Aging Cell. 2024 May 16:e14165. doi: 10.1111/acel.14165. Online ahead of print.

ABSTRACT

Impaired mitochondrial function is a hallmark of aging and a major contributor to neurodegenerative diseases. We have shown that disrupted mitochondrial dynamics typically found in aging alters the fate of neural stem cells (NSCs) leading to impairments in learning and memory. At present, little is known regarding the mechanisms by which neural stem and progenitor cells survive and adapt to mitochondrial dysfunction. Using Opa1-inducible knockout as a model of aging and neurodegeneration, we identify a decline in neurogenesis due to impaired stem cell activation and progenitor proliferation, which can be rescued by the mitigation of oxidative stress through hypoxia. Through sc-RNA-seq, we identify the ATF4 pathway as a critical mechanism underlying cellular adaptation to metabolic stress. ATF4 knockdown in Opa1-deficient NSCs accelerates cell death, while the increased expression of ATF4 enhances proliferation and survival. Using a Slc7a11 mutant, an ATF4 target, we show that ATF4-mediated glutathione production plays a critical role in maintaining NSC survival and function under stress conditions. Together, we show that the activation of the integrated stress response (ISR) pathway enables NSCs to adapt to metabolic stress due to mitochondrial dysfunction and metabolic stress and may serve as a therapeutic target to enhance NSC survival and function in aging and neurodegeneration.

PMID:38757355 | DOI:10.1111/acel.14165

Mater Today Bio. 2024 May 6;26:101072. doi: 10.1016/j.mtbio.2024.101072. eCollection 2024 Jun.

ABSTRACT

Osteoarthritis (OA) is a highly disabling pathology, characterized by synovial inflammation and cartilage degeneration. Orthobiologics have shown promising results in OA treatment thanks to their ability to influence articular cells and modulate the inflammatory OA environment. Considering their complex mechanism of action, the development of reliable and relevant joint models appears as crucial to select the best orthobiologics for each patient. The aim of this study was to establish a microfluidic OA model to test therapies in a personalized human setting. The joint-on-a-chip model included cartilage and synovial compartments, containing hydrogel-embedded chondrocytes and synovial fibroblasts, separated by a channel for synovial fluid. For the cartilage compartment, a Hyaluronic Acid-based matrix was selected to preserve chondrocyte phenotype. Adding OA synovial fluid induced the production of inflammatory cytokines and degradative enzymes, generating an OA microenvironment. Personalized models were generated using patient-matched cells and synovial fluid to test the efficacy of mesenchymal stem cells on OA signatures. The patient-specific models allowed monitoring changes induced by cell injection, highlighting different individual responses to the treatment. Altogether, these results support the use of this joint-on-a-chip model as a prognostic tool to screen the patient-specific efficacy of orthobiologics.

PMID:38757057 | PMC:PMC11097088 | DOI:10.1016/j.mtbio.2024.101072

Front Immunol. 2024 May 2;15:1371708. doi: 10.3389/fimmu.2024.1371708. eCollection 2024.

ABSTRACT

Impaired metabolism is recognized as an important contributor to pathogenicity of T cells in Systemic Lupus Erythematosus (SLE). Over the last two decades, we have acquired significant knowledge about the signaling and transcriptomic programs related to metabolic rewiring in healthy and SLE T cells. However, our understanding of metabolic network activity derives largely from studying metabolic pathways in isolation. Here, we argue that enzymatic activities are necessarily coupled through mass and energy balance constraints with in-built network-wide dependencies and compensation mechanisms. Therefore, metabolic rewiring of T cells in SLE must be understood in the context of the entire network, including changes in metabolic demands such as shifts in biomass composition and cytokine secretion rates as well as changes in uptake/excretion rates of multiple nutrients and waste products. As a way forward, we suggest cell physiology experiments and integration of orthogonal metabolic measurements through computational modeling towards a comprehensive understanding of T cell metabolism in lupus.

