Biology subjects

Sharma, K.

Publications and source records attributed to Sharma, K..

At least 91 records · Page 5Linked to original sources

bioRxiv2021

Quality-controlled R-loop meta-analysis reveals the characteristics of R-Loop consensus regions

R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA during transcription. While the pathological consequences of R-loops have been well-studied to date, the locations, classes, and dynamics of physiological R-loops remain poorly understood. R-loop mapping studies provide insight into R-loop dynamics, but their findings are challenging to generalize. This is due to the narrow biological scope of individual studies, the limitations of each mapping modality, and, in some cases, poor data quality. In this study, we reprocessed 693 R-loop mapping datasets from a wide array of biological conditions and mapping modalities. From this data resource, we developed an accurate method for R-loop data quality control, and we reveal the extent of poor-quality data within previously published studies. We then identified a set of high-confidence R-loop mapping samples and used them to define consensus R-loop sites called "R-loop regions" (RL regions). In the process, we revealed the stark divergence between S9.6 and dRNH-based R-loop mapping methods and identified biologically meaningful subtypes of both constitutive and variable R-loops. Taken together, this work provides a much-needed method to assess R-loop data quality and reveals intriguing aspects of R-loop biology.

bioinformatics↗

bioRxiv2021

Exploration and analysis of R-loop mapping data with RLBase

R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA during nascent transcription. In 2012, Ginno et al. introduced the first R-loop mapping method, DNA:RNA immunoprecipitation (DRIP) sequencing. Since that time, dozens of studies have implemented R-loop mapping and new high-resolution techniques have been developed. The resulting datasets have tremendous potential to reveal the causes and consequences of R-loops genome-wide. However, poor quality and variability between mapping approaches pose serious barriers to the meta-analysis of these data. In our recent work, we reprocessed 693 R-loop mapping samples, devising new quality methods, defining a set of high-confidence mapping samples, and then deriving R-loop regions, consensus sites of R-loop formation. This analysis yielded the largest R-loop data resource to date along with novel computational approaches for R-loop mapping analysis. Now, we introduce RLBase, an innovative web server which builds upon those data and software by providing users with the capability to (1) explore hundreds of public R-loop mapping datasets, (2) explore consensus R-loop regions, (3) analyze user-supplied datasets to generate an HTML quality report, and (4) download all the processed data for the 693 samples we previously reprocessed and standardized. In addition to RLBase, we also describe the other software which, along with RLBase, provides a computational framework for R-loop bioinformatics. RLBase, and the rest of these software (termed "RLSuite"), are provided freely under an MIT license and made publicly available: https://gccri.bishop-lab.uthscsa.edu/rlsuite/. RLBase is directly accessible via the following URL: https://gccri.bishop-lab.uthscsa.edu/rlbase/.

bioinformatics↗

bioRxiv2021

The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder

Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. The present study shows the miR-124-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered upregulation of miR-124 in biopsied neuronal cells and postmortem prefrontal cortex from both SZ and BP patients, implying its role not only as a biomarker, but also as a pathophysiological mediator. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124 in the medial prefrontal cortex, which includes brain regions homologous to sub-regions of the human prefrontal cortex. We demonstrated that upregulation of miR-124 increases GRIA2-lacking calcium permeable-AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP.

neuroscience↗

bioRxiv2021

A novel innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins

Sensing of pathogens by ubiquitination is critical for maintaining cytosolic sanctity. However, universal ubiquitination targets on bacteria, especially of proteinaceous origin, remain unidentified. Here, we unveil a novel strategy, involving recognition of degron-like motifs for identification of first protein-based ubiquitination substrates on phylogenetically distinct bacteria. Such motifs can form a new class of intra-cytosolic pathogen associated molecular patterns (PAMPs) as their incorporation enables identification of non-ubiquitin targets by host Ub-ligases. We find SCFFBW7 E3-ligase, supported by the regulatory kinase, GSK3{beta}, is crucial for effective pathogen detection and clearance. This may explain the enhanced risk of infections in Chronic Lymphocytic Leukaemia patients bearing FBXW7 mutations. We conclude that exploitation of such ubiquitous pathogen sensing strategy allows conservation of cellular resources and boost anti-microbial immunity. One Sentence SummaryUbiquitination of bacterial surface proteins fosters sensing and clearance of diverse pathogens

