Synthetic approaches to polyoxygenated chromone and chromanome natural products

The work described in this thesis is concerned with the chemistry ofpolymethoxylated aromatic carbonyl compounds bearing a 2,6-dioxygenatedsubstitution pattern, with particular regard to establishing synthetic routes tobiologically active chromone and chromanone systems. Syntheses of keyintermediates in the approaches to the natural products stigmatellin, baicalein andLL-D253(x (and related products) were undertaken.In chapter one the reactions of nucleophiles at the carbonyl moieties of 2,6-dioxygenated benzene carbonyl compounds are reviewed. This type of processocan present special difficulties and was to prove particularly significant at variousstageso f the work describedi n subsequenct hapters.Chapter two is a review of the provenance, abundance, biosynthesis, and previoussyntheses of the natural products stigmatellin, baicalein and LL-D253(x, thesebeing the targets of the synthetic work undertaken in the course of the project.Chapter three is concerned with an approach to a fragment of the stigmatellinmolecule (referred to as stigmatellin fragment A) using the Vilsmeier formylationreaction, while chapter four is concerned with an alternative approach tostigmatellin fragment A using Friedel-Crafts acylation methodology. Thestrategies and the results obtained are described and analysed in detail.In chapter five a strategy for the synthesis of baicalein trimethyl ether is describedand the results obtained are discussed

Absence of renal hypoxia in the subacute phase of severe renal ischemia reperfusion injury

 This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this recordTissue hypoxia has been proposed as an important event in renal ischemia reperfusion injury (IRI) particularly during the period of ischemia and in the immediate hours following reperfusion. However, little is known about renal oxygenation during the subacute phase of IRI. We employed four different methods to assess the temporal and spatial changes in tissue oxygenation during the subacute phase (24 h and 5 days after reperfusion) of a severe form of renal IRI in rats. We hypothesized that the kidney is hypoxic 24 h and 5 days after an hour of bilateral renal ischemia, driven by a disturbed balance between renal oxygen delivery (DO2) and oxygen consumption (VO2). Renal DO2 was not significantly reduced in the subacute phase of IRI. In contrast, renal VO2 was 55% less 24 h, and 49% less 5 days after reperfusion than after sham-ischemia. Inner medullary tissue PO2, measured by radiotelemetry was 25 {plus minus} 12% greater 24 h after ischemia than after sham-ischemia. By 5 days after reperfusion, tissue PO2 was similar to that in rats subjected to sham-ischemia. Tissue PO2 measured by Clark electrode was consistently greater 24 h, but not 5 days, after ischemia than after sham-ischemia. Cellular hypoxia, assessed by pimonidazole adduct immunohistochemistry, was largely absent at both time-points and tissue levels of hypoxia inducible factors were downregulated following renal ischemia. Thus, in this model of severe IRI, tissue hypoxia does not appear to be an obligatory event during the subacute phase, likely due to the markedly reduced oxygen consumption.British Heart FoundationBritish Heart FoundationNational Health and Medical Research Council of AustraliaEuropean Union, Seventh Framework Programm

Effects of different culture conditions (photoautotrophic, photomixotrophic) and the auxin indole-butyric acid on the in vitro acclimatization of papaya (Carica papaya L. var. Red Maradol) plants using zeolite as support

Plant regeneration of papaya via organogenesis and somatic embryogenesis has been successful;  however, the biggest problem of in vitro culture of this species is the acclimatization of regenerated  plants, where over 70% of the plants are lost before being planted in the field. Decreasing the relative humidity inside the culture vessel and thus increasing the ventilation, appears to have a greater effect on  the adaptation of papaya plants, strengthening the function of the stomata and with this, allowing better  control of water loss from the leaves. The aim of this study was to determine the effects of different  concentrations of sucrose and indole-butyric acid (IBA) on rooting and in vitro acclimatization of plants  using sterile zeolite as support and culture vessels with increased ventilation. Three concentrations of  sucrose (0, 10 and 20 g L-1) were studied with and without auxin and as the control treatment, the  rooting culture medium with agar during 17, 27 and 37 culture days. The highest percentage of rooting  was recorded at 37 culture days in the treatment without sucrose and IBA with 80.0% and zeolite as  support. The best photosynthetic values were achieved when in vitro shoots were grown in culture  medium with auxin and different concentrations of sucrose, even though they were also high in the  treatment without the presence of IBA and without sucrose at 17 days of culture. The combined effect of the zeolite, auxin (IBA), without sucrose in the culture medium and increased ventilation allowed   photoautotrophic culture conditions which had effect of the increasing plant survival under ex vitro  acclimatization conditions.Key words: Carica papaya, photosynthesis, roots formation

Shade alters savanna grass layer structure and function along a gradient of canopy cover