PMID:38756769 | PMC:PMC11096543 | DOI:10.3389/fimmu.2024.1371708

In Silico Pharmacol. 2024 May 14;12(1):45. doi: 10.1007/s40203-024-00218-z. eCollection 2024.

ABSTRACT

The collagen type I alpha 1 (COL1A1, OMIM #120,150) gene, encoding the alpha-1 chain of type I collagen (UniProt #P02452), plays a key role in life-homeostasis due to its remarkable involvement in collagen synthesis. It is a promising candidate gene implicated in the pathogenesis of cervical insufficiency (CI). This study aimed to identify genetic variations within the COL1A1 gene that contribute to the development of CI. Polymerase chain reaction (PCR) and amplicon sequencing were implemented for single nucleotide polymorphisms (SNPs) detection (+ 1245G/T, SP1 rs1800012), which revealed wild-type sequence for targeted SNPs in enrolled proband indicated negative results regarding COL1A1 gene involvement for current form of CI. It allows further investigation of other closely connected genes probed in this study. Computational approaches viz. Protein-protein interaction (PPI), gene ontology (GO), and pathway participation were used to identify the crucial hub genes and signaling pathways for COL1A1 and CI. Using the Yet Another Scientific Artificial Reality Application (YASARA) software, molecular docking, and molecular dynamic (MD) simulation with the oxytocin (CID 439,302), estradiol (CID 129,728,744), progesterone (CID 5994) and hydroxyprogesterone (CID 150,788) were done. Interactive bioinformatics analysis demonstrated that the COL1A1 and more than 10 collagen sister genes had a strong connection with CI. In sum, the findings of this study provide insights into a modus operandi that can be utilized to illuminate the path toward studying sister genes and smooth diagnosis of CI. These findings have implications for understanding the foundational process of the condition and potentially developing screening, diagnostic, and therapeutic interventions.

PMID:38756679 | PMC:PMC11093961 | DOI:10.1007/s40203-024-00218-z

MedComm (2020). 2024 May 15;5(6):e568. doi: 10.1002/mco2.568. eCollection 2024 Jun.

ABSTRACT

Parkinson's disease (PD) is a mitochondria-related neurodegenerative disease characterized by locomotor deficits and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Majority of PD research primarily focused on neuronal dysfunction, while the roles of astrocytes and their mitochondria remain largely unexplored. To bridge the gap and investigate the roles of astrocytic mitochondria in PD progression, we constructed a specialized optogenetic tool, mitochondrial-targeted anion channelrhodopsin, to manipulate mitochondrial membrane potential in astrocytes. Utilizing this tool, the depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ-aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. Consequently, in vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. Furthermore, 1 h/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction, α-synuclein aggregation, and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD-like phenotype. In summary, our findings suggest the maintenance of proper astrocytic mitochondrial function and the reinstatement of a balanced neurotransmitter profile may provide a new angle for mitigating neuronal dysfunction during the initial phases of PD.

PMID:38756440 | PMC:PMC11094672 | DOI:10.1002/mco2.568

Front Cell Infect Microbiol. 2024 May 2;14:1384420. doi: 10.3389/fcimb.2024.1384420. eCollection 2024.

ABSTRACT

Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host's defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

PMID:38756232 | PMC:PMC11096519 | DOI:10.3389/fcimb.2024.1384420

Rev Fish Biol Fish. 2024;34(2):781-804. doi: 10.1007/s11160-024-09838-2. Epub 2024 Mar 14.

