From Stonehenge to the Gherkin

Isotope analysis of tooth enamel from humans is a rapidly developing technique for looking at the childhood origins of people from the past. It provides a direct measurement from the person and does not depend upon the assumption that artefacts within a burial provide a direct link with the person’s origins. In other words, just because some one is buried with a Scandinavian sword does not mean the person themselves was from Norway or Sweden; the sword might have been a prized possession won in battle. Isotopes can distinguish between these two possibilities

Prenatal programming of neuroendocrine reproductive function

It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the “prenatal programming” of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be “shaped” both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent “normal function”. The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on reproductive potential

The Soldier as I -Witness in Novels by Barbusse and Ehni

In her article The Soldier as \u27I\u27-Witness in Novels by Barbusse and Ehni Jane E. Evans discusses the representation of the French soldier in two first-person accounts based on life writing journals. The first, set during World War I, describes the simple ground soldier or troufion (Le Feu). The second, set during the Algerian War for Independence and later, sketches the life of the French army conscript. Three themes in Evans\u27s analysis predominate: the narrators\u27 reliance on life writing as sources of inspiration in both Henri Barbusse\u27s 1916 Le Feu and René-Nicolas Ehni\u27s 2002 Algérie roman, the narrator\u27s perception of his role as storyteller and writer including Ehni\u27s idea of the paramyth juxtaposing the individual and the collective whole, and the manner in which the narration is presented through the narrator\u27s point-of-view, format for addressing his audience, imagery, and language style. Evans also considers differences in narrative perspective, attitude, tone, and register in relation to the subjects of war and the soldier, as well as to what they suggest about the narrator\u27s reliability as a witness

An In-Service Model for the Training of Secondary Special Education Instructional Aides

The purpose of the project was to develop a workshop to provide on the job training for aides in secondary special education programs in Bremerton, Washington. A needs assessment was conducted to determine the validity of the perceived need and to identify and prioritize training areas. Existing training programs were examined and a literature search conducted. The resulting training model was designed to increase the effectiveness of aides and thereby maximize the delivery of instruction in special education

Developing novel molecular contrast agents for imaging vulnerable plaques

This thesis describes the design, synthesis, and testing of novel MRI contrast agents based on iron oxide nanoparticles for the specific detection and identification of vulnerable plaque. Cardiovascular disease remains the leading cause of death worldwide, primarily due to heart attacks and strokes resulting from vulnerable plaque rupture. Vulnerable plaque occurs in atherosclerosis, when plaque is deposited in the walls of blood vessels and can take on vulnerable or stable phenotypes. There is an urgent need for an imaging biomarker to enable the specific detection of vulnerable plaque to facilitate treatment and prevent future heart attacks and strokes. MRI is a non-ionising, non-invasive imaging modality with the potential for highly customisable contrast agents. Chapter 2 discusses the design and synthesis of a library of superparamagnetic iron oxide nanoparticle-based contrast agents through thermal decomposition and coating with different surface ligands, including poly (maleic anhydride-alt-1-octadecene), alendronate, and poly (ethyleneimine). The agents were characterised through transmission electron microscopy, dynamic light scattering, zeta potential and relaxivity measurements. Chapter 3 presents the results of biological tests performed using the lead candidate from the synthesis carried out in chapter 2, including the coupling of a targeting antibody to the contrast agent, in vitro testing, and MR imaging in a preclinical model with histological verification of the results. Chapter 4 builds on the initial design and synthetic work of Chapter 2 with the introduction of a gold shell, moving towards multi-modality imaging. Several synthetic routes for the introduction of the gold shell and a selection of surface ligands including poly (maleic anhydride-alt-1-octadecene), homocysteine, and citrate were studied, and characterised through transmission electron microscopy, dynamic light scattering, and zeta potential measurements. Chapter 5 summarises the conclusions of the project, presents potential areas for future work and concludes the thesis. Open Acces

Working with the public: how an unusual museum enquiry turned into travels through time and space

Museum enquiries offer a unique opportunity to engage on a one-to-one level with members of the public. This paper covers an unusual enquiry from 2013 of an unknown tooth that was brought into Plymouth City Museum and Art Gallery for identification. We highlight how museum enquiries can engage with members of the public by involving them directly with original scientific research. The tooth was found in a garden in Plymouth with no associated data of about where it originated. We identified the tooth, and the enquirer researched the history of the house. The tooth gave the appearance of a sub-fossil so with the large number of Quaternary sites in Plymouth, together with the identification of the previous owner on the site, there were valid reasons to undertake testing of the tooth to determine its origin. Strontium (Sr) isotope analysis of the tooth was carried out to determine if the tooth was British and radiocarbon dating was undertaken to work out the age of the tooth. The 87Sr /86Sr of the leopard tooth gave a value of 0.716131, with Sr concentrations at 568ppm. This is a high concentration of Sr ppm relative to other British data, suggesting a non-British origin. The radiocarbon measurement was 187 ± 24 years BP (University of Oxford Radiocarbon Accelerator Unit reference OxA-30390). This places the tooth not in the Pleistocene, but between 1739 and 1787 AD. The site where the tooth was discovered was owned by the brother of Linnaeus Tripe who travelled across India and Burma. We argue that the results of this study demonstrate that this leopard tooth was originally from India or Burma, and brought into Britain by Tripe

