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Carlson, J.

Publications and source records attributed to Carlson, J..

At least 19 recordsLinked to original sources

Cyclic AMP compartmentalization drives signal specificity to control vector colonization and mammalian host infection by American trypanosomes

Cyclic AMP (cAMP) signaling is crucial for environmental sensing and response to stress conditions in trypanosomatids. However, the mechanisms driving the specificity of cAMP signals remain poorly understood in these protozoan parasites. We recently identified two putative cAMP microdomains in Trypanosoma cruzi, the causative agent of Chagas disease. Here, considering the localization of three phosphodiesterases, PDEC at the contractile vacuole complex (CVC), and PDEB1 and PDEB2 along the flagellum, we modulated their expression to functionally characterize the flagellar tip (FT) and the CVC as individual cAMP microdomains, named FT-cAMP and CVC-cAMP, respectively. We generated PDE knockout and overexpression cell lines to selectively alter cAMP signals generated in each compartment. Our results indicate that FT-cAMP mediates cell adhesion, metacyclogenesis, host cell invasion, and intracellular replication, while CVC-cAMP is required for osmoregulation and epimastigote proliferation. In addition, ablation of flagellar PDEB1 and PDEB2 enhanced the parasites ability to colonize the hindgut of the triatomine vector, whereas PDEC-KO parasites were impaired in their establishment in the insects hindgut. The observed phenotypes were compartment-specific, demonstrating functional segregation between the two cAMP microdomains. Our data provide robust evidence on the presence of compartmentalized cAMP signals in T. cruzi, linking the role of locally synthesized cAMP pools to specific cellular responses during the parasites life cycle. Author summaryChagas disease is a life-threatening infectious disease caused by the protozoan parasite Trypanosoma cruzi, which is spread through the feces of infected kissing bugs. The parasite survives in challenging environments as it transitions between the insect vector and the mammalian host by differentiating into distinct developmental forms. cAMP is a universal second messenger that mediates specific cellular processes in the life cycle of T. cruzi. However, the spatial-temporal dynamics of cAMP signal remain largely unexplored in trypanosomes. We previously reported several cAMP signaling proteins in two compartments of T. cruzi: the contractile vacuole complex (CVC) and the flagellar tip (FT). In this study, we characterized the individual functions of these microdomains. We specifically disturbed cAMP signaling in these compartments by modulating the expression of their resident phosphodiesterases. We observed that the FT microdomain is specifically involved in parasite differentiation, host cell invasion, intracellular replication, and vector colonization, while the CVC microdomain is important for osmoregulation and parasite survival within the kissing bug. Our results unequivocally demonstrate that T. cruzi utilizes specific cAMP pools to address different environmental challenges. These findings highlight cAMP signaling as an essential pathway that could be further explored for the development of novel antiparasitic interventions.

cell biology↗

Hidden Diversity of Threatened Sharks and Rays in the Global Meat Trade

International wildlife trade is a major source of biodiversity loss, yet many species lie hidden within aggregated data that conceals trade impacts. We overcome this problem for the largest vertebrate wildlife trade globally - shark and ray meat - comprising 438 538 mt yr-1 across more than 150 species, 76% of which are Threatened. Revealed trade contains greater quantities of skates (+10%), hammerheads (+8%), and smoothhounds, dogfishes & tope (+5%), and fewer pelagic sharks (-38%) than previously known. Shorttail yellownose skate, smoothound, silky, mako, and blue sharks are the most underreported meat species, due to aggregated landings from China, Argentina, Japan, and Indonesia, demonstrating international trade in shark and ray meat as a diverse, pervasive, and previously hidden source of fishing mortality for many threatened species.

ecology↗

TcCARP3 modulates compartmentalized cAMP signals involved in osmoregulation, infection of mammalian cells, and colonization of the triatomine vector in the human pathogen Trypanosoma cruzi

