Biology subjects

Smith, C. R.

Publications and source records attributed to Smith, C. R..

10 recordsLinked to original sources

bioRxiv2026

Allochthony in stream food webs decreases with temperature across a subcontinental scale

Riverine and riparian food webs are connected via 'allochthonous' resource flows from neighboring ecosystems. These resources, such as terrestrial leaf litter, contribute to benthic macroinvertebrate diets, supporting higher trophic levels. While allochthony occurs in streams globally, its sensitivity to broad environmental gradients remains poorly understood. We explored the drivers of allochthony across six river basins within the contiguous United States, including climate, stream size, and flow permanence. We used Bayesian mixing models to estimate macroinvertebrate dietary proportions in four functional feeding groups. Air temperature best predicted allochthony, with consumers relying less on allochthonous resources with increasing temperature. Our models indicate that macroinvertebrate diets become primarily autochthonous at approximately 15{degrees}C mean annual air temperature, with leaf litter-consuming shredders showing a slightly higher threshold for this shift. We also found increased allochthony in smaller, non-perennial streams. These findings highlight the complexity of stream allochthony and responses to multi-scale environmental factors.

ecology↗

bioRxiv2026

Trajectories of Response Inhibition Development in Adolescence

Adolescence is a pivotal developmental period during which cognitive control and the ability to suppress maladaptive impulses undergo profound refinement. Despite extensive behavioral and imaging studies in humans, the neural circuit mechanisms that drive the maturation of inhibitory control remain poorly understood. To address this gap, we performed a longitudinal multimodal study in macaque monkeys spanning the transition from puberty to adulthood, combining behavioral measurements, prefrontal neurophysiology, and structural neuroimaging within the same individuals. Behavioral performance in multiple variants of the antisaccade task improved dramatically across adolescence. In parallel, prefrontal cortical neurons exhibited robust developmental increases in task-related firing, particularly around the generation of goal-directed saccades, indicating maturation of neural representations supporting inhibitory control. Strikingly, trajectories of behavioral improvement and neural activity maturation were tightly predicted by the development of long-range white matter pathways linking frontal cortex with distributed brain networks. These findings identify white matter development as a key systems-level mechanism underlying the emergence of mature inhibitory control and prefrontal neural dynamics and establish a primate framework for understanding developmental vulnerabilities associated with neuropsychiatric disorders that emerge in adolescence and early adulthood.

neuroscience↗

bioRxiv2025

TSPO deficiency reveals a novel role for porphyrins in regulating white adipose tissue lipid metabolism

The translocator protein (TSPO) is a mitochondrial outer membrane protein with high expression in cells specialized for lipid metabolism, including white adipose tissue (WAT), where its physiological function remains poorly defined. Our previous work demonstrated a role for TSPO in mitochondrial fatty acid oxidation, prompting us to investigate its contribution to adipocyte lipid homeostasis under metabolic stress. We employed a combination of in vivo and in vitro approaches using global Tspo knockout (Tspo-/-) mice, primary adipocyte cultures, and pharmacological TSPO-binding drugs to examine TSPO function. We show that Tspo-/- mice exhibited increased WAT mass and adipocyte hypertrophy following high-fat diet feeding, with no changes in caloric intake. These changes were accompanied by suppression of key lipolytic genes, reduced circulating NEFA and glycerol levels, and altered expression of fatty acid oxidation genes. Lipidomic profiling showed no genotype-dependent changes, indicating impaired mobilization rather than altered lipid composition. In vitro, TSPO deficiency enhanced lipid accumulation during adipocyte diberentiation and impaired expression of lipolytic genes. TSPO-binding drugs phenocopied this response in TSPO-expressing cells. Mechanistically, we identify protoporphyrin IX (PPIX), an endogenous TSPO ligand, as a suppressor of adipogenic and lipolytic programs. PPIX levels increase during adipogenesis, and its accrual inhibits both lipid accumulation and lipolytic response, whereas hemin does not elicit these ebects. Our findings identify TSPO as a regulator of adipocyte lipid metabolism through a previously unrecognized TSPO-PPIX axis that influences lipid mobilization in adipocytes. This mechanism provides insight into TSPOs role in metabolic adaptation and highlights its potential as a therapeutic target in obesity-associated adipose dysfunction.

pathology↗

bioRxiv2024

DNA-Diffusion: Leveraging Generative Models for Controlling Chromatin Accessibility and Gene Expression via Synthetic Regulatory Elements

The challenge of systematically modifying and optimizing regulatory elements for precise gene expression control is central to modern genomics and synthetic biology. Advancements in generative AI have paved the way for designing synthetic sequences with the aim of safely and accurately modulating gene expression. We leverage diffusion models to design context-specific DNA regulatory sequences, which hold significant potential toward enabling novel therapeutic applications requiring precise modulation of gene expression. Our framework uses a cell type-specific diffusion model to generate synthetic 200 bp regulatory elements based on chromatin accessibility across different cell types. We evaluate the generated sequences based on key metrics to ensure they retain properties of endogenous sequences: transcription factor binding site composition, potential for cell type-specific chromatin accessibility, and capacity for sequences generated by DNA diffusion to activate gene expression in different cell contexts using state-of-the-art prediction models. Our results demonstrate the ability to robustly generate DNA sequences with cell type-specific regulatory potential. DNA-Diffusion paves the way for revolutionizing a regulatory modulation approach to mammalian synthetic biology and precision gene therapy.

