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Peterson, B.

Publications and source records attributed to Peterson, B..

12 recordsLinked to original sources

Sleep-Related Respiratory Disruption is Associated with Altered Spindle Morphology and Poorer Attention in Children

Study ObjectivesTo determine whether sleep-related respiratory disruption is associated with regionally specific alterations in sleep spindle topography and whether hypopnea-sensitive spindle features are associated with attentional performance in children. MethodsWe recorded overnight high-density EEG in children across a wide range of respiratory disruption severity. Slow and fast spindle metrics were extracted per channel, and channel-wise regression models characterized topographic associations with hypopnea index (HI). Cluster-based permutation testing controlled for multiple comparisons. Hierarchically defined regions of interest were tested as predictors of attentional performance on the Test of Variables of Attention (TOVA). ResultsCanonical slow-anterior and fast-posterior spindle organization was detectable across the cohort. Two HI-related topographic effects survived cluster-based permutation correction: higher HI was associated with shortened anterior fast spindle duration and with slower anterior slow spindle peak frequency. In cognitive models, anterior fast spindle duration was the strongest and most consistent predictor of attentional performance, associated with higher signal detection sensitivity, fewer omission errors, and fewer commission errors. By contrast, slow spindle peak frequency showed no attentional associations. ConclusionsPediatric respiratory disruption is associated with regionally specific alterations in spindle morphology rather than global spindle reduction. Shortened anterior fast spindle duration showed convergent respiratory and attentional associations, suggesting that localized spindle integrity may provide a neurophysiological marker of cognitive vulnerability in pediatric sleep-disordered breathing beyond conventional clinical respiratory metrics. HighlightsO_LIHigher hypopnea index was associated with shortened anterior fast spindle duration and slower anterior slow spindle peak frequency C_LIO_LIAnterior fast spindle duration predicted attentional performance in children C_LIO_LIRespiratory disruption may impair attention by disrupting thalamocortical spindle activity C_LI Statement of SignificanceChildren with sleep-disordered breathing can show neurocognitive difficulties that are not well explained by standard respiratory indices alone. This study uses high-density EEG to show that hypopnea burden is associated with regionally specific alterations in sleep spindle morphology, particularly shortened anterior fast spindle duration, rather than a global reduction in spindle occurrence. Anterior fast spindle duration was also the spindle feature most consistently associated with attentional performance. These findings suggest that localized spindle morphology may provide a sleep-neurophysiological readout of cognitive vulnerability in pediatric sleep-disordered breathing. Longitudinal and treatment studies are needed to determine whether spindle duration changes with respiratory improvement and whether such changes track cognitive recovery.

neuroscience↗

Streptomyces enrichment in roots during drought is uncoupled from plant benefit and is driven by host suppression of iron uptake and immunity

Drought reshapes plant root microbiota, yet the mechanistic drivers and consequences of this observation remain unclear. We discovered that suppression of host immunity and iron homeostasis is required for Streptomyces enrichment in roots during drought across diverse soils. Genetic and physiological manipulation of these host pathways confirmed their requirement in modulating Streptomyces root enrichment. Drought-induced suppression of iron uptake was conserved across the [~]160 My monocot-eudicot divergence. Some Streptomyces strains enhanced plant growth and rescued iron uptake under drought. These benefits were uncoupled from Streptomyces root enrichment. They were instead shaped by intra-Streptomyces antagonism. We propose a two-step model: drought-driven down regulation of host iron and immune pathways enriches Streptomyces, while intra-genus dynamics fine-tune strain-level assembly and functional outcomes. Our data refine the idea that Streptomyces are enriched in roots during drought in response to a plant cry for help and consequently contribute to alleviation of this abiotic stress.

plant biology↗

Signatures of sex ratio distortion in humans

Segregation distortion, the disproportionate inheritance of selfish genetic elements, is an important evolutionary force. While many species carry distorters, it is not clear if humans do. Major limitations for detecting human distortion are the small size of human families and the lack of genetic markers in most subjects. Here, we present evidence of strong distortion in a large human pedigree. We analyzed pedigrees from the Utah Population Database and identified lineages with a high chance of carrying a distorter. In particular, we identified a family that preferentially produced male offspring at a 2:1 ratio. This pattern is consistent with a distorting Y-chromosome, a rarity in species with degenerate Y-chromosomes. The detection of such non-Mendelian inheritance patterns suggests that human genomes may harbor segregation distorters.

