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OBJECTIVE: Bacterial translocation across the gut barrier has been implicated in the pathogenesis of systemic lupus erythematosus (SLE), though underlying mechanisms remain unclear. This study aimed to investigate the role of translocated bacteria in the context of molecular mimicry by utilizing lupus model mice and blood samples from untreated SLE patients. METHODS: Bacterial translocation was evaluated using nonselective cultured mesenteric lymph nodes (MLNs) from B6SKG mice, a lupus model characterized by impaired TCR signalling and gut dysbiosis. The relationships of detected pathobionts with autoantibody production were examined using in vivo experiments, enzyme-linked immunosorbent assay, immunoblotting, and epitope mapping. RESULTS: Culture-based bacterial profiling in MLNs demonstrated that Lactobacillus murinus was enriched in B6SKG mice with elevated anti-dsDNA IgG levels. Subcutaneous injection of heat-killed L. murinus induced anti-dsDNA IgG production without altering T- or B cell subset composition. Immunoblotting and mass spectrometry analysis identified a peptide ATP-binding cassette (ABC) transporter as a molecular mimicry antigen, with its cross-reactivity in lupus mice confirmed by serological assays and in vivo immunization. The L. murinus ABC transporter exhibited surface epitopes that were cross-reactive with sera from lupus mice and patients. The ABC transporter from R. gnavus, known for its pathogenic role in lupus patients, had a similar epitope sequence to that of the L. murinus ABC transporter and reacted with lupus sera. CONCLUSION: ABC transporters from gut bacteria can serve as cross-reactive antigens that may promote anti-dsDNA antibody production in genetically susceptible mice. These findings underscore the role of commensal-derived molecular mimicry and bacterial translocation in lupus pathogenesis.
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Initial studies using bioinformatics analysis revealed DNA sequence similarities between Trypanosoma cruzi GenBank® M21331, coding for Antigen 36 (Ag 36), and tripartite motif (TRIM) genes. TRIM40 showed 9.7% identity to GenBank M21331, and four additional TRIM genes had identities greater than 5.0%. TRIM37 showed a continuous stretch of identity of 12 nucleotides, that is, at least 25% longer than any of the other TRIMs. When we extended our analysis on the relationships of GenBank M21331 to further innate immune genes, using the Needleman-Wunsch (NW) algorithm for alignment, identities to human IFN-α, IFN-ß, and IFN-γ genes of 13.6%, 12.6%, and 17.9%, respectively, were found. To determine the minimum number of genes coding for proteins closely related to Ag 36, a BLAST-p search was conducted with it versus the T. cruzi genome. The BLAST-p search revealed that T. cruzi GenBank M21331 had 14 gene sequences homologous to microtubule-associated protein (MAP) genes with 100% amino acid sequence identity. To verify the similarities in non-human genes, a study comparing TRIM21 region sequences among mammalian species to the comparable human TRIM21 region showed that related sequences were also present in 11 mammalian species. The MAP genes homologous to Ag 36 form a family of at least 14 genes which mimic human immune genes in the IFN and TRIM families. This mimicry is of gene sequences and not their protein products or epitopes. These results appear to be the first description of molecular mimicry of immune genes in humans by a protozoan parasite.
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Trypanosoma cruzi , Trypanosoma cruzi/genética , Trypanosoma cruzi/inmunología , Humanos , Animales , Proteínas Protozoarias/genética , Interferones/genética , Biología Computacional , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , Proteínas de Motivos Tripartitos/genéticaRESUMEN
Gene expression patterns are very sensitive to external influences and are reflected in phenotypic changes. It was previously described that transferring melanoma cells from a plastic surface to Matrigel led to formation of de novo vascular networks-vasculogenic mimicry-that are characteristic to a stemness phenotype in aggressive tumors. Up to now there was no detailed data about the gene signature accompanying this process. Here, we show that this transfer shortly led to extremely strong epigenetic changes in gene expression in the melanoma cells. We observed that on Matrigel numerous genes controlling ribosome biogenesis were upregulated. However, most of the activated genes were inhibitors of the differentiation genes (ID1, ID2, and ID3). At the same time, the genes that control differentiation were downregulated. Both the upregulated and the downregulated genes are simultaneously targeted by different transcription factors shaping sets of co-expressed genes. The specific group of downregulated genes shaping contacts with rDNA genes are also associated with the H3K27me3 mark and with numerous lincRNAs and miRNAs. We conclude that the stemness phenotype of melanoma cells is due to the downregulation of developmental genes and formation of dedifferentiated cells.
