Biology subjects

Parsons, R.

Publications and source records attributed to Parsons, R..

15 recordsLinked to original sources

bioRxiv2026

The WormFood CURE: Screening for bioactive metabolites that antagonize the Caenorhabditis elegans Ras signaling pathway

Course-based Undergraduate Research Experiences (CUREs) provide an accessible, scalable platform for scientific discovery. Here, we present the WormFood CURE, which mines environmental bacterial isolates for bioactive secondary metabolites using Caenorhabditis elegans phenotype suppression as a functional readout. Utilizing the multivulva (Muv) phenotype, our pilot cohort interrogated 41 wild bacterial isolates for suppression of Ras/MAPK signaling. We identified one Bacillus safensis isolate BAC-08 and one Bacillus altitudinis isolate BAC-44 that significantly inhibited ectopic vulval precursor cell (VPC) induction in Muv strains when fed as a live food source. BAC-08 and BAC-44 also significantly affected wild-type nematode development and growth. Metabolic pathway reconstruction from annotated genome assemblies did not support nutritional deficiency as the potential mechanism; instead, we observed that methanol-soluble intracellular extracts from BAC-44 were sufficient to inhibit pseudovulvae growth. We concluded that the observed Muv suppression is likely driven by a secondary metabolite effect. Comparative genomic analysis further identified unique biosynthetic gene clusters (BGCs) present in both BAC-08 and BAC-44 isolates compared to the other isolated Bacillus species. Altogether, our study demonstrates that the WormFood CURE model successfully identifies novel bacterial-genetic interactions, providing a scalable platform for discovery of new natural microbial products that modulate conserved eukaryotic signaling pathways.

genetics↗

bioRxiv2026

On the correctness of gene tree tagging and the consistency of ASTRAL-pro under a unified model of gene duplication, loss, and coalescence

AO_SCPLOWBSTRACTC_SCPLOWASTRAL-pro is the leading method for reconstructing species trees under complex evolutionary scenarios involving gene duplication, loss, and coalescence, commonly modeled by DLCoal. A unique aspect of A-pro is that it utilizes rooted gene trees, with internal vertices labeled as duplications or speciations, to modify its objective function compared to the traditional ASTRAL method. Although there is a natural event-based definition of correct tagging when genes evolve with only gene duplications and losses, it cannot be applied when there is deep coalescence. Here, we introduce a definition of correct tagging that is broadly applicable, proposing that a gene tree vertex is correctly tagged as a duplication if it is the most recent common ancestor of at least one pair of gene copies related via a duplication event. Using this definition, we study some statistical properties of ASTRAL-pros objective function under the DLCoal model and evaluate the accuracy of ASTRAL-pros tagging algorithm in simulations.

bioinformatics↗

bioRxiv2024

DupLoss-2: Improved Phylogenomic Species Tree Inference under Gene Duplication and Loss

Accurate species tree reconstruction in the presence of widespread gene duplication and loss is a challenging problem in eukaryote phylogenomics. Many phylogenomics methods have been developed over the years to address this challenge; these range from older methods based on gene tree parsimony to newer quartet-based methods. In this work, we introduce improved software for gene tree parsimony-based species tree reconstruction under gene duplication and loss. The new software, DupLoss-2, uses an improved procedure for computing gene losses and is far more accurate and much easier to use than its previous version released over a decade ago. We thoroughly evaluate DupLoss-2 and eight other existing methods, including ASTRAL-Pro, ASTRAL-Pro 2, DISCO-ASTRAL, DISCO-ASTRID, FastMulRFS, and SpeciesRax, using existing benchmarking data and find that DupLoss-2 outperforms all other methods on most of the datasets. It delivers an average of almost 30% reduction in reconstruction error compared to iGTP-Duploss, the previous version of this software, and a 10% reduction compared to the best performing existing method. DupLoss-2 is written in C++ and is freely available open-source.

bioinformatics↗

bioRxiv2024

GLMMcosinor: Flexible cosinor modeling with a generalized linear mixed modeling framework to characterize rhythmic time series.