ABSTRACT

Wave climate is shifting over the last decades along the Atlantic coasts of Europe ultimately driven by large-scale patterns of atmospheric variability forced by anthropogenic global warming. Changes in wave height and surf zone orbital currents are hypothesized to drive marked shifts in the shape of intertidal organisms such as the stalked barnacle Pollicipes pollicipes, whose quality and market price are known to decrease non linearly with the peduncle length: width ratio S. This study evaluates wave trends in NW Iberian Peninsula, using the Spanish Port System 2006-2020 SIMAR wave hindcast. On the other hand, trends in stalked barnacle morphology and quality are estimated from 26 sites at the management regions of Baiona and A Guarda between 2011 and 2020. Results show evidence of temporal changes in barnacle quality and, especially, morphometry caused by simultaneous shifts in winter wave induced orbital currents. Because of the non linear relationship between S and the high quality threshold, large increases in S are usually translated to small reductions in quality. However, we identified a tipping point around S = 2.4 that if surpassed can lead to great drops in barnacle quality. In addition, changes in wave forcing will have different effects at each extraction site, as trends in wave climate are decoupled from barnacle morphometry at steeper sites sheltered from the predominant wave direction. In conclusion, this knowledge could be applied to develop site specific barnacle harvesting strategies based on annual wave climate forecasts.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11160-024-09838-2.

PMID:38756184 | PMC:PMC11093743 | DOI:10.1007/s11160-024-09838-2

Phys Rev E. 2024 Apr;109(4-1):044126. doi: 10.1103/PhysRevE.109.044126.

ABSTRACT

Odd viscoelastic materials are constrained by fewer symmetries than their even counterparts. The breaking of these symmetries allows these materials to exhibit different features, which have attracted considerable attention in recent years. Immersing a bead in such complex fluids allows for probing their physical properties, highlighting signatures of their oddity and exploring the consequences of these broken symmetries. We present the conditions under which the activity of an odd viscoelastic fluid can give rise to linear instabilities in the motion of the probe particle, and we unveil how the features of the probe particle dynamics depend on the oddity and activity of the viscoelastic medium in which it is immersed.

PMID:38755925 | DOI:10.1103/PhysRevE.109.044126

BMJ Glob Health. 2024 May 15;9(5):e014678. doi: 10.1136/bmjgh-2023-014678.

ABSTRACT

INTRODUCTION: Africa is experiencing a gradual demographic shift due to rising life expectancy and increasing urbanisation. In sub-Saharan Africa, elderly individuals typically reside with their children. The rise in life expectancy by almost a decade and the prevalence of precarious living conditions raise concerns about the sustainability of the healthcare system, which has traditionally relied on intergenerational solidarity.

METHODS: The research aims to analyse the evolving role of older adults in Cameroonian society and to examine the potential impact of this change on intergenerational relationships and the health of older adults. A qualitative methodology was employed, using intergenerational focus groups in Cameroon.

RESULTS: Traditionally, older adults held a central role in knowledge transmission through discourse. However, the modernisation of society is challenging this position.The emergence of new technologies, particularly communication tools, is leading to a questioning of older adults' experiential knowledge. Societal changes are contributing to a decline in respect for older adults in discourse. Older adults deplore these societal changes and fear for their place in society while young people are questioning the central role of older people in society.

DISCUSSION: These changes could reduce the sense of usefulness of older people, with negative consequences for their health. Several studies have highlighted the impacts of ageism on the health of older adults in industrialised countries. However, there are little data on the impact of the marginalisation of older adults on their health in industrialising societies. Further research is needed to study the impact on the health of older adults.

PMID:38754898 | DOI:10.1136/bmjgh-2023-014678

J Dairy Sci. 2024 May 14:S0022-0302(24)00773-2. doi: 10.3168/jds.2023-23891. Online ahead of print.

