Biology subjects

Zimmerman, S.

Publications and source records attributed to Zimmerman, S..

15 recordsLinked to original sources

bioRxiv2026

Combined negative effects of simultaneous perturbations on grassland functionality

1. Grassland ecosystems are pivotal for global biodiversity, carbon (C) storage and food security. This biome, however, together with the ecosystem services it provides, is threatened by global change perturbations. These perturbations rarely occur in isolation and most often affect environments simultaneously, which is a pressing issue in ecology. Nevertheless, most of the research conducted so far has focussed on single simultaneous perturbations or pairs thereof. The few examples considering the effect of more than two simultaneous perturbations focussed only on plants or soil separately, which ignores the potential buffering or feedback effects on ecosystem functioning induced by plant-soils interactions. 2. To tackle this knowledge gap, we used an experimental setup involving mesocosms (soil and plants intact) collected in an extensively managed permanent grassland. Mesocosms were arranged in a greenhouse experiment where we applied individual and combined global change perturbations (up to ten in total) including application of fertilisers, pesticides and antibiotics, simulated trampling and grazing, heat stress and drought. Measured ecosystem functions and properties included a large set of biological, physical and chemical soil and plant associated variables. 3. Results showed that multiple perturbations in most cases had negative effects irrespective of the direction found for individual perturbations. However, in contrast to previous bare soil experiments, we only found scarce evidence for substantial synergistic effects of simultaneous perturbations in our experiment conducted with mesocosms that contained vegetation. This suggests a mitigating impact of plants on soil responses to global change. Moreover, we found a strong dominative effect of drought on ecosystem functioning, driving most of the effects observed. 4. Synthesis: Our results highlight the importance of evaluating global change impacts under more realistic settings, i.e., applying multiple perturbations simultaneously and including plant-soil interactions. Mitigation of global change in terrestrial ecosystems will only be possible once we holistically understand how ecosystems respond to altered conditions.

ecology↗

bioRxiv2026

Metabolism in the Solar Photon Field A physical framework for photon-assisted modulation of mitochondrial electron-transfer kinetics

Within a single human lifetime, the spectral environment has been fundamentally reshaped. Broadband daylight, rich in infrared (IR) photons arising from solar and atmospheric physics, has been replaced in the built environment by narrow, engineered spectra that largely exclude long wavelengths. While modern lighting is optimised for vision, the non-visual photobiology of metabolism may depend on spectral components that are now absent. When expressed in photon-energy units, the solar spectrum exhibits a broad maximum near 0.75 eV. This range overlaps with the activation and reorganisation energies governing mitochondrial electron-transfer kinetics. Within a Marcus-type framework, IR photons are therefore positioned to modulate rate-limiting metabolic steps by biasing barrier-crossing probabilities rather than supplying chemical energy. These wavelengths also penetrate deeply into tissue in a scattering-dominated regime, forming a diffuse internal photon field capable of interacting with distributed mitochondrial networks. We propose the term photometabolism: a solar-driven, non-photosynthetic modulation of core metabolic processes. A scaling analysis shows that photon interception in this band varies with body mass in parallel with basal metabolic rate, suggesting that ambient sunlight provides sufficient flux to influence metabolic kinetics across the biosphere. These findings have implications for physiology, ecology and the design of indoor environments whose lighting spectra increasingly diverge from their evolutionary context.

biophysics↗

bioRxiv2026

Oxylipins and Other Natural Products Produced by UV-sterilization Impact Commercial Oyster Larvae Production in a New England Estuary

