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No hemispheric asymmetries in long-acting cortical inhibition in young adults using

It is well established that fine motor control is asymmetrical: this is known as handedness. Handedness is controlled by cortical motor processes, including long-acting inhibition. Long-acting cortical inhibition is asymmetric between the left and right hemispheres. Therefore, asymmetries of handedness may be attributable to asymmetries in long-acting inhibition. Asymmetries of long-acting inhibition have previously been tested using a measure of corticospinal excitability, but have not been previously investigated using combined transcranial magnetic stimulation (TMS) and electroencephalography (TMS-EEG), a measure of cortical inhibition not influenced by spinal excitability. This study aimed to determine if long-acting cortical inhibition is asymmetrical using TMS-EEG and to investigate any associations of asymmetrical inhibition with fine motor control. In young adults (n = 14) fine motor control was measured using the Purdue Pegboard task. EEG was used to record the cortical responses to paired-pulse, single-pulse and sham TMS. Results showed no asymmetry in fine motor control using the Purdue Pegboard task and no asymmetries of long-acting inhibition between the left and right hemispheres using TMS-EEG. There was no significant difference between the response to sham and single-pulse stimulation, suggesting that the cortical response to TMS was influenced by auditory or physiological artefacts. There were no associations between TEPs of long-acting inhibition and fine motor control. Overall, there were no conclusive results whether asymmetries of long-acting inhibition are replicable using TMS-EEG. Further investigation of the importance of LICI as a neural underpinning of handedness is important to better understanding the workings of handedness and fine motor control

Investigating HK2 as a potential therapeutic target in glioblastoma

A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Glioblastoma is the most common high-grade primary brain tumour in adults. Current treatments have limited success with average survival comprehensively low. Effective drug treatments are hindered predominantly by the complex genetic background of glioblastoma heterogeneity, as such there is a compelling need for the development of effective therapeutics. An approach is to target abnormal metabolic pathways that are universally dysregulated in glioblastoma. The identification of potential targets and the development of therapeutic agents is crucial for the advancement of treatment. Hexokinase 2 (HK2) has a prominent role in glycolysis, acting as the rate-limiting step in the pathway. HK2 is highly expressed in many cancers and its role as the rate-limiting step of glycolysis may potentially contribute to tumour growth. Overexpression of HK2 has also been associated with drug resistant phenotypes, in parallel, its inhibition has improved the effectiveness of anticancer agents, suggesting HK2 as a potential therapeutic target. The role of methylation and its association with expression levels of HK2 was determined in glioblastoma fresh frozen biopsies and patient-derived cultures, through pyrosequencing and quantitative PCR. CRISPR knockout was utilised to investigate the effect of inhibiting HK2 on proliferation and to determine the role of HK2 in chemoresistance. The anti-proliferative effects of HK2 inhibitors 3-bromopyruvic-acid (3-BPA) and metformin were investigated via cytotoxic assays and FACS analysis was used to determine their mechanism of action. Additionally, downstream expression changes were investigated via expression profiler arrays, across 84 key genes involved in the regulation and enzymatic pathways of glucose metabolism. Hypomethylation was demonstrated in all biopsies (n=100) and cultures (n=15) compared to normal brain tissue; with average methylation of 4.6% compared to 26% respectively (p1000- fold change in all biopsies and cultures compared to normal brain tissue and a strong correlation between hypomethylation and increased level of expression (p50% genes demonstrated reduced levels of expression compared to the corresponding parent/non-treated cultures. This study demonstrates the predominant role of HK2 within the glycolytic pathway, with overexpression potentially key in driving the genetic alterations downstream. This study also verifies a strong correlation between increased expression of HK2 and hypomethylation, additionally highlighting the impact HK2 has on inferior patient prognosis. HK2-KO revealed considerable ubiquitous reductions in downstream gene expression compared to glioblastoma biopsy tissue and parent cultures. Additionally, an increase in drug sensitivity was depicted with the loss of HK2 signifying the potential of targeting HK2 as a novel therapy in a significant subset of glioblastoma

Reassessing the Scottish Parliamentary Records, 1528-1548 : manuscript, print, bureaucracy and royal authority

This article for the first time correctly identifies a manuscript previously identified as an ‘official record of parliament’ as a draft of the first printed statutes of the Scottish Parliament, the Actis and Constitutionis of 1542. This discovery has a number of implications for our study of parliament in the period 1528 to 1548, encompassing the personal rule of James V and the beginning of his daughter, Mary Queen of Scots's, minority, which the original manuscript covered. Careful attention to these materials exposes a sophisticated administrative culture, characterised by reviewing and repromulgating statutes, as well as revealing the ghosts of further, now lost, records. Considering the printed text, meanwhile, suggests that parliament and the law played as important a role as history and ceremonial in the assertion of James V's kingship in the years 1540–2: indeed, this should not surprise us given that James's administrators were also his poets. While the Actis of 1542 have hitherto provoked little interest from among historians, they emerge as an important influence on the much better known publication of Scottish statutes from James I to Mary in 1567. The administrators who produced this later volume evidently saw themselves as working within the same tradition as their predecessors of 1542: an increased appreciation of the administrative expertise, careful record-keeping, attention to the dissemination of statute and the ways in which this bolstered the power of the crown suggests that we ought to do likewise.PostprintPeer reviewe

