radius variation can be designed to support the reflectionless propagation of these modes. We show that reflectionless modulations can realize control of the transmission amplitude and temporal delay, while enabling close packing due to the absence of cross talk, in contrast to the conventional potentials.

Viral and bacterial septicaemic infections modulate the expression of PACAP splicing variants and VIP/PACAP receptors in brown trout immune organs

Copyright © 2015. Published by Elsevier Ltd. Acknowledgments The authors thank Richard Paley, Georgina Rimmer and Tom Hill for their contribution during the brown trout infection challenges carried out in CEFAS-Weymouth biosecurity facilities. Bartolomeo Gorgoglione and Nick G. H. Taylor were supported by a DEFRA contract C3490

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.

At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca(2+) response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain.

A Central Role for Monocyte-Platelet Interactions in Heart Failure

Heart failure (HF) is an increasingly prevalent and costly multifactorial syndrome with high morbidity and mortality rates. The exact pathophysiological mechanisms leading to the development of HF are not completely understood. Several emerging paradigms implicate cardiometabolic risk factors, inflammation, endothelial dysfunction, myocardial fibrosis, and myocyte dysfunction as key factors in the gradual progression from a healthy state to HF. Inflammation is now a recognized factor in disease progression in HF and a therapeutic target. Furthermore, the monocyte-platelet interaction has been highlighted as an important pathophysiological link between inflammation, thrombosis, endothelial activation, and myocardial malfunction. The contribution of monocytes and platelets to acute cardiovascular injury and acute HF is well established. However, their role and interaction in the pathogenesis of chronic HF are not well understood. In particular, the cross talk between monocytes and platelets in the peripheral circulation and in the vicinity of the vascular wall in the form of monocyte-platelet complexes (MPCs) may be a crucial element, which influences the pathophysiology and progression of chronic heart disease and HF. In this review, we discuss the role of monocytes and platelets as key mediators of cardiovascular inflammation in HF, the mechanisms of cell activation, and the importance of monocyte-platelet interaction and complexes in HF pathogenesis. Finally, we summarize recent information on pharmacological inhibition of inflammation and studies of antithrombotic strategies in the setting of HF that can inform opportunities for future work. We discuss recent data on monocyte-platelet interactions and the potential benefits of therapy directed at MPCs, particularly in the setting of HF with preserved ejection fraction.