Here, oyster larval developmental abnormalities within a New England hatchery were linked to a common UV sterilization technique that has been used for over 20 years. Because of the known link between phytoplankton oxylipins and egg mortality in copepods, we hypothesized that UV pretreatment of seawater results in the production of oxylipins that inhibit larval digestion of microalgae. We used lipidomics to observe changes in the organic compounds dissolved in estuarine seawater when filtered and when filtered and pretreated with UV. UV treatment resulted in an increase in the relative abundance of oxylipins associated with cyanobacteria, fungi, and macroalgae in 2020, whereas oxylipins typically produced by diatoms were more abundant in the UV treatments from 2021. Oxylipin concentrations were higher in 2020, when the hatchery reported the most severe problems with larval development. Removing the UV step allowed continued larval production in both years. However, the lack of UV sterilization led to an unidentified bacterial pathogen in 2021, which nearly decimated the overall seasonal production of oyster seed. To follow up in a more controlled environment, the larvae were exposed to exogenous oxidized lipids, which resulted in the same digestive syndrome and histological symptoms as the endogenous suite of compounds produced by UV. Further investigation of the lipidomes revealed that oxylipins were only one class of potentially harmful compounds linked to UV sterilization, and the dissolved concentrations of secondary metabolites associated with higher plants, a wide range of pharmaceuticals, and anthropogenic organic pollutants also increased under UV light. Future efforts will explore the sources of these compounds, the mechanisms by which they inhibit oysters, and whether this is an emerging environmental problem for other ecosystems and shellfish hatcheries. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/738347v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1427dc0org.highwire.dtl.DTLVardef@4dcbf9org.highwire.dtl.DTLVardef@18a57faorg.highwire.dtl.DTLVardef@195e0ed_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2024

Carbonic anhydrase plays multiple roles in acetotrophic growth of a model marine methanogen from the domain Archaea

Carbonic anhydrase (CA) catalyzes the reversible hydration of CO2 to bicarbonate and a proton. The enzyme is universally distributed in all three domains of life and plays diverse physiological roles in the domains Eukarya and Bacteria. Remarkably, a physiological role has not been identified for any CA from the domain Archaea. Herein are described roles for a gamma class CA (Cam) from the methane-producing marine archaeon Methanosarcina acetivorans. Acetate-dependent growth of a {Delta}cam mutant showed an extended lag phase, lower final cell density, and metabolized acetate to a threshold of 20.0 mM compared to 1.0 mM for wild-type. Molar growth yields (Ymethane) were substantially greater for wild-type compared to the mutant. In contrast, growth parameters were identical for the methanol-grown wild-type and mutant. Rates of methane formation in resting cell suspensions containing 20.0 mM acetate were significantly less in the mutant versus wild-type and dependent on the presence of CO2. Rates for the wild-type decreased with increasing pH that was more pronounced for the mutant. CA activity was 100-fold greater in the membrane versus soluble fraction of acetate-grown cells. Addition of a surrogate CA stimulated acetate-dependent methanogenesis in resting cell suspensions of the mutant. The results support a role for Cam to supply protons for symport of acetate by the AceP symporter that also optimizes and facilitates growth at low acetate concentrations and high pH values encountered in the marine environment where M. acetivorans was isolated. Significance StatementAlthough CA plays major physiological roles in the domains Eukarya and Bacteria, a role has not been reported for the domain Archaea in which methanogens comprise the major group with abundant genomic annotations for CAs. Acetotrophic methanogens account for most of the methane produced in Earths biosphere where it is a major greenhouse gas. Although the biochemistry of the conversion of acetate to methane and carbon dioxide is well known, little is understood of acetate transport. The finding that CA has multiple roles facilitating thermodynamically constrained growth of a model marine acetotrophic methanogen has implications for advancing ecological understanding of the methane cycle that impacts global warming and climate change. Finally, the work is an introduction to anticipated physiological roles of CAs in the domain Archaea for which genomic annotations are abundant.

microbiology↗

bioRxiv2023

Single-cell RNA-seq reveals TCR clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in NOD mice

