Humoral Recognition Research Articles

Interplay between host humoral pattern recognition molecules controls undue immune responses against Aspergillus fumigatus

Pentraxin 3 (PTX3), a long pentraxin and a humoral pattern recognition molecule (PRM), has been demonstrated to be protective against Aspergillus fumigatus, an airborne human fungal pathogen. We explored its mode of interaction with A. fumigatus, and the resulting implications in the host immune response. Here, we demonstrate that PTX3 interacts with A. fumigatus in a morphotype-dependent manner: (a) it recognizes germinating conidia through galactosaminogalactan, a surface exposed cell wall polysaccharide of A. fumigatus, (b) in dormant conidia, surface proteins serve as weak PTX3 ligands, and (c) surfactant protein D (SP-D) and the complement proteins C1q and C3b, the other humoral PRMs, enhance the interaction of PTX3 with dormant conidia. SP-D, C3b or C1q opsonized conidia stimulated human primary immune cells to release pro-inflammatory cytokines and chemokines. However, subsequent binding of PTX3 to SP-D, C1q or C3b opsonized conidia significantly decreased the production of pro-inflammatory cytokines/chemokines. PTX3 opsonized germinating conidia also significantly lowered the production of pro-inflammatory cytokines/chemokines while increasing IL-10 (an anti-inflammatory cytokine) released by immune cells when compared to the unopsonized counterpart. Overall, our study demonstrates that PTX3 recognizes A. fumigatus either directly or by interplaying with other humoral PRMs, thereby restraining detrimental inflammation. Moreover, PTX3 levels were significantly higher in the serum of patients with invasive pulmonary aspergillosis (IPA) and COVID-19-associated pulmonary aspergillosis (CAPA), supporting previous observations in IPA patients, and suggesting that it could be a potential panel-biomarker for these pathological conditions caused by A. fumigatus.

Children's recognition of slapstick humor is linked to their Theory of Mind

Humor is an important component of children's learning and development. Yet, the cognitive mechanisms that underlie humor recognition in children have not been well-researched. In this pre-registered study, we asked whether (1) 4- to 5-year-old children recognize and categorize a misfortunate situation as funny only if the victims show a funny bewildered face (slapstick humor), and not a painful or angry expression, (2) this ability increases with age, (3) it is associated with children's Theory of Mind (ToM) abilities, (4) it is related to the ability to recognize facial emotional expressions. In an online experiment platform, children (N = 61, Mage = 53 months) were asked to point to the funny picture between a funny and an affective picture. Then, children were asked to point to the happy, sad, fearful, or angry face among four faces displaying these emotions. Children's ToM was assessed using the Children's Social Understanding Scale (CSUS), which was filled out online by parents. Results showed that from the earliest age onward, the predicted probability of humor recognition exceeded the chance level. Only ToM but not age was a significant predictor. Children with higher ToM scores showed better humor recognition. We found no evidence for a relation between children's humor recognition and their recognition of any emotion (happy, sad, fearful, or angry). Our findings suggest that 4–5-year-old children recognize facial emotional expressions and slapstick humor, although these abilities seem unrelated. Instead, children's understanding of mental states appears to play a role in their recognition of slapstick humor.

P139 A potential protective rule of Mannose Binding lectin (MBL) against SARS-COV2 infection in IBD patients

