Expanded Systematic Evidence Map for Hundreds of Per- and Polyfluoroalkyl Substances (PFAS) and Comprehensive PFAS Human Health Dashboard.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) encompass a class of chemically and structurally diverse compounds that are extensively used in industry and detected in the environment. The US Environmental Protection Agency (US EPA) 2021 PFAS Strategic Roadmap describes national research plans to address the challenge of PFAS. OBJECTIVES: Systematic Evidence Map (SEM) methods were used to survey and summarize available epidemiological and mammalian bioassay evidence that could inform human health hazard identification for a set of 345 PFAS that were identified by the US EPA's Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing and through interagency discussions on PFAS of interest. This work builds from the 2022 evidence map that collated evidence on a separate set of ∼150 PFAS. Like our previous work, this SEM does not include PFAS that are the subject of ongoing or completed assessments at the US EPA. METHODS: SEM methods were used to search, screen, and inventory mammalian bioassay and epidemiological literature from peer-reviewed and gray literature sources using manual review and machine-learning software. For each included study, study design details and health end points examined were summarized in interactive web-based literature inventories. Some included studies also underwent study evaluation and detailed extraction of health end point data. All underlying data is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 13,000 studies were identified from scientific databases. Screening processes identified 121 mammalian bioassay and 111 epidemiological studies that met screening criteria. Epidemiological evidence (available for 12 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Mammalian bioassay evidence (available for 30 PFAS) commonly assessed effects in the reproductive, whole-body, nervous, and hepatic systems. Overall, 41 PFAS had evidence across mammalian bioassay and epidemiology data streams (roughly 11% of searched chemicals). DISCUSSION: No epidemiological and/or mammalian bioassay evidence were identified for most of the PFAS included in our search. Results from this SEM, our 2022 SEM on ∼150 PFAS, and other PFAS assessment products from the US EPA are compiled into a comprehensive PFAS dashboard that provides researchers and regulators an overview of the current PFAS human health landscape including data gaps and can serve as a scoping tool to facilitate prioritization of PFAS-related research and/or risk assessment activities. https://doi.org/10.1289/EHP13423.

Pre-Glenn aorto-pulmonary collaterals in single-ventricle patients.

BACKGROUND: In single-ventricle patients undergoing staged-bidirectional Glenn, 36-59% have aorto-pulmonary collateral flow, but risk factors and clinical outcomes are unknown. We hypothesise that shunt type and catheter haemodynamics may predict pre-bidirectional Glenn aorto-pulmonary collateral burden, which may predict death/transplantation, pulmonary artery or aorto-pulmonary collateral intervention. METHODS: Retrospective cohort study of patients undergoing a Norwood procedure for single-ventricle anatomy. Covariates included clinical and haemodynamic characteristics up to/including pre-bidirectional Glenn catheterisation and aorto-pulmonary collateral burden at pre-bidirectional Glenn catheterisation. Multivariable models used to evaluate relationships between risk factors and outcomes. RESULTS: From January 2011 to March 2016, 104 patients underwent Norwood intervention. Male sex (odds ratio 3.36, 95% confidence interval 1.17-11.4), age at pre-bidirectional Glenn assessment (2.12, 1.33-3.39 per month), and pulmonary to systemic flow ratio (1.23, 1.08-1.41 per 0.1 unit) were associated with aorto-pulmonary collateral burden. Aorto-pulmonary collateral burden was not associated with death/transplantation (hazard ratio 1.19, 95% confidence interval 0.37-3.85), pulmonary artery (sub-hazard ratio 1.38, 0.32-2.61), or aorto-pulmonary collateral interventions (sub-hazard ratio 1.11, 0.21-5.76). Longer post-Norwood length of stay was associated with greater risk of death/transplantation (hazard ratio 1.22 per week, 95% confidence interval 1.08-1.38), but lower risk of aorto-pulmonary collateral intervention (sub-hazard ratio 0.86 per week, 95% confidence interval 0.75-0.98). Time to pre-bidirectional Glenn catheterisation was associated with lower risk of pulmonary artery (sub-hazard ratio 0.80 per month, 95% confidence interval 0.65-0.98) and aorto-pulmonary collateral intervention (sub-hazard ratio 0.79, 0.63-0.99). Probability of moderate/severe aorto-pulmonary collateral burden increased with left-to-right shunt (22.5% at <1.0, 57.6% at >1.4) and the age at pre-bidirectional Glenn catheterisation (10.6% at <2 months, 56.9% at >5 months). CONCLUSIONS: Aorto-pulmonary collateral burden is common after Norwood procedure and increases as age at bidirectional Glenn increases. As expected, higher pulmonary to systemic flow ratio is a marker for greater aorto-pulmonary collateral burden pre-bi-directional Glenn; aorto-pulmonary collateral burden does not confer risk of death/transplantation or pulmonary artery intervention.

