Biology subjects

Xu, S.

Publications and source records attributed to Xu, S..

At least 415 records · Page 23Linked to original sources

bioRxiv2019

Evolution of a novel and adaptive floral scent in wild tobacco

Many plants emit diverse floral scents that mediate plant-environment interactions and attain reproductive success. However, how plants evolve novel adaptive floral volatiles remains unclear. Here, we show that in the wild tobacco, Nicotiana attenuata, a dominant species-specific floral volatile (benzyl acetone, BA) that attracts pollinators and deters florivore is synthesized by phenylalanine ammonia-lyase 4 (NaPAL4), isoflavone reductase 3 (NaIFR3), and chalcone synthase 3 (NaCHAL3). Transient expression of NaFIR3 alone in N. attenuata leaves is sufficient and necessary for ectopic foliar BA emissions, and the BA emission level is increased by co-expressing NaIFR3 with NaPAL4 and NaCHAL3. Independent changes in transcription in all three genes contributed to intraspecific variations of floral BA emission. However, among species, the gain-of-expression in NaIFR3 resulted in the biosynthesis of BA that was only found in N. attenuata. This study suggests that novel metabolic pathways associated with adaptation can arise via re-configurations of gene expression.

evolutionary biology↗

bioRxiv2019

A mathematical model of mitochondrial calcium-phosphate dissolution as a mechanism for persistent post-CSD vasoconstriction

Cortical spreading depolarization (CSD) is the propagation of a relatively slow wave in cortical brain tissue that is linked to a number of pathological conditions such as stroke and migraine. Most of the existing literature investigates the dynamics of short term phenomena such as the depolarization and repolarization of membrane potentials or large ion shifts. Here, we focus on the clinically-relevant hour-long state of neurovascular malfunction in the wake of CSDs. This dysfunctional state involves widespread vasoconstriction and a general disruption of neurovascular coupling. We demonstrate, using a mathematical model, that dissolution of calcium that has aggregated within the mitochondria of vascular smooth muscle cells can drive an hour-long disruption. We determine the rate of calcium clearance as well as the dynamical implications on overall blood flow. Based on reaction stoichiometry, we quantify a possible impact of calcium phosphate dissolution on the maintenance of F0F1-ATP synthase activity.

systems biology↗

bioRxiv2019

HD-tDCS over mIPS causally modulates online reach correction

Brain lesion and stimulation studies have suggested posterior parietal cortex and the medial intraparietal sulcus in particular as a crucial hub for online movement error corrections. However, causal evidence for this is still sparse. Indeed, lesion studies are potentially confounded by compensatory reorganization mechanisms while brain stimulation studies have produced heterogeneous results when employing transcranial magnetic stimulation. Here we designed a new complementary paradigm using fMRI-guided high-definition transcranial direct current stimulation (HD-tDCS) of the left medial intraparietal sulcus (mIPS) together with regression-based mediation analysis to re-examine the causal role of mIPS in online reach corrections to jumping targets. We obtained two independent measures of stimulation-induced changes in brain activity by modeling current flow in the brain and through EEG recordings before and after HD-tDCS stimulation. Third, to quantify behavioral effects of HD-tDCS we computed movement curvature as a measure of online correction. We demonstrate that both of our measurements of brain activity were consistent with a polarity-specific modulation of the online correction for targets jumping to the contralateral side of the stimulation. Importantly, using a mediation analysis of the relationship between stimulation current and movement curvature suggests that the induced current modifies brain activity, which then leads to the observed behavioral changes. This unique combination of methods and analysis thus provides complementary evidence for the crucial role of the posterior parietal cortex in online error correction, while at the same time setting a new methodological standard with respect to the causal influence of transcranial direct current stimulation. New & NoteworthyTranscranial direct current stimulation (tDCS) is an interesting and potentially useful tool for asking causal scientific questions and design clinical treatments. With our unique combination of highly accurate fMRI guided stimulation, current forward modeling, EEG recordings before and after the stimulation and behavioral changes we could unravel the causal structure of tDCS. Our approach naturally deals with the variability of tDCS results, increasing its potential usefulness as a tool for research and clinical applications.

