Biology subjects

Weiss, D.

Publications and source records attributed to Weiss, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Antagonism between salicylic acid and auxin responses directs root development during Tobamovirus infection

Viral symptoms in plants are structural and physiological changes resulting from virus-induced manipulation of host pathways. While the effects of viruses on above-ground organs have been well-documented, their impact on the root system remains largely understudied. In tomato (Solanum lycopersicum), the emerging tomato brown rugose fruit virus (ToBRFV; Genus: Tobamovirus) causes significant reductions in root branching. However, the mechanisms underlying this symptom remained unexplored. Here, we provide evidence that tobamovirus-mediated suppression of root branching is conserved between ToBRFV and tomato mosaic virus (ToMV), with ToMV exhibiting a more severe effect over root development. Transcriptome analysis of tobamovirus-infected roots revealed a major shift from growth to defense, marked by the early activation of salicylic acid (SA) signaling. Conversely, auxin signaling was extensively reprogrammed; For example, auxin signaling suppressors such as Aux/IAAs were activated while expression of auxin response factors (ARFs), was downregulated. Importantly, SlARF19a showed reduced expression during infection. Functional analysis of Slarf19a mutants confirmed its critical role in root branching and the root's developmental response to ToMV. We conclude that tobamovirus-mediated root suppression involves an inverse relationship between SA-mediated defense and auxin-mediated growth and identify SlARF19a as a key regulator in this developmental trade-off.

plant biology↗

bioRxiv2026

Significant increase in root exudation of 2'-deoxymugineic acid (DMA) as a response to zinc deficiency in rice

1O_LIZinc (Zn) deficiency limits rice productivity and poses a risk to human health, particularly in populations reliant on rice-based diets. Although rice germplasm exhibits wide variation in Zn-deficiency tolerance, the underlying physiological mechanisms remain poorly resolved. Evidence across the literature for Zn-deficiency-induced secretion of 2'-deoxymugineic acid (DMA) is inconsistent. This study clarifies the role of DMA secretion as a Zn-deficiency stress response. C_LIO_LIWe developed and validated a sensitive LC-ESI-Q-TOF-MS method for selective detection of DMA in rice root exudates. Five rice genotypes with contrasting Zn-deficiency tolerance were grown hydroponically and DMA secretion measured. C_LIO_LIZn-deficiency increased DMA exudation across all genotypes, with sensitive genotypes also showing higher secretion compared with control, supporting DMAs role as a general response to Zn stress rather than being restricted to efficient genotypes. C_LIO_LIFold-change responses exceeded previous studies, likely due to more severe stress exposure. Our results confirm that DMA secretion is induced under Zn-deficiency in rice as part of the micronutrient stress response. However, the lack of increased Zn uptake indicates that additional tolerance mechanisms are involved. These findings reconcile inconsistencies in the literature and position DMA secretion as an important, but not exclusive, component of Zn-deficiency adaptation in rice. C_LI

plant biology↗

bioRxiv2026

Rapid Bacterial Identification and Antibiotic Susceptibility Testing through Interferometry-based Surface Topography Measurement

Scientists have long classified organisms based on shared morphological characteristics. However, modern taxonomy, particularly for bacteria, is largely defined at the genetic level. Yet the information encoded in genetics propagates through many levels of biological organization: genes determine patterns of gene expression and protein production which, in turn, influence cellular physiology and behavior which, in turn, influence the collective morphology of growing populations. It is unclear how far up this hierarchy that the lower level taxonomic information remains preserved. Here, we show that bacterial genera can be identified from differences in the three-dimensional topographies of their growing populations. Using coherence-scanning white-light interferometry (WLI), which is capable of nanometer-resolution, we measure bacterial population topographies of 77 different clinical isolates representing four different genera. We then extract ten biophysically relevant features describing their surface structure. Using a simple machine-learning classifier, these topographic features identified bacterial genus with 97% accuracy, demonstrating that genus-level information remains present at the scale of population morphology. We hypothesize that these topographic "fingerprints" arise because differences in the underlying biophysics of bacterial growth propagate upward into measurable differences in population structure. To test this hypothesis, we performed biophysical simulations of bacterial population growth and applied our experimentally trained classifier directly to the resulting simulated topographies. By systematically modifying simulation parameters, we determined which changes were necessary to generate topographies classified as each of the experimentally observed genera. We find that a relatively small number of differences in cellular growth, cell-surface interactions, and initial conditions are sufficient to recreate the genus-associated differences observed experimentally, and we then show that using the topographic features from the simulations we can recover the underlying parameters used to simulate the topographies. Together, these results show that differences in lower-level bacterial behavior can propagate into distinct population-scale morphologies, and that taxonomic information can remain recoverable far above the molecular scale at which bacterial identity is conventionally defined.

