Biology subjects

Nelson, C.

Publications and source records attributed to Nelson, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Signaling metabolites spatially organize a multispecies mutualism in the soil microbiome

A plant-independent avenue for N2-fixation takes place in desert topsoils through a "C-for-N" mutualism between heterodiazotrophs and the cyanobacterium Microcoleus vaginatus. These partners come together within a diverse soil microbiome under conditions of N-limitation for the phototroph and C limitation for the heterotrophs. We hypothesized that extracellular chemical signaling might enable partner selection and collocation, though infomolecules shaping inter-microbial architecture were unknown. We show that the complex chemical composition of M. vaginatus exometabolome depends on its N-limitation status, thus potentially offering information to mutualists. In chemotactic assays, the exometabolome effectively repelled most native soil bacteria, particularly intensely when under N-limitation. Bacterial assemblages circumventing the repulsion were enriched in species that are rare in the soil microbiome, and that functionally resemble mutualistic cyanospheres (showing high N2-fixation potential, secretion of urea, and copiotrophy), setting the stage for a working symbiosis. Further, we could reproduce the enrichment of copiotrophs and nitrogen-fixers using mixtures of N-acetylglutamic acid, N-acetylmethionine, indole-3-acetic acid, and 5'-methylthioadenosine, all preferentially released by M. vaginatus under N-limitation. These signaling molecules did not result in an enrichment of urea producers, however. The results demonstrate that trans-species communication through specific infochemicals, together with already known quorum-sensing-like intraspecific communication in M. vaginatus, act as a tool to organize microbiomes spatially and to attain mutualistic partner specificity in an open, crowded background.

microbiology↗

bioRxiv2026

Evaluating AI-Assisted Customer Verification for Synthetic Nucleic Acid Screening

Legitimacy screening, the process of verifying the identity and purpose of customers ordering synthetic nucleic acids, is a primary safeguard against the misuse of synthetic biology. However, the associated costs discourage the adoption of screening practices. To evaluate whether AI tools can facilitate this process, we tested five large language models on five verification tasks using customer profiles of life sciences researchers from around the world. We compared AI performance against an expert human baseline on flag accuracy, source quality, source fidelity, and cost. Flag accuracy of the best-performing model (Gemini 2.5 Pro with four bibliographic and sanctions APIs) was statistically indistinguishable from the human baseline at 90.2% and 89.0% (n = 41). Gemini 2.5 Pro performed at or above the human baseline on source quality and fidelity, at roughly one-tenth of the cost ($1.18 vs. $14.04 per customer). For information-gathering tasks, which excluded the human review step, costs averaged $0.23 per customer, around 50 times cheaper than human screening. These results support piloting AI assistance at the information-gathering step of legitimacy screening at providers of synthetic nucleic acids and other dual-use biotechnology products, with human reviewers retaining authority over follow-up communication and order fulfillment decisions.

synthetic biology↗

bioRxiv2026

Mechanistic machine learning enables interpretable and generalizable prediction of prime editing outcomes

Although prime editing (PE) can effect virtually any specified local change to genomic DNA in living systems, its efficient application currently requires extensive optimization of prime editing guide RNA (pegRNA) sequences. We present OptiPrime, a machine learning model of PE efficiency based on our current understanding of the mechanism of prime editing. OptiPrime achieves state-of-the-art accuracy on PE efficiency prediction and also enables prediction of nicking guide RNA (PE3) and dual pegRNA (twinPE) outcomes. We validated that OptiPrime has learned the determinants of mammalian mismatch repair (MMR), and is therefore well suited for nominating MMR-evasive silent edits that improve PE efficiency. We demonstrate the utility of OptiPrime in a variety of prospective therapeutic contexts, including in primary human and mouse cells. Finally, we show how OptiPrime can be used to achieve highly streamlined and efficient in vivo correction of a pathogenic mutation in the brain of a mouse model of KIF1A-associated neurological disorder.

