Lymphopenia is a prominent part of SARS-CoV infection and lymphocyte counts may be useful in predicting the severity and clinical outcomes. Possible reasons for the SARS-associated lymphopenia may be direct infection of lymphocytes by SARS-CoV, lymphocyte sequestration in the lung or cytokine-mediated lymphocyte trafficking. There may also be immune-mediated lymphocyte destruction, bone marrow or thymus suppression, or apoptosis.

In plant immunity, pathogen-activated intracellular nucleotide binding/leucine rich repeat (NLR) receptors mobilize disease resistance pathways, but the downstream signaling mechanisms remain obscure. Enhanced disease susceptibility 1 (EDS1) controls transcriptional reprogramming in resistance triggered by Toll-Interleukin1-Receptor domain (TIR)-family NLRs (TNLs). Transcriptional induction of the salicylic acid (SA) hormone defense sector provides one crucial barrier against biotrophic pathogens. Here, we present genetic and molecular evidence that in Arabidopsis an EDS1 complex with its partner PAD4 inhibits MYC2, a master regulator of SA-antagonizing jasmonic acid (JA) hormone pathways. In the TNL immune response, EDS1/PAD4 interference with MYC2 boosts the SA defense sector independently of EDS1-induced SA synthesis, thereby effectively blocking actions of a potent bacterial JA mimic, coronatine (COR). We show that antagonism of MYC2 occurs after COR has been sensed inside the nucleús but before or coincident with MYC2 binding to a target promoter, pANAC019. The stable interaction of PAD4 with MYC2 in planta is competed by EDS1-PAD4 complexes. However, suppression of MYC2-promoted genes requires EDS1 together with PAD4, pointing to an essential EDS1-PAD4 heterodimer activity in MYC2 inhibition. Taken together, these results uncover an immune receptor signaling circuit that intersects with hormone pathway crosstalk to reduce bacterial pathogen growth.

Key Points Question What is the association between physical activity and the risk of Parkinson disease? Findings In this systematic review and meta-analysis of more than half a million unique participants, physical activity, particularly moderate to vigorous physical activity, was associated with a significant reduction in Parkinson disease risk. This association was stronger among men than women. Meaning Physical activity may be an important protective factor for preventing the development of Parkinson disease among at-risk men; thus, large prospective studies should be performed to examine this association and to investigate the factors that underlie the observed sex difference.

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Calcium (Ca 2+) is a second messenger for plant cell surface and intracellular receptors mediating pattern-triggered and effector-triggered immunity (respectively, PTI and ETI). Several CYCLIC NUCLEOTIDE-GATED CHANNELS (CNGCs) were shown to control transient cytosolic Ca 2+ influx upon PTI activation. The contributions of specific CNGC members to PTI and ETI remain unclear. ENHANCED DISEASE SUSCEPTIBLITY1 (EDS1) regulates ETI signaling. In an Arabidopsis genetic screen for suppressors of eds1, we identify a recessive gain-of-function mutation in CNGC20, denoted cngc20-4, which partially restores disease resistance in eds1. cngc20-4 enhances PTI responses and ETI hypersensitive cell death. A cngc20-4 single mutant exhibits autoimmunity, which is dependent on genetically parallel EDS1 and salicylic acid (SA) pathways. CNGC20 self-associates, forms heteromeric complexes with CNGC19, and is phosphorylated and stabilized by BOTRYTIS INDUCED KINASE1 (BIK1). The cngc20-4 L371F exchange on a predicted transmembrane channel inward surface does not disrupt these interactions but leads to increased cytosolic Ca 2+ accumulation, consistent with mis-regulation of CNGC20 Ca 2+-permeable channel activity. Our data show that ectopic Ca 2+ influx caused by a mutant form of CNGC20 in cngc20-4 affects both PTI and ETI responses. We conclude that tight control of the CNGC20 Ca 2+ ion channel is important for regulated immunity.