biophysics↗

bioRxiv2025

Tomato drought-responsive transcription factor TINY1 suppresses embryonic growth

Dehydration-Responsive Element-Binding (DREB) transcription factors play an important role in plant responses to drought. DREB subfamily A4, contains a sub-group named TINY. Previous studies in Arabidopsis suggest that TINYs suppress plant growth and mediate abscisic acid (ABA)-induced stomatal closure. In this study, we investigated the function of the tomato drought-induced TINY1. Under drought conditions, tiny1 mutant lost turgor and wilted more rapidly than control M82 plants. However, this sensitivity was attributed to its larger leaf area, rather than intrinsic differences in drought response. Measurements of stomatal conductance, leaf temperature, and osmotic adjustment revealed no significant differences between tiny1 and M82. Furthermore, whole plant daily transpiration of M82 and tiny1 with similar leaf area, showed no differences. Interestingly, the growth-promoting effect of tiny1 was confined to early developmental stages; enhanced embryo growth and hypocotyl elongation, and accelerated emergence of the first true leaves--trait that later contributed to increased leaf area. At later stages, the mutation had no observable impact on growth rate. Our results show increased gibberellin (GA) activity in the mature tiny1 embryo and suggest that TINY1 suppresses embryonic growth by repressing GA biosynthesis through downregulation of GA 20-oxidase 4 (GA20ox4) gene expression.

plant biology↗

bioRxiv2025

Recapitulating apicobasal tissue polarity in extracellular matrix incorporated airway organoids

The airway epithelium is a dynamic barrier that interfaces with the external environment and internal matrix along its apicobasal axis. To recapitulate this tissue arrangement in an organoid format, we present the decellularized ExtraCellular Matrix-incorporated Apical-out Airway Organoid (dECM-AoAO) that integrates basolateral matrix cues through incorporation of human lung dECM microparticles, while maintaining direct apical exposure to the exterior. Compared to the ECM-free AoAO, dECM incorporation effectively diversifies lineage distribution that better recapitulates native epithelial composition. Harnessing dECM-AoAO locomotion powered by its outward-facing ciliary beating, we developed an experimental and computational pipeline for swarm analysis of organoid group motility as a functional readout of ciliary function. Lastly, dECM-AoAO withstood cryopreservation and revival with sustained viability, lineage composition, and ciliary function, enabling future scalability and broad distribution. Together, this work establishes dECM-AoAO as a more physiologically relevant model system for investigating epithelial-ECM crosstalk during airway homeostasis, pathogenesis, and injury responses.

cell biology↗

bioRxiv2025

Growth Arrest of Thoracic Aortic Aneurysms in Aging Marfan Mice

There is a pressing need to identify pathologic mechanisms that render a thoracic aortic aneurysm susceptible to continued enlargement, dissection, or rupture, but additional insight can be gleaned by understanding potential compensatory mechanisms that prevent disease progression and thereby stabilize a lesion. Our biomechanical data suggest that the ascending aorta within a common mouse model of Marfan syndrome, Fbn1C1041G/+, exhibits progressive disease from 12 weeks to 1 year of age, but near growth arrest from 1 to 2 years of age. Comparison of the biomechanical phenotype, histological characteristics, proteomic signature, and transcriptional profile from 12 weeks to 1 year to 2 years suggests that numerous differentially expressed genes (including downregulated Ilk, Ltbp3, and Rictor) and associated proteins may contribute to late-term growth arrest. There is also a conspicuous absence of proteins associated with inflammation from 1 to 2 years of age. Although there is a need to understand better the interconnected roles of temporal changes in differential gene expression and protein abundance, reducing mTOR signaling and reducing excessive inflammation appears to merit increased attention in preventing continued aneurysmal expansion in Marfan syndrome.

