The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana

Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific ‘‘avirulent’’ pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4) and RRS1 (resistance to Ralstonia solanacearum 1), function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NBLRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1) mutant encodes an RRS1 allele (RRS1SLH1) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi) mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector

Predictors of health decline in older adults with pneumonia: findings from the Community Acquired Pneumonia Impact Study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify predictors of health decline among older adults with clinically diagnosed community acquired pneumonia (CAP). It was hypothesized that older adults with CAP who had lower levels of social support would be more likely to report a decline in health.</p> <p>Methods</p> <p>A telephone survey was used to collect detailed information from older adults about their experiences with CAP. A broader determinants of health framework was used to guide data collection. This was a community wide study with participants being recruited from all radiology clinics in one Ontario community.</p> <p>Results</p> <p>The most important predictors of a health decline included: two symptoms (no energy; diaphoresis), two lifestyle variables (being very active; allowing people to smoke in their home), one quality of life variable (little difficulty in doing usual daily activities) and one social support variable (having siblings).</p> <p>Conclusions</p> <p>A multiplicity of factors was found to be associated with a decline in health among older adults with clinically diagnosed CAP. These findings may be useful to physicians, family caregivers and others for screening older adults and providing interventions to help ensure positive health outcomes.</p

Association of Dyslipidemia and Concomitant Risk Factors with In-Hospital Mortality in Acute Coronary Syndrome in Switzerland

Background: Although dyslipidemia is one of the main risk factors for cardiovascular diseases, very few randomized trials have provided data on the association of dyslipidemia and in-hospital mortality in patients with acute coronary syndrome (ACS). Objective: The study assessed the association of dyslipidemia and concomitant risk factors, and early lipid-lowering therapy (LLD) on in-hospital mortality in patients admitted for ACS. Methods: Using AMIS Plus registry data, 13,482 patients admitted between January 1997 and October 2003 were analyzed, and logistic regression was used for predicting in-hospital mortality. Results: Baseline characteristics of patients with dyslipidemia (n = 6,079) significantly differed from those without, and in-hospital mortality was lower (5.5 vs. 9.4%; p < 0.001). Subgroup analyses of 9,383 patients with one or more of four preexisting main risk factors (hypertension, diabetes, coronary heart disease, CHD, or dyslipidemia) showed that whenever dyslipidemia was combined with another risk factor, the mortality rate clearly decreased. Patients with dyslipidemia were, in all subgroups, significantly younger (p < 0.001) and predominantly male, and they had more frequently primary percutaneous coronary intervention (PCI). However, this was only significant in patients with hypertension or hypertension and CHD. Independent in-hospital mortality predictors were age (odds ratio, OR: 1.08 per year, 95% confidence interval, CI, 1.07-1.09), diabetes (OR: 1.96, 95% CI: 1.56-2.46, p < 0.0001) and primary PCI (OR: 0.62, 95% CI: 0.44-0.86, p < 0.0001). In patients who received LLD, mortality was significantly lower regardless of the total cholesterol level measured within 24 h after symptom onset. Conclusion: Patients with dyslipidemia admitted for ACS had significantly lower in-hospital mortality than patients without dyslipidemia, mainly but not only due to the younger age of these patients. Early administration of LLD was associated with lower in-hospital mortality