New species of African Straphylindae part III

Volume: XX

Tumours of Salivary Tissue: A Clinico-Pathological and Experimental Study

i. A clinical study has been made of 401 cases of tumours of salivary tissue and the results reported; familial incidence being noted on 3 occasions. ii. A histological study has been made of those cases seen at the Southern General Hospital, Glasgow. Attempts were made to clarify the presence or absence of "cartilage" in pleomorphic adenomata using Sulphur-35 with no result. iii. Blood-grouping was carried out in 341 patients from this series, and a highly significant preponderance of group-A was noted as compared with the control series. This preponderance was also present in the separate types of salivary tumours as well as in salivary tumours in general. iv. The results of attempts to produce salivary tumours experimentally in animals is discussed. v. The literature is reviewed in all parts of the thesis

Use of gamification to improve student revision of physiological and pharmacological concepts

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Use of gamification to improve student revision of physiological and pharmacological concepts—a pilot study

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Phosphodiesterase 4 isoforms in macrophage development and function

Phosphodiesterase 4 (PDE4) is a family of around 20 cyclic AMP (cAMP) hydrolysing enzymes. Expression of each isoform is regulated in a tissue and developmental specific manner. Such regulation suggests as yet undefined functions for each isoform. Understanding these functions will highlight likely therapeutic targets. I have employed various methods to identify possible functional roles for various PDE4 isoforms. PDE4B4 is a novel enzyme cloned from a rat brain cDNA library. By characterising the biochemical properties of this isoform in comparison to known, previously characterised members of the PDE4B family, I highlighted similarities and differences within this subfamily. Recombinant PDE4B4 was characterised in a COS-1 cell, temporary expression system. I demonstrated that PDE4B4 has a molecular weight lying between PDE4B1 and PDE4B2, is largely cytosolic, has a relatively low Km cAMP and is highly sensitive to inhibition by rolipram. As it has a UCR1 region it conforms to long form structure and is activated by PKA. It has an extreme N-terminal region homologous to PDE4D3 and behaves in a similar way in response to PKA phosphorylation. Development of macrophages from monocytes involves differential expression of various biochemical mediators. I developed a cell line model using the U937 pro-monocytic cell line and compared it against ex-vivo monocytes cultured in plastic. Using this model I identifies developmental changes in PDE4 isoform expression. PDE4A activity increased dramatically which was due in part to novel expression of PDE4A10. PDE4D isoform expression was entirely lost with no immunologically detectable enzyme present in macrophage like cells. PDE4B2 expression more than doubled in the mature cell. Loss of PDE4D and gain of PDE4B2 represents a shift from long to short form PDE4 dominance. I demonstrated a resultant switch in PDE4 response to extracellular signal related kinase (ERK) activation. Thus in monocytic cells EGF resulted in a decrease in total PDE4 activity, while in macrophage like cells PDE4 activity increased. To demonstrate a role for PDE4 in regulating macrophage function I stimulated the RAW 264.7-macrophage cell line with LPS in the presence of rolipram. I demonstrated a PGE2 dependent increase in iNOS expression and a PGE2 independent increase in COX2 expression. Such differential effects, suggests a compartmentalisation of rolipram's action. Inhibition of TNF? production was not dependent on PGE2 production. I then found that LPS activates PDE4 in an ERK dependent manner, but inhibits PDE3, highlighting further compartmentalisation of cAMP regulation. PDE4 activation was in part due to ERK dependent activation of the short form PDE4B2, downstream of LPS stimulation of RAW cells. Such activation may be associated with physical interaction between members of the ERK signalling cascade and PDE4B2. Next I demonstrated that crosstalk between ERK signalling and cAMP occurs in the opposite direction as rolipram leads to an early and elevated activation of ERK 1/2 in LPS stimulated RAW 264.7 macrophages. In an attempt to explain this effect I used rap 1 activation and PKA phosphorylation mutants, transfected into RAW cells to interfere with normal inflammatory signalling. No significant changes were observed in these studies. Finally I attempted to develop HIV-tat, PDE4 N-terminal, fusion proteins to inhibit individual PDE4 isoforms. I used primers encoding the HIV-tat peptide and PDE4 sequence to produce a cDNA fusion. This was cloned into a GST-expression vector and transformed into E-coli. Recombinant protein was expressed and purified using sepharose beads. Various problems were encountered in the course of this project, including the development of appropriate cloning primers and the production of proteins in inclusion bodies. The strategies employed to resolve these difficulties are discussed. Two further experiments are discussed. Firstly rolipram was found not to affect tritiated thymidine incorporation into proliferating HEK cells. This work argues against a role for PDE4 in regulating cell cycle in these cells. I also attempted to characterise PDE4 activity from the induced sputum of normal subjects. While PDE4 activity was found to survive the isolation process the intra-subject variability meant that useful interpretation of fluctuations based on therapeutic intervention would be impossible. In conclusion I have characterised a new member of the PDE4B family. It shares many characteristics with other members of the sub-family and long form PDE4 enzymes in general. I have shown upregulation of PDE4A10 and PDE4B2 in the maturation of macrophages and the loss of long form PDE4D3 and PDE4D5. This was found to have biochemical significance. PDE4B2 was shown to be important in the regulation of LPS activation of RAW cells and ERK/PDE4 crosstalk was found to occur in both directions. Rolipram was demonstrated to influence the behaviour of stimulated macrophages in a compartmentalised fashion, while LPS was found to activate PDE4 and inhibit PDE3. Finally I was unsuccessful in the development of a novel strategy for inhibiting individual PDE4 isoforms, by developing an HIV-tat fusion protein

