Search Results (138)

The role of extracellular vesicle non-coding RNAs in host–parasite interactions remains poorly understood, particularly for human liver flukes. Although tRNA-derived small RNAs (tsRNAs) are emerging as new regulatory molecules in parasite exosomes, they have not yet been characterized for the liver flukes. We performed small RNA sequencing to profile tsRNAs in the exosome-like vesicles derived from the liver fluke Opisthorchis felineus. Transcriptomic data from human cholangiocytes were analyzed to assess the enrichment of the predicted target genes among differentially expressed genes. We identified 247 functional tRNA genes in the O. felineus genome. Exosome-like vesicles were highly enriched for particular tsRNAs: derived from tRNA-Asp-GTC, tRNA-Ile-AAT, tRNA-Lys, tRNA-His, and tRNA-Tyr. This enrichment was independent of both genomic tRNA copy number and the amino acid composition of the trematode proteome. In silico prediction revealed that these tsRNAs target human genes involved in cell cycle, migration, and proliferation. Notably, these predicted target genes were significantly enriched among the differentially expressed genes in treated cholangiocytes. Our study provides the first evidence that O. felineus exosomes carry a specific repertoire of tsRNAs with the potential to regulate host gene networks. We propose that tsRNAs may contribute to host cell manipulation during O. felineus infection. Full article

Calcium (Ca²⁺) is a signal messenger for ion flow in and out of microbial, parasitic, and host defense cells. Manipulation of calcium ion signaling with ion blockers and calcineurin inhibitors may improve host defense while decreasing microbial/parasitic resistance to therapy. Ca²⁺ release from intracellular storage sites controls many host defense functions (cell integrity, movement, and growth). The transformation of phospholipids in the erythrocyte membrane is associated with changes in deformability. This type of lipid bilayer defense mechanism helps to prevent attack by Plasmodium. Patients with sickle cell disease (SS hemoglobin) do not have this protection and are extremely vulnerable to massive hemolysis from parasitic infestation. Patients with thalassemia major also lack parasite protection. Alteration of Ca²⁺ ion channels responsive to environmental stimuli (transient receptor potential) results in erythrocyte protection from Plasmodium. Similarly, calcineurin inhibitors (cyclosporine) reduce heart and brain inflammation injury with Trypanosoma and Taenia. Ca²⁺ channel blockers interfere with malarial life cycles. Several species of parasites are known to invade hepatocytes: Plasmodium, Echinococcus, Schistosoma, Taenia, and Toxoplasma. Ligand-specific membrane channel constituents (inositol triphosphate and sphingosine phospholipid) constitute membrane surface signal messengers. Plasmodium requires Ca²⁺ for energy to grow and to occupy red blood cells. A cascade of signals proceeds from Ca²⁺ to two proteins: calmodulin and calcineurin. Inhibitors of calmodulin were found to blunt the population growth of Plasmodium. An inhibitor of calcineurin (cyclosporine) was found to retard population growth of both Plasmodium and Schistosoma. Calcineurin also controls sensitivity and resistance to antibiotics. After exposure to cyclosporine, the liver directs Ca²⁺ ions into storage sites in the endoplasmic reticulum and mitochondria. Storage of large amounts of Ca²⁺ would be useful if pathogens began to occupy both red blood cells and liver cells. We present scientific evidence supporting the benefits of calcium channel blockers and calcineurin inhibitors to potentiate current antiparasitic therapies. Full article