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Regulación Neoplásica de la Expresión Génica , Proteína 1 Inhibidora de la Diferenciación , Proteína 2 Inhibidora de la Diferenciación , Proteínas Inhibidoras de la Diferenciación , Melanoma , Melanoma/genética , Melanoma/patología , Melanoma/metabolismo , Humanos , Proteínas Inhibidoras de la Diferenciación/genética , Proteínas Inhibidoras de la Diferenciación/metabolismo , Proteína 2 Inhibidora de la Diferenciación/genética , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Proteína 1 Inhibidora de la Diferenciación/genética , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Línea Celular Tumoral , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Fenotipo , Diferenciación Celular/genética , Epigénesis Genética , Combinación de Medicamentos , Colágeno , Proteoglicanos , Laminina , Proteínas de NeoplasiasRESUMEN
Mesenchymal stromal/stem cells (MSC) play a crucial role in promoting neovascularization, which is essential for wound healing. They are commonly utilized as an autologous source of progenitor cells in various stem cell-based therapies. However, incomplete MSC differentiation towards a vascular endothelial cell phenotype questions their involvement in an alternative process to angiogenesis, namely vasculogenic mimicry (VM), and the signal transducing events that regulate their in vitro priming into capillary-like structures. Here, human MSC were primed on top of Cultrex matrix to recapitulate an in vitro phenotype of VM. Total RNA was extracted, and differential gene expression assessed through RNA-Seq analysis and RT-qPCR. Transient gene silencing was achieved using specific siRNA. AG490, Tofacitinib, and PP2 pharmacological effects on VM structures were analyzed using the Wimasis software. In vitro VM occurred within 4 h and was prevented by the JAK/STAT3 inhibitors AG490 and Tofacitinib, as well as by the Src inhibitor PP2. RNA-Seq highlighted STAT3 as a signaling hub contributing to VM when transcripts from capillary-like structures were compared to those from cell monolayers. Concomitant increases in IL6, IL1b, CSF1, CSF2, STAT3, FOXC2, RPSA, FN1, and SNAI1 transcript levels suggest the acquisition of a combined angiogenic, inflammatory and epithelial-to-mesenchymal transition phenotype in VM cultures. Increases in STAT3, FOXC2, RPSA, Fibronectin, and Snail protein expression were confirmed during VM. STAT3 and RPSA gene silencing abrogated in vitro VM. In conclusion, in vitro priming of MSC into VM structures requires Src/JAK/STAT3 signaling. This molecular evidence indicates that a clinically viable MSC-mediated pseudo-vasculature process could temporarily support grafts through VM, allowing time for the host vasculature to infiltrate and remodel the injured tissues.
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Quinasas Janus , Células Madre Mesenquimatosas , Neovascularización Fisiológica , Factor de Transcripción STAT3 , Transducción de Señal , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Factor de Transcripción STAT3/metabolismo , Quinasas Janus/metabolismo , Familia-src Quinasas/metabolismo , Células Cultivadas , Diferenciación CelularRESUMEN
OBJECTIVE: To investigate the impact of vasculogenic mimicry (VM) and postoperative adjuvant therapy on the prognosis and survival of patients with esophageal squamous cell carcinoma (ESCC), as well as to assess whether VM affects the clinical benefit of postoperative adjuvant therapy. METHODS: This single-center retrospective analysis included patients who underwent radical surgery for ESCC, which was documented in the medical record system. The presence or absence of VM in surgical specimens was determined using double staining with PAS/CD31. Stratification was applied based on adjuvant therapy and VM status. Survival curves and COX modeling were used to analyze the impact of the presence or absence of VM on the benefit of adjuvant therapy and the survival prognosis of patients. RESULTS: VM-positive patients were more prone to postoperative recurrence and metastasis. VM was identified as an independent risk factor for progression-free survival (PFS) (p < 0.001, 95% CI:1.809-3.852) and overall survival (OS) (p < 0.001, 95% CI:1.603-2.786) in postoperative ESCC. Postoperative adjuvant therapy significantly prolonged PFS (p = 0.008) and OS time (p < 0.001) in patients with stage II and III ESCC, with concurrent chemoradiotherapy being the most effective. However, the presence of VM significantly reduced the benefits of postoperative adjuvant therapy (p < 0.001). CONCLUSION: VM negatively impacts the prognosis of postoperative ESCC patients and reduces the efficacy of postoperative adjuvant therapy.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Recurrencia Local de Neoplasia , Humanos , Masculino , Femenino , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Persona de Mediana Edad , Estudios Retrospectivos , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Pronóstico , Anciano , Neovascularización Patológica , Quimioterapia Adyuvante/métodos , Esofagectomía , Resistencia a Antineoplásicos , Estadificación de NeoplasiasRESUMEN