biochemistry↗

bioRxiv2026

Deletion of NLRP3 gene blocks traumatic brain injury induced abnormal immune response in 3xTg AD mice

Traumatic brain injury (TBI) is a significant risk factor for the development of Alzheimers disease (AD) and related dementia. In both TBI and AD, inflammation plays a pivotal role. It is known that NLRP3 inflammasome plays an important role in pathogenesis of AD while TBI triggers activation of NLRP3 inflammasome in the brain. To evaluate the importance of NLRP3 inflammasome in mediating TBI-induced immune response in the context of predisposition of AD, we have examined the immune profiles in the brain using a novel transgenic AD mouse line with the NLRP3 gene deleted. Briefly, a group of 4 months old male and female 3xTg and 3xTg/NLRP3-/- mice received a moderate lateral fluid percussive injury or sham. Immune cell phenotypes and cytokine gene expression were assessed at 3- and 7-days post injury (dpi). We found that NLRP3 gene deletion counteracted injury-induced alteration of immune response in AD mice with a significant sex-related difference. Specifically, TBI induced a significant brain infiltration of neutrophils, macrophages and {gamma}{delta} T-cells in 3xTg mice in both sexes at 3dpi, and NLRP3 gene deletion blocked this injury effect only in males not in females. NLRP3 gene deletion also blocked injury-enhanced IL-1{beta}, TNF- gene expression in male AD mice, but not in female mice. In conclusion, our study has confirmed that TBI significantly alters the immune response in 3xTg-AD mice and NLRP3 inflammasome is important in mediating these TBI-induced changes with significant sex-related differences.

immunology↗

bioRxiv2025

Multi-dimensional regulation of LIN-28 temporal expression dynamics in the C. elegans heterochronic gene cascade

LIN-28 is an evolutionarily conserved RNA-binding protein that plays critical roles in regulating pluripotency and cell fate determination during animal development. In Caenorhabditis elegans, lin-28 is an integral component of the heterochronic (developmental timing) gene regulatory cascade. Loss-of-function mutations in lin-28 result in precocious cell fate determination during larval development. Previous studies showed that the proper progression of stage specific cell fates during larval development depends on the progressive downregulation of LIN-28, which is negatively regulated by the lin-4 microRNA through complementary sequences located in the lin-28 3 UTR. In this study, we employ CRISPR/Cas9 editing of the endogenous lin-28 locus to demonstrate that the robust developmental downregulation of LIN-28 involves contributions from multiple inputs. These include a convergent action of the let-7 family and lin-4 microRNAs via adjacent complementary sites in the lin-28 3 UTR, in conjunction with the previously described post-translational inhibition of LIN-28 by the lep-5 long non-coding RNA, which all together account for virtually the entirety of LIN-28 repression. Furthermore, through the systematic testing of a series of truncations of the lin-28 3 UTR, we identify three positive regulatory regions that enhance LIN-28 expression, thereby counterbalancing the negative effects of the let-7 and lin-4 microRNAs and the lep-5 long non-coding RNA.

developmental biology↗

bioRxiv2025

Reduced melanocortin tone mediates increased feeding during pregnancy in mice

During pregnancy mammals increase their food intake to accommodate the elevated metabolic demands associated with fetal growth and development. However, the molecular and neural circuit mechanisms mediating increased feeding during pregnancy are largely unknown. Here, we demonstrate that arcuate nucleus agouti-related peptide (AgRP) neurons are activated and pro-opiomelanocortin (POMC) neurons are inhibited during pregnancy in mice. These changes are required for promoting hyperphagia during pregnancy as chemogenetic inhibition of AgRP neurons or activation of POMC neurons both reduced the feeding of pregnant mice to non-pregnant levels. Finally, we utilized single cell resolution spatial transcriptomics in the arcuate nucleus of non-pregnant and pregnant mice to characterize pregnancy-induced changes in the transcriptomic state of arcuate nucleus neurons, including significant changes in both AgRP and POMC neurons. Together, these findings outline a circuit mechanism mediating increased feeding during pregnancy, providing important mechanistic insights related to conditions at the intersection of reproduction and metabolism. HighlightsO_LIAgRP neuron activity is increased and POMC neuron activity is decreased in pregnant mice C_LIO_LIIncreased AgRP neuron activity and reduced POMC neuron activity is required for increased feeding during pregnancy C_LIO_LIPregnancy enhances responsivity of AgRP neurons to palatable food C_LIO_LIPregnancy drastically alters the transcriptional state of both AgRP and POMC neurons towards positive energy balance C_LI

