The ontogeny and regulation of human natural killer cells

Natural Killer (NK) cells are members of the innate lymphoid cell (ILC) family and take part in the detection and eradication of virus-infected and transformed cells. In this thesis, together with my colleagues I have investigated how NK cells and other ILCs develop and function during human fetal development, how NK cells are functionally regulated (educated) via the activating receptor KIR2DS1, and how NK cells in our body are affected during the early phase of an acute viral infection. Little is known about the ontogeny of NK cells and other ILCs in fetal development. The characterization of ILCs has been hampered by their overlapping surface phenotypes. In contrast, ILC transcription factor expression is more specific, and by combining multicolor flow cytometry analysis of transcription factors and surface markers expressed by different fetal ILC subsets, we were able to study and model their development and differentiation. All ILC subsets were detected as early as gestational week six, and their distribution varied depending on both tissue and gestational age. Moreover, putative precursors of NK cells were identified as cells that sequentially lost CD34 and acquired CD122, Eomes, CD94/NKG2A, T-bet, and CD16. In addition putative CD34+ progenitors of RORγt+ ILCs were identified. In the second trimester of fetal development, analysis of mature fetal NK cell subsets revealed that stage 4 and stage 5 NK cells differed in frequency in fetal organs, and the highest NK cell frequency was found in the fetal liver and lung. The vast majority of fetal NK cells were NKG2A+, and fetal lung NK cells also frequently expressed killercell immunoglobulin-like receptors (KIR). Interestingly, while NKG2A educated fetal NK cells similar to adult NK cells, KIR expression on fetal NK cells was linked to hyporesponsiveness, thus contrasting education of NK cells after birth. Nevertheless, fetal NK cells were highly responsive to cytokines, as well as to antibody-coated target cells, suggesting they may take part in fetal immune responses against in utero infections, while remaining tolerant to maternal cells crossing the placenta. While it is established that NK cells in adults are educated via inhibitory KIRs, it is not known how activating KIRs such as KIR2DS1 affects NK cells. By combining antibodies against four inhibitory KIRs, NKG2A, and KIR2DS1, we were able to interrogate the regulation of NK cells by KIR2DS1. We found that KIR2DS1 singlepositive NK cells exist in vivo, and that the presence of the ligand for KIR2DS1, HLAC2, resulted in hyporesponsiveness of such NK cells, thus ensuring self-tolerance. Our findings represent the first identification of NK cell education via activating KIR. The human NK cell response to viral infections is not well understood. To this end we employed the live attenuated yellow fever vaccine 17D as an in vivo model of an acute viral infection. Our results show that the vaccine primed NK cells, and that less differentiated CD57- NK cells dominated the response, which peaked at day 6-10 post vaccination. Moreover, KIR expression on NK cells did not affect their response to the vaccine, indicating that NK cells expressing self-KIR and non-self KIR contributed equally to the NK cell response to the vaccination

Exploring longitudinal measurement invariance and the continuum hypothesis in the Swedish version of the Behavioral Regulation in Sport Questionnaire (BRSQ): An exploratory structural equation modeling approach

Objectives: The aims of the present study were to: (a) examine longitudinal measurement invariance in the Swedish version of the Behavioral Regulations in Sport Questionnaire (BRSQ) and (b) examine the continuum hypothesis of motivation as postulated within self-determination theory. Design: Two-wave survey. Method: Young competitive athletes (N = 354) responded to the BRSQ early in the season (November) and at the end of the athletic season (April). Data were analyzed using exploratory structural equation modeling (ESEM) and bifactor ESEM. Results: We found support for strict longitudinal measurement invariance in the BRSQ. Latent mean comparisons showed an increase in external regulation and amotivation across the season. The latent factor correlations indicated some deviations from a simplex pattern related to amotivation, external regulation, and introjected regulation. In the bifactor model, intrinsic motivation items had negative factor loadings on the global factor, identified regulation items had factor loadings approaching zero, and introjected and external regulation and amotivation items all had moderate to strong positive factor loadings. Conclusion: The present study adds longitudinal measurement invariance to the psychometric evidence of the BRSQ. Research on why the latent means of the behavioral regulations changed over the athletic season is warranted. The continuum hypothesis was partially supported. Latent factor correlations and factor loadings on the global factor in the bifactor ESEM highlighted that the discriminant validity of the controlled regulations and amotivation needs further investigation

Basic psychological needs satisfaction and frustration, stress, and sports injury among university athletes: A four-wave prospective survey

© 2019 Li, Ivarsson, Lam and Sun. The prevalence of sports injury among athletes is rather high, suggesting the need to better understand the causes of sports injury, including the risk factors, for preventive purposes. Grounded in basic psychological needs theory (BPNT) and the Model of Stress and Athletic Injury, the aim of this four-wave prospective survey study was to investigate the relationships among basic psychological needs satisfaction and frustration, stress responses, and sports injury. Study variables, including basic psychological need satisfaction/frustration, and perceived stress, were measured using a survey from 112 university athletes at the 1st, 2nd, and 3rd months of the study. Sports injury was assessed using a self-report form at the 2nd, 3rd, and 4th months of study. Results of the Bayesian multilevel analysis showed that basic psychological need satisfaction negatively predicted sports injuries, whereas stress was a positive predictor. In addition, basic psychological need satisfaction had an indirect effect on injury occurrence via stress. However, basic psychological need frustration did not predict sports injury. BPNT is a viable model to provide additional explanations to psychological risk factors of injury. Intervention programs may be formulated based on the evidence obtained on the model

Response-order effects in survey methods: A randomized controlled crossover study in the context of sport injury prevention

