Individual Repertoires Research Articles

In depth sequencing of a serially sampled household cohort reveals the within-host dynamics of Omicron SARS-CoV-2 and rare selection of novel spike variants.

SARS-CoV-2 has undergone repeated and rapid evolution to circumvent host immunity. However, outside of prolonged infections in immunocompromised hosts, within-host positive selection has rarely been detected. The low diversity within-hosts and strong genetic linkage among genomic sites make accurately detecting positive selection difficult. Longitudinal sampling is a powerful method for detecting selection that has seldom been used for SARS-CoV-2. Here we combine longitudinal sampling with replicate sequencing to increase the accuracy of and lower the threshold for variant calling. We sequenced 577 specimens from 105 individuals from a household cohort primarily during the BA.1/BA.2 variant period. There was extremely low diversity and a low rate of divergence. Specimens had 0-12 intrahost single nucleotide variants (iSNV) at >0.5% frequency, and the majority of the iSNV were at frequencies <2%. Within-host dynamics were dominated by genetic drift and purifying selection. Positive selection was rare but highly concentrated in spike. Two individuals with BA.1 infections had S:371F, a lineage defining substitution for BA.2. A Wright Fisher Approximate Bayesian Computational model identified positive selection at 14 loci with 7 in spike, including S:448 and S:339. We also detected significant genetic hitchhiking between synonymous changes and nonsynonymous iSNV under selection. The detectable immune-mediated selection may be caused by the relatively narrow antibody repertoire in individuals during the early Omicron phase of the SARS-CoV-2 pandemic. As both the virus and population immunity evolve, understanding the corresponding shifts in SARS-CoV-2 within-host dynamics will be important.

Reconstructed influenza A/H3N2 infection histories reveal variation in incidence and antibody dynamics over the life course.

Humans experience many influenza infections over their lives, resulting in complex and varied immunological histories. Although experimental and quantitative analyses have improved our understanding of the immunological processes defining an individual's antibody repertoire, how these within-host processes are linked to population-level influenza epidemiology in humans remains unclear. Here, we used a multilevel mathematical model to jointly infer antibody dynamics and individual-level lifetime influenza A/H3N2 infection histories for 1,130 individuals in Guangzhou, China, using 67,683 haemagglutination inhibition (HI) assay measurements against 20 A/H3N2 strains from repeat serum samples collected between 2009 and 2015. These estimated infection histories allowed us to reconstruct historical seasonal influenza patterns in humans and to investigate how influenza incidence varies over time, space, and age in this population. We estimated median annual influenza infection rates to be approximately 19% from 1968 to 2015, but with substantial variation between years; 88% of individuals were estimated to have been infected at least once during the study period (2009 to 2015), and 20% were estimated to have 3 or more infections in that time. We inferred decreasing infection rates with increasing age, and found that annual attack rates were highly correlated across all locations, regardless of their distance, suggesting that age has a stronger impact than fine-scale spatial effects in determining an individual's antibody profile. Finally, we reconstructed each individual's expected antibody profile over their lifetime and inferred an age-stratified relationship between probability of infection and HI titre. Our analyses show how multi-strain serological panels provide rich information on long-term epidemiological trends, within-host processes, and immunity when analysed using appropriate inference methods, and adds to our understanding of the life course epidemiology of influenza A/H3N2.

T-Cell Receptors Cross-Reactive to Coronaviral Epitopes Homologous to the SPR Peptide.