Trypanosoma cruzi is the causative agent of Chagas disease, a zoonotic infectious disease considered a leading cause of cardiomyopathy, disability, and premature death in the Americas. This parasite spends its life between a mammalian host and an arthropod vector, undergoing essential transitions among different developmental forms. How T. cruzi senses microenvironmental changes that trigger cellular responses necessary for parasite survival has remained largely unknown. Cyclic AMP (cAMP) is a universal second messenger that has been shown to regulate key cellular processes in trypanosomes, in which cyclic AMP response proteins (CARPs) have been proposed to be modulators or effectors of a PKA-independent signaling pathway. In this study we aimed to investigate the role of TcCARP3 in cAMP signaling throughout T. cruzi life cycle. Our results show that TcCARP3 shares a dual localization (flagellar tip and contractile vacuole complex) with adenylate cyclase 1 (TcAC1) in the main developmental stages of the parasite. We also found that TcCARP3 directly interacts with several TcACs, modulating the intracellular content of cAMP. Through generation of TcCARP3 knockout, addback, and overexpression cell lines we showed that modulation of gene expression affects the parasites ability to differentiate, respond to osmotic stress, invade mammalian cells and replicate within them, and colonize the hindgut of the triatomine vector. In addition, we identified several signaling proteins interacting with TcCARP3 in what we propose are cAMP signaling microdomains. Our results unveil a key role for TcCARP3 as modulator of cAMP signals necessary for parasite differentiation and survival throughout T. cruzi life cycle. IMPORTANCECyclic AMP signaling pathways are poorly understood in the stercorarian parasite Trypanosoma cruzi. Specifically, the mechanisms driving the activation of TcACs in response to microenvironmental stress are completely unknown. This study unveils the role of TcCARP3 in modulating the content of cAMP through the interaction with several TcACs and putative cAMP effectors in T. cruzi. Particularly, TcCARP3 interacts with TcAC1 in the main developmental stages of this parasites life cycle, where both proteins display a dual localization pattern. These results provide new evidence supporting the compartmentalization of cAMP signals in trypanosomes. Moreover, our data unequivocally demonstrates that TcCARP3 is required for key cellular processes for parasite survival, such as response to osmotic stress, host cell invasion, intracellular replication, and the ability to colonize the hindgut of the triatomine vector. In summary, we found that TcCARP3 is an adenylate cyclase regulator, necessary for the life cycle progression of T. cruzi.

microbiology↗

The battle of the sexes in humans is highly polygenic

Sex-differential selection (SDS), which occurs when the fitness effects of alleles differ between males and females, can have profound impacts on the maintenance of genetic variation, disease risk, and other key aspects of natural populations. Because the sexes mix their autosomal genomes each generation, quantifying SDS is not possible using conventional population genetic approaches. Here, we introduce a novel method that exploits subtle sex differences in haplotype frequencies resulting from SDS acting in the current generation. Using data from 300K individuals in the UK Biobank, we estimate the strength of SDS throughout the genome. While only a handful of loci under SDS are individually significant, we uncover polygenic signals of genome-wide SDS for both viability and fecundity. An interesting life-history tradeoff emerges: alleles that increase viability more in one sex increase fecundity more in the other sex. Lastly, we find evidence of SDS on fecundity acting on alleles affecting arm fat-free mass. Taken together, our findings connect the long-standing evidence of SDS acting on human phenotypes with its impact on the genome. Significance statementSelection often acts differently on females and males, as evidenced by the striking sexual dimorphism found in many taxa. As a result, alleles can have different fitness effects in each sex. Consequences can include higher levels of genetic variation and higher disease burdens in populations. This study introduces a novel method to quantify this sex-differential selection (SDS) and reveals that it acts throughout the human genome. We discovered a life history tradeoff between survival and fecundity in females and males and that SDS on fecundity acts on alleles affecting arm fat-free mass.

evolutionary biology↗

Diversification of gene expression across extremophytes and stress-sensitive species in the Brassicaceae

