Single T Cell Sequencing Demonstrates the Functional Role alpha beta TCR Pairing in Cell Lineage and Antigen Specificity

Although structural studies of individual T cell receptors (TCRs) have revealed important roles for both the alpha and beta chain in directing MHC and antigen recognition, repertoire-level immunogenomic analyses have historically examined the beta chain alone. To determine the amount of useful information about TCR repertoire function encoded within alpha beta pairings, we analyzed paired TCR sequences from nearly 100,000 unique CD4+ and CD8+ T cells captured using two different high-throughput, single-cell sequencing approaches. Our results demonstrate little overlap in the healthy CD4+ and CD8+ repertoires, with shared TCR sequences possessing significantly shorter CDR3 sequences corresponding to higher generation probabilities. We further utilized tools from information theory and machine learning to show that while alpha and beta chains are only weakly associated with lineage, of pairings appear to synergistically drive TCR-MHC interactions. V alpha beta gene pairings were found to be the TCR feature most informative of T cell lineage, supporting the existence of germline-encoded paired alpha beta TCR-MHC interaction motifs. Finally, annotating our TCR pairs using a database of sequences with known antigen specificities, we demonstrate that approximately a third of the T cells possess alpha and beta chains that each recognize different known antigens, suggesting that alpha beta pairing is critical for the accurate inference of repertoire functionality. Together, these findings provide biological insight into the functional implications of alpha beta pairing and highlight the utility of single-cell sequencing in immunogenomics

Computational strategies for dissecting the high-dimensional complexity of adaptive immune repertoires

The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV). Adaptive immune receptor repertoire sequencing (AIRR-seq) has driven the quantitative and molecular-level profiling of immune repertoires thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity in order to understand the dynamics of adaptive immunity. Here, we review the current research on (i) diversity, (ii) clustering and network, (iii) phylogenetic and (iv) machine learning methods applied to dissect, quantify and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology towards coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.Comment: 27 pages, 2 figure

Corporate Social Responsibility and the Values in Schwartz Value Theory : Case: Botnia Events

In recent years, corporate social responsibility has gained growing recognition as a new concept to be integrated in companies' strategies and operations. The approach is becoming more widely accepted, which increase the interest in responsible business. Corporate social responsibility goes beyond philanthropy and the values that guide human actions have to be realized to contribute to its philosophical perspective. Values work as a guiding principles in human lives and this work applies universal Schwartz Value Theory as a framework to distinct those values. The fundamental reason for this study was to reveal the corporate values measuring the case company’s performance and to indicate individual values determining customers’ personal values. Thereby it was important to specify the general ratings on the company’s performance what concerns responsible business as well as to indicate the level of corporate social responsibility among the customers. The main aim of this thesis was to verify whether the case company’s values meet the values of their customers. The method to reach the goal of the study was the quantitative approach based on descriptive-causal research. The main findings revealed that the customers of the case company are aware of corporate social responsibility and they give rather high ratings on the company’s performance. Regarding the relationship between company’s and they customers’ values, gaps requiring improvements were noticed. Also the significant importance of socio-demographics in determining the values was acknowledged. The study concludes the noteworthiness of value examination to comprehend the patterns of human behaviour within the business environment.Viime vuosina yritysten sosiaalinen vastuu on saanut kasvavaa huomiota, kun tämä konsepti on sisällytetty yritysten strategioihin ja toimiin. Kyseinen lähestymistapa on yhä laajemmin hyväksytty, mikä lisää kiinnostusta vastuulliseen yritystoimintaan. Yritysten sosiaalinen vastuu ottaa huomioon ihmisyyden ja arvot, jotka ohjaavat ihmisten toimia. Nämä arvot ovat ymmärrettävä, jotta niiden filosofinen näkökulma vaikuttaisi yritysten vastuuseen. Tämän työn viitekehyksenä on yleismaailmallinen Schwartz -arvoteoria, joka selkeyttää ihmisiä ohjaavia arvoja. Olennaisin syy tämän tutkimuksen tekemiseen oli tuoda ilmi yritysarvot mittaamalla case-yrityksen arvoja ja osoittaa yksilölliset arvot määrittelemällä asiakkaiden henkilökohtaiset arvot. Tämän vuoksi oli tärkeää määrittää yleisarvosana yrityksen vastuullisesta toiminnasta sekä osoittaa yrityksen sosiaalisen vastuun taso asiakkaiden keskuudessa. Opinnäytetyön päätavoite oli varmistaa vastaavatko case-yrityksen arvot heidän asiakkaidensa arvoja. Tavoitteen saavuttamisessa käytettiin kvantitatiivista lähestymistapaa perustuen kuvailevaan-kausaaliseen tutkimukseen. Tutkimuksen tärkeimmät löydökset osoittavat, että case-yrityksen asiakkaat ovat tietoisia yritysten sosiaalisesta vastuusta ja he antavat melko korkeat arvosanat case-yrityksen toiminnasta. Ottaen huomioon yrityksen arvojen ja sen asiakkaiden arvojen välisen suhteen, parannusta tarvitsevat seikat huomattiin. Lisäksi otettiin huomioon sosio-demokraafisten tekijöiden merkittävä vaikutus asiakkaiden ilmoittamiin arvoihinsa. Tutkimuksesta voi päätellä arvotarkastelun tärkeyden ihmiskäyttäytymisen ymmärtämisessä liiketoiminnallisessa ympäristössä