The COVID-19 pandemic caused by the rapid spread of the novel coronavirus SARS-CoV-2, has promoted an interest in studying the T-cell immune response. It was found that the polyclonal and cross-reactive T-cell response against seasonal coronaviruses and other SARS-CoV-2 strains reduced disease severity. We investigated the immunodominant T-cell epitope SPRWYFYYYL from the nucleocapsid protein of SARS-CoV-2. The immune response to this epitope is characterized by the formation of highly homologous (convergent) receptors that have been found in the T-cell receptor (TCR) repertoires of different individuals. This epitope belongs to a group of highly conserved peptides that are rarely mutated in novel SARS-CoV-2 strains and are homologous to the epitopes of seasonal coronaviruses. It has been suggested that the cross-reactive response to homologous peptides contributes to the reduction of COVID-19 severity. However, some investigators have questioned this hypothesis, suggesting that the low affinity of the cross-reactive receptors reduces the strength of the immune response. The aim of this study was to evaluate the effect of amino acid substitutions in the SPR epitope on its binding affinity to specific TCRs. For this, we performed antigen-dependent cellular expansions were performed using samples from four COVID-19-transfected donors and sequenced their TCR repertoires. The resulting SPR-specific repertoire of β-chains in TCRs had a greater sequence diversity than the repertoire of α-chains. However, the TCR repertoires of all four donors contained public receptors, three of which were cloned and used to generate the Jurkat E6-1 TPR cell line. Only one of these receptors was activated by the SPR peptide and recognized with the same affinity by its mutant homologue LPRWYFYYY from seasonal coronaviruses. This indicates that the presence of the mutation did not affect the strength of the immune response, which may explain why the cross-reactive response to the SPR epitope is so frequent and contributes positively to COVID-19 infection.

Multilingual and multimodal methods to examining the situated communication among deaf children and their caregivers

ABSTRACT This paper discusses methodologies for examining the multilingual language experiences of young deaf children that are sensitive to different cultural contexts of childhood, caregiving and language practices. We argue that in the context of early support, the combined use of situated multilingual and multimodal approaches to examine and assess individual language resources can provide rich and reliable information about individual communicative repertoires in their given context. This approach extends commonly used monolingual and unimodal research and assessment tools that lack the inclusivity of reach and granularity of analysis needed to inform contextually appropriate early intervention for multilingual and migrant deaf learners. We illustrate the potential of these methods using case study examples from multimodal video-based and ethnographic data gathering and analysis techniques deployed across three projects in different multilingual contexts, in Ghana and the UK. We use these case studies to examine the methodological choices, challenges and opportunities of researching different multilingual environments in culturally sensitive ways as a basis for supporting and assessing the language and communication development of young deaf children in multilingual and migrant contexts. We discuss how the resulting new knowledge base can extend Euro-Western epistemologies that are currently leading models of early intervention and support.

Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes.

BACKGROUNDTeplizumab, a non-FcR-binding anti-CD3 mAb, is approved to delay progression of type 1 diabetes (T1D) in at-risk patients. Previous investigations described the immediate effects of the 14-day treatment, but longer-term effects of the drug remain unknown.METHODSWith an extended analysis of study participants, we found that 36% were undiagnosed or remained free of clinical diabetes after 5 years, suggesting operational tolerance. Using single-cell RNA sequencing, we compared the phenotypes, transcriptome, and repertoire of peripheral blood CD8+ T cells including autoreactive T cells from study participants before and after teplizumab and features of responders and non-responders.RESULTSAt 3 months, there were transcriptional signatures of cell activation in CD4+ and CD8+ T cells including signaling that was reversed at 18 months. At that time, there was reduced expression of genes in T cell receptor and activation pathways in clinical responders. In CD8+ T cells, we found increased expression of genes associated with exhaustion and immune regulation with teplizumab treatment. These transcriptional features were further confirmed in an independent cohort. Pseudotime analysis showed differentiation of CD8+ exhausted and memory cells with teplizumab treatment. IL7R expression was reduced, and patients with lower expression of CD127 had longer diabetes-free intervals. In addition, the frequency of autoantigen-reactive CD8+ T cells, which expanded in the placebo group over 18 months, did not increase in the teplizumab group.CONCLUSIONThese findings indicate that teplizumab promotes operational tolerance in T1D, involving activation followed by exhaustion and regulation, and prevents expansion of autoreactive T cells.TRIAL REGISTRATIONClinicalTrials.gov NCT01030861.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases/NIH, Juvenile Diabetes Research Foundation.

Healthcare Professionals' Discursive Constructions of Parental Vaccine Hesitancy: A Tale of Multiple Moralities.

