High-energy phase-contrast X-ray microscopy and tomography of protein crystals in an optically opaque matrix is demonstrated with micrometre resolution on the macromolecular crystallography beamline P14 at PETRA III.
BACKGROUND
Protoporphyrinogen IX oxidase 2 (PPO2) inhibitors are important for the management of glyphosate‐ and acetolactate synthase‐resistant Palmer amaranth [Amaranthus palmeri (S.) Wats.]. The evolving resistance to PPO inhibitors is of great concern. We surveyed the evolution of resistance to fomesafen in the US Mid‐south and determined its correlation with the known functional PPO2 target‐site mutations (TSM).
RESULTS
The 167 accessions analyzed were grouped into five categories, four resistant (147) and one susceptible (20). Arkansas accessions constituted 100% of the susceptible group while the Missouri accessions comprised 60% of the most resistant category. The majority of Mississippi accessions (88%) clustered in the high‐survival‐high‐injury category, manifesting an early‐stage resistance evolution. One hundred and fifteen accessions were genotyped for four known TSMs; 74% of accessions carried at least one TSM. The most common single TSM was ΔG210 (18% of accessions) and the predominant double mutation was ΔG210 + G399A (17%). Other mutations are likely less favorable, hence are rare. All TSMs were detected in three accessions. Further examination revealed that 9 and two individuals carried G399A + G210 and G399A + R128G TSM in the same allele, respectively. The existence of these combinations is supported by molecular modeling.
CONCLUSIONS
Resistance to PPO inhibitors is widespread across the Mid‐southern USA. Highly resistant field populations have plants with multiple mutations. G399A is the most prone to co‐occur with other ppo2 mutations in the same allele. Mutation at R128 in the configuration of the PPO2 catalytic domain restrains the co‐occurrence of R128G with ΔG210, making ΔG210 + G399A the most plausible, tolerable functional mutation combination to co‐occur in the same ppo2 allele.
BACKGROUND: Understanding the mode and site of action of a herbicide is key for its efficient development, the evaluation of its toxicological risk, efficient weed control and resistance management. Recently, the mode of action (MoA) of the herbicide cinmethylin was identified in lipid biosynthesis with acyl-ACP thioesterase (FAT) as the site of action (SoA). Cinmethylin was registered for selective use in cereal crops for the control of grass weeds in 2020.RESULTS: Here, we present a high-resolution co-crystal structure of FAT in complex with cumyluron identified by a high throughput crystallization screen. We show binding to and inhibition of FAT by cumyluron. Furthermore, in an array of experiments consisting of FAT binding assays, FAT inhibition assays, physiological and metabolic profiling, we tested compounds that are structurally related to cumyluron and identified the commercial herbicides oxaziclomefone, methyldymron, tebutam and bromobutide, with so far unknown sites of action, as FAT inhibitors. Additionally, we show that the previously described FAT inhibitors cinmethylin and methiozolin bind to FAT in a nanomolar range, inhibit FAT enzymatic activity and lead to similar metabolic changes.CONCLUSION: Based on presented data, we corroborate cinmethylin and methiozolin as potent FAT inhibitors and identify FAT as the SoA of the herbicides cumyluron, oxaziclomefone, bromobutide, methyldymron and tebutam.
Background: Airway management in children is challenging due to anatomical and physiological differences. This randomized trial investigates whether anaesthesia residents can intubate the paediatric trachea more quickly and with a higher success rate using the King Vision™ Paediatric aBlade™ video laryngoscope (KVL) compared to conventional direct laryngoscopy (DL). Methods: Eleven anaesthesia residents (mean age: 31 years, mean training status 47 months) were each asked to perform intubations with the KVL and DL in paediatric patients. The primary outcome was the first-attempt success rate. Secondary outcomes were the time to best view (TTBV), time to placement of the tracheal tube (TTP), time to ventilation (TTV), and participant-reported ease of use on a Likert scale. Results: 105 intubations with the KVL and 106 DL were performed by the residents. The success rate on the first attempt with the KVL was 81%, and the success rate on the first attempt within a given time limit of 30 s was 45%, which was lower than with DL (93% and 77% with time limit, p < 0.01). The median TTBV [IQR] on the first attempt with KVL was 7 [5–10] s, the median TTP was 28 [19–44] s, and the median TTV was 51 [39–66] s. DL-mediated intubation was significantly faster (TTP: 17 [13–23] s; p < 0.0001 and TTV: 34 [28–44] s; p < 0.001). Application of the KVL was rated as difficult or very difficult by 60% of the residents (DL: 5%). Conclusion: In contrast to promising data on the paediatric training manikin, residents took longer to intubate the airway in children with the KVL and were less successful compared to the DL. Therefore, the KVL should not be recommended for learning paediatric intubation by residents.
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