microbiology↗

bioRxiv2021

Allosteric cooperation in β-lactam binding to a non-classical transpeptidase

Mycobacterium tuberculosis peptidoglycan (PG) is atypical as its synthesis involves a new enzyme class, L,D-transpeptidases. Prior studies of L,D-transpeptidases have identified only the catalytic site that binds to peptide moiety of the PG substrate or {beta}-lactam antibiotics. This insight was leveraged to develop mechanism of its activity and inhibition by {beta}-lactams. Here we report identification of an allosteric site at a distance of 21 [A] from the catalytic site that binds the sugar moiety of PG substrates (hereafter referred to as the S-pocket). This site also binds a second {beta}-lactam molecule and influences binding at the catalytic site. We provide evidence that two {beta}-lactam molecules bind co-operatively to this enzyme, one non-covalently at the S-site and one covalently at the catalytic site. This dual {beta}-lactam binding phenomenon is previously unknown and is an observation that may offer novel approaches for the structure-based design of new {beta}-lactam antibiotics for M. tuberculosis.

biochemistry↗

bioRxiv2021

Multifunctional optrode for opsin delivery, optical stimulation, and electrophysiological recordings in freely moving rats

ObjectiveOptogenetics involves delivery of light-sensitive opsins to the target brain region, as well as introduction of optical and electrical devices to manipulate and record neural activity, respectively, from the targeted neural population. Combining these functionalities in a single implantable device is of great importance for a precise investigation of neural networks while minimizing tissue damage. ApproachWe report on the development, characterization, and in vivo validation of a multifunctional optrode that combines a silicon-based neural probe with an integrated microfluidic channel, and an optical glass fiber in a compact assembly. The silicon probe comprises an 11-m-wide fluidic channel and 32 recording electrodes (diameter 30 m) on a tapered probe shank with a length, thickness, and maximum width of 7.5 mm, 50 m, and 150 m, respectively. The size and position of fluidic channels, electrodes, and optical fiber can be precisely tuned according to the in vivo application. Main resultsWith a total system weight of 0.97 g, our multifunctional optrode is suitable for chronic in vivo experiments requiring simultaneous drug delivery, optical stimulation, and neural recording. We demonstrate the utility of our device in optogenetics by injecting a viral vector carrying a ChR2-construct in the prefrontal cortex and subsequent photostimulation of the transfected neurons while recording neural activity from both the target and adjacent regions in a freely moving rat. Additionally, we demonstrate a pharmacological application of our device by injecting GABA antagonist bicuculline in an anesthetized rat brain and simultaneously recording the electrophysiological response. SignificanceOur triple-modality device enables a single-step optogenetic surgery. In comparison to conventional multi-step surgeries, our approach achieves higher spatial specificity while minimizing tissue damage. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/441836v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@11fa19org.highwire.dtl.DTLVardef@3ab5b6org.highwire.dtl.DTLVardef@6fe1b2org.highwire.dtl.DTLVardef@14a7bb3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Distinct sub-cellular autophagy impairments occur independently of protein aggregation in induced neurons from patients with Huntington's disease

Huntingtons disease (HD) is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling HD has remained challenging, as rodent and cellular models poorly recapitulate the disease. To address this, we generated induced neurons (iNs) through direct reprogramming of human skin fibroblasts, which retain age-dependent epigenetic characteristics. HD-iNs displayed profound deficits in autophagy, characterised by reduced transport of late autophagic structures from the neurites to the soma. The neurite-specific alterations in autophagy resulted in shorter, thinner and fewer neurites presented by HD-iNs. CRISPRi-mediated silencing of HTT did not rescue this phenotype but rather resulted in additional autophagy alterations in ctrl-iNs, highlighting the importance of wild type HTT in neuronal autophagy. In summary, our work identifies a distinct subcellular autophagy impairment in aged patient derived HD-neurons and provides a new rational for future development of autophagy activation therapies.