Healthcare professionals play a crucial role in addressing the concerns of vaccine-hesitant parents since they form a trusted source for vaccine-related information. An increasing body of evidence suggests that healthcare professionals are faced with complexities when navigating the sensitive topic of parental vaccine hesitancy, as they balance their own vaccine- and context-specific concerns with institutional and societal pressures to vaccinate. Furthermore, health choices, such as parental choices for childhood vaccination, are often linked to moralisation. Given the emphasis on effective communication with vaccine-hesitant parents in the patient-centred care literature, it is important to consider healthcare professionals' interpretations of parental vaccine hesitancy. Hence, a deeper understanding of how healthcare professionals make sense of, and moralise, childhood vaccination can help us understand how moralisation might appear in their communication with hesitant parents (in)directly. Drawing on a critical social-psychological framework for discourse analysis, this study analyses 39 semi-structured interviews with healthcare professionals in Flanders, Belgium, and presents the discursive patterns articulated by healthcare professionals on parental vaccine hesitancy. The findings elucidate how healthcare professionals perpetuate, or resist, moral discourse in their accounts of vaccine hesitancy by constructing five different interpretative repertoires, that is, a "good" or "bad" parenting repertoire, a freedom of choice repertoire, an individual risk-benefit repertoire, a public health repertoire, and an accessibility repertoire. Our study highlights the complexities healthcare professionals experience in negotiating vaccine hesitancy, as their understandings of vaccine hesitancy are affected by, and contribute to, existing moral dilemmas and dominant discourses surrounding health and parenting.

Shannon index analysis in TCR sequencing for patients with lung adenocarcinoma: The clinical implications.

e20053 Background: Immune repertoire (IR) is the collection of functionally diverse T and B cells in an individual's circulatory repertoire at a particular time. The CDR3 is the main variation region of the CDR of T cell receptors (TCRs), which directly determines the antigen specificity of the receptor. The purpose of this study was to investigate the differences in TCRs between tumor patients and healthy people by using NGS sequencing of the CDR3 region of the human TRB. Shannon indices and Simpson indices were used to evaluate the TCR richness and evenness. Methods: From 2018 to 2022, a total of 537 cases of lung adenocarcinoma and 85 cases of healthy individual PBMC in China were collected. We identified 59 V and 14 J genes in the TRB CDR3 region by amplicon sequencing, and analyzed the differences between Shannon_index and simpson index. Results: TCR diversity were significantly higher in healthy people compared to lung adenocarcinoma patients as determined by Shannon index analysis ( P = 0.006), and the uniformity of TCRs in the latter group was lower (Simpson index 0.997 and 0.992 for controls and cases, respectively). For different age groups of lung cancer patients (age 20-44, n = 66; age 45-59, n = 205; age 60-74, n = 221; age 75-90, n = 45), the overall abundance and uniformity of T cells in lung cancer patients decreased with the increase of age (Shannon index: 7.91, 7.63, 7.38, 6.99, respectively. Simpson Index: 0.996, 0.994, 0.991, 0.986 respectively). The downward trend in the Shannon index between healthy individuals and lung adenocarcinoma patients exhibit a high correlation (spearman r = 1, P &lt; 0.01), indicating that age rather than cancer may be the main factor in immune decline in patients with lung adenocarcinoma. In terms of gender, the abundance and uniformity of T cell types in male patients were lower than that in female patients (male: Shannon index = 7.36, Simpson index = 0.991; Female: Shannon index = 7.61, Simpson index = 0.994), suggesting higher levels of immunity in the female patients. Conclusions: The Shannon index (immune diversity) in TCR sequencing was significantly different between lung adenocarcinoma patients and healthy individuals. In patients with lung adenocarcinoma, immunity declines more due to aging than the cancer itself. TCR diversity was lower in male lung adenocarcinoma patients than in female patients. In conclusion, Shannon index (immune diversity) in TCR sequencing can be used as a predictor of lung adenocarcinoma.

