-
Chemosphere Jul 2024Arsenic, ubiquitous in various industrial processes and consumer products, presents both essential functions and considerable toxicity risks, driving extensive research...
Arsenic, ubiquitous in various industrial processes and consumer products, presents both essential functions and considerable toxicity risks, driving extensive research into safer applications. Our investigation, drawing from 7182 arsenic-containing molecules in the Cambridge Structural Database (CSD), outlines their diverse bonding patterns. Notably, 51% of these molecules exhibit cyclic connections, while 49% display acyclic ones. Arsenic forms eight distinct bonding types with other elements, with significant interactions observed, particularly with phenyl rings, O and F moieties. Top interactions involve carbon, nitrogen, oxygen, fluorine, sulfur, and arsenic itself. We meticulously evaluated average bond lengths under three conditions: without an R-factor cut-off, with R-factor ≤0.075, and with R-factor ≤0.05, supporting the credibility of our results. Comparative analysis with existing literature data enriches our understanding of arsenic's bonding behaviour. Our findings illuminate the structural attributes, molecular coordination, geometry, and bond lengths of arsenic with 68 diverse atoms, enriching our comprehension of arsenic chemistry. These revelations not only offer a pathway for crafting innovative and safer arsenic-based compounds but also foster the evolution of arsenic detoxification mechanisms, tackling pivotal health and environmental challenges linked to arsenic exposure across different contexts.
Topics: Arsenic; Data Mining; Databases, Chemical; Molecular Structure; Arsenicals
PubMed: 38763400
DOI: 10.1016/j.chemosphere.2024.142349 -
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 -
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 -
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 -
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 -
Acta Crystallographica. Section E,... Feb 2024The ()-(+)-1-(4-bromo-phen-yl)--[(4-methoxyphen-yl)methyl-idene]ethyl-amine ligand, CHBrNO, (I), was synthesized through the reaction of 4-meth-oxy-anisaldehyde with...
()-(+)-1-(4-Bromo-phen-yl)--[(4-methoxyphen-yl)methyl-idene]ethyl-amine and bis-{()-(+)-1-(4-bromo-phen-yl)--[(4-methoxyphen-yl)methyl-idene]ethyl-amine-κ}di-chlorido-palladium(II).
The ()-(+)-1-(4-bromo-phen-yl)--[(4-methoxyphen-yl)methyl-idene]ethyl-amine ligand, CHBrNO, (I), was synthesized through the reaction of 4-meth-oxy-anisaldehyde with ()-(-)-1-(4-bromo-phen-yl)ethyl-amine. It crystallizes in the ortho-rhom-bic space group 222 belonging to the Sohncke group, featuring a single mol-ecule in the asymmetric unit. The refinement converged successfully, achieving an factor of 0.0508. The Pd com-plex bis-{()-(+)-1-(4-bromo-phen-yl)--[(4-methoxyphen-yl)methyl-idene]ethyl-amine-κ}di-chlorido-pal-ladium(II), [PdCl(CHBrNO)], (II), crystallizes in the monoclinic space group 2 belonging to the Sohncke group, with two mol-ecules in the asymmetric unit. The central atom is tetra-coordinated by two N atoms and two Cl atoms, resulting in a square-planar configuration. The imine moieties exhibit a configuration around the Pd centre, with average Cl-Pd-N angles of approximately 89.95 and 90°. The average distances within the palladium com-plex for the two mol-ecules are ∼2.031 Å for Pd-N and ∼2.309 Å for Pd-Cl.
PubMed: 38333132
DOI: 10.1107/S2056989024000690 -
Scientific Reports Feb 2024Based on the nonlinear algorithmic theory, the R-SVM water source discrimination model and prediction method were established by using the piper qualitatively to compare...
Based on the nonlinear algorithmic theory, the R-SVM water source discrimination model and prediction method were established by using the piper qualitatively to compare the differences between the ionic components and R-type factor approximation indicator input dimensions. Taking the mine water samples of Zhaogezhuang Coal Mine as an example, according to the chemical composition analysis of the water samples from different monitoring points, six indexes of Na, Ca, Mg, Cl, SO and HCO were selected as the discrimination factors. According to the water characteristics of each aquifer and the actual needs of discrimination, the water inrush sources in the mining area were divided into four categories: The goaf water is class I, Ordovician carbonate is class II, Sandstone fracture water from the 13 coal system is class III, and Sandstone fracture water from the 12 coal system is class IV. Taking 56 typical water inrush samples as training samples, 11 groups for prediction samples, establish the input index as typical ion content, output as water source type, using SPSS statistics and MATLAB to realize the R-SVM water source discriminant analysis model, automatically establishing the mapping relationship between the water quality indexes and the evaluation standards, which can achieve the purpose of rapid and accurate discrimination of the water sample data. The results showed that the accuracy of the R-SVM model classification was 90.90% in the verification of the water source discrimination example of Zhaogezhuang mine and the coupled model has high accuracy, good applicability and discriminant ability, and has certain guiding significance for the prevention and control of water damage and the related field work.
PubMed: 38332044
DOI: 10.1038/s41598-024-53877-5 -
Cureus Dec 2023Hepatic injuries attributable to terbinafine usage are a well-documented yet infrequent phenomenon. This case study details the clinical presentation and management of a...
