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The Journal of Chemical Physics Jun 2024Drachmann's regularization approach is implemented for floating explicitly correlated Gaussians (fECGs) and molecular systems. Earlier applications of drachmannized...
Drachmann's regularization approach is implemented for floating explicitly correlated Gaussians (fECGs) and molecular systems. Earlier applications of drachmannized relativistic corrections for molecular systems were hindered due to the unknown analytic matrix elements of 1/rix1/rjy-type operators with fECGs. In the present work, one of the 1/r factors is approximated by a linear combination of Gaussians, which results in calculable integrals. The numerical approach is found to be precise and robust over a range of molecular systems and nuclear configurations, and thus, it opens the route toward an automated evaluation of high-precision relativistic corrections over potential energy surfaces of polyatomic systems. Furthermore, the newly developed integration approach makes it possible to construct the matrix representation of the square of the electronic Hamiltonian relevant for energy lower-bound as well as time-dependent computations of molecular systems with a flexible and high-precision fECG basis representation.
PubMed: 38828828
DOI: 10.1063/5.0213079 -
Toxicology in Vitro : An International... Dec 2023Cytotoxicity of some pesticides is a disadvantage for the Salmonella/microsome assay with regard to the equivalence assessment of pesticide technical grade active...
Cytotoxicity of some pesticides is a disadvantage for the Salmonella/microsome assay with regard to the equivalence assessment of pesticide technical grade active ingredients to the original products and detection of low-level impurities. The technical grade active ingredients (TGAIs) of pesticides from certain chemical classes were found to be toxic for Salmonella typhimurium strains. Among the highly cytotoxic compounds were sulfonylureas, which include 20 active ingredients. In addition, this class includes active pharmaceutical ingredients used for the manufacture of antidiabetics drugs. A traditional selection methodology was applied using the cultivation of S. typhimurium TA100 in the presence of high concentrations of thifensulfuronmethyl (TFSM) to obtain a resistant test strain insusceptible to sulfonylurea toxic effect. Two strains resistant not only to sulfonylureas (SFU) but also triazolepyrimidines were received. The first mutant strain (deposited as S. typhimurium VKPM B-14099 in the Russian National Collection of Industrial Microorganisms) demonstrated the TA100 phenotypic characteristics: hisG46, rfa, ΔuvrB-bio, pKM101. The second strain (deposited as S. typhimurium VKPM B-14359) showed the TA1535 phenotypic characteristics and probably lost the R-factor due to the selection using the poor Gm-media with TFSM. Positive controls caused pronounced mutagenic effects (±S9) in both strains, consequently the mutants did not lose the ability to respond to induction of the reverse gene mutations. The maximum non-cytotoxic concentrations of SFUs and triazole-pyrimidines for the Ames test strains did not exceed 0.05-0.125 mg/plate, while no evidence of cytotoxicity was observed for the mutants up to 5.0 mg/plate. Electron microscopy of the ultrathin sections of Salmonella cells grown with and without TFSM showed an obvious difference in the structure of the cell wall and cytoplasm in mutant and parental cultures. The concurrent resistance both to SFU and triazolepyrimidines was assumed to be mediated by the same mechanism of action of the pesticides from these classes - inhibition of acetohydroxyacid synthase. To confirm this hypothesis, the tests in the presence of branched-chain amino acids were carried out. The enrichment of agar with isoleucine prevented the toxic effects of SFU and triazolepyrimidines for all Ames test strains used in the study, while strong cytotoxicity was observed in the presence of valine and leucine. Considering the tolerance of strains both to SFU and triazolpyrimidines and the results with branched-chain amino acids, the modification of target acetohydroxyacid synthase was supposed the key to the acquired resistance. The new strains resistant to sulfonylureas and triazole-pyrimidines expands the possibilities to reveal mutagenic impurities that may occur in TGAIs in small amounts.
Topics: Mutagenicity Tests; Herbicides; Mutagens; Salmonella typhimurium; Amino Acids, Branched-Chain; Pyrimidines; Triazoles
PubMed: 37751784
DOI: 10.1016/j.tiv.2023.105699 -
Scientific Reports Sep 2023To explore the connection between chloroplast and coffee resistance factors, designated as S1 to S9, whole genomic DNA of 42 coffee genotypes was sequenced, and entire...
To explore the connection between chloroplast and coffee resistance factors, designated as S1 to S9, whole genomic DNA of 42 coffee genotypes was sequenced, and entire chloroplast genomes were de novo assembled. The chloroplast phylogenetic haplotype network clustered individuals per species instead of S factors. However, for the first time, it allowed the molecular validation of Coffea arabica as the maternal parent of the spontaneous hybrid "Híbrido de Timor". Individual reads were also aligned on the C. arabica reference genome to relate S factors with chloroplast metabolism, and an in-silico analysis of selected nuclear-encoded chloroplast proteins (132 proteins) was performed. The nuclear-encoded thioredoxin-like membrane protein HCF164 enabled the discrimination of individuals with and without the S9 factor, due to specific DNA variants linked to chromosome 7c (from C. canephora-derived sub-genome). The absence of both the thioredoxin domain and redox-active disulphide center in the HCF164 protein, observed in S9 individuals, raises the possibility of potential implications on redox regulation. For the first time, the identification of specific DNA variants of chloroplast proteins allows discriminating individuals according to the S profile. This study introduces an unexplored strategy for identifying protein/genes associated with S factors and candidate targets of H. vastatrix effectors, thereby creating new perspectives for coffee breeding programs.
