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Kaiser, S.

Publications and source records attributed to Kaiser, S..

At least 19 recordsLinked to original sources

EigenBrain maps cortical molecular architecture from functional, geometric, and structural eigenmodes

Neurotransmitter receptor and transporter distributions shape neural communication across the cortex and underpin mechanistic interpretations of brain function. Magnetic resonance imaging (MRI)-derived eigenmodes, low-dimensional spatial patterns that capture the principal axes of cortical organization, are increasingly used to reconstruct brain maps and offer a potential route to approximating molecular topographies in large cohorts where direct measurements are unavailable. Yet whether the type of MRI data used to derive these eigenmodes determines which receptor and transporter distributions can be approximated, and which molecular systems are accessible through this approach at all, remains unknown. Using a spatial reconstruction framework applied to 23 molecular systems spanning neurotransmitter, metabolic, and pathological markers, we show that eight receptor and transporter maps, spanning serotonin, dopamine, histamine, cholinergic, and opioid markers, can be selectively approximated from functional eigenmodes but not structural or geometric ones. This selectivity also reveals that functional brain organization encodes a specific subset of neuromodulatory topographies that structural and geometric organization does not. To illustrate translational potential in clinical cohorts where molecular imaging is unavailable, we applied individual-level eigenmode decompositions of MRI data projected onto the eight validated molecular systems and detected cross-sectional differences in autism and longitudinal changes in schizophrenia. Together, these findings reveal a difference in how geometric, structural, and functional brain organization relate to molecular architecture, offering a method for approximating validated molecular profiles in population neuroimaging cohorts that lack direct molecular imaging.

neuroscience↗

Harmonized nucleoside mass spectrometry enables reproducible cross-platform RNA modification quantification

RNA modification analysis by LC-MS/MS is central to epitranscriptomics, yet quantitative comparison across laboratories and instrument platforms remains poorly standardized. Here, we performed a community-driven benchmarking study during the first Human RNome Project workshop to systematically evaluate cross-platform reproducibility of ribonucleoside mass spectrometry workflows. Using the same analytical column and gradient, standardized RNA samples, and shared reagents, we compared nucleoside quantification across quadrupole, time-of-flight, and orbitrap-based LC-MS platforms employing distinct acquisition strategies. While chromatographic separation was highly reproducible across systems, nucleoside-specific MS response behavior differed substantially between platforms and limited direct comparability of relative signal intensities. These response differences varied across analytes and concentration ranges, demonstrating that harmonized chromatography alone is insufficient for transferable quantitative analysis. Stable isotope-labeled internal standard (SILIS) normalization substantially reduced platform-and method-dependent response and improved agreement for most evaluated modifications. External calibration improved agreement between qTOF and Orbitrap workflows for a subset of modifications but did not fully resolve residual intersystem differences. Based on these findings, we establish benchmark-derived recommendations for harmonized relative and absolute RNA modification quantification, including guidance for calibration design, quality control, and data reporting. Together, this work provides a methodological framework for reproducible nucleoside LC-MS/MS workflows and establishes a foundation for large-scale comparative epitranscriptomic studies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/739095v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@6e4e98org.highwire.dtl.DTLVardef@1ea13beorg.highwire.dtl.DTLVardef@b65858org.highwire.dtl.DTLVardef@1623337_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

Human 28S rRNA analysed by state-of-the-art oligonucleotide mass spectrometry: benchmarking current capabilities and a call to action for MS-Seq

Oligonucleotide mass spectrometry (MS-Seq) is emerging as a powerful approach for sequence-resolved RNA modification analysis, yet the field lacks standards for experimental workflows, data analysis and reporting. To assess current capabilities, the Human RNome Project Consortium conducted a cross-platform benchmarking study using a common RNA sample. A partial RNase T1 digest of human 28S rRNA was distributed to participating laboratories and analysed using existing LC-MS/MS workflows spanning different chromatographic strategies and mass spectrometers. To enable direct comparison, datasets were analysed using a harmonized NucleicAcidSearchEngine (NASE) workflow. Despite substantial methodological differences, laboratories recovered highly overlapping oligonucleotide sets and generated similar sequence coverage maps with a global coverage of 54.16%, demonstrating reproducible sequence information across platforms under standardized sample and analysis conditions. The benchmark further revealed incomplete sequence coverage, platform-specific differences in data architecture and increased assignment ambiguity during dynamic modification searches. Together with the community consensus developed during the HRPC workshop, these findings define priorities for the field, including improved sensitivity, standardized data analysis and reporting, community repositories, and robust bioinformatic workflows for confident de novo RNA modification discovery. This study provides an experimental benchmark and roadmap toward routine MS-based mapping of the human RNome. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/739151v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1fb1b9borg.highwire.dtl.DTLVardef@d172a5org.highwire.dtl.DTLVardef@bdc185org.highwire.dtl.DTLVardef@1ec1cc9_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Acyl amides derived from a bacterial symbiont control development of its nematode host

