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Petersen, M.

Publications and source records attributed to Petersen, M..

At least 19 recordsLinked to original sources

TPS Expression, Not Copy Number, Explains Aroma Diversity among Grapevine (Vitis vinifera L.) Cultivars

Terpenoids are major contributors to grapevine berry and wine aroma, with mono- and sesquiterpenoids exhibiting substantial variation among cultivars. However, the genetic basis of cultivar-specific terpenoid profiles remains only partially understood due to gene duplications that expanded the terpenoid synthase (TPS) gene family across different cultivars. Here, we compared haplotype-resolved genome assemblies for seven cultivars to analyze copy number variation and expression profiles of terpenoid biosynthesis genes and terpenoid accumulation throughout flower and berry development. These assemblies resolved duplicated TPS loci at the haplotype level, revealing extensive copy number variation across cultivars and between haplotypes within a cultivar, with up to 44 mono-TPS genes on a single haplotype. We identified eight specific monoterpenoids as key drivers of cultivar-specific profiles in ripe berries. Total TPS transcript abundance correlated strongly with total terpenoid accumulation over time. In contrast, TPS copy number was largely decoupled from both expression and terpenoid accumulation, indicating that expression regulation, rather than gene dosage, underlies aroma differences among cultivars. Transcript-metabolite network analysis revealed both expected correlations between specific TPS genes and putative products as well as novel associations. We functionally validated selected candidate TPS in Nicotiana benthamiana, characterizing -farnesene, {beta}-ocimene, and multi-product -terpineol synthases. The in vivo characterization demonstrated that minor sequence variations can alter catalytic activity and product profile. Together, these findings show that the extensive duplication of TPS genes in grapevine does not itself determine terpenoid output; instead, cultivar-specific aroma arises from how these genes are expressed and from sequence differences that shape enzyme activity.

plant biology↗

Capillary-based Subcellular Sampling Uncovers the Stress Granule Proteome in Single Cells

Many diseases arise from dysfunction within specific organelles or biomolecular condensates, highlighting the value of analysing proteins at subcellular resolution to uncover new biological mechanisms. We report a novel capillary-based subcellular sampling workflow coupled with liquid chromatography-mass spectrometry (LC-MS) for proteomic analysis of defined subcellular regions of individual cells. We applied this methodology to stress granules (SGs), membrane-less biomolecular condensates that form in response to cellular stress (including viral infection), and are implicated in infection, neuropathology and cancer. Comprehensive characterisation of SG protein composition remains limited by technical challenges associated with bulk purification, including loss of spatial context, dynamic behaviour and contamination from cytosolic material. Using our novel method, we identified a high-confidence set of 405 SG-associated proteins, including 46 established SG residents alongside numerous previously unreported candidates. Functional enrichment analysis revealed pathways consistent with known SG biology, while comparison with an independent cytosolic proteome dataset demonstrated minimal overlap, supporting the specificity of the sampling strategy. Selected novel SG protein candidates (AHNAK2, DDX39B, NUDT1 and FKBP2) were validated using immunofluorescence microscopy. These findings establish capillary-based subcellular sampling as a viable approach for proteomic analysis of SGs with preserved spatial context and provide a framework for analysing other subcellular compartments. Table of contentsWe report an LC-MS-based capillary sampling workflow for proteomic analysis of subcellular structures within single cells. This methodology identified 405 high-confidence stress granule-associated proteins, including 46 previously established and numerous novel candidates. The approach demonstrated high specificity and preserved spatial context, expanding the capabilities of subcellular proteomics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=55 SRC="FIGDIR/small/724230v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1fa0bb0org.highwire.dtl.DTLVardef@1158524org.highwire.dtl.DTLVardef@1d82812org.highwire.dtl.DTLVardef@2ee4d9_HPS_FORMAT_FIGEXP M_FIG C_FIG Figure made in Biorender.com.

cell biology↗

A moss N-Acetyltransferase-MAPK protein controls 2D to 3D developmental transition via acetylation and phosphorylation changes