Plants are composed of diverse cell types that facilitate adaptations to the environment, yet cross-species comparisons of such response programs at single-cell resolution remain scarce. To explore this diversity, here we profiled >200,000 root cells from five Brassicaceae species, including stress-sensitive species (Arabidopsis thaliana, Sisymbrium irio), extremophytes (Eutrema salsugineum, Schrenkiella parvula), and the polyploid crop Camelina sativa under control, NaCl, and abscisic acid (ABA) treatments. We developed a computational pipeline to characterize the conservation and divergence of cell-type gene expression across the Brassicaceae, revealing that approximately half of previously defined Arabidopsis cell-type markers fail to maintain conserved expression in one or more non-Arabidopsis species. Therefore, we curated a refined set of pan-Brassicaceae markers and identified orthologs whose expression profiles have diverged across lineages. Using in situ hybridization, we mapped distinct cortex subpopulations to specific cortical layers across species, and found flavonoid biosynthesis programs preferentially localized to the inner cortex layer, linking cortex-layer specification to metabolic specialization. Cell-type contributions to stress responses differed among species and across treatments, with lineage-specific losses of responsiveness occurring less frequently but evolutionarily more favored than lineage-specific gains. In C. sativa, sub-genomes contributed equally to stress responses, and homeologs with divergent responses typically lacked other signatures of functional divergence. Together, this work establishes a foundational root single-cell atlas and an analytical framework for multi-species comparative transcriptomics, providing insights into how stress responses diversify across cell types, stress-sensitive to stress-adapted species, and in crop lineages.

plant biology↗

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↗

Clark (2023) and the Persistence of Hereditarian Fallacies

The scientific literature has seen a resurgence of interest in genetic influences on human behavior and socioeconomic outcomes. Such studies face the central difficulty of distinguishing possible causal influences, in particular genetic and non-genetic ones. When confounding between possible influences is not rigorously addressed, it invites over- and misinterpretation of data. We illustrate the breadth of this problem through a discussion of the literature and a reanalysis of two examples. Clark (2023) suggested that patterns of similarity in social status between relatives indicate that social status is largely determined by ones DNA. We show that the papers conclusions are based on the conflation of genetic and non-genetic transmission (for example, of wealth) within families. Song & Zhang (2024) posited that genetic variants underlying bisexual behavior are maintained in the population because they also affect risk-taking behavior, thereby conferring an evolutionary fitness advantage through increased sexual promiscuity. In this case, too, we show that possible explanations cannot be distinguished, but only one is chosen and presented as a conclusion. We discuss how issues of confounding apply more broadly to studies that claim to establish genetic underpinnings to human behavior and societal outcomes.

genetics↗

JGI Plant Gene Atlas: An updateable transcriptome resource to improve structural annotations and functional gene descriptions across the plant kingdom

Gene functional descriptions, which are typically derived from sequence similarity to experimentally validated genes in a handful of model species, offer a crucial line of evidence when searching for candidate genes that underlie trait variation. Plant responses to environmental cues, including gene expression regulatory variation, represent important resources for understanding gene function and crucial targets for plant improvement through gene editing and other biotechnologies. However, even after years of effort and numerous large-scale functional characterization studies, biological roles of large proportions of protein coding genes across the plant phylogeny are poorly annotated. Here we describe the Joint Genome Institute (JGI) Plant Gene Atlas, a public and updateable data resource consisting of transcript abundance assays from 2,090 samples derived from 604 tissues or conditions across 18 diverse species. We integrated across these diverse conditions and genotypes by analyzing expression profiles, building gene clusters that exhibited tissue/condition specific expression, and testing for transcriptional modulation in response to environmental queues. For example, we discovered extensive phylogenetically constrained and condition-specific expression profiles across many gene families and genes without any functional annotation. Such conserved expression patterns and other tightly co-expressed gene clusters let us assign expression derived functional descriptions to 64,620 genes with otherwise unknown functions. The ever-expanding Gene Atlas resource is available at JGI Plant Gene Atlas (https://plantgeneatlas.jgi.doe.gov) and Phytozome (https://phytozome-next.jgi.doe.gov), providing bulk access to data and user-specified queries of gene sets. Combined, these web interfaces let users access differentially expressed genes, track orthologs across the Gene Atlas plants, graphically represent co-expressed genes, and visualize gene ontology and pathway enrichments.

plant biology↗

Efficacy and safety of glycosphingolipid SSEA-4 targeting CAR-T cells in solid tumors

