The bromodomains of BAZ2A and BAZ2B (bromodomain adjacent to zinc finger domain proteins 2) are among the most hard to drug of the 61 human bromodomains. While little is known about the role of ...BAZ2B, there is strong evidence for the opportunity of targeting BAZ2A in various cancers. Here, a benzimidazole–triazole fragment that binds to the BAZ2A acetyl lysine pocket was identified by a molecular docking campaign and validated by competitive binding assays and X-ray crystallography. Another ligand was observed in close proximity by soaking experiments using the BAZ2A bromodomain preincubated with the benzimidazole–triazole fragment. The crystal structure of BAZ2A with the two ligands was employed to design a few benzimidazole–triazole derivatives with increased affinity. We also present the engineering of a BAZ2A bromodomain mutant for consistent, high-resolution crystallographic studies.
APTw CEST MRI suffers from long preparation times and consequently long acquisition times (~5 min). Recently, a consensus on the preparation module for clinical APTw CEST at 3 T was found in the ...community, and we present a fast whole-brain APTw CEST MRI sequence following this consensus preparation of pulsed RF irradiation of 2 s duration at 90% RF duty-cycle and a B
of 2 μT. After optimization of the snapshot CEST approach for APTw imaging regarding flip angle, voxel size and frequency offset sampling, we extend it by undersampled GRE acquisition and compressed sensing reconstruction. This allows 2 mm isotropic whole-brain APTw imaging for clinical research at 3 T below 2 min. With this sequence, a fast snapshot APTw imaging method is now available for larger clinical studies of brain tumors.
To substantially shorten the acquisition time required for quantitative three-dimensional (3D) chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow ...for rapid chemical exchange parameter map reconstruction.
Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at three different sites, using three different scanner models and coils. A saturation transfer-oriented generative adversarial network (GAN-ST) supervised framework was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content.
The GAN-ST 3D acquisition time was 42-52 s, 70% shorter than CEST-MRF. The quantitative reconstruction of the entire brain took 0.8 s. An excellent agreement was observed between the ground truth and GAN-based L-arginine concentration and pH values (Pearson's r > 0.95, ICC > 0.88, NRMSE < 3%). GAN-ST images from a brain-tumor subject yielded a semi-solid volume fraction and exchange rate NRMSE of
and
, respectively, and SSIM of
and
, respectively. The mapping of the calf-muscle exchange parameters in a cardiac patient, yielded NRMSE < 7% and SSIM > 94% for the semi-solid exchange parameters. In regions with large susceptibility artifacts, GAN-ST has demonstrated improved performance and reduced noise compared to MRF.
GAN-ST can substantially reduce the acquisition time for quantitative semi-solid MT/CEST mapping, while retaining performance even when facing pathologies and scanner models that were not available during training.
Purpose
Amide proton transfer‐weighted (APTw) MRI at 3T provides a unique contrast for brain tumor imaging. However, APTw imaging suffers from hyperintensities in liquid compartments such as cystic ...or necrotic structures and provides a distorted APTw signal intensity. Recently, it has been shown that heuristically motivated fluid suppression can remove such artifacts and significantly improve the readability of APTw imaging.
Theory and Methods
In this work, we show that the fluid suppression can actually be understood by the known concept of spillover dilution, which itself can be derived from the Bloch‐McConnell equations in comparison to the heuristic approach. Therefore, we derive a novel post‐processing formula that efficiently removes fluid artifact, and explains previous approaches. We demonstrate the utility of this APTw assessment in silico, in vitro, and in vivo in brain tumor patients acquired at MR scanners from different vendors.
Results
Our results show a reduction of the CEST signals from fluid environments while keeping the APTw‐CEST signal intensity almost unchanged for semi‐solid tissue structures such as the contralateral normal appearing white matter. This further allows us to use the same color bar settings as for conventional APTw imaging.
Conclusion
Fluid suppression has considerable value in improving the readability of APTw maps in the neuro‐oncological field. In this work, we derive a novel post‐processing formula from the underlying Bloch‐McConnell equations that efficiently removes fluid artifact, and explains previous approaches which justify the derivation of this metric from a theoretical point of view, to reassure the scientific and medical field about its use.
Purpose: To substantially shorten the acquisition time required for quantitative 3D chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid ...chemical exchange parameter map reconstruction. Methods: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at 3 different sites, using 3 different scanner models and coils. A generative adversarial network supervised framework (GAN-CEST) was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content. Results: The GAN-CEST 3D acquisition time was 42-52 seconds, 70% shorter than CEST-MRF. The quantitative reconstruction of the entire brain took 0.8 seconds. An excellent agreement was observed between the ground truth and GAN-based L-arginine concentration and pH values (Pearson's r > 0.97, NRMSE < 1.5%). GAN-CEST images from a brain-tumor subject yielded a semi-solid volume fraction and exchange rate NRMSE of 3.8\(\pm\)1.3% and 4.6\(\pm\)1.3%, respectively, and SSIM of 96.3\(\pm\)1.6% and 95.0\(\pm\)2.4%, respectively. The mapping of the calf-muscle exchange parameters in a cardiac patient, yielded NRMSE < 7% and SSIM > 94% for the semi-solid exchange parameters. In regions with large susceptibility artifacts, GAN-CEST has demonstrated improved performance and reduced noise compared to MRF. Conclusion: GAN-CEST can substantially reduce the acquisition time for quantitative semisolid MT/CEST mapping, while retaining performance even when facing pathologies and scanner models that were not available during training.