neuroscience↗

bioRxiv2019

An updated analysis of opioids increasing the risk of fractures

ObjectiveTo assess the relationship between opioid therapy for chronic noncancer pain and fracture risk by a meta-analysis of cohort studies and case-control studies.\n\nMethodsThe included cohort studies and case-control studies were identified by searching the PubMed and EMBASE databases from their inception until May 24, 2019. The outcome of interest was a fracture. This information was independently screened by two authors. When the heterogeneity among studies was significant, a random effects model was used to determine the overall combined risk estimate.\n\nResultsIn total, 12 cohort studies and 6 case-control studies were included. We used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature, and 14 of the studies were considered high-quality studies. The overall relative risk of opioid therapy and fractures was 1.78 (95% confidence interval (CI) 1.53 - 2.07). Subgroup analyses revealed sources of heterogeneity, sensitivity analysis was stable, and no publication bias was observed.\n\nConclusionsThe meta-analysis showed that the use of opioids significantly increased the risk of fracture.

pharmacology and toxicology↗

bioRxiv2019

Mapping Vector Field of Single Cells

Single-cell RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires dynamical models capable of predicting cell fate and unveiling the governing regulatory mechanisms. Here, we introduce dynamo, an analytical framework that reconciles intrinsic splicing and labeling kinetics to estimate absolute RNA velocities, reconstructs velocity vector fields that predict future cell fates, and finally employs differential geometry analyses to elucidate the underlying regulatory networks. We applied dynamo to a wide range of disparate biological processes including prediction of future states of differentiating hematopoietic stem cell lineages, deconvolution of glucocorticoid responses from orthogonal cell-cycle progression, characterization of regulatory networks driving zebrafish pigmentation, and identification of possible routes of resistance to SARS-CoV-2 infection. Our work thus represents an important step in going from qualitative, metaphorical conceptualizations of differentiation, as exemplified by Waddingtons epigenetic landscape, to quantitative and predictive theories.

systems biology↗

bioRxiv2019

Novel genetic loci affecting facial shape variation in humans

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited despite the relevance for various fields of science and application. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching genome-wide significant association, among which 17 were previously unreported. A multi-ethnic study in additional 7,917 individuals confirmed 13 loci including 8 unreported ones. A global map of polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

genomics↗

bioRxiv2019

Genome-wide Association study of facial morphology identifies novel genetic loci in Han Chinese

Human face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack for the Han Chinese population. We report a genome-wide association analysis of 3D normal human faces in 2659 Han Chinese with two groups of phenotypes, the partial and whole face phenotypes and the distance and angle phenotypes. We found significant signals in five genomic regions with traits related to nose or eyes, including rs970797 in 2q31.1 near HOXD1 and MTX2, rs16897517 in 8q22.2 at intron of VPS13B, rs9995821 in 4q31.3 near DCHS2 and SFRP2, rs12636297 in 3q23 near PISRT1, and rs12948076 in 17q24.3 near SOX9 and CASC17. We visualized changes in facial morphology by comparing the volume of local areas and observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, suggesting that the nose underlies precise genetic regulation. These results provide a more comprehensive understanding of the relationship between genetic loci and human facial morphology.\n\nAuthor SummaryHuman face as a combination of delicate sensory organs has a strong genetic component, as evidenced by the identical appearance in twins and shared facial features in close relatives. Although facial genetics have been studied in different populations, our knowledge between genetic markers with facial features is still limited. In this paper, we found genetic variants associated with nose and eyes through a large-scale high-resolution 3D facial genetic study on the Han Chinese population. We observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, which suggests the nose underlies precise genetic regulation. Intriguingly, we noted that genes (DCHS2 and SFRP2) related to one of these loci are differentially expressed in human and chimp cranial neural crest cells, which plays a crucial role in the early formation of facial morphology. The ongoing genetic studies of facial morphology will improve our understanding of human craniofacial development, and provide potential evolution evidence of human facial features.

