The circadian clock and the cell cycle

The circadian clock is an endogenous time-keeping mechanism that allows an organism to coordinate its biology with the 24 hour variations in its external environment. Epidemiological studies have linked clock disruption to an increase incidence of cancer, in particular breast malignancy. On a molecular level, clock components have been shown to regulate cell cycle gene expression and its progression in a number of models. This thesis set out to further dissect the link between these two important systems. Within the zebrafish cell-line, PAC2, mitosis was demonstrated to be under circadian control via clock regulation of the cell cycle mediator, Cyclin B1. Techniques used were then translated into a human cell-line model to study species specific clock function, with particular reference to breast epithelial tissue. Glucocorticoids, putative clock synchronisation agents in vivo, were observed to induce cellular clock synchronisation in HEK 293 cells and the benign breast epithelial cell-line MCF10A. Clock disruption inhibited cell growth. Study of the breast epithelial cell cycle mutant, MDA-MB-231, demonstrated a functional clock, revealing no reciprocal regulation. In contrast, decreased expression levels of clock gene and putative tumour suppressor, Per1, were observed within the malignant breast epithelial cell-line, MCF7, leading to greatly disrupted clock function and circadian independent cell growth. Unlike the zebrafish model, no intracellular clock regulation of cell cycle genes expression or function was observed, expression being preferentially modified by homeral circadian regulators such as glucocorticoids and melatonin. This also contradicts mammalian in vivo studies, leading to the hypothesis that the clock and cell cycle maybe uncoupled in immortalised cell cultures. In conclusion this study has demonstrated that clock regulation of the cell cycle in mammalian system is a multifactorial process and that disruption of this system leads to changes in the character of the cell cycle within the host tissue. Further work must explore this relationship in an in vivo setting

Poly(n-butyl Methacrylate) with Primary Amine End Groups for Supporting Cell Adhesion and Proliferation of Renal Epithelial Cells

Polymer coatings that support epithelial cell culture have been developed. Ozonolysis and subsequent work up of poly(butyl methacrylate-co-butadiene) copolymers is used to form oligomers with carboxylic acid end groups, which are then further reacted with diamines to provide poly(butyl methacrylate)s with primary amine end groups. The polymers are cast as films and used as cell culture substrates for human dermal fibroblasts and human renal epithelial cells. Fibroblast and epithelial cells adhere and proliferate on acid functional materials but on amine functional films epithelial cells show greater viability than fibroblasts

Predicting climate change impacts on maritime Antarctic soils: A space-for-time substitution study

We report a space-for-time substitution study predicting the impacts of climate change on vegetated maritime Antarctic soils. Analyses of soils from under Deschampsia antarctica sampled from three islands along a 2,200 km climatic gradient indicated that those from sub-Antarctica had higher moisture, organic matter and carbon (C) concentrations, more depleted δ13C values, lower concentrations of the fungal biomarker ergosterol and higher concentrations of bacterial PLFA biomarkers and plant wax n-alkane biomarkers than those from maritime Antarctica. Shallow soils (2 cm depth) were wetter, and had higher concentrations of organic matter, ergosterol and bacterial PLFAs, than deeper soils (4 cm and 8 cm depths). Correlative analyses indicated that factors associated with climate change (increased soil moisture, C and organic matter concentrations, and depleted δ13C contents) are likely to give rise to increases in Gram negative bacteria, and decreases in Gram positive bacteria and fungi, in maritime Antarctic soils. Bomb-14C analyses indicated that sub-Antarctic soils at all depths contained significant amounts of modern 14C (C fixed from the atmosphere post c. 1955), whereas modern 14C was restricted to depths of 2 cm and 4 cm in maritime Antarctica. The oldest C (c. 1,745 years BP) was present in the southernmost soil. The higher nitrogen (N) concentrations and δ15N values recorded in the southernmost soil were attributed to N inputs from bird guano. Based on these analyses, we conclude that 5–8 °C rises in air temperature, together with associated increases in precipitation, are likely to have substantial impacts on maritime Antarctic soils, but that, at the rates of climate warming predicted under moderate greenhouse gas emission scenarios, these impacts are likely to take at least a century to manifest themselves