A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

Systematic evidence map (SEM) template: Report format and methods used for the US EPA Integrated Risk Information System (IRIS) program, Provisional Peer Reviewed Toxicity Value (PPRTV) program, and other "fit for purpose" literature-based human health analyses.

BACKGROUND: Systematic evidence maps (SEMs) are gaining visibility in environmental health for their utility to serve as problem formulation tools and assist in decision-making, especially for priority setting. SEMs are now routinely prepared as part of the assessment development process for the US Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) and Provisional Peer Reviewed Toxicity Value (PPRTV) assessments. SEMs can also be prepared to explore the available literature for an individual chemical or groups of chemicals of emerging interest. OBJECTIVES: This document describes the typical methods used to produce SEMs for the IRIS and PPRTV Programs, as well as "fit for purpose" applications using a variety of examples drawn from existing analyses. It is intended to serve as an example base template that can be adapted as needed for the specific SEM. The presented methods include workflows intended to facilitate rapid production. The Populations, Exposures, Comparators and Outcomes (PECO) criteria are typically kept broad to identify mammalian animal bioassay and epidemiological studies that could be informative for human hazard identification. In addition, a variety of supplemental content is tracked, e.g., studies presenting information on in vitro model systems, non-mammalian model systems, exposure-level-only studies in humans, pharmacokinetic models, and absorption, distribution, metabolism, and excretion (ADME). The availability of New Approach Methods (NAMs) evidence is also tracked (e.g., high throughput, transcriptomic, in silico, etc.). Genotoxicity studies may be considered as PECO relevant or supplemental material, depending on the topic and context of the review. Standard systematic review practices (e.g., two independent reviewers per record) and specialized software applications are used to search and screen the literature and may include the use of machine learning software. Mammalian bioassay and epidemiological studies that meet the PECO criteria after full-text review are briefly summarized using structured web-based extraction forms with respect to study design and health system(s) assessed. Extracted data is available in interactive visual formats and can be downloaded in open access formats. Methods for conducting study evaluation are also presented which is conducted on a case-by-case basis, depending on the usage of the SEM.

Use of systematic evidence maps within the US environmental protection agency (EPA) integrated risk information system (IRIS) program: Advancements to date and looking ahead.

Systematic evidence maps (SEMs) are increasingly used to inform decision-making and risk management priority-setting and to serve as problem formulation tools to refine the focus of questions that get addressed in full systematic reviews. Within the U.S. Environmental Protection Agency (EPA) Office of Research and Development (ORD) Integrated Risk Information System (IRIS), SEMs have been used to inform data gaps, determine the need for updated assessments, inform assessment priorities, and inform development of study evaluation considerations, among other uses. Increased utilization of SEMs across the environmental health field has the potential to increase transparency and efficiency for data gathering, problem formulation, read-across, and evidence surveillance. Use of the SEM templates published in the companion text (Thayer et al.) can promote harmonization in the environmental health community and create more opportunities for sharing extracted content.

Lead exposure and antisocial behavior: A systematic review protocol.

BACKGROUND: Lead exposure remains highly prevalent worldwide despite decades of research highlighting its link to numerous adverse health outcomes. In addition to well-documented effects on cognition, there is growing evidence of an association with antisocial behavior, including aggression, conduct problems, and crime. An updated systematic review on this topic, incorporating study evaluation and a developmental perspective on the outcome, can advance the state of the science on lead and inform global policy interventions to reduce exposure. OBJECTIVES: We aim to evaluate the link between lead exposure and antisocial behavior. This association will be investigated via a systematic review of human epidemiological and experimental nonhuman mammalian studies. METHODS: The systematic review protocol presented in this publication is informed by recommendations for the conduct of systematic reviews in toxicology and environmental health research (COSTER) and follows the study evaluation approach put forth by the U.S. EPA Integrated Risk Information System (IRIS) program. DATA SOURCES: We will search the following electronic databases for relevant literature: PubMed, BIOSIS and Web of Science. Search results will be stored in EPA's Health and Environmental Research Online (HERO) database. STUDY ELIGIBILITY AND CRITERIA: Eligible human epidemiological studies will include those evaluating any population exposed to lead at any lifestage via ingestion or inhalation exposure and considering an outcome of antisocial behavior based on any of the following criteria: psychiatric diagnoses (e.g., oppositional defiant disorder (ODD), conduct disorder (CD), disruptive behavior disorders (DBD)); violation of social norms (e.g., delinquency, criminality); and aggression. Eligible experimental animal studies will include those evaluating nonhuman mammalian studies exposed to lead via ingestion, inhalation, or injection exposure during any lifestage. The following outcomes will be considered relevant: aggression; antisocial behavior; and altered fear, anxiety, and stress response. STUDY APPRAISAL AND SYNTHESIS METHODS: Screening will be conducted with assistance from an artificial intelligence application. Two independent reviewers for each data stream (human, animal) will screen studies with highest predicted relevance against pre-specified inclusion criteria at the title/abstract and full-text level. Study evaluation will be conducted using methods adapted from the U.S. EPA IRIS program. After data extraction, we will conduct a narrative review and quantitative meta-analysis on the human epidemiological studies as well as a narrative review of the experimental animal studies. We will evaluate the strength of each evidence stream separately and then will develop a summary evidence integration statement based on inference across evidence streams.