genetics↗

bioRxiv2019

Mesenchymal stem cells restore local microenvironment and systemically suppress leukemia via reprogramming macrophages

Bone marrow (BM) mesenchymal stem cells (MSCs) are critical components of the BM microenvironment and play an essential role in supporting hematopoiesis. Dysfunction of MSCs is associated with the impaired BM microenvironment that promotes leukemia development. However, whether and how restoration of the impaired BM microenvironment can inhibit leukemia development remain unknown. Using an established leukemia model and the RNA-seq analysis, we discovered functional degeneration of MSCs during leukemia progression. Importantly, intra-BM instead of systemic transfusion of donor healthy MSCs restored the BM microenvironment, thus systemically altering cytokine expression patterns, improving normal hematopoiesis, reducing tumor burden, and ultimately prolonging survival of the leukemia-bearing mice. Donor MSC treatment restored the function of host MSCs and reprogrammed host macrophages to fulfill tissue-repair function. Transfusion of MSC-reprogrammed macrophages largely recapitulated the therapeutic effects of MSCs. Further, we found that donor MSCs reprogrammed macrophages to reduce leukemia burden through autocrine of IL-6. Taken together, our study reveals that donor MSCs reprogram host macrophages to restore the BM microenvironment and inhibit leukemia development, thus offering rationales for local MSC administration as a potentially effective therapy for leukemia.\n\nKey PointsKey Point 1: Intra-BM transfusion of MSCs restores the BM microenvironment, improves thrombopoiesis, and suppresses MDS/MPN initiated by Nras mutation.\n\nKey Point 2: Donor MSCs reprogram macrophages to restore the BM microenvironment, improve thrombopoiesis, and suppress leukemia.

cancer biology↗

bioRxiv2019

Adaptive laboratory evolution of Escherichia coli under acid stress

The ability of Escherichia coli to tolerate acid stress is important for its survival and colonization in the human digestive tract. Here, we performed adaptive laboratory evolution of the laboratory strain E. coli K-12 MG1655 at pH 5.5 in glucose minimal medium. By 800 generations, six independent populations under evolution reached 18.0% higher growth rates than their starting strain at pH 5.5, while maintaining comparable growth rates to the starting strain at pH 7. We characterized the evolved strains to find that: (1) whole genome sequencing of isolated clones from each evolved population revealed mutations in rpoC appearing in 5 of 6 sequenced clones; (2) gene expression profiles revealed different strategies to mitigate acid stress, that are related to amino acid metabolism and energy production and conversion. Thus, a combination of adaptive laboratory evolution, genome resequencing, and expression profiling reveals, on a genome-scale, the strategies that E. coli deploys to mitigate acid stress.

microbiology↗

bioRxiv2019

Proximity labeling of protein complexes and cell type-specific organellar proteomes in Arabidopsis enabled by TurboID

Defining specific protein interactions and spatially or temporally restricted local proteomes improves our understanding of all cellular processes, but obtaining such data is challenging, especially for rare proteins, cell types, or events. Proximity labeling enables discovery of protein neighborhoods defining functional complexes and/or organellar protein compositions. Recent technological improvements, namely two highly active biotin ligase variants (TurboID and miniTurboID), allowed us to address two challenging questions in plants: (1) what are in vivo partners of a low abundant key developmental transcription factor and (2) what is the nuclear proteome of a rare cell type? Proteins identified with FAMA-TurboID include known interactors of this stomatal transcription factor and novel proteins that could facilitate its activator and repressor functions. Directing TurboID to stomatal nuclei enabled purification of cell type- and subcellular compartment-specific proteins. Broad tests of TurboID and miniTurboID in Arabidopsis and N. benthamiana and versatile vectors enable customization by plant researchers.