Chimeric antigen receptor (CAR) T-cell immunotherapies for solid tumors face critical challenges such as heterogeneous antigen expression. We characterized SSEA-4 cell-surface glycolipid as a target for CAR-T cell therapy. SSEA-4 is mainly expressed during embryogenesis but is also found in several cancer types making it an attractive tumor-associated antigen. Anti-SSEA-4 CAR-T cells were generated and assessed pre-clinically in vitro and in vivo for anti-tumor response and safety. SSEA-4 CAR-T cells effectively eliminated SSEA-4 positive cells in all tested cancer cell lines whereas SSEA-4 negative cells lines were not targeted. In vivo efficacy and safety studies using NSG mice and the high-grade serous ovarian cancer cell line OVCAR4 demonstrated a remarkable and specific anti-tumor response at all CAR-T cell doses used. At high T cell doses, CAR-T cell-treated mice showed signs of health deterioration after a follow-up period. However, severity of toxicity was reduced with delayed onset when lower CAR-T cell doses were used. Our data demonstrate the efficacy of anti-SSEA-4 CAR-T therapy; however, safety strategies, such as dose-limiting and/or equipping CAR-T cells with combinatorial antigen recognition should be implemented for its potential clinical translation.

cancer biology↗

Drosophila Keap1 oxidative/xenobiotic response factor interacts with B-type lamin to regulate nuclear lamina and heterochromatin

The essential function of the Keap1-Nrf2 pathway in mediating transcriptional response to xenobiotic and oxidative stimuli has been well established. However, the mechanisms whereby Keap1 and Nrf2 regulate developmental genes remains unclear. We hypothesized that Drosophila Keap1 (dKeap1) and Nrf2 (CncC) proteins regulate transcription through controlling high-order chromatin structure. Here, we describe evidence supporting that dKeap1 can regulate chromatin through interaction with lamin, the intermediate filament proteins that form nuclear lamina and organize the overall chromatin architecture. dKeap1 and lamin Dm0, the B-type lamin in Drosophila, interact with each other and form complexes in the nucleus. Overexpression of dKeap1 resulted in a redistribution of lamin Dm0 to the intra-nuclear area and consistently, caused a spreading of the heterochromatin marker H3K9me2 from the pericentromeric region to chromosome arms. Overexpression of dKeap1 fusion proteins in the dKeap1 null background significantly disrupted the nuclear lamina morphology, indicating that dKeap1 is required for the maintenance of a normal nuclear lamina. Knock down of dKeap1 partially rescued the lethality caused by lamin Dm0 overexpression, suggesting that dKeap1 and lamin Dm0 function in the same pathway during development. Taken together, these results support a model where dKeap1 regulates chromatin structure and developmental transcription through interaction with lamin proteins, revealing a novel epigenetic function of the Keap1 oxidative/xenobiotic response factor.

cell biology↗

The apportionment of citations: A scientometric analysis of Lewontin, 1972

"The Apportionment of Human Diversity" (1972) is the most highly cited research article published by geneticist Richard Lewontin in his career. This studys primary result--that most genetic diversity in humans can be accounted for by within-population differences, not between-population differences--along with Lewontins outspoken, politically-charged interpretations thereof, has become foundational to the scientific and cultural discourse pertaining to human genetic variation. The article has an unusual bibliometric trajectory in that it is much more salient in the bibliographic record today compared to the first 20 years after its publication. Here, we show how the papers fame was shaped by four factors: 1) citations in influential publications across several disciplines; 2) Lewontins own popular books and media appearances; 3) the renaissance of population genetics research of the early 1990s; and 4) the serendipitous collision of scientific progress, influential books/papers, and heated controversies in the year 1994. We conclude with an analysis of Twitter data to characterize the communities and conversations that continue to keep this study at the epicenter of discussions about race and genetics, prompting new challenges for scientists who have inherited Lewontins legacy.