Peculiarities of teaching a second/third foreign language based on English

Problem. The article deals with general issues relating to the main features of teaching a second or third foreign language (German and French, based on English) to students specializing in applied linguistics. A short list of similarities and differences between English, German and French in the context of their learning is given. This study presents an overview of the concept of multilingual education and analyses the main methods of teaching a third language. The problems associated with teaching a second foreign language are not sufficiently revealed, as this discipline is not very widespread in non-language educational institutions. It generally holds that the methodology of teaching a second foreign language does not differ from that of teaching a first foreign language, except that the second language is taught to a lesser extent. This approach does not take into account a number of characteristics that affect the effectiveness of learning the subject. Goal. The aim is to present the main features of teaching the second/third foreign language (German and French based on previously learnt English) to students majoring in Applied Linguistics. The relevance of the study is determined by the need to find more effective methods of teaching a second foreign language. Methodology. To achieve this goal, a number of research methods were used: theoretical analysis and generalization of pedagogical and methodological sources on the issues of third language teaching didactics and the concept of multilingual education. The term «multilingualism» is used in official European terminology to refer to both the linguistic diversity of a society and the ability of a person to speak several languages. The concept of "multilingual education" applies to both the development of an individual language repertoire and to «plurilingual education» i.e., education in a context of linguistic and cultural diversity. English, German and French have many things in common: Latin spelling and lexical similarities. All three languages contain many cognates - words that are similar in spelling and pronunciation and mean the same thing. All of these languages have a subject-verb-object syntactic structure. Consequently, the main problems in learning a second/third language after learning English, in the context of three foreign languages in contact with the mother tongue, are interference not only from the mother tongue but also from the second/third language, as well as positive language transfer, given that they both belong to the same Roman language group. Originality. The modern didactic approaches to multilingualism cause a major change not only in the way we teach, but also in the way we learn, develop curricula, and train future professionals. Practical value. The integration of work on language representation and multilingual learning, as well as explaining the plurilingual didactic approach to students, will make the language learning process more focused on students' real skills, more flexible and more creative.

Tumor Antigens beyond the Human Exome.

With the advent of immunotherapeutics, a new era in the combat against cancer has begun. Particularly promising are neo-epitope-targeted therapies as the expression of neo-antigens is tumor-specific. In turn, this allows the selective targeting and killing of cancer cells whilst healthy cells remain largely unaffected. So far, many advances have been made in the development of treatment options which are tailored to the individual neo-epitope repertoire. The next big step is the achievement of efficacious "off-the-shelf" immunotherapies. For this, shared neo-epitopes propose an optimal target. Given the tremendous potential, a thorough understanding of the underlying mechanisms which lead to the formation of neo-antigens is of fundamental importance. Here, we review the various processes which result in the formation of neo-epitopes. Broadly, the origin of neo-epitopes can be categorized into three groups: canonical, noncanonical, and viral neo-epitopes. For the canonical neo-antigens that arise in direct consequence of somatic mutations, we summarize past and recent findings. Beyond that, our main focus is put on the discussion of noncanonical and viral neo-epitopes as we believe that targeting those provides an encouraging perspective to shape the future of cancer immunotherapeutics.

Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires.

An individual's T-cell repertoire constantly changes under the influence of external and internal factors. Cells that do not receive a stimulatory signal die, while those that encounter and recognize a pathogen or receive a co-stimulatory signal divide, resulting in clonal expansions. T-cell clones can be traced by monitoring the presence of their unique T-cell receptor (TCR) sequence, which is assembled de novo through a process known as V(D)J rearrangement. Tracking T cells can provide valuable insights into the survival of cells after hematopoietic stem cell transplantation (HSCT) or cancer treatment response and can indicate the induction of protective immunity by vaccination. In this study, we report a bioinformatic method for quantifying the T-cell repertoire dynamics from TCR sequencing data. We demonstrate its utility by measuring the T-cell repertoire stability in healthy donors, by quantifying the effect of donor lymphocyte infusion (DLI), and by tracking the fate of the different T-cell subsets in HSCT patients and the expansion of pathogen-specific clones in vaccinated individuals.

The self-reactive FVIII T cell repertoire in healthy individuals relies on a short set of epitopes and public clonotypes.

