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Fitzsimmons, S.

Publications and source records attributed to Fitzsimmons, S..

3 recordsLinked to original sources

From Kernel to Kitchen: Asparagine Synthetase 3 is Involved in Free Asparagine Accumulation in Maize Kernels

Acrylamide is a probable dietary carcinogen formed through high-temperature cooking processes from one of its precursors, free asparagine (Asn). To reduce acrylamide formation potential in maize-based food products, the genetic basis for the accumulation of free Asn in maize kernels must be elucidated. In this study we integrated complementary quantitative genetic approaches including quantitative trait locus (QTL) mapping of a biparental population and genome-wide association studies (GWAS) in a diverse inbred panel. We ultimately identified one major QTL for free Asn which was not reflected in the GWAS results. Subsequent sequence analysis of the QTL mapping population parents revealed a 921bp deletion in As-paragine Synthetase 3 (ASN3) in the low Asn parent. Validation is underway with rtPCR, genotyping the association panel for the deletion, and evaluation of a CRISPR-Cas9 knockout of ASN3. This work provides a foundation for breeding and genome-editing strategies to reduce acrylamide-forming potential in maize-based foods.

Plant Biology↗

Whole-genome resequencing reveals the population structure, genomic diversity, and demographic history of American chestnut (Castanea dentata)

American chestnut (Castanea dentata) was once the most economically and ecologically important hardwood species in the United States. In the first half of the 20th century, an exotic fungal pathogen - Cryphonectria parasitica - decimated the species, killing approximately four billion trees. Two approaches to developing blight resistant American chestnut populations show promise, but both will require introduction of adaptive genomic diversity from wild germplasm to produce diverse, locally adapted reforestation populations. Here we characterize population structure, demographic history, and genomic diversity in a range-wide sample of 384 wild American chestnuts to inform conservation and breeding with blight resistant varieties. Population structure analyses with DAPC and ADMIXTURE suggest that the chestnut range can be roughly divided into northeast, central, and southwest populations. Within-population genomic diversity estimates revealed a clinal pattern with the highest diversity in the southwest, which likely reflects bottleneck events associated with Quaternary glaciation. Finally, we identified genomic regions under positive selection within each population, which suggests that defense against fungal pathogens is a common target of selection across all populations. Taken together, these results show that American chestnut underwent a postglacial expansion from the southern portion of its range leading to three extant populations. These populations will serve as management units for breeding adaptive genetic variation into the blight-resistant tree populations for targeted reintroduction efforts.

genomics↗

Resting-state and task-based centrality of dorsolateral prefrontal cortex predict resilience to inhibitory repetitive transcranial magnetic stimulation

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties.\n\nObjective/HypothesisA previous study by our group showed that virtually lesioning the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using inhibitory rTMS reduced performance on a set-shifting task. We aimed to determine whether this behavioural response was related to topological features of pre-TMS resting-state and task-based functional networks.\n\nMethodsInhibitory (1Hz) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set-shifting task during fMRI at baseline and directly after a single rTMS session 1-2 weeks later. Functional network topology measures were calculated from resting-state and task-based fMRI scans using graph theoretical analysis.\n\nResultsThe dlPFC-stimulated group, but not the vertex group, showed reduced set shifting performance after rTMS associated with lower task-based betweenness centrality of the dlPFC at baseline (p=.030) and a smaller reduction in task-based betweenness centrality after rTMS (p=.024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p=.017).\n\nConclusionsOur results suggest that behavioural response to inhibitory rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to inhibitory rTMS, while individuals with more locally well-connected regions show greater vulnerability.\n\nHighlightsO_LIFunctional brain network properties predict behavioural response to 1Hz DLPFC rTMS\nC_LIO_LIGlobally integrated stimulated regions are resilient to effects of inhibitory rTMS\nC_LIO_LISegregated, locally well-connected regions are vulnerable to inhibitory rTMS\nC_LIO_LIChange in performance after rTMS correlates with change in network properties\nC_LI

neuroscience↗