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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2026

DNA Sequence-Programmed Protein Coronas Determine Intracellular Fate and Proteostatic Stress of Carbon Nanotubes

Single-walled carbon nanotubes (SWCNTs) show promise for optical biosensing, imaging, and drug delivery, but turning them into safe, precision nanomedicine tools requires understanding how nanotube surface chemistry dictates recognition and processing by cells. Like other nanomaterials, carbon nanotubes acquire a biomolecular corona on contact with biological fluids, and corona identity is increasingly recognized as central to sensor performance and drug delivery efficacy. However, whether corona identity also governs the intracellular fate of carbon nanotubes remains largely unknown. Here, we show that the single-stranded DNA wrapping of (6,5)-enriched single-walled carbon nanotubes reprograms their protein corona, intracellular trafficking, and macrophage response. By profiling (AT)15, (GT)15, and (CT)15 wrapped SWCNTs, we show that the wrapping sequence programs both the protein corona and the resulting proteostatic stress on macrophages. Photoluminescence imaging and confocal Raman measurements reported that (AT)15 is internalized the most yet leaves the proteome and nanotube structure largely undisturbed, whereas (CT)15, taken up the least, undergoes the most aggressive intracellular degradation and drives the highest oxidative and proteostatic stress. Corona proteomics indicated that all three tested nanotubes form coronas with distinct functional identities that are responsible for divergent intracellular routes. Time-resolved intracellular proteomics combined with functional assays resolved how the host cell reorganizes its biomolecular complexity over time, including oxidative outputs, aside from a sequence-independent core response involving particle engagement, phagosomal sorting, and lysosomal processing. These findings provide mechanistic insight into nanomaterial-cell interactions and the wrapping sequence as a tunable, nucleotide-level design handle for controlling the intracellular fate of carbon nanomaterials, with potential implications for safe and effective nanomedicine platforms.

bioengineering↗

bioRxiv2026

A novel target associated with senescence and inflammatory signaling in human intervertebral disc degeneration

Background Intervertebral disc degeneration (IDD) is a leading cause of chronic low back pain and disability worldwide, affecting most individuals over 50 years of age. Despite its prevalence, no disease-modifying therapies exist, and current interventions are limited to reducing pain. Cellular senescence and the associated secretory phenotype (SASP) have been increasingly recognized as major drivers of disc matrix degradation and inflammation. However, the upstream molecular mechanisms that lead to IDD degeneration are still unknown. Connexin 43 (Cx43), a gap junction protein implicated in progression of age-related diseases, has emerged as a key regulator of cellular senescence and inflammatory signalling in musculoskeletal tissues. Methods Human primary cells were isolated from intervertebral disc samples obtained from patients classified into clinically meaningful groups: healthy controls, chronic/mechanical degeneration (DDD, ADJ, ASD), and acute/inflammatory event (herniated nucleus pulposus, HNP). Cx43 expression was assessed by qPCR and Western blotting. Cellular senescence was evaluated through SA-{beta}-gal staining and analysis of p53/p21 expression. SASP factors and EMT-related markers were measured by qPCR. Protein expression was quantified by immunoblotting across different age groups and degeneration grades. Results In this current study Cx43, was identified as the most abundant connexin isoform in human intervertebral discs, showing a progressive increase in expression with age and disc degeneration. Also, high Cx43 expression correlated with increased expression of the senescent markers p53 and p21 and increased SA-{beta}-gal activity. Besides, increased expression of EMT-related and differentiation markers has been correlated with high Cx43 levels in human IDD samples, consistent with fibrotic remodeling processes. Conclusions These findings identify aberrant upregulation of Cx43 signaling as a potential mechanistic link between intervertebral disc cellular senescence and extracellular matrix degradation, with the ensuing inflammatory response, representing a novel potential therapeutic target to modulate senescence-driven pathogenesis and modulate IDD progression.

molecular biology↗

bioRxiv2026

Predicting Cerebral Pericyte Contractility Across Experimental and Physiological Conditions: an in-silico framework

