120 research outputs found
Towards take-all control:A C-â21β oxidase required for acylation of triterpene defence compounds in oat
Oats produce avenacins, antifungal triterpenes that are synthesized in the roots and provide protection against take-all and other soilborne diseases. Avenacins are acylated at the carbon-21 position of the triterpene scaffold, a modification critical for antifungal activity. We have previously characterized several steps in the avenacin pathway, including those required for acylation. However, transfer of the acyl group to the scaffold requires the C-21β position to be oxidized first, by an as yet uncharacterized enzyme. We mined oat transcriptome data to identify candidate cytochrome P450 enzymes that may catalyse C-21β oxidation. Candidates were screened for activity by transient expression in Nicotiana benthamiana. We identified a cytochrome P450 enzyme AsCYP72A475 as a triterpene C-21β hydroxylase, and showed that expression of this enzyme together with early pathway steps yields C-21β oxidized avenacin intermediates. We further demonstrate that AsCYP72A475 is synonymous with Sad6, a previously uncharacterized locus required for avenacin biosynthesis. sad6 mutants are compromised in avenacin acylation and have enhanced disease susceptibility. The discovery of AsCYP72A475 represents an important advance in the understanding of triterpene biosynthesis and paves the way for engineering the avenacin pathway into wheat and other cereals for control of take-all and other diseases
Prognostic evaluation in patients with advanced cancer in the last months of life:ESMO Clinical Practice Guideline
: ⢠This ESMO Clinical Practice Guideline provides key recommendations for using prognostic estimates in advanced cancer. ⢠The guideline covers recommendations for patients with cancer and an expected survival of months or less. ⢠An algorithm for use of clinical predictions, prognostic factors and multivariable risk prediction models is presented. ⢠The author group encompasses a multidisciplinary group of experts from different institutions in Europe, USA and Asia. ⢠Recommendations are based on available scientific data and the authorsâ collective expert opinion
Finland
Peer reviewe
Active ageing, pensions and retirement in the UK
The ageing population has led to increasing concerns about pensions and their future
sustainability. Much of the dominant policy discourse around ageing and pension provision
over the last decade has focussed on postponing retirement and prolonging employment.
These measures are central to productive notions of âactive ageingâ. Initially the paper briefly
sets out the pension developments in the UK. Then it introduces active ageing and active
ageing policy, exploring its implications for UK pension provision. It demonstrates that a
more comprehensive active ageing framework, which incorporates a life-course perspective,
has the potential to assist the UK to respond to the challenges of an ageing population. In
doing so it needs to highlight older people as an economic and social resource, and reduce
barriers to older peopleâs participation in society
No Need for a Cognitive Map: Decentralized Memory for Insect Navigation
In many animals the ability to navigate over long distances is an important prerequisite for foraging. For example, it is widely accepted that desert ants and honey bees, but also mammals, use path integration for finding the way back to their home site. It is however a matter of a long standing debate whether animals in addition are able to acquire and use so called cognitive maps. Such a âmapâ, a global spatial representation of the foraging area, is generally assumed to allow the animal to find shortcuts between two sites although the direct connection has never been travelled before. Using the artificial neural network approach, here we develop an artificial memory system which is based on path integration and various landmark guidance mechanisms (a bank of individual and independent landmark-defined memory elements). Activation of the individual memory elements depends on a separate motivation network and an, in part, asymmetrical lateral inhibition network. The information concerning the absolute position of the agent is present, but resides in a separate memory that can only be used by the path integration subsystem to control the behaviour, but cannot be used for computational purposes with other memory elements of the system. Thus, in this simulation there is no neural basis of a cognitive map. Nevertheless, an agent controlled by this network is able to accomplish various navigational tasks known from ants and bees and often discussed as being dependent on a cognitive map. For example, map-like behaviour as observed in honey bees arises as an emergent property from a decentralized system. This behaviour thus can be explained without referring to the assumption that a cognitive map, a coherent representation of foraging space, must exist. We hypothesize that the proposed network essentially resides in the mushroom bodies of the insect brain
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A psychosocial goal-setting and manualised support intervention for independence in dementia (NIDUS-Family) versus goal setting and routine care: a single-masked, phase 3, superiority, randomised controlled trial
Summary
Background Although national guidelines recommend that everyone with dementia receives personalised post-diagnostic support, few do. Unlike previous interventions that improved personalised outcomes in people with dementia, the NIDUS-Family intervention is fully manualised and deliverable by trained and supervised, non-clinical facilitators. We aimed to investigate the effectiveness of home-based goal setting plus NIDUS-Family in supporting the attainment of personalised goals set by people with dementia and their carers.
Methods We did a two-arm, single-masked, multi-site, randomised, clinical trial recruiting patientâcarer dyads from community settings. We randomly assigned dyads to either home-based goal setting plus NIDUS-Family or goal setting and routine care (control). Randomisation was blocked and stratified by site (2:1; intervention to control), with allocations assigned via a remote web-based system. NIDUS-Family is tailored to goals set by dyads by selecting modules involving behavioural interventions, carer support, psychoeducation, communication and coping skills, enablement, and environmental adaptations. The intervention involved six to eight video-call or telephone sessions (or in person when COVID-19-related restrictions allowed) over 6 months, then telephone follow-ups every 2â3 months for 6 months. The primary outcome was carer-rated goal attainment scaling (GAS) score at 12 months. Analyses were done by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN11425138.
Findings Between April 30, 2020, and May 9, 2021, we assessed 1083 potential dyads for eligibility, 781 (72¡1%) of whom were excluded. Of 302 eligible dyads, we randomly assigned 98 (32¡4%) to the control group and 204 (67¡5%) to the intervention group. The mean age of participants with dementia was 79¡9 years (SD 8¡2), 169 (56%) were women, and 133 (44%) were men. 247 (82%) dyads completed the primary outcome, which favoured the intervention (mean GAS score at 12 months 58¡7 [SD 13¡0; n=163] vs 49¡0 [14¡1; n=84]; adjusted difference in means 10¡23 [95% CI 5¡75â14¡71]; p<0¡001). 31 (15¡2%) participants in the intervention group and 14 (14¡3%) in the control group experienced serious adverse events.
Interpretation To our knowledge, NIDUS-Family is the first readily scalable intervention for people with dementia and their family carers that improves attainment of personalised goals. We therefore recommend that it be implemented in health and care services
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