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G cells in the antrum region of the murine stomach produce gastrin, the central hormone for controlling gastric activities. Secretion of gastrin is induced mainly by protein breakdown products but also by distensions of the stomach wall. Although G cells respond to protein fragments via distinct chemosensory receptor types, the mechanism underlying G cell activation upon distention is entirely ambiguous. Mechanosensitive ion channels are considered as potential candidates for such a task. Therefore, we explore the possibility of whether Piezo1, a polymodal sensor for diverse mechanical forces, is expressed in antral G cells. The experimental analyses revealed that the vast majority of G cells indeed expressed Piezo1. Within flask-like G cells at the base of the antral invaginations, the Piezo1 protein was primarily located at the basolateral portion, which is thought to be the release site for the exocytic secretion of gastrin. In the spindle-like G cells, which are oriented parallel to the invaginations, Piezo1 protein was restricted to the cell body where the hormone was also located, whereas the long processes appeared to be devoid of Piezo1 protein. Our results suggest that mechanosensitive channels such as Piezo1, located in close proximity to hormone-release sites, enable G cells to respond directly to antrum distensions with gastrin secretion. [ABSTRACT FROM AUTHOR]

Cochlear implants are neuroprostheses that are inserted into the inner ear to directly electrically stimulate the auditory nerve, thus replacing lost cochlear receptors, the hair cells. The reduction of the gap between electrodes and nerve cells will contribute to technological solutions simultaneously increasing the frequency resolution, the sound quality and the amplification of the signal. Recent findings indicate that neurotrophins (NTs) such as brain derived neurotrophic factor (BDNF) stimulate the neurite outgrowth of auditory nerve cells by activating Trk receptors on the cellular surface (1–3). Furthermore, small-size TrkB receptor agonists such as di-hydroxyflavone (DHF) are now available, which activate the TrkB receptor with similar efficiency as BDNF, but are much more stable (4). Experimentally, such molecules are currently used to attract nerve cells towards, for example, the electrodes of cochlear implants. This paper analyses the scenarios of low dose aspects of controlled release of small-size Trk receptor agonists from the coated CI electrode array into the inner ear. The control must first ensure a sufficient dose for the onset of neurite growth. Secondly, a gradient in concentration needs to be maintained to allow directive growth of neurites through the perilymph-filled gap towards the electrodes of the implant. We used fluorescein as a test molecule for its molecular size similarity to DHF and investigated two different transport mechanisms of drug dispensing, which both have the potential to fulfil controlled low-throughput drug-deliverable requirements. The first is based on the release of aqueous fluorescein into water through well-defined 60-μm size holes arrays in a membrane by pure osmosis. The release was both simulated using the software COMSOL and observed experimentally. In the second approach, solid fluorescein crystals were encapsulated in a thin layer of parylene (PPX), hence creating random nanometer-sized pinholes. In this approach, the release occurred due to subsequent water diffusion through the pinholes, dissolution of the fluorescein and then release by out-diffusion. Surprisingly, the release rate of solid fluorescein through the nanoscopic scale holes was found to be in the same order of magnitude as for liquid fluorescein release through microscopic holes. [ABSTRACT FROM AUTHOR]

Accurate numerical weather prediction of intense snowfall events requires the correct representation of dynamical and physical processes on various scales. In this study, a specific event of high-impact wet snowfall is examined that occurred in the northwestern part of Germany in November 2005. First, the synoptic evolution is presented, together with observations of precipitation type and vertical temperature profiles, which reveal the existence of a so-called potential melting layer during the early period of wet snowfall. During the main part, the performance of the operational forecasts from the European Centre for Medium-Range Weather Forecasts (ECMWF) is investigated. It is shown that only the short-term predictions captured the snowfall event, whereas earlier forecasts were in error concerning the phase and/or amount of precipitation. However, even the short-term forecasts produced the onset of surface snowfall too late (i.e., during the dry snowfall period). Reasons for the misforecasts are errors on various scales. For the early forecasts, they include an inaccurate representation of the upper-level trough and a misplacement of the surface cyclone. For the later forecasts, a slight overestimation of the depth of the potential melting layer and a potentially too fast snow melting process in the model lead to the erroneous prediction of surface rainfall during the wet snowfall period. Hindcast experiments with the high-resolution Consortium for Small-Scale Modeling (COSMO) model also point to the necessity of improving its snow melting parameterization in order to provide useful predictions of potentially high-impact wet snowfall events. [ABSTRACT FROM AUTHOR]

Background Histological analysis of the cochlea is required to understand the physiological and pathological processes in the inner ear. In the past, many embedding techniques have been tested in the cochlea to find an optimal protocol that gives both good morphological and immunohistochemical results. Resins provide high quality cochlear morphology with reduced immunogenicity due to the higher polymerization temperature. New method We used Technovit 9100 New ® , a low temperature embedding system based on methyl methacrylate, on adult guinea pig and mouse cochleae to evaluate preservation of the morphology and maintenance of the antigenicity. Results Conventional toluidine blue staining, as well as immunohistochemical staining with a set of commonly used antibodies, showed highly preserved morphology and immunogenicity of decalcified adult guinea pig and mouse cochleae. Comparison with existing method(s) We demonstrate both, well-preserved morphology and preservation of antigenicity, superior to other embedding techniques. Conclusions Our results showed that the Technovit 9100 New ® embedding system provided highly preserved morphology and immunogenicity with our protocol in adult guinea pig and mouse cochleae. [ABSTRACT FROM AUTHOR]

Background: The spatial gap between cochlear implants (CIs) and the auditory nerve limits frequency selectivity as large populations of spiral ganglion neurons (SGNs) are electrically stimulated synchronously. To improve CI performance, a possible strategy is to promote neurite outgrowth toward the CI, thereby allowing a discrete stimulation of small SGN subpopulations. Brain-derived neurotrophic factor (BDNF) is effective to stimulate neurite outgrowth from SGNs., Method: TrkB (tropomyosin receptor kinase B) agonists, BDNF, and five known small-molecule BDNF mimetics were tested for their efficacy in stimulating neurite outgrowth in postnatal SGN explants. To modulate Trk receptor-mediated effects, TrkB and TrkC ligands were scavenged by an excess of recombinant receptor proteins. The pan-Trk inhibitor K252a was used to block Trk receptor actions., Results: THF (7,8,3'-trihydroxyflavone) partly reproduced the BDNF effect in postnatal day 7 (P7) mouse cochlear spiral ganglion explants (SGEs), but failed to show effectiveness in P4 SGEs. During the same postnatal period, spontaneous and BDNF-stimulated neurite outgrowth increased. The increased neurite outgrowth in P7 SGEs was not caused by the TrkB/TrkC ligands, BDNF and neurotrophin-3 (NT-3)., Conclusions: The age-dependency of induction of neurite outgrowth in SGEs was very likely dependent on presently unidentified factors and/or molecular mechanisms which may also be decisive for the age-dependent efficacy of the small-molecule TrkB receptor agonist THF.

Chemokines belong to a superfamily of small, cytokine-like proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20 (CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer (CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.