genetics↗

Prostaglandin E2 Reverses Myofibroblast Differentiation in Eosinophilic Esophagitis

Background & AimsUnchecked inflammation in Eosinophilic esophagitis (EoE) leads to esophageal fibrosis and eventual stricture. Differentiated fibroblasts, termed myofibroblasts, are the main effector cells in fibrosis, responsible for secreting extracellular matrix proteins leading to tissue stiffness. Regulating myofibroblasts has not been explored as a therapeutic possibility in the fibrostenotic esophagus. Herein, we aim to investigate the efficacy of Prostaglandin E2 (PGE2) in dedifferentiation of the EoE myofibroblast. MethodsWe evaluated the efficacy and mechanism of myofibroblast dedifferentiation using fetal esophageal fibroblasts (FEF3), patient-derived fibroblasts, and a murine model of EoE. ResultsFibrosis markers (SMA, FN1, and COL1A1) and contractility of myofibroblasts were significantly decreased by PGE2 via the cAMP pathway. PGE2 treatment decreased nuclear accumulation of phospho-Smad2/3-YAP complex and induced phospho-YAP proteasomal degradation. Transcriptome analyses of FEF3 treated with TGF{beta} or PGE2 revealed that the Integrin1 pathway, and specifically thrombospondin 1 (THBS-1), was significantly upregulated by TGF{beta} and downregulated by PGE2, as supported by pseudo-bulk single-cell RNA-seq of EoE biopsies. THBS-1 was shown to be regulated by PGE2 via the cAMP/YAP pathway, and its knockdown induced myofibroblasts dedifferentiation. In a murine model of EoE, Butaprost, agonist of the E-prostanoid G protein-coupled receptor 2, treatment significantly reduced the expression of THBS-1, SMA, and FN1 along with a decrease in YAP nuclear translocation. Additionally, collagen fiber organization in the lamina propria was markedly reduced. ConclusionPGE2 promotes dedifferentiation of myofibroblasts in EoE via the cAMP/YAP/ THBS-1 pathway. Our data suggest that PGE2 is a promising treatment strategy for EoE with stenosis. What You Need to KnowO_ST_ABSBackground and ContextC_ST_ABSIn Eosinophilic esophagitis, unchecked inflammation and tissue stiffness drives fibroblast differentiation and fibrostenosis of the esophagus, yet targeting myofibroblasts as regulators of extracellular matrix deposition in fibrostenotic disease remains clinically unexplored. New FindingsProstaglandin E2 promotes dedifferentiation of myofibroblasts in eosinophilic esophagitis via the cAMP/YAP pathway, with Thrombospondin-1 identified as a critical YAP regulated target driving fibrostenosis. LimitationsThis study focused on fibroblast-specific mechanisms. The effects of PGE2 on esophageal epithelial differentiation, barrier function, and immune cell recruitment in EoE remain to be determined. Clinical Research RelevanceThis study demonstrates proof-of-concept that pharmacological reversal of established fibrosis is achievable in EoE. PGE2 and its EP2-selective agonists represent translatable therapeutic targets for fibrostenotic EoE--a patient population that remains treatment-refractory to current immunosuppressive approaches. Basic Research RelevanceThe cAMP/YAP/THBS-1 signaling in fibroblasts emerges as a critical therapeutic target for esophageal fibrosis. Importantly, this work demonstrates that terminally differentiated myofibroblasts retain remarkable plasticity and can dedifferentiate--challenging the paradigm that fibrosis is irreversible.

