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At least 109 records · Page 6

Conservation of endo -glucanase 16 (EG16) activity across highly divergent plant lineages

Plant cell walls are highly dynamic structures that are composed predominately of polysaccharides. As such, endogenous carbohydrate active enzymes (CAZymes) are central to the synthesis and subsequent modification of plant cells during morphogenesis. The endo-glucanase 16 (EG16) members constitute a distinct group of plant CAZymes, angiosperm orthologs of which were recently shown to have dual β-glucan/xyloglucan hydrolase activity. Molecular phylogeny indicates that EG16 members comprise a sister clade with a deep evolutionary relationship to the widely studied apoplastic xyloglucan endo-transglycosylases/hydrolases (XTH). A cross-genome survey indicated that EG16 members occur as a single ortholog across species and are widespread in early diverging plants, including the non-vascular bryophytes, for which functional data were previously lacking. Remarkably, enzymological characterization of an EG16 ortholog from the model moss Physcomitrella patens (PpEG16) revealed that EG16 activity and sequence/structure are highly conserved across 500 million years of plant evolution, vis-à-vis orthologs from grapevine and poplar. Ex vivo biomechanical assays demonstrated that the application of EG16 gene products caused abrupt breakage of etiolated hypocotyls rather than slow extension, thereby indicating a mode-of-action distinct from endogenous expansins and microbial endo-glucanases. As a result, the biochemical data presented here will inform future genomic, genetic, and physiological studies of EG16 enzymes.

59 BASIC BIOLOGICAL SCIENCES↗

Soil metabolome response to whole-ecosystem warming at the Spruce and Peatland Responses under Changing Environments experiment

In this study, a suite of complementary environmental geochemical analyses, including NMR and gas chromatography-mass spectrometry (GC-MS) analyses of central metabolites, Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) of secondary metabolites, and lipidomics, was used to investigate the influence of organic matter (OM) quality on the heterotrophic microbial mechanisms controlling peatland CO2, CH4, and CO2:CH4 porewater production ratios in response to climate warming. Our investigations leverage the Spruce and Peatland Responses under Changing Environments (SPRUCE) experiment, where air and peat warming were combined in a whole-ecosystem warming treatment. We hypothesized that warming would enhance the production of plant-derived metabolites, resulting in increased labile OM inputs to the surface peat, thereby enhancing microbial activity and greenhouse gas production. Because shallow peat is most susceptible to enhanced warming, increases in labile OM inputs to the surface, in particular, are likely to result in significant changes to CO2 and CH4 dynamics and methanogenic pathways. In support of this hypothesis, significant correlations were observed between metabolites and temperature consistent with increased availability of labile substrates, which may stimulate more rapid turnover of microbial proteins. An increase in the abundance of methanogenic genes in response to the increase in the abundance of labile substrates was accompanied by a shift toward acetoclastic and methylotrophic methanogenesis. Our results suggest that as peatland vegetation trends toward increasing vascular plant cover with warming, we can expect a concomitant shift toward increasingly methanogenic conditions and amplified climate–peatland feedbacks.

Wilson, Rachel M.↗

The C2 domain augments Ras GTPase-activating protein catalytic activity

Regulation of Ras GTPases by GTPase-activating proteins (GAPs) is essential for their normal signaling. Nine of the ten GAPs for Ras contain a C2 domain immediately proximal to their canonical GAP domain, and in RasGAP (p120GAP, p120RasGAP;RASA1) mutation of this domain is associated with vascular malformations in humans. Here, we show that the C2 domain of RasGAP is required for full catalytic activity toward Ras. Analyses of the RasGAP C2-GAP crystal structure, AlphaFold models, and sequence conservation reveal direct C2 domain interaction with the Ras allosteric lobe. This is achieved by an evolutionarily conserved surface centered around RasGAP residue R707, point mutation of which impairs the catalytic advantage conferred by the C2 domain in vitro. In mice,R707Cmutation phenocopies the vascular and signaling defects resulting from constitutive disruption of theRASA1gene. In SynGAP, mutation of the equivalent conserved C2 domain surface impairs catalytic activity. Our results indicate that the C2 domain is required to achieve full catalytic activity of GAPs for Ras.