Post-translational modifications (PTMs) finetune plant responses to developmental and environmental cues by impacting protein activity, stability, localization and interaction landscape. In this study we identified a moss specific protein which combines two common PTMs: acetylation and phosphorylation. This protein originated from the fusion of a MAPK with an N-acetyltransferase, for which we named it Rosetta NATD-MAPK 1 (RAK1). Using biochemical methods, we demonstrated that RAK1 has acetyltransferase activity that is enhanced by activation of its MAPK domain. Phenotypical studies of rak1 knockout mutants revealed a role for RAK1 in the regulation of the 2D-to-3D growth transition. Through Mass Spectrometry we verified that defective 2D-to-3D transition in the mutants was caused by differentially regulated acetylation and phosphorylation events associated to metabolic reprogramming and 3D differentiation. Collectively, this study uncovers a previously unknown multidomain protein and provides insights into the interplay of PTMs during developmental reprogramming. TeaserAcetylation and phosphorylation changes modulate the 2D to 3D developmental transition in Physcomitrium patens.

plant biology↗

Trypstatin as a Novel TMPRSS2 Inhibitor with Broad-Spectrum 1 Efficacy Against Corona and Influenza Viruses

Respiratory viruses, such as SARS-CoV-2 and influenza, exploit host proteases like TMPRSS2 for entry, making TMPRSS2 a prime antiviral target. Here, we report the identification and characterization of Trypstatin, a 61-amino acid Kunitz-type protease inhibitor derived from human hemofiltrate. Trypstatin inhibits TMPRSS2 and related proteases, with IC50 values in the nanomolar range, comparable to the small molecule inhibitor camostat mesylate. In vitro assays demonstrated that Trypstatin effectively blocks spike-driven entry of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and hCoV-NL63, as well as hemagglutinin-mediated entry of influenza A and B viruses. In primary human airway epithelial cultures, Trypstatin significantly reduced SARS-CoV-2 replication and retained activity in the presence of airway mucus. In vivo, intranasal administration of Trypstatin to SARS-CoV-2-infected Syrian hamsters reduced viral titers and alleviated clinical symptoms. These findings highlight Trypstatins potential as a broad-spectrum antiviral agent against TMPRSS2-dependent respiratory viruses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/632953v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1b90566org.highwire.dtl.DTLVardef@117293org.highwire.dtl.DTLVardef@1794959org.highwire.dtl.DTLVardef@1be9090_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

BrainACTIV: Identifying visuo-semantic properties driving cortical selectivity using diffusion-based image manipulation

The human brain efficiently represents visual inputs through specialized neural populations that selectively respond to specific categories. Advancements in generative modeling have enabled data-driven discovery of neural selectivity using brain-optimized image synthesis. However, current methods independently generate one sample at a time, without enforcing structural constraints on the generations; thus, these individual images have no explicit point of comparison, making it hard to discern which image features drive neural response selectivity. To address this issue, we introduce Brain Activation Control Through Image Variation (BrainACTIV), a method for manipulating a reference image to enhance or decrease activity in a target cortical region using pretrained diffusion models. Starting from a reference image allows for fine-grained and reliable offline identification of optimal visuo-semantic properties, as well as producing controlled stimuli for novel neuroimaging studies. We show that our manipulations effectively modulate predicted fMRI responses and agree with hypothesized preferred categories in established regions of interest, while remaining structurally close to the reference image. Moreover, we demonstrate how our method accentuates differences between brain regions that are selective to the same category, and how it could be used to explore neural representation of brain regions with unknown selectivities. Hence, BrainACTIV holds the potential to formulate robust hypotheses about brain representation and to facilitate the production of naturalistic stimuli for neuroscientific experiments.

neuroscience↗

Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants

Selective autophagy is a fundamental protein quality control pathway that safeguards proteostasis by degrading damaged or surplus cellular components, particularly under stress. This process is orchestrated by selective autophagy receptors (SARs) that direct specific cargo for degradation. While significant strides have been made in understanding the molecular framework of selective autophagy, the diversity of SAR repertoires across species remain largely unexplored. Through a comparative interactome analysis across five model organisms, we identified a suite of conserved and lineage-specific SAR candidates. Among these, we validated CESAR as a conserved SAR critical for proteostasis under heat stress. CESAR specifically facilitates the degradation of hydrophobic, ubiquitinated protein aggregates and is indispensable for heat stress tolerance. Our study offers a rich resource for SAR discovery and positions CESAR as a pivotal regulator of proteostasis, with broad implications for improving stress resilience in plants.

plant biology↗

BZR1 promotes pluripotency acquisition and callus development through direct regulation of ARF7 and ARF19