Pericytes (PCs) have recently emerged as critical regulators of cerebral blood flow (CBF) and represent a promising therapeutic target for various cerebrovascular pathologies. Given the complex array of biochemical and mechanical stimuli these cells integrate, a multiscale modeling framework is essential to quantify the impact of selective interventions on pericyte contractile machinery and blood flow restoration. Here, we introduce a computational framework to evaluate capillary pericyte responses across diverse experimental interventions and conditions (ex vivo and in vivo). To capture pharmacological modulation of the contractile apparatus, we developed a homogeneous intracellular model that incorporates key properties of robust control systems. In this framework, vascular tone generation depends strictly on intracellular calcium concentration (Ca2+), which emerges from a complex electrochemical equilibrium established by transmembrane ion (Na+, K+, Cl-) gradients, luminal mechanical forces, and external ligand concentrations. The resulting fraction of phosphorylated cross-bridges generates contractility, which is integrated into the strain energy function governing the constitutive behavior of the vascular wall. The model was successfully validated across four distinct experimental and pharmacological interventions (including pinacidil, high external K+, U46619, and nimodipine), demonstrating close agreement with observed ex vivo and in vivo vascular responses. By establishing a quantitative bridge between pericyte electrophysiology and microvascular mechanics, this framework provides a valuable foundation for evaluating targeted therapeutic strategies to alleviate tissue ischemia in stroke and vascular dementia.

systems biology↗

bioRxiv2026

A transcriptomic and spatial map of serotonin autoreceptor expression in Drosophila

Serotonin is an evolutionarily ancient neurotransmitter that modulates an array of behaviors such as mood, sleep, and appetite across species. Serotonin acts primarily by binding to serotonin receptors, which are expressed in post-synaptic neurons (heteroreceptors) and serotonergic neurons themselves (autoreceptors). Serotonin autoreceptors modulate serotonergic tone, the foundational principles of which have been excellently demonstrated in vertebrate and invertebrate models. However, many aspects of the mechanisms and contexts in which this modulation occurs are still unclear. Drosophila melanogaster is a powerful model organism that can provide unique insights into autoreceptor function by the ability to perform precise spatial and temporal genetic manipulation with structural and functional readouts / behaviors of serotonin systems. However, a systematic characterization of serotonin autoreceptor expression in Drosophila has not been conducted. Here we use single-cell sequencing and genetic labeling to show that all five serotonin receptors are expressed in serotonergic neurons and map their expression at both the larval and adult stages of development. This is the first evidence of 5-HT2A and 5-HT7 expression in serotonergic neurons in any organism. Moreover, the unique combinations of autoreceptor expression in specific neuronal clusters will aid in the development of novel hypotheses for autoreceptor function, and demonstrates the utility of Drosophila as a model organism to study the function of serotonin autoreceptors.

neuroscience↗

bioRxiv2026

Low-Density Lipoprotein Modulates Plasma Fibrin Network Architecture and Impairs Fibrinolysis

Low-density lipoprotein (LDL) is a major atherogenic lipoprotein, yet its potential to directly modify the fibrin scaffold of blood clots is incompletely understood. Here, we investigated how LDL alters plasma fibrin network architecture and internal fibrinolysis across defined fibrinogen/thrombin conditions. Pooled normal human plasma was supplemented with LDL and clotted with controlled concentrations of fibrinogen and thrombin. Fibrin architecture was visualized by confocal microscopy and quantified by pore-size analysis; clot formation and lysis were monitored turbidimetrically in the presence of tissue plasminogen activator (tPA). Increasing LDL produced a pronounced reduction in fibrin-network pore size across the tested fibrinogen/thrombin conditions. The LDL dependence of pore diameter was well described by a power-law relationship, D_pore=(6.54 +/- 0.11)[LDL]^(-0.12 +/- 0.02) , (R^2 = 0.90), with a significant negative LDL exponent (p = 4 x 10^5). Increasing LDL also prolonged clot lysis time and altered turbidity kinetics. These findings extend epidemiologic and clinical associations between ApoB-containing lipoproteins and hypofibrinolytic clot phenotypes by demonstrating, in a controlled plasma system, that LDL itself can modify fibrin network architecture and fibrinolytic susceptibility. The results support a structure-function role for LDL within the fibrin biomaterial and motivate direct tests of LDL incorporation, protofibril packing, fibrinolytic-protein binding, and single-fiber mechanics.