scientific communication and education↗

Host genomic influence on bacterial composition in the switchgrass rhizosphere

Host genetic variation can shape the diversity and composition of associated microbiomes, which may reciprocally influence host traits and performance. While the genetic basis of phenotypic diversity of plant populations in nature has been studied, comparatively little research has investigated the genetics of host effects on their associated microbiomes. Switchgrass (Panicum virgatum) is a highly outcrossing, perennial, grass species with substantial locally adaptive diversity across its native North American range. Here, we compared 383 switchgrass accessions in a common garden to determine the host genotypic influence on rhizosphere bacterial composition. We hypothesized that the composition and diversity of rhizosphere bacterial assemblages would differentiate due to genotypic differences between hosts (potentially due to root phenotypes and associated life history variation). We observed higher alpha diversity of bacteria associated with upland ecotypes and tetraploids, compared to lowland ecotypes and octoploids, respectively. Alpha diversity correlated negatively with flowering time and plant height, indicating that bacterial composition varies along switchgrass life history axes. Narrow-sense heritability (h2) of the relative abundance of twenty-one core bacterial families was observed. Overall compositional differences among tetraploids, due to genetic variation, supports wide-spread genotypic influence on the rhizosphere microbiome. Lastly, a genome-wide association study identified 1,861 single-nucleotide polymorphisms associated with 110 families and genes containing them related to potential regulatory functions. Our findings suggest that switchgrass genomic and life-history variation influences bacterial composition in the rhizosphere, potentially due to host adaptation to local environments.

plant biology↗

Mutationathon: towards standardization in estimates of pedigree-based germline mutation rates

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various non-human species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and how to appropriately account for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a "Mutationathon", a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a two-fold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees.

evolutionary biology↗

Chromosome evolution and the genetic basis of agronomically important traits in greater yam

The nutrient-rich tubers of the greater yam Dioscorea alata L. provide food and income security for millions of people around the world. Despite its global importance, however, greater yam remains an "orphan crop." Here we address this resource gap by presenting a highly-contiguous chromosome-scale genome assembly of greater yam combined with a dense genetic map derived from African breeding populations. The genome sequence reveals an ancient lineage-specific genome duplication, followed by extensive genome-wide reorganization. Using our new genomic tools we find quantitative trait loci for susceptibility to anthracnose, a damaging fungal pathogen of yam, and several tuber quality traits. Genomic analysis of breeding lines reveals both extensive inbreeding as well as regions of extensive heterozygosity that may represent interspecific introgression during domestication. These tools and insights will enable yam breeders to unlock the potential of this staple crop and take full advantage of its adaptability to varied environments.

genomics↗

Differential taphonomic effects of petroleum seeps and karstic sinkholes on ancient dire wolf teeth: Hydrocarbon impregnation preserves fossils for chemical and histological analysis

Histological analysis of teeth can yield information on an organisms growth and development, facilitating investigations of diet, health, environment, and long-term responses to selective pressures. In the Americas, an extraordinary abundance of Late Pleistocene fossils including teeth has been preserved in petroleum seeps, constituting a major source of information about biotic changes and adaptations at the end of the last glacial period. However, the usefulness of these fossils for histological studies is unclear, due to the unknown taphonomic effects of long-term deposition in petroleum. Here, we compare histological and chemical analyses on dire wolf (Canis dirus) teeth obtained from two different environments, i.e. a petroleum seep (Rancho La Brea tar pits, California) and a carstic sinkhole (Cutler Hammock sinkhole, Florida). Optical and scanning electron microscopy (SEM) together with X-ray diffraction (XRD) analysis revealed excellent preservation of dental microstructure in the seep sample, and the petroleum-induced discoloration was found not to interfere with the histological and chemical examination. By comparison, teeth from the sinkhole sample showed severe degradation and contamination of the dentine by exogenous substances. These results indicate that petroleum seep assemblages are useful, or even ideal, environments for preserving the integrity of fossil material for chemical and histological analysis.

paleontology↗

Genome-wide Spatial Expression Profiling in FFPE Tissues

Formalin-fixed paraffin embedding (FFPE) is the most widespread long-term tissue preservation approach. Here we present a procedure to perform genome-wide spatial analysis of mRNA in FFPE tissue sections. The procedure takes advantage of well-established, commercially available methods for imaging and spatial barcoding using slides spotted with barcoded oligo(dT) probes to capture the 3 end of mRNA molecules in tissue sections. First, we conducted expression profiling and cell type mapping in coronal sections from the mouse brain to demonstrate the methods capability to delineate anatomical regions from a molecular perspective. Second, we explored the spatial composition of transcriptomic signatures in ovarian carcinosarcoma samples using data driven analysis methods, exemplifying the methods potential to elucidate molecular mechanisms in heterogeneous clinical samples.

genetics↗

Spatiotemporal single-cell profiling of gastrointestinal GVHD reveals invasive and resident memory T cell states.

