Identification of QTLs for zinc deficiency tolerance in a recombinant inbred population of rice (Oryza sativa L.).

BACKGROUND: Deficiency of Zn is a major soil constraint in rice plant growth and yield. Edaphic factors such as Zn deficiency in soil in relation to plant performance are still poorly understood. Here, we report promising quantitative trait loci (QTL) conferring tolerance to Zn deficiency, which were identified through biparental mapping. The experiment was conducted using the 236 F7 recombinant inbred line mapping population derived from the cross of Kinandang Patong (Zn deficiency sensitive) and A69-1 (Zn deficiency tolerant). RESULTS: A total of six QTLs (qLB-2B, qLB-4B, qPM-4B, qPM-6B, qRZC-4B, qSZC-4B) on chromosomes 2, 4 and 6 were identified for environment 1, whereas five QTLs (qLB-2 N, qLB-4 N, qPM-4 N, qRZC-4 N, qSZC-4 N) on chromosomes 2 and 4 were detected for environment 2. Among these, five major (51.30, 48.70, 28.60, 56.00, 52.00 > 10 R2 ) and one minor (5.40 < 10 R2 ) QTLs for environment 1 and four major (51.48, 50.20, 53.00, 48.00 > 10 R2 ) and one minor (4.44 < 10) QTLs for environment 2 for Zn deficiency tolerance with a logarithm of odd threshold value higher than 3 were identified. The QTLs (qLB-4B, qPM-4B, qRZC-4B, qSZC-4B, qLB-4 N, qPM-4 N, qRZC-4 N, qSZC-4 N) for leaf bronzing, plant mortality root zinc concentration and shoot zinc concentration identified on chromosome 4 were found to be the most promising and highly reproducible across the locations that explained phenotypic variation from 48.00% to 56.00% with the same marker interval RM6748-RM303. CONCLUSION: The new QTLs and its linked markers identified in the present study can be utilized for Zn deficiency tolerance in elite cultivars using marker-assisted backcrossing. © 2022 Society of Chemical Industry.

Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial.

INTRODUCTION/AIMS: Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene resulting in the absence of dystrophin. Casimersen is a phosphorodiamidate morpholino oligomer designed to bypass frameshift DMD mutations and produce internally truncated, yet functional, dystrophin protein in patients amenable to exon 45 skipping. Our primary study objective was to evaluate safety and tolerability of casimersen; the secondary objective was to characterize the plasma pharmacokinetics. METHODS: This multicenter, phase 1/2 trial enrolled 12 participants (aged 7-21 years, who had limited ambulation or were nonambulatory) and comprised a 12-week, double-blind dose titration, then an open-label extension for up to 132 weeks. During dose titration, participants were randomized 2:1 to weekly casimersen infusions at escalating doses of 4, 10, 20, and 30 mg/kg (≥2 weeks per dose), or placebo. RESULTS: Participants received casimersen for a mean 139.6 weeks. Treatment-emergent adverse events (TEAEs) occurred in all casimersen- and placebo-treated participants and were mostly mild (over 91.4%) and unrelated to casimersen or its dose. There were no deaths, dose reductions, abnormalities in laboratory parameters or vital signs, or casimersen-related serious AEs. Casimersen plasma concentration increased with dose and declined similarly for all dose levels over 24 hours postinfusion. All pharmacokinetic parameters were similar at weeks 7 and 60. DISCUSSION: Casimersen was well tolerated in participants with DMD amenable to exon 45 skipping. Most TEAEs were mild, nonserious, and unrelated to casimersen. Plasma exposure was dose proportional with no suggestion of plasma accumulation. These results support further studies of casimersen in this population.

Physiological and molecular implications of multiple abiotic stresses on yield and quality of rice.

Abiotic stresses adversely affect rice yield and productivity, especially under the changing climatic scenario. Exposure to multiple abiotic stresses acting together aggravates these effects. The projected increase in global temperatures, rainfall variability, and salinity will increase the frequency and intensity of multiple abiotic stresses. These abiotic stresses affect paddy physiology and deteriorate grain quality, especially milling quality and cooking characteristics. Understanding the molecular and physiological mechanisms behind grain quality reduction under multiple abiotic stresses is needed to breed cultivars that can tolerate multiple abiotic stresses. This review summarizes the combined effect of various stresses on rice physiology, focusing on grain quality parameters and yield traits, and discusses strategies for improving grain quality parameters using high-throughput phenotyping with omics approaches.

Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials.

OBJECTIVE: Further understand the safety profile of celecoxib and provide safety information for important adverse events (AEs). METHODS: Analysis of randomized controlled trials from the Pfizer clinical trial repository (final study reports completed by 31 July 2011) in which celecoxib was compared with placebo or non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) for treatment of pain or inflammation in adults. Safety end points comprised 18 terms that had been identified as important AEs among all NSAIDs. RESULTS: There was a greater risk of edema (risk difference (95% confidence interval) 0.77% (0.45, 1.09)); hypertension (0.28% (-0.01, 0.57)); angioedema (0.16% (-0.06, 0.39) and allergic reactions (0.15% (-0.10, 0.40)) with celecoxib than with placebo, while a greater risk of gastrointestinal (GI) hemorrhage (-0.15% (-0.47, 0.16)) was seen with placebo. There was a greater risk of GI hemorrhage (-0.53% (-0.72, -0.33)), GI ulceration (-0.46% (-0.60, -0.33)), edema (-0.62% (-0.89, -0.35)) and hypertension (-0.57% (-0.82, -0.33)) with nsNSAIDs than with celecoxib. CONCLUSIONS: The magnitude of risks associated with NSAIDs is small and similar in celecoxib-, nsNSAID- and placebo-treated patients. This analysis provides safety information that will allow physicians to make informed treatment decisions for patients who are appropriate candidates for celecoxib use.