Abstract Background Since the beginning of the COVID-19 pandemic, IBD patients have appeared to be less susceptible to a severe form of the disease, despite undergoing immunosuppressive treatments. Mannose binding lectin (MBL) is a humoral fluid-phase pattern recognition molecule (PRM) crucial for activating the lectin complement pathway. It is capable of binding to the spike protein and blocking SARS-CoV-2 infection. Low MBL expression has been linked to poor outcomes in both SARS and SARS- CoV-2 infections. In IBD patients, the role of MBL is controversial; low concentrations seem to predispose individuals to the development of IBD, while high concentrations have been observed in severe forms of Crohn's disease. Methods Since April 2020, 104 IBD patients have been enrolled, with 20% treated with mesalazine, 50% with Anti-TNFa, 20% with Vedolizumab, and 20% receiving no treatment. Additionally, 45 healthy controls (HC) from North Italy were included. Serum samples and colon biopsies from inflamed and non- inflamed mucosa were collected. Serum samples underwent an ELISA test to quantify circulating MBL concentration, and MBL gene expression in biopsies was analyzed using qPCR. Results Both Crohn's disease and Ulcerative Colitis patients exhibited significantly higher circulating MBL levels than HC (411.6 ± 45.5 ng/ml vs. 160.9 ± 35.3 ng/ml, p < 0.05). Patients treated with Anti-TNFa showed significantly higher circulating MBL levels compared to those not undergoing therapy (530.1 ± 76.5 ng/ml vs. 225.4 ± 61.6 ng/ml, p < 0.05) and patients receiving Vedolizumab (530.1 ± 76.5 ng/ml vs. 155.3 ± 32.1 ng/ml, p < 0.05). MBL intestinal gene expression is higher in IBD patients than HC (5.55 ± 0.9 vs. 2.36 ± 0.6; p=0.591) and tended to be elevated at similar levels in inflamed and non-inflamed mucosa (5.14 ± 1.4 vs. 5.79 ± 1.1; p=0.337), suggesting a prevalent genetic determination of MBL concentration regardless of the inflammatory background. Conclusion MBL appears to play a key role in SARS-CoV-2 infection. We demonstrate that IBD patients have, on average, higher circulating MBL levels than HC independently of their inflammatory status. The highest MBL levels were observed in patients treated with Anti-TNFa. These findings contribute to understanding the reported low mortality and hospitalization for COVID-19 among IBD patients treated with Anti-TNFa.

A study on how gender and stream of studies impact social intelligence of undergraduates in Sri Lanka

Humans are masters at social interaction. The ability to make sense of other people's behavior is essential in people's daily functioning. As a result, they want to know that people's activities are motivated by aims and driven by motives. At present, it has been observed that undergraduates face many issues such as a lack of empathy, suicidal thoughts, and causing disturbances to the peace of the society. This dilemma highlights the need to study social intelligence, especially among undergraduates in Sri Lanka. The present study attempted to determine whether students from different genders and streams of studies show differences, in terms of social intelligence and its related components. The questionnaire survey method was employed to collect data from 200 undergraduates from a selected university, in Sri Lanka which includes students from nine faculties. The research gathered responses from 182 students, which is 91%. Descriptive analysis was performed to identify the social intelligence among undergraduates regarding their gender and the subject stream. Inferential analysis was performed to identify the differences in social intelligence among undergraduates concerning their gender and subject stream. Results showed that there was no significant difference between the genders on their total score measuring spiritual intelligence dimensions of cooperativeness, confidence, patience, social environment recognition, tactfulness, memory, and sense of humor, but the genders did tend to differ in sensitivity dimension. It may be observed from the data that undergraduates in the Technology stream are more cooperative than students in other streams. Agriculture faculty undergraduates showed a higher level of confidence in contrast to other students. Commerce students showed more patient than students from other faculties. Nursing students are better than other faculty students at recognizing the social context. Undergraduates in Physical Science appeared to be more tactful than other students. Undergraduates in the Medical faculty displayed a strong sense of humor, while students in the Arts and Culture faculty were found to have a higher memory power than undergraduate students in other faculties.

Hypo- and hyper-activation in frontotemporal lobe during humor processing in patients with first episode schizophrenia

BackgroundPatients with schizophrenia present difficulties in humor recognition and appreciation, but the neural mechanism of these deficits remains unclear. This study aimed to elucidate neural substrates underlying humor processing in patients with first episode schizophrenia (FES). MethodsThis study recruited 40 patients with FES (illness duration ≤ 4 years) and 31 healthy controls matching for age, gender and education level. Participants completed a fMRI verbal humor processing paradigm comprising 96 stories, half for funny punch-line condition and the other half for unfunny condition. Participants were required to judge whether the story was funny or not. Signal detection theory (SDT) analysis was used to calculate d' and β values which represented sensitivity and inner criteria for humor signals respectively. The funny-unfunny contrast was analyzed to identify the brain regions related with humor processing. d' and β values were put into the imaging regression analysis. ResultsPatients with FES showed significantly lower hit rate and sensitivity of humor signals (d'). At the neural level, patients with FES hypo-activated in ventral medial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) while hyper-activated in middle temporal gyrus (MTG) and superior temporal gyrus (STG) compared to controls. In addition, activity in vmPFC and ACC was positively associated with d’ and β values, while activity in STG was positively associated with β values in the clinical group. ConclusionsPatients with FES exhibited decreased sensitivity to humor signals. Hypo-activation in frontal regions and hyper-activation in temporal regions were associated with the humor processing deficits.

