Search Results (239)

This study identifies and classifies resistance gene analogues (RGAs) in the genomes of Brassica nigra, Sinapis arvensis and Sinapis alba using the RGAugury pipeline. RGAs were categorised into four main classes: receptor-like kinases (RLKs), receptor-like proteins (RLPs), nucleotide-binding leucine-rich repeat (NLR) proteins and transmembrane-coiled-coil (TM-CC) genes. A total of 4499 candidate RGAs were detected, with species-specific proportions. RLKs were the most abundant across all genomes, followed by TM-CCs and RLPs. The sub-classification of RLKs and RLPs identified LRR-RLKs, LRR-RLPs, LysM-RLKs, and LysM-RLPs. Atypical NLRs were more frequent than typical ones in all species. Atypical NLRs were more frequent than typical ones in all species. We explored the relationship between chromosome size and RGA count using regression analysis. In B. nigra and S. arvensis, larger chromosomes generally harboured more RGAs, while S. alba displayed the opposite trend. Exceptions were observed in all species, where some larger chromosomes contained fewer RGAs in B. nigra and S. arvensis, or more RGAs in S. alba. The distribution and density of RGAs across chromosomes were examined. RGA distribution was skewed towards chromosomal ends, with patterns differing across RGA types. Sequence hierarchical pairwise similarity analysis revealed distinct gene clusters, suggesting evolutionary relationships. The study also identified homologous genes among RGAs and non-RGAs in each species, providing insights into disease resistance mechanisms. Finally, RLKs and RLPs were co-localised with reported disease resistance loci in Brassica, indicating significant associations. Phylogenetic analysis of cloned RGAs and QTL-mapped RLKs and RLPs identified distinct clusters, enhancing our understanding of their evolutionary trajectories. These findings provide a comprehensive view of RGA diversity and genomics in these Brassicaceae species, providing valuable insights for future research in plant disease resistance and crop improvement. Full article

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Increasing evidence reveals that the deregulation of cellular antioxidant response with advancing age, resulting in the continuing amplification of oxidative stress-induced inflammatory response, is a pre-eminent cause for the onset of aging-related disease states, including blinding diseases. However, several safeguards, like an antioxidant defense system, are genetically in place to maintain redox homeostasis. Nonetheless, if the homeostatic capacity of such systems fails (like in aging), an inflammatory pathway elicited by excessive oxidative stress-evoked aberrant NLRP3 (NOD, LRR- and pyrin domain-containing protein 3) inflammasome activation can become pathogenic and lead to disease states. Among all known inflammasomes, NLRP3 is the most studied and acts as an intracellular sensor to detect danger(s). Upon activation, NLRP3 recruits apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization and facilitates the recruitment of activated Caspase-1 (Cas-1), which results in the release of inflammatory cytokines, IL-1β and IL-18 and the activation of GasderminD, an executor of pyroptosis. NLRP3 inflammasome is tightly regulated in favor of cell health. However, when and how the activation of NLRP3 and its inflammatory components goes awry, leading to cellular derangement, and what regulatory factors are involved in the normal physiological and aging/oxidative conditions will be included in this review. Also, we address the latest findings to highlight the connection between oxidative stress, antioxidants, and NLRP3 activation as this begets aging diseases and explore the cellular pathways that are in place to regulate oxidative-induced inflammations and the pathobiological consequences of dysregulated inflammatory responses and vice versa. Full article

Wheat (Triticum aestivum L.), a staple crop of global significance, faces constant biotic stress threats, with powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) being particularly damaging. In this study, a multi-year single-site experiment was conducted to minimize the environmental impacts, and a five-level classification system was used to assess powdery mildew resistance. A 660K SNP array genotyped 204 wheat germplasms, followed by GWAS. SNP loci with a −log₁₀(p) > 3.0 were screened and validated across repeats to identify those associated with powdery mildew (Pm) resistance. Twelve SNPs were consistently associated with Pm resistance across multiple years. Of these, three colocalized with previously reported Pm-resistance gene or QTL regions, and the remaining nine represented potentially novel loci. The candidate genes identified included leucine-rich repeat (LRR) and NB-ARC immune receptors, as well as pathogen-related, thioredoxin, and serine threonine-protein kinase genes. Overall, the SNP loci and candidate genes identified in this study provide a basis for further fine mapping and cloning of the genes involved in relation to Pm resistance. Full article

Leucine-rich repeat receptor-like kinases (LRR-RLKs) have evolved to perceive environmental changes. Among LRR-RLKs, PEPR1 perceives the pep1 peptide and triggers defense signal transduction in Arabidopsis thaliana. In the present study, we focused on PEPR1 and PEPR2, which are the receptors of pep1, to understand the role of tyrosine phosphorylation. PEPR1-CD (cytoplasmic domain) recombinant protein exhibited strong tyrosine autophosphorylation, including threonine autophosphorylation. We subjected all tyrosine residues in PEPR1-CD to site-directed mutagenesis. The recombinant proteins were purified along with PEPR1-CD, and Western blotting was performed using a tyrosine-specific antibody. Among the 13 tyrosine residues in PEPR1-CD, the PEPR1(Y995F)-CD recombinant protein showed significantly reduced tyrosine autophosphorylation intensity compared to PEPR1-CD and other tyrosine mutants, despite little change in threonine autophosphorylation. To confirm the autophosphorylation site, we generated a phospho-specific peptide Ab, pY995. As a result, Tyr-995 of PEPR1-CD was a major tyrosine autophosphorylation site in vitro. To understand the function of tyrosine phosphorylation in vivo, we generated transgenic plants, expressing PEPR1-Flag, PEPR1(Y995F)-Flag, and PEPR1(Y995D)-Flag in a pepr1/2 double mutant background. Interestingly, the root growths of PEPR1(Y995F)-Flag and PEPR1(Y995D)-Flag were not inhibited by pep1 peptide treatment, compared to Col-0 and PEPR1-Flag (pepr1/2) transgenic plants. Also, we analyzed downstream components, which included PROPEP1, MPK3, WRKY33, and RBOHD gene expressions in four different genotypes (Col-0, PEPR1-Flag, PEPR1(Y995F)-Flag, and PEPR1(Y995D)-Flag) of plants in the presence of the pep1 peptide. Interestingly, the expressions of PROPEP1, MPK3, WRKY33, and RBOHD were not regulated by pep1 peptide treatment in PEPR1(Y995F)-Flag and PEPR1(Y995D)-Flag transgenic plants, in contrast to Col-0 and PEPR1-Flag. These results suggest that specific tyrosine residues play an important role in vivo in the plant receptor function. Full article

Introduction: Rice, a cornerstone of global food security, faces escalating demands for enhanced yield and disease resistance. We collected 300 high-quality genomes, representing both cultivated (Oryza sativa indica, O. sativa japonica, and O. sativa aus) and wild species (O. rufipogon, O. glaberrima, and O. barthii). Methods: Leveraging HMMER, NLR-Annotator, and OrthoFinder, we systematically identified 148,077 leucine-rich repeat (LRR) and 143,459 nucleotide-binding leucine-rich repeat (NLR) genes, with LRR receptor-like kinases (LRR-RLKs) dominating immune receptor proportions, followed by coiled-coil domain containing (CNL)-type NLRs and LRR receptor-like proteins (LRR-RLPs). Results: Benchmarking Universal Single-Copy Orthologs (BUSCO) assessments confirmed robust genome quality (average score: 94.78). Strikingly, 454 TIR-NB-LRR (TNL) genes—typically rare in monocots—were detected, challenging prior assumptions. Phylogenetic analysis with Arabidopsis TNLs highlighted five O. glaberrima genes clustering with dicot TNLs; these genes featured truncated PLN03210 motifs fused to nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC) and LRR domains. Conclusions: By bridging structural genomics, evolutionary dynamics, and domestication-driven adaptation, this work provides a foundation for targeted breeding strategies and advances functional studies of plant immunity in rice. Full article

Brassica napus is one of the most extensively cultivated oilseed crops in China, but its yield is significantly impacted by stem rot caused by Sclerotinia sclerotiorum. Receptor-like proteins (RLPs) and receptor-like kinases (RLKs) play essential roles in plant–pathogen interactions; however, their regulatory mechanisms remain largely unknown in B. napus. In this study, we investigated the function of the leucine-rich repeat receptor-like protein BnaRLP-G13-1 in Brassica napus immunity. Previous observations indicated that B. napus plants expressing BnaRLP-G13-1 exhibited enhanced resistance to Sclerotinia sclerotiorum. We hypothesized that BnaRLP-G13-1 mediates pathogen recognition and immune signaling. To test this, we employed mitogen-activated protein kinase (MAPK) activity assays, transgenic overexpression analyses, and pathogen infection assays. Our results demonstrated that BnaRLP-G13-1 recognizes the conserved necrosis- and ethylene-inducing peptide Ssnlp24_SsNEP2 derived from S. sclerotiorum, triggering MAPK cascades and subsequent immune responses. Furthermore, protein interaction studies revealed that BnaRLP-G13-1 physically interacts with the receptor-like kinase BnaSOBIR1, which is essential for full antifungal defense activation. These results elucidate the molecular basis of BnaRLP-G13-1-mediated immunity, providing insights into improving disease resistance in oilseed crops. Full article

Dictyostelium is a unique model used to study the complex and interactive cyclic nucleotide signaling pathways that regulate multicellular development. Dictyostelium grow as individual single cells, but in the absence of nutrients, they initiate a multicellular developmental program. Central to this is secreted cAMP, a primary GPCR-response signal. Activated cAMP receptors at the cell surface direct a number of downstream signaling pathways, including synthesis of the intracellular second messengers cAMP and cGMP. These, in turn, activate a series of downstream targets that direct chemotaxis within extracellular cAMP gradients, multicellular aggregation, and, ultimately, cell-specific gene expression, morphogenesis, and cytodifferentiation. Extracellular cAMP and intracellular cAMP and cGMP exhibit rapid fluctuations in concentrations and are, thus, subject to exquisite regulation by both synthesis and degradation. The Dictyostelium genome encodes seven phosphodiesterases (PDEs) that degrade cyclic nucleotides to nucleotide 5’-monophosphates. Each PDE has a distinct structure, substrate specificity, regulatory input, cellular localization, and developmentally regulated expression pattern. The intra- or extra-cellular localizations and enzymatic specificities for cAMP or cGMP are essential for degradative precision at different developmental stages. We discuss the diverse PDEs, the nucleotide cyclases, and the target proteins for cAMP and cGMP in Dictyostelium. We further outline the major molecular, cellular, and developmental events regulated by cyclic nucleotide signaling, with emphasis on the input of each PDE and consequence of loss-of-function mutations. Finally, we relate the structures and functions of the Dictyostelium PDEs with those of humans and in the context of potential therapeutic understandings. Full article

This study investigates the role of the Opnod1, Opnod2, and Optbk1 genes in antiviral and antibacterial immunity of spotted knifejaw (Oplegnathus punctatus). The expression patterns of these genes were analyzed using qRT-PCR in different tissues and at different time points. The open reading frame (ORF) of the Opnod1 gene was 2757 bp in length and encoded 918 amino acids, the ORF of the Opnod2 gene was 2970 bp in length and encoded 990 amino acids, while the Optbk1 gene was 2172 bp in length and encoded 723 amino acids. The Opnod1 and Opnod2 proteins contained three conserved domains (CARD, NOD, and LRR), and Optbk1 contained an STKc domain. The Opnod1, Opnod2, and Optbk1 genes were mainly expressed in immune-related tissues of spotted knifejaw, with the highest relative expression of the Opnod1 in the skin, the Opnod2 in the gill, and the Optbk1 in the liver. The expression of these genes changed significantly in the immune tissues following infection with SKIV-SD and Vibrio harveyi. In kidney cells, the Opnod1, Opnod2, and Optbk1 expression was up-regulated after stimulation by poly I:C and LPS in vitro. The results suggest that the NOD1/2-TBK1 signal pathway may play an important role in the resistance of the spotted knifejaw to virus and bacteria, providing valuable insights for disease-resistant breeding. Full article

The hybrid offspring of barbel chub Squaliobarbus curriculus and grass carp Ctenopharyngodon idella exhibit stronger resistance to the grass carp reovirus (GCRV) infection than grass carp. Toll-like receptors (TLRs) play indispensable roles in the antiviral immunity of fish. In this study, the structures and antiviral immune functions of barbel chub TLR19 (ScTLR19) and grass carp TLR19 (CiTLR19) were compared. The amino acid sequence of ScTLR19 shared high similarity (97.4%) and identity (94.0%) with that of CiTLR19, and a phylogenetic tree revealed the close evolutionary relationship between ScTLR19 and CiTLR19. Protein domain composition analyses showed that ScTLR19 possessed an additional leucine-rich repeat (designated as LRR9) located at amino acid positions 654–677 in the extracellular region, which was absent in CiTLR19. Multiple sequence alignment and three-dimensional structure comparison also indicated that the extracellular regions of ScTLR19 and CiTLR19 exhibited greater differences compared to their intracellular regions. Molecular docking revealed that the extracellular region of ScTLR19 (docking score = −512.31) showed a stronger tendency for binding with polyI:C, compared to the extracellular region of CiTLR19 (docking score = −474.90). Replacing LRR9 in ScTLR19 with the corresponding amino acid sequence from CiTLR19 reduced the binding activity of ScTLR19 to polyI:C, as confirmed by an ELISA. Moreover, overexpression experiments suggested that ScTLR19 could regulate both the IRF3–TRIF and IRF3–MyD88 signaling pathways during GCRV infection, while CiTLR19 only regulated the IRF3–MyD88 signaling pathway. Importantly, replacing LRR9 in ScTLR19 with the corresponding amino acid sequence from CiTLR19 altered the expression regulation on IRF3, MyD88, and TRIF during GCRV infection. These findings collectively reveal the structural and functional differences between ScTLR19 and CiTLR19, and they may provide data to support a deeper understanding of the molecular mechanisms underlying the differences in GCRV resistance between barbel chub and grass carp, as well as the genetic basis for the heterosis of GCRV resistance in their hybrid offspring. Full article

As one of the largest gene families in plants, the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) genes are involved in important biological processes, such as plant growth and development and response to bio-/abiotic stresses. The rubber tree (Hevea brasiliensis Müll. Arg.) is the primary commercial source of natural rubber globally. In this study, 274 LRR-RLK genes were comprehensively identified and classified into 21 subclades of the rubber tree genome. Members belonging to the same subclade exhibited comparable gene structures and possessed conserved protein motifs. Gene duplication analysis detected 35 tandem duplication genes and 81 segmental duplication genes. Cis-element analysis of HbLRR-RLK promoters identified light, hormone, stress, and development-related cis-elements. Tissue-specific expression profiling revealed that 73% (200/274) of HbLRR-RLKs were expressed in at least one of seven analyzed tissues. Protein–protein interaction (PPI) network identified 584 potential interactions among the HbLRR-RLKs. Additionally, subcellular localization analysis suggested that HbPSKR2 (HbLRR-RLK174) is a plasma membrane-localized receptor, and the gene could restore the short-root phenotype of the atpskr mutant in Arabidopsis. These results provide a comprehensive structure to facilitate analysis of the evolution and functional diversification of LRR-RLKs in the rubber tree. Full article

Plants are challenged regularly with multiple types of biotic stress factors, such as pathogens or insect herbivores, in their environment. To detect and defend against pathogens, plants have evolved an innate immune system in which intracellular receptors in the so-called effector-triggered immunity play a vital role. In Arabidopsis thaliana the Toll/interleukin-1 receptors (TIRs) domain is related to intracellular immunity receptors, for example in TIR-NBS-LRR (TNL) proteins. Among the TIR domain carrying proteins, very little is known about the function of the TIR-X proteins. Here, we focus on the recently described TIR-X (TIRP; At5g44900) to analyze its role in phytohormone-mediated plant defense through gene expression and phytohormone quantification. Therefore, we employed two fungal pathogens, the necrotrophic Alternaria brassicicola and the hemibiotrophic Verticillium dahliae, to infect A. thaliana WT (Col-0), TIRP knock-out, and TIRP overexpressing lines for comparative analyses. Furthermore, we included the insect herbivore Spodoptera littoralis and a treatment with S. littoralis egg extract on the plants to analyze any role of TIRP during these attacks. We found that both A. brassicicola and V. dahliae infections increased TIRP gene expression systemically. The salicylic acid content was higher in the TIRP overexpressing line, corresponding to a better S. littoralis larval growth performance in feeding assays. However, since we never observed clear infection-related differences in jasmonate or salicylic acid levels between the wild type and the two transgenic Arabidopsis lines, our results rule out the possibility that TIRP acts via the regulation of phytohormone synthesis and accumulation. Full article

Seborrheic dermatitis (SD) is a chronic inflammatory skin condition often involving the sebaceous-rich areas, characterized by erythematous scaly lesions. It is frequently observed in individuals with immune dysregulation, suggesting the interplay between the immune system and disease development. An altered immune environment leads to an exaggerated inflammatory response with the activation of innate immunity, involving the participation of mast cells, γδ T cells, and the NOD–LRR–pyrin-domain-containing protein 3 (NLRP3) inflammasome. This review aims to assess the complex relationship between Malassezia and the immune system in the pathogenesis of SD. We will explore how an impaired immune response predisposes the skin to Malassezia overgrowth and infection. We will examine the role of adaptive immunity, particularly T helper cells, in driving chronic inflammation in SD. All actors involved, whether part of innate or adaptive immunity, are responsible for the release of pro-inflammatory cytokines, which contribute to the progression of the disease. Therapeutic strategies aimed at the modulation of the immune response in SD have been tested in clinical trials evaluating the efficacy of immunomodulatory treatments in the management of SD. This review synthesizes insights from immunological studies and clinical trials to present an in-depth analysis of the immune mechanisms underpinning SD, thereby proposing targeted therapeutic strategies for its management. Full article

Experimental evidence suggests that alkaloids have anti-influenza and anti-inflammatory effects. However, the risk of translating existing evidence into clinical practice is relatively high. We conducted a systematic review and meta-analysis of animal studies to evaluate the therapeutic effects of alkaloids in treating influenza, providing valuable references for future studies. Seven electronic databases were searched until October 2024 for relevant studies. The Review Manager 5.2 software was utilized to perform the meta-analysis. Our study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42024607535. Alkaloids are significantly correlated with viral titers, pulmonary inflammation scores, survival rates, lung indices, and body weight. However, alkaloid therapy is not effective in reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, the therapeutic effects of alkaloids may be related to the inhibition of the Toll-like receptor 4 or 7/Nuclear factor (NF)-κB signaling pathway, NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome pathway, and the Antiviral innate immune response receptor RIG-I (RIG-I) pathway. Alkaloids are potential candidates for the prevention and treatment of influenza. However, extensive preclinical studies and clinical studies are needed to confirm the anti-influenza and anti-inflammatory properties of alkaloids. Full article

Casparian strip integrity factors (CIFs), which are tyrosine-sulfated small peptides, are crucial genes involved in the formation and regulation of the Casparian strip and play an important role in the regulation of plant stress response. In order to explore the evolution, characteristics, role, and function of CIFs in response to continuous cropping obstacles (CCOs), the bioinformatics and gene expression analysis of CIF genes in Pogostemon cablin was carried out by determining the phylogenetic relationship, chromosome location, gene structure, and RT–qPCR results. Results showed that a total of 12 PatCIF family genes were identified on 12 different chromosomes. Promoter prediction analysis revealed 16 different cis-regulatory elements. A systematic evolutionary study of 33 species indicates CIF family genes originated from Spermatophyta. Collinearity analysis revealed P. cablin shared 19 syntenic genes with Solanum lycopersicum and only 8 with Oryza sativa. Transcriptome analysis indicated that the expression of PatCIF1–4 and PatGSO1b/1c/1f genes decreased under p-hydroxybenzoic acid treatment, and further RT–qPCR validation of four PatCIF genes was consistent with the results. AlphaFold prediction showed a protein interaction region between PatCIF1–4 mature peptide and PatGSO1b/1c/1f via the LRR domain, which provides a key binding surface for mature PatCIFs. This study offers a theoretical basis to investigate the roles of PatCIFs and PatGSO1s in CCOs and their protein interactions in P. cablin. Full article