A Generic Pharmacokinetic Model for Quantifying Mother-to-Offspring Transfer of Lipophilic Persistent Environmental Chemicals.

Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman's body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs.

Describing communication during a forensic investigation using the Pebbles on a Scale metaphor.

During the investigation of a crime, evidence is collected, analyzed, interpreted, and discussed by various stakeholders. This article examines the communication that may occur between two of these stakeholders: detectives and forensic analysts, and how their interaction influences the interpretation of evidence as the investigation proceeds and the theory of the case evolves. Such communication can be understood as sets of actions that are inter-dependent: for example, a request for a specific analysis by a detective leads to analyses and conclusions that the analyst shares with the detective, which leads to an assessment of these conclusions relative to the theory of the case, which leads to further analysis requests, and so forth. We present the Pebbles on a Scale metaphor, which describes how communication and the understanding of evidence takes place between the detective and analysts, and the different ways in which they consider the information as a function of their roles in the investigation. Using a hypothetical case for illustration, we discuss communicative challenges, the evolving theory of the case, the language that is used by analysts to discuss "yes", "no" and "I don't know" conclusions, and how those conclusions are used by detectives during the progression of the investigation.

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS).

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS. OBJECTIVE: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA's Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing. METHODS: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement-only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams. DISCUSSION: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343.

Glycine betaine uptake and metabolism in marine microbial communities.

Glycine betaine (GBT) is a compatible solute in high concentrations in marine microorganisms. As a component of labile organic matter, GBT has complex biochemical potential as a substrate for microbial use that is unconstrained in the environment. Here we determine the uptake kinetics and metabolic fate of GBT in two natural microbial communities in the North Pacific characterized by different nitrate concentrations. Dissolved GBT had maximum uptake rates of 0.36 and 0.56 nM h-1 with half-saturation constants of 79 and 11 nM in the high nitrate and low nitrate stations respectively. During multiday incubations, most GBT taken into cells was retained as a compatible solute. Stable isotopes derived from the added GBT were also observed in other metabolites, including choline, carnitine and sarcosine, suggesting that GBT was used for biosynthesis and for catabolism to pyruvate and ammonium. Where nitrate was scarce, GBT was primarily metabolized via demethylation to glycine. Gene transcript data were consistent with SAR11 using GBT as a source of methyl groups to fuel the methionine cycle. Where nitrate concentrations were higher, more GBT was partitioned for lipid biosynthesis by both bacteria and eukaryotic phytoplankton. Our data highlight unexpected metabolic pathways and potential routes of microbial metabolite exchange.

Enhancing Recovery in Congenital Cardiac Surgery.

BACKGROUND: The benefits of a comprehensive enhanced recovery after surgery (ERAS) program for patients with congenital heart disease are largely unknown. This study evaluated adherence and to outcomes of a recently implemented enhanced recovery program (ERP) in congenital cardiac surgery. METHODS: Patients undergoing elective procedures for simple and moderately complex congenital cardiac surgery have followed institutional ERP guidelines since October 2018. Adherence to guidelines over a 12-month period (P2) was compared with implementation data (P1, 5 months). The association of outcomes with continuous time was estimated using linear regression. RESULTS: Among 559 patients (representing 40% of the cardiac surgical volume) following the ERP over a period of 17 months, no differences in patient characteristics were observed between periods, except a higher incidence of previous operations in P2. Adherence to many aspects of guidelines improved from P1 to P2. The following improvements were notable: operating room extubation, 27% in P2 vs16% in P1 (P = .006); and a decrease in median ventilation time, 6.0 hours (interquartile range [IQR], 0-9.2 hours) in P2 vs 7.6 hours (IQR, 3.8-12.3 hours) in P1 (P = .002). In addition, there was a reduction in opioids, reported as oral morphine equivalents, that was most significant for intraoperative oral morphine equivalents: 5.00 mg/kg (IQR, 3.11-7.60 mg/kg) in P2 vs 6.05 mg/kg (IQR, 3.77-9.78 mg/kg) in P1 (P = .001). There was no difference in overall intensive care unit and postoperative lengths of stay, except in lower-risk surgical procedures. Surgical outcomes were similar in the 2 periods. CONCLUSIONS: An enhanced recovery program reduced the use of opioids, led to more extubation in the operating room, and reduced mechanical ventilation duration in patients undergoing congenital cardiac surgery.