Beta-spike-containing boosters induce robust and functional antibody responses to SARS-CoV-2 in macaques primed with distinct vaccines

The reduced effectiveness of COVID-19 vaccines due to the emergence of variants of concern (VOCs) necessitated the use of vaccine boosters to bolster protection against disease. However, it remains unclear how boosting expands protective breadth when primary vaccine platforms are distinct and how boosters containing VOC spike(s) broaden humoral responses. Here, we report that boosters composed of recombinant spike antigens of ancestral (prototype) and Beta VOCs elicit a robust, pan-VOC, and multi-functional humoral response in non-human primates largely independent of the primary vaccine series platform. Interestingly, Beta-spike-containing boosters stimulate immunoglobulin A (IgA) with a greater breadth of recognition in protein-primed recipients when administered with adjuvant system 03 (AS03). Our results highlight the utility of a component-based booster strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for broad humoral recognition, independent of primary vaccine series. This is of high global health importance given the heterogeneity of primary vaccination platforms distributed.

Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals

In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.

Modified vaccinia Ankara–Bavarian Nordic vaccine against mpox in children

Modified vaccinia Ankara–Bavarian Nordic vaccine against mpox in children

Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara–Bavaria Nordic vaccine against mpox in children: a national outbreak response

In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA-BN in children. This is an assessment of children receiving MVA-BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA-BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox. Between June 1 and Nov 30, 2022, 87 children had one MVA-BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5-9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0-6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14-15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD450nm 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4+ and CD8+ T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination. A single dose of MVA-BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA-BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response. UK Health Security Agency.

Multidimensional Latent Semantic Networks for Text Humor Recognition.

Humor is a special human expression style, an important “lubricant” for daily communication for people; people can convey emotional messages that are not easily expressed through humor. At present, artificial intelligence is one of the popular research domains; “discourse understanding” is also an important research direction, and how to make computers recognize and understand humorous expressions similar to humans has become one of the popular research domains for natural language processing researchers. In this paper, a humor recognition model (MLSN) based on current humor theory and popular deep learning techniques is proposed for the humor recognition task. The model automatically identifies whether a sentence contains humor expression by capturing the inconsistency, phonetic features, and ambiguity of a joke as semantic features. The model was experimented on three publicly available wisecrack datasets and compared with state-of-the-art language models, and the results demonstrate that the proposed model has better humor recognition accuracy and can contribute to the research on discourse understanding.

STAT3 Activates the Pentraxin 3 Gene in Chronic Lymphocytic Leukemia Cells.

Pentraxin-related protein 3 (PTX3), commonly produced by myeloid and endothelial cells, is a humoral pattern recognition protein of the innate immune system. Because PTX3 plasma levels of patients with chronic lymphocytic leukemia (CLL) are high and most circulating cells in patients with CLL are CLL cells, we reasoned that CLL cells produce PTX3. Western immunoblotting revealed that low-density cells from seven of seven patients with CLL produce high levels of PTX3, flow cytometry analysis revealed that the PTX3-producing cells are B lymphocytes coexpressing CD19 and CD5, and confocal microscopy showed that PTX3 is present in the cytoplasm of CLL cells. Because STAT3 is constitutively activated in CLL cells, and because we identified putative STAT3 binding sites within the PTX3 gene promoter, we postulated that phosphorylated STAT3 triggers transcriptional activation of PTX3. Immunoprecipitation analysis of CLL cells' chromatin fragments showed that STAT3 Abs precipitated PTX3 DNA. STAT3 knockdown induced a marked reduction in PTX3 expression, indicating a STAT3-induced transcriptional activation of the PTX3 gene in CLL cells. Using an EMSA, we established and used a dual-reporter luciferase assay to confirm that STAT3 binds the PTX3 gene promoter. Downregulation of PTX3 enhanced apoptosis of CLL cells, suggesting that inhibition of PTX3 might benefit patients with CLL.

