OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory

A healthy mitochondrial network is essential for the maintenance of neuronal synaptic integrity. Mitochondrial and metabolic dysfunction contributes to the pathogenesis of many neurodegenerative diseases including dementia. OPA1 is the master regulator of mitochondrial fusion and fission and is likely to play an important role during neurodegenerative events. To explore this, we quantified hippocampal dendritic and synaptic integrity and the learning and memory performance of aged Opa1 haploinsufficient mice carrying the Opa1Q285X mutation (B6; C3-Opa1Q285STOP; Opa1+/−). We demonstrate that heterozygous loss of Opa1 results in premature age-related loss of spines in hippocampal pyramidal CA1 neurons and a reduction in synaptic density in the hippocampus. This loss is associated with subtle memory deficits in both spatial novelty and object recognition. We hypothesize that metabolic failure to maintain normal neuronal activity at the level of a single spine leads to premature age-related memory deficits. These results highlight the importance of mitochondrial homeostasis for maintenance of neuronal function during ageing

Exile Vol. XXIX No. 2

Photo by John Taylor 2 Poem by Ezra Pound 3 Photo by James Lundy 4 Balanced Budget by August West 5 The Lighter by John Zarchen 6-7 Photo by Theodore Granberg 8 Uptown by Christopher B. Brougham 9 Photo by Jeff Russell 9 Heartstrings by Pete Waters 10 Spell by Eric Stevenson 10 Mums by Mandy Wilson 10 A New Day by Chad Hussey 11 Photo by Chad Hussey 12 Solitare by Gordon Black 13-14 Photo by James Lundy 15 A Grave Day-Dream by John Zarchen 16 Photo by James Lundy 17 Photo by Pauela Theodotou 18 Reconciliation by R. T. Hayashi 19 Michigan Rt. 37 by Ruth Wick 20 Shenango Valley by August West 20 Photo by James Lundy 21 Drawing by Adrienne Wehr 22 Ultraviolet Blues by Kathy Shelton 23 New Orleans & The Silky Black Seams Of My Stockings by Kate Reynolds 23 Refraction by Pam Houston 23-31 Photo by James Lundy 32 A Midsummer Night\u27s... by R. T. Hayashi 33 Couch sleeping by Eric Stevenson 33 Before We Could Build by Kim Kiefer 34 Photo by Chad Hussey 35 The Legend Of The Bear Mother by Amy Pence 36 Photo by James Lundy 37 Cover Drawing by Peter Brooke -title pag

The environmental costs and benefits of high-yield farming

How we manage farming and food systems to meet rising demand is pivotal to the future of biodiversity. Extensive field data suggest impacts on wild populations would be greatly reduced through boosting yields on existing farmland so as to spare remaining natural habitats. High-yield farming raises other concerns because expressed per unit area it can generate high levels of externalities such as greenhouse gas (GHG) emissions and nutrient losses. However, such metrics underestimate the overall impacts of lower-yield systems, so here we develop a framework that instead compares externality and land costs per unit production. Applying this to diverse datasets describing the externalities of four major farm sectors reveals that, rather than involving trade-offs, the externality and land costs of alternative production systems can co-vary positively: per unit production, land-efficient systems often produce lower externalities. For GHG emissions these associations become more strongly positive once forgone sequestration is included. Our conclusions are limited: remarkably few studies report externalities alongside yields; many important externalities and farming systems are inadequately measured; and realising the environmental benefits of high-yield systems typically requires additional measures to limit farmland expansion. Yet our results nevertheless suggest that trade-offs among key cost metrics are not as ubiquitous as sometimes perceived. There is an author correction to this article. See: https://doi.org/10.1038/s41893-018-0138-5We are grateful for funding from the Cambridge Conservation Initiative Collaborative Fund and Arcadia, the Grantham Foundation for the Protection of the Environment, the Kenneth Miller Trust the UK-China Virtual Joint Centre for Agricultural Nitrogen (CINAg, 780 BB/N013468/1, financed by the Newton Fund via BBSRC and NERC), BBSRC (BBS/E/C/000I0330), DEVIL (NE/M021327/1), U-GRASS (NE/M016900/1), Soils-R-GRREAT (NE/P019455/1), N-Circle (BB/N013484/1), BBSRC Soil to Nutrition (S2N) strategic programme (BBS/E/C/000I0330), UNAM-PAPIIT (IV200715), the Belmont Forum/FACEE-JPI (NE/M021327/1 ‘DEVIL’), and the Cambridge Earth System Science NERC DTP (NE/L002507/1); AB is supported by a Royal Society Wolfson Research Merit award

The LeVe CPAP System for Oxygen-Efficient CPAP Respiratory Support: Development and Pilot Evaluation

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a significant demand on healthcare providers (HCPs) to provide respiratory support for patients with moderate to severe symptoms. Continuous Positive Airway Pressure (CPAP) non-invasive ventilation can help patients with moderate symptoms to avoid the need for invasive ventilation in intensive care. However, existing CPAP systems can be complex (and thus expensive) or require high levels of oxygen, limiting their use in resource-stretched environments. Technical Development + Testing: The LeVe (“Light”) CPAP system was developed using principles of frugal innovation to produce a solution of low complexity and high resource efficiency. The LeVe system exploits the air flow dynamics of electric fan blowers which are inherently suited to delivery of positive pressure at appropriate flow rates for CPAP. Laboratory evaluation demonstrated that performance of the LeVe system was equivalent to other commercially available systems used to deliver CPAP, achieving a 10 cm H2O target pressure within 2.4% RMS error and 50–70% FiO2 dependent with 10 L/min oxygen from a commercial concentrator. Pilot Evaluation: The LeVe CPAP system was tested to evaluate safety and acceptability in a group of ten healthy volunteers at Mengo Hospital in Kampala, Uganda. The study demonstrated that the system can be used safely without inducing hypoxia or hypercapnia and that its use was well-tolerated by users, with no adverse events reported. Conclusions: To provide respiratory support for the high patient numbers associated with the COVID-19 pandemic, healthcare providers require resource efficient solutions. We have shown that this can be achieved through frugal engineering of a CPAP ventilation system, in a system which is safe for use and well-tolerated in healthy volunteers. This approach may also benefit other respiratory conditions which often go unaddressed in Low and Middle Income Countries (LMICs) for want of context-appropriate technology designed for the limited oxygen resources available

One Hundred Years of Sound: Institutional Recordings at the Curtis Institute of Music

This presentation will narrate a history of Curtis’s institutional recordings, a collection that spans much of the Institute’s nearly 100-year existence. As an archive of student and faculty recitals recorded on a range of formats, the collection constitutes an audio and video history of musical training, performance practice, and recording technologies in European classical music throughout the 20th century, as well as a glimpse into wider cultural and social issues in Philadelphia and the U.S. This history will be presented in the context of professional concerns such as preservation, digitization, access, and metadata, as well as administrative concerns like budgeting, collection development policies, and the library’s relationship to the Institute as a whole

Teacher supply in Cumbria: the contribution of teacher education

A research study carried out jointly by the University of Cumbria and the Local Authority in Cumbria aimed at influencing policy and practice by investigating how the work of the Faculty of Education, in partnership with the secondary schools in Cumbria and the local authority, influences teacher supply in Cumbria

Author Correction: The environmental costs and benefits of high-yield farming

In the version of this Article originally published, ammonia and NO emissions (and associated N deposition), nitrate leaching, and the CO emitted during urea hydrolysis following application to land were all accidentally omitted in the comparison of the greenhouse gas impacts of using ammonium nitrate and urea to produce wheat grain