Biology subjects

Nelson, D.

Publications and source records attributed to Nelson, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Predicting cyanobacterial oxic diazotrophy and prioritizing candidate protein families beyond known Nif proteins

Diazotrophic cyanobacteria must reconcile oxygenic photosynthesis with the oxygen sensitivity of nitrogenase. Engineering studies have demonstrated nitrogenase activity in a non-diazotrophic cyanobacterium while highlighting the importance of accessory functions and oxygen management. Robust aerobic nitrogen fixation remains challenging, motivating systematic identification of candidate support functions beyond the canonical Nif machinery. We modeled nifHDK-defined diazotrophic potential from protein-family presence or absence in 426 cyanobacterial assemblies. Four classifiers evaluated with genus-blocked cross-validation achieved mean ROC AUCs of 0.853 to 0.893, with purity and genus-breadth filters fitted within training folds. Restricting the panel to 401 assemblies with current NCBI status gave AUCs of 0.806 to 0.881. Family-content logistic regression outperformed a genome-size-only baseline across ten genus partitions. Two inventories describe candidates across the full panel: 981 high-purity families and 473 families with positive residual associations (accompanied by three ubiquitous controls). Model importance orders the residual-association inventory. A separate heuristic score combines inventory membership with proteomics, condensate-driver ranks and genus-based morphotype proxies to prioritize 167 families for experiments. Proteomics annotations tracked detection opportunity; the condensate contrast between inventories attenuated after prevalence adjustment. These annotations help choose experiments but do not independently validate accessory functions. Protein-family content predicts nifHDK-defined diazotrophic potential, with performance sensitive to assembly inclusion, taxonomy, genome size and taxonomic weighting. The two candidate inventories distinguish high carrier purity from residual association, providing complementary resources for prioritizing previously uncharacterized functions associated with cyanobacterial oxic diazotrophy.

bioinformatics↗

bioRxiv2026

Copper chelation reprograms the tumour microenvironment to enhance immune checkpoint blockade therapy in preclinical mesothelioma

Immune checkpoint blockade provides durable benefit to only a minority of patients with pleural mesothelioma. Here we investigated whether targeting copper homeostasis could enhance anti-tumour immunity and improve responses to immune checkpoint blockade. Copper homeostasis genes were upregulated in human mesothelioma, localised to malignant and stromal cells but downregulated in lymphocytes. In murine mesothelioma, these genes were dynamically regulated during anti-CTLA-4 and anti-PD-1 therapy. Treatment with copper chelator triethylenetetramine reduced intratumoural copper, increased cytotoxic lymphocytes, and enriched inflammatory genes in tumour-infiltrating myeloid and lymphoid compartments. Furthermore, copper chelation enhanced anti-CTLA-4 and anti-PD-1 therapy in immunocompetent mesothelioma mouse models, leading to durable tumour control. Our findings identify copper homeostasis as a therapeutic vulnerability in mesothelioma and support clinical evaluation of copper depletion with first-line immune checkpoint blockade.

immunology↗

bioRxiv2026

Rapid urban evolution of the dengue mosquito in West African cities

Aedes aegypti is an exceptionally effective global vector of human disease because of its strong specialization on human hosts and habitats. However, in its native range in Africa, many populations never specialized on humans and retained an ancestral generalist ecology. Now, in the rapidly growing cities of Kumasi, Ghana and Ouagadougou, Burkina Faso, we directly document genomic and behavioral evidence of a sudden shift towards greater specialization on humans over just five years. These changes are likely to enhance the ability of these urban mosquito populations to serve as effective vectors of human disease and may have played a role in unprecedented recent outbreaks of dengue fever in West African cities.

evolutionary biology↗

bioRxiv2026

Nitrosomes: protein language modeling and live-cell imaging reveal condensate-like nitrogenase organization in heterocysts