biophysics↗

bioRxiv2026

Whole-body Super-resolution Functional and Molecular Imaging with Panoramic Photoacoustic-Ultrasound Tomography

Photoacoustic (PA) and ultrasound (US) imaging provide complementary molecular, functional, and anatomical contrasts. Here, we present a panoramic PA-US imaging platform that integrates multispectral PA computed tomography (PACT) along with reflection-mode and transmission-mode US imaging through a single shared full-ring ultrasound array. We employ an ultrafast planewave transmission scheme in reflection-mode US for power Doppler (PWD) imaging and ultrasound localization microscopy (ULM). Additionally, we use the transmission-mode US to reconstruct a spatially resolved speed of sound (SoS) map that corrects both PA and US reconstruction. Such correction sharpens the resolution of PACT, suppresses the artifacts of PWD, and improves microbubble localization of ULM. Elevational scanning further enables whole-body volumetric imaging with co-registered PA and US contrasts. The integrated system maps photoswitchable DrBphP1-expressing tumors alongside their blood perfusion and oxygenation environment. Applying the platform to monitor unilateral renal ischemia-reperfusion injury, we report that microvascular perfusion and renal oxygenation recover at different rates. Collectively, we demonstrate that the integrated PA-US imaging platform provides a unified framework for multiparametric study of anatomy, perfusion, microvascular flow, oxygenation, and molecular activities.

bioengineering↗

bioRxiv2026

Germ granules act as repositories for RNA and protein molecules essential for zebrafish germline development

Germ granules are conserved, phase-separated ribonucleoprotein condensates enriched in germline determinants, yet their precise function remains unclear. Using quantitative live imaging, translational reporters, and targeted disruption of germ granule assembly in zebrafish primordial germ cells, we show that germ granules are dispensable for germ cell fate, migration, and gamete production. Instead, granules act as reservoirs, sequestering transcripts and releasing them gradually for cytoplasmic translation. Under heat stress or translational inhibition, granules further accumulate mRNAs and canonical stress granule factors, indicating a role in buffering RNA and regulatory protein availability rather than serving as sites of localized translation, as previously proposed. Consistent with this reservoir model, cytoplasmic expression of the germline determinants Nanos3 and Dead end is sufficient to direct somatic cells toward a germline fate even in the absence of germ granules. Correspondingly, germ cells lacking granules develop normally but show reduced persistence of germline RNA expression and impaired fertility. Together, these findings establish zebrafish germ granules as protective condensates that safeguard germline determinants and enhance developmental robustness by buffering the timing and rate of RNA translation.

cell biology↗

bioRxiv2026

Genetic diversity within and between polyploid sugarcane (Saccharum spp.) families obtained via caryopsis using microsatellite markers and multicategory model

