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Dickson, C.

Publications and source records attributed to Dickson, C..

5 recordsLinked to original sources

Preserved self-other integration during social decision making among individuals with elevated autistic traits

Autistic people can find social interactions difficult to navigate, traditionally attributed to difficulties in taking others perspectives. However, we have a limited understanding of how autistic people integrate self and other information efficiently during social decision-making. We conducted four highly powered experiments (total N = 1,621) to determine whether autistic traits affect two aspects of self-other integration during social decision making: self-bias and social basis function use. Using Bayesian analyses, we found strong support for the absence of a relationship between autistic traits and either aspect of social decision making, even after controlling for potential confounds (BF01 = 32.13 for self-bias, BF01 = 7.04 for social basis function use). Our results indicate that variations along autistic traits do not impact how people prioritise self-relevant information (self-bias) or utilize compressed social patterns of interaction (social basis function use) to guide their decisions about oneself and other people. These findings nuance the conceptualisation of social-cognitive processes across autistic traits while highlighting the need for large samples to validate null effects.

neuroscience↗

Manipulation of Photosensory and Circadian Signalling Restricts Developmental Plasticity in Arabidopsis

AbstractPlants exploit developmental plasticity to adapt their growth and development to prevailing environmental cues. This developmental plasticity provides a selective and competitive advantage in nature but is obstructive during large-scale, intensive agricultural practices since economically important traits (including vegetative growth and flowering time) can widely vary depending on local environmental conditions. This prevents accurate prediction of harvesting times and produces a variable crop. We sought to restrict developmental plasticity by manipulating signalling systems that govern plants responses to environmental signals. Mathematical modelling of plant growth and development predicted a reduction in plant responses to changing environments when circadian and light signaling pathways were manipulated. We tested this hypothesis by utilising a constitutively-active allele of the plant photoreceptor phytochromeB, along with disruption of the circadian system via mutation of EARLY FLOWERING3. We found that the combination of these manipulations produced plants that are less responsive to light and temperature cues. These engineered plants have uniform vegetative growth and flowering time and demonstrate how developmental plasticity can be limited whilst maintaining plant productivity. This has significant implications for future agriculture in both open fields and controlled environments.

plant biology↗

EXORIBONUCLEASE4 integrates metabolic signals induced by osmotic stress into the circadian system

The circadian clock system acts as an endogenous timing reference that coordinates many metabolic and physiological processes in plants. Previous studies have shown that the application of osmotic stress delays circadian rhythms via 3-Phospho-Adenosine 5-Phosphate (PAP), a retrograde signalling metabolite that is produced in response to redox stress within organelles. PAP accumulation leads to the inhibition of EXORIBONUCLEASEs (XRNs), which are responsible for RNA degradation. Interestingly, we are now able to demonstrate that post-transcriptional processing is crucial for the circadian response to osmotic stress. Our data show that degradation of specific circadian clock transcripts is modulated by osmotic stress, suggesting that RNA metabolism plays a vital role in circadian clock coordination during drought. Inactivation of XRN4 is sufficient to extend circadian rhythms, with LWD1, LWD2, and PRR7 identified as specific XRN4 targets that are post-transcriptionally regulated to delay circadian progression. One Sentence SummaryPost-transcriptional regulation of specific transcripts enables the circadian system to respond to osmotic stress.

plant biology↗

Macrophage activation of cGAS and TRIM5 distinguish pandemic and non-pandemic HIV

Pandemic viruses remain a global threat to health and economics but how they adapt to become pandemic remains poorly understood. Here we compare pandemic HIV-1(M) and non-pandemic HIV-(O) and HIV-2 strains finding that non-pandemic HIV replicate poorly in myeloid cell models due to activation of cGAS and TRIM5, and ensuing antiviral responses. We use phylogenetics and viral capsid structural biology to define specific differences between pandemic and non-pandemic HIV capsids and demonstrate that their genetic reversal in HIV-1(M) mutants causes TRIM5, cGAS and innate immune activation. We propose a model in which the parental lineage of pandemic HIV-1(M) has uniquely evolved a dynamic capsid that avoids activation of cGAS and TRIM5 to establish cloaked replication in myeloid cells. The unique adaptations of the pandemic virus lineage suggests a role in effective human-to-human transmissibility and highlight the importance of avoiding innate immune activation during pandemic human-to-human viral transmission.

immunology↗

Substrate-induced clustering activates Trim-Away of pathogens and proteins

Trim-Away is a powerful new technology that exploits off-the-shelf antibodies and the E3 RING ligase and cytosolic antibody receptor TRIM21 to carry out rapid protein depletion. How TRIM21 is catalytically-activated upon substrate engagement during either its normal immune function or when re-purposed for targeted protein degradation is unknown. Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away. We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically. This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.

molecular biology↗