Alzheimer's disease: Clues from flies and worms

AbstractPresenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid β peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked

The potential role of genetic markers in talent identification and athlete assessment in elite sport

In elite sporting codes, the identification and promotion of future athletes into specialized talent pathways is heavily reliant upon objective physical, technical, and tactical characteristics, in addition to subjective coach assessments. Despite the availability of a plethora of assessments, the dependence on subjective forms of identification remain commonplace in most sporting codes. More recently, genetic markers, including several single nucleotide polymorphisms (SNPs), have been correlated with enhanced aerobic capacity, strength, and an overall increase in athletic ability. In this review, we discuss the effects of a number of candidate genes on athletic performance, across single-skilled and multifaceted sporting codes, and propose additional markers for the identification of motor skill acquisition and learning. While displaying some inconsistencies, both the ACE and ACTN3 polymorphisms appear to be more prevalent in strength and endurance sporting teams, and have been found to correlate to physical assessments. More recently, a number of polymorphisms reportedly correlating to athlete performance have gained attention, however inconsistent research design and varying sports make it difficult to ascertain the relevance to the wider sporting population. In elucidating the role of genetic markers in athleticism, existing talent identification protocols may significantly improve—and ultimately enable—targeted resourcing in junior talent pathways

Intra- and extra-euro area import demand for manufactures

The aim of this paper is to improve our understanding of the key determinants of intra- and extra-euro area imports. Using a simultaneous equation estimation framework, and pooling the data across nine euro area countries as an approximation of the euro area, we estimate intra- and extra-euro area import demand functions and impose various restrictions within and across equations. We find that there are significant substitution effects between intra- and extra-euro area imports due to changes in their relative prices, while exchange rate volatility decreases trade vis-à-vis regions characterised by volatility and leads to substitution of trade away from higher-volatility regions towards lower-volatility regions. JEL Classification: C32, C33, E00, E32, O3intra- and extra-euro area imports, substitution, three stage least squares, trade integration

Mass Atrocities and their Prevention

Counting conservatively, and ignoring physical injuries and mental trauma, data show about 100 million mass atrocity-related deaths since 1900. Occurring in war and in peacetime, and of enormous scale, severity, and brutality, they are geographically widespread, occur with surprising frequency, and can be long-lasting in their adverse effects on economic and human development, wellbeing, and wealth. As such, they are a major economic concern. This article synthesizes very diverse and widely dispersed theoretical and empirical literatures, addressing two gaps: a “mass atrocities gap” in the economics literature and an “economics gap” in mass atrocities scholarship. Our goals are, first, for noneconomists to learn how economic inquiry contributes to understanding the causes and conduct of mass atrocities and possibly to their mitigation and prevention and, second, to survey and synthesize for economists a broad sweep of literatures to serve as a common platform on which to base further work in this field

Economia de conflito e paz

We present an overview of the field of conflict economics. We begin by explaining important distinctions between standard textbook economics and conflict economics regarding assumptions, subject matter, and interrelations between economics and conflict. We then provide summaries of selected economic theories and empirical evidence that together help reveal important aspects of conflict – and peace – through an economics lens. Among the topics covered in the theoretical and empirical overview are why violence is sometimes chosen over peaceful approaches to address intergroup disputes, why it is “rational” for political leaders to sometimes mass kill civilians (and what can be done to prevent this), how social norms of committing harm against outgroups can propagate (or be stopped), why it can be difficult to develop laws and institutions to promote stable peace, and how third-party efforts to promote peace can sometimes make things worse. Lastly, we provide samples of data resources, working paper archives and journals, and readings consisting of major textbooks, handbooks, and edited books in the field of conflict economics.Apresentamos uma visão geral do campo da economia de conflito. Começamos explicando distinções importantes entre a economia padrão de livros didáticos e economia de conflito em relação a suposições, assunto e inter-relações entre economia e conflito. Em seguida, fornecemos resumos de teorias econômicas selecionadas e evidências empíricas que, juntos, ajudam a revelar aspectos importantes do conflito - e da paz - por meio de uma lente econômica. Entre os tópicos abordados na visão teórica e empíricau, por que é “racional” que líderes políticos às vezes matem civis em massa (e o que pode ser feito para evitar isso), como normas sociais de cometer danos contra grupos externos podem se propagar (ou ser interrompido), por que pode ser difícil desenvolver leis e instituições para promover a paz estável e como os esforços de terceiros para promover a paz podem às vezes piorar as coisas. Por último, fornecemos amostras de recursos de dados, arquivos e periódicos de trabalho, e leituras que consistem em grandes livros-texto, manuais e livros editados no campo da economia de conflito