Biological nitrogen fixation in some filamentous cyanobacteria occurs in heterocysts, yet the subcellular organization of nitrogenase in these cells remains poorly defined. Using fluorescence microscopy of living Anabaena sp. PCC 7120, we found that a NifH-GFP fusion forms discrete puncta restricted to mature heterocysts, whereas constitutively expressed GFP in vegetative cells and a nifB-linked GFP reporter remained diffuse. To contextualize this phenotype, we built a homology-aware cyanobacterial condensate-prioritization framework across 31,028 proteins from seven proteomes, integrating ESM-2 embeddings, 27 biophysical features, and 44 curated condensate-associated positives. Because direct positives remain limited, we present the model as a ranking resource rather than a calibrated classifier. Under a deliberately conservative nitrogenase-withheld analysis that removed nitrogenase-family labels and homologous clusters from the training data, NifH retained a median rank in the highest-scoring 4.8% of cyanobacterial proteins. catGRANULE 2.0 also assigned high scores to nitrogenase iron proteins, while having only modest rank concordance to the whole atlas. Together, these data identify heterocyst-restricted NifH-GFP puncta as evidence of sub-cellular spatial organization and provide a curated resource for prioritizing cyanobacterial condensate candidates, some of which are also important for nitrogen fixation.

molecular biology↗

bioRxiv2026

Identification and classification of all Cytochrome P450 deposits in the Protein Data Bank

Cytochrome P450 monooxygenases (CYPs/P450s) form a highly diverse enzyme superfamily central to biotechnology, pharmacology, and environmental science. Despite the large number of available structures, identifying and comparing P450 entries in structural repositories remains challenging due to their extreme sequence divergence and inconsistent annotation practices. In particular, many deposits lack the standardized nomenclature (CYPid) and rather rely on legacy or author-defined common names (like P450cam, P450BM-3 and P450-PCN1), which are often inconsistent in formatting and specificity. This is particularly difficult for a superfamily as sequentially diverse as P450s. This hinders reliable retrieval and cross-referencing, making even identification all P450 structures in the database nontrivial. To overcome these obstacles, we developed a structure-guided discovery and validation workflow combining keyword search, Hidden Markov Models, and structural alignment, enabling robust detection and annotation. This strategy identified 1,513 deposits representing 674 unique sequences. All sequences were reannotated using the P450Atlas server and manually verified, confirming high assignment accuracy. In the process, we have also identified five new CYP subfamilies. The resulting dataset constitutes the first rigorously curated, structure-linked registry of P450 enzymes, integrated into a publicly accessible resource and supported by an automated pipeline that periodically scans newly released entries. By unifying structurally validated identification with standardized CYP nomenclature, this work establishes a reliable framework for accurate retrieval, comparison, and future large-scale analyses of P450 enzymes.

bioinformatics↗

bioRxiv2026

Ecological genomics of preference for human hosts in the native range of the dengue mosquito

The arbovirus transmitting mosquito Aedes aegypti has African origins where it maintains generalist and human specialist feeding forms, the latter of which has recently expanded their range worldwide. These two different forms appear to be directly linked to discrete genetic lineages, where the relative proportion of each ancestry dictates a mosquitos standing on the human specialist-generalist behavior spectrum. Here we take a population genomics approach to develop a predictive model for describing the distribution of human specialist behavior across Africa. We show genome-wide ancestry is predictive of human specialist behavior, but a subset of the genome offers even greater predictability. We also show that an ecological model incorporating precipitation, temperature and human density explains the geographic patterning of human specialist behavior in Africa.

evolutionary biology↗

bioRxiv2026

Consumption of processed foods impairs memory function through dietary advanced glycation end-products