neuroscience↗

bioRxiv2024

Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids

Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MeCP2 mutations - a missense mutation (R306C) and a truncating mutation (V247X) - using calcium imaging with three-photon microscopy. Compared to isogenic controls, we found abnormal neuronal activity in Rett organoids and altered network function based on graph theoretic analyses, with V247X mutations impacting functional responses and connectivity more severely than R306C mutations. These changes paralleled EEG data obtained from patients with comparable mutations. Labeling DLX promoter-driven inhibitory neurons demonstrated differences in activity and functional connectivity of inhibitory and excitatory neurons in the two types of mutation. Transcriptomic analyses revealed HDAC2-associated impairment in R306C organoids and decreased GABAA receptor expression in excitatory neurons in V247X organoids. These findings demonstrate mutation-specific mechanisms of vulnerability in Rett syndrome and suggest targeted strategies for their treatment.

bioengineering↗

bioRxiv2024

Neuroanatomical dissection of the MC3R circuitry regulating energy rheostasis

Although mammals resist both acute weight loss and weight gain, the neural circuitry mediating bi-directional defense against weight change is incompletely understood. Global constitutive deletion of the melanocortin-3-receptor (MC3R) impairs the behavioral response to both anorexic and orexigenic stimuli, with MC3R knockout mice demonstrating increased weight gain following anabolic challenges and increased weight loss following anorexic challenges (i.e. impaired energy rheostasis). However, the brain regions mediating this phenotype remain incompletely understood. Here, we utilized MC3R floxed mice and viral injections of Cre-recombinase to selectively delete MC3R from medial hypothalamus (MH) in adult mice. Behavioral assays were performed on these animals to test the role of MC3R in MH in the acute response to orexigenic and anorexic challenges. Complementary chemogenetic approaches were used in MC3R-Cre mice to localize and characterize the specific medial hypothalamic brain regions mediating the role of MC3R in energy homeostasis. Finally, we performed RNAscope in situ hybridization to map changes in the mRNA expression of MC3R, POMC, and AgRP following energy rheostatic challenges. Our results demonstrate that MC3R deletion in MH increased feeding and weight gain following acute high fat diet feeding in males, and enhanced the anorexic effects of semaglutide, in a sexually dimorphic manner. Additionally, activation of DMH MC3R neurons increased energy expenditure and locomotion. Together, these results demonstrate that MC3R mediated effects on energy rheostasis result from the loss of MC3R signaling in the medial hypothalamus of adult animals and suggest an important role for DMH MC3R signaling in energy rheostasis. Key Points: O_LIMC3R signaling regulates energy rheostasis in adult mice C_LIO_LIMedial hypothalamus regulates energy rheostasis in adult mice C_LIO_LIEnergy rheostasis alters mRNA levels of AgRP and MC3R in DMH C_LIO_LIDMH MC3R neurons increase locomotion and energy expenditure C_LIO_LIMC3R expression in DMH is sexually dimorphic C_LI

neuroscience↗

bioRxiv2024

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging

The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these cells and their spatial organization remain largely uncharacterized as they have been technically challenging to study in humans. Here, we used fresh femoral head samples and performed single-cell RNA sequencing (scRNA-Seq) to profile 29,325 enriched non-hematopoietic bone marrow cells and discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, niche for early hematopoietic stem and progenitor cells. We used our atlas to predict cell type labels in new bone marrow images and used these predictions to uncover mesenchymal stromal cell (MSC) expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. Our work represents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow and will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

cell biology↗

bioRxiv2024

Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. As these outcomes are related to alterations in developmental processes, growing evidence suggests that deficits in executive functions-inhibitory control in particular-may, in part, explain this relationship. However, literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how low resource settings might exacerbate the link between inhibitory control and health outcomes. In this context, we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The childrens mothers completed behavioral questionnaires to assess the childs PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyri, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

neuroscience↗

bioRxiv2023

Developmental trajectories of EEG aperiodic and periodic power suggest timing of thalamocortical development during infancy.

