Embryonic development of selectively vulnerable neurons in Parkinson's disease

A specific set of brainstem nuclei are susceptible to degeneration in Parkinson’s disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative result of a transcriptional regulatory program that is active during the development. By manual curation of the developmental biology literature, we comprehensively reconstructed an anatomically resolved cellular developmental lineage for the adult neurons in five brainstem regions that are selectively vulnerable to degeneration in prodromal or early Parkinson’s disease. We synthesised the literature on transcription factors that are required to be active, or required to be inactive, in the development of each of these five brainstem regions, and at least two differentially vulnerable nuclei within each region. Certain transcription factors, e.g., Ascl1 and Lmx1b, seem to be required for specification of many brainstem regions that are susceptible to degeneration in early Parkinson’s disease. Some transcription factors can even distinguish between differentially vulnerable nuclei within the same brain region, e.g., Pitx3 is required for specification of the substantia nigra pars compacta, but not the ventral tegmental area. We do not suggest that Parkinson’s disease is a developmental disorder. In contrast, we consider identification of shared developmental trajectories as part of a broader effort to identify the molecular mechanisms that underlie the phenotypic features that are shared by selectively vulnerable neurons. Systematic in vivo assessment of fate determining transcription factors should be completed for all neuronal populations vulnerable to degeneration in early Parkinson’s disease

‘Green’ on the ground but not in the air: Pro-environmental attitudes are related to household behaviours but not discretionary air travel

The rise in greenhouse gas emissions from air travel could be reduced by individuals voluntarily abstaining from, or reducing, flights for leisure and recreational purposes. In theory, we might expect that people with pro-environmental value orientations and concerns about the risks of climate change, and those who engage in more pro-environmental household behaviours, would also be more likely to abstain from such voluntary air travel, or at least to fly less far. Analysis of two large datasets from the United Kingdom, weighted to be representative of the whole population, tested these associations. Using zero-inflated Poisson regression models, we found that, after accounting for potential confounders, there was no association between individuals’ environmental attitudes, concern over climate change, or their routine pro-environmental household behaviours, and either their propensity to take non-work related flights, or the distances flown by those who do so. These findings contrasted with those for pro-environmental household behaviours, where associations with environmental attitudes and concern were observed. Our results offer little encouragement for policies aiming to reduce discretionary air travel through pro-environmental advocacy, or through ‘spill-over’ from interventions to improve environmental impacts of household routines

Normal-state conductivity in underdoped La_{2-x}Sr_xCuO_4 thin films: Search for nonlinear effects related to collective stripe motion

We report a detailed study of the electric-field dependence of the normal-state conductivity in La_{2-x}Sr_xCuO_4 thin films for two concentrations of doped holes, x=0.01 and 0.06, where formation of diagonal and vertical charged stripes was recently suggested. In order to elucidate whether high electric fields are capable of depinning the charged stripes and inducing their collective motion, we have measured current-voltage characteristics for various orientations of the electric field with respect to the crystallographic axes. However, even for the highest possible fields (~1000 V/cm for x=0.01 and \~300 V/cm for x=0.06) we observed no non-linear-conductivity features except for those related to the conventional Joule heating of the films. Our analysis indicates that Joule heating, rather than collective electron motion, may also be responsible for the non-linear conductivity observed in some other 2D transition-metal oxides as well. We discuss that a possible reason why moderate electric fields fail to induce a collective stripe motion in layered oxides is that fairly flexible and compressible charged stripes can adjust themselves to the crystal lattice and individual impurities, which makes their pinning much stronger than in the case of conventional rigid charge-density waves.Comment: 10 pages, 10 figures, accepted for publication in Phys. Rev.

Pedagogies for the 'dis‐engaged': diverse experiences of the young people’s Arts Award programme

Art education is often praised for its engaging programmes and inclusive pedagogies, with many initiatives created with the intention of widening access for those who are deemed to be lacking. This article investigates one such programme – the young people’s Arts Award, which is a nationally recognised qualification for young people aged 11–25. I call upon a range of pedagogies in order to critique the Arts Award within the context of informal and alternative education settings in the United Kingdom. Drawing on a 12‐month ethnographic study, the research was conducted across five diverse programmes which included youth work projects and alternative provision. I present two cases – ‘learning to be an artist’ and ‘learning to behave’ – which demonstrate a hierarchy of pedagogy in the application of this programme across these particular contexts. Artists’ Signature Pedagogies are used as an analytical framework to explore the affordances of working with artists through the programme. Further, I engage with the Pedagogy of Poverty to demonstrate that young people who were classified as ‘dis‐engaged’ were more likely to receive lower quality programmes, low‐level work and over‐regulated teaching. I argue that despite changes to the ways that young people access art education, there continues to be unequal opportunities. This finding is significant for not only creative practitioners and youth arts workers, but also arts education policy makers and programmers

Entanglement generation and transfer between remote atomic qubits interacting with squeezed field

A pair of two level atoms A1A2, prepared either in a separable state or in an entangled state, interacts with a single mode of two mode squeezed cavity field while a third atomic qubit B interacts with the second mode of the squeezed field in a remote cavity. We analyze, numerically, the generation, sudden death and revival of three qubit entanglement as a function of initial entanglement of qubits A1A2 and degree of squeezing of electromagnetic field. Global negativity of partially transposed state operator is used to quantify the entanglement of three atom state. It is found that the initial entanglement of two mode field as well as that of the pair A1A2, both, contribute to three atom entanglement. A maximally entangled single excitation Bell pair in first cavity and two mode field with squeeze parameter s=0.64 are the initial conditions that optimize the peak value of three qubit mixed state entanglement. A smaller value of s=0.4 under similar conditions is found to generate a three qubit mixed state with comparable entanglement dynamics free from entanglement sudden death.Comment: 14 pages, 7 figures, sections III and IV merged with section II and analytic expressions moved to Appendices A and B. Figures improved and corrected typo

Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies

Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, as well as variants rare in European populations, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conducted genome-wide association studies (GWAS) of 31 serum and urine biomarker quantitative traits in African (n = 9354), East Asian (n = 2559), and South Asian (n = 9823) ancestry UK Biobank (UKBB) participants. We adjusted for all known GWAS catalog variants for each trait, as well as novel signals identified in a recent European ancestry-focused analysis of UKBB participants. We identify 7 novel signals in African ancestry and 2 novel signals in South Asian ancestry participants (p < 1.61E−10). Many of these signals are highly plausible, including a cis pQTL for the gene encoding gamma-glutamyl transferase and PIEZO1 and G6PD variants with impacts on HbA1c through likely erythrocytic mechanisms. This work illustrates the importance of using the genetic data we already have in diverse populations, with novel discoveries possible in even modest sample sizes