‘We achieve the impossible’: discourses of freedom and escape at music festivals and free parties

In this article, we explore the notion of freedom as a form of governance within contemporary consumer culture in a sphere where ‘freedom’ appears as a key component: outdoor music-based leisure events, notably music festivals and free parties. ‘Freedom’ is commodified as central to the marketing of many music festivals, which now form a highly commercialised sector of the UK leisure industry, subject to various regulatory restrictions. Free parties, in contrast, are unlicensed, mostly illegal and far less commercialised leisure spaces. We present data from two related studies to investigate how participants at three major British outdoor music festivals and a small rural free party scene draw on discourses of freedom, escape and regulation. We argue that major music festivals operate as temporary bounded spheres of ‘licensed transgression’, in which an apparent lack of regulation operates as a form of governance. In contrast, free parties appear to ‘achieve the impossible’ by creating alternative (and illegal) spaces in which both freedom and regulation are constituted in different ways compared to music festival settings

Differential effects of apolipoprotein E isoforms on phosphorylation at specific sites on tau by glycogen synthase kinase-3β identified by nano-electrospray mass spectrometry

AbstractPreviously published data have shown an allele-specific variation in the in vitro binding of apolipoprotein E (apoE) to tau, which prompted the hypothesis that apoE binding may protect tau from phosphorylation, apoE3 being more efficient than apoE4. We have, therefore, investigated the effects of apoE on tau phosphorylation in vitro by the proline-directed kinase, glycogen synthase kinase (GSK)-3β. The phosphopeptide maps of tau alone, of tau with apoE3 and of tau with apoE4 were very similar. When apoE2 was present a further four spots were evident. Additionally, of the 15 peptides phosphorylated in the presence or absence of apoE, subtle differences, some isoform-specific, in the relative amounts of phosphorylation were observed

Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: Involvement of src family protein kinases

The increased production of amyloid beta -peptide (A beta) in Alzheimer's disease is acknowledged to be a key pathogenic event. In this study, we examined the response of primary human and rat brain cortical cultures to A beta administration and found a marked increase in the tyrosine phosphorylation content of numerous neuronal proteins, including tau and putative microtubule-associated protein 2c (MAP2c). We also found that paired helical filaments of aggregated and hyperphosphorylated tau are tyrosine phosphorylated, indicating that changes in the phosphotyrosine content of cytoplasmic proteins in response to A beta are potentially an important process. Increased tyrosine phosphorylation of cytoskeletal and other neuronal proteins was specific to fibrillar A beta (25-35) and A beta (1-42). The tyrosine phosphorylation was blocked by addition of the Src family tyrosine kinase inhibitor 4-amino-5-( 4-chlorophenyl)- 7(t-butyl) pyrazol(3,4-D) pyramide (PP2) and the phosphatidylinositol 3-kinase inhibitor LY 294002. Tyrosine phosphorylation of tau and MAP2c was concomitant with an increase in the tyrosine phosphorylation and subsequent putative activation of the non-receptor kinase, focal adhesion kinase (FAK). Immunoprecipitation of Fyn, a member of the Src family, from A beta (25-35)-treated neurons showed an increased association of Fyn with FAK. A beta treatment of cells also stimulated the sustained activation of extracellular regulated kinase-2, which was blocked by addition of PP2 and LY 294002, suggesting that FAK/Fyn/PI3-kinase association is upstream of mitogen-activated protein (MAP) kinase signaling in A beta -treated neurons. This cascade of signaling events contains the earliest biochemical changes in neurons to be described in response to A beta exposure and may be critical for subsequent neurodegenerative changes