neuroscience↗

bioRxiv2021

PDE9 Inhibition Activates PPARa to Stimulate Mitochondrial Fat Metabolism and Reduce Cardiometabolic Syndrome

Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show inhibiting cyclic-GMP selective phosphodiesterase-9A (PDE9-I) suppresses established diet-induced obesity and CMS in ovariectomized female and male mice. PDE9-I reduces abdominal, hepatic, and myocardial fat accumulation, stimulates mitochondrial activity in brown and white fat, and improves CMS, without altering activity or food intake. PDE9 localizes to mitochondria, and its inhibition stimulates lipolysis and mitochondrial respiration coupled to PPAR-dependent gene regulation. PPAR upregulation is required for PDE9-I metabolic efficacy and is absent in non-ovariectomized females that also display no metabolic benefits from PDE9-I. The latter is compatible with estrogen receptor- altering PPAR chromatin binding identified by ChIPSeq. In humans with heart failure and preserved ejection fraction, myocardial expression of PPARA and its regulated genes is reduced versus control. These findings support testing PDE9-I to treat obesity/CMS in men and postmenopausal women. SummaryOral inhibition of phosphodiesterase type 9 stimulates mitochondrial fat metabolism and lipolysis, reducing central obesity without changing appetite

physiology↗

bioRxiv2021

Multichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation

Simultaneous large-scale recordings and optogenetic interventions hold the promise to decipher the fast-paced and multifaceted dialogue between neurons that sustains brain function. Here we developed unprecedentedly thin, cell-sized Lambertian side-emitting optical fibers and combined them with silicon probes to achieve high quality recordings and ultrafast multichannel optogenetic inhibition in freely moving animals. Our new framework paves the way for large-scale photo tagging and controlled interrogation of rapid neuronal communication in any combination of brain areas. HighlightsTo combine large-scale recordings with optical perturbation we have developed a number of new techniques such as thin optical side-emitting fibers, a fiber matrix connector for thin fibers, an electro-optical commutator for multiple thin fibers, an active patch cord, a flexible fiber bundle ribbon cable, and a modular multi-optrode implantation holder.

neuroscience↗

bioRxiv2021

Dynamic persistence of intracellular bacterial communities of uropathogenic Escherichia coli in a human bladder-chip model of urinary tract infections

Uropathogenic Escherichia coli (UPEC) proliferate within superficial bladder umbrella cells to form intracellular bacterial communities (IBCs) during early stages of urinary tract infections. However, the dynamic responses of IBCs to host stresses and antibiotic therapy are difficult to assess in situ. We develop a human bladder-chip model wherein umbrella cells and bladder microvascular endothelial cells are co-cultured under flow in urine and nutritive media respectively, and bladder filling and voiding mimicked mechanically by application and release of linear strain. Using time-lapse microscopy, we show that rapid recruitment of neutrophils from the vascular channel to sites of infection leads to swarm and neutrophil extracellular trap formation but does not prevent IBC formation. Subsequently, we tracked bacterial growth dynamics in individual IBCs through two cycles of antibiotic administration interspersed with recovery periods which revealed that the elimination of bacteria within IBCs by the antibiotic was delayed, and in some instances, did not occur at all. During the recovery period, rapid proliferation in a significant fraction of IBCs reseeded new foci of infection through bacterial shedding and host cell exfoliation. These insights reinforce a dynamic role for IBCs as harbours of bacterial persistence, with significant consequences for non-compliance with antibiotic regimens.

microbiology↗

bioRxiv2020

Scalable production of tissue-like vascularised liver organoids from human PSCs.