cell biology↗

Cryptic cycling by electroactive bacterioplankton in Trout Bog Lake

The genetic potential for extracellular electron transfer (EET)-based metabolism has been shown to be a prevailing feature of humic lakes where bacterioplankton may be able to use EET to cycle dissolved organic matter (DOM) extracellularly between oxidized and reduced states, but measurable abiotic features resulting from this phenomenon have yet to be demonstrated. We observed an anoxygenic photosynthetic Chlorobium sp. bloom each summer in Trout Bog Lake in northern WI, USA. Given this blooms characteristics, we hypothesized that EET-based metabolisms of Chlorobium sp. and accompanying bacteria cycle DOM between oxidized and reduced states with seasonal or diel-timescale oscillations; therefore, we anticipated this could be measured by weekly and subdaily sampling. We collected vertical profiles on these timescales using a multiparameter sonde, including oxidation-reduction potential measurement, and we assayed for inorganic electron donors. We also developed and deployed a buoy to measure electric current flow between many pairs of electrodes simultaneously. Using metagenomics analyses, we examined the EET genes and other oxidoreductases of bacteria from water column samples at select depths and from biofilms that developed on electrodes at similar depths. Our results indicate the occurrence of diel electron cycling between phototrophic oxidation (electrotrophic metabolism) and anaerobic respiration (electrogenic metabolism), likely involving DOM. We also observed a gradual seasonal increase in hypolimnion oxidation-reduction potential. These diel and seasonal patterns have implications for carbon emissions and the ecology of electroactive bacteria in lakes. IMPORTANCEWe investigated the physical, chemical, and redox characteristics of a bog lake and electrodes hung therein to test the hypothesis that dissolved organic matter is being cycled between oxidized and reduced states by electroactive bacterioplankton powered by phototrophy. To do so we performed field-based analyses on multiple timescales using both established and novel instrumentation. We paired these analyses with recently developed bioinformatics pipelines for metagenomics data to investigate genes that enable electroactive metabolism and accompanying metabolisms. Our results are consistent with our hypothesis and yet upend some of our other expectations. Our findings have implications for understanding greenhouse gas emissions from lakes, including electroactivity as an integral part of lake metabolism throughout more of the anoxic parts of lakes and for a longer portion of the summer than expected. Our results also give a sense of what electroactivity occurs at given depths and provide a strong basis for future studies.

microbiology↗

Viral impacts on microbial activity and biogeochemical cycling in a seasonally anoxic freshwater lake

Microbial biogeochemical cycling relies on alternative electron acceptors when oxygen is unavailable, yet the role of viruses (bacteriophages) in these processes is understudied. We investigated how seasonal anoxia impacts viral and microbial biogeochemical cycling, by using paired total metagenomes, viromes, and metatranscriptomes, that were collected weekly. Stratification and anoxia drove microbial community composition, but dataset origin impacted the interpretation of viral community structure, activity, and function. Importantly, taxa abundance did not correlate with activity for both microbes and viruses. We identified virus-host linkages for 116 phages across 55 distinct hosts, many of which expressed genes for aerobic methane oxidation, nitrogen fixation, denitrification, and sulfate reduction. Overall, this work demonstrates the breadth and dynamics of virus-host interactions in mediating biogeochemistry. Additionally, we propose that viral community detection, functional potential, and activity are sensitive to pre-sequencing decisions, which must be kept in mind when interpreting genomic data in a biologically meaningful way.

microbiology↗

Circadian regulation of glutamate release pathways shapes synaptic throughput in the brainstem nucleus of the solitary tract (NTS)

Circadian regulation of autonomic reflex pathways pairs physiological function with the daily light cycle. The brainstem nucleus of the solitary tract (NTS) is a key candidate for rhythmic control of the autonomic nervous system. Here we investigated circadian regulation of NTS neurotransmission and synaptic throughput using patch-clamp electrophysiology in brainstem slices from mice. We found that spontaneous quantal glutamate release on to NTS neurons showed strong circadian rhythmicity, with the highest rate of release during the light phase and the lowest in the dark, that were sufficient to drive day / night differences in constitutive postsynaptic action potential firing. In contrast, afferent-evoked action potential throughput was enhanced during the dark and diminished in the light. Afferent-driven synchronous release pathways showed a similar decrease in release probability that did not explain the enhanced synaptic throughput during the night. However, analysis of postsynaptic membrane properties revealed diurnal changes in conductance; which, when coupled with the circadian changes in glutamate release pathways, tuned synaptic throughput between the light and dark phases. These coordinated pre- / postsynaptic changes encode nuanced control over synaptic performance and pair NTS action potential firing and vagal throughput with time of day.

neuroscience↗

The generation of the first chromosome-level de-novo genome assembly and the development and validation of a 50K SNP array for North American Atlantic salmon