The transfer of fibres in the carding machine

The problem of understanding the transfer of fibres between carding-machine surfaces is addressed by considering the movement of a single fibre in an airflow. The structure of the aerodynamic flow field predicts how and when fibres migrate between the different process surfaces. In the case of a revolving-flats carding machine the theory predicts a “strong” aerodynamic mechanism between taker-in and cylinder and a “weak” mechanism between cylinder and removal cylinder resulting in effective transfer in the first case and a more limited transfer in the second

Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort

STUDY FUNDING The data were collected by a Research into Ageing programme grant; research continues as part of the Age UK–funded Disconnected Mind project. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1), with funding from the BBSRC and Medical Research Council. Imaging and image analysis was performed at the Brain Research Imaging Centre (sbirc.ed.ac.uk/), Edinburgh, supported by the Scottish Funding Council SINAPSE Collaboration. Derivation of mean cortical thickness measures was funded by the Scottish Funding Council’s Postdoctoral and Early Career Researchers Exchange Fund awarded by SINAPSE to David Alexander Dickie. L.C.A.C. acknowledges funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division.Peer reviewedPublisher PD

Atomic and Electronic Structures of Unreconstructed Polar MgO(111) Thin Film on Ag(111)

Atomic and electronic structures of a polar surface of MgO formed on Ag(111) was investigated by using reflection high energy electron diffraction (RHEED), Auger electron spectroscopy, electron energy loss spectroscopy (EELS), and ultraviolet photoemission spectroscopy (UPS). A rather flat unreconstructed polar MgO(111) 1$\times$1 surface could be grown by alternate adsorption of Mg and O$_{2}$ on Ag(111). The stability of the MgO(111) surface was discussed in terms of interaction between Ag and Mg atoms at the interface, and charge state of the surface atoms. EELS of this surface did not show a band gap region, and finite density of states appeared at the Fermi level in UPS. These results suggest that a polar MgO(111) surface was not an insulating surface but a semiconducting or metallic surface.Comment: 6 figures, to be published in Phys. Rev.

Resultados de la enseñanza de estrategias de lectura y escritura en la alfabetización temprana de niños con riesgo social

Introducción: La evidencia científica reciente destaca la importancia de la alfabetización temprana como fundamento del aprendizaje lector posterior, especialmente en niños en riesgo social, pero no existen las condiciones adecuadas para alcanzar su desarrollo. El objetivo del estudio fue evaluar los resultados de una intervención focalizada en el aprendizaje temprano de la lectura y la escritura de niños con riesgo social (5 años 3 meses promedio). Material y Métodos: Se evaluaron 339 niños(as) (132 grupo intervención/207 grupo comparación), al inicio y al fin del año escolar. Los profesores del grupo de intervención participaron en un programa de desarrollo profesional de un año que incluyó capacitación y acompañamiento para la aplicación de estrategias de enseñanza de la alfabetización temprana. Resultados: Se observó un resultado positivo en el conocimiento del alfabeto, la escritura emergente y el reconocimiento visual de palabras, no en comprensión oral. Discusión: Se contrastan los resultados con otros programas de intervención en niños con riesgo social, resaltando la importancia de la capacitación y el acompañamiento a los educadores

Herd-level risk factors of bovine tuberculosis in England and Wales after the 2001 foot-and-mouth disease epidemic

We present the results of a 2005 case–control study of bovine tuberculosis (bTB) breakdowns in English and Welsh herds. The herd management, farming practices, and environmental factors of 401matched pairs of case and control herds were investigated to provide a picture of herd-level risk factors in areas of varying bTB incidence. A global conditional logistic regression model, with region-specific variants, was used to compare case herds that had experienced a confirmed bTB breakdown to contemporaneous control herds matched on region, herd type, herd size, and parish testing interval. Contacts with cattle from contiguous herds and sourcing cattle from herds with a recent history of bTB were associated with an increased risk in both the global and regional analyses. Operating a farm over several premises, providing cattle feed inside the housing, and the presence of badgers were also identified as significantly associated with an increased bTB risk. Steps taken to minimize cattle contacts with neighboring herds and altering trading practices could have the potential to reduce the size of the bTB epidemic. In principle, limiting the interactions between cattle and wildlife may also be useful; however this study did not highlight any specific measures to implement