Biology subjects

Simmons, D.

Publications and source records attributed to Simmons, D..

6 recordsLinked to original sources

bioRxiv2026

From Metabolomics to Function: Ranking Plant Stem Cell Metabolomes for Use in Health and Cosmetics

BackgroundPlants produce diverse metabolites with potential benefits for human health. However, the metabolomes of plant callus cultures--cell cultures analogous to stem cells--remain poorly characterized in terms of their functional relevance. MethodsWe profiled the metabolomes of six plant calli: Acacia concinna (Shikakai), Daucus carota (carrot), Hibiscus sabdariffa (hibiscus), Linum usitatissimum (flax), Ocimum sanctum (tulsi), and the Nicotiana tabacum Bright-Yellow 2 (BY-2) cell line. To facilitate functional interpretation, we developed Metabolite2Function (M2F), a pipeline that annotates metabolites with biological functions using scientific literature and large language modeling. ResultsUntargeted metabolomics identified 177 metabolites, revealing clustering patterns independent of genetic relationships, culture age, or growth rate. Tulsi and carrot calli exhibited enrichment in metabolites relative to the tobacco reference line, whereas flax and hibiscus were comparatively depleted. Most metabolites varied across at least four calli, and 10% were unique to a single species. Using M2F, we annotated 87 metabolites with beneficial activities, including antioxidant, anti-glycation, anti-inflammatory, and anti-senescence functions, as well as skin-related effects such as collagen production and brightening. Notably, antioxidant and anti-senescence metabolite levels correlated with corresponding biological activities in human cells. ConclusionsPlant callus cultures generate distinct and functionally diverse bioactive metabolomes. M2F provides a scalable framework for systematic functional annotation relevant to human health and cosmetic applications.

biochemistry↗

bioRxiv2026

Yeast-Plant-Derived Consortia Factors Exhibit A Distinct And Enriched Beneficial Metabolome For Health And Beauty

Cells secrete metabolites and other factors into the extracellular medium, collectively referred to as the secretome. The effect of co-culturing cells from different species on their combined secretome remains poorly understood. Here, we investigated the effect of co-culturing plant and yeast cells to produce a unique set of secretory factors collectively termed Consortia Factors (CFx). Specifically, a yeast suspension of Ustilago cynodontis (Ustilago) was co-cultured with plant cells derived from Ocimum sanctum (Tulsi). The metabolome of the Ustilago-Tulsi CFx (termed CFx-1) was then profiled and compared with that of the individual cultures. Statistical clustering analyses revealed that the CFx-1 metabolome was substantially different from either culture grown alone and was enriched in metabolites relative to single cultures. Notably, significant enrichment was observed among metabolites mutually upregulated in CFx compared with both single cultures, with approximately one-third absent from either culture alone. Using an algorithm designed to identify scientifically validated antioxidant metabolites, the CFx-1 was found to be enriched in antioxidants relative to the single cultures, including vitamin C. Accordingly, the CFx-1 exhibited stronger antioxidant activity than either of the single-culture secretomes, and even than the combination of the two single-culture secretomes. These findings suggest that consortia factors derived from co-culturing yeast and plant cells can generate a unique and more potent secretome that is enriched in bioactive metabolites beneficial for human health.

cell biology↗

bioRxiv2025

Targeting BRAF kinase fusions with pan-RAF and vertical MAPK inhibition

BRAF kinase fusions are a form of structural variation in the genome and are recurrent events in driver-negative melanomas. While BRAF fusions reproducibly conserve the kinase domain, there is genetic variability with 5 gene partners and specific BRAF breakpoints. We investigated how genetic diversity of BRAF kinase fusions affects dimeric signaling and ERK activation. We overexpressed BRAF fusions with 5 gene partners including AGK, ZKSCAN1, ARMC10, PPFIBP2, and TRIM24 and found fusion dependent signaling and inhibitor sensitivity. Despite the development of next generation RAF inhibitors, there was paradoxical ERK phosphorylation with multiple pan-RAF inhibitors, which was ameliorated in certain BRAF fusions with vertical RAF/MEK inhibition using trametinib and LY3009120. Collectively, we observed some fusion-dependent effects but also tumor growth suppression and resolution of paradoxical activation with vertical pathway inhibition.