Federated Learning for Personalized Humor Recognition

Computational understanding of humor is an important topic under creative language understanding and modeling. It can play a key role in complex human-AI interactions. The challenge here is that human perception of humorous content is highly subjective. The same joke may receive different funniness ratings from different readers. This makes it highly challenging for humor recognition models to achieve personalization in practical scenarios. Existing approaches are generally designed based on the assumption that users have a consensus on whether a given text is humorous or not. Thus, they cannot handle diverse humor preferences well. In this article, we propose the FedHumor approach for the recognition of humorous content in a personalized manner through Federated Learning (FL). Extending a pre-trained language model, FedHumor guides the fine-tuning process by considering diverse distributions of humor preferences from individuals. It incorporates a diversity adaptation strategy into the FL paradigm to train a personalized humor recognition model. To the best of our knowledge, FedHumor is the first text-based personalized humor recognition model through federated learning. Extensive experiments demonstrate the advantage of FedHumor in recognizing humorous texts compared to nine state-of-the-art humor recognition approaches with superior capability for handling the diversity in humor labels produced by users with diverse preferences.

Proteome Changes Associated with the VEGFR Pathway and Immune System in Diabetic Macular Edema Patients at Different Diabetic Retinopathy Stages

Purpose Diabetic macular edema (DME) is a major cause of vision loss in all stages of diabetic retinopathy (DR). However, there is limited recognition of aqueous humor (AH) proteome profiles of DME patients at different DR stages. In this study, we aimed to investigate the AH proteome changes between DME patients at the nonproliferative diabetic retinopathy (NPDR) stage and those at the proliferative diabetic retinopathy (PDR) stage. Methods A label-free data-independent acquisition based liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis was performed to profile the abundances of AH proteins in 73 eyes from DME patients at different DR stages. Enzyme-linked immunosorbent assay (ELISA) was used to confirm the proteomics results with AH samples from non-diabetic patients and DME patients at the NPDR or PDR stage. Results LC-MS/MS results showed significantly changed expression of 308 proteins between DME patients in the NPDR and PDR groups. Compared to the NPDR group, the proteins relatively up-regulated in the PDR group are involved in the immune system and/or negative regulation of the cell cycle, while proteins relatively down-regulated in the PDR group are associated with the vascular endothelial growth factor receptor (VEGFR) pathway and/or metabolism. ELISA results further verified the proteomic result of down-regulated expression of the immune-associated protein cystatin C (CST3) in the PDR group compared to that in the NPDR and non-diabetic groups. Conclusions In this study, we reported for the first time the decreased abundances of AH proteins associated with the VEGFR pathway and both down- and up-regulated expression of AH proteins associated with the immune system in the PDR group compared to that in the NPDR group. Furthermore, we found negative correlations of immune-associated protein, CST3 concentration in AH with DR severity and central retinal thickness, suggesting CST3 as a promising target independent of the VEGFR pathway in DME-involved DR treatment.

Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules.

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.

Multi-view informed attention-based model for Irony and Satire detection in Spanish variants

Making machines understand language and reasoning on it has been one of the most challenging problems addressed by Artificial Intelligent researchers. This challenge increases when figurative language is used for communicating complex meanings, intentions, emotions and attitudes in creative and funny ways. In fact, sentiment analysis approaches struggle when facing irony, satire and other figurative languages, particularly those where the explanation of a prediction might arguably be as necessary as the prediction itself. This paper describes a new model MvAttLSTM based on deep learning for irony and satire detection in tweets written in distinct Spanish variants. The proposed model is based on an attentive-LSTM informed with three additional views learned from distinct perspectives. We investigate two strategies to pass these views into MvAttLSTM. We perform an extensive evaluation on three corpora, one for irony detection and two for satire detection. Moreover, in order to study the robustness of our proposed model, we investigate its performance on humor recognition. Experiments confirm that the proposed views help our model to improve its performance. Moreover, they show that affective information benefits our model to detect irony and satire. In particular, a first analysis of the results highlights the discriminating power of emotional features obtained from SenticNet and SEL lexicon. Overall, our system achieves the state-of-the-art performance in irony and satire detection in Spanish variants and competitive results in humor recognition.