Breast cancer is a malignant tumor that poses a serious threat to women's health, and vasculogenic mimicry (VM) is strongly associated with bad prognosis in breast cancer. However, the relationship between VM and immune infiltration in breast cancer and the underlying mechanisms have not been fully studied. On the basis of the Cancer Genome Atlas (TCGA), Fudan University Shanghai Cancer Center (FUSCC) database, GSCALite database, and gene set enrichment analysis (GSEA) datasets, we investigated the potential involvement of VM-related genes in the development and progression of breast cancer. We analyzed the differential expression, mutation status, methylation status, drug sensitivity, tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoints, tumor microenvironment (TME), and immune cell infiltration levels associated with VM-related genes in breast cancer. We created two VM subclusters out of breast cancer patients using consensus clustering, and discovered that patients in Cluster 1 had better survival outcomes compared to those in Cluster 2. The infiltration levels of T cells CD4 memory resting and T cells CD8 were higher in Cluster 1, indicating an immune-active state in this cluster. Additionally, we selected three prognostic genes (LAMC2, PIK3CA, and TFPI2) using Lasso, univariate, and multivariate Cox regression and constructed a risk model, which was validated in an external dataset. The prognosis of patients is strongly correlated with aberrant expression of VM-related genes, which advances our knowledge of the tumor immune milieu and enables us to identify previously unidentified breast cancer subtypes. This could direct more potent immunotherapy approaches.
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Cutibacterium acnes, common resident of the human skin, can establish both commensal and pathogenic relations with the human host; however, long-term consequences of C. acnes-induced inflammation remained un(der)explored. To infer the capacity of triggering autoimmunity in humans via molecular mimicry, a comprehensive immunoinformatics analysis of the experimentally characterized C. acnes proteome was performed. The protocol included homology screening between the C. acnes and the human proteome, and validation of shared specificity regions against the collection of experimentally characterized T-cell epitopes, related to autoimmunity. To obtain highly reliable predictions, the results were subjected to additional cross-validation by a dedicated MHC-restriction analysis, including a docking study of C. acnes mimotopes and human counterparts with the highest degree of sequence similarity to MHCII molecules representing the highest risk for detected autoimmune pathologies. Due to mimicking of highly immunogenic, but also evolutionary conserved autoantigens from the Heat Shock protein family, association between C. acnes and the pathogenesis of highly incident autoimmune diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Juvenile Idiopathic Arthritis, was found. To the best of our knowledge, this study is the first one to provide preliminary information and a mechanistic link on the putative involvement of C. acnes in the pathogenesis of autoimmunity in humans.
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Multiple sclerosis (MS) is a prototypical autoimmune disease of the central nervous system (CNS). In addition to CD4+ T cells, memory B cells are now recognized as a critical cell type in the disease. This is underlined by the fact that the best-characterized environmental risk factor for MS is the Epstein-Barr virus (EBV), which can infect and persist in memory B cells throughout life. Several studies have identified changes in anti-EBV immunity in patients with MS. Examples include elevated titers of anti-EBV nuclear antigen 1 (EBNA1) antibodies, interactions of these with the MS-associated HLA-DR15 haplotype, and molecular mimicry with MS autoantigens like myelin basic protein (MBP), anoctamin-2 (ANO2), glial cell adhesion molecule (GlialCAM), and alpha-crystallin B (CRYAB). In this study, we employ a simple in vitro assay to examine the memory B cell antibody repertoire in MS patients and healthy controls. We replicate previous serological data from MS patients demonstrating an increased secretion of anti-EBNA1380-641 IgG in cell culture supernatants, as well as a positive correlation of these levels with autoantibodies against GlialCAM262-416 and ANO21-275. For EBNA1380-641 and ANO21-275, we provide additional evidence suggesting antibody cross-reactivity between the two targets. Further, we show that two efficacious MS treatments - natalizumab (NAT) and autologous hematopoietic stem cell transplantation (aHSCT) - are associated with distinct changes in the EBNA1-directed B cell response and that these alterations can be attributed to the unique mechanisms of action of these therapies. Using an in vitro system, our study confirms MS-associated changes in the anti-EBNA1 memory B cell response, EBNA1380-641 antibody cross-reactivity with ANO21-275, and reveals treatment-associated changes in the immunoglobulin repertoire in MS.
