Siderophore-Based Microbial Adaptations to Iron Scarcity Across the Eastern Pacific Ocean

Nearly all iron dissolved in the ocean is complexed by strong organic ligands of unknown composition. The effect of ligand composition on microbial iron acquisition is poorly understood, but amendment experiments using model ligands show they can facilitate or impede iron uptake depending on their identity. Here we show that siderophores, organic compounds synthesized by microbes to facilitate iron uptake, are a dynamic component of the marine ligand pool in the eastern tropical Pacific Ocean. Siderophore concentrations in iron-deficient waters averaged 9 pM, up to fivefold higher than in iron-rich coastal and nutrient-depleted oligotrophic waters, and were dominated by amphibactins, amphiphilic siderophores with cell membrane affinity. Phylogenetic analysis of amphibactin biosynthetic genes suggests that the ability to produce amphibactins has transferred horizontally across multiple Gammaproteobacteria, potentially driven by pressures to compete for iron. In coastal and oligotrophic regions of the eastern Pacific Ocean, amphibactins were replaced with lower concentrations (1-2 pM) of hydrophilic ferrioxamine siderophores. Our results suggest that organic ligand composition changes across the surface ocean in response to environmental pressures. Hydrophilic siderophores are predominantly found across regions of the ocean where iron is not expected to be the limiting nutrient for the microbial community at large. However, in regions with intense competition for iron, some microbes optimize iron acquisition by producing siderophores that minimize diffusive losses to the environment. These siderophores affect iron bioavailability and thus may be an important component of the marine iron cycle

Hydrothermal trace metal release and microbial metabolism in the northeastern Lau Basin of the South Pacific Ocean

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cohen, N. R., Noble, A. E., Moran, D. M., McIlvin, M. R., Goepfert, T. J., Hawco, N. J., German, C. R., Horner, T. J., Lamborg, C. H., McCrow, J. P., Allen, A. E., & Saito, M. A. Hydrothermal trace metal release and microbial metabolism in the northeastern Lau Basin of the South Pacific Ocean. Biogeosciences, 18(19), (2021): 5397–5422, https://doi.org/10.5194/bg-18-5397-2021.Bioactive trace metals are critical micronutrients for marine microorganisms due to their role in mediating biological redox reactions, and complex biogeochemical processes control their distributions. Hydrothermal vents may represent an important source of metals to microorganisms, especially those inhabiting low-iron waters, such as in the southwest Pacific Ocean. Previous measurements of primordial 3He indicate a significant hydrothermal source originating in the northeastern (NE) Lau Basin, with the plume advecting into the southwest Pacific Ocean at 1500–2000 m depth (Lupton et al., 2004). Studies investigating the long-range transport of trace metals associated with such dispersing plumes are rare, and the biogeochemical impacts on local microbial physiology have not yet been described. Here we quantified dissolved metals and assessed microbial metaproteomes across a transect spanning the tropical and equatorial Pacific with a focus on the hydrothermally active NE Lau Basin and report elevated iron and manganese concentrations across 441 km of the southwest Pacific. The most intense signal was detected near the Mangatolo Triple Junction (MTJ) and Northeast Lau Spreading Center (NELSC), in close proximity to the previously reported 3He signature. Protein content in distal-plume-influenced seawater, which was high in metals, was overall similar to background locations, though key prokaryotic proteins involved in metal and organic uptake, protein degradation, and chemoautotrophy were abundant compared to deep waters outside of the distal plume. Our results demonstrate that trace metals derived from the NE Lau Basin are transported over appreciable distances into the southwest Pacific Ocean and that bioactive chemical resources released from submarine vent systems are utilized by surrounding deep-sea microbes, influencing both their physiology and their contributions to ocean biogeochemical cycling.This research has been supported by the National Science Foundation (grant nos. 1031271, 1924554, 1850719, 1736599, and 1851007); the Gordon and Betty Moore Foundation (grant no. 3782); and the Simons Foundation (grant no. 544236)

Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders

Background: Externalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs. Methods: Multi-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6–18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive–compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined. Results: No significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results. Conclusions: The current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations

Variability in the analysis of a single neuroimaging dataset by many teams

Data analysis workflows in many scientific domains have become increasingly complex and flexible. To assess the impact of this flexibility on functional magnetic resonance imaging (fMRI) results, the same dataset was independently analyzed by 70 teams, testing nine ex-ante hypotheses. The flexibility of analytic approaches is exemplified by the fact that no two teams chose identical workflows to analyze the data. This flexibility resulted in sizeable variation in hypothesis test results, even for teams whose statistical maps were highly correlated at intermediate stages of their analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Importantly, meta-analytic approaches that aggregated information across teams yielded significant consensus in activated regions across teams. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset. Our findings show that analytic flexibility can have substantial effects on scientific conclusions, and demonstrate factors related to variability in fMRI. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for multiple analyses of the same data. Potential approaches to mitigate issues related to analytical variability are discussed

Variability in the analysis of a single neuroimaging dataset by many teams

Data analysis workflows in many scientific domains have become increasingly complex and flexible. To assess the impact of this flexibility on functional magnetic resonance imaging (fMRI) results, the same dataset was independently analyzed by 70 teams, testing nine ex-ante hypotheses. The flexibility of analytic approaches is exemplified by the fact that no two teams chose identical workflows to analyze the data. This flexibility resulted in sizeable variation in hypothesis test results, even for teams whose statistical maps were highly correlated at intermediate stages of their analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Importantly, meta-analytic approaches that aggregated information across teams yielded significant consensus in activated regions across teams. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset. Our findings show that analytic flexibility can have substantial effects on scientific conclusions, and demonstrate factors related to variability in fMRI. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for multiple analyses of the same data. Potential approaches to mitigate issues related to analytical variability are discussed

A longitudinal human phantom reliability study of multi-center T1-weighted, DTI, and resting state fMRI data

© 2018 Multi-center MRI studies can enhance power, generalizability, and discovery for clinical neuroimaging research in brain disorders. Here, we sought to establish the utility of a clustering algorithm as an alternative to more traditional intra-class correlation coefficient approaches in a longitudinal multi-center human phantom study. We completed annual reliability scans on ‘travelling human phantoms’. Acquisitions across sites were harmonized prospectively. Twenty-seven MRI sessions were available across four participants, scanned on five scanners, across three years. For each scan, three metrics were extracted: cortical thickness (CT), white matter fractional anisotropy (FA), and resting state functional connectivity (FC). For each metric, hierarchical clustering (Ward\u27s method) was performed. The cluster solutions were compared to participant and scanner using the adjusted Rand index (ARI). For all metrics, data clustered by participant rather than by scanner (ARI \u3e 0.8 comparing clusters to participants, ARI \u3c 0.2 comparing clusters to scanners). These results demonstrate that hierarchical clustering can reliably identify structural and functional scans from different participants imaged on different scanners across time. With increasing interest in data-driven approaches in psychiatric and neurologic brain imaging studies, our findings provide a framework for multi-center analytic approaches aiming to identify subgroups of participants based on brain structure or function

Siderophore-based microbial adaptations to iron scarcity across the eastern Pacific Ocean

Nearly all iron dissolved in the ocean is complexed by strong organic ligands of unknown composition. The effect of ligand composition on microbial iron acquisition is poorly understood, but amendment experiments using model ligands show they can facilitate or impede iron uptake depending on their identity. Here we show that siderophores, organic compounds synthesized by microbes to facilitate iron uptake, are a dynamic component of the marine ligand pool in the eastern tropical Pacific Ocean. Siderophore concentrations in iron-deficient waters averaged 9 pM, up to fivefold higher than in iron-rich coastal and nutrient-depleted oligotrophic waters, and were dominated by amphibactins, amphiphilic siderophores with cell membrane affinity. Phylogenetic analysis of amphibactin biosynthetic genes suggests that the ability to produce amphibactins has transferred horizontally across multiple Gammaproteobacteria, potentially driven by pressures to compete for iron. In coastal and oligotrophic regions of the eastern Pacific Ocean, amphibactins were replaced with lower concentrations (1–2 pM) of hydrophilic ferrioxamine siderophores. Our results suggest that organic ligand composition changes across the surface ocean in response to environmental pressures. Hydrophilic siderophores are predominantly found across regions of the ocean where iron is not expected to be the limiting nutrient for the microbial community at large. However, in regions with intense competition for iron, some microbes optimize iron acquisition by producing siderophores that minimize diffusive losses to the environment. These siderophores affect iron bioavailability and thus may be an important component of the marine iron cycle.National Science Foundation (U.S.) (OCE-1356747)National Science Foundation (U.S.) (OCE-1233261)National Science Foundation (U.S.) (OCE-1237034)National Science Foundation (U.S.) (DBI-0424599)Gordon and Betty Moore Foundation (Grant GBMF3298)Gordon and Betty Moore Foundation (Grant GBMF3934)Simons Foundation (329108