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On the importance of being amidated: analysis of the role of the conserved C-terminal amide of amylin in amyloid formation and cytotoxicity
Get PDFThe polypeptide hormone Amylin (also known as islet amyloid polypeptide) plays a role in regulation of glucose metabolism, but forms pancreatic islet amyloid deposits in type 2 diabetes. The process of islet amyloid formation contributes to β-cell dysfunction and the development of the disease. Amylin is produced as a pro-from and undergoes processing prior to secretion. The mature hormone contains an amidated C-terminus. Analysis of an alignment of vertebrate amylin sequences reveals that the processing signal for amidation is strictly conserved. Furthermore, the enzyme responsible for C-terminal amidation is found in all of these organisms. Comparison of the physiologically relevant amidated form to a variant with a free C-terminus (Amylin-COO-) shows that replacement of the C-terminal amide with a carboxylate slows, but does not prevent amyloid formation. Pre-fibrillar species produced by both variants are toxic to cultured β-cells, although hAmylin-COO- is moderately less so. Amyloid fibrils produced by either peptide are not toxic. Prior work (ACS Pharmacol. Translational. Sci. 1, 132–49 (2018)) shows that Amylin- COO- exhibits a 58-fold reduction in activation of the Amylin1 receptor and 20-fold reduction in activation of the Amylin3 receptor. Thus, hAmylin-COO- exhibits significant toxicity, but significantly reduced activity and offers a reagent for studies which aim to decouple hAmylin’s toxic effects from its activity. The different behaviours of free and c-terminal amidated Amylin should be considered when designing systems to produce the polypeptide recombinantly
'Begin at the beginning, the King said, very gravely': Serious Openings and Subversive Epigraphs in the Novels of Thomas Pynchon
Get PDFThe American author, Thomas Pynchon, the focus of this paper, is famed, it could be argued, mostly for three things. The first is the extreme lengths of his novels and the bewildering numbers of characters and plotlines in said books. Gravity’s Rainbow, his 1973 work that remains unfinished by most who own a copy, contains over 400 characters for example. The second, and the point to which this paper is devoted, is the famous opening to that novel, which most readers do reach, the howl of the V-2 rocket that soars at supersonic speed above the landscape: “a screaming comes across the sky” it reads. The third is that this novel was nominated for the Pulitzer Prize but denied the prize at the last minute on the grounds of being “turgid, overwritten, and obscene”
The thesis writing journeys of bachelor's and master's students: a transnational European perspective
No full textBook synopsis: Completing a thesis is a crucial final stage in many Bachelor's and Master's programmes across Europe and beyond. However, the process of thesis writing, how it is experienced by the writers, and how those experiences impact on writing remain under-explored. This book explores the student experience of thesis writing through an interdisciplinary perspective drawing on theories of learning, emotions, and genre and narrative/discursive analysis. As a result of this approach, the thesis is reconceptualised as a multilayered experience from the point of view of student writers. The chapters, which arose out of a collaborative research project across 11 European countries, use an innovative combination of methods including the use of journey plots to provide a complex picture of the thesis writing process, which will be of interest to readers involved in academic writing at all levels
Bachelor’s and master’s thesis writing: a research agenda
No full textBook synopsis: Completing a thesis is a crucial final stage in many Bachelor's and Master's programmes across Europe and beyond. However, the process of thesis writing, how it is experienced by the writers, and how those experiences impact on writing remain under-explored. This book explores the student experience of thesis writing through an interdisciplinary perspective drawing on theories of learning, emotions, and genre and narrative/discursive analysis. As a result of this approach, the thesis is reconceptualised as a multilayered experience from the point of view of student writers. The chapters, which arose out of a collaborative research project across 11 European countries, use an innovative combination of methods including the use of journey plots to provide a complex picture of the thesis writing process, which will be of interest to readers involved in academic writing at all levels
Investigating bachelor’s and master’s thesis writing: the research context and methodology of the project
No full textBook synopsis: Completing a thesis is a crucial final stage in many Bachelor's and Master's programmes across Europe and beyond. However, the process of thesis writing, how it is experienced by the writers, and how those experiences impact on writing remain under-explored. This book explores the student experience of thesis writing through an interdisciplinary perspective drawing on theories of learning, emotions, and genre and narrative/discursive analysis. As a result of this approach, the thesis is reconceptualised as a multilayered experience from the point of view of student writers. The chapters, which arose out of a collaborative research project across 11 European countries, use an innovative combination of methods including the use of journey plots to provide a complex picture of the thesis writing process, which will be of interest to readers involved in academic writing at all levels
Introduction: power, processes and patterns in early modern petitioning
Get PDFBook synopsis: The ‘humble petition’ was ubiquitous in early modern society and featured prominently in crucial moments such as the outbreak of the civil wars and in everyday local negotiations about taxation, welfare and litigation. People at all levels of society – from noblemen to paupers – used petitions to make their voices heard and these are valuable sources for mapping the structures of authority and agency that framed early modern society.
