Notes

Inflammation-Induced Tumorigenesis and Metastasis.
Human reticulocyte 15-lipoxygenase-1 (h15-LOX-1 or ALOX15) and platelet 12-lipoxygenase (h12-LOX or ALOX12) catalysis of docosahexaenoic acid (DHA) and the maresin precursor, 14S-hydroperoxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid (14S-HpDHA), were investigated to determine their product profiles and relative rates in the biosynthesis of the key maresin intermediate, 13S,14S-epoxy-4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid (13S,14S-epoxy-DHA). Both enzymes converted DHA to 14S-HpDHA, with h12-LOX having a 39-fold greater kcat/KM value (14.0 ± 0.8 s-1 μM-1) than that of h15-LOX-1 (0.36 ± 0.08 s-1 μM-1) and a 1.8-fold greater 14S-HpDHA product selectivity, 81 and 46%, respectively. However, h12-LOX was markedly less effective at producing 13S,14S-epoxy-DHA from 14S-HpDHA than h15-LOX-1, with a 4.6-fold smaller kcat/KM value, 0.0024 ± 0.0002 and 0.11 ± 0.006 s-1 μM-1, respectively. This is the first evidence of h15-LOX-1 to catalyze this reaction and reveals a novel in vitro pathway for maresin biosynthesis. In addition, epoxidation of 14S-HpDHA is negatively regulated through allosteric oxylipin binding to h15-LOX-1 and h12-LOX. For h15-LOX-1, 14S-HpDHA (Kd = 6.0 μM), 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12S-HETE) (Kd = 3.5 μM), and 14S-hydroxy-7Z,10Z,12E,16Z,19Z-docosapentaenoic acid (14S-HDPAω-3) (Kd = 4.0 μM) were shown to decrease 13S,14S-epoxy-DHA production. h12-LOX was also shown to be allosterically regulated by 14S-HpDHA (Kd = 3.5 μM) and 14S-HDPAω-3 (Kd = 4.0 μM); however, 12S-HETE showed no effect, indicating for the first time an allosteric response by h12-LOX. Finally, 14S-HpDHA inhibited platelet aggregation at a submicrololar concentration, which may have implications in the benefits of diets rich in DHA. These in vitro biosynthetic pathways may help guide in vivo maresin biosynthetic investigations and possibly direct therapeutic interventions.We randomly selected 100 journal articles published in five proteomics journals in 2019 and manually examined each of them against a set of 13 criteria concerning the statistical analyses used, all of which were based on items mentioned in the journals' instructions to authors. This included questions such as whether a pilot study was conducted and whether false discovery rate calculation was employed at either the quantitation or identification stage. These data were then transformed to binary inputs, analyzed via machine learning algorithms, and classified accordingly, with the aim of determining if clusters of data existed for specific journals or if certain statistical measures correlated with each other. We applied a variety of classification methods including principal component analysis decomposition, agglomerative clustering, and multinomial and Bernoulli naïve Bayes classification and found that none of these could readily determine journal identity given extracted statistical features. Logistic regression was useful in determining high correlative potential between statistical features such as false discovery rate criteria and multiple testing corrections methods, but was similarly ineffective at determining correlations between statistical features and specific journals. This meta-analysis highlights that there is a very wide variety of approaches being used in statistical analysis of proteomics data, many of which do not conform to published journal guidelines, and that contrary to implicit assumptions in the field there are no clear correlations between statistical methods and specific journals.Arsenic pollution in drinking water is a widespread public health problem, and it affects approximately 200 million people in over 70 countries. Many human diseases, including neurodegenerative disorders, are engendered by the malfunction of proteins involved in important biological processes and are elicited by protein misfolding and/or loss of protein quality control during translation. Arsenic exposure results in proteotoxic stress, though the detailed molecular mechanisms remain poorly understood. Here, we showed that arsenite interacts with ZNF598 protein in cells and exposure of human skin fibroblasts to arsenite results in significant decreases in the ubiquitination levels of lysine residues 138 and 139 in RPS10 and lysine 8 in RPS20, which are regulatory post-translational modifications important in ribosome-associated protein quality control. Furthermore, the arsenite-elicited diminutions in ubiquitinations of RPS10 and RPS20 gave rise to augmented read-through of poly(adenosine)-containing stalling sequences, which was abolished in ZNF598 knockout cells. Together, our study revealed a novel mechanism underlying the arsenic-induced proteostatic stress in human cells.Conformational transitions in proteins facilitate precise physiological functions. Therefore, it is crucial to