plant biology↗

bioRxiv2019

Genomic islets in a sea of introgressions between sympatric species

In the conventional view, species are separate gene pools delineated by reproductive isolation (RI). However, species may also be delineated by merely a small set of "speciation genes" without full RI. It is thus important to know whether "good species" (defined by the "secondary sympatry" test) do continue to exchange genes. Here, we carry out sequencing and de novo high-quality assembly of the genomes of two closely related mangrove species (Rhizophora mucronata and R. stylosa). Whole-genome re-sequencing of individuals across their range on the tropical coasts shows their genomes to be well delineated in allopatry. They became sympatric in northeastern Australia but remain distinct species in contact. Nevertheless, their genomes harbor [~] 4,000 to 10,000 introgression blocks, each averaging only about 3-4 Kb. These fine-grained introgressions indicate that gene flow has continued long after speciation. Non-introgressable "genomic islets," averaging only 1.4 Kb, may contribute to speciation as they often harbor diverging genes underlying flower development and gamete production. In conclusion, RI needs not be the main criterion of species delineation even though all species would eventually be fully reproductively isolated.

evolutionary biology↗

bioRxiv2019

The Escherichia coli Transcriptome Consists of Independently Regulated Modules

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we applied unsupervised learning to a compendium of high-quality Escherichia coli RNA-seq datasets to identify 70 statistically independent signals that modulate the expression of specific gene sets. We show that 50 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals was validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provided: (1) a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations, (2) a guide to gene and regulator function discovery, and (3) a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation forms an underlying principle that describes the composition of a model prokaryotic transcriptome.

systems biology↗

bioRxiv2019

Contraction of the ROS scavenging enzyme glutathione S-transferase gene family in cetaceans

Cetaceans are a group of marine mammals whose ancestors were adaptated for life on land. Life in an aquatic environment poses many challenges for air-breathing mammals. Diving marine mammals have adapted to rapid reoxygenation and reactive oxygen species (ROS)-mediated reperfusion injury. Here, we considered the evolution of the glutathione transferase (GST) gene family which has important roles in the detoxification of endogenously-derived ROS and environmental pollutants. We characterized the cytosolic GST gene family in 21 mammalian species; cetaceans, sirenians, pinnipeds, and their terrestrial relatives. All seven GST classes were identified, showing that GSTs are ubiquitous in mammals. Some GST genes are the product of lineage-specific duplications and losses, in line with a birth-and-death evolutionary model. We detected sites with signatures of positive selection that possibly influence GST structure and function, suggesting that adaptive evolution of GST genes is important for defending mammals from various types of noxious environmental compounds. We also found evidence for loss of alpha and mu GST subclass genes in cetacean lineages. Notably, cetaceans have retained a homolog of at least one of the genes GSTA1, GSTA4, and GSTM1; GSTs that are present in both the cytosol and mitochondria. The observed variation in number and selection pressure on GST genes suggest that the gene family structure is dynamic within cetaceans. Taken together, our results indicate that the cytosolic GST family in cetaceans reflects unique evolutionary dynamics related to oxygen-poor aquatic environments.

evolutionary biology↗

bioRxiv2019

Prototheca zopfii Genotype II induces mitochondrial apoptosis in models of bovine mastitis