The cotton aphid Aphis gossypii is a globally significant agricultural pest that threatens crop production through its prolific reproduction. While the parasitoid wasp Binodoxys communis offers promising potential for biological control, the molecular mechanisms underlying its reproductive manipulation of aphid hosts remain poorly understood. Here, we investigated the stage-specific parasitism strategies of B. communis on A. gossypii using integrated biological observations and transcriptomic analysis. Parasitism significantly prolonged aphid development and suppressed reproduction across all host stages, with severity inversely correlated with host age at parasitism. Transcriptomic analysis of ovaries of parasitized aphids revealed 1168 differentially expressed genes, with temporal progression from minimal changes in nymphs (7 DEGs at day 1) to extensive disruption in adults (549 DEGs at day 3). Notably, juvenile hormone acid methyltransferase (JHAMT), the rate-limiting enzyme in juvenile hormone biosynthesis, emerged as a master regulator that is differentially targeted across host stages. In 3rd instar nymphs, single-gene suppression of JHAMT (−3.23-fold change) achieved effective reproductive control, whereas adult parasitism required progressive manipulation of multiple genes including JHAMT, FOHSDR, ALDH, and JHEH. The vitellogenin-vitellogenin receptor system only showed coordinated downregulation in adults, whereas nymphs exhibited preemptive receptor suppression before vitellogenesis onset. These findings demonstrate that B. communis has evolved to exploit a developmental window where host manipulation is most efficient—3rd instar nymphs, which possess sufficient resources for parasitoid development and lack the complex compensatory mechanisms found in adults. This “low-cost, high-reward” strategy based on precision targeting of master regulators in nymphs compared to multi-gene assault in adults, revealing the evolutionary optimization of parasitoid manipulation strategies. Our results provide molecular insights into parasitoid-host coevolution and identified key regulatory targets for developing innovative biological control strategies against this important agricultural pest. Full article

Arthur Conan Doyle’s most famous creation, Sherlock Holmes, is a determined rationalist, yet Doyle was himself a convert to spiritualism. Doyle’s interest in spiritualism informs four, somewhat neglected Gothic tales written during the last decades of the century: “The Winning Shot” (1883); “John Barrington Cowles” (1884); the short novel The Parasite (1894); and “Playing with Fire” (1900). These narratives are notable not only because they respond to the contemporary fascination with spiritualism, but because, in doing so, they explore (sometimes explode) the gendered assumptions of a heteronormative and patriarchal society, which carried over into the close, if erroneous, association of women with the powers of mediumship and mesmerism. Doyle complicates this binary: in his own stories, he presents women as victims of spiritualist power as well as manipulators of it. And while his fictional women do sometimes use that power for their own, self-serving ends, they also use it as a means of taking control back in a male-dominated world. While fascinating in itself, I argue, Doyle’s creation of a Gothicized spiritualism reflects a nuanced engagement with the gendered politics of his historical moment, as the “New Woman” sought to assert herself over the domestic ideology of the day. Full article

Plasmodesmata (PD) are dynamic nanochannels interconnecting plant cells and coordinating development, nutrient distribution, and systemic defense. Their permeability is tightly regulated by callose turnover, PD-localized proteins, lipid microdomains, and endoplasmic reticulum (ER)–plasma membrane (PM) tethers, which together form regulatory nodes that gate symplastic exchange. Increasing evidence demonstrates that effectors from diverse kingdoms—fungi, oomycetes, bacteria, viruses, viroids, phytoplasmas, nematodes, insects, parasitic plants, and symbiotic microbes—converge on these same nodes to modulate PD gating. Pathogens typically suppress callose deposition or destabilize PD regulators to keep channels open, whereas mutualists fine-tune PD conductivity to balance resource exchange with host immunity. This review synthesizes current knowledge of effector strategies that remodel PD architecture or exploit PD for intercellular movement, highlighting novel cross-kingdom commonalities–callose manipulation, reprogramming of PD proteins, lipid rewiring, and co-option of ER-PM tethers. We outline unresolved questions on effector–PD target specificity and dynamics, and identify prospects in imaging, proteomics, and synthetic control of PD. Understanding how effectors reprogram PD connectivity can enable engineering of crops that block pathogenic trafficking while safeguarding beneficial symbioses. Full article

Toxoplasma gondii, the causative agent of toxoplasmosis widespread in animals and humans, is an intracellular apicomplexan protozoan parasite infecting a variety of host cells. Gene editing using CRISPR-Cas9 has become a standard tool to investigate the molecular genetics of this interaction. With respect to gene knock-out (KO) studies, the general paradigm implies that the gene of interest is expressed in the wildtype and that only the gene of interest is affected by the knock-out. Consequently, the observed phenotype depends on the presence or absence of genes of interest. To challenge this paradigm, we knocked out two open reading frames (ORFs) constitutively expressed in T. gondii ShSp1 tachyzoites, but not essential, namely ORF 297720 encoding a trehalose-6-phosphatase homolog and ORF 319730 encoding a You2 C2C2 zinc finger homolog. We analyzed the proteomes of tachyzoites isolated at a late stage of infection, as well as intracellular tachyzoites and host cells at an early stage of infection. The intended KO proteins were present in the T. gondii Sp1 wildtype but absent in the KO clones. Moreover, besides differentially expressed (DE) proteins specific to each KO, 17 DE proteins common to both KOs were identified in isolated tachyzoites and 39 in intracellular tachyzoites. Moreover, 76 common DE proteins were identified in host cells. Network and enrichment analyses showed that these proteins were functionally related to antiviral defense mechanisms. These results indicate that the KO of a gene of interest may not only affect the expression of other genes of the target organism, which in our case is T. gondii, but also the gene expression of its host cells. Therefore, phenotypes of KO strains may not be causally related to the KO of a given gene. Overall, this study highlights that genetic manipulation in T. gondii can lead to system-wide proteomic shifts in both parasite and host, emphasizing the need for cautious interpretation of knock-out-based functional analyses. Full article