bioengineering↗

bioRxiv2025

Postnatal Pulmonary Artery Development from Transcript to Tissue

Many congenital conditions and surgical interventions perturb the hemodynamics experienced by proximal pulmonary arteries during early postnatal development, thus leading to differential gene expression and associated changes in vascular structure and function. Among these, pathologic conditions include patent ductus arteriosus, pulmonary atresia and stenosis, and hypoxemia-induced pulmonary hypertension while surgical interventions include the placement of a Blalock-Taussig shunt as well as Glenn, Fontan, and Norwood procedures. Despite the significant morbidity associated with these diverse conditions, there has been little attention directed towards understanding natural postnatal development of pulmonary arteries from both biological and mechanical perspectives. With-out such information, we cannot truly understand the phenotype of the affected pulmonary artery, which is fundamental to improving diagnosis, treatment, and prognosis. In this paper, we present novel data from wild-type mice that document normal postnatal changes in select gene expression, vascular wall composition, and biomechanical properties of proximal pulmonary arteries. These findings enabled the establishment of a novel, data-informed computational model of pulmonary artery development capable of simulating outcomes in response to perturbations in the pulmonary artery hemodynamic environment.

bioengineering↗

bioRxiv2025

Metabolic heterogeneity coupled with a resistance gene generates antibiotic heteroresistance

Heteroresistance is a form of antibiotic resistance in which a phenotypically unstable subpopulation of resistant cells exists within a majority population of susceptible cells. The impact of the extracellular environment on mechanisms of heteroresistance is unclear. Studying fosfomycin heteroresistance in an Enterobacter cloacae complex isolate, we observed that glucose availability greatly increased the frequency of the resistant subpopulation. Glucose downregulated the glycerol and fosfomycin importer GlpT, whose expression was heterogenous at the single cell level. This heterogeneous expression of GlpT, in combination with the expression of the fosfomycin resistance gene fosA, which acted as a resistance enhancer, led to the generation of heteroresistance. Correspondingly, the frequency of the fosfomycin resistant subpopulation was increased in murine models of hyperglycemia/diabetes. These data demonstrate how metabolic heterogeneity and carbon source availability can impact antibiotic resistance phenotypes in the infection environment.

microbiology↗

bioRxiv2025

Insights From Protein Frustration Analysis Of BRD4-Cereblon Degrader Ternary Complexes Show Separation of Strong from Weak Degraders

PROteolysis TArgeting Chimeras (PROTACs), also known as Ligand-Directed Degraders (LDDs), are an innovative class of small molecules that leverage the ubiquitin-proteasome system to induce the degradation of target proteins. Structure based design methods are not readily applicable for designing LDDs due to the dynamic nature of the ternary complexes. This study investigates the dynamic properties of five LDD-mediated BRD4-Cereblon complexes, focusing on the challenges of evaluating linker efficiency due to the difficulty in identifying suitable computational metrics that correlate well with the cooperativity or degradation propensity of LDDs. We uncovered that protein frustration, a concept originally developed to understand protein folding, calculated for the residues in the protein-protein interface of the LDD-mediated ternary complexes recapitulate the strength of degradation of the LDDs. Our findings indicated that hydrophobic residues in the interface are among the highly frustrated residues pairs, and they are crucial in distinguishing strong degraders from weak ones. By analyzing frustration patterns, we identified key residues and interactions critical to the effectiveness of the ternary complex. These insights provide practical guidelines for designing and prioritizing more efficient degraders, paving the way for the development of next-generation LDDs with improved therapeutic potential.