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordData availability statement: Data used for this study are available as supporting information.Aim: In savannas, a grass-dominated ground layer is key to ecosystem function via grass–fire feedbacks that maintain open ecosystems. With woody encroachment, tree density increases, thereby decreasing light in the ground layer and potentially altering ecosystem function. We investigated how light availability can filter individual grass species distributions and whether different functional traits are associated with response to a shade gradient in a landscape experiencing woody encroachment. Location: Savanna–forest mosaic in the Cerrado domain, southeastern Brazil. Methods: Along an encroachment gradient of increasing tree leaf area index (LAI) and shade, we determined how changing light availability alters grass diversity and ground layer structure relative to grass cover and grass functional traits (photosynthetic pathway, underground storage organs, bud protection and traits related to grass shape, size and leaf dimensions). Results: Increasing shade led to a decrease in grass cover and grass species richness, and also compositional and functional changes. We found that where tree LAI reached 1, grass cover was reduced by 50% and species richness by 30%. While C4 grass species abundances decreased with increasing shade, the opposite pattern was true for C3 grasses. There were only small differences in light preferences among C4 subtypes, with phosphoenolpyruvate carboxykinase (PCK) species tolerating slightly more shaded conditions. Persistence of some C4 species under more shaded conditions was possible, likely due to an ability to store starch reserves via underground storage organs. Conclusions: Woody encroachment changes diversity and structure of the grassy layer that is critical to the functioning of savanna ecosystems, highlighting the dependence of the diverse grass layer on open and sunny conditions. Our results suggest a threshold of tree cover close to LAI ≈ 1 as being critical to cerrado grassy layer conservation.National Science Foundation (NSF)São Paulo Research Foundation (FAPESP)National Council for Scientific and Technological DevelopmentCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Radiographer involvement in mammography image interpretation: a survey of United Kingdom practice

Breast cancer is most often diagnosed using x-ray mammography. Traditionally mammography images have been interpreted and reported by medically qualified practitioners - radiologists. Due to radiologist workforce shortages in recent years some nonmedical practitioners, radiographers, now interpret and report mammography images. The aims of this survey were to describe the characteristics and practices of radiographers who interpret and report mammography images in NHS hospitals in the UK, and in particular to establish the extent of their practice beyond low-risk asymptomatic screening cases. This service evaluation demonstrated that UK radiographers are interpreting and reporting images across the full spectrum of clinical indications for mammography including: low-risk population screening, symptomatic, annual surveillance, family history and biopsy / surgical cases. The survey revealed that radiographers are involved in a diverse range of single and double reading practices where responsibility for diagnostic decision making is shared or transferred between radiologists and / or other radiographers. Comparative analysis of subgroup data suggested that there might be differences in the characteristics and practices of radiographers who interpret only low-risk screening mammograms and those who interpret and report a wider range of cases. The findings of this survey provide a platform for further research to investigate how and why the roles and responsibilities of radiographers who interpret and report mammograms vary between organisations, between practitioners and across different examinations. Further research is also needed to explore the implications of variation in practice for patients, practitioners and service providers

Anatomical and/or pathological predictors for the “incorrect” classification of red dot markers on wrist radiographs taken following trauma

OBJECTIVE: To establish the prevalence of red dot markers in a sample of wrist radiographs and to identify any anatomical and/or pathological characteristics that predict “incorrect” red dot classification. METHODS: Accident and emergency (A&E) wrist cases from a digital imaging and communications in medicine/digital teaching library were examined for red dot prevalence and for the presence of several anatomical and pathological features. Binary logistic regression analyses were run to establish if any of these features were predictors of incorrect red dot classification. RESULTS: 398 cases were analysed. Red dot was “incorrectly” classified in 8.5% of cases; 6.3% were “false negatives” (“FNs”)and 2.3% false positives (FPs) (one decimal place). Old fractures [odds ratio (OR), 5.070 (1.256–20.471)] and reported degenerative change [OR, 9.870 (2.300–42.359)] were found to predict FPs. Frykman V [OR, 9.500 (1.954–46.179)], Frykman VI [OR, 6.333 (1.205–33.283)] and non-Frykman positive abnormalities [OR, 4.597 (1.264–16.711)] predict “FNs”. Old fractures and Frykman VI were predictive of error at 90% confidence interval (CI); the rest at 95% CI. CONCLUSION: The five predictors of incorrect red dot classification may inform the image interpretation training of radiographers and other professionals to reduce diagnostic error. Verification with larger samples would reinforce these findings. ADVANCES IN KNOWLEDGE: All healthcare providers strive to eradicate diagnostic error. By examining specific anatomical and pathological predictors on radiographs for such error, as well as extrinsic factors that may affect reporting accuracy, image interpretation training can focus on these “problem” areas and influence which radiographic abnormality detection schemes are appropriate to implement in A&E departments

Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium

10.1186/bcr3381Breast Cancer Research15

Investigation into mercury bound to biothiols: structural identification using ESI–ion-trap MS and introduction of a method for their HPLC separation with simultaneous detection by ICP-MS and ESI-MS

Mercury in plants or animal tissue is supposed to occur in the form of complexes formed with biologically relevant thiols (biothiols), rather than as free cation. We describe a technique for the separation and molecular identification of mercury and methylmercury complexes derived from their reactions with cysteine (Cys) and glutathione (GS): Hg(Cys)2, Hg(GS)2, MeHgCys, MeHgGS. Complexes were characterised by electrospray mass spectrometry (MS) equipped with an ion trap and the fragmentation pattern of MeHgCys was explained by using MP2 and B3LYP calculations, showing the importance of mercury–amine interactions in the gas phase. Chromatographic baseline separation was performed within 10 min with formic acid as the mobile phase on a reversed-phase column. Detection was done by online simultaneous coupling of ES-MS and inductively coupled plasma MS. When the mercury complexes were spiked in real samples (plant extracts), no perturbation of the separation and detection conditions was observed, suggesting that this method is capable of detecting mercury biothiol complexes in plants