Consumption of processed foods is associated with dementia, obesity, and other negative health outcomes. Sustained heat treatment, a common food processing approach to enhance flavor, induces the chemical Maillard reaction that promotes the formation of dietary advanced glycation end-products (AGEs). The neurocognitive impacts of consuming dietary AGEs are poorly understood. Here we modeled an AGE-rich diet through heat treatment fed to rats during adolescence, a critical period of neural development, to mechanistically evaluate the long-term impact of early life dietary AGEs on behavioral and neural processes. Consuming the AGE-rich diet impaired hippocampal-dependent memory function and altered the gut microbiome without inducing obesity or nonspecific behavioral deficits. AGE-induced memory deficits were coupled with impaired hippocampal glutamatergic synaptic neurotransmission and altered expression in the synapse-pruning complement system. Hippocampal synaptic deficits likely result from direct AGE-complement interactions, as our extended studies reveal competitive antagonist action of AGEs on complement receptors. Memory impairments were prevented by administration of the AGE-inhibitor, alagebrium, and by supplementation with an AGE-inhibiting bacterial taxon, Lactococcus lactis, which was depleted in the heat-treated diet. These findings reveal a functional connection between early life dietary AGEs, the microbiome, and memory impairments, thus illuminating mechanisms through which food processing negatively impacts neurocognition.

neuroscience↗

bioRxiv2025

ACUTE AMYLOID-B 40 EXPOSURE DISRUPTS METABOLIC INSULIN SIGNALING IN BLOOD-BRAIN BARRIER ENDOTHELIAL CELLS

BackgroundBrain insulin resistance and cerebrovascular dysfunction emerge early in late-onset Alzheimers disease, but how amyloid-{beta} (A{beta}) disrupts insulin signaling at the cerebrovascular blood-brain barrier--the principal site of insulin receptor signaling and transport into the brain--remains unclear. MethodsWe exposed two distinct human blood-brain-barrier endothelial cell models to soluble A{beta}40 or A{beta}42 for 1 h, followed by 100 nM insulin for 10 min. Protein and phosphoprotein responses were quantified by reverse-phase protein array, and differential expression was evaluated using empirical-Bayes-stabilized linear models with FDR correction. ResultsA{beta}40 reduced insulin-stimulated Akt phosphorylation and converted insulins normal inhibition of AMPK into modest stimulation, increasing AMPK Thr172 and ACC Ser79 phosphorylation. A{beta}42 did not alter insulin-stimulated Akt signaling, indicating isoform-specific disruption of endothelial insulin responses. Without insulin, both A{beta}40 and A{beta}42 showed modest stimulation of ribosomal protein s6. ConclusionsThese findings show that A{beta}40 acutely impairs insulin signal transduction in BBB endothelial cells, supporting a model in which vascular amyloid exposure contributes directly to the early development of brain insulin resistance in AD.

molecular biology↗

bioRxiv2025

Lambda Theta Reflectometry: a new technique to measure optical film thickness applied to planar protein arrays

Quantitative protein measurements provide valuable information about biological pathways, immune system functionality, and mechanisms of disease. The most accurate methods for detecting proteins are label-free and preserve native protein binding interactions. Label-free biomolecular interaction analysis includes reflectometry, a group of techniques that detect proteins by measuring the reflectance properties of a thin film on a substrate. Most of these techniques are limited in some way by instrument complexity, sensitivity, or consumable manufacturing requirements. To address these issues, we introduce Lambda Theta Reflectometry (LTR), a new reflectometric technique that measures changes in film thickness by determining the location of null reflectivity as a function of wavelength (lambda) and angle of incidence (theta). The substrate is simultaneously illuminated with a range of angles and wavelengths and reflected light is angularly and spectrally resolved. Our prototype LTR reflectometer can measure SiO2 layer thickness with milli-[A]ngstrom precision. LTR measurements of Si/SiO2 oxide films are in excellent agreement with spectroscopic ellipsometry for film thicknesses ranging from 1390-1465 [A]. This technique enables sensitive measurements across a range of biological analyte concentrations without requiring stringent control over probe deposition thickness or substrate manufacturing.

