Bidirectional transport between the trans-Golgi network and the endosomal system

The exchange of proteins and lipids between the trans-Golgi network (TGN) and the endosomal system requires multiple cellular machines, whose activities are coordinated in space and time to generate pleomorphic, tubulo-vesicular carriers that deliver their content to their target compartments. These machines and their associated protein networks are recruited and/or activated on specific membrane domains where they select proteins and lipids into carriers, contribute to deform/elongate and partition membrane domains using the mechanical forces generated by actin polymerization or movement along microtubules. The coordinated action of these protein networks contributes to regulate the dynamic state of multiple receptors recycling between the cell surface, endosomes and the TGN, to maintain cell homeostasis as exemplified by the biogenesis of lysosomes and related organelles, and to establish/maintain cell polarity. The dynamic assembly and disassembly of these protein networks mediating the exchange of membrane domains between the TGN and endosomes regulates cell-cell signalling and thus the development of multi-cellular organisms. Somatic mutations in single network components lead to changes in transport dynamics that may contribute to pathological modifications underlying several human diseases such as mental retardation.

Long-range translational coupling in single-stranded RNA bacteriophages: an evolutionary analysis

In coliphage MS2 RNA a long-distance interaction (LDI) between an internal segment of the upstream coat gene and the start region of the replicase gene prevents initiation of replicase synthesis in the absence of coat gene translation. Elongating ribosomes break up the repressor LDI and thus activate the hidden initiation site. Expression studies on partial MS2 cDNA clones identified base pairing between 1427-1433 and 1738-1744, the so-called Min Jou (MJ) interaction, as the molecular basis for the long-range coupling mechanism. Here, we examine the biological significance of this interaction for the control of replicase gene translation. The LDI was disrupted by mutations in the 3'-side and the evolutionary adaptation was monitored upon phage passaging. Two categories of pseudorevertants emerged. The first type had restored the MJ interaction but not necessarily the native sequence. The pseudorevertants of the second type acquired a compensatory substitution some 80 nt downstream of the MJ interaction that stabilizes an adjacent LDI. In one examined case we confirmed that the second site mutations had restored coat-replicase translational coupling. Our results show the importance of translational control for fitness of the phage. They also reveal that the structure that buries the replicase start extends to structure elements bordering the MJ interaction.

Toward the discovery of vaccine adjuvants:coupling in silico screening and in vitro analysis of antagonist binding to human and mouse CCR4 receptors

Background Adjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. Methodology Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of using virtual screening to identify potential small molecule chemokine antagonists. A combination of homology modelling and molecular docking was used to create a model of the CCR4 receptor in order to investigate potential lead compounds that display antagonistic properties. Three-dimensional structure-based virtual screening of the CCR4 receptor identified 116 small molecules that were calculated to have a high affinity for the receptor; these were tested experimentally for CCR4 antagonism. Fifteen of these small molecules were shown to inhibit specifically CCR4-mediated cell migration, including that of CCR4+ Tregs. Significance Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice.

Bidirectional nonreciprocal wavelength-interleaving coherent fiber transversal filter

A bidirectional nonreciprocal wavelength-interleaving filter based on an optically coherent high birefringence fiber transversal filter structure is demonstrated. Stable, low loss, low dispersion, and high isolation operation is demonstrated with reconfigurable transfer characteristics for interleaved channel spacing of 0.8 nm.

Photorefractive subharmonics - a beam-coupling effect?

Using the so-called ac field technique, we investigate experimentally the influence of optical beam coupling on the generation of subharmonic gratings in a photorefractive sillenite crystal. By the use of two different recording configurations, we are able to distinguish between effects caused by material nonlinearities and effects caused by optical beam coupling.

Influence of beam-coupling on photorefractive parametric oscillation in a dc-field-biased Bi12SiO20 crystal

The influence of beam coupling on photorefractive parametric oscillation generated in a Bi12SiO20 crystal is investigated experimentally by comparing two configurations with and without the presence of beam coupling. It is shown that beam coupling has a great influence; for example, the transversal split of the K/2 subharmonic grating is seen only in the beam-coupling geometry. A case that resembles K/4 subharmonic generation can, however, still be found in the absence of beam coupling.

Photorefractive subharmonics - a beam-coupling effect?

Using the so-called ac field technique, we investigate experimentally the influence of optical beam coupling on the generation of subharmonic gratings in a photorefractive sillenite crystal. By the use of two different recording configurations, we are able to distinguish between effects caused by material nonlinearities and effects caused by optical beam coupling.

Generation of spatial subharmonic gratings in the absence of photorefractive beam coupling

Using a new experimental geometry, we have proved for the first time that the generation of spatial subharmonic gratings in photorefractive crystals is not dependent on optical nonlinearity. We present results which confirm that the subharmonic gratings result from a parametric excitation of ultra low-frequency eigenmodes of a crystal by a time modulated fundamental grating.

Co-propagating cladding modes coupling assisted by tilted Bragg grating with large tilting angle

We report for the first time forward propagating cladding modes coupling by using tilted gratings. The spectral responses of these gratings were investigated and their thermal characteristics and sensitivity to environmental refractive index were evaluated.