CEST suffers from two main problems long acquisitin times or restricted coverage as well as incoherent protocol settings. In this paper we give suggestions on how to optimise your protocol settings ...fro CEST and present one setting for APT CEST. To increase the coverage while keeping the acquisition time constant we suggest using a spatial temporal Compressed Sensing approach. Finally, 1.8mm isotropic whole brain APT CEST maps can be acquired in a little bit less than 2min with a fully integrated online reconstruction. This will pave the way to an even further clinical use of CEST.
Phosphates are known to be essential for plant growth and development, with phosphorus compounds being involved in various physiological and biochemical reactions. Phosphates are known as one of the ...most important factors limiting crop yields. The problem of phosphorus deficiency in the soil has traditionally been solved by applying phosphate fertilizers. However, chemical phosphate fertilizers are considered ineffective compared to the organic fertilizers manure and compost. Therefore, increasing the bioavailability of phosphates for plants is one of the primary goals of sustainable agriculture. Phosphate-solubilizing soil microorganisms can make soil-insoluble phosphate bioavailable for plants through solubilization and mineralization. These microorganisms are currently in the focus of interest due to their advantages, such as environmental friendliness, low cost, and high biological efficiency. In this regard, the solubilization of phosphates by soil microorganisms holds strong potential in research, and inoculation of soils or crops with phosphate-solubilizing bacteria is a promising strategy to improve plant phosphate uptake. In this review, we analyze all the species of phosphate-solubilizing bacteria described in the literature to date. We discuss key mechanisms of solubilization of mineral phosphates and mineralization of organic phosphate-containing compounds: organic acids secreted by bacteria for the mobilization of insoluble inorganic phosphates, and the enzymes hydrolyzing phosphorus-containing organic compounds. We demonstrate that phosphate-solubilizing microorganisms have enormous potency as biofertilizers since they increase phosphorus bioavailability for the plant, promote sustainable agriculture, improve soil fertility, and raise crop yields. The use of phosphate-solubilizing microbes is regarded as a new frontier in increasing plant productivity.
Siderophores are synthesized and secreted by many bacteria, yeasts, fungi, and plants for Fe (III) chelation. A variety of plant-growth-promoting bacteria (PGPB) colonize the rhizosphere and ...contribute to iron assimilation by plants. These microorganisms possess mechanisms to produce Fe ions under iron-deficient conditions. Under appropriate conditions, they synthesize and release siderophores, thereby increasing and regulating iron bioavailability. This review focuses on various bacterial strains that positively affect plant growth and development through synthesizing siderophores. Here we discuss the diverse chemical nature of siderophores produced by plant root bacteria; the life cycle of siderophores, from their biosynthesis to the Fe-siderophore complex degradation; three mechanisms of siderophore biosynthesis in bacteria; the methods for analyzing siderophores and the siderophore-producing activity of bacteria and the methods for screening the siderophore-producing activity of bacterial colonies. Further analysis of biochemical, molecular-biological, and physiological features of siderophore synthesis by bacteria and their use by plants will allow one to create effective microbiological preparations for improving soil fertility and increasing plant biomass, which is highly relevant for sustainable agriculture.
This review covers the literature data on plant growth-promoting bacteria in soil, which can fix atmospheric nitrogen, solubilize phosphates, produce and secrete siderophores, and may exhibit several ...different behaviors simultaneously. We discuss perspectives for creating bacterial consortia and introducing them into the soil to increase crop productivity in agrosystems. The application of rhizosphere bacteria-which are capable of fixing nitrogen, solubilizing organic and inorganic phosphates, and secreting siderophores, as well as their consortia-has been demonstrated to meet the objectives of sustainable agriculture, such as increasing soil fertility and crop yields. The combining of plant growth-promoting bacteria with mineral fertilizers is a crucial trend that allows for a reduction in fertilizer use and is beneficial for crop production.
Plant growth-promoting bacteria are commonly used in agriculture, particularly for seed inoculation. Multispecies consortia are believed to be the most promising form of these bacteria. However, ...designing and modeling bacterial consortia to achieve desired phenotypic outcomes in plants is challenging. This review aims to address this challenge by exploring key antimicrobial interactions. Special attention is given to approaches for developing soil plant growth-promoting bacteria consortia. Additionally, advanced omics-based methods are analyzed that allow soil microbiomes to be characterized, providing an understanding of the molecular and functional aspects of these microbial communities. A comprehensive discussion explores the utilization of bacterial preparations in biofertilizers for agricultural applications, focusing on the intricate design of synthetic bacterial consortia with these preparations. Overall, the review provides valuable insights and strategies for intentionally designing bacterial consortia to enhance plant growth and development.
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