Non-mutated FVIII-specific CD4 T cell epitopes have been recently found to contribute to the development of inhibitors in patients with hemophilia A (HA), while auto-reactive CD4 T cells specific to FVIII circulate in the blood of healthy individuals at a frequency close to the foreign protein ovalbumin. Thus, although FVIII is a self-protein, the central tolerance raised against FVIII appears to be low. In this study, we conducted a comprehensive analysis of the FVIII CD4 T cell repertoire in 29 healthy donors. Sequencing of the CDR3β TCR region from isolated FVIII-specific CD4 T cells revealed a limited usage and pairing of TRBV and TRBJ genes as well as a mostly hydrophobic composition of the CDR3β region according to their auto-reactivity. The FVIII repertoire is dominated by a few clonotypes, with only 13 clonotypes accounting for half of the FVIII response. Through a large-scale epitope mapping of the full-length FVIII sequence, we identified 18 immunodominant epitopes located in the A1, A3, C1, and C2 domains and covering half of the T cell response. These epitopes exhibited a broad specificity for HLA-DR or DP molecules or both. T cell priming with this reduced set of peptides revealed that highly expanded clonotypes specific to these epitopes were responsible individually for up to 32% of the total FVIII repertoire. These FVIII T cell epitopes and clonotypes were shared among HLA-unrelated donors tested and previously reported HA patients. Our study highlights the role of the auto-reactive T cell response against FVIII in HA and its similarity to the response observed in healthy individuals. Thus, it provides valuable insights for the development of new tolerance induction and deimmunization strategies.

Gestural communication in wild spider monkeys (Ateles geoffroyi)

Gestures play a central role in the communication systems of several animal families, including primates. In this study, we provide a first assessment of the gestural systems of a Platyrrhine species, Geoffroy’s spider monkeys (Ateles geoffroyi). We observed a wild group of 52 spider monkeys and assessed the distribution of visual and tactile gestures in the group, the size of individual repertoires and the intentionality and effectiveness of individuals’ gestural production. Our results showed that younger spider monkeys were more likely than older ones to use tactile gestures. In contrast, we found no inter-individual differences in the probability of producing visual gestures. Repertoire size did not vary with age, but the probability of accounting for recipients’ attentional state was higher for older monkeys than for younger ones, especially for gestures in the visual modality. Using vocalizations right before the gesture increased the probability of gesturing towards attentive recipients and of receiving a response, although age had no effect on the probability of gestures being responded. Overall, our study provides first evidence of gestural production in a Platyrrhine species, and confirms this taxon as a valid candidate for research on animal communication.

CD8+ T cell memory induced by successive SARS-CoV-2 mRNA vaccinations is characterized by shifts in clonal dominance

mRNA vaccines against the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicit strong Tcell responses. However, a clonal-resolution analysis of Tcell responses to mRNA vaccination has not been performed. Here, we temporally track the CD8+ Tcell repertoire in individuals who received three shots of the BNT162b2 mRNA vaccine through longitudinal Tcell receptor sequencing with peptide-human leukocyte antigen (HLA) tetramer analysis. We demonstrate a shift in Tcell responses between the clonotypes with different kinetics: from early responders that expand rapidly after the first shot to main responders that greatly expand after the second shot. Although the main responders re-expand after the third shot, their clonal diversity is skewed, and newly elicited third responders partially replace them. Furthermore, this shift in clonal dominance occurs not only between, but also within, clonotypes specific for spike epitopes. Our study will be a valuable resource for understanding vaccine-induced Tcell responses in general.

Chronic infection control relies on T cells with lower foreign antigen binding strength generated by N-nucleotide diversity.