One of the central challenges in the field of allo-immunity is deciphering the mechanisms driving T cells to infiltrate and subsequently occupy target organs to cause disease. The act of CD8-dominated T cell infiltration is critical to acute graft-versus-host disease (aGVHD), wherein donor T cells become activated, tissue-infiltrating and highly cytotoxic, causing wide-spread tissue damage after allogeneic hematopoietic stem cell transplant (allo-HCT). However, in human and non-human primate studies, deconvolving the transcriptional programs of newly recruited relative to resident memory T cells in the gastrointestinal (GI) tract has remained a challenge. In this study, we combined the novel technique of Serial Intravascular Staining (SIVS) with single-cell RNA-Seq (scRNA-seq) to enable detailed dissection of the tightly connected processes by which T cells first infiltrate tissues and then establish a pathogenic tissue residency program after allo-HCT in non-human primates. Our results have enabled the creation of a spatiotemporal map of the transcriptional drivers of CD8 T cell infiltration into the primary aGVHD target-organ, the GI tract. We identify the large and small intestines as the only two sites demonstrating allo-specific, rather than lymphdepletion-driven T cell infiltration. The donor CD8 T cells that infiltrate the GI tract demonstrate a highly activated, cytotoxic phenotype while simultaneously rapidly developing canonical tissue-resident memory (TRM) protein expression and transcriptional signatures, driven by IL-15/IL-21 signaling. Moreover, by combining SIVS and transcriptomic analysis, we have been able to work backwards from this pathogenic TRM programing, and, for the first time, identify a cluster of genes directly associated with tissue invasiveness, prominently including specific chemokines and adhesion molecules and their receptors, as well as a central cytoskeletal transcriptional node. The clinical relevance of this new tissue invasion signature was validated by its ability to discriminate the CD8 T cell transcriptome of patients with GI aGVHD. These results provide new insights into the mechanisms controlling tissue infiltration and pathogenic CD8 TRM transcriptional programing, uncovering critical transitions in allo-immune tissue invasion and destruction. One sentence summaryFlow cytometric and transcriptomic analysis reveals coordinated tissue-infiltration and tissue-residency programs driving gastrointestinal aGVHD.

immunology↗

Quantifying and contextualizing the impact of bioRxiv preprints through social media audience segmentation

Engagement with scientific manuscripts is frequently facilitated by Twitter and other social media platforms. As such, the demographics of a papers social media audience provide a wealth of information about how scholarly research is transmitted, consumed, and interpreted by online communities. By paying attention to public perceptions of their publications, scientists can learn whether their research is stimulating positive scholarly and public thought. They can also become aware of potentially negative patterns of interest from groups that misinterpret their work in harmful ways, either willfully or unintentionally, and devise strategies for altering their messaging to mitigate these impacts. In this study, we collected 331,696 Twitter posts referencing 1,800 highly tweeted bioRxiv preprints and leveraged topic modeling to infer the characteristics of various communities engaging with each preprint on Twitter. We agnostically learned the characteristics of these audience sectors from keywords each users followers provide in their Twitter biographies. We estimate that 96% of the preprints analyzed are dominated by academic audiences on Twitter, suggesting that social media attention does not always correspond to greater public exposure. We further demonstrate how our audience segmentation method can quantify the level of interest from non-specialist audience sectors such as mental health advocates, dog lovers, video game developers, vegans, bitcoin investors, conspiracy theorists, journalists, religious groups, and political constituencies. Surprisingly, we also found that 10% of the highly tweeted preprints analyzed have sizable (>5%) audience sectors that are associated with right-wing white nationalist communities. Although none of these preprints intentionally espouse any right-wing extremist messages, cases exist where extremist appropriation comprises more than 50% of the tweets referencing a given preprint. These results present unique opportunities for improving and contextualizing research evaluation as well as shedding light on the unavoidable challenges of scientific discourse afforded by social media.

scientific communication and education↗