Plants have the remarkable ability to regenerate whole organisms through formation of pluripotent cell masses from somatic cells. Cellular programs leading to fate change of somatic to pluripotent cells resembles lateral root (LR) formation and both are chiefly regulated by auxin. Brassinosteroid signalling also plays an important role during LR formation but little is known about the direct link between auxin and brassinosteroid components, such as BZR1 and BES1, in relation to pluripotency acquisition. Here we show that gain-of-function mutants bzr1-D and bes1-D exhibit altered callus formation, yet disruption of these transcription factors does not produce major changes to callus formation or de novo organogenesis. Moreover, our data reveals that BZR1 displays enhanced expression in callus tissue and directly binds to the promoters of ARF7 and ARF19, two master pluripotency regulators, leading to their enhanced transcription. Remarkably, we see abrogation of callus formation in bzr1-D upon disruption of ARF7 and ARF19, emphasizing that BZR1 callus phenotype is dependent on these two auxin signalling components. In conclusion, we depict a link between ARF7, ARF19 and BZR1 in the promotion of pluripotency acquisition, portraying BZR1 as a major supporting factor in callus formation. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

plant biology↗

Internal regulation between constitutively expressed T cell coinhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants

Several coinhibitory receptors are upregulated upon activation, whereas a small number of coinhibitory receptors are expressed constitutively by naive T cells. The relationship between constitutively expressed coinhibitors is unknown. We found an inverse relationship between two constitutively expressed coinhibitors, CD5 and BTLA; BTLA expression was low in the thymus and high in the periphery, corresponding respectively with high and low CD5 expression. Germline or induced deletion of Btla in somatic cells demonstrated a causal relationship between BTLA expression and CD5 levels in T cells of central and peripheral lymphoid tissues. The effect of BTLA on CD5 expression on thymic and peripheral CD4 T cells was due to BTLA signaling, rather than signaling by its ligand, the herpes virus mediator (HVEM). Regulation was maintained in mice with a non-signaling HVEM mutant but was lost in Tnfrsf14-/- (Hvem-/-) mice. Increased CD5 levels have been positively associated with increased recognition of self-peptide MHC complexes. Thus, control of CD5 expression by BTLA signals early in T cell ontogeny suggested that BTLA might be important for establishing self-tolerance in newly generated T cells. Consistent with this concept, we found that BTLA, as well as the inducible coinhibitor PD-1, were needed post thymic selection in recent thymic emigrants (RTE) to establish self-tolerance. RTE lacking BTLA caused a multiorgan autoimmune disease whose development required CD4 T cells and MHC class II. Together, our findings identify a negative regulatory pathway allowing constitutively expressed coinhibitory receptors to calibrate their expression in thymic T cell differentiation. Expression of constitutive and induced coinhibitory receptors is needed to establish tolerance in the periphery for RTE.

immunology↗

Chewing Through Challenges: Exploring the Evolutionary Pathways to Wood-Feeding in Insects

Decaying wood, while an abundant and stable resource, presents considerable nutritional challenges due to its structural rigidity, chemical recalcitrance, and low nitrogen content. Despite these challenges, certain insect lineages have successfully evolved saproxylophagy (consuming and deriving sustenance from decaying wood), impacting nutrient recycling in ecosystems and carbon sequestration dynamics. This study explores the uneven phylogenetic distribution of saproxylophagy across insects and delves into the evolutionary origins of this trait in disparate insect orders. Employing a comprehensive analysis of gut microbiome data, encompassing both previously published datasets and newly generated data, from both saproxylophagous insects and their non-saproxylophagous relatives, this Hypothesis paper discusses the broader phylogenetic context and potential morphological, physiological, and symbiotic adaptations necessary for this dietary specialization. The study proposes the "Detritivore-First Hypothesis," suggesting an evolutionary pathway to saproxylophagy through detritivory, and highlights the critical role of symbiotic gut microbiomes in the digestion of decaying wood. The article aims to provide a deeper understanding of the macroevolutionary landscape and mechanisms underpinning the multiple origins and distribution of saproxylophagy in insects.

evolutionary biology↗

A Latent Clinical-anatomical Dimension Relating Metabolic Syndrome to Brain Morphology - Evidence from a Multivariate Imaging Analysis of 40,087 Individuals

The link between metabolic syndrome (MetS) and neurodegenerative as well cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, cortical morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

neuroscience↗

Is resting state fMRI better than individual characteristics at predicting cognition?