The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2-44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Consistent with the transient developmental progression of thalamocortical circuitry, we observe the presence and then absence of periodic alpha and high beta peaks across the three-year period, as well as the emergence of a low beta peak (12-20Hz) after six months of age. We present preliminary evidence that the emergence of the low beta peak is associated with higher thalamocortical-dependent, anesthesia-induced alpha coherence. Together, these findings suggest that early age-dependent changes in alpha and beta periodic peaks may reflect the state of thalamocortical network development.

neuroscience↗

bioRxiv2022

Age, experience, social goals, and engagement with research scientists may promote innovation in ecological restoration

Innovation in ecological restoration is necessary in order to achieve the ambitious targets established in United Nations conventions and other global restoration initiatives. Innovation is also crucial for navigating uncertainties in repairing and restoring ecosystems, and thus practitioners often develop innovations at project design and implementation stages. However, innovation in ecological restoration can be hindered by many factors (e.g., time and budget constraints, project complexity, and others). Theory and research on innovation has been formally applied in many fields, yet explicit study of innovation in ecological restoration remains nascent. In order to assess the use of innovation in restoration projects, including its drivers and inhibitors, we conducted a social survey of restoration practitioners in the United States. Specifically, we assessed relationships between project-based innovation and traits of: the individual practitioner (including, for example, age, gender, experience); company (including, for example, company size and companys inclusion of social goals); project (including, for example, complexity and uncertainty); and project outcomes (such as completing the project on time/on budget and personal satisfaction with the work). We found positive relationships between project-based innovation and practitioner traits (age, gender, experience, engagement with research scientists), one company trait (companys inclusion of social goals in their portfolio), and project traits (project complexity and length). In contrast, two practitioner traits, risk aversion and the use of industry-specific information, were negatively related to project-based innovation. Satisfaction with work outcomes was positively correlated with project-based innovation. Collectively, the results provide insights into the drivers and inhibitors of innovation in restoration and suggest opportunities for research and application.

ecology↗

bioRxiv2022

Trait variation between and within Andes and coastal mountain ranges in the iconic South American tree Araucaria araucana in Chile

As global commitments to restoration are underway, science is needed to support capacity to achieve meaningful gains for ecosystems and human communities. In Chile, identification and generation of appropriate plant material is a barrier to achieving major restoration goals under the Paris Climate Agreement. Understanding genetic differentiation among plant populations is needed to maximize restoration success. For Araucaria araucana, a highly threatened iconic South American tree, this information is greatly needed to guide restoration and conservation efforts because this species occurs across a strong climate gradient. We grew seedlings from 12 populations of A. araucana across its range in Chile in a common garden to assess regional (coastal versus Andes mountain ranges) and population variation in key plant traits and relate this variation to environmental variables. We demonstrate that A. araucana is differentiated within regions and populations across its range in Chile by a suite of traits, particularly branch number and length (showing plant architectural differences) and needle width (showing leaf investment differences). We show that this variation is at least partly explained by climate and soil variables, with the most variation explained by differences between regions in temperature annual range. Thus, we recommend that restoration efforts focus on conserving genetic variation among and within regions and their populations and preventing the translocations of genotypes between coastal and Andes populations.

plant biology↗

bioRxiv2021

BugSplit: highly accurate taxonomic binning of metagenomic assemblies enables genome-resolved metagenomics