biophysics↗

bioRxiv2025

GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration

GPR15LG, a chemokine-like ligand for the G-protein coupled receptor 15 (GPR15), is abundantly expressed in the gastrointestinal mucosa and inflamed skin. Emerging evidence suggests its involvement in inflammatory disorders and cancers. This study investigates the effects of GPR15LG on the signaling and downstream functions of C-X-C chemokine receptor type 4 (CXCR4), which plays a critical role in immune cell trafficking and cancer metastasis. The results demonstrate that GPR15LG binds to the orthosteric site of CXCR4, modulating downstream signaling in a context-dependent manner. Specifically, GPR15LG enhances CXCL12-mediated CXCR4 signaling synergistically, promoting wound healing and cell migration across various cell types, including CD4+ T cells and cancer cells. These findings underscore the role of GPR15LG in inflammation and metastasis, offering potential therapeutic avenues for CXCR4-mediated diseases. TeaserGPR15LG binds CXCR4 thereby modulating CXCL12/CXCR4 signaling and immune and cancer cell trafficking.

cell biology↗

bioRxiv2024

Temperate bacteriophage induced in Pseudomonas aeruginosa biofilms can modulate bacteriophage and antibiotic resistance

Given the high levels of resistance in Gram-negative bacteria, phage therapy is garnering increasing attention. In Germany, a clinical study is already underway investigating a phage cocktail for the treatment of Pseudomonas aeruginosa in cystic fibrosis (CF) patients. In our study, we examined susceptibility to virulent phages and the PF1-like prophage and antimicrobial profiles and of P. aeruginosa isolates from a local cystic fibrosis cohort to identify correlations and lysogenic conversion of the prophegs. Consistent with other studies, prophage Pf4 is the most prevalent in this cohort and is activated in the absence of other influences during biofilm formation. These phages can be transferred to other strains that do not contain Pf1-like prophages, thereby influencing the dynamics of bacterial populations in the CF lung. This also rapidly leads to the emergence of a subpopulation resistant to the virulent phages, potentially complicating phage therapy. However, this subset also becomes more susceptible to most antibiotics commonly used in CF, which could be a useful treatment strategy. Interestingly, this bacterial subset lost its susceptibility to colistin, an important inhaled antibiotic in CF, which could lead to treatment failure. Our research highlights both the difficulties and potential strategies to improve treatment options for CF patients. Author summaryWe investigated 51 P. aeruginosa isolates obtained from CF patients for the presence of PF1-like prophages and characterized their susceptibility prior and after lysogenig conversion of the prophages to three virulent phages. Our study revealed that the temperate phage Pf4 is the most prominent PF1-like prophage in this cohort, undergoing lysogenic conversion during biofilm formation. The virions identified in the biofilm supernatants are superinfective and transferable to other prophage-free P. aeruginosa isolates, shaping population dynamics in the CF lung. Prophage reactivation results in the survival of a sub-population with reduced susceptibility to virulent phages, posing a potential challenge for phage therapy. However, this sub-population exhibited restored susceptibility to most CF-relevant antibiotics, presenting an intriguing therapeutic opportunity. Targeted prophage reactivation could sensitize multidrug-resistant P. aeruginosa in CF patients, enhancing or even restoring antimicrobial efficacy. Notably, this sub-population also showed a loss of colistin susceptibility, which may lead to treatment failure when colistin is used as an inhaled antipseudomonal antibiotic. Our findings highlight both significant challenges and potential therapeutic opportunities for optimizing the treatment of CF patients. However, these findings are preliminary and require further investigation, particularly regarding the possibility of lysogenic conversion in other prophages (such as Siphoviridae) and how these interplays with resistance to virulent phages. Further studies are ongoing and will enhance our understanding of the role of prophages in the pathophysiology of CF.

microbiology↗

bioRxiv2024

Serum Proteome Profiling Identifies N-Cadherin and C-Met as Early Marker Candidates of Therapeutic Response to Neoadjuvant Chemotherapy in Breast Cancer

