Balancing roles between phosphatidylinositols and sphingolipids in regulating immunity and ER stress responses in pi4kß1,2.

Plant immune regulation is complex. In addition to proteins, lipid molecules play critical roles in modulating immune responses. The mutant pi4kß1,2 is mutated in two phosphatidylinositol 4-kinases PI4Kß1 and ß2 involved in the biosynthesis of phosphatidylinositol 4-phosphate (PI4P). The mutant displays autoimmunity, short roots, aberrant root hairs, and a heightened sensitivity to ER stress. In a forward genetic screen designed to dissect pi4kß1,2 autoimmunity, we found that Orosomucoid-like 1 (ORM1) is required for the phenotypes of pi4kß1,2, including short root and ER stress sensitivity. The orm1 mutations lead to increased long-chain base and ceramide levels in the suppressors. We also found that the basic region/leucine Zipper motif (bZIP) 28 and 60 transcription factors, central regulators of ER stress response, are required for its autoimmunity and root defect. In comparison, the defense-related phytohormones salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are required for its autoimmunity but plays a minor role in its root phenotypes. Further, we found that wild-type plants overexpressing ORM1 are autoimmune, displaying short roots and increased ceramide levels. The autoimmunity of the ORM1 overexpression lines is dependent on SA, NHP, and bZIP60. As ORM1 is a known negative regulator of sphingolipid biosynthesis, our study uncovers a balancing role between PIs and sphingolipids in regulating immunity and ER stress responses in pi4kß1,2.

Signal Peptide Peptidase and PI4Kß1/2 play opposite roles in plant ER stress response and immunity.

The Arabidopsis pi4kß1,2 mutant is mutated in the phosphatidylinositol 4-kinase (PI4K) ß1 and PI4Kß2 enzymes which are involved in the biosynthesis of phosphatidylinositol 4-phosphate (PI4P), a minor membrane lipid with important signaling roles. pi4kß1,2 plants display autoimmunity and shorter roots. Though the pi4kß1,2 mutant has been extensively characterized, the source of its autoimmunity remains largely unknown. In this study, through a genetic suppressor screen, we identified multiple partial loss-of-function alleles of signal peptide peptidase (spp) that can suppress all the defects of pi4kß1,2. SPP is an intramembrane cleaving aspartic protease. Interestingly, pi4kß1,2 plants display enhanced ER stress response and mutations in SPP can suppress such phenotype. Furthermore, reduced ER stress responses were observed in the spp single mutants. Overall, our study reveals a previously unknown function of PI4Kß and SPP in ER stress and plant immunity.

Immune receptor mimicking hormone receptors: a new guarding strategy.

Plant intracellular nucleotide-binding domain leucine-rich repeat (NLR) receptors play crucial roles in immune responses against pathogens. How diverse NLRs recognize different pathogen effectors remains a significant question. A recent study published in Nature uncovered how pepper NLR Tsw detects phytohormone receptors' interference caused by tomato spotted wilt virus (TSWV) effector, triggering a robust immune response, showcasing a new manner of NLR guarding.

Acylprolinamides: a new class of peptide deformylase inhibitors with in vivo antibacterial activity.

A new class of PDF inhibitor with potent, broad spectrum antibacterial activity is described. Optimization of blood stability and potency provided compounds with improved pharmacokinetics that were suitable for in vivo experiments. Compound 5c, which has robust antibacterial activity, demonstrated efficacy in two respiratory tract infection models.

Developing an mHealth app for post-stroke upper limb rehabilitation: Feedback from US and Ethiopian rehabilitation clinicians.

Stroke is the leading cause of adult disability worldwide, with 70 percent of survivors exhibiting residual impairments of the upper limb that require frequent in-person visits to rehabilitation clinic over several months. This study explored rehabilitation clinician's preferences for design features to be included in an mHealth-enabled app for post-stroke upper limb rehabilitation. Data were collected via online survey, sampling participants from Ethiopia (n = 69) and the United States (n = 75). Survey results indicated that Ethiopian and US rehabilitation clinicians have different opinions about the importance of design features that should be included in a stroke tele-rehabilitation system which are likely due to differences in culture, the availability of human and physical resources, and how the field of rehabilitation is organized and managed. Our results, thus, indicate that mHealth technologies must be tailored to the geographical and cultural context of the end users.