Cultivating Compassion: School Discipline Through a Lens of Equity, Wellbeing, and Decolonization

Punitive and exclusionary discipline practices cause harm to elementary aged students weakening their connection to school. Such practices are reactive in nature and fail to understand the needs of students who demonstrate challenging behaviour. This organizational improvement plan provides a framework to reimagine school discipline through a lens of equity, wellbeing, and decolonization. It is an invitation to look under the surface to better understand students who struggle with behaviour in elementary classrooms. The school discussed is a large, suburban public school in British Columbia serving students in kindergarten through to grade seven. A conceptual change model, the transformative wheel, is applied to the problem of practice blending the work of transformative learning theory, compassionate systems leadership, and Indigenous ways of knowing. The change model and suggested strategies align with the BC Teaching Standards and BC Mental Health in Schools Strategy. Three solutions are presented, each built around the development of a school-based learning team or professional learning community and an established vision for change. The solutions include building professional capacity, embracing Indigenous wisdom, and recognizing systemic inequities to improve practice. The chosen solution blends professional development and Indigenous knowledge to create a community of care built on the premise that all children belong, and that school communities benefit when students with challenging behaviour are wrapped in love and support and pulled closer rather than pushed away. Keywords: School discipline, transformative learning theory, compassionate systems, student behaviour, equity, decolonizatio

Scottish history in the eyes of sixteenth-century France

I gratefully acknowledge that research for this article was partly funded by the British Academy.Scotland's mythical and medieval history has long been acknowledged as of critical importance in its sixteenth-century present. This article tracks these discourses across the channel, showing for the first time the limited circulation of Scottish histories in France and the dominance of English versions of the past in French texts, ranging from short, printed books to royal presentation manuscripts. This Anglocentric view not only helps to explain the discordant French views of the Scots (as loyal yet uncivil, and above all warlike) but also contributes to the ongoing reassessment that the auld alliance was not permanently binding but, rather, intermittently activated when political or economic interests required.Peer reviewe

Writing Scottish Parliamentary history, c.1500 – 1707

In the 19th and 20th centuries, scholarship on the Scottish parliament was heavily informed by a narrative of ‘failure’, directed at explaining why its members voted it out of existence in 1707. Part of the problem was the tendency to see any deviation from the practices of the Westminster parliament as weakness. By reappraising parliament in terms of its utility to those who comprised its membership, notably the titled peerage and the monarch, historians have revealed its adaptability and inventiveness, especially in times of crisis. This essay considers how fresh approaches both to what constituted the parliamentary record and what can – and cannot – be found within it have exerted a transformative influence on our understanding of parliament's evolving role in Scottish political life. Although the Reformation crisis of 1560 and the accession of the ruling house of Stewart to the English throne in 1603 effected profound changes on parliamentary culture, this essay emphasises how parliament sustained its legitimacy and relevance, in part, by drawing on past practices and ideas. Historians have become more attentive in recent years to the means by which social groupings ordinarily excluded from formal parliamentary activity were nonetheless able to engage with, and influence, its proceedings. Gaps remain in our knowledge, however. Some periods have been more intensively studied than others, while certain aspects of parliamentary culture are understudied. The writing of Scottish parliamentary history will continue to offer rich possibilities in future.Publisher PDFPeer reviewe

Introduction: biography and James VI’s Scotland

Introduction to a special issue of journal on the theme of biography in the Scotland of James VI, 1567-1625

Geomorphology and late Holocene accretion history of Adele Reef: a northwest Australian mid-shelf platform reef

The mid-shelf reefs of the Kimberley Bioregion are one of Australia’s more remote tropical reef provinces and such have received little attention from reef researchers. This study describes the geomorphology and late Holocene accretion history of Adele Reef, a mid-shelf platform reef, through remote sensing of contemporary reef habitats, shallow seismic profiling, shallow percussion coring and radiocarbon dating. Seismic profiling indicates that the Holocene reef sequence is 25 to 35 m thick and overlies at least three earlier stages of reef build-up, interpreted as deposited during marine isotope stages 5, 7 and 9 respectively. The cored shallow subsurface facies of Adele Reef are predominantly detrital, comprising small coral colonies and fragments in a sandy matrix. Reef cores indicate a ‘catch-up’ growth pattern, with the reef flat being approximately 5–10 m deep when sea level stabilised at its present elevation 6,500 years BP. The reef flat is rimmed by a broad low-relief reef crest only 10–20 cm high, characterised by anastomosing ridges of rhodoliths and coralliths. The depth of the Holocene/last interglacial contact (25–30 m) suggests a subsidence rate of 0.2 mm/year for Adele Reef since the last interglacial. This value, incorporated with subsidence rates from Cockatoo Island (inshore) and Scott Reefs (offshore), provides the first quantitative estimate of hinge subsidence for the Kimberley coast and adjacent shelf, with progressively greater subsidence across the shelf