T cells primarily drive the autoimmune destruction of pancreatic beta cells in Type 1 diabetes (T1D). However, the profound yet uncharacterized diversity of the T cell populations in vivo has hindered obtaining a clear picture of the T cell changes that occur longitudinally during T1D onset. This study aimed to identify T cell clonal expansion and distinct transcriptomic signatures associated with T1D progression in Non-Obese Diabetic (NOD) mice. Here we profiled the transcriptome and T cell receptor (TCR) repertoire of T cells at single-cell resolution from longitudinally collected peripheral blood and pancreatic islets of NOD mice using single-cell RNA sequencing technology. Surprisingly, we detected a considerable high frequency of islet-matching T cell clones in the peripheral circulation and blood-matching T cell clones in the islets. Our analysis showed that transcriptional signatures of the T cells are associated with the matching status of the T cells, suggesting potential future applications as a marker for early prediction of diabetes onset using peripheral T cells. In addition, we discovered a high frequency of transcriptionally distinct double negative (DN) T cells that might arise from naive and effector backgrounds through the loss of CD4 or CD8 in a yet unknown biological pathway. This study provides a single-cell level transcriptome and TCR repertoire atlas of T cells in NOD mice and opens the door for more research into the causes of type 1 diabetes and inflammatory autoimmune disease using mouse models.

immunology↗

bioRxiv2023

A modular metagenomics analysis system for integrated multi-step data exploration

MotivationComputational analysis of large-scale metagenomics sequencing datasets have proven to be both incredibly valuable for extracting isolate-level taxonomic, and functional insights from complex microbial communities. However, due to an ever-expanding ecosystem of metagenomics-specific methods and file-formats, designing seamless and scalable end-to-end workflows, and exploring the massive amounts of output data have become studies unto themselves. One-click bioinformatics pipelines have helped to organize these tools into targeted workflows, but they suffer from general compatibility and maintainability issues, and preclude replication. MethodsTo address the gap in easily extensible yet robustly distributable metagenomics workflows, we have developed a module-based metagenomics analysis system "Core Analysis Modular Pipeline" (CAMP), written in Snakemake, a popular workflow management system, along with a standardized module and working directory architecture. Each module can be run independently or conjointly with a series of others to produce the target data format (e.g. short-read preprocessing alone, or short-read preprocessing followed by de novo assembly), and outputs aggregated summary statistics reports and semi-guided Jupyter notebook-based visualizations. ResultsWe have applied CAMP to a set of ten metagenomics samples to demonstrate how a modular analysis system with built-in data visualization at intermediate steps facilitates rich and seamless inter-communication between output data from different analytic purposes. AvailabilityThe CAMP ecosystem (module template and analysis modules) can be found https://github.com/Meta-CAMP.

bioinformatics↗

bioRxiv2022

Quantifying shared and unique gene content across 17 microbial ecosystems

Measuring microbial diversity is traditionally based on microbe taxonomy. Here, in contrast, we aimed to quantify heterogeneity in microbial gene content across 14,183 metagenomic samples spanning 17 ecologies including -- 6 human-associated, 7 non-human-host-associated, and 4 in other non-human host environments. In total, we identified 117,629,181 non-redundant genes. The vast majority of genes (66%) occurred in only one sample (i.e. "singletons"). By contrast, we found 1,864 sequences present in every metagenome, but not necessarily every bacterial genome. Additionally, we report datasets of other ecology-associated genes (e.g. abundant in only gut ecosystems) and simultaneously demonstrated that prior microbiome gene catalogs are both incomplete and inaccurately cluster microbial genetic life (e.g. at gene-sequence identifies that are too restrictive). We provide our results and the sets of environmentally-differentiating genes described above at http://www.microbial-genes.bio. ImportanceThe amount of shared genetic elements has not been quantified between the human microbiome and other host and non-host associated microbiomes. Here we made a gene catalog of 17 different microbial ecosystems and compared them. We show that most species shared between environment and human gut microbiomes are pathogens and that prior gene catalogs described as "near-complete" are far from it. Additionally, over two-thirds of all genes only appear in a single sample and only 1,864 genes (0.001%) are found in all types of metagenomes. These results highlight the large diversity between metagenomes and reveal a new, rare class of genes, those found in every type of metagenome, but not every microbial genome.

microbiology↗

bioRxiv2022

Background modeling, Quality Control and Normalization for GeoMx RNA data with GeoDiff