Increasing generosity by disrupting prefrontal cortex

Recent research suggests that prosocial outcomes in sharing games arise from prefrontal control of self-maximizing impulses. We used continuous Theta Burst Stimulation (cTBS) to disrupt the functioning of two prefrontal areas, the right dorsolateral prefrontal cortex (DLPFC) and dorsomedial prefrontal cortex (DMPFC). We used cTBS in the right MT/V5, as a control area. We then tested subjects' prosocial inclinations with an unsupervised Dictator Game in which they allocated real money anonymously between themselves and low and high socioeconomic status (SES) players. cTBS over the two prefrontal sites made subjects more generous compared to MT/V5. More specifically, cTBS over DLPFC increased offers to high SES players, while cTBS over DMPFC caused increased offers to low SES players. These data, the first to demonstrate an effect of disruptive neuromodulation on costly sharing, suggest that DLPFC and MPFC exert inhibitory control over prosocial inclinations during costly sharing, though they may do so in different ways. DLPFC may implement contextual control, while DMPFC may implement a tonic form of control. This study demonstrates that humans' prepotent inclination is toward prosocial outcomes when cognitive control is reduced, even when prosocial decisions carry no strategic benefit and concerns for reputation are minimized

Social Integration and Attitudes Towards the Integration of Immigrants in Relation to Witnessing Domestic Aggression

The association between witnessing domestic aggression and respondents' level of social integration and their proactive attitudes towards the integration of immigrants was assessed with a questionnaire in a sample of the Swedish-speaking minority in Ostrobothnia, Western Finland (n = 298; 208 females and 90 males). The age span was between 16 and 90 years with a mean age of 31.6 years (SD = 13.5). Respondents scoring higher than average on witnessing domestic aggression scored lower than others on the following scales measuring social integration: Access to Social Benefits, Positive Social Relations, and Trust in the Finnish Judiciary System. They also scored lower than others on the following scales measuring proactive attitudes towards the integration of immigrants: (the need for making) Cultural Efforts, Structural Efforts, and Openness to Diversity. They also tended to have a lower level of education than other respondents. The implications of the findings are discussed.

Empathy: Gender effects in brain and behavior

Evidence suggests that there are differences in the capacity for empathy between males and females. However, how deep do these differences go? Stereotypically, females are portrayed as more nurturing and empathetic, while males are portrayed as less emotional and more cognitive. Some authors suggest that observed gender differences might be largely due to cultural expectations about gender roles. However, empathy has both evolutionary and developmental precursors, and can be studied using implicit measures, aspects that can help elucidate the respective roles of culture and biology. This article reviews evidence from ethology, social psychology, economics, and neuroscience to show that there are fundamental differences in implicit measures of empathy, with parallels in development and evolution. Studies in nonhuman animals and younger human populations (infants/children) offer converging evidence that sex differences in empathy have phylogenetic and ontogenetic roots in biology and are not merely cultural byproducts driven by socialization. We review how these differences may have arisen in response to males’ and females’ different roles throughout evolution. Examinations of the neurobiological underpinnings of empathy reveal important quantitative gender differences in the basic networks involved in affective and cognitive forms of empathy, as well as a qualitative divergence between the sexes in how emotional information is integrated to support decision making processes. Finally, the study of gender differences in empathy can be improved by designing studies with greater statistical power and considering variables implicit in gender (e.g., sexual preference, prenatal hormone exposure). These improvements may also help uncover the nature of neurodevelopmental and psychiatric disorders in which one sex is more vulnerable to compromised social competence associated with impaired empathy