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Allison, S.

Publications and source records attributed to Allison, S..

4 recordsLinked to original sources

Single-Cell and Spatial Methods for Multimodal Functional Glycan Profiling in Tissues

Glycans regulate multiple physiological processes, including immune recognition and cancer progression. In disease, altered glycan landscapes are interpreted by human lectins. Functional glycan-lectin interactions are difficult to profile because glycans are not genome-encoded and their changes are poorly captured by existing multimodal methods. We present two platforms, single-cell outlining and transcriptome sequencing (scGOAT-seq) and GlycoScope, which use human lectins to enable functional glycan accessibility into single-cell and spatial multiomic measurements. ScGOAT-seq quantifies lectin-accessible glycan states with gene expression, while GlycoScope enables multiplexed in situ co-detection of glycans and proteins in tissues. Applying these approaches to immune cells, we identify stimulus-specific glycan remodeling and show that distinct Siglec-ligand-defined programs stratify immune activation states not captured by traditional methods; in follicular lymphoma, GlycoScope, resolves spatial glycan programs associated with malignant B cells and localized immune microenvironments. The presented methods provide a general framework for integrating functional glycan accessibility into single-cell and spatial multiomics.

molecular biology↗

Plant litter chemistry and associated changes in microbial decomposition under drought

Drought has consequences for microbial decomposition rates, including indirect effects through changes in plant litter chemistry. Here we studied the impact of a decade-long drought on plant litter chemistry and microbial decomposition traits in a semi-arid ecosystem during an 18-month litter bag experiment. We investigated litter sourced from four conditions: grass and shrub vegetation under ambient and reduced precipitation. We hypothesized that litter chemistry drives microbial decomposition capabilities and enzyme activity, either due to vegetation differences or drought effects on litter chemistry. Fourier Transform Infrared Spectroscopy was used to characterize litter chemistry; we found that carbohydrate-rich grass litter decomposed faster than more recalcitrant shrub litter which was richer in lignin and lipids. There were significant changes in litter chemistry under drought but no increase in lignin fraction suggesting that drought does not make litter more recalcitrant. Metagenomics-derived decomposition genes and extracellular enzyme activity were higher in grass litter; patterns related to differences in substrate supply. Genes linked to lignin depolymerization decreased in abundance under drought. However, most decomposition genes and enzyme activities were not significantly affected by drought thereby maintaining decomposition rates. Microbial community succession with higher abundance of fungi at early and bacteria at later stages of decomposition corresponded with genes for fungal and bacterial necromass recycling along with protein accumulation over time. We demonstrate minimal litter chemistry-mediated effects of drought but show significant changes in community composition and their decomposition capabilities over time highlighting that complex microbial-chemical interactions under climate change can influence ecosystem-scale processes. ImportanceClimate change is causing more severe and frequent droughts in semi-arid ecosystems, affecting soil microbes breaking down plant litter. Our research focusses on understanding the less studied pathway of drought impact on microbes via changes in plant litter chemistry. Drought can alter the plant litter chemistry, by changing the composition and physiology of plants, which can alter microbial decomposition and ecosystem-level carbon cycling. We investigated litter decomposition traits of microbial communities in grass and shrub litter under long-term drought. There were significant changes in litter chemistry under drought but no increase in lignin fraction. Despite this, microbial communities maintained their decomposition capabilities under drought highlighting ability of microbes to adapt and continue functioning. We also demonstrate unique microbial community succession patterns and dead biomass recycling which can have implications for carbon cycling rates in the ecosystem. This study sheds light on the complex microbial interactions that affect ecosystem functioning under climate change.

ecology↗

Self-reported health behaviors and longitudinal cognitive performance: Results from the Wisconsin Registry for Alzheimer’s Prevention

BackgroundStudies have suggested associations between self-reported engagement in health behaviors and reduced risk of cognitive decline. Most studies explore these relationships using one health behavior, often cross-sectionally or with dementia as the outcome. In this study, we explored whether several individual self-reported health behaviors were associated with cognitive decline when considered simultaneously, using data from the Wisconsin Registry for Alzheimers Prevention (WRAP), an Alzheimers disease risk-enriched cohort who were non-demented and in late midlife at baseline.\n\nMethodWe analyzed longitudinal cognitive data from 828 participants in WRAP, with a mean age at baseline cognitive assessment of 57 (range = 36-78, sd = 6.8) and an average of 6.3 years (standard deviation = 1.9, range = 2-10) of follow-up. The primary outcome was a multi-domain cognitive composite, and secondary outcomes were immediate/delayed memory and executive function composites. Predictors of interest were self-reported measures of physical activity, cognitive activity, adherence to a Mediterranean-style diet (MIND), and interactions with each other and age. We conducted linear mixed effects analyses within an Information-theoretic (IT) model averaging (MA) approach on a set of models including covariates and combinations of these 2- and 3-way interactions. The IT approach was selected due to the large number of interactions of interest and to avoid pitfalls of traditional model selection approaches.\n\nResultsModel-averaged results identified no significant modifiable behavior*age interactions in relationship to the primary composite outcome. In secondary outcomes, higher MIND diet scores associated with slower decline in executive function. Men showed faster decline than women on delayed memory, independent of health behaviors. There were no other significant interactions among any other health behaviors and cognitive trajectories.\n\nConclusionsWhen multiple covariates and health behaviors were considered simultaneously, there were limited weak associations with cognitive decline in this age range. These results may be explained alone or in combination by three alternative explanations: 1) the range of cognitive decline is in middle age is too small to observe relationships with health behaviors, 2) the putative associations of these health behaviors on cognition may not be robust in this age range, or 3) the self-reported measures of the health behaviors may not be optimal for predicting cognitive decline. More study may be needed that incorporates sensitive measures of health behaviors, AD biomarker profiles, and/or other disease comorbidities.

neuroscience↗

Cis-Compound Mutations are Prevalent in Triple Negative Breast Cancer and Can Drive Tumor Progression

About 16% of breast cancers fall into a clinically aggressive category designated triple negative (TNBC) due to a lack of ERBB2, estrogen receptor and progesterone receptor expression1-3. The mutational spectrum of TNBC has been characterized as part of The Cancer Genome Atlas (TCGA)4; however, snapshots of primary tumors cannot reveal the mechanisms by which TNBCs progress and spread. To address this limitation we initiated the Intensive Trial of OMics in Cancer (ITOMIC)-001, in which patients with metastatic TNBC undergo multiple biopsies over space and time5. Whole exome sequencing (WES) of 67 samples from 11 patients identified 426 genes containing multiple distinct single nucleotide variants (SNVs) within the same sample, instances we term Multiple SNVs affecting the Same Gene and Sample (MSSGS). We find that >90% of MSSGS result from cis-compound mutations (in which both SNVs affect the same allele), that MSSGS comprised of SNVs affecting adjacent nucleotides arise from single mutational events, and that most other MSSGS result from the sequential acquisition of SNVs. Some MSSGS drive cancer progression, as exemplified by a TNBC driven by FGFR2(S252W;Y375C). MSSGS are more prevalent in TNBC than other breast cancer subtypes and occur at higher-than-expected frequencies across TNBC samples within TCGA. MSSGS may denote genes that play as yet unrecognized roles in cancer progression.

clinical trials↗