BackgroundModeling rhythmic biological processes, such as gene expression and sleep-wake cycles, is critical for understanding physiological mechanisms and their dysregulation in disease. Traditional cosinor analysis, commonly used to model rhythmic data, assumes Gaussian-distributed residuals and does not account for hierarchical data, limiting its applicability in modern biological datasets. ResultsWe present GLMMcosinor, an R package that integrates cosinor modeling into the Generalized Linear Mixed Modeling (GLMM) framework using glmmTMB. GLMMcosinor enables analysis of a broad spectrum of non-Gaussian and hierarchical data structures, including count, positive-only, and zero-inflated distributions. By incorporating mixed-effects modeling, GLMMcosinor improves parameter estimation and biological interpretability. The package includes functions for group comparisons of rhythmic parameters and visualization tools such as polar and time series plots. Additionally, GLMMcosinor is available as a Shiny app for intuitive, code-free analysis. ConclusionsGLMMcosinor significantly extends the flexibility and scope of rhythmic data analysis by incorporating GLMM functionality. It is freely available on GitHub, CRAN, rOpenSci, and the R-universe, with comprehensive documentation and reproducible examples, making it a robust tool for researchers analyzing complex rhythmic datasets.

bioinformatics↗

bioRxiv2024

Terrestrial 3D Laser Scanning for Ecosystem and Fire Effects Monitoring

Long-term terrestrial ecosystem monitoring is a critical component of documenting outcomes of land management actions, assessing progress towards management objectives, and guiding realistic long-term ecological goals, all through repeated observation and measurement. Traditional monitoring methods have evolved for specific applications in forestry, ecology, and fire and fuels management. While successful monitoring programs have clear goals, trained expertise, and rigorous sampling protocols, new advances in technology and data management can help overcome the most common pitfalls in data quality and repeatability. This paper presents Terrestrial Laser Scanning (TLS), a specific form of LiDAR (Light Detection and Ranging), as an emerging sampling method that can complement and enhance existing monitoring methods. TLS captures in high resolution the 3D structure of a terrestrial ecosystem (forest, grassland, etc.), and is increasingly efficient and affordable (<$30,000). Integrating TLS into ecosystem monitoring can standardize data collection, improve efficiency, and reduce bias and error. Streamlined data processing pipelines can rigorously analyze TLS data and incorporate constant improvements to inform management decisions and planning. The approach described in this paper utilizes portable, push-button TLS equipment that, when calibrated with initial transect sampling, captures detailed forestry, fuels, and ecological features in less than 5 minutes per plot. We also introduce an interagency automated processing pipeline and dashboard viewer for instant, user-friendly analysis, and data retrieval of hundreds of metrics. Forest metrics and inventories produced with these methods offer effective decision-support data for managers to quantify landscape-scale conditions and respond with efficient action. This protocol further supports interagency compatibility for efficient natural resource monitoring across jurisdictional boundaries with uniform data, language, methods, and data analysis. With continued improvement of scanner capabilities and affordability, these data will shape the future of terrestrial ecosystem monitoring as an important means to address the increasingly fast pace of ecological change facing natural resource managers.

ecology↗

bioRxiv2024

Seasonal exometabolites are regulated by essential microbial metabolisms in the oligotrophic ocean