Symbiotic bacteria frequently regulate host development through small-molecule signals. In the entomopathogenic Steinernema nematode - Xenorhabdus bacterium symbiosis, which is widely used in biological pest control, the signals that trigger nematode development have remained unknown. Using a phenotypic screen of Xenorhabdus mutants, we identified bacterial acyl amides, which we named stripteamides, as signals required for efficient recovery of Steinernema infective juveniles. Stripteamides are synthesized from phenylethylamine and activated fatty acid substrates by StaS, a previously uncharacterized amide synthase. Mechanistic and structural analyses indicate that StaS evolved from the initiation module of a nonribosomal peptide synthetase (NRPS) and was repurposed to generate signaling metabolites for host development. Stripteamide signaling is conserved across Xenorhabdus species and operates in different Steinernema hosts. These findings reveal a new function for widespread bacterial acyl amides that previously have been shown as cytotoxic and affecting bacterial quorum sensing, highlighting the context dependence of microbial natural product language.

microbiology↗

Host tRNA modifications drive efficient translation of influenza A virus genome and impact host antiviral stress responses

Influenza A virus (IAV), as all other viruses, is completely dependent on the host translation machinery components, including host transfer RNAs (tRNAs), to effectively decode its genome. However, while the human genome is biased towards cytosine (C) and guanosine (G)-ending codons, the IAV genome is skewed towards adenine (A) and uridine (U)-ending codons. Nevertheless, translation of IAVs RNA genome is highly efficient. Here we show that host tRNA and tRNA epitranscriptome dynamics are important regulators of IAV RNA translation and host antiviral responses. We show that the levels of several tRNA modifications, including 5-methylcarboxymethyluridine (mcm5U34) and 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34), and their cognate writers, vary over the course of IAV infection. Additionally, we demonstrate that a set of tRNAs are preferentially recruited to ribosomes upon IAV infection, in line with IAV codon usage requirements. We further show that loss of ELP3, the catalytic subunit of the elongator complex, which is involved in the catalysis of mcm5U34 and of mcm5s2U34, induces tRNA hypomodifications, impairs translation of codon biased IAV genes and triggers the integrated stress response (ISR), interfering with IAV propagation. Taken together, our results uncover the relevance of host tRNAs and their modifications for optimal expression of viral genomes and host antiviral responses, setting the tRNA epitranscriptome as a promising target for the development of host-based antiviral therapies.

molecular biology↗

Drift, selection and convergence in the evolution of a nonribosomal peptide

Nonribosomal peptides play important roles in microbial ecology and medicine, for example as toxins and antibiotics such as penicillin1. Like ordinary proteins, nonribosomal peptides are subject to evolutionary change, which is driven by rampant recombinations of their synthetases2. This makes it difficult to study the evolutionary histories of nonribosomal peptides, because recombination is a serious challenge for phylogenetic inference3. Here we use recombination-aware phylogenetics and ancestral sequence reconstruction to retrace the evolution of GameXPeptides, nonribosomal peptides entomopathogenic bacteria use to kill their insect prey4. By untangling the complex histories of their synthetases, we discover dozens of new GameXPeptides and show striking patterns of structural convergence. In analogy to classic statistical test for natural selection acting on nucleotide mutations, we develop a similar test for whether selection acts to fix recombinations. We provide statistical and experimental evidence of both neutral genetic drift and natural selection in the diversification of GameXPeptides. GameXPeptides variants rapidly evolved highly insect specific toxicities, suggesting that their diversification may be driven by an evolutionary arms race. Our work suggests that small, fast evolving alteration to nonribosomal peptides can overcome host resistance on short timescales, with important implications for the evolution of resistance evading antibiotics.

evolutionary biology↗

Salicylic acid-induced alkalinization of the apoplast requires TRANSMEMBRANE KINASE 1 and results in growth attenuation