ABML: attention-based multi-task learning for jointly humor recognition and pun detection

ABML: attention-based multi-task learning for jointly humor recognition and pun detection

How Funny Was That? Discoveries From Measuring Leader Humor

We introduce a multimodal approach to conducting nuanced, unobtrusive measurements of leader humor expressions, and we exploratively test it using a sample of press conferences held by professional soccer coaches in the German Bundesliga. First, we discover that although most of the humor recognized across leaders was affiliative humor, individual leaders still exhibited unique patterns in their use of humor. For instance, some coaches almost exclusively employed others-directed humor, and we found differences in the total amount of humor expressed per press conference and the number of humorous instances per press conference. Second, we uncover general patterns in the timing of both humor overall and individual humor styles. For example, most humor occurred towards the end of press conferences. Third, we propose a novel framework, that enables us to identify differences in the audience’s recognition of leader humor and their perceptions of humor clarity, and find that some leaders communicate their humor more clearly to an audience than others. Our exploratory approach provides a solid foundation for additional empirical research on executive communication, especially leader humor. Ultimately, our findings reconfirm the need for a nuanced perspective on leader humor and contribute to extant research on leader rhetoric and executive communication.

An attention network via pronunciation, lexicon and syntax for humor recognition

An attention network via pronunciation, lexicon and syntax for humor recognition

Detection of Complement Factor B Autoantibodies by ELISA.

Antibodies to autoantigens are implicated in a large number of diseases. Such autoantibodies may cause pathological activation of complement, an ancient humoral recognition and effector system of innate immunity; in addition, complement components or regulators may be target of autoantibodies and cause abnormal complement activation or function. Autoantibodies to complement proteins are in particular involved in kidney diseases. Those binding to complement convertase enzymes can cause enhanced stability of convertases and their increased resistance to regulation, thus promoting complement turnover. Here, we describe an ELISA method to detect factor B autoantibodies that bind to and stabilize the alternative complement pathway C3 convertase enzyme, C3bBb.

Combinatorial Resurfacing of Dengue Envelope Protein Domain III Antigens Selectively Ablates Epitopes Associated with Serotype-Specific or Infection-Enhancing Antibody Responses.

Mutagenesis of surface-exposed residues, or "resurfacing", is a protein engineering strategy that can be utilized to disrupt antibody recognition or modulate the capacity of a protein to elicit antibody responses. We apply resurfacing to engineer Dengue virus envelope protein domain III (DENV DIII) antigens with the goal of focusing humoral recognition on epitopes of interest by selective ablation of irrelevant and undesired epitopes. Cross-reactive but non-neutralizing antibodies have the potential to enhance Dengue virus (DENV) infection by a process called antibody-dependent enhancement, thought to be associated with severe secondary heterotypic infection. Thus, a focus on epitopes associated with broadly neutralizing antibodies is important both for understanding human antibody responses against DENV and for the development of a successful DENV vaccine. To engineer DENV DIII antigens focusing on the AG strand epitope associated with broadly neutralizing antibody responses, we generated yeast surface display libraries of DENV2 DIII where the AB loop (associated with cross-reactive but non-neutralizing antibody responses) and FG loop (associated with serotype-specific antibody responses) were mutagenized to allow for all possible amino acid substitutions. Loop variants that maintained the AG strand epitope and simultaneously disrupted the AB and FG loop epitopes exhibited high and diverse mutational loads that were amenable to loop exchange and transplantation into a DENV4 DIII background. Thus, several loop variants fulfill this antigenicity criteria regardless of serotype context. The resulting resurfaced DIII antigens may be utilized as AG strand epitope-focusing probes or immunogen candidates.