The Arabidopsis protein phosphatase PP2C38 negatively regulates the central immune kinase BIK1

Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface-localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity (PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of several PRR complexes. How plant PTI is negatively regulated is not fully understood. Here, we identify the protein phosphatase PP2C38 as a negative regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co-receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1 activation. Together with our recent work on the control of BIK1 turnover, this study reveals another important regulatory mechanism of this central immune component

LABORATORY STUDY OF LOCAL BUCKLING, WRINKLE DEVELOPMENT, AND STRAINS FOR NPS12 LINEPIPE

ABSTRACT Buried pipelines are subjected to fluid pressure (oil/gas/water), axial loads, moments, and complex load combination histories. As a result, they may develop large compressive strains and curvatures leading to formation of localized buckles or wrinkles in the pipe shell. Recently, fullscale tests on 12.75" diameter (NPS12) energy pipes have been carried out at the University of Alberta to study the behavior of wrinkle development and the ultimate limiting strains at the wrinkle locations. Different internal pressures, and axial loads were applied to produce a wrinkle, followed by load variations intended to produce fracture that could develop in buried pipelines in the field. Three different axially loaded tests are reported. Two different internal pressures were applied, namely, (i) 0.8py and (ii) 0.4p y , where p y is the required internal pressure to cause the yield stress of the pipe material to be developed in the circumferential direction. Also, two different specimen lengths were adopted. They are: (i) 406 mm (16 inch) and (ii) 736 mm (29 inch). All specimens were loaded axially until the wrinkle formed. It was observed that the pipes are highly ductile and very large compressive strains can be developed without fracture or leakage in the pipe wall. Because the pipe specimens of the first two tests did not fail (i.e. fracture) under monotonically increasing displacements and strains, the third wrinkled specimen was subjected to load histories involving strain reversals. This load history resulted in a low cycle failure after a very few cycles. The paper addresses test procedures, buckling and postbuckling behavior of NPS12 energy pipelines and relates them to three different types of strain measures, namely, material strain, wrinkle strain and overall strain as observed from these tests

Potentiating AZT activation: structures of wild−type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP

The 60−fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti−HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P−loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20−fold faster than the wild−type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P−loop conformatio

Branch angle and leaflet shape are associated with canopy coverage in soybean

Abstract Early canopy coverage is a desirable trait that is a major determinant of yield in soybean (Glycine max). Variation in traits comprising shoot architecture can influence canopy coverage, canopy light interception, canopy‐level photosynthesis, and source‐sink partitioning efficiency. However, little is known about the extent of phenotypic diversity of shoot architecture traits and their genetic control in soybean. Thus, we sought to understand the contribution of shoot architecture traits to canopy coverage and to determine the genetic control of these traits. We examined the natural variation for shoot architecture traits in a set of 399 diverse maturity group I soybean (SoyMGI) accessions to identify relationships between traits, and to identify loci that are associated with canopy coverage and shoot architecture traits. Canopy coverage was correlated with branch angle, number of branches, plant height, and leaf shape. Using previously collected 50K single nucleotide polymorphism data, we identified quantitative trait locus (QTL) associated with branch angle, number of branches, branch density, leaflet shape, days to flowering, maturity, plant height, number of nodes, and stem termination. In many cases, QTL intervals overlapped with previously described genes or QTL. We also found QTL associated with branch angle and leaflet shape located on chromosomes 19 and 4, respectively, and these QTL overlapped with QTL associated with canopy coverage, suggesting the importance of branch angle and leaflet shape in determining canopy coverage. Our results highlight the role individual architecture traits play in canopy coverage and contribute information on their genetic control that could help facilitate future efforts in their genetic manipulation

Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor

We studied the role of PDZ proteins GRIP, ABP, and PICK1 in GluR2 AMPA receptor trafficking. An epitope-tagged MycGluR2 subunit, when expressed in hippocampal cultured neurons, was specifically targeted to the synaptic surface. With the mutant MycGluR2?1-10, which lacks the PDZ binding site, the overall dendritic intracellular transport and the synaptic surface targeting were not affected. However, over time, MycGluR2?1-10 accumulated at synapses significantly less than MycGluR2. Notably, a single residue substitution, S880A, which blocks binding to ABP/GRIP but not to PICK1, reduced synaptic accumulation to the same extent as the PDZ site truncation. We conclude that the association of GluR2 with ABP and/or GRIP but not PICK1 is essential for maintaining the synaptic surface accumulation of the receptor, possibly by limiting its endocytotic rate

Efficacy, Safety and Immunogenicity of Sun’s Ranibizumab Biosimilar in Neovascular Age-Related Macular Degeneration: A Phase 3, Double-Blind Comparative Study

Abstract Introduction The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun’s ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). Methods This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun’s ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). Results Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun’s ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at −1% (−2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun’s ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun’s ranibizumab group and 14.6 letters in the reference ranibizumab group (p < 0.001 within both groups and p = 0.5275 between groups). The mean change in central macular thickness was comparable between groups (p = 0.7946). Anti-ranibizumab antibodies were found in one patient of the reference ranibizumab group, while neutralising antibodies were not found in any patients. Both products were well tolerated. Conclusion Sun’s ranibizumab biosimilar is found to be therapeutically equivalent to reference ranibizumab in patients with nAMD. There were no additional safety or immunogenicity concerns. Trial Registration CTRI/2020/09/027629, registered on 07 September 2020