The phytohormone salicylic acid (SA) has a key role in regulating plant growth and stress response. In the past, most of the growth-related SA functions have been explained by crosstalk with the master growth regulator auxin. By affecting polarity of auxin transporters, SA changes auxin distribution in the root and inhibits growth of the main root and activates lateral root formation. However, only recently there is evidence emerging that SA impacts growth processes independently of nuclear auxin signalling, possessing yet unknown mechanistic functions. Here we show that SA activity depends on TRANSMEMBRANE KINASE 1 (TMK1) resulting in apoplast alkalinization and growth restriction. SA treatment prevents phosphorylation and activation of plasma membrane (PM) H+-ATPases at the cell surface and does not depend on the auxin receptor Auxin Binding Protein 1 (ABP1). We suggest that alkalinization of the apoplast by SA serves as mechanism to balance stress response and growth.

plant biology↗

Ion-Pair-Free Nanoflow HILIC-MS With RNase Benchmarking for Native RNA

RNA modifications play crucial roles in regulating cellular processes, but comprehensive mapping of the human RNome still remains limited by technological challenges. Mass spectrometry (MS) is a valuable tool to analyse RNA modifications complementing sequencing-based analysis. Current MS-based oligonucleotide workflows have limited sensitivity, requiring micrograms of RNA inputs and thus hindering studies on native RNAs. Additionally, environmentally toxic ion-pairing reagents are often required. Here, we report a highly sensitive, broadly applicable oligonucleotide-MS workflow that enables analysis of nanogram-scale RNA hydrolysates and we benchmark the substrate specificity of three nucleases: RNase T1, RNase 4, and colicin E5. We developed a nano-flow hydrophilic interaction liquid chromatography (HILIC) setup compatible with common MS buffers and coupled this with high-resolution MS. Using modified NucleicAcidSearchEngine (NASE), we confidently assigned RNA hydrolysates with diverse 3-end chemistries. Furthermore, we demonstrate that RNase 4 and colicin E5 efficiently cleave modified RNAs including pseudouridine-containing transcripts, enabling high sequence coverages. Using this workflow, we successfully mapped modifications in 25 ng of native yeast tRNAPhe and verified the sequence of 250 ng of a synthetic mRNA. Overall, our method provides a sensitive, high-resolution platform for oligonucleotide mass spectrometry, facilitating comprehensive analysis of RNA modifications and advancing efforts toward complete epitranscriptomic mapping. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=58 SRC="FIGDIR/small/689004v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@ed3dc3org.highwire.dtl.DTLVardef@171d3d6org.highwire.dtl.DTLVardef@a9ce2org.highwire.dtl.DTLVardef@c1d940_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

ALKBH1 activity in vitro and human cell lines by isotope dilution mass spectrometry

AlkB homolog 1 (ALKBH1) is a member of the AlkB family of Fe(II) and -ketoglutarate (-KG)-dependent dioxygenases, known for its enzymatic activity on various nucleic acid substrates. Its known targets include N1-methyladenosine (m1A), N6-methyladenosine (m6A), N3-methylcytidine (m3C), and 5-methylcytosine (m5C) in RNA, as well as N6-methyladenine (N6-mA, 6mA) in DNA and the histone protein H2A. Moreover, dysregulation or dysfunction of ALKBH1 has been implicated in a broad spectrum of human diseases. In order to shed further light on the substrate scope and role of ALKBH1, we used quantitative mass spectrometry to assess its activity in vitro and in human cell lines. To study ALKBH1 activity on defined substrates in vitro, we enzymatically generated tRNAs specifically carrying the m3C32 (tRNA-ThrUGU and tRNA-SerUCN) and i6A37 (tRNA-SerUCN) modifications. Here we show that ALKBH1 reduces m3C, m1A and m5C in vitro in total extracts of tRNAs, but does not impact on rRNA modifications in human cell lines. However, upon overexpression or siRNA-mediated knock-down of alkbh1 in human cell lines no impact on the modification of total tRNA extracts or specifically enriched RNAs could be observed. In addition, varying the glucose and fetal bovine serum (FBS) concentration in the growth medium of HEK293T cells, in combination with alkbh1 siRNA-mediated knock-down, also shows no impact on the tRNA modification spectra. Based on our data, we conclude that in human cells lines grown under optimal conditions ALKBH1 does not play an important role in the demethylation of tRNAs.

