RESUMO
This paper presents a moderation-mediation model suggesting that proactivity and job autonomy moderate the mediating effects of engagement on the relationship of servant leadership with job performance and lateness. Data were collected from a sample of 50 bank departments from three sources: managers (n = 50), employees (n = 165), and objective data provided by human resources departments. The results show that as expected, the association of servant leadership with work engagement was stronger for employees with low levels of proactivity and job autonomy. Proactivity moderated the mediating effect of engagement on the relationship of servant leadership with both job performance and lateness; autonomy moderated the mediating effect of engagement on the relationship between servant leadership and lateness. The results imply that placing employees with low levels of proactivity and job autonomy under the supervision of servant leaders can engender higher job engagement and better organizational outcomes (AU)
El artículo presenta un modelo de moderación-mediación que indica que la proactividad y la autonomía en el puesto de trabajo moderan los efectos mediadores de la implicación en la relación del liderazgo de servicio con el desempeño e impuntualidad de los empleados. Se recogieron datos de una muestra de 50 departamentos bancarios procedentes de tres fuentes: directivos (n = 50), empleados (n = 165) y datos objetivos facilitados por los departamentos de recursos humanos. Los resultados muestran que, tal y como se esperaba, la asociación del liderazgo de servicio y la implicación en el trabajo era mayor en los empleados con baja proactividad y autonomía en el puesto. La proactividad moderaba el efecto mediador de la implicación en la relación del liderazgo de servicio con el desempeño y la impuntualidad. La autonomía moderaba el efecto mediador de la implicación en el puesto en la relación entre el liderazgo de servicio y la impuntualidad de los empleados. Los resultados indican que poner a los empleados con bajo nivel de proactividad y autonomía en el puesto bajo la supervisión de líderes servidores puede mejorar la implicación en el puesto y los resultados organizativos (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Liderança , Autonomia Profissional , Desempenho de Papéis , Engajamento no TrabalhoRESUMO
OBJECTIVE: Through intensive experience sampling, we studied the practice and development of mindfulness as a dynamic process in time and context. We focused on role(s) and salutary function(s) of mindfulness and decentering for emotional experience over the course of mindfulness practice and development. METHOD: Eighty-two meditation-naive adults from the general community, 52% women, Mage (SD) = 25.05 (3.26) years, participated in a 1-month, 6-session, Mahasi-based mindfulness-training intervention (Mahasi, 1978). We collected 52 digital experience samples of mindfulness, decentering, and emotional experience, in the context of daily living and meditative states, over the course of the program. RESULTS: Data were analyzed via time-varying effects models (TVEMs) and mixed-linear models (MLMs) within a single-subject, multiple-baseline experimental design. First, over the course of the intervention, participants grew more mindful and decentered in daily living and meditative states. Second, the association between mindfulness and decentering was significant in daily living, although the magnitude of this association was stronger in meditative states. Third, we observed the same contextualized pattern of relations between mindfulness and emotional valence (happy > sad) as well as arousal (calm > nervous). Finally, whereas decentering mediated the effect of mindfulness on reduced emotional arousal in meditative states, it did not similarly mediate the effect of mindfulness on positive emotional valence. CONCLUSIONS: The present findings illustrate the insights that may be gained about mindfulness mechanisms broadly and decentering specifically through the study of mindfulness as a dynamic, contextualized developmental process over time. (PsycINFO Database Record
Assuntos
Avaliação Momentânea Ecológica , Atenção Plena/métodos , Adulto , Feminino , Humanos , Masculino , Estudos de Amostragem , TempoRESUMO
Adoptive transfer of Ag-specific T lymphocytes is an attractive form of immunotherapy for cancers. However, acquiring sufficient numbers of host-derived tumor-specific T lymphocytes by selection and expansion is challenging, as these cells may be rare or anergic. Using engineered T cells can overcome this difficulty. Such engineered cells can be generated using a chimeric Ag receptor based on common formats composed from Ag-recognition elements such as αß-TCR genes with the desired specificity, or Ab variable domain fragments fused with T cell-signaling moieties. Combining these recognition elements are Abs that recognize peptide-MHC. Such TCR-like Abs mimic the fine specificity of TCRs and exhibit both the binding properties and kinetics of high-affinity Abs. In this study, we compared the functional properties of engineered T cells expressing a native low affinity αß-TCR chains or high affinity TCR-like Ab-based CAR targeting the same specificity. We isolated high-affinity TCR-like Abs recognizing HLA-A2-WT1Db126 complexes and constructed CAR that was transduced into T cells. Comparative analysis revealed major differences in function and specificity of such CAR-T cells or native TCR toward the same antigenic complex. Whereas the native low-affinity αß-TCR maintained potent cytotoxic activity and specificity, the high-affinity TCR-like Ab CAR exhibited reduced activity and loss of specificity. These results suggest an upper affinity threshold for TCR-based recognition to mediate effective functional outcomes of engineered T cells. The rational design of TCRs and TCR-based constructs may need to be optimized up to a given affinity threshold to achieve optimal T cell function.