Digital solution for follow-up in congenital cardiac surgery.

BACKGROUND: In this era of public scrutiny, there is an ongoing need for innovative methods for patient follow-up. OBJECTIVES: As part of a quality initiative, we developed an automated post-operative follow-up system for patients following discharge after cardiac surgery at Boston Children's Hospital. METHODS: Discharge Communication (DisCo) is a web-based system developed at Boston Children's Hospital. An automated text and e-mail with a link to a health status survey are sent at 30 days and 1 year post-discharge in English/Spanish. If there is no response, surveys are completed via phone calls to the patient/patient's physician or chart review. Responses are stored in the DisCo database and the patient's medical record. Patients who underwent cardiac surgery and survived to hospital discharge from October, 2016 received the surveys. RESULTS: Overall, 3345 30-day and 2563 1-year surveys were sent between October, 2016 and June, 2020. Of 3345 30-day surveys, there were 3191 responses (95%). Of 2563 1-year surveys, there were 1807 responses (71%). Most patients/families responded directly to the link at 30 days (65% for paediatrics/75% for adults) and at 1 year (72% for paediatrics/78% for adults). Multi-variable logistic regression revealed that higher complexity of cardiac lesion, presence of major non-cardiac anomalies and presence of major residua were associated with readmission and catheter/surgical reinterventions. Non-cardiac anomalies were associated with increased need for services for learning, development or behaviour. CONCLUSIONS: DisCo provides a successful web-based health status assessment of patients following congenital cardiac surgery. It helps to identify high-risk patients who need closer follow-up.

Prochlorococcus extracellular vesicles: molecular composition and adsorption to diverse microbes.

Extracellular vesicles are small (~50-200 nm diameter) membrane-bound structures released by cells from all domains of life. While vesicles are abundant in the oceans, their functions, both for cells themselves and the emergent ecosystem, remain a mystery. To better characterize these particles - a prerequisite for determining function - we analysed the lipid, protein, and metabolite content of vesicles produced by the marine cyanobacterium Prochlorococcus. We show that Prochlorococcus exports a diverse array of cellular compounds into the surrounding seawater enclosed within discrete vesicles. Vesicles produced by two different strains contain some materials in common, but also display numerous strain-specific differences, reflecting functional complexity within vesicle populations. The vesicles contain active enzymes, indicating that they can mediate extracellular biogeochemical reactions in the ocean. We further demonstrate that vesicles from Prochlorococcus and other bacteria associate with diverse microbes including the most abundant marine bacterium, Pelagibacter. Together, our data point toward hypotheses concerning the functional roles of vesicles in marine ecosystems including, but not limited to, possibly mediating energy and nutrient transfers, catalysing extracellular biochemical reactions, and mitigating toxicity of reactive oxygen species.

Left Pulmonary Artery Sling: Postoperative Outcomes for Patients at a Single Center.

BACKGROUND: Left pulmonary artery (LPA) sling is a rare anomaly characterized by the origin of the LPA from the right pulmonary artery with a course between the trachea and esophagus. It is often associated with airway and cardiac anomalies. METHODS: This is a retrospective case series of consecutive patients who underwent LPA sling repair (LPASR) at a tertiary care center over a 35-year period with a focus on tracheal and/or LPA reinterventions and survival. RESULTS: Between June 1983 and July 2018, 42 patients were identified: isolated LPASR was performed in 16 (38%), LPASR/intracardiac repair in 10 (24%), and LPASR/tracheal repair in 16 (38%). There were 5 (12%) in-hospital and 4 (10%) late deaths. Survival rates (15 years) were as follows: 100% (isolated LPASR), 65% (concomitant intracardiac repair), and 52% (concomitant tracheal surgery). Preoperative intensive care unit (ICU) hospitalization was associated with future intervention on the LPA/trachea (61%, 11/18). The median distribution of blood flow to the left lung post-index surgery was 38%. Freedom from isolated LPA intervention was 100% after isolated LPASR, 93% after LPASR/tracheal surgery, and 69% after LPASR/intracardiac repair. Freedom from isolated tracheal intervention was 92% after isolated LPASR, 73% after LPASR/tracheal surgery, and 78% after LPASR/intracardiac repair. CONCLUSIONS: ICU hospitalization prior to index surgery may indicate the severity of associated cardiac/tracheal abnormalities as this is associated with increased morbidity and mortality. Patients who underwent LPASR/intracardiac surgery were more likely to undergo isolated LPA intervention and those who underwent LPASR/tracheal surgery were more likely to undergo isolated tracheal intervention.