Interaction between pathogenic human RNA viruses and host stress granules is an active area of research. Understanding how viruses manipulate, evade, and/or parasitize stress granules and related assemblies may lead to novel approaches for therapeutic and vaccine development. However, knowledge gaps remain, and the field is laden with conflicting conclusions. Stress granules have been implicated to serve as hubs for antiviral signaling pathways, thereby serving to indirectly restrict virus infection through enhancing innate immune responses. More recent evidence suggests that stress granules can exert intrinsic anti-viral properties through direct sequestration of viral RNAs without impacting immune signaling. Here we critically review the literature relevant to specific members of the Flaviviridae with particular focus on Zika virus. Full article

Parasitoids exhibit remarkable abilities to manipulate host physiology, ensuring offspring survival and development. This study investigated the molecular mechanisms underlying how the parasitoid Cotesia chilonis modulates cold tolerance in its host, the rice stem borer Chilo suppressalis, using transcriptome sequencing. We found that the host larvae’s supercooling point was lowest at 3 days post-parasitism but increased significantly by day 4. Transcriptome analysis identified 507 differentially expressed genes (DEGs), including 235 up-regulated by parasitism. Functional enrichment revealed that these DEGs were primarily associated with ribosome biogenesis, protein processing in the endoplasmic reticulum (ER), and oxidative phosphorylation under parasitism stress. Notably, 24 DEGs linked to temperature tolerance were predominantly heat shock proteins (HSPs) and calcium signaling-related genes. The reliability of transcriptome data was confirmed via RT-qPCR for eight randomly selected DEGs. Functional assays demonstrated that parasitism stress significantly inhibited ER activity. However, HSP expression did not significantly affect ER activity or cytosolic Ca²⁺ concentration in the hemolymph cells of C. suppressalis larvae. This research provides insights into the complex physiological and molecular mechanisms through which C. suppressalis responds to parasitism stress, particularly concerning cold tolerance modulation. Full article

The zoonotic disease fasciolosis poses a significant global threat to both humans and livestock. The causative agent of fasciolosis is Fasciola hepatica, which is commonly referred to as liver fluke. The emergence of drug resistance has underscored the urgent need for new therapeutic treatments against F. hepatica. The tegument surface of F. hepatica is characterized by a dynamic syncytial layer surrounded by a glycocalyx, which serves as a crucial interface in host–parasite interactions, facilitating functions such as nutrient absorption, sensory input, and defense against the host immune response. Despite its pivotal role, only recently have we delved deeper into understanding glycans at the host–parasite interface and the glycosylation of hidden antigens. These glycan antigens have shown promise for vaccine development or as targets for drug manipulation across various pathogenic species. This review aims to consolidate current knowledge on the glycosylation of F. hepatica, exploring glycan motifs identified through generic lectin probing and mass spectrometry. Additionally, it examines the interaction of glycoconjugates with lectins from the innate immune systems of both ruminant and human host species. An enhanced understanding of glycans’ role in F. hepatica biology and their critical involvement in host–parasite interactions will be instrumental in developing novel strategies to combat these parasites effectively. In the future, a more comprehensive approach may be adopted in selecting and designing potential vaccine targets, integrating insights from glycosylation studies to improve efficacy. Full article