biophysics↗

bioRxiv2024

Informing biologically relevant signal from spatial transcriptomic data

Visium is a spatial sequencing technology that utilizes messenger RNA (mRNA) to spatially map gene expression within tissues. Despite its potential, research utilizing deconvolution tools and exploring microenvironment dynamics remains challenging. We address this gap by benchmarking deconvolution tools across diverse biological contexts, identifying optimal methodologies. Subsequently, we introduce a novel pipeline integrating advanced deconvolution techniques and novel tools for reproducible tissue microenvironment analysis. Through this approach, we uncover intricate immune aggregate biology, highlighting the power of our methodology in unraveling complex biological phenomena.

bioinformatics↗

bioRxiv2024

A haplotype-resolved reference genome of Quercus alba sheds light on the evolutionary history of oaks

O_LIWhite oak (Quercus alba) is an abundant forest tree species across eastern North America that is ecologically, culturally, and economically important. C_LIO_LIWe report the first haplotype-resolved chromosome-scale genome assembly of Q. alba and conduct comparative analyses of genome structure and gene content against other published Fagaceae genomes. In addition, we probe the genetic diversity of this widespread species and investigate its phylogenetic relationships with other oaks using whole-genome data. C_LIO_LIOur genome assembly comprises two haplotypes each consisting of 12 chromosomes. We found that the species has high genetic diversity, much of which predates the divergence of Q. alba from other oak species and likely impacts divergence time estimation in Quercus. Our phylogenetic results highlight phylogenetic discordance across the genus and suggest different relationships among North American oaks than have been reported previously. Despite a high preservation of chromosome synteny and genome size across the Quercus phylogeny, certain gene families have undergone rapid changes in size including resistance genes (R genes). C_LIO_LIThe white oak genome represents a major new resource for studying genome diversity and evolution in Quercus and forest trees more generally. Future research will continue to reveal the full scope of genomic diversity across the white oak clade. C_LI

genomics↗

bioRxiv2024

Macrophages protect against sensory axon degeneration in diabetic neuropathy

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain1,2. Although the onset and progression of DPN have been linked with dyslipidemia and hyperglycemia3, the contribution of inflammation in the pathogenesis of DPN has not been investigated. Here, we use a High Fat High Fructose Diet (HFHFD) to model DPN and the diabetic metabolic syndrome in mice. Diabetic mice develop persistent heat hypoalgesia after three months, but a reduction in epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, we find that CCR2+ macrophages infiltrate the sciatic nerves of diabetic mice well before axonal degeneration is detectable. We show that these infiltrating macrophages share gene expression similarities with nerve crush-induced macrophages4 and express neurodegeneration-associated microglia marker genes5 although there is no axon loss or demyelination. Inhibiting this macrophage recruitment in diabetic mice by genetically or pharmacologically blocking CCR2 signaling results in a more severe heat hypoalgesia and accelerated skin denervation. These findings reveal a novel neuroprotective recruitment of macrophages into peripheral nerves of diabetic mice that delays the onset of terminal axonal degeneration, thereby reducing sensory loss. Potentiating and sustaining this early neuroprotective immune response in patients represents, therefore, a potential means to reduce or prevent DPN.

neuroscience↗

bioRxiv2023

Soil fungi remain active and invest in storage compounds during drought independent of future climate conditions

Microbial growth is central to soil carbon cycling. However, how microbial communities grow under climate change is still largely unexplored. In an experiment simulating future climate conditions (increased atmospheric CO2 and temperature) and drought, we traced 2H or 18O applied via water-vapor exchange into fatty acids or DNA, respectively, allowing to measure community- and group-level adjustments in soil microbial physiology (replication, storage product synthesis, and carbon use efficiency, CUE). We show, that while overall community-level growth decreased by half during drought, fungal growth remained stable demonstrating an astonishing resistance of fungal activity against soil moisture changes. In addition, fungal investment into storage triglycerides increased more than five-fold under drought. CUE (the balance between anabolism and catabolism) was unaffected by drought but decreased in future climate conditions. Our results highlight that accounting for different growth strategies can foster our understanding of soil microbial contribution to C cycling and feedback to climate change.