Genetic diversity analyses are essential for sugarcane (Saccharum spp.) breeding programs. Crossbreeding, based on genetic distances between parental plants, is a tool used to increase genetic variability and enhance plant selection; however, quantifying variation in highly polyploid species remains a challenge. The present study aimed to evaluate the diversity within and between 12 families of sugarcane derived from caryopses, analyzing 120 individual seedlings arranged in an augmented block design. Genotyping was performed using primers for 16 microsatellite loci, five simple sequence repeat (SSR) loci, and 11 expressed sequence tag-SSR (EST-SSR) loci. To accurately account for polyploidy, similarity calculations were performed using Bruvos distances among individuals and RST distances among the families. Analysis of molecular variance (AMOVA) indicated that most of the genetic variability was within families (72%), with only 28% found between them. This high level of intra-family variation demonstrates that a significant reservoir of genetic diversity remains available within the crosses. The highest genetic similarity was observed between the families RB986952 x RB986960 and RB036122 x RB03611, whereas the lowest genetic similarity was observed between the families RB97319 x RB966928 and RB106802 x RB855036. Although the evaluated families shared high genetic similarity, the pronounced genetic variation within them demonstrates a robust recombination potential, indicating that the genetic basis of sugarcane can be better explored using the high variability that already exists in the selection of desirable morpho-agronomic characteristics within the families. Furthermore, this study highlights the importance of using appropriate distances for diversity studies with codominant markers, such as microsatellites, in polyploid species.

genetics↗

bioRxiv2026

HIF1A recruits primate-specific endogenous retroviruses into the human hypoxic and immune responses

Oxygen availability varies profoundly across the human body and changes further during inflammation, infection, tissue injury and disease. Immune cells must therefore continuously adapt their transcriptional and metabolic state based on the oxygen availability to them. Hypoxia-inducible factor 1 (HIF1A) is central to this adaptation and a marker of the cellular response to low oxygen, yet its genomic targets have been assembled from a non-repetitive fraction of the genome, leaving nearly half of the human genome largely unexplored. Here we define the gene and transposable-element (TE) landscape of the human hypoxic response across different human tissues, cell lines, and conditions. This directional TE response was reproduced in transformed cells and in primary immune cells isolated from blood and the physiologically oxygen-restricted tonsil. Single-cell profiling of peripheral blood mononuclear cells (PBMC) under hypoxia, pharmacological HIF stabilization, and interferon stimulation revealed a striking difference between the gene and retrotranscriptome responses. While gene responses were strongly cell-type dependent and in a bidirectional manner, TEs were overwhelmingly activated. This pattern extended to blood and tonsil immune cells, where ~70-90% of tested TE families were induced under hypoxia, with activated tonsil cells showing exclusively induced significant families, including THE1B, alongside increased LTR7 and HERVH. Integrating HIF1A ChIP-seq with transcriptional responses revealed that HIF1A does not engage repetitive DNA indiscriminately. Instead, its binding converged on LTR7, the promoter long terminal repeat of the HERVH endogenous retrovirus. Approximately 80% of HIF1A-bound LTR7 elements contained a canonical hypoxia-response element, and disruption of HIF1A DNA binding dramatically reduced the expression of occupied HERVH loci. CRISPR deletion of individual LTR7/HERVH loci altered the expression of distant and neighboring genes, demonstrating that hypoxia-responsive retroelements can participate directly in host gene regulation and contribute to overall physiology. Our findings reveal the repetitive genome as a previously underappreciated component of oxygen sensing. We propose that HIF1A recruits selected endogenous retroviral elements into the human hypoxic response, extending oxygen-dependent regulation beyond conventional gene promoters and providing an additional regulatory layer through which tissue oxygenation can shape immune-cell state and human physiology.

genomics↗

bioRxiv2026

Effects of Instructional Context on Neural Features of Attention during Learning Activities in Children with and without ADHD

Attention is foundational to learning, yet the extent to which features of the instructional environment differentially shape attentional engagement is not well understood. Here we leveraged mobile EEG and video-coded behavioral observation to examine attentional engagement in 6 to 10 years old children with and without a diagnosis of ADHD across instructional conditions varying in delivery modality (video watching, online, in-person) and management of learning (teacher-led versus student-led). EEG measures, including alpha-band (8-12Hz) oscillations, spectral slope and offset, and behavioral measures of active engagement (AE%), passive engagement (PE%), fidgeting, off-task behavior, were examined as a function of instructional context. Attentional engagement, as indicated by higher AE%, lower alpha power, flatter spectral slope and lower offset, was greatest in student-led learning, followed by teacher-led in person learning, synchronous online learning, and asynchronous learning, respectively. Child by instructional context interactions revealed that patterns of attentional engagement were largely consistent regardless of diagnosis, with group effects observed for motor behaviors (PE%, fidgeting) but not for measures of visual attention. Similarly, age showed only main effects, whereby older children showed higher passive engagement, lower fidgeting and off-task behavior, flatter spectral slope, and lower offset. The results underscore: (i) the importance of considering environmental context, such as instructional modality and management of learning, when examining mechanisms of attention and individual differences therein, and (ii) the value of recording multiple behavioral and neural measures, as not all indices commonly assumed to reflect attention capture the same underlying processes.