The breadth of pathogens to which T cells can respond is determined by the T cell receptors (TCRs) present in an individual's repertoire. Although more than 90% of the sequence diversity among TCRs is generated by terminal deoxynucleotidyl transferase (TdT)-mediated N-nucleotide addition during V(D)J recombination, the benefit of TdT-altered TCRs remains unclear. Here, we computationally and experimentally investigated whether TCRs with higher N-nucleotide diversity via TdT make distinct contributions to acute or chronic pathogen control specifically through the inclusion of TCRs with lower antigen binding strengths (i.e., lower reactivity to peptide-major histocompatibility complex (pMHC)). When T cells with high pMHC reactivity have a greater propensity to become functionally exhausted than those of low pMHC reactivity, our computational model predicts a shift toward T cells with low pMHC reactivity over time during chronic, but not acute, infections. This TCR-affinity shift is critical, as the elimination of T cells with lower pMHC reactivity in silico substantially increased the time to clear a chronic infection, while acute infection control remained largely unchanged. Corroborating an affinity-centric benefit for TCR diversification via TdT, we found evidence that TdT-deficient TCR repertoires possess fewer T cells with weaker pMHC binding strengths in vivo and showed that TdT-deficient mice infected with a chronic, but not an acute, viral pathogen led to protracted viral clearance. In contrast, in the case of a chronic fungal pathogen where T cells fail to clear the infection, both our computational model and experimental data showed that TdT-diversified TCR repertoires conferred no additional protection to the hosts. Taken together, our in silico and in vivo data suggest that TdT-mediated TCR diversity is of particular benefit for the eventual resolution of prolonged pathogen replication through the inclusion of TCRs with lower foreign antigen binding strengths.

Wild and captive immature orangutans differ in their non-vocal communication with others, but not with their mothers

In many group-living species, individuals are required to flexibly modify their communicative behaviour in response to current social challenges. To unravel whether sociality and communication systems co-evolve, research efforts have often targeted the links between social organisation and communicative repertoires. However, it is still unclear which social or interactional factors directly predict communicative complexity. To address this issue, we studied wild and zoo-housed immature orangutans of two species to assess the impact of the socio-ecological setting on the production of non-vocal signal repertoires. Specifically, we compared repertoire size, dyadic repertoire similarity, and number of social goals (i.e. observer’s estimate of the signaller’s intended interaction outcome) for communicative interactions with mothers versus other conspecifics, controlling for critical individual and environmental factors. In this small sample of immature orangutans, wild-captive contrasts were statistically significant only for other-directed repertoires, but not for mother-directed repertoires, and not for the number of social goals that immatures communicated towards. While the repertoires of individuals living in the same research setting were more similar than those living in contrasting settings, this difference was most pronounced for other-directed repertoires of the less socially tolerant orangutan species. These results suggest that the boosted interactional opportunities in captivity rather than mere differences in environmental affordances or communicative needs drive the wild-captive contrast in orangutan communicative repertoires. Overall, this fine-grained analysis of repertoires further underscores that not only a species’ social organisation but also the targeted audience may have a profound impact on communicative behaviour.Significance statementNavigating a dynamic social environment often requires flexible signal use. While it has repeatedly been shown that the social organisation and structure of species predict the complexity of their communication systems, the mechanisms underlying these relationships are largely unknown. Because targeted studies to assess this issue in great apes are difficult, we take an alternative approach here: we compare the same species living in the wild and in artificial habitats in captivity. This contrast allows a direct test of how repertoires respond to the relevant difference in socio-ecological conditions. Our results show that the diversity of interaction partners (i.e. social opportunities), but not the diversity of social goals (i.e. possible interaction outcomes) or the broader physical opportunities (i.e. safe ground use), predict the size and consistency of wild and captive signalling repertoires.

Dermatophagoides pteronyssinus proteins and their role in the diagnostics and management of house dust mite allergy: exploring allergenic components.

Component-resolved diagnostics enables the detection of allergen-specific immunoglobulins E (asIgE) to house dust mite (HDM) proteins, which may help clinicians to face the difficulties in diagnostics of HDM allergy. Currently, almost 40 proteins of Dermatophagoides species, that are able to bind asIgE, have been identified, and this number will certainly increase. The association between sensitisation to particular molecules and allergy symptoms is extensively studied. This investigation enables us to identify HDM molecules that promote respiratory, skin, or food allergies, and it could help us predict the possible course of allergic diseases. The individual repertoire of asIgE improves our understanding of immunological response, which underlies allergy symptoms, and helps to form individual therapeutic regimens. This review provides clinicians with information on Dermatophagoides pteronyssinus proteins available in commercial arrays, and their role in the diagnostics and management of HDM allergy.