biochemistry↗

Epitranscriptomic control of stress adaptations in Escherichia coli

Bacterial stress responses have been studied at the phenotypic, transcriptional, and translational levels, demonstrating the presence of an "alarm" phase immediately after stress exposure. However, the contributions of RNA modifications during stress adaptation remain largely unexplored. Here, we map the epitranscriptomic changes of Escherichia coli after exposure to oxidative and acid stress using direct RNA sequencing of mRNA, rRNA, and tRNA, combined with mass spectrometry, deletion mutant phenotyping, and single-nucleotide PCR. We identified widespread, dynamic RNA modifications that include central metabolism transcripts and increased levels of rRNA methylations (m4Cm and m5C) under both stresses, with potential consequences for translation. In uncharged tRNAs, stress-specific modifications via the Mnm and Q pathways accumulated at the wobble position; these modifications proved crucial for survival. Together, these findings reveal a multifaceted layer of post-transcriptional regulation, establishing the first comprehensive view of the bacterial epitranscriptome during the alarm phase of stress adaptation.

microbiology↗

Neuroanatomical Correlates of Negative Symptoms in Schizophrenia

BackgroundSchizophrenia is characterized by widespread structural brain abnormalities, but associations between structural abnormalities and negative symptom severity are not well understood. Negative symptoms have been conceptualized in a hierarchical structure of two second-order dimensions--motivation and pleasure (MAP) and expression (EXP)--and five first-order domains: anhedonia, avolition, and asociality (MAP), and blunted affect and alogia (EXP). A better understanding of the neural circuitry underlying negative symptom dimensions and domains is important given their reported association with poor functional outcome and lack of available treatments. Study DesignThe meta-analysis included 1,591 individuals with schizophrenia across 16 samples with structural imaging and Scale for Assessment of Negative Symptoms data. The study generated correlations of cortical thickness and subcortical volumes with the negative symptom dimensions and domains. Study resultsNegative symptoms showed mainly negative associations with cortical thickness and subcortical volumes. The effect sizes were small but there was a pattern of associations in predominantly frontal lobe cortical thickness and limbic subcortical volumes. The regional correlation patterns of cortical thickness and subcortical volumes with symptom domains support the conceptualized hierarchical structure of negative symptoms: correlations of MAP domains were stronger with the MAP than EXP dimension, and vice versa. Exploratory analyses with receptor densities further supported the hierarchy. ConclusionOur findings reveal small but consistent associations between negative symptom dimensions and predominantly prefrontal region cortical thickness, and limbic region volumes. These findings advance our understanding of the network of anatomical regions that may contribute to the severity of negative symptoms in schizophrenia.

neuroscience↗

Purity and stability of modified nucleosides in the context of accurate quantification by LC-MS

Accurate LC-MS (liquid chromatography coupled mass spectrometry) analysis of RNA modifications relies on synthetic nucleoside standards whose chemical integrity determines both qualitative identification and quantitative measurements. While the purity of these standards is typically verified prior to use, their long-term chemical stability during storage has not been systematically investigated. Here, we evaluated the stability of 44 canonical and modified ribonucleosides in aqueous solution during storage at -80 {degrees}C and -20 {degrees}C. Initial quality control confirmed the identity of all tested standards and revealed purity issues in selected compounds, including contamination of 1-methyladenosine (m1A) with 6-methyladenosine (m6A) and the presence of S- and R-isomers of 5-(carboxyhydroxymethyl)-2'-O-methyluridine (mchm5Um). Long-term LC-UV-MS monitoring over 12 months showed that 30 nucleosides remained stable, two were stable for at least six months, and 12 exhibited substantial quantitative changes. Seven nucleosides formed detectable degradation products, most of which could be structurally assigned. Quantum-chemical calculations of reaction free energies for deglycosylation, deamination, deacetylation and desulfurization correlated with the experimentally observed stability trends. Based on these results, we propose a practical guideline for the preparation, storage and analytical quality control of nucleoside standards, including recommendations for purity verification by UV spectroscopy and quantitative NMR. These guidelines provide an experimental framework to improve the robustness and inter-laboratory comparability of LC-MS-based RNA modification analysis.

molecular biology↗

Temporal and spatial profiling of ALKBH5 activity through NAIL-MS and compartmentalized RNA Isolation