Predictions of how the biogeochemical reservoir of marine dissolved organic matter (DOM) will respond to future ocean changes require an improved understanding of the thousands of individual microbe-molecule interactions which regulate the transformation and fate of DOM. Bulk characterizations of organic matter can mask this complex network of interactions comprised of rich chemical and taxonomic diversity. Here, we present a three-year, depth-resolved time-series of the seasonal dynamics of the exometabolome and the bacterioplankton community at the Bermuda Atlantic Time-series Study (BATS) site. We find both time-series to be highly structured and compositionally distinct across sampling depths. Putative exometabolite identifications (gonyol, glucose 6-sulfate, succinate, and trehalose) indicate that at least a portion of the exometabolome contains rapidly remineralized, labile molecules. We hypothesize that apparent seasonal accumulation of these labile molecules could result from environmental conditions that alter community composition on a seasonal timescale and thus shift the relative proportions of microbial functions that produce and consume the substrates. Critically, we found the composition of seasonal DOM features was more stable interannually than the microbial community structure. By estimating redundancy of metabolic functions responsible for cycling these molecules in BATS metagenomes, we propose a paradigm whereby core microbial metabolisms, either those utilized by all or by a subset of marine microbes, are better predictors of DOM composition than microbial taxonomies. The molecular-level characterization of DOM achieved herein highlights the metabolic imprint of microbial activity in DOM composition and greatly enhances our understanding of the dynamics regulating Earths largest reservoir of organic carbon. Significance statementMarine dissolved organic matter (DOM) is a major carbon reservoir that acts as a critical control on Earths climate. DOM dynamics are largely regulated by a complex web of microbial interactions, but the mechanisms underpinning these processes are not well understood. In a three-year time-series, we found thousands of DOM molecules and microbial taxa exhibited seasonal patterns. Critically, the identity of the microbes was more variable between years than the composition of the DOM molecules. We suggest that shared metabolisms encoded by genes that conduct core microbial functions are responsible for the more stable composition of DOM. This work links DOM molecules with microbial biodiversity, and presents testable predictors of DOM composition in our changing oceans.

microbiology↗

bioRxiv2024

SARS-CoV-2 Omicron lineage XBB spike structures, conformations, antigenicity, and receptor recognition

A recombinant lineage of the SARS-CoV-2 Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for their improved immune evasion and transmissibility. Here, we determine cryo-EM structures of XBB.1.5, XBB.1.16, EG.5 and EG.5.1 spike (S) ectodomains to reveal reinforced 3-RBD-down receptor inaccessible closed states mediated by interprotomer receptor binding domain (RBD) interactions previously observed in BA.1 and BA.2. Improved XBB.1.5 and XBB.1.16 RBD stability compensated for stability loss caused by early Omicron mutations, while the F456L substitution reduced EG.5 RBD stability. S1 subunit mutations had long-range impacts on conformation and epitope presentation in the S2 subunit. Our results reveal continued S protein evolution via simultaneous optimization of multiple parameters including stability, receptor binding and immune evasion, and the dramatic effects of relatively few residue substitutions in altering the S protein conformational landscape.

biochemistry↗

bioRxiv2023

Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice

Thyroid hormones (THs) are important regulators of systemic energy metabolism. In the liver, they stimulate lipid and cholesterol turnover and increase systemic energy bioavailability. It is still unknown how the TH state interacts with the circadian clock, another important regulator of energy metabolism. We addressed this question using a mouse model of hypothyroidism and performed circadian analyses. Low TH levels decreased locomotor activity, food intake, and body temperature mostly in the active phase. Concurrently, liver transcriptome profiling showed only subtle effects compared to elevated TH conditions. Comparative circadian transcriptome profiling revealed alterations in mesor, amplitude, and phase of transcript levels in the livers of low-TH mice. Genes associated with cholesterol uptake, biosynthesis, and bile acid secretion showed reduced mesor. Increased and decreased cholesterol levels in the serum and liver were identified, respectively. Combining data from low- and high-TH conditions allowed the identification of 516 genes with mesor changes as molecular markers of the liver TH state. These genes participate in many known TH-associated processes. We further explored these genes and created a unique expression panel that can assess liver TH state in a time-of-day dependent manner. Our findings suggest that the liver has a low TH state under physiological conditions. Circadian profiling reveals genes as potential markers of liver TH state in one-time point studies.

physiology↗

bioRxiv2023

Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted / founder sensitivity to broadly neutralizing antibodies