INTRODUCTION

Articles in this special issue put the audience in the forefront of examining new communication platforms, narrative structures, as well as new challenges to the freedom of expression and audience participation in public and political life, such as the war in Ukraine, widespread misinformation and conspiracy theories. The new communication technologies have fundamentally changed how we communicate and connect with each other from the interpersonal level to the mass level. In seeking information, entertainment, diversion, socialization, and expression, people turn to diversified communication platforms and channels. Individual media repertoires have become so complex, fluent, and unpredictable that academic research is constantly struggling to keep up with emerging trends. On the one hand, new media and new ways of using existing media constantly emerge, while scholars strive to understand it. On the other hand, diverse malicious phenomena appear, limiting possibilities for expressing thoughts, emotions, attitudes, as well as participating in public and civic life. Articles in this special issue examine how we use new media and address disinformation on the Internet and in traditional media. In the first article, Ivana Stamenković and Marta Mitrović examine how young people in Serbia use TikTok, the fastest growing social media platform today. The authors apply uses and gratification theory and explore which motivations drive TikTok uses, including the needs for information, building personal identity, integration and social interaction, entertainment, and self-expression. According to their results, TikTok is a relevant source of information for the students from the south of Serbia, especially about hobbies. Students commonly join TikTok to learn about the activities of other people and gratify needs for relaxation and filling spare time. Most students are not active content contributors on TikTok but rather behave like traditional TV viewers.

Naïve, adult, captive chimpanzees do not socially learn how to make and use sharp stone tools

Although once regarded as a unique human feature, tool-use is widespread in the animal kingdom. Some of the most proficient tool-users are our closest living relatives, chimpanzees. These repertoires however consist primarily of tool use, rather than tool manufacture (for later use). Furthermore, most populations of chimpanzees use organic materials, such as sticks and leaves, rather than stones as tools. This distinction may be partly ecological, but it is also important as chimpanzees are often used as models for the evolution of human material culture, the oldest traces of which consist of manufactured sharp stone tools (so-called “flakes”). Thus, examining the conditions (if any) under which chimpanzees may develop flake manufacture and use can provide insight into the drivers of these behaviours in our own lineage. Previous studies on non-human apes’ ability to make and use flakes focused on enculturated apes, giving them full demonstrations of the behaviour immediately, without providing social information on the task in a stepwise manner. Here we tested naïve, captive chimpanzees (N = 4; three potentially enculturated and one unenculturated subject) in a social learning experimental paradigm to investigate whether enculturated and/or unenculturated chimpanzees would develop flake making and use after social information of various degrees (including a human demonstration) was provided in a scaffolded manner. Even though social learning opportunities were provided, neither the unenculturated subject nor any of the potentially enculturated subjects made or used flakes, in stark contrast to previous studies with enculturated apes. These data suggest that flake manufacture and use is outside of our tested group of captive chimpanzees’ individual and social learning repertoires. It also suggests that high levels of enculturation alongside human demonstrations (and/or training) may be required before captive chimpanzees can develop this behaviour.

‘One is allowed to show the reality’: The creation of panoptic structures in social media communication

Abstract This article aims to introduce the notion of panoptic structures as a way of theorizing how people strategically exploit the affordances of digital devices to expose other people's behavior. I argue that Foucault's notion of panopticism becomes relevant in new ways in social life as a consequence of the polymedia repertoires of networked individuals. Central here is the ability to store digital communication and repost it for selected audiences. The data I analyze here were collected from a group of students who had just entered the gymnasium (the Danish equivalent of high school). During the months of multi-sited, online and offline ethnography, a conflict occurred between two groups of students. During this conflict, a repeated activity involved students confronting students from the opposing group with screenshots of their earlier social media activities and doing so in front of larger audiences of other students. On this basis, I argue that a theory of such panoptic practices belongs in the sociolinguistic toolbox. (Panopticism, social media, conflict, polymedia repertoire, audience)*