A large gap remains between sequencing a microbial community and characterizing all of the organisms inside of it. Here we develop a novel method to taxonomically bin metagenomic assemblies through alignment of contigs against a reference database. We show that this workflow, BugSplit, bins metagenome-assembled contigs to species with a 33% absolute improvement in F1-score when compared to alternative tools. We perform nanopore mNGS on patients with COVID-19, and using a reference database predating COVID-19, demonstrate that BugSplits taxonomic binning enables sensitive and specific detection of a novel coronavirus not possible with other approaches. When applied to nanopore mNGS data from cases of Klebsiella pneumoniae and Neisseria gonorrhoeae infection, BugSplits taxonomic binning accurately separates pathogen sequences from those of the host and microbiota, and unlocks the possibility of sequence typing, in silico serotyping, and antimicrobial resistance prediction of each organism within a sample. BugSplit is available at https://bugseq.com/academic.

bioinformatics↗

bioRxiv2021

Time-resolved multivariate pattern analysis of infant EEG data

Time-resolved multivariate pattern analysis (MVPA), a popular technique for analyzing magneto- and electro-encephalography (M/EEG) neuroimaging data, quantifies the extent and time-course by which neural representations support the discrimination of relevant stimuli dimensions. As EEG is widely used for infant neuroimaging, time-resolved MVPA of infant EEG data is a particularly promising tool for infant cognitive neuroscience. MVPA methods have recently been applied to common infant imaging methods such as EEG and fNIRS. In this tutorial, we provide and describe code to implement time-resolved, within-subject MVPA with infant EEG data. A pipeline for time-resolved MVPA based on linear SVM classification is described and implemented with accompanying code in both Matlab and Python. Results from a test dataset indicated that in both infants and adults this method reliably produced above chance classification accuracy. Extensions of the core pipeline are presented including both geometric- and accuracy-based representational similarity analysis, implemented in Python. Common choices of implementation are presented and discussed. As the amount of artifact-free EEG data contributed by each participant is lower in studies of infants than in studies of children and adults, we also explore and discuss the impact of varying participant-level inclusion thresholds on resulting MVPA findings in these datasets.

neuroscience↗

bioRxiv2021

Eosinophils are an integral component of the pulmonary granulocyte response in Tuberculosis and promote host resistance in mice

Host resistance to Mycobacterium tuberculosis infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. Influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, employing complementary genetic models of eosinophil deficiency, we demonstrate that, in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.

immunology↗

bioRxiv2021

Identification and quantification of SARS-CoV-2 leader subgenomic mRNA gene junctions in nasopharyngeal samples shows phasic transcription in animal models of COVID-19 and aberrant pattens in humans

IntroductionSARS-CoV-2 has a complex strategy for the transcription of viral subgenomic mRNAs (sgmRNAs), which are targets for nucleic acid diagnostics. Each of these sgRNAs has a unique 5 sequence, the leader-transcriptional regulatory sequence gene junction (leader-TRS-junction), that can be identified using sequencing. ResultsHigh resolution sequencing has been used to investigate the biology of SARS-CoV-2 and the host response in cell culture models and from clinical samples. LeTRS, a bioinformatics tool, was developed to identify leader-TRS-junctions and be used as a proxy to quantify sgmRNAs for understanding virus biology. This was tested on published datasets and clinical samples from patients and longitudinal samples from animal models with COVID-19. DiscussionLeTRS identified known leader-TRS-junctions and identified novel species that were common across different species. The data indicated multi-phasic abundance of sgmRNAs in two different animal models, with spikes in sgmRNA abundance reflected in human samples, and therefore has implications for transmission models and nucleic acid-based diagnostics.

microbiology↗

bioRxiv2020

A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA

let-7 is a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using C. sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 orthologs -- also known as the let-7-family of microRNAs -- that have apparently assumed the role of targeting the lin-41 mRNA. Summary StatementWe have identified a group of Caenorhabditis species that lack let-7a, an otherwise highly conserved and nearly ubiquitous microRNA that was previously thought to be critical to bilaterian animal development.

genetics↗