Exploring the role of the Kölliker-Fuse nucleus in breathing variability by mathematical modelling.

The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. KEY POINTS: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

Assessing normal pulse wave velocity in the proximal pulmonary arteries using transit time: a feasibility, repeatability, and observer reproducibility study by cardiovascular magnetic resonance.

PURPOSE: To calculate pulse wave velocity (PWV) in the proximal pulmonary arteries (PAs) by cardiovascular magnetic resonance (CMR) using the transit-time method, and address respiratory variation, repeatability, and observer reproducibility. MATERIALS AND METHODS: A 1.9-msec interleaved phase velocity sequence was repeated three times consecutively in 10 normal subjects. Pulse wave (PW) arrival times (ATs) were determined for the main and branch PAs. The PWV was calculated by dividing the path length traveled by the difference in ATs. Respiratory variation was considered by comparing acquisitions with and without respiratory gating. RESULTS: For navigated data the mean PWVs for the left PA (LPA) and right PA (RPA) were 2.09 +/- 0.64 m/second and 2.33 +/- 0.44 m/second, respectively. For non-navigated data the mean PWVs for the LPA and RPA were 2.14 +/- 0.41 m/second and 2.31 +/- 0.49 m/second, respectively. No statistically significant difference was found between respiratory non-navigated data and navigated data. Repeated on-table measurements were consistent (LPA non-navigated P = 0.95, RPA non-navigated P = 0.91, LPA navigated P = 0.96, RPA navigated P = 0.51). The coefficients of variation (CVs) were 12.2% and 12.5% for intra- and interobserver assessments, respectively. CONCLUSION: One can measure PWV in the proximal PAs using transit-time in a reproducible manner without respiratory gating.

Attachment of oral bacteria to a basement-membrane-like matrix and to purified matrix proteins.

The purpose of this study was to investigate the adherence of oral bacteria to an in vitro basement-membrane-like matrix and to selected individual macromolecular constituents of this matrix. Radiolabeled bacteria were incubated with basement-membrane-like matrices isolated from PF HR-9 cells. Bacteroides gingivalis 33277, Fusobacterium nucleatum FN-2, and Actinobacillus actinomycetemcomitans GA3(A) bound to the matrix in the range of 44 to 70%, considerably higher than the ranges of A. actinomycetemcomitans GA3(NA) and SUNY AB67 (range, 20 to 25%). The attachment of selected strains of gram-positive bacteria such as Streptococcus and Actinomyces spp. was much less frequent (range, 6 to 25%). Competitive inhibition studies demonstrated that preincubating the bacteria with fibronectin significantly decreased the binding of B. gingivalis by 51% but increased the binding of other gram-negative and gram-positive organisms tested. Similarly, preincubating the matrices with antifibronectin antibodies decreased the binding of B. gingivalis by 31%, whereas the other bacteria tested were either unaffected or binding was increased. The adherence of bacteria to purified basement membrane proteins was also investigated. Strain and species differences were seen in binding, but no clear relationship emerged between binding to an intact matrix and binding to isolated matrix proteins. The results of this study suggest that some gram-negative oral bacteria commonly associated with periodontal disease, such as B. gingivalis, A. actinomycetemcomitans, and F. nucleatum, bound in high numbers to basement-membrane-like matrices in vitro. On the other hand, the gram-positive strains tested bound in much fewer numbers. The results suggest that further studies with this in vitro model may aid in understanding the mechanisms by which oral bacteria adhere to basement membranes.