HIV-1 envelope glycoproteins (Envs) mediate viral entry and are the sole target of neutralizing antibodies. Envs of most primary HIV-1 strains exist in a closed conformation and occasionally sample more open states. Thus, current knowledge guides immunogen design to mimic the closed Env conformation as the preferred target for eliciting broadly neutralizing antibodies (bnAbs) to block HIV-1 entry. Here we show that Env-preferred conformations of 6 out of 13 (46%) transmitted/founder (T/F) strains tested are incompletely closed. As a result, entry of these T/Fs into target cells is sensitive to antibodies that recognize internal epitopes exposed on open Env conformations. A cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) at 3.6 [A] resolution exhibits an asymmetric configuration of Env protomers with increased sampling of states with incompletely closed trimer apex. Double electron-electron resonance spectroscopy provided further evidence for enriched occupancy of more open Env conformations. Consistent with conformational flexibility, 1059 Envs were associated with resistance to most bnAbs that exhibit reduced potency against functional Env intermediates. To follow the fate of incompletely closed Env in patients, we reconstructed de novo the post-transmission evolutionary pathway of a second T/F Env (CH040), which is sensitive to the V3-targeting antibody 19b and highly resistant to most bnAbs. Evolved viruses exhibited increased resistance to cold, soluble CD4 and 19b, all of which correlate with closing of the adapted Env trimer. Lastly, we show a correlation between efficient neutralization of multiple Env conformations and increased antiviral breadth of CD4-binding site (CD4bs) bnAbs. In particular, N6 bnAb, which uniquely recognizes different Env conformations, efficiently neutralizes 50% of the HIV-1 strains that were resistant to VRC01 and transmitted during the first-in-humans antibody-mediated prevention trial (HVTN 704). VRC01-resistant Envs are incompletely closed based on their sensitivity to cold and on partial sensitivity to antibodies targeting internal, typically occluded, epitopes. Most VRC01-resistant Envs retain the VRC01 epitope according to VRC01 binding to their gp120 subunit at concentrations that have no significant effect on virus entry, and they exhibit cross resistance to other CD4bs bnAbs that poorly recognize functional Env intermediates. Our findings refine current knowledge of Env conformational states and provide guidance for developing new strategies for bnAb immunotherapy and Env-based immunogen design.

microbiology↗

bioRxiv2023

Sex difference in the facilitation of fear learning by prior fear conditioning.

There is now ample evidence that the strength and underlying mechanisms of memory formation can be drastically altered by prior experience. However, the prior work using rodent models on this topic has used only males as subjects, and as a result, we do know whether or not the effects of prior experience on subsequent learning are similar in both sexes. As a first step towards addressing this shortcoming rats of both sexes were given auditory fear conditioning, or fear conditioning with unsignaled shocks, followed an hour or a day later by a single pairing of light and shock. Fear memory for each experience was assessed by measuring freezing behavior to the auditory cue and fear-potentiated startle to the light. Results showed that males trained with auditory fear conditioning showed facilitated learning to the subsequent visual fear conditioning session when the two training sessions were separated by one hour or one day. Females showed evidence of facilitation in rats given auditory conditioning when they were spaced by an hour, but not when they were spaced by one day. Contextual fear conditioning did not support the facilitation of subsequent learning under any conditions. These results indicate that the mechanism by which prior fear conditioning facilitates subsequent learning differs between sexes, and they set the stage for mechanistic studies to understand the neurobiological basis of this sex difference.

neuroscience↗

bioRxiv2022

Seasonal and daily patterns in known dissolved metabolites in the northwestern Sargasso Sea

Organic carbon in seawater plays a significant role in the global carbon cycle. The concentration and composition of dissolved organic carbon, operationally defined in this project as organic carbon that passes through a 0.2 {micro}m filter, reflect the activity of the biological community and chemical reactions that occur in seawater. From 2016 to 2019, we repeatedly sampled the oligotrophic northwest Sargasso Sea in the vicinity of the Bermuda Atlantic Time-series Study site (BATS) to quantitatively follow known compounds within the pool of dissolved organic matter in the upper 1000 meters of the water column. Dissolved metabolite concentrations revealed patterns with depth and time with most metabolites showing surface enrichment and lower concentrations with increasing depth. Select metabolites displayed seasonal patterns throughout the year, and this seasonality was repeated in each of the years sampled. Concentrations of vitamins, including pantothenic acid (vitamin B5) and riboflavin (vitamin B2), increased annually during winter periods when mixed layer depths were deepest. During diel sampling, light-sensitive riboflavin decreased significantly during daylight hours. Metabolite concentrations over time at BATS showed less variability compared to a previous sample set collected over a broad latitudinal range in the western Atlantic Ocean. The metabolites examined in this study are all components of central carbon metabolism. By examining these metabolites at finer resolution and in a relatively long time series, we have insights into microbial biogeochemical activity, data which are fundamental to understanding the chemical response of marine systems to future changes in climate.

