Investigations into the organisation and morphology of vagal preganglionic neurones and the anatomical identification of the chemistry and origin of some of their synaptic inputs

The investigations in this thesis involve the use of neuroanatomical techniques in the study of vagal preganglionic neurones (VPNs) in the medulla oblongata of the rat and cat. Light microscopic examination of VPNs identified by the injection of horseradish peroxidase (HRP) into the cervical vagus nerve of the rat revealed that they lay mainly in two areas of the medulla - the dorsal vagal nucleus (DVN) and the nucleus ambiguus (NA). Labelled cells in the DVN (median diameter 18jim) were arranged in a tightly packed group. In contrast, labelled neurones in the NA were arranged in two identifiable groups. The most dorsal of these groups consisted of tightly packed cells with median diameter of 30μm (compact group - cNA) whereas the other group were smaller (median D 25μm) and were scattered in ventrolateral regions of the medulla (vINA). Neurones in each group were identified as being statistically different in diameter and soma area from those in other groups (Student's t-test). Cardiac vagal preganglionic neurones (CVPNs), retrogradely labelled by the injection of cholera toxin-HRP into the right atrium, were located mainly in the vINA with median soma diameter 25μm. Ultrastructural examination of the groups of VPNs revealed that they shared some morphological characteristics. VPNs in the NA, particularly those in the vINA, were observed to be intermingled with neurones retrogradely labelled from the phrenic motor nucleus in the spinal cord and were often morphologically indistinguishable. VPNs in the NA were also intermingled with neuropeptide Y immunoreactive neurones. The chemistry of inputs to VPNs was examined using a combination of retrograde tracing to identify VPNs, immunocytochemistry to detect various neurotransmitter chemicals, and electron microscopy. Serotonin, substance P and neuropeptide Y were identified in boutons forming asymmetric type synaptic contacts with VPNs in the nucleus ambiguus of the rat which were retrogradely labelled from the heart or the cervical vagus nerve. The origin of inputs to VPNs was investigated by the ionophoretic injection of HRP into regions of the cat ventral medulla where antidromic potentials were recorded to stimulation of the cervical vagus nerve. Retrogradely labelled cells were localised both contralaterally and ipsilateral ly in the nucleus tractus solitarius, raphe nuclei, parabrachial nucleus, periaqueductal gray matter and the NA. To determine if the NTS was a source of synaptic input to VPNs in the NA, VPNs were identified by retrograde tracing followed by the ionophoretic injection of the anterograde tracer biocytin into regions of the NTS where evoked potentials were recorded to stimulation of the carotid sinus or cervical vagus nerve. Light microscopic examination revealed anterogradely labelled boutons and fibres in the NA, some of which were in close association with retrogradely labelled VPNs. Subsequent electron microscopic examination revealed some of these boutons form synaptic specialisations with retrogradely labelled VPNs

War research projects : A. A Study of pro knock activity. B. The dynamic sorption of ammonia and butane on charcoal.

Various compounds were investigated to determine their pro knock activity by adding them to the air intake of, or to the gasoline used by and Ethyl 30 B Knock Testing Engine. The best compound tested was arsenic tri chloride which requires 5.8 parts per million of air by volume to cause a decrease of ten octane units in a leaded gasoline. It was found that the best knock inducer elements were in order of effectiveness: arsenic, antimony and phosphorous. Mercury, vanadium and chromium were also found to be effective. Among the radicals the halogens were most effective, the order being bromine, chlorine, iodine and fluorine. Effectiveness of halogens appeared to be enhanced by the presence of a nitro and methyl groups. [...] The dynamic sorption of butane and amnonia on charcoal was studied using an apparatus which followed the sorption by weight as a function of time and permitted measurement of temperature rise and analysis of the effluent gas stream over a wide range of sorbate concentrations and flowrates. The data were applied to the theories of Danby et al and of Mecklenberg and were found to be essentially in good agreement

Detection of angiotensin II mediated nitric oxide release within the nucleus of the solitary tract using electron-paramagnetic resonance (EPR) spectroscopy