RNA modifications, especially m6A in human mRNA, are believed to be dynamically regulated through RNA writers and erasers. The key eraser of m6A is ALKBH5 with its function well proven in vitro, while in vivo evidence is lacking. Here, we set out to exploit nucleic acid isotope labelling coupled mass spectrometry (NAIL-MS) in a pulse chase set-up to study the in vivo function of ALKBH5 on human RNAs. For this we purified poly(A) from whole cell total RNA and found that, steady-state m6A levels and turnover dynamics were nearly identical between WT and ALKBH5 KO, despite clear evidence of robust RNA turnover within an 8-hour labeling period. To assess whether ALKBH5 might act in a compartment-specific manner, we employed an advanced subcellular fractionation strategy, allowing for the isolation of chromatin-associated, nucleoplasmic, and cytoplasmic RNA. These analyses confirmed that m6A accumulates during transcript maturation, with levels peaking in nuclear fractions and decreasing following export to the cytoplasm, supporting the thesis m6A is a dynamic modification. Notably, however, spatial and temporal profiles of m6A distribution and decay were unaffected by ALKBH5 KO. Even in chromatin-associated and nucleolar mRNA, where co-transcriptional modification and potential demethylation would be most plausible, m6A dynamics remained indistinguishable between WT and KO cells in the NAIL-MS context. We thus conclude that ALKBH5 has no major role in mRNA m6A demethylation in HEK 293T cells grown under optimal conditions.

molecular biology↗

Environmental dynamics influence scale cortisol levels in Mexican cavefish

Cortisol is a key hormone involved in stress responses, and its regulation reflects how organisms cope with environmental stressors. While acute stress responses are well studied, much less is known about how cumulative, long-term stress shapes the responses of populations adapted to different habitats. Here, we investigated scale cortisol - a biomarker of long-term stress exposure in fish - in wild and laboratory reared populations of Astyanax mexicanus, a species with surface and cave-dwelling ecotypes adapted to contrasting environments. We measured scale cortisol levels in six populations (four cave and two surface) over two consecutive years, alongside abiotic parameters in the respective habitats. Some cave populations exhibited lower scale cortisol levels than surface fish under both wild and laboratory conditions, suggesting a genetically based enhancement of stress-coping ability or altered cortisol-mediated metabolic and osmoregulatory processes. Moreover, populations experiencing more environmental variability - such as the lake surface habitat and hydrologically dynamic cave systems - showed higher scale cortisol levels and increased inter-individual variation. These results suggest that evolutionary adaptations to different habitats shape long-term stress physiology in A. mexicanus, and they highlight scale cortisol as a valuable tool for assessing how organisms physiologically cope with diverse and extreme environments.

ecology↗

Identification of an Outbreak of Bivalve Transmissible Neoplasia in Soft-Shell Clams (Mya arenaria) in the Puget Sound Using Hemolymph and eDNA Surveys

Bivalve transmissible neoplasia (BTN) is one of three known types of naturally transmissible cancer-- cancers in which the whole cancer cells move from individual to individual, spreading through natural populations. BTN is a lethal leukemia-like cancer that has been observed throughout soft-shell clam (Mya arenaria) populations on the east coast of North America, with two distinct sublineages circulating at low enzootic levels in New England, USA, and Prince Edward Island, Canada. Major cancer outbreaks likely due to Mya arenaria BTN (MarBTN) were reported in 1980s and the 2000s and the disease has been observed since the 1970s, but it has not been observed in populations of this clam species on the US west coast. In 2022, we collected soft-shell clams from several sites in Puget Sound, Washington, USA, and unexpectedly found high prevalence of BTN in two sites (Triangle Cove on Camano Island and near Stanwood in South Skagit Bay). Prevalence of BTN increased in subsequent years, reaching >75% in both sites in 2024, while it was not observed in other sites, suggesting the early stages of a severe disease outbreak following recent introduction. We observed that these cancer cells contain several somatic transposing insertion sites found only in the USA-sublineage of MarBTN, showing that it likely was recently transplanted from New England to this location. We then developed a sensitive environmental DNA (eDNA) assay, using qPCR to target somatic mutations in the MarBTN mitogenome, and showed that MarBTN can be detected in seawater at Triangle Cove, as well as several kilometers outside of the cove. We then used this assay to survey 50 sites throughout Puget Sound, confirming that the disease can be detected at high levels at Triangle Cove and South Skagit Bay, and showing that it extends beyond these known sites. However, while normal soft-shell clam mtDNA was widely detected, MarBTN was undetectable throughout most of Puget Sound and currently remains limited to the South Skagit Bay area and north Port Susan. These results identify a previously unknown severe outbreak of a transmissible cancer due to long-distance transplantation of disease from another ocean, and they demonstrate the utility of eDNA methods to track the spread of BTN through the environment.