Science & Technology - Other Topics↗

Insights into community of photosynthetic microorganisms from permafrost

ABSTRACT This work integrates cultivation studies of Siberian permafrost and analyses of metagenomes from different locations in the Arctic with the aim of obtaining insights into the community of photosynthetic microorganisms in perennially frozen deposits. Cyanobacteria and microalgae have been described in Arctic aquatic and surface soil environments, but their diversity and ability to withstand harsh conditions within the permafrost are still largely unknown. Community structure of photosynthetic organisms in permafrost sediments was explored using Arctic metagenomes available through the MG-RAST. Sequences affiliated with cyanobacteria represented from 0.25 to 3.03% of total sequences, followed by sequences affiliated with Streptophyta (algae and vascular plants) 0.01–0.45% and Chlorophyta (green algae) 0.01–0.1%. Enrichment and cultivation approaches revealed that cyanobacteria and green algae survive in permafrost and they could be revived during prolonged incubation at low light intensity. Among photosynthetic microorganisms isolated from permafrost, the filamentous Oscillatoria-like cyanobacteria and unicellular green algae of the genus Chlorella were dominant. Our findings suggest that permafrost cyanobacteria and green algae are expected to be effective members of the re-assembled community after permafrost thawing and soil collapse.

Vishnivetskaya, Tatiana A.↗

Differential response of the photosynthetic machinery to dehydration in older and younger resurrection plants

Abstract A group of vascular plants called homoiochlorophyllous resurrection plants evolved unique capabilities to protect their photosynthetic machinery against desiccation-induced damage. This study examined whether the ontogenetic status of the resurrection plant Craterostigma pumilum has an impact on how the plant responds to dehydration at the thylakoid membrane level to prepare cells for the desiccated state. Thus, younger plants (<4 months) were compared with their older (>6 months) counterparts. Ultrastructural analysis provided evidence that younger plants suppressed senescence-like programs that are realized in older plants. During dehydration, older plants degrade specific subunits of the photosynthetic apparatus such as the D1 subunit of PSII and subunits of the cytochrome b6f complex. The latter leads to a controlled down-regulation of linear electron transport. In contrast, younger plants increased photoprotective high-energy quenching mechanisms and maintained a high capability to replace damaged D1 subunits. It follows that depending on the ontogenetic state, either more degradation-based or more photoprotective mechanisms are employed during dehydration of Craterostigma pumilum.

Plant Sciences↗

Stress-regulated Arabidopsis GAT2 is a low affinity γ-aminobutyric acid transporter

Abstract The four-carbon non-proteinogenic amino acid γ-aminobutyric acid (GABA) accumulates to high levels in plants in response to various abiotic and biotic stress stimuli, and plays a role in C:N balance, signaling, and as a transport regulator. Expression in Xenopus oocytes and voltage-clamping allowed the characterization of Arabidopsis GAT2 (At5g41800) as a low affinity GABA transporter with a K0.5GABA ~8 mM. l-Alanine and butylamine represented additional substrates. GABA-induced currents were strongly dependent on the membrane potential, reaching the highest affinity and highest transport rates at strongly negative membrane potentials. Mutation of Ser17, previously reported to be phosphorylated in planta, did not result in altered affinity. In a short-term stress experiment, AtGAT2 mRNA levels were up-regulated at low water potential and under osmotic stress (polyethylene glycol and mannitol). Furthermore, AtGAT2 promoter activity was detected in vascular tissues, maturating pollen, and the phloem unloading region of young seeds. Even though this suggested a role for AtGAT2 in long-distance transport and loading of sink organs, under the conditions tested neither AtGAT2-overexpressing plants, atgat2 or atgat1 T-DNA insertion lines, nor atgat1 atgat2 doubleknockout mutants differed from wild-type plants in growth on GABA, amino acid levels, or resistance to salt and osmotic stress.

Plant Sciences↗

JACC: Leveraging HPC Meta-Programming and Performance Portability with the Just-in-Time and LLVM-based Julia Language

We present JACC (Julia for Accelerators), the first high-level, and performance-portable model for the just-in-time and LLVM-based Julia language. JACC provides a unified and lightweight front end across different back ends available in Julia, enabling the same Julia code to run efficiently on many HPC CPU and GPU targets. We evaluated the performance of JACC for common HPC kernels as well as for the most computationally demanding kernels used in applications, HPCCG, a supercomputing benchmark test for sparse domains, and HARVEY, a blood flow simulator to assist in the diagnosis and treatment of patients suffering from vascular diseases. We carried out the performance analysis on the most advanced US DOE supercomputers: Aurora, Frontier, and Perlmutter. Overall, we show that JACC has a negligible overhead versus vendor-specific solutions, reporting GPU speedups with no extra cost to programmability.