A lack of physiological parity between 2D cell culture and in vivo, has paved the way towards more organotypic models. Organoids exist for a number of tissues, including the liver. However, current approaches to generate hepatic organoids suffer drawbacks, including a reliance on extracellular matrices (ECM), the requirement to pattern in 2D culture, costly growth factors and a lack of cellular diversity, structure and organisation. Current hepatic organoid models are generally simplistic, composed of hepatocytes or cholangiocytes, which renders them less physiologically relevant when compared to native tissue. Here we aim to address these drawbacks. To address this, we have developed an approach that does not require 2D patterning, is ECM independent combined with small molecules to mimic embryonic liver development that produces massive quantities of liver like organoids. Using single-cell RNA sequencing and immunofluorescence we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, innervation and a population of resident macrophage - the Kupffer cells. The organoids exhibit key liver functions including drug metabolism, serum protein production, coagulation factor production, bilirubin uptake and urea synthesis. The organoids can be transplanted and maintained in mice producing human albumin long term. The organoids exhibit a complex cellular repertoire reflective of the organ, have de novo vascularization and innervation, enhanced function and maturity. This is a pre-requisite for a myriad of applications from cellular therapy, tissue engineering, drug toxicity assessment, disease modeling, to basic developmental biology.

cell biology↗

bioRxiv2020

Invasion into the bladder wall generates solitary subpopulations of uropathogenic Escherichia coli that are protected from killing by antibiotics and neutrophil swarms in an organoid model

Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infections (UTIs) requiring antibiotic therapy. Recurrent infections, which occur in a quarter of treated individuals, may arise from "quiescent intracellular reservoirs" of bacteria that invade deeper layers of the bladder wall following infection and exfoliation of superficial umbrella cells. Here, we present a novel bladder organoid model of UPEC infection that recapitulates the stratified bladder architecture within a small volume suitable for live-cell imaging of host-pathogen dynamics with high spatiotemporal resolution. We confirm that bacteria injected into the organoid lumen rapidly enter superficial cells that resemble umbrella cells and proliferate to generate tightly packed colonies that resemble intracellular bacterial communities (IBCs), a hallmark of UPEC pathogenesis. Unexpectedly, at early stages of infection we detect individual "solitary" bacteria that penetrate deeper layers of the organoid wall, where they evade killing by antibiotics and neutrophils. Volumetric serial block face scanning electron microscopy of infected organoids reveals that solitary bacteria can be found throughout the bladder wall and may be intracellular or pericellular (sandwiched between uroepithelial cells). Unlike bacteria within IBCs, which are coccoid-shaped and non-flagellated, solitary bacteria within the bladder wall are rod-shaped and flagellated. We conclude that early invasion of deeper layers of the bladder wall, independent of IBC formation, results in the establishment of reservoirs of solitary bacteria that resist elimination by antibiotics and the host innate immune response.

microbiology↗

bioRxiv2020

The new kid on the block: A dominant-negative mutation of phototropin1 enhances carotenoid content in tomato fruits

Phototropins, the UVA-blue light photoreceptors, endow plants to detect the direction of light and optimize photosynthesis by regulating chloroplasts positioning and stomatal gas exchange. Little is known about their functions in other developmental responses. A tomato Non-phototropic seedling1 (Nps1) mutant, bearing an Arg495His substitution in the vicinity of LOV2 domain in phototropin1, dominant-negatively blocks phot1 and phot2 responses. The fruits of Nps1 mutant were enriched in carotenoids, particularly lycopene, than its parent, Ailsa Craig. Contrarily, CRISPR/CAS9-edited loss of function phototropin1 mutants displayed subdued carotenoids than the parent. The enrichment of carotenoids in Nps1 fruits is genetically linked with the mutation and exerted in a dominant-negative fashion. Nps1 also altered volatile profiles with high levels of lycopene-derived 6-methyl 5-hepten2-one. The transcript levels of several MEP and carotenogenesis pathways genes were upregulated in Nps1. Nps1 fruits showed altered hormonal profiles with subdued ethylene emission and reduced respiration. Proteome profiles showed a causal link between higher carotenogenesis and increased levels of protein protection machinery, which may stabilize proteins contributing to MEP and carotenogenesis pathways. Given the enhancement of carotenoid content by Nps1 in a dominant-negative fashion, it offers a potential tool for high lycopene-bearing hybrid tomatoes. One-sentence summaryA dominant-negative phototropin1 mutation enhances carotenoid levels, alters metabolite homeostasis, and protein quality control machinery in tomato fruits.