Changes in spontaneous brain activity at rest provide rich information about behavior and cognition. The mathematical properties of resting-state functional magnetic resonance imaging (rsfMRI) are a depiction of brain function and are frequently used to predict cognitive phenotypes. Individual characteristics such as age, gender, and total intracranial volume (TIV) play an important role in predictive modeling of rsfMRI (for example, as "confounders" in many cases). It is unclear, however, to what extent rsfMRI carries independent information from the individual characteristics that is able to predict cognitive phenotypes. Here, we used predictive modeling to thoroughly examine the predictability of four cognitive phenotypes in 20,000 healthy UK Biobank subjects. We extracted common rsfMRI features of functional brain connectivity (FC) and temporal complexity (TC). We assessed the ability of these features to predict outcomes in the presence and absence of age, gender, and TIV. Additionally, we assessed the predictiveness of age, gender, and TIV only. We find TC and FC features to perform comparably with regard to predicting cognitive phenotypes. As compared to rsfMRI features, individual characteristics provide systematically better predictions with smaller sample sizes and, to some extent, in larger cohorts. It is also consistent across different levels of inherent temporal noise in rsfMRI. Our results suggest that when the objective is to perform cognitive predictions as opposed to understanding the relationship between brain and behavior, individual characteristics are more applicable than rsfMRI features.

neuroscience↗

Sensing of viral RNA in plants via a DICER-LIKE Ribonuclease

Sensors of intracellular double-stranded RNA are central components of metazoan innate antiviral immunity, but such sensors have not been identified in plants. RNA interference (RNAi) constitutes a potent plant antiviral defense mechanism that relies on conversion of viral RNA into small interfering RNAs by two DICER-LIKE (DCL) ribonucleases, DCL4 and DCL2. Here, we show that while plant DCL4 is dedicated to RNAi, cytoplasmic dicing by DCL2 also triggers RNAi-independent defense gene expression via at least two intracellular nucleotide-binding domain/leucine-rich repeat (NLR) immune receptors. Combined DCL4/NLR inactivation abrogates basal resistance to a positive strand RNA virus. Our results redefine the basis of plant antiviral immunity, including autoimmunity as an explanation for DCL2-dependent growth arrest in dcl and RNA decay mutants in several plant species. One sentence summaryThe plant immune system uses Dicer-like ribonucleases for both antiviral RNA interference and double-stranded RNA sensing.

plant biology↗

Tyramine and its AmTYR1 receptor modulate attention in honey bees (Apis mellifera)

Animals must learn to ignore stimuli that are irrelevant to survival and attend to ones that enhance survival. When a stimulus regularly fails to be associated with an important consequence, subsequent excitatory learning about that stimulus can be delayed, which is a form of non-associative conditioning called latent inhibition. Honey bees show latent inhibition toward an odor they have experienced without association with food reinforcement. Moreover, individual honey bees from the same colony differ in the degree to which they show latent inhibition, and these individual differences have a genetic basis. To investigate the mechanisms that underly individual differences in latent inhibition, we selected two honey bee lines for high and low latent inhibition, respectively. We crossed those lines and mapped a Quantitative Trait Locus (QTL) for latent inhibition to a region of the genome that contains the tyramine receptor gene Amtyr11. We then show that disruption of Amtyr1 signaling either pharmacologically or through RNAi qualitatively changes the expression of latent inhibition but has little effect on appetitive conditioning, and these results suggest that AmTYR1 modulates inhibitory processing in the CNS. Electrophysiological recordings from the brain during pharmacological blockade are consistent with a model that AmTYR1 indirectly regulates Hebbian plasticity at inhibitory synapses in the CNS. Finally, sequencing Amtyr1 and its up and downstream genomic region for high and low line workers suggested that individual differences might arise from variation in transcriptional control rather than structural changes in the coding region. Our results therefore identify a distinct modulatory pathway for this type of non-associative learning, and we propose a model for how it modulates Hebbian plasticity at defined synapses in the CNS. We have shown elsewhere how this modulation also underlies potentially adaptive intracolonial learning differences among individuals that benefit colony survival.

animal behavior and cognition↗

Brain Network Architecture Constrains Age-related Cortical Thinning

Age-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including "hotspots" of strong age effects located in brain areas with high centrality (structural network hubs). Regional age-related differences were furthermore strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences as well as its change throughout the later lifespan was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks might act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.

neuroscience↗

PAT mRNA decapping factors function specifically and redundantly during development in Arabidopsis