synthetic biology↗

bioRxiv2023

In defense of Apocynaceae: inference on evolution of pyrrolizidine alkaloids from evolution of an enzyme in their biosynthetic pathway, homospermidine synthase

PremiseWhen enzymes encoded by paralogous genes produce identical specialized metabolites in distantly related plant lineages, it is strong evidence of parallel phenotypic evolution. Inference of phenotypic homology for metabolites produced by orthologous genes is not so straightforward, however, since orthologs may be recruited in parallel into novel pathways. Prior research on pyrrolizidine alkaloids (PAs), specialized metabolites of Apocynaceae, reconstructed evolution of homospermidine synthase (HSS), an enzyme of PA biosynthesis, and inferred a single origin of PAs because HSS enzymes of all known PA-producing Apocynaceae species are orthologous and descended from an ancestral enzyme with the predicted motif (VXXXD) of an optimized HSS. MethodsWe increased sampling, tested the effect of amino acid motif on HSS function, revisited motif evolution, and tested for selection to infer evolution of HSS function and its correlation with phenotype. Key resultsSome evidence supports a single origin of PAs: an IXXXD HSS, similar in function to VXXXD HSS, evolved in the shared ancestor of all PA-producing species; loss of optimized HSS occurred multiple times via pseudogenization and perhaps via evolution of an IXXXN motif. Other evidence indicates multiple origins: the VXXXD motif, highly correlated with the PA phenotype, evolved two or four times independently; the ancestral IXXXD gene was not under positive selection while some VXXXD genes were; substitutions at sites experiencing positive selection occurred on multiple branches in the HSS-like gene tree. ConclusionsComplexity of the genotype-function-phenotype map confounds inference of PA homology from HSS evolution in Apocynaceae.

evolutionary biology↗

bioRxiv2023

The Antarctic Seafloor Annotated Imagery Database

Marine imagery is a comparatively cost-effective way to collect data on seafloor organisms, biodiversity and habitat morphology. However, annotating these images to extract detailed biological information is time-consuming and expensive, and reference libraries of consistently annotated seafloor images are rarely publicly available. Here, we present the Antarctic Seafloor Annotated Imagery Database (AS-AID), a result of a multinational collaboration to collate and annotate regional seafloor imagery datasets from 19 Antarctic research cruises between 1985 and 2019. AS-AID comprises of 3,599 georeferenced downward facing seafloor images that have been labelled with a total of 615,051 expert annotations. Annotations are based on the CATAMI (Collaborative and Automated Tools for Analysis of Marine Imagery) classification scheme and have been reviewed by experts. In addition, because the pixel location of each annotation within each image is available, annotations can be viewed easily and customised to suit individual research priorities. This dataset can be used to investigate species distributions, community patterns, it provides a reference to assess change through time, and can be used to train algorithms to automatically detect and annotate marine fauna.

ecology↗

bioRxiv2020

Chemotaxonomic Investigation of Apocynaceae for Retronecine-Type Pyrrolizidine Alkaloids Using HPLC-MS/MS

Apocynaceae are well-known for diverse specialized metabolites that are distributed in a phylogenetically informative manner. Pyrrolizidine alkaloids (PAs) have been reported sporadically in one lineage in the family, the APSA clade, but few species had been studied to date. We conduct the first systematic survey of Apocynaceae for retronecine-type PAs, sampling leaves from 231 species from 13 of 16 major lineages within the APSA clade using HPLC-MS/MS. We also follow up on preliminary evidence for infra-specific variation of PA detectability in Echites umbellatus Jacq. Four precursor ion scans (PREC) were developed for a high-throughput survey for chemicals containing a structural moiety common to many PAs, the retronecine core. We identified with high confidence PAs in 7 of 8 sampled genera of tribe Echiteae, but not in samples from the closely related Odontadenieae and Mesechiteae, confirming the utility of PAs as a taxonomic character in tribal delimitation. The presence of PAs in Malouetieae was confirmed, as we report with high confidence their presence in Galactophora schomburgkiana Woodson and Eucorymbia alba Stapf, but currently we have low confidence of their presence in Holarrena pubescens Wall. ex G. Don (the one Malouetieae species where they were previously reported), as well as in Kibatalia macrophylla (Pierre ex Hua) Woodson and in Holarrena curtisii King & Gamble. For the first time the presence of PAs in species of Wrightia R. Br. (Wrightieae) and Marsdenia R. Br. (Marsdenieae) was confirmed. Detectability of PAs was found to vary among samples of Echites umbellatus and intra-individual plasticity contributes to this variation. Of toxicological importance, novel potential sources of human exposure to pro-toxic PAs were identified in the medicinal plants, Wrightia tinctoria R.Br. and Marsdenia tinctoria R.Br., and the food plant, Echites panduratus A. DC., warranting immediate further research to elucidate the structures of the candidate PAs identified. Method development and limitations are discussed.