Hepatic injuries attributable to terbinafine usage are a well-documented yet infrequent phenomenon. This case study details the clinical presentation and management of a 70-year-old Hispanic female, with no previous medical history, subsequently hospitalized for progressive jaundice, right upper quadrant abdominal discomfort, and worsening pruritus. A comprehensive review of her prior records revealed a recent terbinafine prescription for onychomycosis, which she took consistently for five weeks and then self-discontinued four weeks before her current admission. Laboratory tests on admission revealed a cholestatic pattern of liver injury, evident by transaminitis and conjugated hyperbilirubinemia. The R factor used to determine whether a liver injury is hepatocellular or cholestatic was 0.9. Further diagnostic imaging, including abdominal ultrasound, CT of the abdomen, and magnetic resonance cholangiopancreatography, failed to disclose an obstructive pathology, revealing only cholelithiasis and chronic cholecystitis. Therapeutically, the patient was initiated on hydroxyzine to address symptoms of pruritus, and then subsequently underwent a liver biopsy. Histopathologic findings from the biopsy revealed benign hepatic parenchyma demonstrating focal canalicular cholestasis, mild chronic inflammation involving select portal tracts, and chronic lobular inflammation, suggesting terbinafine-induced hepatotoxicity. This case highlights the challenges of diagnosing terbinafine-induced liver injury, emphasizing the need for a high index of clinical suspicion and recognizing the potential for prolonged symptomatic manifestation after drug discontinuation. This article provides valuable insights into the complexities inherent in such diagnoses and significantly enriches a medical provider's approach to diagnosing and treating unexplained liver injuries.
PubMed: 38239534
DOI: 10.7759/cureus.50749 -
Acta Crystallographica. Section D,... Dec 2023Hydrogen (H) atoms are abundant in macromolecules and often play critical roles in enzyme catalysis, ligand-recognition processes and protein-protein interactions....
Hydrogen (H) atoms are abundant in macromolecules and often play critical roles in enzyme catalysis, ligand-recognition processes and protein-protein interactions. However, their direct visualization by diffraction techniques is challenging. Macromolecular X-ray crystallography affords the localization of only the most ordered H atoms at (sub-)atomic resolution (around 1.2 Å or higher). However, many H atoms of biochemical significance remain undetectable by this method. In contrast, neutron diffraction methods enable the visualization of most H atoms, typically in the form of deuterium (H) atoms, at much more common resolution values (better than 2.5 Å). Thus, neutron crystallography, although technically demanding, is often the method of choice when direct information on protonation states is sought. REFMAC5 from the Collaborative Computational Project No. 4 (CCP4) is a program for the refinement of macromolecular models against X-ray crystallographic and cryo-EM data. This contribution describes its extension to include the refinement of structural models obtained from neutron crystallographic data. Stereochemical restraints with accurate bond distances between H atoms and their parent atom nuclei are now part of the CCP4 Monomer Library, the source of prior chemical information used in the refinement. One new feature for neutron data analysis in REFMAC5 is refinement of the protium/deuterium (H/H) fraction. This parameter describes the relative H/H contribution to neutron scattering for hydrogen isotopes. The newly developed REFMAC5 algorithms were tested by performing the (re-)refinement of several entries available in the PDB and of one novel structure (FutA) using either (i) neutron data only or (ii) neutron data supplemented by external restraints to a reference X-ray crystallographic structure. Re-refinement with REFMAC5 afforded models characterized by R-factor values that are consistent with, and in some cases better than, the originally deposited values. The use of external reference structure restraints during refinement has been observed to be a valuable strategy, especially for structures at medium-low resolution.
Topics: Proteins; Deuterium; Models, Molecular; Crystallography, X-Ray; Neutron Diffraction; Hydrogen; Neutrons; Macromolecular Substances
PubMed: 37921806
DOI: 10.1107/S2059798323008793 -
BMC Medical Informatics and Decision... Oct 2023This article focuses on the development of algorithms for a smart neurorehabilitation system, whose core is made up of artificial neural networks. The authors of the...
This article focuses on the development of algorithms for a smart neurorehabilitation system, whose core is made up of artificial neural networks. The authors of the article have proposed a completely unique transfer of ACE-R results to the CHC model. This unique approach allows for the saturation of the CHC model domains according to modified ACE-R factor analysis. The outputs of the proposed algorithm thus enable the automatic creation of a personalized and optimized neurorehabilitation plan for individual patients to train their cognitive functions. A set of tasks in 6 levels of difficulty (level 1 to level 6) was designed for each of the nine CHC model domains. For each patient, the results of the ACE-R screening helped deter-mine the specific CHC domains to be rehabilitated, as well as the initial gaming level for rehabilitation in each domain. The proposed artificial neural network algorithm was adapted to real data from 703 patients. Experimental outputs were compared to the outputs of the initially designed fuzzy expert system, which was trained on the same real data, and all outputs from both systems were statistically evaluated against expert conclusions that were available. It is evident from the conducted experimental study that the smart neurorehabilitation system using artificial neural networks achieved significantly better results than the neurorehabilitation system whose core is a fuzzy expert system. Both algorithms are implemented into a comprehensive neurorehabilitation portal (Eddie), which was supported by a research project from the Technology Agency of the Czech Republic.
Topics: Humans; Expert Systems; Fuzzy Logic; Neural Networks, Computer; Algorithms; Neurological Rehabilitation
PubMed: 37845677
DOI: 10.1186/s12911-023-02321-1