The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system - the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man - is comprised of varying amplitude pulses that exist due to a sub-hypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behaviour, affective state and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment. © Endocrine Society 2020.As a plant hormone, salicylic acid (SA) plays essential roles in plant defense against biotrophic and hemibiotrophic pathogens. Significant progress has been made in understanding the SA biosynthesis pathways and SA-mediated defense signaling networks in the past two decades. Plant defense responses involve rapid and massive transcriptional reprogramming upon the recognition of pathogens. Plant transcription factors and their co-regulators are critical players in establishing a transcription regulatory network and boosting plant immunity. A multitude of transcription factors and epigenetic regulators have been discovered, and their roles in SA-mediated defense responses have been reported. However, our understanding of plant transcriptional networks is still limited. As such, novel genomic tools and bioinformatic techniques will be necessary if we are to fully understand the mechanisms behind plant immunity. Here, we discuss current knowledge, provide an update on the SA biosynthesis pathway, and describe the transcriptional and epigenetic regulation of SA-mediated plant immune responses. Published by Oxford University Press on behalf of the Society for Experimental Biology 2020.Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1 ng/ml) than that in invasive pulmonary aspergillosis patients (0.53 ng/ml) and the negative control (0.49 ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis. © The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.BACKGROUND A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of post-vaccine serum anti-rotavirus immunoglobulin A (IgA) that serves as an individual-level immune correlate of protection against rotavirus gastroenteritis. METHODS Individual-level data on 5,074 infants enrolled in nine GlaxoSmithKline Rotarix Phase II/III clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis. RESULTS Seroconversion (IgA ≥20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis up to 1 year of age. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR=0.04, 95% confidence interval (CI)=0.01-0.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (0.46, 0.25-0.86). As the IgA threshold increased, the risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings. DISCUSSION Post-vaccination anti-rotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis up to 1 year of age. https://www.selleckchem.com/products/neo2734.html Seroconversion provides an informative threshold for assessing rotavirus vaccine performance. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.