microbiology↗

bioRxiv2023

Resolving the unsolved: Comprehensive assessment of tandem repeats at scale

Tandem repeat (TR) variation is associated with gene expression changes and over 50 rare monogenic diseases. Recent advances in sequencing have enabled accurate, long reads that can characterize the full-length sequence and methylation profile of TRs. However, despite these advances in sequencing technology, computational methods to fully profile tandem repeats across the genome do not exist. To address this gap, we introduce tools for tandem repeat genotyping (TRGT), visualization and an accompanying TR database. TRGT accurately resolves the length and sequence composition of TR regions in the human genome. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of 99.56%, allowing a single repeat unit difference. In six samples with known repeat expansions, TRGT detected all repeat expansions while also identifying methylation signals, mosaicism, and providing finer resolution of repeat length. Additionally, we release a database with allele sequences and methylation levels for 937,122 TRs across 100 genomes.

genomics↗

bioRxiv2022

Engineering High Throughput Screening Platforms of Cervical Cancer

There is a critical need for complex multicellular three-dimensional physiomimetic models of cancer that can interface with high throughput drug screening methods to assess anti-metastatic and anti-angiogenic drug efficacy in a rapid yet high content manner. We report a multilayer multicellular platform of human cervical cancer cell lines and primary human microvascular endothelial cells that incorporates critical biophysical and extracellular matrix cues, interfaces with standard high throughput drug screening methods, and can evaluate cervical cancer invasion and endothelial microvessel formation over time. Through the use of Design of Experiments statistical optimization, we identified the specific concentrations of collagen I, fibrinogen, fibronectin, GelMA, and PEGDA in each hydrogel layer that maximized cervical cancer invasion and endothelial microvessel length simultaneously. We then validated the optimized platform and assessed the viscoelastic properties of the composite hydrogels as well as their individual constituents. Finally, using this optimized platform, we conducted a targeted drug screen of four clinically relevant drugs on two cervical cancer cell lines. From these data we identified each of the cervical cancer cell lines (SiHa and Ca Ski) as either responsive or refractive to Paclitaxel, Dasitinib, Dovitinib, or Pazopanib. Overall, we developed a phenotypic drug screening platform of cervical cancer that captures cell behavior present in the cervical cancer tumor microenvironment, captures patient to patient variability, and integrates with standard high throughput high content drug screening methods. This work provides a valuable platform that can be used to screen large compound libraries for mechanistic studies, drug discovery, and precision oncology for cervical cancer patients.

bioengineering↗

bioRxiv2022

On the Genes, Genealogies, and Geographies of Quebec

Population genetic models only provide coarse representations of real-world ancestry. We use a pedigree compiled from four million parish records and genotype data from 2,276 French and 20,451 French Canadian (FC) individuals, to finely model and trace FC ancestry through space and time. The loss of ancestral French population structure and the appearance of spatial and regional structure highlights a wide range of population expansion models. Geographic features shaped migrations throughout, and we find enrichments for migration, genetic and genealogical relatedness patterns within river networks across Quebec regions. Finally, we provide a freely accessible simulated whole-genome sequence dataset with spatiotemporal metadata for 1,426,749 individuals reflecting intricate FC population structure. Such realistic populations-scale simulations provide new opportunities to investigate population genetics at an unprecedented resolution. Lay SummaryWe all share common ancestors ranging from a couple generations ago to hundreds of thousands of years ago. The genetic differences between individuals today mostly depends on how closely related they are. The only problem is that the actual genealogies that relate all of us are often forgotten over time. Some geneticists have tried to come up with simple models of our shared ancestry but they dont really explain the full, rich history of humanity. Our study uses a multi-institutional project in Quebec that has digitized parish records into a single unified genealogical database that dates back to the arrival of the first French settlers four hundred years ago. This genealogy traces the ancestry of millions of French-Canadian and we have used it to build a very high resolution genetic map. We used this genetic map to study in detail how certain historical events, and landscapes have influenced the genomes of French-Canadians today. One-Sentence SummaryWe present an accurate and high resolution spatiotemporal model of genetic variation in a founder population.

