BackgroundConcerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects.ObjectivesIn this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor–responsive and calcium signaling bioassays.Materials and methodsWe determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor–responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1).ResultsSome carbanilide compounds, including TCC (1–10 μM), enhanced estradiol (E2)-dependent or testosterone-dependent activation of ER- and AR-responsive gene expression up to 2.5-fold but exhibited little or no agonistic activity alone. Some carbanilides and TCS exhibited weak agonistic and/or antagonistic activity in the AhR-responsive bioassay. TCS exhibited antagonistic activity in both ER- and AR-responsive bioassays. TCS (0.1–10 μM) significantly enhanced the binding of [3H]ryanodine to RyR1 and caused elevation of resting cytosolic [Ca2+] in primary skeletal myotubes, but carbanilides had no effect.ConclusionsCarbanilides, including TCC, enhanced hormone-dependent induction of ER- and AR-dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted poly-chlorinated biphenyls, exhibited weak AhR activity but interacted with RyR1 and stimulated Ca2+ mobilization. These observations have potential implications for human and animal health. Further investigations are needed into the biological and toxicologic effects of TCC, its analogs, and TCS.
These authors have contributed equally to this work. SUMMARYThe identification of genes that improve the salt tolerance of crops is essential for the effective utilization of saline soils for agriculture. Here, we use fine mapping in a soybean (Glycine max (L.) Merr.) population derived from the commercial cultivars Tiefeng 8 and 85-140 to identify GmSALT3 (salt tolerance-associated gene on chromosome 3), a dominant gene associated with limiting the accumulation of sodium ions (Na + )in shoots and a substantial enhancement in salt tolerance in soybean. GmSALT3 encodes a protein from the cation/H + exchanger family that we localized to the endoplasmic reticulum and which is preferentially expressed in the salt-tolerant parent Tiefeng 8 within root cells associated with phloem and xylem. We identified in the salt-sensitive parent, 85-140, a 3.78-kb copia retrotransposon insertion in exon 3 of Gmsalt3 that truncates the transcript. By sequencing 31 soybean landraces and 22 wild soybean (Glycine soja) a total of nine haplotypes including two salt-tolerant haplotypes and seven salt-sensitive haplotypes were identified. By analysing the distribution of haplotypes among 172 Chinese soybean landraces and 57 wild soybean we found that haplotype 1 (H1, found in Tiefeng 8) was strongly associated with salt tolerance and is likely to be the ancestral allele. Alleles H2-H6, H8 and H9, which do not confer salinity tolerance, were acquired more recently. H1, unlike other alleles, has a wide geographical range including saline areas, which indicates it is maintained when required but its potent stress tolerance can be lost during natural selection and domestication. GmSALT3 is a gene associated with salt tolerance with great potential for soybean improvement.
Many xenobiotics have been associated with endocrine effects in a wide range of biological systems. These associations are usually between small nonsteroid molecules and steroid receptor signaling systems. In this report, triclocarban (TCC; 3,4,4'-trichlorocarbanilide), a common ingredient in personal care products that is used as an antimicrobial agent was evaluated and found to represent a new category of endocrine-disrupting substance. A cell-based androgen receptor-mediated bioassay was used to demonstrate that TCC and other urea compounds with a similar structure, which have little or no endocrine activity when tested alone, act to enhance testosterone (T)-induced androgen receptor-mediated transcriptional activity in vitro. This amplification effect of TCC was also apparent in vivo when 0.25% TCC was added to the diet of castrated male rats that were supported by exogenous testosterone treatment for 10 d. All male sex accessory organs increased significantly in size after the T+TCC treatment, compared with T or TCC treatments alone. The data presented here suggest that the bioactivity of endogenous hormones may be amplified by exposure to commercial personal care products containing sufficient levels of TCC.
Short, strong hydrogen bonds are common in charged systems in the gas phase, but the importance of such bonding in enzymatic catalysis has been the subject of considerable controversy. Confusion has arisen about the relationship among bond strength, the "low-barrier" or "no-barrier" nature of the hydrogen bonding, the role of pK a matching, the covalent or electrostatic nature of the bonding, and the role of solvation on the strengths of these types of hydrogen bonds. We have attempted to strip away the "Alice in Wonderland" quality of the definitions in this field by defining, through high-level calculations, when short-strong hydrogen bonds do and do not occur. The strengths and geometries of several types of hydrogen bonds involving anions have been investigated by ab initio quantum mechanical calculations. For a series of enols hydrogen-bonded to enolates, the strengths of the short, strong gas-phase hydrogen bonds are linearly related to the differences between the proton affinities (PA) of the two anions which share the proton. The bond strength is also related to the O‚‚‚O distance between them. There is no discontinuity at ∆PA ) 0, and hydrogen-bonding becomes even stronger in a computational experiment when the PA of the H-bond acceptor exceeds that of the donor. "Low-barrier" hydrogen bonds with single-well minima after inclusion of zero-point energies occur when ∆PA is near 0, but no special stability accrues when the double-well minimum becomes single-well. The maleic/fumaric and mesaconic/citraconic systems studied by Drueckhammer have been investigated computationally. The influence of solvation on hydrogen-bond strength was studied using solvent cavity models. Small increases in dielectric constant from the gas-phase value ( ) 1) rapidly reduce the strengths of charged hydrogen bonds. Short, strong hydrogen bonds occur only with charged systems, and only then in nonpolar ( < 10) environments. Alternative mechanisms are often available to account for enzymatic catalysis; the example of orotidine monophosphate decarboxylase is discussed.
The demand for computing power has been increasing exponentially since the emergence of artificial intelligence (AI), internet of things (IoT), and machine learning (ML), where novel computing primitives are required. Brain inspired neuromorphic computing systems, capable of combining analog computing and data storage at the device level, have drawn great attention recently. In addition, the basic electronic devices mimicking the biological synapse have achieved significant progress. Owing to their atomic thickness and reduced screening effect, the physical properties of 2D materials could be easily modulated by various stimuli, which is quite beneficial for synaptic applications. In this article, aiming at high‐performance and functional neuromorphic computing applications, a comprehensive review of synaptic devices based on 2D materials is provided, including the advantages of 2D materials and heterostructures, various robust multifunctional 2D synaptic devices, and associated neuromorphic applications. Challenges and strategies for the future development of 2D synaptic devices are also discussed. This review will provide an insight into the design and preparation of 2D synaptic devices and their applications in neuromorphic computing.
The crystal structure of an efficient Diels-Alder antibody catalyst at 1.9 angstrom resolution reveals almost perfect shape complementarity with its transition state analog. Comparison with highly related progesterone and Diels-Alderase antibodies that arose from the same primordial germ line template shows the relatively subtle mutational steps that were able to evolve both structural complementarity and catalytic efficiency.
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