Tumor-Infiltrating Normal B Lymphocytes Have Remarkable Prognostic Effects and Are Crucial for Antitumor Immune Responses in Diffuse Large B-Cell Lymphoma

Introduction: In recent years, increasing evidence suggests an important role of tumor-infiltrating B lymphocytes (TIL-Bs) in cancer immunity. In various types of solid tumors, high density of TIL-Bs and presence of mature tertiary lymphoid structures consistently correlate with better prognosis and response to immune checkpoint blockade therapies. Diffuse large B-cell lymphoma (DLBCL) is a type of aggressive lymphoma arising from mature B cells. TIL-Bs have been identified in DLBCL based on single-cell gene-expression data in several previous studies, but their prognostic significance in DLBCL is unknown. In this study, we determined the clinical significance of TIL-B abundance and investigated the potential underlying mechanisms. Patients and Methods: This abstract includes a discovery study in which we distinguished TIL-Bs from malignant B-cells by immunoglobulin gene (IG) clonotype analysis and a validation study using flow cytometry. In the discovery study, a molecularly well-characterized DLBCL cohort assembled by the International DLBCL R-CHOP Consortium Program was analyzed. DNA samples from DLBCL patients were sequenced by high-throughput ultra-deep sequencing assays using multiplexed forward and reverse primers. Based on the IG heavy chain (IGH) sequencing results, malignant B-cell and TIL-B VDJ clonotypes were identified for 138 patients, and the frequencies and numbers of TIL-B clonotypes in individual sequence repertoires were calculated. In 79 DLBCL cases, a DJ-only sequence was predominant and no productive VDJ sequences met the criteria for diagnostic sequences. Total frequencies of productive VDJ sequences in the sequence repertoires were then used to access high and low TIL-B frequencies. TIL-B frequencies were also evaluated by IG light chain clonotypes for these 217 patients and additional 52 patients. The TIL-B frequencies were correlated with patient survival, gene-expression profiling (GEP) data GSE31312, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex immunohistochemistry (mIHC). To validate the prognostic significance of TIL-B frequencies, we assembled a validation cohort of 94 DLBCL patients treated at Duke University Medical Center. TIL-Bs in tissues were quantified by flow cytometry immunophenotyping. Ratios of TIL-Bs to abnormal B cells were assessed for prognostic effects. Results: First, we found thathigh frequencies of TIL-Bs and clonotypic diversity were associated with significantly favorable prognostic effects in 138 DLBCL patients with their malignant B-cell IGH-VDJ clonotypes identified (Figure A). The prognostic effects of TIL-Bs outweighed those of the germinal center B-cell-like/activated B-cell-like classification (Figure B). Second, patients with high frequencies of TIL-Bs compared with those without had significant upregulation of immune response genes by GEP (Figure C), higher CD4 T cell infiltration quantified by fluorescent mIHC (Figure D), and enrichment of EcoTyper-defined specific cell states, including significantly increased frequencies of B cell state S2 (pre-memory), CD4 T cell state S3 (naïve), follicular helper T cell state S3, and endothelial cell state S3, whereas lower frequencies of B cell state S5 (plasmablast) and follicular helper T cell state S1. Third, high TIL-B abundance in 79 ‘DJ-only’ clonotype cases and additional 52 cases assessed by light chain clonotype analysis showed similar favorable prognostic effects and associations with upregulated immune gene expression and CD4 T cell infiltration. Fourth, the identified GEP signatures, prominent with genes involved in T-dependent B cell activation and T cell activation and differentiation, showed significant prognostic effects in two GEO datasets. Fifth, TIL-B abundance showed significant prognostic effects in DLBCL cases infiltrated with T-cells in both the discovery study (Figure E) and validation study (Figure F, flow cytometry cohort). Conclusions: TIL-B frequencies and clonotypic diversity have remarkable prognostic and biological effects in DLBCL, which has significant implications for developing novel therapeutic strategies. Our study identified a new prognostic biomarker in DLBCL and an important player in anti-lymphoma immune responses, providing a new point of view to analyze the tumor biology in aggressive B-cell lymphoma and precisely identify prognostic determinants.