genomics↗

bioRxiv2021

PDFGRα+ Stromal Cells Promote Salivary Gland Proacinar Differentiation Through FGF2-dependent BMP7 Signaling.

3.0Stromal cells can direct epithelial differentiation during organ development; however, these pathways remain poorly defined. FGF signaling is essential for submandibular salivary gland development, and FGF2 can regulate proacinar cell differentiation in organoids through autocrine signaling in stromal cells. We performed scRNA Seq and identified stromal cell subsets expressing Fgf2 and Fgf10 that also express Pdgfr. When combined with epithelial cells in organoids, MACS-sorted PDGFR+ cells sufficiently promoted proacinar differentiation. Gene expression analysis revealed FGF2 activates the gene Bmp7 in the stroma. BMP7 could replace stromalsignaling and stimulate epithelial acinar differentiation but not branching. However, in the absence of FGF2, pathway analysis revealed that the stromal cells differentiated into myofibroblasts. Myofibroblast differentiation was induced when we treated organoids with TGF{beta}1, which also prevented proacinar differentiation. Conversely, FGF2 reversed TGF{beta}s effects. Dissecting pathways driving acinar differentiation will facilitate development of regenerative therapies. 2.0 Summary StatementEmbryonic salivary glands contain multiple stromal cell populations. FGF2 maintains the stromal Pdgfr+ population in-vitro. The PDGFR+ stromal cells drive early epithelial secretory cell differentiation using BMP7.

developmental biology↗

bioRxiv2021

Hybridization and Low Genetic Diversity in the Endangered Alabama Red-Bellied Turtle (Pseudemys alabamensis)

Pseudemys alabamensis is one of the most endangered turtle species in the United States due to its small population size and restricted geographic distribution in coastal Alabama and Mississippi. Increased urbanization and climate change impacts in the region further threaten this species. Populations of P. alabamensis are geographically isolated from one another by land and salt water, which could act as barriers to intraspecific gene flow. It is currently unknown how differentiated these isolated populations are from one another or whether they have experienced reductions in population size. Previous work found morphological differences between Alabama and Mississippi populations, suggesting that they may be evolutionarily distinct. Other Pseudemys turtles such as P. concinna and P. floridana occur within the same geographic area as P. alabamensis and are known to hybridize with each other. These more abundant species could further threaten the unique genetic identity of P. alabamensis through introgression. In order to evaluate the endangered status of P. alabamensis and the level of hybridization with other species, we used the mitochondrial (mtDNA) control region and nuclear microsatellite markers to assess genetic variation within and among populations of this species throughout its range and estimate admixture with co-occurring Pseudemys species. Genetic diversity of P. alabamensis was lower than expected at both markers (no variation in mtDNA and excess of homozygosity in microsatellites). We found evidence of genetic differentiation between Alabama and Mississippi populations as well as two populations (Fowl River, Alabama and Biloxi, Mississippi) with low estimated breeding sizes and signs of inbreeding. Finally, we found evidence of admixture of P. alabamensis with P. concinna/P. floridana and Pseudemys peninsularis (a species not native to Alabama or Mississippi). Our results indicate that P. alabamensis is highly endangered throughout its range and threatened by both low population sizes and hybridization. In order to improve the species chances of survival, focus should be placed on habitat preservation, maintenance of genetic diversity within both Mississippi and Alabama populations, and regular population monitoring activities such as nest surveillance and estimates of recruitment.

evolutionary biology↗