Self-reinforcing Feedback Loop Research Articles

Coordinate Regulation of TCR signaling, Notch, and Gata3 in T Cell Development (138.27)

Abstract The transcription factors, Notch and Gata3, are both involved in the intrathymic development of CD4 lineage T cells. It has been proposed that Gata3 is critical in CD4 T cell maturation after lineage commitment. To the contrary, we find that disruption of the Gata3 gene re-directs a fraction of MHC II-restricted thymocytes to the CD8 lineage. Moreover, Gata3 binds regulatory regions of the ThPOK (Zbtb7b) gene in vivo and is required for the ThPOK expression that enforces CD4 lineage commitment (Nature Immunol. 9:1122). Collectively, these findings place Gata3 developmentally upstream of the CD4/CD8 lineage decision and raise the question of how Gata3 itself is regulated. Our data and that of others suggest that Gata3 expression is regulated by TCR signaling, but Gata3 can also promote TCR signaling/expression. Therefore, Gata3 may operate in a self-reinforcing feedback loop during positive selection to achieve the levels of TCR signaling required for ThPOK induction and CD4 lineage commitment. In the differentiation of peripheral Th2 cells, Gata3 transcription can be regulated by Notch. We find that Notch and Gata3 promote TCR signal transduction prior to positive selection, as well as the selection/maturation of CD4/CD8 T lineages. Thus, we have designed genetic and expression studies to investigate whether Notch regulates Gata3 in thymocytes. Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

Functional brain interactions that serve cognitive–affective processing during pain and placebo analgesia

Pain requires the integration of sensory, cognitive, and affective information. The use of placebo is a common methodological ploy in many fields, including pain. Neuroimaging studies of pain and placebo analgesia (PA) have yet to identify a mechanism of action. Because PA must result from higher order processes, it is likely influenced by cognitive and affective dimensions of the pain experience. A network of brain regions involved in these processes includes the anterior and posterior insula (A-Ins, P-Ins), dorsal anterior cingulate cortex (DACC), dorsolateral prefrontal cortex (DLPFC), and the supplementary motor area (SMA). We used connectivity analyses to investigate the underlying mechanisms associated with Placebo analgesia in a group of chronic pain patients. Structural equation models (SEM) of fMRI data evaluated the inter-regional connectivity of these regions across three conditions: (1) initial Baseline (B1), (2) placebo (PA), and (3) Placebo Match (PM). SEM results of B1 data in the left hemisphere confirmed hypothesized regional relationships. However, inter-regional relationships were dynamic and the network models varied across hemispheres and conditions. Deviations from the B1 model in the PA and PM conditions correspond to our manipulation of expectation for pain. The dynamic changes in inter-regional influence across conditions are interpreted in the context of a self-reinforcing feedback loop involved in the induction and maintenance of PA. Although it is likely that placebo analgesia results partly from afferent inhibition of a nociceptive signal, the mechanisms likely involve the interaction of a cognitive–affective network with input from both hemispheres.

Editorial. JNM editorial for May 2005 - Managing nursing in an increasingly complex environment of care

Editorial. JNM editorial for May 2005 - Managing nursing in an increasingly complex environment of care

Psychological predictors of sudden death in myocardial infarction

Physical inactivity and psychosocial stress are prevalent in residents of the United States. The purpose of this article is to review the interaction between these 2 conditions and examine the effects of exercise on stress and cardiovascular (CV) health. A query of scientific references between 1974 to 2018 was performed using the PubMed search engine accessing the MEDLINE database using the search terms psychosocial stress, CV disease (CVD), physical activity, exercise, cardiac rehabilitation, and team sports. Psychosocial stress is a strong independent risk factor for adverse CV events. Conversely, people who experience CV events subsequently have drastically elevated rates of new-onset mental health disorders, including depression and anxiety. Psychosocial stress and CVD often trigger self-reinforcing feedback loops that can worsen mental health and cardiac prognosis. Exercise predictably improves CV health and prognosis and also is effective at lowering levels of psychosocial stress. Group exercise in particular seems to provide social support while at the same time boosting fitness levels and, thus, may be the single most important intervention for patients with concomitant CVD and emotional stress. Collaborative physical activity, such as group exercise, team sports, interactive physical play, and cardiac rehabilitation programs, have the potential to improve mental health and CV prognosis.