ABSTRACT

The welfare of calves is important to both farmers and consumers. Practices that increase the proportion of calves born alive and enable them to thrive through to weaning contribute to improved sustainability. Stillbirths (SB) are calvings where the calf dies at birth or within 24 h after birth. Pre-weaning mortality (PWM) refers to calves that die after the first day of life but before weaning based on termination data. Both SB and PWM are binary traits characterized by low heritability. Data collection for these traits is incomplete, compared with traits like milk yield in cows. Despite these challenges, genetic variation can be measured and used to produce breeding tools, such as estimated breeding values (EBV), to reduce calf mortality over time. The aim of this study was to compare the performance of various linear models to predict SB and PWM traits in Holstein and Jersey cattle and evaluate their applicability for industry-wide use in the Australian dairy industry. Calving records from around 2.25 million Holstein and Jersey dams were obtained from DataGene's Central Data Repository from 2000 onwards to calculate genetic parameters. About 7% of calves were recorded as stillborn in the period 2000-2021 (n = 1.48 million calvings). The prevalence of PWM was much lower than stillbirth during the same period at 2% (n = 0.89 million calves). Genetic parameters were estimated for SB direct, SB maternal and PWM using bivariate linear models with calving ease (CE) as the second trait in the model. The heritability of these calf traits was low and varied between 1 to 5% depending on the breed, trait and model. In Holstein cattle, heritabilities were 2% for PWM and SB direct and 1% for SB maternal while in Jersey cattle heritabilities were 5% for PWM, 2% for SB direct and 1% for SB maternal. The genetic trends for both SB direct and maternal in Holstein cattle indicate improvement in both traits whereas there was no apparent increase or decrease in PWM in the past 2 decades. The coefficient of genetic variation for SB direct and PWM was between 11.7 and 23.0% in Holstein and Jersey cattle demonstrating that there was considerable genetic variation in calf survival traits as a first step to using genetic selection to increase the proportion of calves born alive and calves weaned. A focus on improved calf and calving recording practices is expected to increase the reliability of genetic predictions.

PMID:38754831 | DOI:10.3168/jds.2023-23891

Biotechnol Adv. 2024 May 14:108379. doi: 10.1016/j.biotechadv.2024.108379. Online ahead of print.

ABSTRACT

Biological production of hydrogen has a tremendous potential as an environmentally sustainable technology to generate a clean fuel. Among the different available methods to produce biohydrogen, dark fermentation features the highest productivity and can be used as a means to dispose of organic waste biomass. Within this approach, Clostridia have the highest theoretical H2 production yield. Nonetheless, most strains show actual yields far lower than the theoretical maximum: improving their efficiency becomes necessary for achieving cost-effective fermentation processes. This review aims at providing a survey of the metabolic network involved in H2 generation in Clostridia and strategies used to improve it through metabolic engineering. Together with current achievements, a number of future perspectives to implement these results will be illustrated.

PMID:38754796 | DOI:10.1016/j.biotechadv.2024.108379

Stud Hist Philos Sci. 2024 May 15;105:50-58. doi: 10.1016/j.shpsa.2024.03.003. Online ahead of print.

ABSTRACT

In this essay I suggest that we view design principles in systems biology as minimal models, for a design principle usually exhibits universal behaviors that are common to a whole range of heterogeneous (living and nonliving) systems with different underlying mechanisms. A well-known design principle in systems biology, integral feedback control, is discussed, showing that it satisfies all the conditions for a model to be a minimal model. This approach has significant philosophical implications: it not only accounts for how design principles explain, but also helps clarify one dispute over design principles, e.g., whether design principles provide mechanistic explanations or a distinct kind of explanations called design explanations.

PMID:38754358 | DOI:10.1016/j.shpsa.2024.03.003

Clin Nutr. 2024 May 9;43(6):1532-1543. doi: 10.1016/j.clnu.2024.05.017. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder, characterized by the accumulation of excess fat in the liver, and is a driving factor for various severe liver diseases. These multi-factorial and multi-timescale changes are observed in different clinical studies, but these studies have not been integrated into a unified framework. In this study, we aim to present such a unified framework in the form of a dynamic mathematical model.

METHODS: For model training and validation, we collected data for dietary or drug-induced interventions aimed at reducing or increasing liver fat. The model was formulated using ordinary differential equations (ODEs) and the mathematical analysis, model simulation, model formulation and the model parameter estimation were all performed in MATLAB.

RESULTS: Our mathematical model describes accumulation of fat in the liver and predicts changes in lipid fluxes induced by both dietary and drug interventions. The model is validated using data from a wide range of drug and dietary intervention studies and can predict both short-term (days) and long-term (weeks) changes in liver fat. Importantly, the model computes the contribution of each individual lipid flux to the total liver fat dynamics. Furthermore, the model can be combined with an established bodyweight model, to simulate even longer scenarios (years), also including the effects of insulin resistance and body weight. To help prepare for corresponding eHealth applications, we also present a way to visualize the simulated changes, using dynamically changing lipid droplets, seen in images of liver biopsies.

CONCLUSION: In conclusion, we believe that the minimal model presented herein might be a useful tool for future applications, and to further integrate and understand data regarding changes in dietary and drug induced changes in ectopic TAG in the liver. With further development and validation, the minimal model could be used as a disease progression model for steatosis.

PMID:38754305 | DOI:10.1016/j.clnu.2024.05.017

Mol Cancer. 2024 May 16;23(1):105. doi: 10.1186/s12943-024-02010-1.

ABSTRACT

BACKGROUND: The main drawback of BRAF/MEK inhibitors (BRAF/MEKi)-based targeted therapy in the management of BRAF-mutated cutaneous metastatic melanoma (MM) is the development of therapeutic resistance. We aimed to assess in this context the role of mTORC2, a signaling complex defined by the presence of the essential RICTOR subunit, regarded as an oncogenic driver in several tumor types, including MM.

METHODS: After analyzing The Cancer Genome Atlas MM patients' database to explore both overall survival and molecular signatures as a function of intra-tumor RICTOR levels, we investigated the effects of RICTOR downregulation in BRAFV600E MM cell lines on their response to BRAF/MEKi. We performed proteomic screening to identify proteins modulated by changes in RICTOR expression, and Seahorse analysis to evaluate the effects of RICTOR depletion on mitochondrial respiration. The combination of BRAFi with drugs targeting proteins and processes emerged in the proteomic screening was carried out on RICTOR-deficient cells in vitro and in a xenograft setting in vivo.

RESULTS: Low RICTOR levels in BRAF-mutated MM correlate with a worse clinical outcome. Gene Set Enrichment Analysis of low-RICTOR tumors display gene signatures suggestive of activation of the mitochondrial Electron Transport Chain (ETC) energy production. RICTOR-deficient BRAFV600E cells are intrinsically tolerant to BRAF/MEKi and anticipate the onset of resistance to BRAFi upon prolonged drug exposure. Moreover, in drug-naïve cells we observed a decline in RICTOR expression shortly after BRAFi exposure. In RICTOR-depleted cells, both mitochondrial respiration and expression of nicotinamide phosphoribosyltransferase (NAMPT) are enhanced, and their pharmacological inhibition restores sensitivity to BRAFi.

CONCLUSIONS: Our work unveils an unforeseen tumor-suppressing role for mTORC2 in the early adaptation phase of BRAFV600E melanoma cells to targeted therapy and identifies the NAMPT-ETC axis as a potential therapeutic vulnerability of low RICTOR tumors. Importantly, our findings indicate that the evaluation of intra-tumor RICTOR levels has a prognostic value in metastatic melanoma and may help to guide therapeutic strategies in a personalized manner.

PMID:38755661 | DOI:10.1186/s12943-024-02010-1

Nat Immunol. 2024 May 16. doi: 10.1038/s41590-024-01864-3. Online ahead of print.

NO ABSTRACT

PMID:38755325 | DOI:10.1038/s41590-024-01864-3

Nat Commun. 2024 May 16;15(1):4177. doi: 10.1038/s41467-024-48556-y.

ABSTRACT

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.

PMID:38755196 | DOI:10.1038/s41467-024-48556-y

Nat Commun. 2024 May 16;15(1):4176. doi: 10.1038/s41467-024-48504-w.

ABSTRACT

SETD3 is an essential host factor for the replication of a variety of enteroviruses that specifically interacts with viral protease 2A. However, the interaction between SETD3 and the 2A protease has not been fully characterized. Here, we use X-ray crystallography and cryo-electron microscopy to determine the structures of SETD3 complexed with the 2A protease of EV71 to 3.5 Å and 3.1 Å resolution, respectively. We find that the 2A protease occupies the V-shaped central cleft of SETD3 through two discrete sites. The relative positions of the two proteins vary in the crystal and cryo-EM structures, showing dynamic binding. A biolayer interferometry assay shows that the EV71 2A protease outcompetes actin for SETD3 binding. We identify key 2A residues involved in SETD3 binding and demonstrate that 2A's ability to bind SETD3 correlates with EV71 production in cells. Coimmunoprecipitation experiments in EV71 infected and 2A expressing cells indicate that 2A interferes with the SETD3-actin complex, and the disruption of this complex reduces enterovirus replication. Together, these results reveal the molecular mechanism underlying the interplay between SETD3, actin, and viral 2A during virus replication.

PMID:38755176 | DOI:10.1038/s41467-024-48504-w

Sci Data. 2024 May 16;11(1):503. doi: 10.1038/s41597-024-03324-x.

ABSTRACT

Nanomaterials hold great promise for improving our society, and it is crucial to understand their effects on biological systems in order to enhance their properties and ensure their safety. However, the lack of consistency in experimental reporting, the absence of universally accepted machine-readable metadata standards, and the challenge of combining such standards hamper the reusability of previously produced data for risk assessment. Fortunately, the research community has responded to these challenges by developing minimum reporting standards that address several of these issues. By converting twelve published minimum reporting standards into a machine-readable representation using FAIR maturity indicators, we have created a machine-friendly approach to annotate and assess datasets' reusability according to those standards. Furthermore, our NanoSafety Data Reusability Assessment (NSDRA) framework includes a metadata generator web application that can be integrated into experimental data management, and a new web application that can summarize the reusability of nanosafety datasets for one or more subsets of maturity indicators, tailored to specific computational risk assessment use cases. This approach enhances the transparency, communication, and reusability of experimental data and metadata. With this improved FAIR approach, we can facilitate the reuse of nanosafety research for exploration, toxicity prediction, and regulation, thereby advancing the field and benefiting society as a whole.

PMID:38755173 | DOI:10.1038/s41597-024-03324-x

Science. 2024 May 17;384(6697):744. doi: 10.1126/science.adp9584. Epub 2024 May 16.

ABSTRACT

Trailblazing biochemist and author.

PMID:38753772 | DOI:10.1126/science.adp9584

Plant Physiol. 2024 May 16:kiae286. doi: 10.1093/plphys/kiae286. Online ahead of print.

ABSTRACT

Sclerotinia disease is one of the most devastating fungal diseases worldwide, as it reduces the yields of many economically important crops. Pathogen-secreted effectors play crucial roles in infection processes. However, key effectors of Ciboria shiraiana, the pathogen primarily responsible for sclerotinia disease in mulberry (Morus spp.), remain poorly understood. In this study, we identified and functionally characterized the effector Cs02526 in C. shiraiana and found that Cs02526 could induce cell deathin a variety of plants. Moreover, Cs02526-induced cell death was mediated by the central immune regulator BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1 (BAK1), dependent on a 67-amino acid fragment. Notably, Cs02526 homologues were widely distributed in hemibiotrophic and necrotrophic phytopathogenic fungi, but the homologues failed to induce cell death in plants. Pre-treatment of plants with recombinant Cs02526 protein enhanced resistance against both C. shiraiana and Sclerotinia sclerotiorum. Furthermore, the pathogenicity of C. shiraiana was diminished upon spraying plants with synthetic dsRNA-Cs02526. In conclusion, our findings highlight the cell death-inducing effector Cs02526 as a potential target for future biological control strategies against plant diseases.

PMID:38753366 | DOI:10.1093/plphys/kiae286