plant biology↗

bioRxiv2020

Reference genome and demographic history of the most endangered marine mammal, the vaquita

The vaquita is the most critically endangered marine mammal, with fewer than 19 remaining in the wild. First described in 1958, the vaquita has been in rapid decline resulting from inadvertent deaths due to the increasing use of large-mesh gillnets for more than 20 years. To understand the evolutionary and demographic history of the vaquita, we used combined long-read sequencing and long-range scaffolding methods with long- and short-read RNA sequencing to generate a near error-free annotated reference genome assembly from cell lines derived from a female individual. The genome assembly consists of 99.92% of the assembled sequence contained in 21 nearly gapless chromosome-length autosome scaffolds and the X-chromosome scaffold, with a scaffold N50 of 115 Mb. Genome-wide heterozygosity is the lowest (0.01%) of any mammalian species analyzed to date, but heterozygosity is evenly distributed across the chromosomes, consistent with long-term small population size at genetic equilibrium, rather than low diversity resulting from a recent population bottleneck or inbreeding. Historical demography of the vaquita indicates long-term population stability at less than 5000 (Ne) for over 200,000 years. Together, these analyses indicate that the vaquita genome has had ample opportunity to purge highly deleterious alleles and potentially maintain diversity necessary for population health.

genomics↗

bioRxiv2020

From sea surface to seafloor: a benthic allochthonous eDNA survey for the abyssal ocean

Diverse and remote deep-sea communities are critically under-sampled and increasingly threatened by anthropogenic impacts. Environmental DNA (eDNA) metabarcoding could facilitate rapid and comprehensive biotic surveys in the deep ocean, yet many aspects of the sources and distribution of eDNA in the deep sea are still poorly understood. In order to examine the influence of the water column on benthic eDNA surveys in regions targeted for deep-sea polymetallic nodule mining, we investigated the occurrence of pelagic eDNA across: (1) two different deep-sea habitat types, abyssal plains and seamounts, (2) benthic sample types, including nodules, sediment, and seawater within the benthic boundary layer (BBL), and (3) sediment depth horizons (0-2 cm, 3-5 cm). Little difference was observed between seamounts and the adjacent abyssal plains in the proportion of legacy pelagic eDNA sampled in the benthos, despite an > 1000 m depth difference for these habitats. In terms of both reads and amplicon sequence variants (ASVs), pelagic eDNA was minimal within sediment and nodule samples (< 2%), and is unlikely to affect benthic surveys that monitor resident organisms at the deep seafloor. However, pelagic eDNA was substantial within the BBL (up to 13 % ASVs, 86% reads), deriving both from the high biomass upper ocean as well as deep pelagic residents. While most pelagic eDNA found in sediments and on nodules could be sourced from the epipelagic for metazoans, protist legacy eDNA sampled on these substrates appeared to originate across a range of depths in the water column. Some evidence of eDNA degradation across a vertical sediment profile was observed for protists, with higher diversity in the 0-2 cm layer and a significantly lower proportion of legacy pelagic eDNA in deeper sediments (3-5 cm). Study-wide, our estimated metazoan sampling coverage ranged from 40% to 74%, despite relatively large sample size. Future deep-sea eDNA surveys should examine oceanographic influences on eDNA transport and residence times, consider habitat heterogeneity at a range of spatial scales in the abyss, and aim to process large amounts of material per sample (with replication) in order to increase the sampling coverage in these diverse deep ocean communities.

ecology↗

bioRxiv2019

Functional insights from the GC-poor genomes of two aphid parasitoids, Aphidius ervi and Lysiphlebus fabarum

BackgroundParasitoid wasps have fascinating life cycles and play an important role in trophic networks, yet little is known about their genome content and function. Parasitoids that infect aphids are an important group with the potential for biocontrol, and infecting aphids requires overcoming both aphid defenses and their defensive endosymbionts. ResultsWe present the de novo genome assemblies, detailed annotation, and comparative analysis of two closely related parasitoid wasps that target pest aphids: Aphidius ervi and Lysiphlebus fabarum (Hymenoptera: Braconidae: Aphidiinae). The genomes are small (139 and 141 Mbp), highly syntenic, and the most AT-rich reported thus far for any arthropod (GC content: 25.8% and 23.8%). This nucleotide bias is accompanied by skewed codon usage, and is stronger in genes with adult-biased expression. AT-richness may be the consequence of reduced genome size, a near absence of DNA methylation, and age-specific energy demands. We identify expansions of F-box/Leucine-rich-repeat proteins, suggesting that diversification in this gene family may be associated with their broad host range or with countering defenses from aphids endosymbionts. The absence of some immune genes (Toll and Imd pathways) resembles similar losses in their aphid hosts, highlighting the potential impact of symbiosis on both aphids and their parasitoids. ConclusionsThese findings are of fundamental interest for insect evolution and beyond. This will provide a strong foundation for further functional studies including coevolution with respect to their hosts, the basis of successful infection, and biocontrol. Both genomes are available at https://bipaa.genouest.org.

genomics↗