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Reacciones Cruzadas , Antígenos Nucleares del Virus de Epstein-Barr , Células B de Memoria , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/inmunología , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Reacciones Cruzadas/inmunología , Femenino , Masculino , Adulto , Células B de Memoria/inmunología , Herpesvirus Humano 4/inmunología , Persona de Mediana Edad , Anticuerpos Antivirales/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Linfocitos B/inmunología , Memoria InmunológicaRESUMEN
BACKGROUND: Vasculogenic mimicry (VM) is a potential cause of resistance to antiangiogenic therapy and is closely related to the malignant progression of tumors. It has been shown that noncoding RNAs play an important role in the formation of VM in malignant tumors. However, the role of circRNAs in VM of bladder cancer and the regulatory mechanisms are unclear. METHODS: Firstly, hsa_circ_0000520 was identified to have circular character by Sanger sequencing and Rnase R assays. Secondly, the potential clinical value of hsa_circ_0000520 was explored by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) of clinical specimens. Thirdly, the role of hsa_circ_0000520 in bladder cancer invasion, migration, and VM formation was examined by in vivo and in vitro experiments. Finally, the regulatory mechanisms of hsa_circ_0000520 in the malignant progression of bladder cancer were elucidated by RNA binding protein immunoprecipitation (RIP), RNA pulldown, co-immunoprecipitation (co-IP), qRT-PCR, Western blot (WB), and fluorescence co-localization. RESULTS: Hsa_circ_0000520 was characterized as a circular RNA and was lowly expressed in bladder cancer compared with the paracancer. Bladder cancer patients with high expression of hsa_circ_0000520 had better survival prognosis. Functionally, hsa_circ_0000520 inhibited bladder cancer invasion, migration, and VM formation. Mechanistically, hsa_circ_0000520 acted as a scaffold to promote binding of UBE2V1/UBC13 to Lin28a, further promoting the ubiquitous degradation of Lin28a, improving PTEN mRNA stability, and inhibiting the phosphorylation of the PI3K/AKT pathway. The formation of hsa_circ_0000520 in bladder cancer was regulated by RNA binding protein QKI. CONCLUSIONS: Hsa_circ_0000520 inhibits metastasis and VM formation in bladder cancer and is a potential target for bladder cancer diagnosis and treatment.
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Movimiento Celular , Fosfohidrolasa PTEN , Fosfatidilinositol 3-Quinasas , ARN Circular , Proteínas de Unión al ARN , Transducción de Señal , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Transducción de Señal/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Movimiento Celular/genética , Masculino , Animales , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Femenino , Neovascularización Patológica/genética , Ratones Desnudos , Ratones , Persona de Mediana Edad , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Individuals with Borderline Personality Disorder (BPD) are theorized to experience lower cognitive empathy but heightened affective empathy. Despite meta-analyses addressing cognitive empathy, affective empathy remains unexplored. This pre-registered systematic review and meta-analysis investigated affective empathy in individuals with BPD or high BPD traits relative to healthy comparisons, using a multidimensional approach including, early affective empathy, emotion contagion, and empathic concern. METHODS: Systematic search of SCOPUS, PubMed, Medline COMPLETE, and PsycINFO (June 27, 2022, May 14, 2023, and July 1, 2024) was completed. Included studies compared affective empathy in those with BPD/high BPD traits with healthy comparisons, utilized experimental or self-report designs, and were peer-reviewed or PhD theses. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Among 22 eligible studies identified, results revealed individuals with BPD/high BPD traits showed significantly higher emotion contagion (Npooled = 1797, g = -1.10, 95 % CI [-1.57, -0.62]). No significant differences were found in empathic concern (Npooled = 1545, g = 0.06, 95 % CI [-0.10, 0.22]), or early affective empathy for anger (Npooled = 245, g = 0.28, 95 % CI [-0.0.53, 1.09]) and happiness, (Npooled = 189, g = 0.34, 95 % CI [-0.1.50, 2.18]). LIMITATIONS: Few included studies for early affective empathy, methodological shortcomings in the broader literature and study heterogeneity suggest caution when interpreting these effects, emphasizing the need for targeted research. CONCLUSIONS: While individuals with BPD/high BPD traits are more likely to subjectively experience others' distress through emotion contagion, no differences were found in early affective empathy or ability to direct sympathy and concern towards others.