plant biology↗

bioRxiv2020

Spatial variation in population-density of snow leopards in a multiple use landscape in Spiti Valley, Trans-Himalaya

The endangered snow leopard Panthera uncia occurs in human use landscapes in the mountains of South and Central Asia. Conservationists generally agree that snow leopards must be conserved through a land-sharing approach, rather than land-sparing in the form of strictly protected areas. Effective conservation through land-sharing requires a good understanding of how snow leopards respond to human use of the landscape. Snow leopard density is expected to show spatial variation within a landscape because of variation in the intensity of human use and the quality of habitat. However, snow leopards have been difficult to enumerate and monitor. Variation in the density of snow leopards remains undocumented, and the impact of human use on their populations is poorly understood. We examined spatial variation in snow leopard density in Spiti Valley, an important snow leopard landscape in India, via spatially explicit capture recapture analysis of camera trap data. We camera trapped an area encompassing a minimum convex polygon of 953 km2. We estimated an overall density of 0.49 (95% CI: 0.39-0.73) adult snow leopards per 100 km2. Using AIC, our best model showed the density of snow leopards to depend on wild prey density, movement about activity centres to depend on altitude, and the expected number of encounters at the activity centre to depend on topography. Models that also used livestock biomass as a density covariate ranked second, but the effect of livestock was weak. Our results highlight the importance of maintaining high density pockets of wild prey populations in multiple use landscapes to enhance snow leopard conservation.

ecology↗

bioRxiv2020

Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model

Severe cases of COVID-19 present with hypercoagulopathies and systemic endothelialitis of the lung microvasculature. The dynamics of vascular damage, and whether it is a direct consequence of endothelial infection or an indirect consequence of immune cell mediated cytokine storms is unknown. This is in part because in vitro models are typically epithelial cell monocultures or fail to recapitulate vascular physiology. We use a vascularised lung-on-chip model where, consistent with monoculture reports, low numbers of SARS-CoV-2 virions are released apically from alveolar epithelial cells. However, rapid infection of the underlying endothelial layer leads to the generation of clusters of endothelial cells with low or no CD31 expression, a progressive loss of endothelial barrier integrity, and a pro-coagulatory microenvironment. These morphological changes do not occur if these cells are exposed to the virus apically. Viral RNA persists in individual cells, which generates a response that is skewed towards NF-KB mediated inflammation, is typified by IL-6 secretion even in the absence of immune cells, and is transient in epithelial cells but persistent in endothelial cells. Perfusion with Tocilizumab, an inhibitor of trans IL-6 signalling slows the loss of barrier integrity but does not prevent the formation of endothelial cell clusters with reduced CD31 expression. SARS-CoV-2 mediated endothelial cell damage occurs despite a lack of rapid viral replication, in a cell-type specific manner and independently of immune-cell mediated cytokine storms, whose effect would only exacerbate the damage.

microbiology↗

bioRxiv2020

Towards Building a Smart Kidney Atlas: Network-based integration of multimodal transcriptomic, proteomic, metabolomic and imaging data in the Kidney Precision Medicine Project

