NFATc1 controls the cytotoxicity of CD8+ T cells

NFAT nuclear translocation has been shown to be required for CD8+ T cell cytokine production in response to viral infection. Here the authors show NFATc1 controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells

Digital NFATc2 Activation per Cell Transforms Graded T Cell Receptor Activation into an All-or-None IL-2 Expression

The expression of interleukin-2 (IL-2) is a key event in T helper (Th) lymphocyte activation, controlling both, the expansion and differentiation of effector Th cells as well as the activation of regulatory T cells. We demonstrate that the strength of TCR stimulation is translated into the frequency of memory Th cells expressing IL-2 but not into the amount of IL-2 per cell. This molecular switch decision for IL-2 expression per cell is located downstream of the cytosolic Ca2+ level. Here we show that in a single activated Th cell, NFATc2 activation is digital but NF-κB activation is graded after graded T cell receptor (TCR) signaling. Subsequently, NFATc2 translocates into the nucleus in an all-or-none fashion per cell, transforming the strength of TCR-stimulation into the number of nuclei positive for NFATc2 and IL-2 transcription. Thus, the described NFATc2 switch regulates the number of Th cells actively participating in an immune response

Weak correlations between serum and cerebrospinal fluid levels of estradiol, progesterone and testosterone in males

Abstract Background Neuroactive steroids seem to be implicated in a variety of neurophysiological and behavioral processes, such as sleep, learning, memory, stress, feeding and aging. Numerous studies have also addressed this implication in various cerebral disorders and diseases. Yet, the correlation and association between steroids in the periphery, e.g. blood, and the central compartments, e.g. cerebrospinal fluid (CSF), have not yet been comprehensively assessed. As the brain is not directly accessible, and the collection of human CSF usually requires invasive procedures, easier accessible compartments, such as blood, have always attracted attention. However, studies in humans are scarce. In the present study we determined estradiol, progesterone and testosterone levels in CSF and serum of 22 males without cerebral disorders or diseases. Results Samples were taken under conditions corresponding closest to basal conditions with patients expecting only spinal anesthesia and minor surgery. All samples per patient were collected concomitantly. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. Correlation analysis revealed merely weak to very weak correlations for estradiol, progesterone and testosterone respectively between the CSF and serum compartments. Conclusions Total steroid levels of estradiol, progesterone and testosterone in CSF and serum of males without neurological disorders were determined. Weak to very weak correlations between CSF and serum were found thus suggesting that concentrations in the periphery do not parallel concentrations in the central compartments. Further research is needed to clarify to what extent and under which conditions serum levels of estradiol, progesterone and testosterone may possibly serve as a biomarker reflecting the respective concentrations in the CSF or in the brain. </jats:sec

Digitale Personaleinsatzplanung in ambulanten und stationären anästhesiologischen Versorgungseinrichtungen: Ergebnisse einer Online-Umfrage

Background: Our country still needs to catch up with others when it comes to digitisation in the health sector. This does not only apply to patient care. The aim of this paper is to record the status quo of personnel management in German outpatient and inpatient anaesthesiologic care facilities. Methodology: This article presents the second part of a survey conducted in October 2021, which focused on the state of digitisation in German anaesthesiology. The link to the survey was sent to a total of 2,930 heads of anaesthesia departments in hospitals as well as practice owners. Results: A total of 635 persons participated in the survey. We found that software for staff planning is less frequently used in the outpatient as compared to the inpatient sector. Large facilities use software more often than smaller ones do; this is applies to both outpatient and inpatient facilities. Most of the software tools used offer documentation and working time recording options. Automated duty scheduling and the consideration of staff preferences play a subordinate role in the software functions.Conclusion: Digital personnel management is predominantly operated by larger out-patient facilities and clinics. As such, it primarily serves to comply with legal requirements. More advanced functions, for example, automated duty scheduling, which would save the departments a lot of work and time, are usually not provided by other software tools used</div

Polyfunctional responses by human T cells result from sequential release of cytokines

The release of cytokines by T cells defines a significant part of their functional activity in vivo, and their ability to produce multiple cytokines has been associated with beneficial immune responses. To date, time-integrated end-point measurements have obscured whether these polyfunctional states arise from the simultaneous or successive release of cytokines. Here, we used serial, time-dependent, single-cell analysis of primary human T cells to resolve the temporal dynamics of cytokine secretion from individual cells after activation ex vivo. We show that multifunctional, Th1-skewed cytokine responses (IFN-γ, IL-2, TNFα) are initiated asynchronously, but the ensuing dynamic trajectories of these responses evolve programmatically in a sequential manner. That is, cells predominantly release one of these cytokines at a time rather than maintain active secretion of multiple cytokines simultaneously. Furthermore, these dynamic trajectories are strongly associated with the various states of cell differentiation suggesting that transient programmatic activities of many individual T cells contribute to sustained, population-level responses. The trajectories of responses by single cells may also provide unique, time-dependent signatures for immune monitoring that are less compromised by the timing and duration of integrated measures.National Institute of Allergy and Infectious Diseases (U.S.) (grant no. 1U19AI089992)National Institute of Allergy and Infectious Diseases (U.S.) (grant no. 5P01AI045757)National Institute of Allergy and Infectious Diseases (U.S.) (grant no. 1R21AI088590)National Institute of Allergy and Infectious Diseases (U.S.) (grant no. 1RC1AI086152