Prototheca zopfii is an alga increasingly isolated from bovine mastitis. Of the two genotypes of P. zopfii (genotype I and II (GT-I and II)), P. zopfii GT-II is the genotype associated with acute mastitis and decreased milk production by unknown mechanisms. The objective was to determine inflammatory and apoptotic roles of P. zopfii GT-II in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis. Prototheca zopfii GT-II (but not GT-I) invaded bovine and murine mammary epithelial cells (MECs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. This P. zopfii GT-II driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance ({Delta}{Psi}m) was altered and modulation of mitochondrion-mediated apoptosis regulating genes changed (increased transcriptional Bax, cytochrome-c and Apaf-1 and downregulated Bcl-2), whereas caspase-9 and -3 expression increased. Apoptotic effects by P. zopfii GT-II were more pronounced in macrophages compared to MECs. In a murine mammary infection model, P. zopfii GT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-, IL-1{beta} and Cxcl-1) and also apoptosis of epithelial cells. Thus, we concluded P. zopfii GT-II is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis. Author summaryBovine mastitis (inflammation of the udder) reduces milk production and quality, causing huge economic losses in the dairy industry worldwide. Although the alga Prototheca zopfii is a major cause of mastitis in dairy cows, mechanisms by which it damages mammary tissues are not well known. Here, we used cell cultures and a mouse model of mastitis to determine how Prototheca caused inflammation and cell death in mammary tissues. Prototheca invaded mammary gland cells, from cattle and mice, as well as macrophages (white cells that take up and kill pathogens) and caused cell death by interfering with mitochondria. Furthermore, Prototheca causes severe inflammation and tissue damage when injected into the mammary glands of mice. Although there are two genotypes of P. zopfii, only genotype II causes tissue damage, whereas gentotype I, common in farm environments, does not damage mammary tissues. Since P. zopfii is an alga and not a bacterium, antibiotic treatments, frequently used to treat mastitis in cattle, are not effective against this organism. Understanding how P. zopfii damages mammary tissue and causes mastitis is important new knowledge to promote future development of evidence-based approaches to prevent and treat mammary gland infections with this organism.

microbiology↗

bioRxiv2019

Identification and characterization of a novel pic gene cluster responsible for picolinic acid degradation in Alcaligenes faecalis JQ135

Picolinic acid (PA) is a natural toxic pyridine derivative. Microorganisms can degrade and utilize PA for growth. However, the full metabolic pathway and its physiological and genetic foundation remain unknown. In this study, we identified the pic gene cluster responsible for the complete degradation of PA from Alcaligenes faecalis JQ135. PA was initially 6-hydroxylated into 6-hydroxypicolinic acid (6HPA) by PA dehydrogenase (PicA). 6HPA was then 3-hydroxylated by a four-component 6HPA monooxygenase (PicB) to form 3,6-dihydroxypicolinic acid (3,6DHPA), which was then converted into 2,5-dihydroxypyridine (2,5DHP) by a decarboxylase (PicC). The 2,5DHP was further degraded into fumaric acid, through PicD (2,5DHP dioxygenase), PicE (N-formylmaleamic acid deformylase), PicF (maleamic acid amidohydrolase), and PicG (maleic acid isomerase). Homologous pic gene clusters with diverse organizations were found to be widely distributed in -, {beta}-, and{gamma} -Proteobacteria. Our findings provide new insights into the microbial metabolism of environmental toxic pyridine derivatives. ImportancePicolinic acid is a common metabolite of L-tryptophan and some aromatic compounds and is an important intermediate of industrial concern. Although the microbial degradation/detoxification of picolinic acid has been studied for over 50 years, the underlying molecular mechanisms are still unknown. Here, we show the pic gene cluster responsible for the complete degradation of picolinic acid into the tricarboxylic acid cycle. This gene cluster was found to be widespread in other -, {beta}-, and{gamma} -Proteobacteria. These findings provide new perspective for understanding the mechanisms of picolinic acid biodegradation in bacteria.