BackgroundNanoStrings GeoMx Digital Spatial Profiler (DSP) RNA assay can measure mRNA from hundreds of regions of customizable shape and size, yet it gives unique challenge in Quality Control(QC) and normalizating due to the omnipresent background noise incurred by the non-specific probe binding, which could not be addressed by conventional methods. Results and discussionUsing Poisson Background model, Background Score Test, Negative Binomial threshold model and Poisson threshold model for normalization from the R package GeoDiff, we perform tasks including size factor estimation, QC and normalization on GoeMx RNA assay data. They are shown to outperform conventional methods like Limit of Quantification for QC as to consistency/false positive rate and 75% quantile normalization as to eliminating technical variability and recovering true signal. ConclusionsWe present a statistical model based workflow for QC and normalizing GeoMx RNA data using GeoDiff, justified by statistical theory and validated by real/simulated data.

bioinformatics↗

bioRxiv2021

Stat3 co-operates with mutant Ezh2Y641F to regulate gene expression and limit the anti-tumor immune response in melanoma

One of the most frequently genetically altered chromatin modifiers in melanoma is the Enhancer of Zeste Homolog 2 (EZH2), the catalytic component of the Polycomb Repressive Complex 2 (PRC2), which methylates lysine 27 on histone 3 (H3K27me3), a chromatin mark associated with transcriptional repression. Genetic alterations in EZH2 in melanoma include amplifications and activating point mutations at tyrosine 641 (Y641). The oncogenic role of EZH2 in melanoma has previously been identified; however, its downstream mechanisms remain underexplored. We found that in genetically engineered mouse models, Ezh2Y641F expression causes upregulation of a subset of interferon-regulated genes in melanoma cells, suggesting a potential role of the immune system in the pathogenesis of these mutations. Upregulation of these interferon genes was not a result of changes in H3K27me3, but through a direct and non-canonical interaction between Ezh2 and Signal Transducer and Activator of Transcription 3 (Stat3). Ezh2 directly binds Stat3, and, in the presence of Ezh2Y641F, Stat3 protein is hypermethylated. Expression of Stat3 was required to maintain an anti-tumor immune response and its depletion resulted in faster melanoma progression and disease recurrence. Molecularly, Stat3 and Ezh2 bind together at many genomic loci, and can both activate and repress gene expression in association with the rest of the PRC2 complex. These results suggest that Ezh2 can mediate melanomagenesis through evasion of the anti-tumor immune response, and that the immunomodulatory properties of Stat3 are context dependent.

cancer biology↗

bioRxiv2021

The central nucleus of the amygdala and gustatory cortex assess affective valence during CTA learning and expression in male and female rats

This study evaluated behavior (Boost(R) intake, LiCl-induced behaviors, ultrasonic vocalizations (USVs), task performance) and c-Fos activation during conditioned taste aversion (CTA), the reinforced task (Boost(R) task) and control task (cage only) to understand how male and female rats balance the relative danger or safety of a stimulus in learning and performing a task. Females drank more Boost(R) than males but showed similar aversive behaviors after LiCl treatment. Males produced 55 kHz USVs (indicating positive valence) when anticipating Boost(R) and inhibited these calls after pairing with LiCl. Females produced 55 kHz USVs based on their estrous cycle but were more likely to make 22 kHz USVs than males (indicating negative valence) after pairing with LiCl. c-Fos responses were similar in males and females after Boost(R) or LiCl. Females engaged the gustatory cortex and ventral tegmental area more than males during the Boost(R) task and males engaged the amygdala more than females in both the reinforcing and devalued tasks. Network analysis of correlated c-Fos responses across brain regions identified two unique networks characterizing the Boost(R) and LiCl (CTA) tasks, in both of which the VTA played a central role. RNAscope identified a population of D1-receptor expressing cells in the CeA that responded to Boost(R) and D2 receptor-expressing cells that responded to LiCl. The present study suggests that males and females differentially process the affective valence of a stimulus to produce the same goal-directed behavior.

animal behavior and cognition↗

bioRxiv2020

A genetic screen identifies dreammist as a regulator of sleep

Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+,K+-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na+ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na+ pump function modulates neuronal excitability to maintain normal sleep behaviour. Significance statementSleep is an essential behavioral state, but the genes that regulate sleep and wake states are still being uncovered. A viral insertion screen in zebrafish identified a novel sleep mutant called dreammist, in which a small, highly-conserved transmembrane protein is disrupted. The discovery of dreammist highlights the importance of a class of small transmembrane-protein modulators of the sodium pump in setting appropriate sleep duration.