Valero-Lara, Pedro↗

Divergent species-specific impacts of whole ecosystem warming and elevated CO 2 on vegetation water relations in an ombrotrophic peatland

Boreal peatland forests have relatively low species diversity and thus impacts of climate change on one or more dominant species could shift ecosystem function. Despite abundant soil water availability, shallowly rooted vascular plants within peatlands may not be able to meet foliar demand for water under drought or heat events that increase vapor pressure deficits while reducing near surface water availability, although concurrent increases in atmospheric CO 2 could buffer resultant hydraulic stress. We assessed plant water relations of co-occurring shrub (primarily Rhododendron groenlandicum and Chamaedaphne calyculata) and tree (Picea mariana and Larix laricina) species prior to, and in response to whole ecosystem warming (0 to +9°C) and elevated CO 2 using 12.8-m diameter open-top enclosures installed within an ombrotrophic bog. Water relations (water potential [Ψ], turgor loss point, foliar and root hydraulic conductivity) were assessed prior to treatment initiation, then Ψ and peak sap flow (trees only) assessed after 1 or 2 years of treatments. Under the higher temperature treatments, L. laricina Ψ exceeded its turgor loss point, increased its peak sap flow, and was not able to recover Ψ overnight. In contrast, P. mariana operated below its turgor loss point and maintained constant Ψ and sap flow across warming treatments. Similarly, C. calyculata Ψ stress increased with temperature while R. groenlandicum Ψ remained at pretreatment levels. The more anisohydric behavior of L. laricina and C. calyculata may provide greater net C uptake with warming, while the more conservative P. mariana and R. groenlandicum maintained greater hydraulic safety. These latter species also responded to elevated CO 2 by reduced Ψ stress, which may also help limit hydraulic failure during periods of extreme drought or heat in the future. Along with Sphagnum moss, the species-specific responses of peatland vascular communities to drier or hotter conditions will shape boreal peatland composition and function in the future.

59 BASIC BIOLOGICAL SCIENCES↗

Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature

Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT 2A and 5-HT 1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77 mg ergovaline/hd/d) or a control total mixed ration (CON; 0 mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein were exposed to increasing concentrations of a 5-HT 1B/1D agonist and 5-HT 2A agonist. The 5-HT 1B/1D agonist did not stimulate a contractile response in artery or vein or either gestation time point. 5-HT 2A agonist caused large responses in artery with greatest occurring at d-110 and decreasing in magnitude as days of gestation increased ( p < 0.05). On d-110 and 133 of gestation, arteries from CON ewes had greater contractile response than arteries collected from E+ ewes ( p < 0.05). Veins responded to increasing concentrations of the 5-HT 2A agonist. Maximal d-110 vein response was greater than d-133 when exposed to 5-HT 2A agonist ( p < 0.05). Unlike the artery, veins from E+ ewes had greater d-133 contractile response than CON ( p < 0.05). Vascular contractions of umbilical artery and vein are induced by 5-HT 2A receptor activity and not 5-HT 1B/1D . Umbilical artery 5-HT 2A receptor activity was more sensitive to seed treatment and could be responsible for ergot alkaloid-induced intra-uterine growth restriction.

Toxicology↗

Locating Methyl-Etherified and Methyl-Esterified Uronic Acids in the Plant Cell Wall Pectic Polysaccharide Rhamnogalacturonan II