Certain parasites manipulate host behavior following infection to enhance their own dispersal and transmission. Lepidopteran larvae infected with baculoviruses exhibit increased locomotion, ascending to the apex of their host plant where they ultimately die in a characteristic inverted, liquefied posture suspended by their prolegs—a phenomenon termed “tree-top disease”. Although numerous studies have investigated the underlying causes of this behavior, the precise mechanism governing tree-top disease formation remains unresolved. In this study, Lymantria dispar larvae were infected with Metarhizium anisopliae and Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV). We compared symptom profiles across infection modes and assessed virulence, demonstrating that M. anisopliae infection alters the hyperactive state induced by LdMNPV in larvae exhibiting tree-top disease. Specifically, M. anisopliae promoted tree-top disease behavior during early infection stages but suppressed it during later stages. Furthermore, the symptomatology of larvae co-infected with both pathogens differed significantly from that observed in larvae infected with either M. anisopliae or LdMNPV alone. Co-infected larvae also exhibited accelerated mortality compared to those infected with a single pathogen. The above findings indicate that L. dispar larvae, when co-infected with LdMNPV and M. anisopliae may change behavioral responses that could further modulate the pathogenesis of LdMNPV-induced tree-top disease. Furthermore, a synergistic interaction between M. anisopliae and LdMNPV was observed in the biocontrol of L. dispar. Full article

Over the past three turbulent decades, research has profoundly reshaped our understanding of chronic Toxoplasma gondii infection—traditionally regarded as harmless in immunocompetent individuals—unveiling its surprising impact on human health, performance, and behavior. This review emphasizes the effects of chronic Toxoplasma infection on physical and mental health, cognitive performance, and behavioral changes, highlighting key findings from studies investigating these domains, with a particular focus on both ultimate and proximate mechanisms underlying the observed effects. To this end, the primary focus will be on human studies; however, animal model studies will also be thoroughly considered when necessary and appropriate, to provide context and additional important information. Research demonstrates that chronic Toxoplasma infection may contribute to a broad spectrum of physical health issues. Ecological studies have revealed correlations between toxoplasmosis prevalence and increased morbidity and mortality from various conditions, including cardiovascular diseases, neurological disorders, and certain cancers. Large-scale cross-sectional studies have further shown that infected individuals report a higher incidence of numerous health complaints and diagnosed diseases, suggesting a significant impact on overall physical well-being. In addition to physical health, lifelong Toxoplasma infection (subclinical toxoplasmosis) has been implicated in cognitive impairments and behavioral changes. Studies have reported associations between infection and poorer performance in areas such as reaction time, processing speed, working memory, and executive function. Many of these behavioral changes likely relate to worsened health and a shift towards a “fast life history strategy.” These cognitive deficits can have significant implications for daily functioning and performance. Furthermore, the role of Toxoplasma infection in the development or exacerbation of mental health disorders has been extensively investigated. Meta-analyses, ecological studies, and large-scale observational studies have demonstrated associations between Toxoplasma infection and an increased risk of disorders such as schizophrenia and obsessive–compulsive disorder. While the precise mechanisms underlying these associations remain under investigation, research suggests that neuroinflammation and alterations in neurotransmitter systems are likely to play a role. Far from being harmless, subclinical toxoplasmosis is increasingly recognized as a hidden factor influencing human health, behavior, and cognitive performance—with implications that extend well beyond the individual to public health at large. Further research is warranted to elucidate the complex interplay between Toxoplasma infection, host physiology, and the development of various physical, cognitive, behavioral, and mental health conditions. Full article

Regulating lamprey populations is crucial for maintaining ecological equilibrium. However, the unique sex determination process of lampreys is constrained by multiple factors, complicating intuitive analysis of population dynamics and their impact on the natural environment. This study employed a two-species competition mechanism to elucidate the factors influencing sex ratios and their mechanistic effects on lamprey population size. Using the Lotka–Volterra equations, we investigated how sex ratios affect trophic levels both upstream and downstream of lampreys in the food web. A logistic population growth model was applied to assess the impact of sex ratio variations on symbiotic parasitic species, while the Analytic Hierarchy Process (AHP) was utilized to explore the dynamic relationship between sex ratio changes and ecosystem stability. To validate model efficacy, we manipulated temperature and food availability under controlled disturbance conditions, analyzing temporal variations in lamprey population size across different disturbance intensities to evaluate model sensitivity. The findings indicate that the variable sex ratio’s benefit is in facilitating the lampreys’ population’s enhanced adaptation to environmental shifts. The coexisting species exhibit a similar pattern of population alteration as the lampreys, albeit with a minor delay. A definitive link between the quantity of lampreys and the parasitic species is absent. A male ratio of 0.6 optimally contributes to the ecosystem’s equilibrium. Over time, the configuration of our model’s parameters proves to be sensible. This research provides robust theoretical support for developing scientific strategies to regulate lamprey populations. Full article