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The transcriptional repressor REST is a critical regulator of the neurosecretory phenotype

Release of distinct cellular cargoes in response to specific stimuli is a process fundamental to all higher eukaryotes and controlled by the regulated secretory pathway (RSP). However, the mechanism by which genes involved in the RSP are selectively expressed, leading to the establishment and appropriate functioning of regulated secretion remaining largely unknown. Using the rat pheochromocytoma cell line PC12, we provide evidence that, by controlling expression of many genes involved in the RSP, the transcriptional repressor REST can regulate this pathway and hence the neurosecretory phenotype. Introduction of REST transgenes into PC12 cells leads to the repression of many genes, the products of which are involved in regulated secretion. Moreover, chromatin immunoprecipitation assays show that many of the repressed genes recruit the recombinant REST protein to RE1 sites within their promoters and abrogation of REST function leads to reactivation of these transcripts. In addition to the observed transcriptional effects, PC12 cells expressing REST have fewer secretory granules and a reduction in the ability to store and release noradrenaline. Furthermore, an important trigger for synaptic release, influx of calcium through voltage-operated calcium channels, is compromised. This is the first demonstration of a transcription factor that directly controls expression of many major components of the RSP and provides further insight into the function of REST

Sociology and international relations: legacies and prospects

While sociological concepts have often been implicitly used in International Relations (IR), recent years have seen a more explicit engagement between IR and Sociology. As with any such interdisciplinary assignation, there are both possibilities and challenges contained within this move: possibilities in terms of reducing IR's intellectual autism and opening the discipline towards potentially fertile terrain that was never, actually, that distant; challenges in that interdisciplinary raiding parties can often serve as pseudonyms for cannibalism, shallowness and dilettantism. This forum reviews the sociological turn in IR and interrogates it from a novel vantage point—how sociologists themselves approach IR concepts, debates and issues. Three sociological approaches—classical social theory, historical sociology and Foucauldian analysis—are critically deployed to illuminate IR concerns. In this way, the forum offers the possibility of (re)establishing exchanges between the two disciplines premised on a firmer grasp of social theory itself. The result is a potentially more fruitful sociological turn, one with significant benefits for IR as a whole

The Golgi apparatus is a functionally distinct Ca2+ store regulated by the PKA and Epac branches of the β1-adrenergic signaling pathway

Ca²+ release from the Golgi apparatus regulates key functions of the organelle, including vesicle trafficking. We found that the Golgi apparatus was the source of prolonged Ca²+ release events that originated near the nuclei of primary cardiomyocytes. Golgi Ca²+ release was unaffected by depletion of sarcoplasmic reticulum Ca²+, and disruption of the Golgi apparatus abolished Golgi Ca²+ release without affecting sarcoplasmic reticulum function, suggesting functional and spatial independence of Golgi and sarcoplasmic reticulum Ca²+ stores. β₁-Adrenoceptor stimulation triggers the production of the second messenger cAMP, which activates the Epac family of Rap guanine nucleotide exchange factors and the kinase PKA (protein kinase A). Phosphodiesterases (PDEs), including those in the PDE3 and PDE4 families, degrade cAMP. Activation of β1-adrenoceptors stimulated Golgi Ca²+ release, an effect that required activation of Epac, PKA, and the kinase CaMKII. Inhibition of PDE3s or PDE4s potentiated β₁-adrenergic-induced Golgi Ca²+ release, which is consistent with compartmentalization of cAMP signaling near the Golgi apparatus. Interventions that stimulated Golgi Ca²+ release appeared to increase the trafficking of vascular endothelial growth factor receptor-1 (VEGFR-1) from the Golgi apparatus to the surface membrane of cardiomyocytes. In cardiomyocytes from rats with heart failure, decreases in the abundance of PDE3s and PDE4s were associated with increased Golgi Ca²+ release events. These data suggest that the Golgi apparatus is a focal point for β₁- adrenergicstimulated Ca²+ signaling and that the Golgi Ca²+ store functions independently from the sarcoplasmic reticulum and the global Ca²+ transients that trigger contraction in cardiomyocytes