External jasmonic acid isoleucine mediates amplification of plant elicitor peptide receptor (PEPR) and jasmonate-based immune signalling.

Jasmonic acid-isoleucine (JA-Ile) is a plant defence hormone whose cellular levels are elevated upon herbivory and regulate defence signalling. Despite their pivotal role, our understanding of the rapid cellular perception of bioactive JA-Ile is limited. This study identifies cell type-specific JA-Ile-induced Ca2+ signal and its role in self-amplification and plant elicitor peptide receptor (PEPR)-mediated signalling. Using the Ca2+ reporter, R-GECO1 in Arabidopsis, we have characterized a monophasic and sustained JA-Ile-dependent Ca2+ signature in leaf epidermal cells. The rapid Ca2+ signal is independent of positive feedback by the JA-Ile receptor, COI1 and the transporter, JAT1. Microarray analysis identified up-regulation of receptors, PEPR1 and PEPR2 upon JA-Ile treatment. The pepr1 pepr2 double mutant in R-GECO1 background exhibits impaired external JA-Ile induced Ca2+ cyt elevation and impacts the canonical JA-Ile responsive genes. JA responsive transcription factor, MYC2 binds to the G-Box motif of PEPR1 and PEPR2 promoter and activates their expression upon JA-Ile treatment and in myc2 mutant, this is reduced. External JA-Ile amplifies AtPep-PEPR pathway by increasing the AtPep precursor, PROPEP expression. Our work shows a previously unknown non-canonical PEPR-JA-Ile-Ca2+ -MYC2 signalling module through which plants sense JA-Ile rapidly to amplify both AtPep-PEPR and jasmonate signalling in undamaged cells.

Stroke incidence, mortality, subtypes in rural and urban populations in five geographic areas of India (2018-2019): results from the National Stroke Registry Programme.

Background: Increasing stroke burden in India demands a long-term stroke surveillance framework. Earlier studies in India were urban-based, short term and provided limited data on stroke incidence and its outcomes. This gap is addressed by the establishment of five population-based stroke registries (PBSRs) of the National Stroke Registry Programme, India. This paper describes stroke incidence, mortality and age, sex, and subtypes distribution in the five PBSRs with urban and rural populations. Methods: First-ever incident stroke patients in age group ≥18 years, resident for at least one year in the defined geographic area, identified from health facilities were registered. Death records with stroke as the cause of death from the Civil Registration System (CRS) were included. Transient ischemic attack (TIA) was excluded. Three PBSRs (Cuttack, Tirunelveli, Cachar) included urban and rural populations. PBSRs in Kota and Varanasi were urban areas. The crude and age-standardized incidence rate (ASR) by age, sex, and residence (urban and rural), rate ratios of ASR, case fatality proportions and rates at day 28 after onset of stroke were calculated for years 2018-2019. Findings: A total of 13,820 registered first-ever stroke cases that included 985 death certificate-only cases (DCOs) were analysed. The pooled crude incidence rate was 138.1 per 100,000 population with an age-standardized incidence rate (ASR) of 103.4 (both sexes), 125.7 (males) and 80.8 (females). The risk of stroke among rural residents was one in seven (Cuttack), one in nine (Tirunelveli), and one in 15 (Cachar). Ischemic stroke was the most common type in all PBSRs. Age-standardized case fatality rates (ASCFR) per 100,000 population for pooled PBSRs was 30.0 (males) and 18.8 (females), and the rate ratio (M/F) ranged from 1.2 (Cuttack) to 2.0 (Cachar). Interpretation: Population-based registries have provided a comprehensive stroke surveillance platform to measure stroke burden and outcomes by age, sex, residence and subtype across India. The rural-urban pattern of stroke incidence and mortality shall guide health policy and programme planning to strengthen stroke prevention and treatment measures in India. Funding: The National Stroke Registry Programme is funded through the intramural funding of the Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, India.