Shrub expansion in the Arctic may induce large-scale carbon losses due to changes in plant-soil interactions

Background Tall deciduous shrubs are increasing in range, size and cover across much of the Arctic, a process commonly assumed to increase carbon (C) storage. Major advances in remote sensing have increased our ability to monitor changes aboveground, improving quantification and understanding of arctic greening. However, the vast majority of C in the Arctic is stored in soils, where changes are more uncertain. Scope We present pilot data to argue that shrub expansion will cause changes in rhizosphere processes, including the development of new mycorrhizal associations that have the potential to promote soil C losses that substantially exceed C gains in plant biomass. However, current observations are limited in their spatial extent, and mechanistic understanding is still developing. Extending measurements across different regions and tundra types would greatly increase our ability to predict the biogeochemical consequences of arctic vegetation change, and we present a simple method that would allow such data to be collected. Conclusions Shrub expansion in the Arctic could promote substantial soil C losses that are unlikely to be offset by increases in plant biomass. However, confidence in this prediction is limited by a lack of information on how soil C stocks vary between contrasting Arctic vegetation communities; this needs to be addressed urgently

Fusion Learning Colloquium 2022 - Proceedings

This is the proceedings of the 2022 Fusion Learning Colloquium held at Bournemouth University in the UK

Preclinical characterization and first-in-human administration of a selective monoacylglycerol Lipase inhibitor, ABX-1431

Preclinical characterization and first-in-human administration of a selective monoacylglycerol lipase inhibitor, ABX-1431 Iain Fraser1*, Jacqueline Blankman1, Jason Clapper1, Cheryl Grice1, Gary O'Neill1, Alan Ezekowitz1, Archie Thurston2, Els Geenens3, Corinne Vandermeulen3 and Jan De Hoon3 1 Abide Therapeutics, N/A, United States 2 Seventh Wave Laboratories, N/A, United States 3 UZ Leuven, Center for Clinical Pharmacology, Belgium Background: Monoacylglycerol lipase (MGLL) is a serine hydrolase that breaks down 2-arachidonoylglycerol (2-AG), the major endocannabinoid. Inhibiting MGLL enhances 2-AG concentrations locally, which is expected to rectify neurotransmitter balance through activation of presynaptic CB1 receptors. ABX-1431 is a first-in-class, orally-available, selective, and potent covalent inhibitor of MGLL being developed for the treatment of diseases like multiple sclerosis, movement disorders and pain. Methods: ABX-1431 entered clinical studies supported by a comprehensive preclinical dossier. Selectivity for MGLL amongst other serine hydrolases was profiled using activity-based protein profiling, and MGLL enzyme-recovery kinetics were established. A translatable assay using peripheral blood mononuclear cells (PBMC) was developed to monitor clinical target engagement. ABX-1431 was evaluated in sequential single-, and multiple-ascending dose panels of healthy volunteers. Results: ABX-1431 doses administered orally were 2 to 200 mg as single doses, and 10 to 40 mg daily as multiple doses. Plasma concentrations of ABX-1431 increased in a dose-related fashion, with minimal accumulation. MGLL activity in PBMC was inhibited in a time- and dose-related fashion, with recovery of enzyme activity as drug concentrations declined. Central nervous system manifestations, consistent with activation of the endocannabinoid system were observed at higher doses of ABX-1431. Additional clinical assessments of mood, suicidality, cutaneous nociception and cognition revealed no clinically significant abnormalities. Conclusions: At oral doses that were generally safe and well-tolerated, ABX-1431 plasma concentrations and magnitude of inhibition of PBMC MGLL enzyme activity were similar to those associated with efficacy in preclinical models, supporting the continued clinical evaluation of this first-in-mechanism MGLL inhibitor.status: Published onlin

Tapology:a game-based platform to facilitate e-health and e-inclusion

We have developed a tablet computer game app for low vision users that can be used to introduce a platform for gaming, internet and visual rehabilitation to older users who have not had prior experience with information communication technology (ICT). Our target user group is people diagnosed with Age Related Macular Degeneration (AMD). The primary goal of the app is to present a fun and engaging means for participants to engage with Information Communication Technology (ICT). A long-term goal of the project is to build a platform to gather data on current and on-going visual function by creating a suite of games that could generate sufficient regular visual engagement to enable perceptual learning in the preserved peripheral retina that is spared in AMD.The inclusive design process took into consideration the perceptual and cognitiveconstraints of the user group in. The ‘Tapology©’ app was formally launched at a large computer games festival where we gathered data from a range of users to inform the development of the gameplay. The initial results and feedback inform the ultimate goal of creating a suite of applications that have a wide social and geographic reach to promote and inform e-inclusion and e-health

Il gioco dell'agente segreto

Published version of a chapter in the book: Universal Access in Human-Computer Interaction. Aging and Assistive Environments. Also available from the publisher at: http://dx.doi.org/10.1007/978-3-319-07446-7_36We have developed a tablet computer game app for low vision users that can be used to introduce a platform for gaming, internet and visual rehabilitation to older users who have not had prior experience with information communication technology (ICT). Our target user group is people diagnosed with Age Related Macular Degeneration (AMD). The primary goal of the app is to present a fun and engaging means for participants to engage with Information Communication Technology (ICT). A long-term goal of the project is to build a platform to gather data on current and on-going visual function by creating a suite of games that could generate sufficient regular visual engagement to enable perceptual learning in the preserved peripheral retina that is spared in AMD. The inclusive design process took into consideration the perceptual and cognitive constraints of the user group in. The 'Tapology©' app was formally launched at a large computer games festival where we gathered data from a range of users to inform the development of the gameplay. The initial results and feedback inform the ultimate goal of creating a suite of applications that have a wide social and geographic reach to promote and inform e-inclusion and e-health

Profiling gut microbiota and bile acid metabolism in critically ill children

Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the Lachnospiraceae recovered during the late-acute phase (days 8–10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in Lachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids

Profiling gut microbiota and bile acid metabolism in critically ill children.

Funder: Great Ormond Street Hospital Charity; doi: http://dx.doi.org/10.13039/501100001279Funder: Imperial College London; doi: http://dx.doi.org/10.13039/501100000761Funder: Evelyn Trust; doi: http://dx.doi.org/10.13039/501100004282Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the Lachnospiraceae recovered during the late-acute phase (days 8-10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in Lachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids