Recognition Pathways Research Articles

The Influence of Influencer Marketing and Brand Knowledge on Brand Switching Local Skincare

This study primarily aims to investigate the causal relationships between influencer marketing and brand knowledge on brand switching behavior among local skincare product consumers in East Jakarta, with particular emphasis on understanding the psychological and behavioral mechanisms driving consumer migration between brands. The research employs a quantitative methodology through a structured online survey distributed via multiple digital platforms (WhatsApp, Instagram, and Twitter), achieving a response rate of 87.5% with 154 valid responses from a target of 176 distributed questionnaires. The study population comprised both female (75.3%) and male (24.7%) consumers aged 17-35 years who have experience using local skincare products. Data analysis was conducted using Structural Equation Modeling-Partial Least Squares (SEM-PLS) through SmartPLS software, incorporating measurement model assessment (convergent and discriminant validity) and structural model evaluation (path coefficients and hypothesis testing). The results demonstrate statistically significant positive effects of both influencer marketing (β = 0.229, t = 3.131, p < 0.002) and brand knowledge (β = 0.242, t = 2.857, p < 0.004) on brand switching behavior. Specifically, influencer marketing's impact is manifested through trustworthiness, expertise, and attractiveness indicators, while brand knowledge influences through brand recognition, recall, and quality perception pathways. These findings have substantial implications for local skincare brands' marketing strategies, suggesting that effective influencer collaboration and comprehensive brand education can significantly influence consumer brand switching decisions. The study contributes to the growing body of literature on digital marketing dynamics in the Indonesian skincare industry while providing practical insights for marketing practitioners in the local beauty sector.

Fungal evasion of Drosophila immunity involves blocking the cathepsin-mediated cleavage maturation of the danger-sensing protease

Entomopathogenic fungi play a critical role in regulating insect populations, and representative species from the Metarhizium and Beauveria genera have been developed as eco-friendly biocontrol agents for managing agricultural insect pests. Relative to the advances in understanding antifungal immune responses in Drosophila, knowledge of how fungi evade insect immune defenses remains limited. In this study, we report the identification and characterization of a virulence-required effector Fkp1 in Metarhizium robertsii. Library screening and protein pull-down analysis unveiled that Fkp1 targets the cathepsin protease CtsK1 to inhibit its cleavage maturation of the danger-sensing serine protease Persephone (Psh), thereby facilitating fungal evasion of the Drosophila immune defenses. The Fkp1-like gene is also required in Beauveria bassiana for insect infection. Transgenic expression of Fkp1 in Drosophila suppressed hemolymph cysteine protease activity and down-regulated the expression of antifungal genes. Fkp1 can also mask the Psh cleavage site without interfering with its ability to bait fungal subtilisin proteases. Given the evident compensatory relationship, our data indicate that the protease cascade is more crucial than the molecular pattern pathway in defending flies against fungal infections. This work reveals that Metarhizium fungi have evolved distinct effectors to block the dual recognition pathways of flies for immune evasion and sheds lights on the effector mechanisms mediating microbe-animal interactions.

Homogeneous and bioluminescent biochemical and cellular assay for monitoring cGAMP and enzymes that generate and degrade cGAMP

The cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) signaling pathway is considered an essential pattern recognition and effector pathway in the natural immune system and is mainly responsible for recognizing DNA molecules present in the cytoplasm and activating downstream signaling pathways to generate type I interferons (IFN-I) and other inflammatory factors. STING, a crucial junction protein in the innate immune system, exerts an essential role in host resistance to external pathogen invasion. The DNA introduced by pathogens or tumors is recognized by the cytoplasmic nucleic acid receptor cGAS, and a second messenger, cGAMP, is generated using intracellular guanosine triphosphate (GTP) and adenosine triphosphate (ATP). Furthermore, cellular and extracellular cGAMP concentrations are also controlled by ENPP1, an enzyme that breaks down cGAMP to AMP and GMP. Therefore, the role of the cGAS-STING signaling pathway has generated great interest in inflammatory and cancer research. To advance our understanding of innate immune system and in particular the STING pathway, we have developed a homogeneous, bioluminescent cGAMP detection assay that is very sensitive and highly selective against other nucleotides, cyclic nucleotides, and dicyclic nucleotides. The assay can be also used to monitor the activity of cGAS and ENPP1 to enable the development of inhibitors of both enzymes which might be used for therapeutic applications.

Complex Genomic Landscape of Inversion Polymorphism in Europe's Most Destructive Forest Pest.

In many species, polymorphic genomic inversions underlie complex phenotypic polymorphisms and facilitate local adaptation in the face of gene flow. Multiple polymorphic inversions can co-occur in a genome, but the prevalence, evolutionary significance, and limits to complexity of genomic inversion landscapes remain poorly understood. Here, we examine genome-wide genetic variation in one of Europe's most destructive forest pests, the spruce bark beetle Ips typographus, scan for polymorphic inversions, and test whether inversions are associated with key traits in this species. We analyzed 240 individuals from 18 populations across the species' European range and, using a whole-genome resequencing approach, identified 27 polymorphic inversions covering ∼28% of the genome. The inversions vary in size and in levels of intra-inversion recombination, are highly polymorphic across the species range, and often overlap, forming a complex genomic architecture. We found no support for mechanisms such as directional selection, overdominance, and associative overdominance that are often invoked to explain the presence of large inversion polymorphisms in the genome. This suggests that inversions are either neutral or maintained by the combined action of multiple evolutionary forces. We also found that inversions are enriched in odorant receptor genes encoding elements of recognition pathways for host plants, mates, and symbiotic fungi. Our results indicate that the genome of this major forest pest of growing social, political, and economic importance harbors one of the most complex inversion landscapes described to date and raise questions about the limits of intraspecific genomic architecture complexity.

Moving and Static Faces, Bodies, Objects, and Scenes Are Differentially Represented across the Three Visual Pathways.

Models of human cortex propose the existence of neuroanatomical pathways specialized for different behavioral functions. These pathways include a ventral pathway for object recognition, a dorsal pathway for performing visually guided physical actions, and a recently proposed third pathway for social perception. In the current study, we tested the hypothesis that different categories of moving stimuli are differentially processed across the dorsal and third pathways according to their behavioral implications. Human participants (n = 30) were scanned with fMRI while viewing moving and static stimuli from four categories (faces, bodies, scenes, and objects). A whole-brain group analysis showed that moving bodies and moving objects increased neural responses in the bilateral posterior parietal cortex, parts of the dorsal pathway. By contrast, moving faces and moving bodies increased neural responses, the superior temporal sulcus, part of the third pathway. This pattern of results was also supported by a separate ROI analysis showing that moving stimuli produced more robust neural responses for all visual object categories, particularly in lateral and dorsal brain areas. Our results suggest that dynamic naturalistic stimuli from different categories are routed in specific visual pathways that process dissociable behavioral functions.

An intrinsic hierarchical, retinotopic organization of visual pulvinar connectivity in the human neonate.

The thalamus plays a crucial role in the development of the neocortex, with the pulvinar being particularly important for visual development due to its involvement in various functions that emerge early in infancy. The development of connections between the pulvinar and the cortex constrains its role in infant visual processing and the maturation of associated cortical networks. However, the extent to which adult-like pulvino-cortical pathways are present at birth remains largely unknown, limiting our understanding of how the thalamus may support early vision. To address this gap, we investigated the organization of pulvino-cortical connections in human neonates using probabilistic tractography analyses on diffusion imaging data. Our analyses identified white matter pathways between the pulvinar and areas across occipital, ventral, lateral, and dorsal visual cortices at birth. These pathways exhibited specificity in their connections within the pulvinar, reflecting both an intra-areal retinotopic organization and a hierarchical structure across areas of visual cortical pathways. This organization suggests that even at birth, the pulvinar could facilitate detailed processing of sensory information and communication between distinct processing pathways. Comparative analyses revealed that while the large-scale organization of pulvino-cortical connectivity in neonates mirrored that of adults, connectivity with the ventral visual cortex was less mature than other cortical pathways, consistent with the protracted development of the visual recognition pathway. These findings advance our understanding of the developmental trajectory of thalamocortical connections and provide a framework for how subcortical structures may support early perceptual abilities and scaffold the development of cortex.

Le bambine e i bambini come soggetti attivi della cura dei luoghi: il caso del Contratto di Fiume Ombrone

Children have long been recognised as capable thinkers and active participants in shared educational experiences. However, in spatial planning practices they are often viewed as mere users of a dedicated space. This contribution presents an action-research experience that retraces the empowerment process of the children in a municipality. It does so through the restitution of the projects resulting from the co-construction of a River Agreement. The aim is to adopt a new perspective that views children as agents of transformation, as active members of the community and its empowerment process, advocates for recognition pathways, and stewards of commons. To this end, the conclusions suggest promoting cooperative planning models with a social function that welcomes children as active participants in the care of public spaces and the promotion of social initiatives.

Ferrimagnet-Based Neuromorphic Device Mimicking the Ventral Visual Pathway for High-Accuracy Target Recognition.

The ventral visual pathway (VVP) of the human brain efficiently implements target recognition by employing a deep hierarchical structure to build complex visual concepts from simple features. Artificial neural networks (ANNs) based on spintronic devices are capable of target recognition, but their poor interpretability and limited network depth hinder ANNs from mimicking the VVP. Hardware implementation of the VVP requires a biorealistic spintronic device as well as the corresponding interpretable and deep network structure, which have not been reported so far. Here, we report a ferrimagnetic neuron with a continuously differentiable exponential linear unit (CeLu) activation function, which is closer to biological neurons and could mitigate the issue of limited network depth. Meanwhile, we also demonstrate that a ferrimagnet can construct artificial synapses with high linearity and symmetry to meet the requirements of weight update algorithms. Based on these neurons and synapses, we propose an all-spin convolutional neural network (CNN) with a high interpretability and deep neural network, to mimic the VVP. Compared to the state-of-the-art spintronic-based neuromorphic computing model, the CNN with bionic function, using experimentally derived device parameters, achieves high recognition accuracies of over 91% and 98% on the CIFAR-10 datasets and the MNIST datasets, respectively, showing improvements of 1.13% and 1.76%. Our work provides a promising method to improve the bionic performance of spintronic device-based neural networks.

Mechanism of Dual-Site Recognition in a Classic DNA Aptamer.

Nucleic acid aptamers possess unique advantages in specific recognition. However, the lack of in-depth investigation into their dynamic recognition mechanisms has restricted their rational design and potential applications in fields such as biosensing and targeted therapy. We herein utilized enhanced sampling molecular dynamics to address affinities of adenosine monophosphate (AMP) to the dual binding sites in the DNA aptamer, focusing on the dynamic recognition mechanism and pathways. The present results indicate that in addition to the widely known intermolecular interactions, inequivalence of chemical environments of the two binding sites leads to slightly higher stability of AMP binding to the site proximal to the aptamer terminus. In the presence of two AMPs captured by the two sites, each binding free energy is enhanced. In particular, an additional hydrogen bond of AMP to A10 is introduced in the dual-site binding complex, which increases the binding energy from -4.25 ± 0.47 to -9.48 ± 0.33 kcal mol-1 in the site close to the loop. For the dual-site recognition process, the free energy landscape and minimum free energy pathway calculations elucidate the crucial role of electrostatic interactions between the AMP phosphate groups and Na+ ions in positively cooperative binding mechanisms.

Sea Country Indigenous Protected Areas: Indigenous leadership in the protection of Australia’s marine environments

Australia’s diverse marine environments have been protected and managed by Aboriginal and Torres Strait Islander People since time immemorial, and as an inherent function of their rights and cultural responsibilities. Aboriginal and Torres Strait Islander People around Australia have successfully established Sea Country Indigenous Protected Areas (IPAs), a system of Indigenous-driven collaborative governance and management for protected areas that is unique to Australia. To date, there are fourteen Sea Country IPAs protecting over four million hectares of Sea Country around Australia. This story of Indigenous-led management of traditional sea estates continues to gain recognition in Australia. Though not established under legislation, marine areas within Sea Country IPAs are consistent with the IUCN protected area definition as areas dedicated and managed “by legal and under effective means” and are formally recognised by the Australian Government as part of Australia’s MPA estate. We discuss the enabling factors that have contributed to the success of IPAs in Australia, drawing on the experiences of Traditional Owners presenting at IMPAC5,11IMPAC5-LCS-1514 Sea Country Indigenous Protected Areas: Indigenous Leadership In The Protection Of Australia’S Marine Environments. 7th February 2023 and also the challenges to fully enable Traditional Owners to affirm their rights, roles and responsibilities as coastal and marine managers. Overcoming these challenges provides a pathway for Indigenous-led frameworks, recognition and practice of Indigenous rights and interests for the active management of Australia’s marine protected areas.

Feasibility and acceptability of implementing an evidence-based ESCALATION system for paediatric clinical deterioration.

The ESCALATION system is a novel paediatric Early Warning System that incorporates family involvement and sepsis recognition. This study aimed to assess the feasibility and iteratively refine the ESCALATION system in a variety of hospital settings in preparation for full-service implementation. A series of four multi-methods studies using an Implementation Science and co-design approach were conducted. We examined concepts of implementation, context, and mechanisms of action across a variety of hospitals. Data collected included practice and chart audits, surveys (health professionals), interviews (families) and focus groups (health professionals). Quantitative data were analysed descriptively with qualitative findings assessed by content analysis or thematic analysis. There were 650 audits (Study I-IV), 205 health professional survey responses (Study I), 154 health professionals participated in focus groups (Study II-IV), 13 parents of hospitalised children interviewed (Study I), and 107 parents reported their involvement in the ESCALATION system (Study III-IV). Each of the studies further refined and confirmed the feasibility, specifically the components of family involvement and the sepsis recognition pathway. The Implementation Science evaluation of the ESCALATION system resulted in a uniform approach that was feasible and acceptable to users and appropriate for full-service implementation. This series of four studies used a co-production approach built on the Medical Research Council framework to understand feasibility and acceptability of an intervention to improve recognition and response to clinical deterioration in children to the point of full-service implementation. We have reported a detailed, systematic approach to assessing feasibility and acceptability of a complex intervention using established methodologies for whole of health system implementation. The ESCALATION System is an evidence based paediatric early warning system that is a highly refined, well accepted and accommodates a health system that has substantial contextual variation.

Reading and Writing the Human Glycocode.

The complex carbohydrate structures decorating human proteins and lipids, also called glycans, are abundantly present at cell surfaces and in the secretome. Glycosylation is vital for biological processes including cell-cell recognition, immune responses, and signaling pathways. Therefore, the structural and functional characterization of the human glycome is gaining more and more interest in basic biochemistry research and in the context of developing new therapies, diagnostic tools, and biotechnology applications. For glycomics to reach its full potential in these fields, it is critical to appreciate the specific factors defining the function of the human glycome. Here, we review the glycosyltransferases (the writers) that form the glycome and the glycan-binding proteins (the readers) with an essential role in decoding glycan functions. While abundantly present throughout different cells and tissues, the function of specific glycosylation features is highly dependent on their context. In this review, we highlight the relevance of studying the glycome in the context of specific carrier proteins, cell types, and subcellular locations. With this, we hope to contribute to a richer understanding of the glycome and a more systematic approach to identifying the roles of glycosylation in human physiology.

RACGAP1 is a pivotal gene in lung adenocarcinoma-associated membranous nephropathy: Based on comprehensive bioinformatics analysis and machine learning

BackgroundThis study performs a detailed bioinformatics and machine learning analysis to investigate the genetic foundations of membranous nephropathy (MN) in lung adenocarcinoma (LUAD). MethodsIn this study, the gene expression profiles of MN microarray datasets (GSE99339) and LUAD dataset (GSE43767) were downloaded from the Gene Expression Omnibus database, common differentially expressed genes (DEGs) were obtained using the limma R package. The biological functions were analyzed with R Cluster Profiler package according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Machine learning algorithms, including LASSO regression, support vector machine (SVM), Random Forest, and Boruta analysis, were applied to identify hubgenes linked to LUAD-associated MN. These genes’ prognostic values were evaluated in the TCGA-LUAD cohort and validated through immunohistochemistry on renal biopsy specimens. ResultsA total of 36 DEGs in common were identified for downstream analyses. Functional enrichment analysis highlighted the involvement of the Toll-like receptor 4 pathway and several immune recognition pathways in LUAD-associated MN. COL3A1, PSENEN, RACGAP1, and TNFRSF10B were identified as hub genes in LUAD-associated MN using machine learning algorithms. ROC analysis demonstrated their effective discrimination of MN with high accuracy. Survival analysis showed that lung adenocarcinoma patients with higher expression of these genes had significantly reduced overall survival. In patients with lung adenocarcinoma-associated MN, RACGAP1, COL3A1, PSENEN, and TNFRSF10B were higher expressed in the glomerular, especially RACGAP1, indicating an important role in the pathogenesis of LUAD-associated membranous nephropathy. ConclusionsOur study underscores the critical role of RACGAP1, COL3A1, PSENEN, and TNFRSF10B in the development of LUAD-associated MN, providing important insights for future research and the development of potential therapeutic strategies.

Robust Landslide Recognition Using UAV Datasets: A Case Study in Baihetan Reservoir

The task of landslide recognition focuses on extracting the location and extent of landslides over large areas, providing ample data support for subsequent landslide research. This study explores the use of UAV and deep learning technologies to achieve robust landslide recognition in a more rational, simpler, and faster manner. Specifically, the widely successful DeepLabV3+ model was used as a blueprint and a dual-encoder design was introduced to reconstruct a novel semantic segmentation model consisting of Encoder1, Encoder2, Mixer and Decoder modules. This model, named DeepLab for Landslide (DeepLab4LS), considers topographic information as a supplement to DeepLabV3+, and is expected to improve the efficiency of landslide recognition by extracting shape information from relative elevation, slope, and hillshade. Additionally, a novel loss function term—Positive Enhanced loss (PE loss)—was incorporated into the training of DeepLab4LS, significantly enhancing its ability to understand positive samples. DeepLab4LS was then applied to a UAV dataset of Baihetan reservoir, where comparative tests demonstrated its high performance in landslide recognition tasks. We found that DeepLab4LS has a stronger inference capability for landslides with less distinct boundary information, and delineates landslide boundaries more precisely. More specifically, in terms of evaluation metrics, DeepLab4LS achieved a mean intersection over union (mIoU) of 76.0% on the validation set, which is a substantial 5.5 percentage point improvement over DeepLabV3+. Moreover, the study also validated the rationale behind the dual-encoder design and the introduction of PE loss through ablation experiments. Overall, this research presents a robust semantic segmentation model for landslide recognition that considers both optical and topographic semantics of landslides, emulating the recognition pathways of human experts, and is highly suitable for landslide recognition based on UAV datasets.

Multi-level transcriptomic analysis of LMNA -related dilated cardiomyopathy identifies disease-driving processes.

LMNA- related dilated cardiomyopathy ( LMNA -DCM) is one of the most severe forms of DCM. The incomplete understanding of the molecular disease mechanisms results in lacking treatment options, leading to high mortality amongst patients. Here, using an inducible, cardiomyocyte-specific lamin A/C depletion mouse model, we conducted a comprehensive transcriptomic study, combining both bulk and single nucleus RNA sequencing, and spanning LMNA -DCM disease progression, to identify potential disease drivers. Our refined analysis pipeline identified 496 genes already misregulated early in disease. The expression of these genes was largely driven by disease specific cardiomyocyte sub-populations and involved biological processes mediating cellular response to DNA damage, cytosolic pattern recognition, and innate immunity. Indeed, DNA damage in LMNA -DCM hearts was significantly increased early in disease and correlated with reduced cardiomyocyte lamin A levels. Activation of cytosolic pattern recognition in cardiomyocytes was independent of cGAS, which is rarely expressed in cardiomyocytes, but likely occurred downstream of other pattern recognition sensors such as IFI16. Altered gene expression in cardiac fibroblasts and immune cell infiltration further contributed to tissue-wide changes in gene expression. Our transcriptomic analysis further predicted significant alterations in cell-cell communication between cardiomyocytes, fibroblasts, and immune cells, mediated through early changes in the extracellular matrix (ECM) in the LMNA -DCM hearts. Taken together, our work suggests a model in which nuclear damage in cardiomyocytes leads to activation of DNA damage responses, cytosolic pattern recognition pathway, and other signaling pathways that activate inflammation, immune cell recruitment, and transcriptional changes in cardiac fibroblasts, which collectively drive LMNA -DCM pathogenesis.

Aging is associated with an insufficient early inflammatory response of lung endothelial cells in SARS-CoV-2 infection.

Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy. Here, we investigated age-associated SARS-CoV-2 pathogenesis and endothelial inflammatory responses using humanized K18-hACE2 mice. Survival was reduced to 20% in aged mice (85-112 weeks) versus 50% in young mice (12-15 weeks) at 10 days post infection (dpi). Bulk RNA-sequencing of endothelial cells from mock and infected mice at 2dpi of both age groups (aged: 72-85 weeks; young: 15 weeks) showed substantially lower significant differentially regulated genes in infected aged mice than in young mice (712 versus 2294 genes). Viral recognition and anti-viral pathways such as RIG-I-like receptor signaling, NOD-like receptor signaling and interferon signaling were regulated in response to SARS-CoV-2. Young mice showed several fold higher interferon responses (Ifitm3, Ifit1, Isg15, Stat1) and interferon-induced chemokines (Cxcl10 and Cxcl11) than aged mice. Endothelial cells from infected young mice displayed elevated expression of chemokines (Cxcl9, Ccl2) and leukocyte adhesion markers (Icam1) underscoring that inflammation of lung endothelium during infection could facilitate leukocyte adhesion and thromboinflammation. TREM1 and acute phase response signaling were particularly prominent in endothelial cells from infected young mice. Immunohistochemistry was unable to detect viral protein in pulmonary endothelium. In conclusion, our data demonstrate that the early host response of the endothelium to SARS-CoV-2 infection declines with aging, which could be a potential contributor to disease severity.

Pathways for macrophage uptake of cell-free circular RNAs

Circular RNAs (circRNAs) are stable RNAs present in cell-free RNA, which may comprise cellular debris and pathogen genomes. Here, we investigate the phenomenon and mechanism of cellular uptake and intracellular fate of exogenous circRNAs. Human myeloid cells and B cells selectively internalize extracellular circRNAs. Macrophage uptake of circRNA is rapid, energy dependent, and saturable. CircRNA uptake can lead to translation of encoded sequences and antigen presentation. The route of internalization influences immune activation after circRNA uptake, with distinct gene expression programs depending on the route of RNA delivery. Genome-scale CRISPR screens and chemical inhibitor studies nominate macrophage scavenger receptor MSR1, Toll-like receptors, and mTOR signaling as key regulators of receptor-mediated phagocytosis of circRNAs, a dominant pathway to internalize circRNAs in parallel to macropinocytosis. These results suggest that cell-free circRNA serves as an "eat me" signal and danger-associated molecular pattern, indicating orderly pathways of recognition and disposal.

Functional characterization of NOD1 from golden pompano Trachinotus ovatus

Fish rely on innate immune system for immunity, and nucleotide-binding oligomerization domain-like receptors (NLRs) are a vital group of receptor for recognition. In the present study, NOD1 gene was cloned and characterized from golden pompano Trachinotus ovatus, a commercially important aquaculture fish species. The ORF of T. ovatus NOD1 was 2820 bp long, encoding 939 amino acid residues with a highly conserved domains containing CARD-NACHT-LRRs. Phylogenetic analysis revealed that the T. ovatus NOD1 clustered with those of fish and separated from those of birds and mammals. T. ovatus NOD1 has wide tissue distribution with the highest expression in gills. Bacterial challenges (Streptococcus agalactiae and Vibrio alginolyticus) significantly up-regulated the expression of NOD1 with different response time. The results of T. ovatus NOD1 ligand recognition and signaling pathway analysis revealed that T. ovatus NOD1 could recognize iE-DAP at the concentration of ≧ 100 ng/mL and able to activate NF-κB signaling pathway. This study confirmed that NOD1 play a crucial role in the innate immunity of T. ovatus. The findings of this study improve our understanding on the immune function of NOD1 in teleost, especially T. ovatus.

Developing standardised pathways for recognition of advanced practice attainment

Developing standardised pathways for recognition of advanced practice attainment

Humoral immune response of Galleria mellonella after mono- and co-injection with Hypericum perforatum extract and Candida albicans.

Galleria mellonella is used as a model organism to study the innate immune response of insects. In this study, the humoral immune response was assessed by examining phenoloxidase activity, fungal burden, and the expression of phenoloxidase and antimicrobial peptide genes at different time point following separate and combined injections of Hypericum perforatum extract and a nonlethal dose of Candida albicans. The administration of a plant extract at low doses increased phenoloxidase activity, while higher doses had no effect. Similarly, co-injection of a low dose of the extract with the pathogen allowed half of the yeast cells to survive after 24 h. Co-injection of plant extract with the pathogen decreased the phenoloxidase activity at the end of 4 h compared to C. albicans mono-injection. The phenoloxidase gene expressions was reduced in all experimental conditions with respect to the control. When plant extracts and the pathogen were administered together, gallerimycin and hemolin gene expressions were considerably higher compared to mono-injections of plant extracts and the pathogen. The results of this study reveal that gene activation and regulatory mechanisms may change for each immune gene, and that recognition and signaling pathways may differ depending on the involved immunoregulator.