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All talkers show some flexibility in their speech, and the ability to imitate an unfamiliar accent is a skill that shows vast individual differences. Yet the source of these individual differences, in particular whether they originate from perceptual, motor, or social/personality factors, is not yet clear. In the current study, we ask how individual differences in these factors predict individual differences in deliberate accent imitation. Participants imitated three accents, and attempts were rated for accuracy. A set of measures tracking individual differences in perceptual, motor, cognitive, personality, and demographic factors were also acquired. Imitation ability was related to differences in musical perception, vocal articulation, and the personality characteristic of "openness to experience," and was affected by attitudes towards the imitated talkers. Taken together, results suggest that deliberate accent imitation skill is modulated not only by core perceptual and motor skills, but also by personality and affinity to the talker, suggesting that some aspects of deliberate imitation are a function of domain-general constraints on perceptual-motor systems, while others may be modulated by social context.
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Background: Clear cell renal cell carcinoma (ccRCC) is a highly aggressive cancer associated with higher death rates. However, traditional anti-angiogenic therapies have limited effectiveness due to drug resistance. Vascular mimicry (VM) provides a different way for tumors to develop blood vessels without relying on endothelial cells or angiogenesis. However, the intricate mechanisms and interplay between it and the immune microenvironment in ccRCC remain unclear. Methods: A PubMed and GeneCards literature review was conducted to identify VM-related genes (VMRGs). VMRGs expression profiles were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), developing a novel VM risk score model and nomogram for ccRCC. The EBI ArrayExpress database (the validation set) was obtained to validate the prognostic model. The relationship between VMRGs risk score clinical characteristics and immune infiltration was investigated. Finally, the expression of six model VMRGs was validated using single-cell analysis, GEPIA, Human Protein Atlas (HPA), and quantitative Real-time PCR (qRT-PCR). Results: Cox regression analysis and nomogram identified L1CAM, TEK, CLDN4, EFNA1, SERPINF1, and MALAT1 as independent prognostic risk factors, which could be used to stratify the ccRCC population into two risk groups with distinct immune profiles and responsiveness to immunotherapy. The results of single-cell analysis, GEPIA, HPA, and qRT-PCR validated the model genes' expression. Conclusions: Our novel findings constructed a convenient and reliable 6 gene signatures as potential immunologic and prognostic biomarkers of VM in ccRCC.
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A priori, early exposure to a wide range of bacteria, viruses, and parasites appears to fortify and regulate the immune system, potentially reducing the risk of autoimmune diseases. However, improving hygiene conditions in numerous societies has led to a reduction in these microbial exposures, which, according to certain theories, could contribute to an increase in autoimmune diseases. Indeed, molecular mimicry is a key factor triggering immune system reactions; while it seeks pathogens, it can bind to self-molecules, leading to autoimmune diseases associated with microbial infections. On the other hand, a hygiene-based approach aimed at reducing the load of infectious agents through better personal hygiene can be beneficial for such pathologies. This review sheds light on how the evolution of the innate immune system, following the evolution of molecular patterns associated with microbes, contributes to our protection but may also trigger autoimmune diseases linked to microbes. Furthermore, it addresses how hygiene conditions shield us against autoimmune diseases related to microbes but may lead to autoimmune pathologies not associated with microbes.