Topics: Humans; Coffea; Coffee; Phylogeny; R Factors; Plant Breeding; Thioredoxins; Nuclear Proteins; Membrane Proteins; Chloroplast Proteins; Chloroplasts; Complement Factor H
PubMed: 37749157
DOI: 10.1038/s41598-023-41950-4 -
Scientific Reports Apr 2024Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit...
Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics. Cobalt complexes possess diverse biological activities, including antimicrobial and anticancer properties. However, their effect on plasmid conjugation has not been explored yet. Here, we assessed the effect of four previously characterised bis(N-picolinamido)cobalt(II) complexes lacking antibacterial activity on plasmid conjugation in Escherichia coli and Klebsiella pneumoniae. Antimicrobial susceptibility testing of these cobalt complexes confirmed the lack of antibacterial activity in E. coli and K. pneumoniae. Liquid broth and solid agar conjugation assays were used to screen the activity of the complexes on four archetypical plasmids in E. coli J53. The cobalt complexes significantly reduced the conjugation of RP4, R6K, and R388 plasmids, but not pKM101, on solid agar in E. coli J53. Owing to their promising activity, the impact of cobalt complexes was tested on the conjugation of fluorescently tagged extended-spectrum β-lactamase encoding pCTgfp plasmid in E. coli and carbapenemase encoding pKpQILgfp plasmid in K. pneumoniae, using flow cytometry. The complexes significantly reduced the conjugation of pKpQILgfp in K. pneumoniae but had no impact on pCTgfp conjugation in E. coli. The cobalt complexes did not have plasmid-curing activity, suggesting that they target conjugation rather than plasmid stability. To our knowledge, this is the first study to report reduced conjugation of clinically relevant plasmids with cobalt complexes. These cobalt complexes are not cytotoxic towards mammalian cells and are not antibacterial, therefore they could be optimised and employed as inhibitors of plasmid conjugation.
Topics: Animals; Agar; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactamases; Escherichia coli; Klebsiella Infections; Klebsiella pneumoniae; Mammals; Microbial Sensitivity Tests; Plasmids
PubMed: 38582880
DOI: 10.1038/s41598-024-58895-x -
Acta Crystallographica. Section C,... Mar 2024Beauveriolides, including the main beauveriolide I {systematic name:...
Beauveriolides, including the main beauveriolide I {systematic name: (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone, CHNO}, are a series of cyclodepsipeptides that have shown promising results in the treatment of Alzheimer's disease and in the prevention of foam cell formation in atherosclerosis. Their crystal structure studies have been difficult due to their tiny crystal size and fibre-like morphology, until now. Recent developments in 3D electron diffraction methodology have made it possible to accurately study the crystal structures of submicron crystals by overcoming the problems of beam sensitivity and dynamical scattering. In this study, the absolute structure of beauveriolide I was determined by 3D electron diffraction. The cyclodepsipeptide crystallizes in the space group I2 with lattice parameters a = 40.2744 (4), b = 5.0976 (5), c = 27.698 (4) Å and β = 105.729 (6)°. After dynamical refinement, its absolute structure was determined by comparing the R factors and calculating the z-scores of the two possible enantiomorphs of beauveriolide I.
Topics: Biological Products; Electrons; Crystallography, X-Ray; Hydrogen Bonding; Cordyceps
PubMed: 38411548
DOI: 10.1107/S2053229624001359 -
Journal of Environmental Management Jul 2023Soil erosion is a common form of land degradation. The Coupled Model Intercomparison Project Phase 6 (CMIP6) provides a scenario framework for global socio-economic...
Spatiotemporal foresting of soil erosion for SSP-RCP scenarios considering local vegetation restoration project: A case study in the three gorges reservoir (TGR) area, China.