neuroscience↗

bioRxiv2020

An optogenetic switch for the Set2 methyltransferase provides evidence for rapid transcription-dependent and independent dynamics of H3K36 methylation

Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification associated with transcription and DNA repair. Although the effects of H3K36 methylation have been studied, the short-term genome-wide dynamics of H3K36me deposition and removal are not known. We established rapid and reversible optogenetic control for Set2, the sole H3K36 methyltransferase in yeast, by fusing the enzyme with the light activated nuclear shuttle (LANS) domain. Early H3K36me3 dynamics identified rapid methylation in vivo, with total H3K36me3 levels correlating with RNA abundance. Although genes exhibited disparate levels of H3K36 methylation, relative rates of H3K36me3 accumulation were largely linear and consistent across genes, suggesting a rate-limiting mechanism for H3K36me3 deposition. Removal H3K36me2/3 was also rapid and highly dependent on the demethylase Rph1. However, the per-gene rate of H3K36me3 loss weakly correlated with RNA abundance and followed exponential decay, suggesting H3K36 demethylases act in a global, stochastic manner.

molecular biology↗

bioRxiv2019

Zebrafish Dscaml1 is Essential for Retinal Patterning and Function of Oculomotor Subcircuits

Down Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the role of dscaml1 in the zebrafish oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Loss of zebrafish dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses showed that mutants have abnormal gaze stabilization, impaired fixation, disconjugation, and faster fatigue. Notably, the saccade and fatigue phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, for which no animal model exists. Two-photon calcium imaging showed that loss of dscaml1 leads to impairment in the saccadic premotor pathway but not the pretectum-vestibular premotor pathway, indicating a subcircuit requirement for dscaml1. Together, we show that dscaml1 has both broad and specific roles in oculomotor circuit function, providing a new animal model to investigate the development of premotor pathways and their associated human ocular disorders.

neuroscience↗

bioRxiv2019

The shape of gene expression distributions matter: how incorporating distribution shape improves the interpretation of cancer transcriptomic data

In genomics, we often impose the assumption that gene expression data follows a specific distribution. However, rarely do we stop to question this assumption or consider its applicability to all genes in the transcriptome. Our study investigated the prevalence of genes with expression distributions that are non-Normal in three different tumor types from the Cancer Genome Atlas (TCGA). Surprisingly, less than 50% of all genes were Normally-distributed, with other distributions including Gamma, Bimodal, Cauchy, and Lognormal were represented. Relevant information about cancer biology was captured by the genes with non-Normal gene expression. When used for classification, the set of non-Normal genes were able to discriminate between cancer patients with poor versus good survival status. Our results highlight the value of studying a genes distribution shape to model heterogeneity of transcriptomic data. These insights would have been overlooked when using standard approaches that assume all genes follow the same type of distribution in a patient cohort.

bioinformatics↗

bioRxiv2018

Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions

Genomic studies have identified hundreds of candidate genes near loci associated with risk for schizophrenia. To define candidates and their functions, we mutated zebrafish orthologues of 132 human schizophrenia-associated genes and created a phenotype atlas consisting of whole-brain activity maps, brain structural differences, and profiles of behavioral abnormalities. Phenotypes were diverse but specific, including altered forebrain development and decreased prepulse inhibition. Exploration of these datasets identified promising candidates in more than 10 gene-rich regions, including the magnesium transporter cnnm2 and the translational repressor gigyf2, and revealed shared anatomical sites of activity differences, including the pallium, hypothalamus or tectum. Single-cell RNA sequencing uncovered an essential role for the understudied transcription factor znf536 in the development of forebrain neurons implicated in social behavior and stress. This phenotypic landscape of schizophrenia-associated genes prioritizes more than 30 candidates for further study and provides hypotheses to bridge the divide between genetic association and biological mechanism.

genetics↗