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Background: In the ongoing battle against breast cancer, a leading cause of cancer-related mortality among women globally, the urgent need for innovative prognostic markers and therapeutic targets is undeniable. This study pioneers an advanced methodology by integrating machine learning techniques to unveil a vascular mimicry signature, offering predictive insights into breast cancer outcomes. Vascular mimicry refers to the phenomenon where cancer cells mimic blood vessel formation absent of endothelial cells, a trait associated with heightened tumor aggression and diminished response to conventional treatments. Methods: The study's comprehensive analysis spanned data from over 6,000 breast cancer patients across 12 distinct datasets, incorporating both proprietary clinical data and single-cell data from 7 patients, accounting for a total of 43,095 cells. By employing an integrative strategy that utilized 10 machine learning algorithms across 108 unique combinations, the research scrutinized 100 existing breast cancer signatures. Empirical validation was sought through immunohistochemistry assays, alongside explorations into potential immunotherapeutic and chemotherapeutic avenues. Results: The investigation successfully identified six genes related to vascular mimicry from multi-center cohorts, laying the groundwork for a novel predictive model. This model outstripped the prognostic accuracy of traditional clinical and molecular indicators in forecasting recurrence and mortality risks. High-risk individuals identified by our model faced worse outcomes. Further validation through IHC assays in 30 patients underscored the model's extensive applicability. Notably, the model unveiled varying therapeutic responses; low-risk patients might achieve greater benefits from immunotherapy, whereas high-risk patients demonstrated a particular sensitivity to certain chemotherapies, such as ispinesib. Conclusions: This model marks a significant step forward in the precise evaluation of breast cancer prognosis and therapeutic responses across different patient groups. It heralds the possibility of refining patient outcomes through tailored treatment strategies, accentuating the potential of machine learning in revolutionizing cancer prognosis and management.
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Neoplasias de la Mama , Aprendizaje Automático , Humanos , Femenino , Neoplasias de la Mama/patología , Pronóstico , Biomarcadores de Tumor , Mimetismo Biológico , Neovascularización PatológicaRESUMEN
Mimicry, that is, the imitation of any unpalatable or defensive species by another, has been of central interest to evolutionary research since Darwin's lifetime. Two ant species, Camponotus guanchus Santschi, 1908 and Crematogaster alluaudi Emery, 1893, endemic to the Canary Islands, occur in two color-morphs: While the head of workers is always reddish and the gaster blackish, the mesosoma (inclusive waist) is either fully reddish or fully blackish. In addition to the obvious morphological and coloration similarities, we provide evidence of mimicry: (i) Ca. guanchus was found only within the area of Cr. alluaudi. (ii) Color morphs are geographically non-randomly distributed: Workers of both species from 16 localities of syntopic occurrences shared in eight cases a blackish and in eight cases a reddish mesosoma. Hence, Ca. guanchus mimics both local color-morphs of Cr. alluaudi. We consider a fascinating analogy with the Mediterranean mimicry system in Camponotus lateralis (Olivier, 1792) and its model species of the Crematogaster scutellaris (Olivier, 1792) group on an island scale. Additionally, we present two endemic bug species, Perenotus stysi (Ribes et al., 2008) and P. malobae Roca-Cusachs & Goula, 2016, as mimics of those Cr. alluaudi workers having a reddish mesosoma. Our distribution, coloration, frequency, and behavioral data as well as the analogy with Ca. lateralis and the Cr. scutellaris group suggest a Batesian-mimicry system in which Ca. guanchus, Perenotus stysi, and P. malobae mimic the unpalatable and aggressive Cr. alluaudi as an antipredator adaptation.
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Introduction: Smiling during conversation occurs interactively between people and is known to build good interpersonal relationships. However, whether and how much the amount that an individual smiles is influenced by the other person's smile has remained unclear. This study aimed to quantify the amount of two individuals' smiles during conversations and investigate the dependency of one's smile amount (i.e., intensity and frequency) on that of the other. Method: Forty participants (20 females) engaged in three-minute face-to-face conversations as speakers with a listener (male or female), under three conditions, where the amount of smiling response by listeners was controlled as "less," "moderate," and "greater." The amount of the smiles was quantified based on their facial movements through automated facial expression analysis. Results: The results showed that the amount of smiling by the speaker changed significantly depending on the listener's smile amount; when the listeners smiled to a greater extent, the speakers tended to smile more, especially when they were of the same gender (i.e., male-male and female-female pairs). Further analysis revealed that the smiling intensities of the two individuals changed in a temporally synchronized manner. Discussion: These results provide quantitative evidence for the dependence of one's smile on the other's smile, and the differential effect between gender pairs.