The Power of Petitioning in Early Modern Britain offers a holistic study of this crucial topic in early modern British history. The contributors survey a vast range of sources, showing the myriad ways people petitioned the authorities from the sixteenth to the eighteenth centuries. They cross the jurisdictional, sub-disciplinary and chronological boundaries that have otherwise constrained the current scholarly literature on petitioning and popular political engagement. Teasing out broad conclusions from innumerable smaller interventions in public life, they not only address the aims, attitudes and strategies of those involved, but also assesses the significance of the processes they used. This volume makes it possible to rethink the power of petitioning and to re-evaluate broad trends regarding political culture, institutional change and state formation
Language policy, development and translanguaging in Africa
No full textThis chapter explores language policy in education in African schools. It explores the history of language policy in education since the colonial period and shows how and why the policy of using a colonial language as the Language of Teaching and Learning (LoTL) continued into the postcolonial period. We then turn to translanguaging as a theory of language learning that can address the apparently intractable problem that language policy in education faces in trying to educate students in a language that they, quite literally, do not understand. We describe the theory of translanguaging and its application in a research project in Amhara region, Ethiopia which led to improvements in student experience and learning outcomes. In conclusion we argue that the highly political character of language policy in Sub-Saharan Africa means that it is unlikely that the use of a European language as the LoTL from grade 4 will change in the near future, however some of the disastrous consequences for learning can be addressed through acknowledging children as skilful communicators and encouraging their development of a meta-theory of language as communication which will support them in the learning a new language and subject content
Examining change in the mental health of young people with epilepsy following a successful psychological intervention
Get PDFObjective: Evaluate the cognitive, behavioural and affective processes involved in therapeutic change for young people with epilepsy and mental health difficulties receiving an integrated mental health intervention.
Methods: As part of a mixed methods convergent design, qualitative data were gathered in parallel to quantitative data at two timepoints in a randomised controlled trial testing the Mental Health Intervention for Children with Epilepsy in addition to usual care. Twenty-five young people and/or their families were interviewed before and after the intervention about the young person’s mental and physical health, and their experience of therapy. Interview data were analysed inductively, idiographically and longitudinally using Interpretative Phenomenological Analysis combined with Framework Analysis.
Results: The young people’s emotional and behaviour problems improved, mirroring the trial’s quantitative outcomes. Their anxiety decreased and behaviour improved as they acquired tools and understanding through therapy. Problems, like aggressive behaviours and emotional outbursts, were also reduced, with young people gaining increased awareness and ability to self-regulate and parents learning to contain their child’s impulsive behaviours.
Conclusions: The qualitative findings complement the MICE trial’s significant positive quantitative results by providing insight and context to the therapeutic change, providing vivid insight into the mechanisms of therapy for individual families
After the photo-copy
No full textAs Olle Essvik and Lars Kristensen suggest, their book Dead & Alive: Reflections on Media / Art is a result of trying to capture the disparate nature of dead media and to present it in yet another edited collection, but within a different casting form. To pursue their book project, they invited a range of international authors including Joanna Zylinska, Sarah Cook, Jesper Olsson among others, who bring different perspectives and approaches to artistic practices, media sociology and technological speculation. At first glance, these disparate contributions to the book might seem out of step, or sometimes even in collision, with each other. In the authors’ words: “Readers of the book will no doubt find this disparity frustrating, or even irritating, but hopefully also exciting and dynamic. Art and technology can intertwine in many different ways, and we wanted to highlight this nature.
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