Constitutive Overexpression of Muscarinic Receptors Leads to Vagal Hyperreactivity

BACKGROUND: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE) activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS). Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity. Rabbits with marked vagal pauses following injection of phenylephrine were selected and crossed to obtain a vagal hyperreactive strain. The density of cardiac muscarinic receptors and acetylcholinesterase (AchE) gene expression were assessed. Blood markers of the observed cardiac abnormalities were also sought. METHODOLOGY/PRINCIPAL FINDINGS: Cardiac muscarinic M(2) and M(3) receptors were overexpressed in hyperreactive rabbits compared to control animals (2.3-fold and 2.5-fold, respectively) and the severity of the phenylephrine-induced bradycardia was correlated with their densities. A similar overexpression of M(2) receptors was observed in peripheral mononuclear white blood cells, suggesting that cardiac M(2) receptor expression can be inferred with high confidence from measurements in blood cells. Sequencing of the coding fragment of the M(2) receptor gene revealed a single nucleotide mutation in 83% of hyperreactive animals, possibly contributing for the transcript overexpression. Significant increases in AchE expression and activity were also assessed (AchE mRNA amplification ratio of 3.6 versus normal rabbits). This phenomenon might represent a compensatory consequence of muscarinic receptors overexpression. Alterations in M(2) receptor and AchE expression occurred between the 5th and the 7th week of age, a critical period also characterized by a higher mortality rate of hyperreactive rabbits (52% in H rabbits versus 13% in normal rabbits) and preceeded the appearance of functional disorders. CONCLUSIONS/SIGNIFICANCE: The results suggest that cardiac muscarinic receptor overexpression plays a critical role in the development of vagal hyperreactivity, whereas AchE hyperactivity appears as a compensatory consequence of it. Since similar vagal disorders were observed recently by us in SIDS, muscarinic receptor overexpression could become a marker of risk of vasovagal syncopes and SIDS

Complete Genome Sequences of Three Novel Pseudomonas fluorescens SBW25 Bacteriophages, Noxifer, Phabio, and Skulduggery.

Three novel bacteriophages, two of which are jumbophages, were isolated from compost in Auckland, New Zealand. Noxifer, Phabio, and Skulduggery are double-stranded DNA (dsDNA) phages with genome sizes of 278,136 bp (Noxifer), 309,157 bp (Phabio), and 62,978 bp (Skulduggery).Published onlin

Assessment of metal implant induced artefacts using photon counting spectral CT

The aim is to perform qualitative and quantitative assessment of metal induced artefacts of small titanium biomaterials using photon counting spectral CT. The energy binning feature of some photon counting detectors enables the measured spectrum to be segmented into low, mid and high energy bins in a single exposure. In this study, solid and porous titanium implants submerged in different concentrations of calcium solution were scanned using the small animal MARS photon counting spectral scanner equipped with a polyenergetic X-ray source operated at 118 kVp. Five narrow energy bins (7-45 keV, 45-55 keV, 55-65 keV, 65-75 keV and 75-118 keV) in charge summing mode were utilised. Images were evaluated in the energy domain (spectroscopic images) as well as material domain (material segmentation and quantification). Results show that calcium solution outside titanium implants can be accurately quantified. However, there was an overestimation of calcium within the pores of the scaffold. This information is critical as it can severely limit the assessment of bone ingrowth within metal structures. The energy binning feature of the spectral scanner was exploited and a correction factor, based on calcium concentrations adjacent to and within metal structures, was used to minimise the variation. Qualitative and quantitative evaluation of bone density and morphology with and without titanium screw shows that photon counting spectral CT can assess bone-metal interface with less pronounced artefacts. Quantification of bone growth in and around the implants would help in orthopaedic applications to determine the effectiveness of implant treatment and assessment of fracture healing

Medipix3RX neutron camera for ambient radiation measurements in the CMS cavern

We describe a CMS-Medipix3RX neutron camera developed by adapting and modifying detector readout electronics developed at the University of Canterbury. The readout electronics are part of the MARS x-ray scanner used for imaging applications [1]. The neutron cameras will be used for the precise evaluation of complex radiation fields in and around the Compact Muon Solenoid (CMS) detector on the Large Hadron Collider (LHC) at CERN. This evaluation will help to ascertain the performance of various sub-systems installed in the cavern as well as to predict their useful lifetimes. Medipix3RX detector can deliver real-time images of the flux and spectral composition of different particles, including slow and fast neutrons. In this neutron camera, slow neutrons are detected using a lithium fluoride conversion layer and fast neutrons by a polypropylene layer. These produce charged particles, which are then detected by a semiconductor sensor material, silicon. We modelled the mixed-field radiation at seven Medipix detector locations in the cavern by scoring the particle travelling through the detector location using FOCUS, a Monte-Carlo simulation tool, analysing the energy as well as their angular distributions of neutrons from the result of simulations.A good agreement was observed between the average flux predicted by standard FLUKA methods and those obtained from FOCUS output data integrated over time. Also, the response function of the Medipix detectors was modelled and simulated for different thicknesses of the neutron conversion layer. An algorithm was developed for track reconstruction and recognition using cluster analysis techniques. This labels and determines the density of clusters formed by groups of particles. The CMS-Medipix detectors with their conversion layers were calibrated in the CERN neutron facility and installed in the CMS cavern at the beginning of 2018. This paper discusses the calibration of the detector installation and presents early results of radiation measurements from 2018 run