Given the genetic and genomic differences between Atlantic salmon of European origin and North American (N.A.) origin, it is crucial to develop unique genomic resources for each lineage. Here we describe the resources that we recently developed for genomic and genetic research in N.A. Atlantic salmon. Firstly, a new single nucleotide polymorphism (SNP) database for N.A. Atlantic salmon consisting of 3.1 million putative SNPs was generated using data from whole genome resequencing of 80 N.A. Atlantic salmon individuals; Secondly, a high density 50K SNP array enriched for the genic regions of the genome and containing three sex determination and 61 continent of origin markers was developed and validated; Thirdly, a genetic map composed of 27 linkage groups with 36K SNP markers, was generated from 2,512 individuals in 141 full-sib families; Finally, a chromosome level de-novo assembly of a male N.A. Atlantic salmon genome was generated using PacBio long-reads. Information from Hi-C proximity ligation sequences and Bionano optical mapping was used to concatenate the contigs into scaffolds. The assembly contains 1,755 scaffolds and only 1,253 gaps, with a total length of 2.83 Gb and N50 of 17.2 Mb. A BUSCO analysis detected 96.2% of conserved Actinopterygii genes in the assembly and the genetic linkage information was used to guide the formation of 27 chromosome sequences. In contrast, the karyotype of the European Atlantic salmon lineage is composed of 29 chromosomes. Comparative analysis with the reference genome assembly of the European Atlantic salmon confirmed that the karyotype differences between the two linages are caused by a fission in chromosome Ssa01 and three chromosome fusions including the p arm of chromosome Ssa01 with Ssa23, Ssa08 with Ssa29 and Ssa26 with Ssa28. The genomic resources we have generated for Atlantic salmon provide a crucial boost for genetic research and for management of farmed and wild populations in this highly valued species.

genomics↗

RGI-GOLVEN signalling promotes FLS2 abundance to regulate plant immunity

Endogenous plant signalling peptides regulate developmental and growth-related processes. Recent research indicates that some of these peptides are classified as phytocytokines as they have regulatory functions during plant immune responses. However, the mechanistic basis for phytocytokine-mediated immune modulation remains largely elusive. Here, we identify GOLVEN2 (GLV2) peptides as novel phytocytokines in Arabidopsis thaliana. By peptide application, precursor overexpression and loss-of-function studies we show that GLV2 enhances sensitivity of plants to elicitation with the bacterial flagellin epitope flg22. GLV2 is perceived by ROOT MERISTEM GROWTH FACTOR 1 INSENSITIVE (RGI) receptors and RGI3 forms an flg22-induced complex with the flg22-receptor FLAGELLIN SENSITIVE 2, suggesting that RGIs are part of activated pattern recognition receptor signalling platforms. GLV2 perception increases posttranscriptional FLS2 abundance and RGIs promote FLS2 protein accumulation. Thus, GLV-RGI signalling controls above ground plant immunity via a novel mechanism of phytocytokine activity.

plant biology↗

Intra-session test-retest reliability of functional connectivity in infants

Resting functional MRI studies of the infant brain are increasingly becoming an important tool in developmental neuroscience. Whereas the test-retest reliability of functional connectivity (FC) measures derived from resting fMRI data have been characterized in the adult and child brain, similar assessments have not been conducted in infants. In this study, we examined the intra-session test-retest reliability of FC measures from 119 infant brain MRI scans from four neurodevelopmental studies. We investigated edge-level and subject-level reliability within one MRI session (between and within runs) measured by the Intraclass correlation coefficient (ICC). First, using an atlas-based approach, we examined whole-brain connectivity as well as connectivity within two common resting fMRI networks - the default mode network (DMN) and the sensorimotor network (SMN). Second, we examined the influence of run duration, study site, and scanning manufacturer (e.g., Philips and General Electric) on ICCs. Lastly, we tested spatial similarity using the Jaccard Index from networks derived from independent component analysis (ICA). Consistent with resting fMRI studies from adults, our findings indicated poor edge-level reliability (ICC = 0.14 - 0.18), but moderate-to-good subject-level intra-session reliability for whole-brain, DMN, and SMN connectivity (ICC = 0.40 - 0.78). We also found significant effects of run duration, site, and scanning manufacturer on reliability estimates. Some ICA-derived networks showed strong spatial reproducibility (e.g., DMN, SMN, and Visual Network), and were labelled based on their spatial similarity to analogous networks measured in adults. These networks were reproducibly found across different study studies. However, other ICA-networks (e.g. Executive Control Network) did not show strong spatial reproducibility, suggesting that the reliability and/or maturational course of functional connectivity may vary by network. In sum, our findings suggest that developmental scientist may be on safe ground examining the functional organization of some major neural networks (e.g. DMN and SMN), but judicious interpretation of functional connectivity is essential to its ongoing success. HighlightsO_LIInfant functional connectivity (FC) shows poor edge-level reliability (ICCs) C_LIO_LIHowever, subject-level infant FC estimates show good-to-excellent ICCs C_LIO_LISpatial reproducibility is better for some resting networks (DMN, SMN) than others (ECN) C_LIO_LIReliability estimates differ across study site and MRI scanner C_LIO_LIConclusion - Infant FC can be a reliable measurement, but judicious use is needed C_LI