biochemistry↗

bioRxiv2022

Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation

Diurnal (i.e., 24-hour) physiological rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, and food intake align physiological circadian rhythms with external time. Thyroid hormones (THs) are major regulators of circadian clock target processes such as energy metabolism, but little is known about how fluctuations in TH levels affect the circadian coordination of tissue physiology. In this study, a high triiodothyronine (T3) state was induced in mice by supplementing T3 in the drinking water, which affected body temperature, and oxygen consumption in a time-of-day dependent manner. 24-hour transcriptome profiling of liver tissue identified 37 robustly and time independently T3 associated transcripts as potential TH state markers in the liver. Such genes participated in xenobiotic transport, lipid and xenobiotic metabolism. We also identified 10 - 15 % of the liver transcriptome as rhythmic in control and T3 groups, but only 4 % of the liver transcriptome (1,033 genes) were rhythmic across both conditions - amongst these several core clock genes. In-depth rhythm analyses showed that most changes in transcript rhythms were related to mesor (50%), followed by amplitude (10%), and phase (10%). Gene set enrichment analysis revealed TH state dependent reorganization of metabolic processes such as lipid and glucose metabolism. At high T3 levels, we observed weakening or loss of rhythmicity for transcripts associated with glucose and fatty acid metabolism, suggesting increased hepatic energy turnover. In sum, we provide evidence that tonic changes in T3 levels restructure the diurnal liver metabolic transcriptome independent of local molecular circadian clocks.

physiology↗

bioRxiv2021

P53 is a direct regulator of the immune co-stimulatory molecule CD80

Increasing evidence indicates oncogenes and tumor suppressors not only influence cell fitness but can also control the immunophenotype of cells. Here, we examined how 34 commonly mutated genes in colorectal cancer (CRC) may influence the expression of 8 key immunomodulatory proteins. To do this, we employed a functional genomics approach utilizing Pro-Code/CRISPR libraries for high-dimensional analysis. We introduced a library of 102 Pro-Code/gRNA combinations, targeting each of the 34 genes, in CT26 cells, a CRC cell model, and measured the expression of each of the immunomodulatory proteins by CyTOF mass cytometry. Notably, cells carrying a Pro-Code/CRISPR targeting the Trp53 lost expression of the immune co-stimulatory molecule CD80. Validation confirmed that Trp53 knockout resulted in the loss of CD80 and that activation of P53, through DNA damage or stabilization, resulted in CD80 upregulation. P53 ChIP-seq identified the CD80 promoter as a direct target of P53. CD80 regulation by P53 was identified in other cells, including normal epithelial cells and macrophages. Functionally, CD80 reduction caused by P53 loss led to a reduced capacity for CRC to prime antigen-specific T cells. These studies establish CD80, a canonical co-stimulatory molecule, as a direct target of the tumor suppressor and DNA damage response gene, P53.

immunology↗

bioRxiv2020

Modelling live fuel moisture content at leaf and canopy scale under extreme drought using SurEau-Ecos, a lumped plant hydraulic model