neuroscience↗

bioRxiv2026

Evolution and Human Neural Individuality

Individuality is a defining feature of human biology. The functional network architecture of the human brain harbors person-specific qualities and forms individualized connectivity profiles that function as a neural fingerprint, both stable and unique across time. Here, using fMRI data from 431 Human Connectome Project participants, we examined whether neural individuality is more strongly exhibited in brain regions bearing signatures of recent human evolution. We calculated region-wise fingerprinting accuracy and associated it with four properties of evolutionary cortical organization: cortical expansion, myelin content estimate (T1w/T2w), human-specific gene-expression profiles, and functional homology to other primates. Across all four measures, neural individuality was strongest in cortical areas showing greater evolutionary novelty in humans, particularly frontoparietal control and default mode networks, and weaker in more conserved primary regions. Our findings connect evolutionary variation across species with stable functional variation among individuals.

neuroscience↗

bioRxiv2026

Designing antimicrobials with programmable mechanism and safety

Antimicrobial peptides (AMPs) are a promising solution to antimicrobial resistance, yet generative models for their design cannot control the physicochemical properties and motifs that shape activity and selectivity. Here, we present OmegAMP, a conditional diffusion framework controlling net charge, mean hydrophobicity, and sequence length, supporting de novo, analog, and motif-guided design. Across 204 wet-lab characterized peptides, de novo generation yielded antimicrobials with broad activity against multidrug-resistant Gram-negative isolates. Analog generation converted six inactive prototypes into antimicrobials, with the prototype determining each analog's membrane-disruption mode and mammalian-cell safety. Motif-guided analog generation preserved lipopolysaccharide engagement of active prototypes, and a redesigned non-antimicrobial leucine zipper acquired antimicrobial activity while retaining DNA-perturbing character in vitro. In murine skin and thigh infection models, leads reduced bacterial burden, with a motif-guided DNA-perturbing lead matching the fluoroquinolone control systemically. OmegAMP opens a programmable route to new peptide antibiotics whose mechanism and safety follow from the chosen prototype.

bioinformatics↗

bioRxiv2026

Transcriptomic profile of a rat jaw opener (anterior digastric) and a jaw closer (superficial masseter).

Mammalian skeletal muscle research predominantly focuses on locomotor muscles, and feeding related muscles remain less extensively characterized despite their role in mastication, mandibular stabilization, and swallowing. In this study, we investigated the transcriptomic specialization of three functionally and developmentally unique rat muscles: the anterior digastric (AD), a jaw opening muscle; the superficial masseter (SM), a jaw closing muscle; and the Sternohyoid (SH), a non-mandibular muscle involved in swallowing. Differential gene expression and weighted gene co-expression network analysis were used to characterize the transcription level features associated with their distinct roles. Our results indicated that all three muscles predominantly expressed fast-twitch contractile isoforms. However, the AD showed lower overall expression of several contractile gene families, including myosin heavy chain, myosin light chain, and tropomyosin isoforms, while exhibiting elevated expression of slow/oxidative myosin isoforms like Myh7 and Myh2. Network analysis revealed that modules correlated with AD are strongly enriched for fatty acid catabolism, mitochondrial energy production, and vascular/extracellular matrix remodeling. Additionally, AD and SM shared a distinct gene set compared to SH, highlighting their common developmental origin from the first branchial arch. Our findings show that the rat feeding related muscles possess unique transcriptomic profiles shaped by their contractile functions, developmental origins, and metabolic functions.

