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Graham, S.

Publications and source records attributed to Graham, S..

3 recordsLinked to original sources

Disrupted reinforcement learning during post-error slowing in ADHD

ADHD is associated with altered dopamine regulated reinforcement learning on prediction errors. Despite evidence of categorically altered error processing in ADHD, neuroimaging advances have largely investigated models of normal reinforcement learning in greater detail. Further, although reinforcement leaning critically relies on ventral striatum exerting error magnitude related thresholding influences on substantia nigra (SN) and dorsal striatum, these thresholding influences have never been identified with neuroimaging. To identify such thresholding influences, we propose that error magnitude related activities must first be separated from opposite activities in overlapping neural regions during error detection. Here we separate error detection from magnitude related adjustment (post-error slowing) during inhibition errors in the stop signal task in typically developing (TD) and ADHD adolescents using fMRI. In TD, we predicted that: 1) deactivation of dorsal striatum on error detection interrupts ongoing processing, and should be proportional to right frontoparietal response phase activity that has been observed in the SST; 2) deactivation of ventral striatum on post-error slowing exerts thresholding influences on, and should be proportional to activity in dorsal striatum. In ADHD, we predicted that ventral striatum would instead correlate with heightened amygdala responses to errors. We found deactivation of dorsal striatum on error detection correlated with response-phase activity in both groups. In TD, post-error slowing deactivation of ventral striatum correlated with activation of dorsal striatum. In ADHD, ventral striatum correlated with heightened amygdala activity. Further, heightened activities in locus coeruleus (norepinephrine), raphe nucleus (serotonin) and medial septal nuclei (acetylcholine), which all compete for control of DA, and are altered in ADHD, exhibited altered correlations with SN. All correlations in TD were replicated in healthy adults. Results in TD are consistent with dopamine regulated reinforcement learning on post-error slowing. In ADHD, results are consistent with heightened activities in the amygdala and non-dopaminergic neurotransmitter nuclei preventing reinforcement learning.

neuroscience

Ring nucleases deactivate Type III CRISPR ribonucleases by degrading cyclic oligoadenylate

The CRISPR-Cas system provides adaptive immunity against mobile genetic elements in prokaryotes, utilising small CRISPR RNAs which direct effector complexes to degrade invading entities. Type III effector complexes were recently demonstrated to synthesise a novel second messenger, cyclic oligoadenylate (cOA), on binding target RNA. cOA in turn binds to and activates a range of downstream effector proteins including ribonucleases (Csm6/Csx1) and transcription factors via a CARF (CRISPR associated Rossman Fold) domain, inducing an antiviral state in the cell that is important for immunity. The mechanism of the \"off-switch\" that resets the system is not understood. Here, we report the identification of the nuclease that degrades these cOA ring molecules. The \"Ring nuclease\" is itself a CARF family protein with a metal independent mechanism, which cleaves cOA4 rings to generate linear di-adenylate species and switches off the antiviral state. The identification of Ring nucleases adds an important insight to the CRISPR-Cas system.

biochemistry

Variation in context dependent foraging behavior across pollinators

Pollinator foraging behavior has direct consequences for plant reproduction and has been implicated in driving floral trait evolution. Exploring the degree to which pollinators exhibit flexibility in foraging behavior will add to a mechanistic understanding of how pollinators can impact selection on plant traits. Although plants have evolved suites of floral traits to attract pollinators, flower color is a particularly important aspect of the floral display. Some pollinators show strong innate color preference, but many pollinators display flexibility in preference due to learning associations between rewards and color, or due to variable perception of color in different environments or plant communities. This study examines the flexibility in flower color preference of two groups of native butterfly pollinators under natural field conditions. Our study reveals that pipevine swallowtails and skippers, the predominate pollinators of the two native Texas Phlox species, display distinct patterns of color preferences across different contexts. Pipevine swallowtails exhibit highly flexible color preferences and likely utilize other floral traits to make foraging decisions. In contrast, skippers have consistent color preferences and likely use flower color as a primary cue for foraging. As a result of this variation in color preference flexibility, the two pollinator groups impose concordant selection on flower color in some contexts but discordant selection in other contexts. This variability could have profound implications for how flower traits respond to pollinator-mediated selection. Our findings suggest that studying dynamics of behavior in natural field conditions is important for understanding plant-pollinator interactions.

animal behavior and cognition