cancer biology↗

bioRxiv2023

A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer's mouse model

IntroductionTrkB and TrkC receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid-{beta} (A{beta})-toxicity. Upregulating TrkB/C signaling could reduce Alzheimers disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction. MethodsPTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APPL/S) and wild-type controls (WT). Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA-sequencing. ResultsMemory and LTP deficits in APPL/S mice were attenuated by treatment with BD10-2. BD10-2 prevented aberrant AKT, CaMKII, and GLUA1 phosphorylation, and enhanced activity-dependent recruitment of synaptic proteins. BD10-2 also had potentially favorable effects on LTP-dependent complement pathway and synaptic gene transcription. ConclusionsBD10-2 prevented APPL/S/A{beta}-associated memory and LTP deficits, reduced abnormalities in synapse-related signaling and activity-dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response.

neuroscience↗

bioRxiv2022

Continent-wide phylogenomic framework reveals introgression as a driver of intra-specific diversity and enriched molecular pathways in caribou

High intra-specific genetic diversity is associated with adaptive potential which is key for resilience to global change. However, high variation may also support deleterious alleles through genetic load, unless purged, thereby increasing the risk of inbreeding depression if population sizes decrease rapidly. Purging of deleterious variation has now been demonstrated in some threatened species. However, less is known about the costs of population declines and inbreeding in species with large population sizes and high genetic diversity even though this encompasses many species globally that have or are expected to undergo rapid population declines. Caribou is a species of ecological and cultural significance in North America with a continental-wide distribution supporting extensive phenotypic variation, but with some populations undergoing significant declines resulting in their at-risk status in Canada. We assessed intra-specific genetic variation, adaptive divergence, inbreeding, and genetic load across populations with different demographic histories using an annotated chromosome-scale reference genome and 66 whole genome sequences. We found high genetic diversity and nine phylogenomic lineages across the continent with adaptive diversification of genes, but also high genetic load among lineages. We also found highly divergent levels of inbreeding across individuals including the loss of alleles by drift (genetic erosion) but not purging, likely due to rapid population declines not allowing time for purging of deleterious alleles. As a result, further inbreeding may need to be mitigated through conservation efforts. Our results highlight the double-edged sword of genetic diversity that may be representative of other species-at-risk affected by anthropogenic activities.

genomics↗

bioRxiv2022

Common insecticide affects spatial navigation in bats at environmentally-realistic doses

Bats are potentially exposed to pesticides via foraging in croplands. Common pesticides like organophosphates are neurotoxic for vertebrates and even low doses can impair essential processes such as locomotion and cognition. These sublethal effects are usually studied using molecular biomarkers with limited ecological relevance. Behavioral studies, in contrast, represent a more informative yet sensitive approach. Spatial navigation, for example, is an ecologically relevant behavior that is modulated by cellular pathways potentially targeted by neurotoxicants. We evaluated whether bats ability to memorize and navigate novel spaces was negatively affected by environmental relevant doses of chlorpyrifos, a common organophosphate insecticide. We also tested how the behavioral response correlated with molecular biomarkers. We orally dosed captive big brown bats (Eptesicus fuscus) with chlorpyrifos and studied exploratory behavior in two testing arenas. We evaluated similarity of stereotype flight trajectories in a flight tent, and associative memory in a Y-maze. We quantified brain cholinesterase (ChE) activity as a cellular biomarker and employed non-targeted proteomics as molecular biomarkers. Bats exposed to chlorpyrifos were less explorative and made more incorrect choices in the Y-maze, but the consistency of their flight trajectories was unaffected. Exposed bats had 30% lower ChE activity, showed down-regulation of proteins involved in memory (VP37D), learning and sound perception (NOX3). Other important nervous system processes such as synaptic function, plasticity, oxidative stress, and apoptosis were enriched in chlorpyrifos-exposed bats. These results support the sensitivity of behavior as a biomarker of toxicity and the importance of considering other levels of organization to help explain the mechanisms underlying altered behavior due to human activities.

pharmacology and toxicology↗