bioinformatics↗

bioRxiv2026

Effects of spectral light quality on growth, photosynthetic pigments and bioactive compounds in Brassicaceae microgreens

LED spectral composition is an important tool for improving the growth and nutritional quality of microgreens cultivated in controlled environments. This study evaluated the effects of three LED light treatments on growth, morphology, pigments, primary metabolites, phenolic composition, and antioxidant capacity in arugula (Eruca sativa), mustard (Brassica juncea), and radish (Raphanus sativus) microgreens. Microgreens were cultivated under controlled environmental conditions and exposed to broad-spectrum white (W), blue-enriched white (WB), and red-enriched white (R) light at a photosynthetic photon flux density of 200 micromol/m2/s. Light quality did not affect yield in any species. However, R increased cotyledon area in arugula by 50 to 60% and promoted hypocotyl elongation in both arugula and radish, whereas W resulted in the longest hypocotyls in mustard. Photosynthetic pigment composition responded differently among species. In mustard, WB increased the chlorophyll a/b ratio (1.12 to 1.18), whereas lutein concentration decreased from 7.06 to 4.20 mg 100 g/FW. Primary metabolism also responded to light treatments in a species-dependent manner. In mustard, W increased glucose (0.43 vs. 0.26 and 0.29 g 100 g/ FW) and fructose (0.33 vs. 0.20 and 0.22 g 100 g/ FW) concentrations compared with WB and R. Organic acid composition was more responsive to light treatments in radish, with higher concentrations under R. Phenolic metabolism also responded in a species-dependent manner. In mustard, W increased total phenolic content to 0.25 mg GAE g/FW compared with 0.15 mg GAE g/FW under WB and R, and ABTS antioxidant capacity to 1.17 mg TE g/FW compared with 0.74 and 0.75 mg TE g/FW under WB and R, respectively. Individual phenolic compounds were also affected by light treatments, particularly in arugula and mustard. These findings demonstrate that the effects of LED spectral composition on microgreen quality are highly species-dependent. Therefore, LED light spectra should be optimized according to the target species and the desired quality attributes rather than applying a single lighting strategy to all Brassicaceae microgreens.

plant biology↗

bioRxiv2026

Compression Sequencing enables ultra-sensitive and scalable scRNA-seq

Current sequencing methods are inefficient and bottlenecked by repeated sampling of highly abundant molecules, which dominate sequencing reads, limit assay throughput and sensitivity for rare targets. For example, single-cell RNA sequencing (scRNA-seq) can profile up to millions of cells, but remains severely constrained by sequencing cost, resulting in shallow gene coverage and high dropout rate. Here we report an information science-inspired method, Compression Sequencing, that tackles this fundamental inefficiency and enables highly improved (>100x) sequencing power. Our method works by performing an accurate and unbiased logarithmic transform on molecular abundances over a wide (5 logs) dynamic range, thus suppressing high-abundance targets and enriching rare ones, while maintaining quantitative accuracy. Applied to scRNA-seq libraries, our method allows ultra-sensitive detection of low-abundance transcripts (2-5x more UMIs), ultra-low sequencing cost (200x reduction), preserves accurate cell types and differential expression analysis over a 500-2,000 gene panel. In AML clinical samples, Compression Sequencing reproduces clinical diagnosis and additionally allows transcriptomic profiling at affordable cost (est. $10 per sample). Our approach thus enables ultra-sensitive and scalable single-cell analysis for large-scale functional genomics studies, drug discovery screens, AI cell model training, as well as affordable single-cell disease diagnostics.

bioengineering↗

bioRxiv2026

A multiscale analysis of liver lobule fibrosis and its impact on drug propagation and metabolism - a DLA approach