Rhamnogalacturonan II (RG-II) is a structurally complex pectic polysaccharide that exists as a borate ester cross-linked dimer in the cell walls of all vascular plants. The glycosyl sequence of RG-II is largely conserved, but there is evidence that galacturonic acid (GalA) methyl etherification and glucuronic acid (GlcA) methyl esterification vary in the A sidechain across plant species. Methyl esterification of the galacturonan backbone has also been reported but not confirmed. Here we describe a new procedure, utilizing aq. sodium borodeuteride (NaBD4)-reduced RG-II, to identify the methyl esterification status of backbone GalAs. Our data suggest that up to two different GalAs are esterified in the RG-II backbone. We also adapted a procedure based on methanolysis and NaBD4 reduction to identify 3-, 4-, and 3,4-O-methyl GalA in RG-II. These data, together with matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF) MS analysis of sidechain A generated from selected RG-IIs and their NaBD4-reduced counterparts, suggest that methyl etherification of the ß-linked GalA and methyl esterification of the GlcA are widespread. Nevertheless, the extent of these modifications varies between plant species. Our analysis of the sidechain B glycoforms in RG-II from different dicots and nonpoalean monocots suggests that this sidechain has a minimum structure of an O-acetylated hexasaccharide (Ara-[MeFuc]-Gal-AceA-Rha-Api-). To complement these studies, we provide further evidence showing that dimer formation and stability in vitro is cation and borate dependent. Taken together, our data further refine the primary sequence and sequence variation of RG-II and provide additional insight into dimer stability and factors controlling dimer self-assembly.

BASIC BIOLOGICAL SCIENCES↗

SPRUCE Aboveground Vegetation Coverage in Root Ingrowth Core Plots, Marcell Experimental Forest, Minnesota, August 2022

This dataset contains vegetation survey measurements from root ingrowth core plots (Määttä et al. 2025) inside SPRUCE Experiment plots at the Marcell Experimental Forest in northern Minnesota. Vegetation surveys were conducted in 0.25 meter2 plots containing root ingrowth cores on August 8th and 9th, 2022 (2022-08-08 to 2022-08-09). The warming and elevated carbon dioxide (CO2) treatments in the dataset include the full treatment gradient: +0 degrees Celsius (C) (+0 and +500 parts per million (ppm) elevated CO2), +2.25 degrees C (+0 and +500 ppm), +4.5 degrees C (+0 and +500 ppm elevated CO2), +6.75 degrees C (+0 and +500 ppm) and +9 degrees C (+0 and +500 ppm elevated CO2) for both hummocks and hollows. This dataset includes measurements of the height and absolute coverage (%) for each vascular plant and moss species, as well as organic litter and dead overstory vascular plants, and the distance from the grid center to the nearest tree and the species of the nearest tree. These data were used as species-specific aboveground plant metadata for assessing the warming and elevated CO2 response of fine roots across different peatland microtopographical features (hummocks and hollows) and plant functional types (shrub, spruce and larch). This dataset contains one data file in comma separate (.csv) format. Additional metadata are provided: one data dictionary and a file-level metadata file in comma separate (.csv) format and a user guide in PDF (*.pdf) format.

ESS-DIVE CSV File Formatting Guidelines Reporting ↗

Enhanced Resistance Pines for Improved Renewable Biofuel and Chemical Production (Technical Report)

We completed phenotyping constitutive and inducible oleoresin flow across two seasons, constitutive resin canal number and density and wood terpene content in our ADEPT2 and CCLONES populations. We completed genetic association between 19 oleoresin phenotypes and a total of 523,192 SNP markers from ADEPT2 and 13,883 SNP markers in CCLONES using four mixed linear models. A total of 293 significant SNPs (FDR = 0.20) were identified. We used the MENTOR tool to mine mechanistic connections from a multiplex network constructed from poplar multi-omic data to construct a conceptual model for a subset of these significant SNPs. Our model contains 6 transcriptional regulators in addition to 3 monoterpene synthases. To generate more lines of evidence for these significant SNPs, we completed a time course RNAseq experiment after inducing vascular zone cells to differentiate into new resin canals with a methyl jasmonate treatment, a single nuclei RNAseq that identified differentiating resin canal epithelial cells and are completing analysis for a QTL study in a hybrid pine population. The time course identified 4634 significantly down and 1890 significantly up regulated transcripts after treatment with methyl jasmonate, an inducer of new resin canal formation in the vascular cambial meristem. To analyze this large set of differentially regulated genes, we created a predictive expression network and analyzed it with random walk restart using 6 seed genes coding for transcription factors regulating xylem differentiation in poplar. Of the top ranked 200 transcripts, 119 transcripts were significant differentially expressed supporting these transcripts as potential candidates regulating resin canal formation. Analysis of single nuclei sequencing of shoot tips that contain differentiating resin canals, identified 10 clusters. One cluster was highly enriched in transcripts coding for 9 of the enzymes in the MEP pathway 3 prenyl synthetases, and 3 monoterpene synthases strongly suggesting that this cluster represents resin canal epithelial cells. We are mining the additional transcripts to create a trajectory analysis. In summary, we have identified > 10 novel genes that are strongly supported candidates for further analysis in breeding lines and for genetic engineering over- and under- expressing lines to increase wood terpene content to improve resistance to insect and fungal pathogens while simultaneously increasing terpene supplies for renewable chemicals and biofuels.