Leishmaniasis are infectious diseases caused by several parasitic species of Leishmania, mainly transmitted by the bite of infected phlebotomine sandflies. Humans, dogs, rodents, and other domestic and wild animals can act as reservoir hosts for the different Leishmania species. It is a neglected tropical disease that is endemic in Asia, the Middle East, North and East Africa, the Mediterranean region, and South and Central America. Clinical manifestations and disease severity depend on the species of the infecting parasites and the immunity status of the host. Leishmania represses the protective host immune response by manipulating the macrophage function, subverting cytokine expression to favor its survival and dissemination. A balance between pro-inflammatory and regulatory cells is necessary to bring a positive outcome. Accurate diagnosis and effective treatment represent the cornerstone in the control of this disease, although these are difficult in an environment of precariousness and poverty. Some recent studies highlighted the progressing work on diagnosis and treatments, such as the development of new benzimidazole-triazole derivatives for blocking the parasite growth, feline leishmaniasis with a comparison of immune responses in cats and dogs, and a transglutaminase that has been purified from L. infantum. The results of these studies could open new avenues in combating leishmaniasis. Full article

Piezo-driven compliant actuators capable of out-of-plane displacement from the substrate are urgently required in the fields of micro/nano manipulations and active optics, where compact size and low-profile configurations are often critical. In this paper, a two-stage amplification mechanism is developed by orthogonal series connection of a bridge-type mechanism and a Scott-Russell mechanism, for the sake of a large amplification ratio and high stiffness. The low-profile configuration is realized by horizontally mounting the piezoelectric actuator within the planar bridge-type amplification mechanism. The bridge-type mechanism initially amplifies the output displacement of the piezoelectric actuator. A compound guiding mechanism at the output end significantly enhances the equivalent stiffness and constrains parasitic displacements of the bridge-type mechanism. The second-stage Scott–Russell mechanism, further amplifies and converts the in-plane displacement into out-of-plane motion. The kinematic and static model of the developed mechanism is established using the compliance matrix method, enabling precise prediction of the amplification ratio and input/equivalent stiffness. Finite element simulations and experimental tests on the prototype validate the modeling accuracy and mechanical performance of the proposed low-profile amplification mechanism, demonstrating a large amplification ratio of 15.70, a high resonant frequency of 312.50 Hz, and a load-bearing capacity up to 20 N. Full article

The treatment of leishmaniasis has limitations due to drug toxicity and the increasing resistance of the parasite. In this study, we analyze the role of oxidative stress in the pathogenesis and treatment of leishmaniasis, as well as in new therapeutic alternatives of natural origin. The evasion mechanisms against the host immune response involve surface molecules present in the parasite, which modulate oxidative stress to ensure its survival. Drug treatment requires strict monitoring to minimize adverse reactions and ensure patient safety, as mechanisms such as lipid peroxidation, mitochondrial dysfunction, and depletion of antioxidant defenses are associated with drug toxicity. Plant-derived products with antileishmanial activity impact the parasite’s redox balance, inducing apoptosis and reducing its parasitic load. Most studies are still in preliminary stages, making in vivo assays and clinical studies essential, along with the development of accessible formulations. Oxidative stress is involved in the pathogenesis of leishmaniasis, as Leishmania manipulates the host’s redox balance to survive. It also contributes to drug toxicity, as antimonials and amphotericin B increase reactive oxygen species, causing cellular damage. Several plant-derived compounds have demonstrated antileishmanial activity by modulating oxidative stress and promoting parasite apoptosis. Examples include alkaloids from Aspidosperma nitidum, lignans from Virola surinamensis, flavonoids from Geissospermum vellosii, and triterpenoids such as β-sitosterol. Although these compounds show promising selectivity, most studies remain in preliminary stages, requiring in vivo assays and clinical studies to confirm efficacy and safety, as well as the development of affordable formulations. Full article