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Human immunodeficiency virus type 1 (HIV-1) vaccine immunogens capable of inducing broadly neutralizing antibodies (bNAbs) remain obscure. HIV-1 evades immune responses through enormous diversity and hides its conserved vulnerable epitopes on the envelope glycoprotein (Env) by displaying an extensive immunodominant glycan shield. In elite HIV-1 viremic controllers, glycan-dependent bNAbs targeting conserved Env epitopes have been isolated and are utilized as vaccine design templates. However, immunological tolerance mechanisms limit the development of these antibodies in the general population. The well characterized bNAbs monoclonal variants frequently exhibit extensive levels of somatic hypermutation, a long third heavy chain complementary determining region, or a short third light chain complementarity determining region, and some exhibit poly-reactivity to autoantigens. This review elaborates on the obstacles to engaging and manipulating the Env glycoprotein as an effective immunogen and describes an alternative reverse vaccinology approach to develop a novel category of bNAb-epitope-derived non-cognate immunogens for HIV-1 vaccine design.
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Vacunas contra el SIDA , Anticuerpos Neutralizantes , Anticuerpos Anti-VIH , VIH-1 , VIH-1/inmunología , Humanos , Vacunas contra el SIDA/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Anti-VIH/inmunología , Polisacáridos/inmunología , Infecciones por VIH/inmunología , Imitación Molecular/inmunología , Epítopos/inmunología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología , LigandosRESUMEN
Immunotherapy has revolutionized cancer treatment by leveraging the immune system's innate capabilities to combat malignancies. Despite the promise of tumor antigens in stimulating anti-tumor immune responses, their clinical utility is hampered by limitations in eliciting robust and durable immune reactions, exacerbated by tumor heterogeneity and immune evasion mechanisms. Recent insights into the immunogenic properties of host homologous microbial antigens have sparked interest in their potential for augmenting anti-tumor immunity while minimizing off-target effects. This review explores the therapeutic potential of microbial antigen peptides in tumor immunotherapy, beginning with an overview of tumor antigens and their challenges in clinical translation. We further explore the intricate relationship between microorganisms and tumor development, elucidating the concept of molecular mimicry and its implications for immune recognition of tumor-associated antigens. Finally, we discuss methodologies for identifying and characterizing microbial antigen peptides, highlighting their immunogenicity and prospects for therapeutic application.
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Antígenos Bacterianos , Antígenos de Neoplasias , Inmunoterapia , Neoplasias , Humanos , Antígenos de Neoplasias/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Inmunoterapia/métodos , Animales , Antígenos Bacterianos/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Imitación Molecular/inmunologíaRESUMEN
T-cell Immunoglobulin and Mucin (TIM)-family proteins facilitate the clearance of apoptotic cells, are involved in immune regulation, and promote infection of enveloped viruses. These processes are frequently studied in experimental animals such as mice or rhesus macaques, but functional differences among the TIM orthologs from these species have not been described. Previously, we reported that while all three human TIM proteins bind phosphatidylserine (PS), only human TIM1 (hTIM1) binds phosphatidylethanolamine (PE), and that this PE-binding ability contributes to both phagocytic clearance of apoptotic cells and virus infection. Here we show that rhesus macaque TIM1 (rhTIM1) and mouse TIM1 (mTIM1) bind PS but not PE and that their inability to bind PE makes them less efficient than hTIM1. We also show that alteration of only two residues of mTIM1 or rhTIM1 enables them to bind both PE and PS, and that these PE-binding variants are more efficient at phagocytosis and mediating viral entry. Further, we demonstrate that the mucin domain also contributes to the binding of the virions and apoptotic cells, although it does not directly bind phospholipid. Interestingly, contribution of the hTIM1 mucin domain is more pronounced in the presence of a PE-binding head domain. These results demonstrate that rhTIM1 and mTIM1 are inherently less functional than hTIM1, owing to their inability to bind PE and their less functional mucin domains. They also imply that mouse and macaque models underestimate the activity of hTIM1.