microbiology↗

bioRxiv2019

Gene Panel Sequencing in a Chinese High-risk Breast Cancer Cohort

Currently, over 20 genes have been defined that can confer susceptibility for high-risk breast cancer. Although research has proved the utility of multiple-gene sequencing in the assessment of breast cancer risk, there is little data from China patients. Here, we use a multiple-gene sequencing panel to identify the variant spectrum in Chinese high-risk breast cancer subjects.\n\nA total of 829 Chinese high-risk breast cancer patients participated in the research. The coding regions of 115 hereditary cancer susceptibility genes were sequenced using a next generation sequencing platform. In total, 193 pathogenic variants were identified in 45 genes from 177 patients. The pathogenic variant carrier rate is 21.4%: with 10.5% patients carrying a BRCA1 or BRCA2 mutation only, 10.0% of patients carried non-BRCA gene mutations only, while 1.0% of patients carried both a BRCA1/2 and a non-BRCA gene mutation. Variants of uncertain significance (VUS) totaling 2632 were identified in 115 genes from 787 of 829 patients: 82.5% patients carried more than one VUS, and only 5.1% patients did not carry any VUS. Families carrying pathogenic variants were tracked and adenoma was founded in three of them. Our data provide a comprehensive analysis of potential susceptibility variations of high-risk for breast cancer in a Chinese population. This data will be useful for the comparison of the susceptibility variation spectrum between different populations and to discover potential pathogenic variants to improve the prevention and treatment of high-risk breast cancer.

cancer biology↗

bioRxiv2019

Molecular basis of P major human rotavirus VP8* domain interactions with histo-blood group antigens

Initial cell attachment of rotavirus (RV) to specific cell surface glycans, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as ligands or receptors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b and H type 1 antigens, while P[6], which is one of the other genotypes in P[II], only recognizes the H type 1 antigen. The molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leb and type 1 HBGAs and for P[6] recognition of H type 1 HBGAs. Unlike P[6] VP8* that recognizes H type 1 HGBAs in a binding surface composed of an -helix and a {beta}-sheet, referred as \"{beta} binding domain\", the P[8] VP8* binds the type 1 HBGAs requiring the presence of the Lewis epitope in a previously undescribed pocket formed by two {beta}-sheets, referred as \"{beta}{beta} binding domain\". The observation that P[6] and P[8] VP8* domains recognize different glycan structures at distinct binding sites supports the hypothesis that RV evolution is driven, at least in part, by selective pressure driven adaptation to HBGA structural diversity of their natural hosts living in the world. Recognition of the role that HBGAs play in driving RV evolution is essential to understanding RV diversity, host ranges, disease burden and zoonosis and to developing strategies to improve vaccines against RV infections.\n\nAuthor summaryRotaviruses (RV)s are the main cause of severe diarrhea in humans and animals. Significant advances in understanding RV diversity, evolution and epidemiology have been made after discovering that RVs recognize histo-blood group antigens (HBGAs) as host cell receptors. While different RV strains are known to have distinct binding preferences for HBGA receptors, the molecular basis in controlling strain-specific host ranges remains unclear. In this study, we used solution nuclear magnetic resonance to determine the molecular level details for interactions of the human P[8] and P[6] RV VP8* domains with their HBGA receptors. The distinct binding patterns observed between these major human RVs and their respective receptor ligands provides insight into the evolutionary relationships between different P[II] genotypes that ultimately determine host ranges, disease burden, zoonosis and epidemiology, which may impact future strategies for vaccine development against RVs.

biochemistry↗

bioRxiv2018

Non-academic employability of life science PhDs: the importance of training beyond the bench

To better understand how PhD graduates have prepared for the non-academic job market, we surveyed life science PhD and postdoctoral graduates from the University of Toronto who were employed in non-academic sectors. We also surveyed life science PhD and postdoctoral trainees to assess their engagement in career preparation activities. PhD professionals employed in non-academic sectors had engaged in various career preparation activities during their training. Some activities had a higher perceived impact on the path to employment than others. Trainees had also engaged in such activities, but those rated by professionals as having a highly positive impact on their path to employment were engaged in by only a minority of trainees. The proportion of trainees who wished to work in a non-academic sector was higher among those who were closer to program completion. Like professionals, many trainees reported facing barriers to pursuing career development activities. Our findings suggest that PhD trainees seeking to work in non-academic sectors should engage in career preparation activities, particularly those that involve experiential learning. By supporting co-curricular programming and reducing barriers to participation in career development activities, academic administrators and faculty have the opportunity to support trainees professional development beyond the laboratory.

scientific communication and education↗