59 BASIC BIOLOGICAL SCIENCES↗

High levels of exfoliated fragments following glycocalyx destruction in hemorrhagic fever with the renal syndrome are associated with mortality risk

Background The glycocalyx is a gel-like structure that covers the luminal side of vascular endothelial cells. It plays an important role in maintaining the integrity of the vascular endothelial barrier structure. However, the presence or absence of glycocalyx destruction in hemorrhagic fever with renal syndrome (HFRS) and its specific mechanism and role is still unclear. Methods In this study, we detected the levels of exfoliated glycocalyx fragments, namely, heparan sulfate (HS), hyaluronic acid (HA), and chondroitin sulfate (CS), in HFRS patients and investigated their clinical application value on the evaluation of disease severity and prognosis prediction. Results The expression of exfoliated glycocalyx fragments in plasma was significantly increased during the acute stage of HFRS. The levels of HS, HA, and CS in HFRS patients during the acute stage were significantly higher than in healthy controls and convalescent stages of the same type. HS and CS during the acute stage gradually increased with the aggravation of HFRS, and both fragments showed a significant association with disease severity. In addition, exfoliated glycocalyx fragments (especially HS and CS) showed a significant correlation with conventional laboratory parameters and hospitalization days. High levels of HS and CS during the acute phase were significantly associated with patient mortality and demonstrated an obvious predictive value for the mortality risk of HFRS. Conclusion Glycocalyx destruction and shedding may be closely associated with endothelial hyperpermeability and microvascular leakage in HFRS. The dynamic detection of the exfoliated glycocalyx fragments may be beneficial for the evaluation of disease severity and prognosis prediction in HFRS.

Du, Hong↗

Localizing Clinical Patterns of Blast Traumatic Brain Injury Through Computational Modeling and Simulation

Blast traumatic brain injury is ubiquitous in modern military conflict with significant morbidity and mortality. Yet the mechanism by which blast overpressure waves cause specific intracranial injury in humans remains unclear. Reviewing of both the clinical experience of neurointensivists and neurosurgeons who treated service members exposed to blast have revealed a pattern of injury to cerebral blood vessels, manifested as subarachnoid hemorrhage, pseudoaneurysm, and early diffuse cerebral edema. Additionally, a seminal neuropathologic case series of victims of blast traumatic brain injury (TBI) showed unique astroglial scarring patterns at the following tissue interfaces: subpial glial plate, perivascular, periventricular, and cerebral gray-white interface. The uniting feature of both the clinical and neuropathologic findings in blast TBI is the co-location of injury to material interfaces, be it solid-fluid or solid-solid interface. This motivates the hypothesis that blast TBI is an injury at the intracranial mechanical interfaces. In order to investigate the intracranial interface dynamics, we performed a novel set of computational simulations using a model human head simplified but containing models of gyri, sulci, cerebrospinal fluid (CSF), ventricles, and vasculature with high spatial resolution of the mechanical interfaces. Simulations were performed within a hybrid Eulerian—Lagrangian simulation suite (CTH coupled via Zapotec to Sierra Mechanics). Because of the large computational meshes, simulations required high performance computing resources. Twenty simulations were performed across multiple exposure scenarios—overpressures of 150, 250, and 500 kPa with 1 ms overpressure durations—for multiple blast exposures (front blast, side blast, and wall blast) across large variations in material model parameters (brain shear properties, skull elastic moduli). All simulations predict fluid cavitation within CSF (where intracerebral vasculature reside) with cavitation occurring deep and diffusely into cerebral sulci. These cavitation events are adjacent to high interface strain rates at the subpial glial plate. Larger overpressure simulations (250 and 500kPa) demonstrated intraventricular cavitation—also associated with adjacent high periventricular strain rates. Additionally, models of embedded intraparenchymal vascular structures—with diameters as small as 0.6 mm—predicted intravascular cavitation with adjacent high perivascular strain rates. The co-location of local maxima of strain rates near several of the regions that appear to be preferentially damaged in blast TBI (vascular structures, subpial glial plate, perivascular regions, and periventricular regions) suggest that intracranial interface dynamics may be important in understanding how blast overpressures leads to intracranial injury.