Consistency tendency is characterized by the propensity for participants responding to subsequent items in a survey consistent with their responses to previous items. This method effect might contaminate the results of sport psychology surveys using cross-sectional design. We present a randomized controlled crossover study examining the effect of consistency tendency on the motivational pathway (i.e., autonomy support → autonomous motivation → intention) of self-determination theory in the context of sport injury prevention. Athletes from Sweden (N = 341) responded to the survey printed in either low interitem distance (IID; consistency tendency likely) or high IID (consistency tendency suppressed) on two separate occasions, with a one-week interim period. Participants were randomly allocated into two groups, and they received the survey of different IID at each occasion. Bayesian structural equation modeling showed that low IID condition had stronger parameter estimates than high IID condition, but the differences were not statistically significant

Elucidation of Short Linear Motif-Based Interactions of the FERM Domains of Ezrin, Radixin, Moesin, and Merlin

The ERM (ezrin, radixin, and moesin) family of proteins and the related protein merlin participate in scaffolding and signaling events at the cell cortex. The proteins share an N-terminal FERM [band four-point-one (4.1) ERM] domain composed of three subdomains (F1, F2, and F3) with binding sites for short linear peptide motifs. By screening the FERM domains of the ERMs and merlin against a phage library that displays peptides representing the intrinsically disordered regions of the human proteome, we identified a large number of novel ligands. We determined the affinities for the ERM and merlin FERM domains interacting with 18 peptides and validated interactions with full-length proteins through pull-down experiments. The majority of the peptides contained an apparent Yx[FILV] motif; others show alternative motifs. We defined distinct binding sites for two types of similar but distinct binding motifs (YxV and FYDF) using a combination of Rosetta FlexPepDock computational peptide docking protocols and mutational analysis. We provide a detailed molecular understanding of how the two types of peptides with distinct motifs bind to different sites on the moesin FERM phosphotyrosine binding-like subdomain and uncover interdependencies between the different types of ligands. The study expands the motif-based interactomes of the ERMs and merlin and suggests that the FERM domain acts as a switchable interaction hub

The role of domain-specific and domain-general cognitive functions and skills in sports performance: A meta-analysis

Cognition plays a key role in sports performance. In this meta-analytic review, we synthesize research that has examined the relationship between cognitive functions, skills, and sports performance. We identified literature by searching Cochrane library, PsychInfo, Pubmed, and Web of Science. We included studies conducted on competitive athletes, assessed cognitive prerequisites, and included performance measures related to the sport. Of the 9433 screened records, 136 reports were included, containing 142 studies, 1227 effect sizes, and 8860 participants. Only 11 studies used a prospective study design. The risk of bias was assessed using The Risk of Bias Assessment Tool for Nonrandomized Studies. The multilevel meta- analysis showed a medium effect size for the overall difference in cognitive functions and skills, with higher-skilled athletes scoring better than lower-skilled athletes (Hedges’ g = 0.59, 95% CI [0.49, 0.69]). The moderator analysis showed larger effect size for tests of cognitive decision-making skills (g = 0.77, 95% CI [0.6, 0.94]) compared to basic (g = 0.39, 95% CI [0.21, 0.56]) and higher cognitive functions (g = 0.44, 95% CI [0.26, 0.62]), as well as larger effect size for sport-specific task-stimuli compared to general ones. We report that higher-skilled athletes perform better on tests of cognitive function compared to lower-skilled athletes. There was insufficient evidence to determine whether cognitive functions and skills can predict future sport performance. We found no evidence to support claims that tests of general cognitive functions, such as executive functioning, should be used by practitioners for talent identification or player selection

Estimation of efficiency of the use of financial resources on enterprises

Стаття присвячена дослідженню теоретичних та практичних питань аналітичного забезпечення управління використанням фінансових ресурсів підприємств. Запропоновані комплексні показники оцінки даного процесуThe article is devoted to research of theoretical and practical questions of the analytical providing of management the use of financial resources of enterprises. The complex indexes of estimation of this process are offere

Non-LTE line formation for Pr II and Pr III in A and Ap stars

Non-LTE line formation for Pr II and Pr III is considered through a range of effective temperatures between 7250 K and 9500 K. A comprehensive model atom for Pr II/III is based on the measured and the predicted energy levels, in total, 6708 levels of Pr II and Pr III. We describe calculations of the Pr II energy levels and oscillator strengths for the transitions in Pr II and Pr III. The influence of departures from LTE on Pr abundance determinations is evaluated. At Teff >= 8000 K departures from LTE lead to overionization of Pr II and to systematically depleted total absorption in the line and positive abundance corrections. At the lower temperatures, different lines of Pr II may be either weakened or amplified depending on the line strength. The non-LTE effects strengthen the Pr III lines and lead to negative abundance corrections. Non-LTE corrections grow with effective temperature for the Pr II lines, and, in contrast, they decline for the Pr III lines. The Pr II/III model atom is applied to determine the Pr abundance in the atmosphere of the roAp star HD 24712 from the lines of two ionization stages. In the chemically uniform atmosphere with [Pr/H] = 3, the departures from LTE may explain only small part (0.3 dex) of the difference between the LTE abundances derived from the Pr II and Pr III lines (2 dex). We find that the lines of both ionization stages are described for the vertical distribution of the praseodymium where the Pr enriched layer with [Pr/H] > 4 exists in the outer atmosphere at log tau_5000 < -4. The departures from LTE for Pr II/III are strong in the stratified atmosphere and have the opposite sign for the Pr II and Pr III lines. Using the revised partition function of Pr II and experimental transition probabilities, we determine the solar non-LTE abundance of Pr as log (Pr/H) = -11.15\pm0.08.Comment: 17 pages, 4 tables, 11 figures, accepted for publication in A&