The enteric nervous system contains excitatory and inhibitory neurons, which control contraction and relaxation of smooth muscle cells as well as gastrointestinal motor activity. Little is known about the exact cellular mechanisms of neuronal signal transduction to smooth muscle cells in the gut. Here we generate a c-Kit CreERT2 knock-in allele to target a distinct population of pacemaker cells called interstitial cells of Cajal. By genetic loss-of-function studies, we show that interstitial cells of Cajal, which generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature, are essential for transmission of signals from enteric neurons to gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore, integrate excitatory and inhibitory neurotransmission with slow-wave activity to orchestrate peristaltic motor activity of the gut. Impairment of the function of interstitial cells of Cajal causes severe gastrointestinal motor disorders. The results of our study show at the genetic level that these disorders are not only due to loss of slow-wave activity but also due to disturbed neurotransmission.

Tachykinins, an evolutionary conserved family of peptide hormones in both invertebrates and vertebrates, are produced by neuronal cells as inactive preprotachykinins that are post-translationally processed into different neuropeptides such as substance P, neurokinin A, and neurokinin B. We show here that furin-mediated cleavage of the bovine respiratory syncytial virus fusion protein results in the release of a peptide that is converted into a biologically active tachykinin (virokinin) by additional posttranslational modifications. An antibody directed to substance P cross-reacted with the C terminus of mature virokinin that contains a classical tachykinin motif. The cellular enzymes involved in the C-terminal maturation of virokinin were found to be present in many established cell lines. Virokinin is secreted by virus-infected cells and was found to act on the tachykinin receptor 1 (TACR1), leading to rapid desensitization of this G protein-coupled receptor as shown by TACR1-green fluorescent protein conjugate translocation from the cell surface to endosomes and by co-internalization of the receptor with ␤-arrestin 1-green fluorescent protein conjugates. In vitro experiments with isolated circular muscle from guinea pig stomach indicated that virokinin is capable of inducing smooth muscle contraction by acting on the tachykinin receptor 3. Tachykinins and their cognate receptors are present in the mammalian respiratory tract, where they have potent effects on local inflammatory and immune processes. The viral tachykinin-like peptide represents a novel form of molecular mimicry, which may benefit the virus by affecting the host immune response. Bovine respiratory syncytial virus (BRSV)1 and human respiratory syncytial virus (HRSV), two closely related RNA viruses of the family Paramyxoviridae, replicate in the lower respiratory tract, causing similar diseases in their respective hosts (1). Young calves and infants are particularly affected and suffer from obstructive bronchitis, wheezing, and hypoxemia. Damage of respiratory epithelial cells due to the infection itself probably plays a minor role in RSV pathogenesis (2). Rather, the inflammatory response triggered by cellular chemokines and cytokines that are released from RSV-infected epithelial cells and lymphocytes is believed to contribute to the severity of the disease (3-9).Several observations indicate that the adaptive immune response to RSV is incomplete and of short duration. Maternally derived virus-neutralizing antibodies do not provide sufficient protection from infection (10, 11). Reinfections, even by RSV of the same serogroup, occur repeatedly during childhood and throughout life (12, 13). There is also evidence that infection with HRSV contributes to increased airway hyperresponsiveness and asthma (14 -17). Recent data suggest that RSV has immunosuppressive properties. In the mouse model, HRSV infection causes suppression of lung CD8 ϩ T-cell effector activity and inhibition of pulmonary CD8 ϩ T-cell memory development (18). In BRSV-infected la...

This paper concerns continuous nondisturbing estimation of blood pressure using mechanical plethysmography in connection with standard electrocardiography (ECG). The plethysmography is given by a novel magnetoelastic skin curvature sensor (SC-sensor) applied on the neck over the carotid artery. The sensor consists of a magnetoelastic bilayer partly enclosed by a coil. Bending the bilayer causes large changes of magnetic permeability which can be measured by the coil. The SC-sensor signal and the ECG signal are adaptively processed in order to estimate blood pressure according to a specifically established theoretical model. The model uses estimated vessel radius changes and pulse transit time as parameters. The results show cross correlation coefficients in the range 0.8 up to 0.9 between reference and estimated values of systolic blood pressure, diastolic blood pressure, and systolic/diastolic blood pressure change, whereas the estimation error was below 4 + 7 mmHg at rest and increased with the stress level. Limitations of the model applicability are given by a hysteretic behavior of both model parameters due to inert changes in artery stiffness. The SC-sensor and the ECG electrodes cause minimal inconvenience to the patient and offer an approach for a continuous nondisturbing monitoring of blood pressure changes, as being relevant for sleep monitoring or biomechanic feedback.Index Terms-Blood pressure, electrocardiography, magnetoelastic amorphous ribbons, mechanical plethysmography, physiological sensors, skin curvature sensor.

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