Risk Management Strategies by Australian Farmers

Australian farmers operate in one of the most risky environment in the world. They have to cope with various sources of risk in their businesses. This paper reports results of two case studies undertaken to examine the issues of farming risks and risk management strategies in Australia. The first case study found that climate variability, financial risk, marketing risk, and personal risk were regarded as the major sources of farming risk in the Upper Eyre Peninsula of South Australia. The main management strategies used by farmers included diversifying varieties, minimising tillage, minimising area of risky crops and maximising area of the least-risky crop, having high equity, having farm management deposits and other off-farm investments, and "leaving marketing to experts". The second case study revealed that climate variability was ranked as the most important source of farming risk in southwest Queensland. This was then followed by financial risks, government policy, and marketing risks. The main management strategies used were enterprise diversification (having predominantly cattle and farming cash crops), conserving moisture, using zero till planting, diversified sales (selling only part of the farm's production at any one time), and having off-farm investments. The paper then attempts to reconcile the two case studies by comparing the results with studies from the United States of America, Canada, Netherlands, and New Zealand.risk, risk management, strategies, farmers, Australia, Farm Management, Risk and Uncertainty,

Use of student-created video resources to enhance science practical skills training

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The Postan Thesis and Beyond: The English Agrarian Economy c.1200-1348

The thirteenth century is generally regarded by economic historians as a period of extremely rapid demographic growth in England. It is believed that this increase in population meant that poorer and poorer lands were gradually taken under the plough. This trend, it is argued, led to an increasing disequilibrium between population and resources. In particular, the assumption is made that the ploughing-up of waste lands once used for grazing resulted in a worsening shortage of livestock and a progressive decline in the fertility of the arable land. ... Despite the progress made in the study of medieval English agriculture over the last two decades, there has been no thorough re-assessment of the Postan's interpretation of English agrarian history in the pre-1348 period. Perhaps because of the range of Postan's arguments, critics and commentators have been reluctant to embark on a comprehensive re-examination of the case upon which the Postan thesis rests. Nor has there been any attempt to draw together the different threads of debate or to examine the full implications of more recent research. A thorough re-assessment of the Postan thesis as it relates to the decades before the Plague is therefore long overdue. This dissertation is intended to provide such a re-examination. The Postan thesis will be reviewed in light of more recent research into English agriculture before the Black Death, and the criticisms made of Postan's model over the last two decades. It will be argued that, although the Postan thesis offers important insights into the pre-1348 period, the opportunities for a successful adaptation to demographic stress before the Black Death were perhaps greater than Postan believed. A case will be made therefore for a more optimistic interpretation of the process of economic change in England during the late thirteenth and early fourteenth centuries

Use of student-created video resources to enhance practical training in Objective Structured Practical Examinations (OSPE's)

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Foam nest components of the túngara frog: a cocktail of proteins conferring physical and biological resilience

The foam nests of the túngara frog (Engystomops pustulosus) form a biocompatible incubation medium for eggs and sperm while resisting considerable environmental and microbiological assault. We have shown that much of this behaviour can be attributed to a cocktail of six proteins, designated ranaspumins (Rsn-1 to Rsn-6), which predominate in the foam. These fall into two discernable classes based on sequence analysis and biophysical properties. Rsn-2, with an amphiphilic amino acid sequence unlike any hitherto reported, exhibits substantial detergent-like surfactant activity necessary for production of foam, yet is harmless to the membranes of eggs and spermatozoa. A further four (Rsn-3 to Rsn-6) are lectins, three of which are similar to fucolectins found in teleosts but not previously identified in a land vertebrate, though with a carbohydrate binding specificity different from previously described fucolectins. The sixth, Rsn-1, is structurally similar to proteinase inhibitors of the cystatin class, but does not itself appear to exhibit any such activity. The nest foam itself, however, does exhibit potent cystatin activity. Rsn-encoding genes are transcribed in many tissues of the adult frogs, but the full cocktail is present only in oviduct glands. Combinations of lectins and cystatins have known roles in plants and animals for defence against microbial colonization and insect attack. Túngara nest foam displays a novel synergy of selected elements of innate defence plus a specialized surfactant protein, comprising a previously unreported strategy for protection of unattended reproductive stages of animals