ecology↗

Temporal placement of RNA modifications under 5-fluorouracil treatment in human cell culture

Recent studies have explored the dynamic changes in RNA modification across various organisms, often in response to stressors like chemical agents or drugs. Among these, the anticancer drug 5-fluorouracil (5-FU) has been evaluated regarding its impact on RNA and DNA. Although different alterations in RNA modification have been associated with 5-FU, a mechanistic insight into the dynamic effects on RNA modification is missing. In this study, we provide a detailed insight into the dynamic modification changes for tRNA and rRNA of HEK293T cells exposed to 5-FU using Nucleic Acid Isotope Labeling coupled Mass Spectrometry (NAIL-MS). Consistent with existing literature, we observed a constant loss of m5U in newly transcribed tRNA during 5-FU exposure. In addition to m5U, we identified a loss of m5Um and an increase of Um within tRNALysUUU. While cells recover from a 24-hour 5-FU treatment, we found changed abundances of modifications like an increase of mcm5U and m5C and a decrease of m7G and m1A in total tRNA. Moreover, we demonstrate that 5-FU affects various rRNA subtypes, altering both their modification stoichiometry and abundance. Taken together, we use NAIL-MS to deconvolute RNA modification abundance changes caused by drug treatment and we uncover patterns of RNA modification adaptation.

genomics↗

Salicylic Acid restricts cell elongation and induces changes of vacuolar morphology and pH

The phytohormone salicylic acid (SA) is a key factor to balance plant defence as well as growth and development. While its role in plant defence has been investigated for decades, regulation of plant growth and development has only come into focus recently. It has been demonstrated that SA application inhibits growth independently of the established Non-expressor of Pathogenesis Related (NPR) receptors. However, the underlying mechanism of this growth inhibition on the cellular level remains largely elusive. Here we show that SA restricts cell elongation and induces changes of vacuolar morphology and pH. Rapidly upon SA application we observe homotypic vacuole fusion and a significant increase in vacuolar pH. These changes seem to be independent of the phytohormone auxin which has been reported to crosstalk with SA. By increasing vacuolar pH, SA directly impacts basic cellular functions such as vesicle trafficking or nutrient storage, leading eventually to cell size restriction and limited growth. Our results demonstrate an NPR-independent mechanism to attenuate growth, potentially allowing free resources to be relocated to withstand environmental stresses. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/611645v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@af7652org.highwire.dtl.DTLVardef@1813f64org.highwire.dtl.DTLVardef@68e2e8org.highwire.dtl.DTLVardef@92a13_HPS_FORMAT_FIGEXP M_FIG C_FIG Salicylic Acid (SA) triggers a reduction in cell size and leads to a spherical vacuolar phenotype. This morphological change is accompanied by an increase in vacuolar pH, potentially due to the enhanced activity of a glycosylated SA (SAG) H+-antiporter and/or the inhibition of V-ATPase activity. In addition, SA disrupts the polarity of PIN2 auxin transporters, resulting in their uniform distribution across the cell membrane.

plant biology↗

The gut microbiota-immune-brain axis in a wild vertebrate: dynamic interactions and health impacts

The gut microbiota-immune-brain axis is a feedback network which influences diverse physiological processes and plays a pivotal role in overall health and well-being. Although research in humans and laboratory mice has shed light into the associations and mechanisms governing this communication network, evidence of such interactions in wild, especially in young animals, is lacking. We therefore investigated these interactions during early development in a population of common buzzards (Buteo buteo) and their effects on individual condition. In a longitudinal study, we used a multi-marker approach to establish potential links between the bacterial and eukaryotic gut microbiota, a panel of immune assays and feather corticosterone measurements as a proxy for long-term stress. Using Bayesian structural equation modelling, we found no support for feedback between gut microbial diversity and immune or stress parameters. However, we did find strong relationships in the feedback network. Immunity was negatively correlated with corticosterone levels, and microbial diversity was positively associated with nestling body condition. Furthermore, corticosterone levels and eukaryotic microbiota diversity decreased with age while immune activity increased. The absence of conclusive support for the microbiota-immune-brain axis in common buzzard nestlings, coupled with the evidence for stress mediated immunosuppression, suggests a dominating role of stress-dominated maturation of the immune system during early development. Confounding factors inherent to wild systems and developing animals might override associations known from adult laboratory model subjects. The positive association between microbial diversity and body condition indicates the potential health benefits of possessing a diverse and stable microbiota.

microbiology↗