AO_SCPLOWBSTRACTC_SCPLOWKidney Precision Medicine Project (KPMP) is building a spatially-specified human tissue atlas at the single-cell resolution with molecular details of the kidney in health and disease. Here, we describe the construction of an integrated reference tissue map of cells, pathways and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 55 subjects. We use single-cell and -nucleus transcriptomics, subsegmental laser microdissection bulk transcriptomics and proteomics, near-single-cell proteomics, 3-D nondestructive and CODEX imaging, and spatial metabolomics data to hierarchically identify genes, pathways and cells. Integrated data from these different technologies coherently describe cell types/subtypes within different nephron segments and interstitium. These spatial profiles identify cell-level functional organization of the kidney tissue as indicative of their physiological functions and map different cell subtypes to genes, proteins, metabolites and pathways. Comparison of transcellular sodium reabsorption along the nephron to levels of mRNAs encoding the different sodium transporter genes indicate that mRNA levels are largely congruent with physiological activity.This reference atlas provides an initial framework for molecular classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.

bioinformatics↗

bioRxiv2020

Phenotypic and molecular characterization of extended spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae isolates from various samples of animal origin from Assam, India

Extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae has become a major threat globally. Here we have characterized ESBL producing E. coli and K. pneumoniae from various sources, studied antibiogram and resistance gene profiles. Out of 385 samples, 31 (8.05%) were positive for ESBL producing E. coli. Such isolates could be recovered from 10.05, 8.33, 15.63, 6.67 and 4.35 per cent of cattle milk, curd, chicken, pork and cattle faeces samples, respectively. A total of 59 (15.32%) samples were positive for ESBL producing K. pneumoniae, which were isolated from 14.35, 6.25, 21.43 and 34.78 per cent cattle milk, chicken, beef and cattle faeces, respectively. All the 90 isolates were confirmed as ESBL producers by CDT and ESBL-E strip tests. Antibiogram revealed that 74.19% and 69.49% of the ESBL producing E. coli and K. pneumoniae isolates, respectively showed resistance to ceftizoxime, 25.81% and 23.73% to both co-trimoxazole and tetracycline, 19.35% and 25.42% to ciprofloxacin, 9.68% and 16.95% to chloramphenicol, 3.23% and 5.08% to pipercillin-tazobactam, and 3.23% and 3.39% to gentamicin. Resistance gene profiling showed blaCTX-M gene as most predominant (100%). The blaTEM gene was found in 54.84% and 55.93%, blaSHV gene in 90.32% and 77.97%, Sul 1 gene in 90.32% and 86.44% of ESBL producing E. coli and K. pneumoniae isolates, respectively. The Int1 gene was detected in 70.97% and 62.71% isolates, while qnrB gene was found in 3.23% and 10.17% of E. coli and K. pneumoniae isolates, respectively.

molecular biology↗

bioRxiv2020

Mutations in Tomato 1-Aminocyclopropane Carboxylic Acid Synthase2 Uncover Its Role in Development beside System II Responses

The role of ethylene in plant development is mostly inferred from its exogenous application. The usage of the mutants affecting ethylene biosynthesis proffers a better alternative to decipher its role. In tomato, 1-aminocyclopropane carboxylic acid synthase2 (ACS2) is a key enzyme regulating ripening-specific ethylene biosynthesis. We characterized two contrasting acs2 mutants; acs2-1 overproduces ethylene, has higher ACS activity, and increased protein levels, while acs2-2 is an ethylene under-producer, displays lower ACS activity, and protein levels than wild type. Consistent with high/low ethylene emission, the mutants show opposite phenotypes, physiological responses, and metabolomic profiles than the wild type. The acs2-1 showed early seed germination, faster leaf senescence, and accelerated fruit ripening. Conversely, acs2-2 had delayed seed germination, slower leaf senescence, and prolonged fruit ripening. The phytohormone profiles of mutants were mostly opposite in the leaves and fruits. The faster/slower senescence of acs2-1/acs2-2 leaves correlated with the endogenous ethylene/zeatin ratio. The genetic analysis showed that the metabolite profiles of respective mutants co-segregated with the homozygous mutant progeny. Our results uncover that besides ripening, ACS2 participates in vegetative and reproductive development of tomato. The distinct influence of ethylene on phytohormone profiles indicates intertwining of ethylene action with other phytohormones in regulating plant development.

plant biology↗