Formaldehyde-releasers: relationship to formaldehyde contact allergy. Contact allergy to formaldehyde and inventory of formaldehyde-releasers

This is one of series of review articles on formaldehyde and formaldehyde-releasers (others: formaldehyde in cosmetics, in clothes and in metalworking fluids and miscellaneous). Thirty-five chemicals were identified as being formaldehyde-releasers. Although a further seven are listed in the literature as formaldehyde-releasers, data are inadequate to consider them as such beyond doubt. Several (nomenclature) mistakes and outdated information are discussed. Formaldehyde and formaldehyde allergy are reviewed: applications, exposure scenarios, legislation, patch testing problems, frequency of sensitization, relevance of positive patch test reactions, clinical pattern of allergic contact dermatitis from formaldehyde, prognosis, threshold for elicitation of allergic contact dermatitis, analytical tests to determine formaldehyde in products and frequency of exposure to formaldehyde and releasers. The frequency of contact allergy to formaldehyde is consistently higher in the USA (8-9%) than in Europe (2-3%). Patch testing with formaldehyde is problematic; the currently used 1% solution may result in both false-positive and false-negative (up to 40%) reactions. Determining the relevance of patch test reactions is often challenging. What concentration of formaldehyde is safe for sensitive patients remains unknown. Levels of 200-300 p.p.m. free formaldehyde in cosmetic products have been shown to induce dermatitis from short-term use on normal skin

Evidence for a Two-Metal-Ion Mechanism in the Cytidyltransferase KdsB, an Enzyme Involved in Lipopolysaccharide Biosynthesis

Lipopolysaccharide (LPS) is located on the surface of Gram-negative bacteria and is responsible for maintaining outer membrane stability, which is a prerequisite for cell survival. Furthermore, it represents an important barrier against hostile environmental factors such as antimicrobial peptides and the complement cascade during Gram-negative infections. The sugar 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is an integral part of LPS and plays a key role in LPS functionality. Prior to its incorporation into the LPS molecule, Kdo has to be activated by the CMP-Kdo synthetase (CKS). Based on the presence of a single Mg2+ ion in the active site, detailed models of the reaction mechanism of CKS have been developed previously. Recently, a two-metal-ion hypothesis suggested the involvement of two Mg2+ ions in Kdo activation. To further investigate the mechanistic aspects of Kdo activation, we kinetically characterized the CKS from the hyperthermophilic organism Aquifex aeolicus. In addition, we determined the crystal structure of this enzyme at a resolution of 2.10 Å and provide evidence that two Mg2+ ions are part of the active site of the enzyme

Scaling-up Engineering Biology for Enhanced Environmental Solutions

Viewpoint.Synthetic biology (SynBio) offers transformative solutions for addressing environmental challenges by engineering organisms capable of degrading pollutants, enhancing carbon sequestration, and valorizing waste (Figure 1).This work is funded by Biotechnology and Biological Sciences Research Council (BBSRC) through an Engineering Biology Hub award (grant number: BB/Y008332/1)

Scaling-up engineering biology for enhanced environmental solutions

Synthetic biology (SynBio) offers transformative solutions for addressing environmental challenges by engineering organisms capable of degrading pollutants, enhancing carbon sequestration, and valorizing waste (Figure 1). These innovations hold the potential to revolutionize bioremediation strategies, ecosystem restoration, and sustainable environmental management. (1) Advances in SynBio, including automation, precise manipulation of genetic material, (2) and design of semisynthetic organisms with enhanced capabilities, can improve the efficiency of microbes for eliminating pollutants such as hydrocarbons and plastics or extracting valuable resources from the environment. (3) Genome editing technologies, such as CRISPR-Cas9, allows the editing of genomes with unprecedented accuracy, facilitating the development of organisms with desired traits or functions. (4) Furthermore, SynBio encompasses the engineering of metabolic enzymes within organisms, leading to the design of microbial factories capable of degrading complex and persistent chemicals, and converting waste to valuable resources. (5) These advancements also facilitate the manipulation of bacterial social behaviors, offering the capacity for tunable control at the multicellular level and engineered biofilms. (5

Biapenem Inactivation by B2 Metallo β-Lactamases: Energy Landscape of the Post-Hydrolysis Reactions

<div><h3>Background</h3><p>The first line of defense by bacteria against <em>β</em>-lactam antibiotics is the expression of β-lactamases, which cleave the amide bond of the β-lactam ring. In the reaction of biapenem inactivation by B2 metallo β-lactamases (MβLs), after the β-lactam ring is opened, the carboxyl group generated by the hydrolytic process and the hydroxyethyl group (common to all carbapenems) rotate around the C5–C6 bond, assuming a new position that allows a proton transfer from the hydroxyethyl group to C2, and a nucleophilic attack on C3 by the oxygen atom of the same side-chain. This process leads to the formation of a bicyclic compound, as originally observed in the X-ray structure of the metallo β-lactamase CphA in complex with product.</p> <h3>Methodology/Principal Findings</h3><p>QM/MM and metadynamics simulations of the post-hydrolysis steps in solution and in the enzyme reveal that while the rotation of the hydroxyethyl group can occur in solution or in the enzyme active site, formation of the bicyclic compound occurs primarily in solution, after which the final product binds back to the enzyme. The calculations also suggest that the rotation and cyclization steps can occur at a rate comparable to that observed experimentally for the enzymatic inactivation of biapenem only if the hydrolysis reaction leaves the N4 nitrogen of the β-lactam ring unprotonated.</p> <h3>Conclusions/Significance</h3><p>The calculations support the existence of a common mechanism (in which ionized N4 is the leaving group) for carbapenems hydrolysis in all MβLs, and suggest a possible revision of mechanisms for B2 MβLs in which the cleavage of the β-lactam ring is associated with or immediately followed by protonation of N4. The study also indicates that the bicyclic derivative of biapenem has significant affinity for B2 MβLs, and that it may be possible to obtain clinically effective inhibitors of these enzymes by modification of this lead compound.</p> </div

Computational models in plant-pathogen interactions: the case of Phytophthora infestans

<p>Abstract</p> <p>Background</p> <p><it>Phytophthora infestans </it>is a devastating oomycete pathogen of potato production worldwide. This review explores the use of computational models for studying the molecular interactions between <it>P. infestans </it>and one of its hosts, <it>Solanum tuberosum</it>.</p> <p>Modeling and conclusion</p> <p>Deterministic logistics models have been widely used to study pathogenicity mechanisms since the early 1950s, and have focused on processes at higher biological resolution levels. In recent years, owing to the availability of high throughput biological data and computational resources, interest in stochastic modeling of plant-pathogen interactions has grown. Stochastic models better reflect the behavior of biological systems. Most modern approaches to plant pathology modeling require molecular kinetics information. Unfortunately, this information is not available for many plant pathogens, including <it>P. infestans</it>. Boolean formalism has compensated for the lack of kinetics; this is especially the case where comparative genomics, protein-protein interactions and differential gene expression are the most common data resources.</p