O_LIWater content in living vegetation (or live fuel moisture content, LFMC), is increasingly recognized as a key factor linked to vegetation mortality and wildfire ignition and spread. Most often, empirical indices are used as surrogates for direct LFMC measurements. C_LIO_LIIn this paper, we explore the functional and ecophysiological drivers of LFMC during drought at the leaf and canopy scale using the SurEau-Ecos model, and a three years dataset of leaf and canopy scale measurements on a mature Quercus ilex forest, including an extreme drought. The model is based on forest hydrology and plant hydraulics and allows to simulate temporal variations of water potential and content at a daily time step. At leaf level, it simulates the relationship between water potential and water content by separating the apoplasm and the symplasm. Symplasm water content is modeled using the pressure volume curve theory, and apoplasm water content is modelled using the xylem vulnerability to cavitation. Fuel moisture content was upscaled to the canopy level by accounting for foliage mortality estimated from drought induced cavitation. C_LIO_LIThe model was parameterized either with site-measured traits or using a calibration procedure, and compared with water potential and LFMC measured at leaf level, and NDVI variation measured at canopy level and taken as a surrogate for foliage mortality. C_LIO_LIAt leaf level, LFMC prediction using measured hydraulic traits could be improved by considering year-to-year osmotic adjustments. At canopy level, foliage mortality due to drought induced cavitation was a key driver of LFMC decline during the most extreme drought. C_LIO_LIA sensitivity analysis showed that parameters driving soil water balance (leaf area index, soil water capacity, and regulation of transpiration) and parameters determining pressure volume curves are key traits driving LFMC dynamics at leaf level. At the canopy level, parameters that drives hydraulic failure were the most sensitive and included, both soil water balance parameters and hydraulic traits (the leaf vulnerability to cavitation) were the main drivers of LFMC decline during extreme drought. C_LIO_LIWe also showed that under normal historic weather conditions, most variation of LFMC are linked to reversible symplasm dehydration, however under future, hotter and dryer conditions, most variations are due to the decline canopy of LFMC driven by foliage mortality. C_LI

ecology↗

bioRxiv2019

Pangenomics reveal diversification of enzyme families and niche specialization in globally abundant SAR202 bacteria

It has been hypothesized that abundant heterotrophic ocean bacterioplankton in the SAR202 clade of the phylum Chloroflexi evolved specialized metabolism for the oxidation of organic compounds that are resistant to microbial degradation via common metabolic pathways. Expansions of paralogous enzymes were reported and implicated in hypothetical metabolism involving monooxygenase and dioxygenase enzymes. In the metabolic schemes proposed, the paralogs serve the purpose of diversifying the range of organic molecules that cells can utilize. To further explore this question, we reconstructed SAR202 single amplified genomes and metagenome-assembled genomes from locations around the world, including the deepest ocean trenches. In analyses of 122 SAR202 genomes that included six subclades spanning SAR202 diversity, we observed additional evidence of paralog expansions that correlated with evolutionary history, and further evidence of metabolic specialization. Consistent with previous reports, families of flavin-dependent monooxygenases were observed mainly in the Group III SAR202, in the proposed class Monstramaria and expansions of dioxygenase enzymes were prevalent in Group IV. We found that Group I SAR202 encode expansions of racemases in the enolase superfamily, which we propose evolved for the degradation of compounds that resist biological oxidation because of chiral complexity. Supporting the conclusion that the paralog expansions indicate metabolic specialization, fragment recruitment and fluorescence in situ hybridization with phylogenetic probes showed that SAR202 subclades are indigenous to different ocean depths and geographical regions. Surprisingly, some of the subclades were abundant in surface waters and contained rhodopsin genes, altering our understanding of the ecological role of SAR202 in stratified water columns.\n\nImportanceThe oceans contain an estimated 662 Pg C of dissolved organic carbon (DOC). Information about microbial interactions with this vast resource is limited, despite broad recognition that DOM turnover has a major impact on the global carbon cycle. To explain patterns in the genomes of marine bacteria we propose hypothetical metabolic pathways for the oxidation of organic molecules that are resistant to oxidation via common pathways. The hypothetical schemes we propose suggest new metabolism and classes of compounds that could be important for understanding of the distribution of organic carbon throughout the biosphere. These genome-based schemes will remain hypothetical until evidence from experimental cell biology can be gathered to test them, but until then they provide a perspective that directs our attention to the biochemistry of resistant DOM metabolism. Our findings also fundamentally change our understanding of the ecology of SAR202, showing that metabolically diverse variants of these cells occupy niches spanning all depths, and are not relegated to the dark ocean.

genomics↗