Soil erosion is a common form of land degradation. The Coupled Model Intercomparison Project Phase 6 (CMIP6) provides a scenario framework for global socio-economic development and climate change by combining Shared Socioeconomic Pathways (SSP) and Representative Concentration Pathways (RCP). The soil erosion estimation under global climate change and land-use change scenarios provided by CMIP6 is valuable for representing future changes and hotspots. This study estimated the future changes in soil erosion in the Three Gorges Reservoir (TGR) area, China, which has suffered severe soil loss over an extended period, and vegetation restoration projects have been conducted since 1999. The scenarios provided by SSP1-2.6, SSP2-4.5, and SSP5-8.5 were coupled with the scenarios of regional vegetation restoration projects to reflect future land use changes (LUC) and climate change. The results showed that future soil erosion from 2020 to 2100 in the TGR area will experience a non-significant decreasing trend (with trend slopes of -0.013, -0.020, and-0.006 in SSP1-2.6, SSP2-4.5, and SSP5-8.5, respectively, with p > 0.05). However, with the R factors calculated by different methods, this decreasing trend becomes either insignificant or a significant increasing trend. SSP1-2.6 will experience the lowest soil erosion in 2100 owing to the large amount of forest increase in this scenario. Furthermore, as estimates, the grain-for-green policy (GGP) will reduce 89353.47, 92737.73 and 42916.52 ton soil erosion per year in SSP1-2.6, SSP2-4.5 and SSP3-8.5 by 2100, respectively. In the future, the GGP will become increasingly important for controlling soil loss in the TGR area owing to the increasing precipitation in all scenarios, which increases the risk of soil loss.
Topics: Soil Erosion; Conservation of Natural Resources; Soil; Forests; China; Climate Change
PubMed: 36958284
DOI: 10.1016/j.jenvman.2023.117717 -
Communications Biology Apr 2024Bacterial cooperation and antagonism mediated by secretion systems are among the ways in which bacteria interact with one another. Here we report the discovery of an...
Bacterial cooperation and antagonism mediated by secretion systems are among the ways in which bacteria interact with one another. Here we report the discovery of an antagonistic property of a type IV secretion system (T4SS) sourced from a conjugative plasmid, RP4, using engineering approaches. We scrutinized the genetic determinants and suggested that this antagonistic activity is independent of molecular cargos, while we also elucidated the resistance genes. We further showed that a range of Gram-negative bacteria and a mixed bacterial population can be eliminated by this T4SS-dependent antagonism. Finally, we showed that such an antagonistic property is not limited to T4SS sourced from RP4, rather it can also be observed in a T4SS originated from another conjugative plasmid, namely R388. Our results are the first demonstration of conjugative T4SS-dependent antagonism between Gram-negative bacteria on the genetic level and provide the foundation for future mechanistic studies.
Topics: Plasmids; Type IV Secretion Systems; Conjugation, Genetic; Gram-Negative Bacteria; Escherichia coli
PubMed: 38664513
DOI: 10.1038/s42003-024-06192-8 -
Communications Biology Mar 2024The increasing rate of carbapenem-resistant bacteria within healthcare environments is an issue of great concern that needs urgent attention. This resistance is driven...
The increasing rate of carbapenem-resistant bacteria within healthcare environments is an issue of great concern that needs urgent attention. This resistance is driven by metallo-β-lactamases (MBLs), which can catalyse the hydrolysis of almost all clinically available β-lactams and are resistant to all the clinically utilized β-lactamase inhibitors. In this study, an uncharacterized MBL is identified in a multidrug resistant isolate of the opportunistic pathogen, Chryseobacterium indologenes. Sequence analysis predicts this MBL (CIM-1) to be a lipoprotein with an atypical lipobox. Characterization of CIM-1 reveals it to be a high-affinity carbapenemase with a broad spectrum of activity that includes all cephalosporins and carbapenems. Results also shown that CIM-1 is potentially a membrane-associated MBL with an uncharacterized lipobox. Using prediction tools, we also identify more potentially lipidated MBLs with non-canonical lipoboxes highlighting the necessity of further investigation of lipidated MBLs.
Topics: Anti-Bacterial Agents; R Factors; beta-Lactamases; Bacterial Proteins
PubMed: 38454015
DOI: 10.1038/s42003-024-05940-0 -
The Protein Journal May 2024Hemoglobin (Hb) is the key metalloprotein within red blood cells involved in oxygen transportation from lungs to body cells. The heme-iron atom inherent within Hb...
Hemoglobin (Hb) is the key metalloprotein within red blood cells involved in oxygen transportation from lungs to body cells. The heme-iron atom inherent within Hb effectuates the mechanism of oxygen transportation and carbon dioxide removal. Structural investigations on avian Hb are limited when compared with the enormous work has been carried out on mammalian Hb. Here, the crystal structure of T-state methemoglobin (T-metHb) from domestic duck (Anas platyrhynchos), a low oxygen affinity avian species, determined to 2.1Å resolution is presented. Duck T-metHb crystallized in the orthorhombic space group C222 with unit cell parameters a = 59.89, b = 109.42 and c = 92.07Å. The final refined model with R-factor: 19.5% and R: 25.2% was obtained. The structural analysis reveals that duck T-metHb adopts a unique quaternary structure that is distinct from any of the avian liganded Hb structures. Moreover, it closely resembles the deoxy Hb of bar-headed goose, a high oxygen-affinity species. Besides the amino acid αPro119 located in the α1β1 interface, a unique quaternary structure with a constrained heme environment is attributed for the intrinsic low oxygen-affinity of duck Hb. This study reports the first protein crystal structure of low oxygen-affinity avian T-metHb from Anas platyrhynchos.
PubMed: 38767790
DOI: 10.1007/s10930-024-10206-z