Assuntos
Anticorpos/imunologia , Vacinas Anticâncer , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/fisiologia , Afinidade de Anticorpos , Citotoxicidade Imunológica , Engenharia Genética , Antígeno HLA-A2/metabolismo , Humanos , Células Jurkat , Neoplasias/imunologia , Ligação Proteica , Transdução de Sinais , Especificidade do Receptor de Antígeno de Linfócitos TRESUMO
Seamless embedment of electronic devices in biological systems is expected to add the outstanding computing power, memory, and speed of electronics to the biochemical toolbox of nature. Such amalgamation requires transduction of electronic signals into biochemical cues that affect cells. Inspired by biology, where pathways are directed by molecular recognition, we propose and demonstrate a generic electrical-to-biological transducer comprising a two-state electronic antigen and a chimeric cell receptor engineered to bind the antigen exclusively in its "on" state. T-cells expressing these receptors remain inactivated with the antigen in its "off" state. Switching the antigen to its "on" state by an electrical signal leads to its recognition by the T-cells and correspondingly to cell activation.
Assuntos
Receptores de Antígenos de Linfócitos T/efeitos da radiação , Anticorpos de Cadeia Única/efeitos da radiação , Linfócitos T/efeitos da radiação , Células Cultivadas , Campos Eletromagnéticos , Humanos , Receptores de Antígenos de Linfócitos T/química , Anticorpos de Cadeia Única/química , Linfócitos T/químicaRESUMO
The glycolipid alpha-galactosylceramide (alpha-GalCer) is a potent activator of invariant natural killer T (iNKT) cells and has been shown to be an effective agent against cancer, infections and autoimmune diseases. The effectiveness of alpha-GalCer and its alkyl chain analogues depends on efficient loading and presentation by the antigen-presenting molecule CD1d. To monitor the ability of CD1d to present the glycolipids, we have used a phage display strategy to generate recombinant antibodies with T cell receptor-like (TCRL) specificity against the human CD1d (hCD1d)-alpha-GalCer complex. These Fab fragments were able to detect specifically hCD1d-alpha-GalCer complexes in cell-free systems such as surface plasmon resonance and ELISA, as well as on the surface of hCD1d(+) antigen-presenting cells (APC) by flow cytometry and immunofluorescence microscopy, the latter of which could also detect intracellular complexes. We show that our TCRL antibodies can stain dendritic cells from CD11c-hCD1d-transgenic mice administered in vivo with alpha-GalCer and its analogues. Furthermore, the antibody was also able to detect the presentation by hCD1d molecules of analogues of alpha-GalCer with the same polar head structure. Using this reagent, we were able to confirm directly that the alpha-GalCer analogue C20:2 preferentially loads onto cell surface CD1d rapidly without the need for internalization, while the loading of alpha-GalCer is improved with longer incubation times on professional APC. This reagent will be essential for assessing the loading and presenting capabilities of hCD1d of alpha-GalCer and its analogues.