Employing DLA methods, this paper explores the self-assembly of collagen fibers and resulting fibrosis at three scales up to the scale of regular lobule models. This allows a mechanistic exploration of the effects of collagen on drug transport (flow and diffusion) and metabolism. In addition, this method permits an analysis of fiber growth characteristics. First, variations of the DLA method of Parkinson et al (1994) will be used to generate multiple explicit collagen microfibril self-assembly using DLA particles in one dimension using cubic grid blocks of (4 mm)3 in a 240 x 20 x 20 grid model. The second stage will be to assess the consequences of various densities of these fibers in three dimensions on flow reductions at a higher scale. Here we utilize DLA methods in cubic grid blocks of (80 nm)3 to mimic 3D collagen self-assembly of fibrils. We then apply a pressure gradient or specified flow rates across a spatially gridded version of these models to quantify flow effects. This region represents a local zone of liver tissue affected by fibrosis. Analytic models of fibrotic effects on flow are employed for comparison. A third stage explores the implications of fibrosis in a liver lobule model using multiple grid blocks of size 3200 mm to represent the lobule tissue. Here, a continuum model of fiber density is employed, based on the previous two scales. The model also includes the effects of additional grid blocks representing sinusoidal flow paths found in the lobule. We contrast and quantify drug propagation and metabolism of molecular dissolved versus nanoparticle delivery vehicles in fibrotic media, achieved by upscaling explicit collagen distributions to appropriate average values.

physiology↗

bioRxiv2026

A single dsRNA spray silences VAMT and shifts habanero pepper fruit metabolism towards capsinoids

Capsaicinoids are synthesized in the placenta of Capsicum fruit, where vanillylamine aminotransferase (VAMT) catalyzes the formation of vanillylamine, the precursor of the pathway. The modulation of pungency has relied on genetic breeding and transgenic approaches, and this pathway has not been addressed by spray-induced gene silencing. The aim of this study was to evaluate whether a single non-invasive spray of double-stranded RNA (dsRNA) targeting VAMT allows the gene to be silenced and capsaicinoid accumulation to be modified in Capsicum chinense fruit. The molecule was designed in silico and applied at 10 days post-anthesis. Pedicel injection reduced the VAMT transcript in a dose-dependent manner, with three levels of inhibition distinguishable from one another. Spraying with surfactant reduced it by 86.2 %, a magnitude statistically indistinguishable from the 90.6 % obtained by injection, and also reduced the Pun1 transcript, a co-regulation previously described only as a difference between cultivars. Analysis by gas chromatography coupled to mass spectrometry showed reductions of 84.4 % in capsaicin and 68.5 % in dihydrocapsaicin, the loss of nonivamide and one further vanillylamine-derived compound, and the detection of capsiate and a second capsinoid, absent in control fruits. The siRNA was detected in non-treated tissues, and a single topical application is therefore sufficient to silence an endogenous biosynthetic gene and shift the metabolic profile of the fruit without genetic modification.

plant biology↗

bioRxiv2026

Activation and inactivation pathways of a p53-like transcription factor govern lipid homeostasis in yeast

Membrane fluidity depends on unsaturated acyl chains that are generated in Saccharomyces cerevisiae by the desaturase Ole1, whose expression is primarily under the control of the transcription factor Mga2. Here, we show that the endoplasmic reticulum-anchored Mga2 precursor is ubiquitinated by the E3 ligase Rsp5 and then processively degraded by the proteasome until proteolysis stalls at a defined site, releasing a soluble fragment that enters the nucleus and activates Ole1 transcription. Unexpectedly, Mga2 contains a DNA-binding domain and a trans-activation-like segment structurally and functionally related to those of the human tumor suppressor p53. The mature transcription factor is degraded in the nucleus in a DNA binding-dependent manner; blocking this degradation causes unsaturated acyl chains to accumulate in lipid droplets, a detoxification response required for cell viability. These findings define the pathways that activate and inactivate Mga2, and uncover an evolutionary connection between the yeast lipid homeostasis regulator Mga2 and p53.

cell biology↗