Evolutionarily conserved PAT1 proteins activate mRNA decay through binding mRNA and recruiting decapping enzymes and other factors hence optimize transcriptional reprogramming during development. Here, we generated multiple mutants of pat1 (Protein Associated with Topoisomerase II), path1 and path2 and inspected their growth and leaf morphology phenotype. pat triple mutants exhibit extreme stunted growth and all mutants with pat1 exhibit leaf serration while mutants with pat1 and path1 all display short petioles. All 3 PATs can be found localized to Prossessing Bodies (PBs) upon auxin treatment and RNA-seq analysis indicate that all 3 PATs redundantly regulate auxin responses. Moreover, shade avoidance and NAC genes are misregulated in pat1path1 double and pat triple mutants suggesting PAT1 and PATH1 function in petiole elongation and leaf patterning. In conclusion, PAT proteins exhibit both specific and overlapping functions during different stages of plant growth and our observations underpin the importance of the mRNA decay machinery for proper development.

plant biology↗

Intrasexual cuticular hydrocarbon dimorphism in a wasp sheds light on hydrocarbon biosynthesis genes in Hymenoptera

Cuticular hydrocarbons (CHCs) cover the cuticle of insects and serve as desiccation barrier and for chemical communication. While the main enzymatic steps of CHC biosynthesis are well understood, few of the underlying genes have been identified. Here we show how exploitation of intrasexual CHC dimorphism in a mason wasp, Odynerus spinipes, in combination with whole-genome sequencing and comparative transcriptomics facilitated identification of such genes. RNAi-mediated knockdown of twelve candidate gene orthologs in honey bees, Apis mellifera, confirmed nine genes impacting CHC profile composition. Most of them have predicted functions consistent with current knowledge of CHC metabolism. However, we found first-time evidence for a fatty acid amide hydrolase also influencing CHC profile composition. In situ hybridization experiments furthermore suggest trophocytes participating in CHC biosynthesis. Our results set the base for experimental CHC profile manipulation in Hymenoptera and imply that the evolutionary origin of CHC biosynthesis predates the arthropods colonization of land.

molecular biology↗

Transposable elements in the genome of the lichen-forming fungus Umbilicaria pustulata, and their distribution in different climate zones along elevation

BackgroundTransposable elements (TEs) are an important source of genome plasticity across the tree of life. Accumulating evidence suggests that TEs may not be randomly distributed in the genome. Drift and natural selection are important forces shaping TE distribution and accumulation, acting directly on the TE element or indirectly on the host species. Fungi, with their multifaceted phenotypic diversity and relatively small genome size, are ideal models to study the role of TEs in genome evolution and their impact on the hosts ecological and life history traits. Here we present an account of all TEs found in a high-quality reference genome of the lichen-forming fungus Umbilicaria pustulata, a macrolichen species comprising two climatic ecotypes: Mediterranean and cold-temperate. We trace the occurrence of the newly identified TEs in populations along three replicated elevation gradients using a Pool-Seq approach, to identify TE insertions of potential adaptive significance. ResultsWe found that TEs cover 21.26 % of the 32.9 Mbp genome, with LTR Gypsy and Copia clades being the most common TEs. Out of a total of 182 TE copies we identified 28 insertions displaying consistent insertion frequency differences between the two host ecotypes across the elevation gradients. Most of the highly differentiated insertions were located near genes, indicating a putative function. ConclusionsThis pioneering study into the content and climate niche-specific distribution of TEs in a lichen-forming fungus contributes to understanding the roles of TEs in fungal evolution. Particularly, it may serve as a foundation for assessing the impact of TE dynamics on fungal adaptation to the abiotic environment, and the impact of TE activity on the evolution and maintenance of a symbiotic lifestyle.

genomics↗

The evolution of the phenylpropanoid pathway entailed pronounced radiations and divergences of enzyme families

Land plants constantly respond to fluctuations in their environment. Part of their response is the production of a diverse repertoire of specialized metabolites. One of the foremost sources for metabolites relevant to environmental responses is the phenylpropanoid pathway, which was long thought to be a land plant-specific adaptation shaped by selective forces in the terrestrial habitat. Recent data have however revealed that streptophyte algae, the algal relatives of land plants, have candidates for the genetic toolkit for phenylpropanoid biosynthesis and produce phenylpropanoid-derived metabolites. Using phylogenetic and sequence analyses, we here show that the enzyme families that orchestrate pivotal steps in phenylpropanoid biosynthesis have independently undergone pronounced radiations and divergence in multiple lineages of major groups of land plants; sister to many of these radiated gene families are streptophyte algal candidates for these enzymes. These radiations suggest a high evolutionary versatility in the enzyme families involved in the phenylpropanoid-derived metabolism across embryophytes. We suggest that this versatility likely translates into functional divergence and may explain the key to one of the defining traits of embryophytes: a rich specialized metabolism.

plant biology↗