59 BASIC BIOLOGICAL SCIENCES↗

Transcriptional regulation of the raffinose family oligosaccharides pathway in Sorghum bicolor reveals potential roles in leaf sucrose transport and stem sucrose accumulation

Bioenergy sorghum hybrids are being developed with enhanced drought tolerance and high levels of stem sugars. Raffinose family oligosaccharides (RFOs) contribute to plant environmental stress tolerance, sugar storage, transport, and signaling. To better understand the role of RFOs in sorghum, genes involved in myo -inositol and RFO metabolism were identified and relative transcript abundance analyzed during development. Genes involved in RFO biosynthesis ( SbMIPS1, SbInsPase, SbGolS1, SbRS ) were more highly expressed in leaves compared to stems and roots, with peak expression early in the morning in leaves. SbGolS, SbRS, SbAGA1 and SbAGA2 were also expressed at high levels in the leaf collar and leaf sheath. In leaf blades, genes involved in myo -inositol biosynthesis ( SbMIPS1, SbInsPase ) were expressed in bundle sheath cells, whereas genes involved in galactinol and raffinose synthesis ( SbGolS1, SbRS ) were expressed in mesophyll cells. Furthermore, SbAGA1 and SbAGA2 , genes that encode neutral-alkaline alpha-galactosidases that hydrolyze raffinose, were differentially expressed in minor vein bundle sheath cells and major vein and mid-rib vascular and xylem parenchyma. This suggests that raffinose synthesized from sucrose and galactinol in mesophyll cells diffuses into vascular bundles where hydrolysis releases sucrose for long distance phloem transport. Increased expression (>20-fold) of SbAGA1 and SbAGA2 in stem storage pith parenchyma of sweet sorghum between floral initiation and grain maturity, and higher expression in sweet sorghum compared to grain sorghum, indicates these genes may play a key role in non-structural carbohydrate accumulation in stems.

60 APPLIED LIFE SCIENCES↗

Applications of Decellularized Plant Tissues in Regenerative Medicine and Tissue Engineering

The development of biomaterials capable of supporting complex tissue growth remains a central challenge in regenerative medicine and tissue engineering, particularly in replicating the structural, mechanical, and transport functions of native extracellular matrices. While decellularized animal tissues have demonstrated significant success as scaffolds for tissue engineering, they are still constrained by cost, immunogenicity, and ethical concerns. In recent years, decellularized plant tissues have emerged as a compelling alternative scaffold platform due to their inherent vascular architectures, ethical sourcing, tunable mechanical properties, cytocompatibility, and sustainability. This review summarizes current strategies for the decellularization of plant tissues, including chemical, enzymatic, and physical approaches, and discusses how these methods preserve plant cell wall structure while removing immunogenic components. Advances in surface loading and functionalization, including protein coatings, oxidation, nanoparticle incorporation, peptide conjugation, and bioactive molecule loading, have further enhanced cell adhesion, differentiation, biodegradability, and immunomodulation. Recent applications of decellularized plant scaffolds in cardiac, skeletal muscle, bone, nerve, and wound healing contexts are reviewed, highlighting proof-of-concept successes and remaining challenges. Beyond therapeutic applications, plant-derived scaffolds have also enabled physiologically relevant in vitro models for vascular biology, mechanotransduction, cancer, metabolic tissues, and drug response studies. Collectively, these advances position decellularized plant tissues as versatile, low-cost, and ethically favorable biomaterials with growing relevance for both regenerative medicine and tissue modeling.

59 BASIC BIOLOGICAL SCIENCES↗

A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm

Neither the disease mechanism nor treatments for COVID-19 are currently known. Here, we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of RAS. Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin 1-9 produced by ACE2. Here, we perform a new analysis on gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus. Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. These bradykinin-driven outcomes explain many of the symptoms being observed in COVID-19.

60 APPLIED LIFE SCIENCES↗