Breast cancer remains the most common cancer in women worldwide. Neoadjuvant chemotherapy (NACT) is often preferred to adjuvant chemotherapy to achieve tumour shrinkage, monitor response to therapy and facilitate surgical removal in the absence of metastases. In addition, there is strong evidence that pathological complete remission (pCR) is associated with prolonged survival. In this study, we sought to identify candidate markers that signal response or resistance to therapy. We present a retrospective longitudinal serum proteomic study of 22 breast cancer patients (11 with pCR and 11 with non-pCR) matched with 21 healthy controls. Serum was analysed by LC-MS/MS after depletion of abundant proteins by immunoaffinity, trypsinisation, isobaric labelling and fractionation by reversed-phase HPLC. We observed an inverse behaviour of the serum proteins c-Met and N-cadherin after the second cycle of chemotherapy with a high predictive value (AUC 0.93). More pronounced changes were observed after the 6th cycle of NACT, with significant changes in the intensity of the proteins contactin-1, centrosomal protein, sex hormone-binding globuline and cholinesterase. Our study highlights the possibility of monitoring response to NACT using serum as a liquid biopsy.

cancer biology↗

bioRxiv2023

Mechanosensing through talin 1 contributes to tissue mechanical homeostasis

It is widely believed that tissue mechanical properties, determined mainly by the extracellular matrix (ECM), are actively maintained. However, despite its broad importance to biology and medicine, tissue mechanical homeostasis is poorly understood. To explore this hypothesis, we developed mutations in the mechanosensitive protein talin1 that alter cellular sensing of ECM stiffness. Mutation of a novel mechanosensitive site between talin1 rod domain helix bundles 1 and 2 (R1 and R2) shifted cellular stiffness sensing curves, enabling cells to spread and exert tension on compliant substrates. Opening of the R1-R2 interface promotes binding of the ARP2/3 complex subunit ARPC5L, which mediates the altered stiffness sensing. Ascending aortas from mice bearing these mutations show increased compliance, less fibrillar collagen, and rupture at lower pressure. Together, these results demonstrate that cellular stiffness sensing regulates ECM mechanical properties. These data thus directly support the mechanical homeostasis hypothesis and identify a novel mechanosensitive interaction within talin that contributes to this mechanism.

cell biology↗

bioRxiv2023

Light perception by the root is essential for gibberellin-induced primary-root elongation in tomato

O_LIThe promoting effect of gibberellin (GA) on primary-root elongation is well-documented in several plant species, yet its influence in others, including tomato (Solanum lycopersicum), remains unclear. C_LIO_LIThe role of GA in primary-root elongation has been studied in tomato using the GA-deficient mutants gib-1 and ga20-oxidase (ga20ox1) and various growth systems, including Dark (D)-root and D-shoot plates. C_LIO_LIGA application to these mutants following germination on vermiculite, promoted primary-root elongation. However, when the roots grew deeper into the dark environment the hormone had no effect. RNA-seq analysis of dark-grown roots, treated with GA, revealed typical transcriptional responses, but the output for cell expansion remained unaffected. When dark-grown roots were illuminated deep in the ground, the hormone promoted their elongation. The results suggest that activation of Phytochrome B (PhyB) in the root, by red light, is essential for GA-induced elongation. C_LIO_LIWe propose that GA promotes tomato root elongation after germination, when roots are exposed to low light underground and this contributes to rapid seedling establishment. As roots penetrate deeper into the soil, insensitivity to GA due to the lack of light may be important for sustained root growth under fluctuating water availability, given that water deficiency suppresses GA accumulation. C_LI

plant biology↗

bioRxiv2023

A fast, robust method for quantitative assessment of collagen fibril architecture from transmission electron micrographs

Collagen is the most abundant protein in mammals; it exhibits a hierarchical organization and provides structural support to a wide range of soft tissues, including blood vessels. The architecture of collagen fibrils dictates vascular stiffness and strength, and changes therein can contribute to disease progression. While transmission electron microscopy (TEM) is routinely used to examine collagen fibrils under normal and pathological conditions, computational tools that enable fast and minimally subjective quantitative assessment remain lacking. In the present study, we describe a novel semi-automated image processing and statistical modeling pipeline for segmenting individual collagen fibrils from TEM images and quantifying key metrics of interest, including fibril crosssectional area and aspect ratio. For validation, we show illustrative results for adventitial collagen in the thoracic aorta from three different mouse models.