Producing emotionally sensed knowledge? Reflexivity and emotions in researching responses to death

This paper reflects on the methodological complexities of producing emotionally-sensed knowledge about responses to family deaths in urban Senegal. Through engaging in ‘uncomfortable reflexivity’, we critically explore the multiple positionings of the research team comprised of UK, Senegalese and Burkinabé researchers and those of participants in Senegal and interrogate our own cultural assumptions. We explore the emotional labour of the research process from an ethic of care perspective and reflect on how our multiple positionings and emotions influence the production and interpretation of the data, particularly exemplified through our differing responses to diverse meanings of ‘family’ and religious refrains. We show how our approach of ‘uncomfortable reflexivity’ helps to reveal the work of emotions in research, thereby producing ‘emotionally sensed knowledge’ about responses to death and contributing to the cross-cultural study of emotions

Pharmacological and functional regulation of two-pore domain potassium channels

Two pore domain potassium (K2P) channels underlie the background potassium leak currents of excitable cells. In this study, the whole cell patch clamp technique was used with transiently transfected human embryonic kidney cells, and cerebellar granule neurones (CGNs) in primary culture, to compare the pharmacological properties of acid sensitive K2P channels. Zn2+, La3+, Cu2+, ruthenium red and Ru-360 blocked TASK-1 and TASK-3 channel currents. Substitution of external sodium ions with N-methyl-D-glucamine and choline also caused a significant reduction in TASK-1 and TASK-3 currents, demonstrating that maximal conductance through these potassium channels requires the presence of external sodium ions. Whilst Cu2+ blocked TASK-1 and TASK-3 channel currents, TASK-2 currents were not affected by the ion. Mannitol, a scavenger of hydroxyl radicals, did not alter Cu2+ block of TASK-3 currents showing hydroxyl radical production was not the underlying mechanism. Application of thiol oxidant, DTNB (5’,5’-dithio-bis(2 nitrobenzoic acid)), showed a potent block, mimicking that of Cu2+ in size and reversibility. DTNB and Cu2+ block were reversed by disulphide-reducing DTT (dithiothreitol), suggesting thiol rich cysteine residues played a fundamental role in <y, TASK-3 current block by Cu . The standing-outward, voltage-insensitive potassium current in CGNs also showed DTNB and copper sensitivity. Substitutions of TASK-3 cysteine residues to alanine and serine retained copper sensitivity while whole cell current amplitude diminished and a sensitivity to alkaline pH (8.4) was introduced to TASK-3. Point mutation of cysteine 110 was found to be key in facilitating the pH 8.4 potentiation of current. Cu2+ and DTNB were applied to a TASK-2/TASK-3 chimera channel where a robust, albeit reduced, block was observed. The central role of the TASK channels in neuronal excitability is demonstrated by their extensive physiological and cross-species distribution and varied mechanisms of regulation. In this study, the interaction of essential trace element Cu2+ was shown to be a significant mechanism of TASK regulation.Open acces

Preparation breeds success: Brain activity predicts remembering

Successful retrieval of episodic information is thought to involve the adoption of memory states that ensure that stimulus events are treated as episodic memory cues (retrieval mode) and which can bias retrieval toward specific memory contents (retrieval orientation). The neural correlates of these memory states have been identified in many neuroimaging studies, yet critically there is no direct evidence that they facilitate retrieval success. We cued participants before each test item to prepare to complete an episodic (retrieve the encoding task performed on the item at study) or a non-episodic task. Our design allowed us to separate event-related potentials (ERPs) elicited by the preparatory episodic cue according to the accuracy of the subsequent memory judgment. We predicted that a correlate of retrieval orientation should be larger in magnitude preceding correct source judgments than that preceding source errors. This hypothesis was confirmed. Preparatory ERPs at bilateral frontal sites were significantly more positive-going when preceding correct source judgments than when preceding source errors or correct responses in a non-episodic baseline task. Furthermore this effect was not evident prior to recognized items associated with incorrect source judgments. This pattern of results indicates a direct contribution of retrieval orientation to the recovery of task-relevant information and highlights the value of separating preparatory neural activity at retrieval according to subsequent memory accuracy. Moreover, at a more general level this work demonstrates the important role of pre-stimulus processing in ecphory, which has remained largely neglected to date