Planktonic Archaeal Ether Lipid Origins in Surface Waters of the North Pacific Subtropical Gyre.

Thaumarchaeota and Thermoplasmatota are the most abundant planktonic archaea in the sea. Thaumarchaeota contain tetraether lipids as their major membrane lipids, but the lipid composition of uncultured planktonic Thermoplasmatota representatives remains unknown. To address this knowledge gap, we quantified archaeal cells and ether lipids in open ocean depth profiles (0-200 m) of the North Pacific Subtropical Gyre. Planktonic archaeal community structure and ether lipid composition in the water column partitioned into two separate clusters: one above the deep chlorophyll maximum, the other within and below it. In surface waters, Thermoplasmatota densities ranged from 2.11 × 106 to 6.02 × 106 cells/L, while Thaumarchaeota were undetectable. As previously reported for Thaumarchaeota, potential homologs of archaeal tetraether ring synthases were present in planktonic Thermoplasmatota metagenomes. Despite the absence of Thaumarchaeota in surface waters, measurable amounts of intact polar ether lipids were found there. Based on cell abundance estimates, these surface water archaeal ether lipids contributed only 1.21 × 10-9 ng lipid/Thermoplasmatota cell, about three orders of magnitude less than that reported for Thaumarchaeota cells. While these data indicate that even if some tetraether and diether lipids may be derived from Thermoplasmatota, they would only comprise a small fraction of Thermoplasmatota total biomass. Therefore, while both MGI Thaumarchaeota and MGII/III Thermoplasmatota are potential biological sources of archaeal GDGTs, the Thaumarchaeota appear to be the major contributors of archaeal tetraether lipids in planktonic marine habitats. These results extend and confirm previous reports of planktonic archaeal lipid sources, and further emphasize the need for Thermoplasmatota cultivation, to better characterize the membrane lipid constituents of marine planktonic Thermoplasmatota, and more precisely define the sources and patterns of archaeal tetraether lipid distributions in marine plankton.

Marine Community Metabolomes Carry Fingerprints of Phytoplankton Community Composition.

Phytoplankton transform inorganic carbon into thousands of biomolecules that represent an important pool of fixed carbon, nitrogen, and sulfur in the surface ocean. Metabolite production differs between phytoplankton, and the flux of these molecules through the microbial food web depends on compound-specific bioavailability to members of a wider microbial community. Yet relatively little is known about the diversity or concentration of metabolites within marine plankton. Here, we compare 313 polar metabolites in 21 cultured phytoplankton species and in natural planktonic communities across environmental gradients to show that bulk community metabolomes reflect the chemical composition of the phytoplankton community. We also show that groups of compounds have similar patterns across space and taxonomy, suggesting that the concentrations of these compounds in the environment are controlled by similar sources and sinks. We quantify several compounds in the surface ocean that represent substantial understudied pools of labile carbon. For example, the N-containing metabolite homarine was up to 3% of particulate carbon and is produced in high concentrations by cultured Synechococcus, and S-containing gonyol accumulated up to 2.5 nM in surface particles and likely originates from dinoflagellates or haptophytes. Our results show that phytoplankton composition directly shapes the carbon composition of the surface ocean. Our findings suggest that in order to access these pools of bioavailable carbon, the wider microbial community must be adapted to phytoplankton community composition.IMPORTANCE Microscopic phytoplankton transform 100 million tons of inorganic carbon into thousands of different organic compounds each day. The structure of each chemical is critical to its biological and ecosystem function, yet the diversity of biomolecules produced by marine microbial communities remained mainly unexplored, especially small polar molecules which are often considered the currency of the microbial loop. Here, we explore the abundance and diversity of small biomolecules in planktonic communities across ecological gradients in the North Pacific and within 21 cultured phytoplankton species. Our work demonstrates that phytoplankton diversity is an important determinant of the chemical composition of the highly bioavailable pool of organic carbon in the ocean, and we highlight understudied yet abundant compounds in both the environment and cultured organisms. These findings add to understanding of how the chemical makeup of phytoplankton shapes marine microbial communities where the ability to sense and use biomolecules depends on the chemical structure.