bioinformatics↗

Expanded Phylogenetic Diversity and Metabolic Flexibility of Microbial Mercury Methylation

Methylmercury is a potent, bioaccumulating neurotoxin that is produced by specific microorganisms by methylation of inorganic mercury released from anthropogenic sources. The hgcAB genes were recently discovered to be required for microbial methylmercury production in diverse anaerobic bacteria and archaea. However, the full phylogenetic and metabolic diversity of mercury methylating microorganisms has not been fully explored due to the limited number of cultured, experimentally verified methylators and the limitations of primer-based molecular methods. Here, we describe the phylogenetic diversity and metabolic flexibility of putative mercury methylating microorganisms identified by hgcA sequence identity from publicly available isolate genomes and metagenome-assembled genomes (MAGs), as well as novel freshwater MAGs. We demonstrate that putative mercury methylators are much more phylogenetically diverse than previously known, and the distribution of hgcA is most likely due to several independent horizontal gene transfer events. Identified methylating microorganisms possess diverse metabolic capabilities spanning carbon fixation, sulfate reduction, nitrogen fixation, and metal resistance pathways. Using a metatranscriptomic survey of a thawing permafrost gradient from which we identified 111 putative mercury methylators, we demonstrate that specific methylating populations may contribute to hgcA expression at different depths. Overall, we provide a framework for illuminating the microbial basis of mercury methylation using genome-resolved metagenomics and metatranscriptomics to identify methylators based upon hgcA presence and describe their putative functions in the environment. IMPORTANCESpecific anaerobic microorganisms among the Deltaproteobacteria, Firmicutes, and Euryarchaeota have been shown to produce the bioaccumulating neurotoxin methylmercury. Accurately assessing the sources of microbial methylmercury production in the context of phylogenetic identification, metabolic guilds, and activity in the environment is crucial for understanding the constraints and effects of mercury impacted sites. Advances in next-generation sequencing technologies have enabled large-scale, cultivation-independent surveys of diverse and poorly characterized microorganisms of numerous ecosystems. We used genome-resolved metagenomics and metatranscriptomics to highlight the vast phylogenetic and metabolic diversity of putative mercury methylators, and their depth-discrete activities in the environment. This work underscores the importance of using genome-resolved metagenomics to survey specific putative methylating populations of a given mercury-impacted ecosystem.

microbiology↗

Peax: Interactive Visual Pattern Search in Sequential Data Using Unsupervised Deep Representation Learning

We present PO_SCPLOWEAXC_SCPLOW, a novel feature-based technique for interactive visual pattern search in sequential data, like time series or data mapped to a genome sequence. Visually searching for patterns by similarity is often challenging because of the large search space, the visual complexity of patterns, and the users perception of similarity. For example, in genomics, researchers try to link patterns in multivariate sequential data to cellular or pathogenic processes, but a lack of ground truth and high variance makes automatic pattern detection unreliable. We have developed a convolutional autoencoder for unsupervised representation learning of regions in sequential data that can capture more visual details of complex patterns compared to existing similarity measures. Using this learned representation as features of the sequential data, our accompanying visual query system enables interactive feedback-driven adjustments of the pattern search to adapt to the users perceived similarity. Using an active learning sampling strategy, PO_SCPLOWEAXC_SCPLOW collects user-generated binary relevance feedback. This feedback is used to train a model for binary classification, to ultimately find other regions that exhibit patterns similar to the search target. We demonstrate PO_SCPLOWEAXC_SCPLOWs features through a case study in genomics and report on a user study with eight domain experts to assess the usability and usefulness of PO_SCPLOWEAXC_SCPLOW. Moreover, we evaluate the effectiveness of the learned feature representation for visual similarity search in two additional user studies. We find that our models retrieve significantly more similar patterns than other commonly used techniques.

genomics↗