bioengineering↗

bioRxiv2023

IVT generation of guideRNAs for Cas9-enrichment Nanopore Sequencing

Generating high-coverage sequencing coverage at select genomic loci has extensive applications in both research science and genetic medicine. Long-read sequencing technologies (e.g. nanopore sequencing) have expanded our ability to generate sequencing data in regions (e.g. repetitive elements) that are difficult to interrogate with short-read sequencing methods. In work presented here, we expand on our previous work using CRISPR/Cas9 for targeted nanopore sequencing by using in vitro transcribed guideRNAs, with 1100 guideRNAs in a single experiment. This approach decreases the cost per guideRNA, increases the number of guideRNAs that can be multiplexed in a single experiment, and provides a way to rapidly screen numerous guideRNAs for cutting efficiency. We apply this strategy in multiple patient-derived pancreatic cancer cell lines, demonstrating its ability to unveil structural variation in "deletion hotspots" around the tumor suppressor genes p16 (CDKN2A), and SMAD4.

molecular biology↗

bioRxiv2023

Loss of PTPMT1 limits mitochondrial utilization of carbohydrates and leads to muscle atrophy and heart failure

While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here we report that the deletion of PTPMT1, a mitochondria-based phosphatase, critically alters mitochondrial fuel selection - the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced. PTPMT1 knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly, PTPMT1 deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that PTPMT1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for both the skeletal muscle and the heart despite the two tissues having different preferred energy sources.

cell biology↗

bioRxiv2022

Irregular optogenetic stimulation waveforms can induce naturalistic patterns of hippocampal spectral activity

IntroductionBrain stimulation is a fundamental and effective therapy for neurological diseases including Parkinsons disease, essential tremor, and epilepsy. One key challenge in delivering effective brain stimulation is identifying the stimulation parameters, such as the amplitude, frequency, contact configuration, and pulse width, that induce an optimal change in symptoms, behavior, or neural activity. Most clinical and translational studies use constant-frequency pulses of stimulation, but stimulation with irregular pulse patterns or non-pulsatile waveforms might induce unique changes in neural activity that could enable better therapeutic responses. Here, we comprehensively evaluate several optogenetic stimulation waveforms, report their differing effects on hippocampal spectral activity, and compare these induced effects to activity recorded during natural behavior. MethodsSprague-Dawley rats were prepared for pan-neuronal excitatory optogenetic stimulation of the medial septum (hSyn-ChR2) and 16-channel microelectrode recording in CA1 and CA3 layers of the hippocampus. We performed grid and random sampling of the parameters comprising several stimulation waveforms, including standard pulse, nested pulse, sinusoid, double sinusoid, and Poisson pulse waveforms. ResultsWe comprehensively report the effects of changing stimulation parameters in these parameter spaces on two key biomarkers of hippocampal function, theta (4-10 Hz) and gamma (32-50 Hz) power. Similarly, robust excitation of hippocampal gamma power was observed across all waveforms, whereas no set of stimulation parameters was sufficient to consistently increase power in the theta band beyond baseline levels of activity (despite the prominent role of the medial septum in pacing hippocampal theta oscillations). Using a manifold learning algorithm to compare high-dimensional neural activity, we show that irregular stimulation patterns produce differing effects with respect to multi-band patterns of activity and can induce activity patterns that more closely resemble activity recorded during natural behavior than conventional parameters. ConclusionOur counter-intuitive findings - that stimulation of the medial septum ubiquitously does not increase hippocampal theta power, and that different waveforms have similar effects on single power bands - contradict recent trends in brain stimulation research, necessitating greater caution and fewer mechanistic assumptions as to how a given stimulation target or waveform will modulate a neurophysiological biomarker of disease. We also reveal that irregular stimulation patterns can have biomimetic utility, promoting their exploration in medical applications where inducing a particular activity pattern can have therapeutic benefit. Last, we demonstrate a scalable data-driven analysis strategy that can make the discovery of such physiologically informed temporal stimulation patterns more empirically tractable in translational settings.

neuroscience↗