understand the mechanisms underlying these processes to modulate protein function. Yet, studying structural and dynamical properties of proteins are notoriously challenging due to the complexity of the underlying potential energy surfaces (PES). We have previously developed the perturbation-response scanning (PRS) method to identify key residues that participate in the communication network responsible for specific conformational transitions. PRS is based on a residue-by-residue scan of the protein to determine the subset of residues/forces which provide the closest conformational change leading to a target conformational state, inasmuch as linear response theory applies to these motions. Here, we develop a novel method to further evaluate if conformational transitions may be triggered on the PES. We aim to study functionally relevant conformational transitions in proteins using results obtained by PRS and feeding them as inputs to steered molecular dynamics simulations. The success and the transferability of the method are evaluated on three protein systems having different complexity of motions on the PES calmodulin, adenylate kinase, and bacterial ferric binding protein. E-64 mw We find that the method captures the target conformation, while providing key residues and the optimum conformational transition paths with relatively low free energy profiles.Transient receptor potential ankyrin 1 (TRPA1) is a cation channel that plays a critical role in the occurrence and transmission of pain. By screening 393 marine invertebrate extracts for their antagonistic activity against TRPA1, it was found that the extract of the edible sea cucumber Bohadschia vitiensis had a remarkable potency. Bioassay-guided separation of the extract resulted in the isolation of six triterpene glycosides, including a novel analog. All six isolated compounds exhibited high inhibitory potency against TRPA1 (IC50 values ranging from 0.60 to 3.26 μM), which is comparable to that of a previously developed synthetic antagonist (A-967079). The discovery of TRPA1 antagonists, originated from this edible sea cucumber, opens the door for the elaboration of the valuable triterpene scaffold for the development of novel safe analgesics.Earlier studies on cerium-loaded naturally occurring silica microparticles (i.e., diatomaceous earth) demonstrated the potential to efficiently protect small scratches in epoxy-coated AA2024-T3 panels during relatively short immersion times. The current work investigates the potential of such inhibitor-loaded microparticles to protect wide and deep scribes (up to 1 mm wide) in long-time immersion testing and during cyclic (wet/dry) conditions. For this, cerium nitrate and 2,5-dimercaptothiadiazole (DMTD) were used as inorganic and organic corrosion inhibitors. The corrosion protection was evaluated using a hyphenated real-time optics/electrochemistry method and two individual local techniques measuring oxygen concentration and electrochemical impedance (LEIM) inside the scribe. SEM/EDS was used to analyze the samples after exposure. The results show significant levels of corrosion protection at damaged locations at low cerium concentrations (3.7 wt % Ce3+ relative to the total coating mass) during 30 days of immersion in salt solution. However, for a given scribe geometry, the protection was found to be dependent on the electrolyte volume with larger electrolyte/exposed metal ratios leading to short protection time. A partial replacement of the Ce3+ by DMTD in the microcarriers resulted in a higher degree of passivation than when DMTD was used alone. Wet/dry cyclic exposure tests showed that cyclic conditions can increase the buildup of stable inhibitor-containing layers in the case of cerium-loaded silica microparticles. This underlines the need for more research using wet/dry exposure conditions.Synthesis of nanocomposites possessing intimately mixed components is highly challenging to bring out the best possible properties of the materials. The challenge is mainly due to the difficulties associated with controlling the phase segregation of individual components as a result of high interfacial tension between them and cohesive forces within each component during the synthesis. Here, we show a single-step synthesis of representative nanocomposites of g-C3N4/AgBr through a rationally designed approach, wherein melamine, the precursor of g-C3N4, has been intimately mixed with the AgBr precursor, silver-tetraoctylammonium bromide. Subsequent calcination of the obtained solid at 500 °C has resulted in the formation of highly dispersed g-C3N4/AgBr. The key to such a high dispersion lies in the surfactant-based AgBr precursor that minimized the interfacial tension during the process. The AgBr content has been varied between 2 and 20 wt % with respect to the g-C3N4 content. The obtained nanocomposites have been thoroughly characterized using XRD, XPS, ED-XRF, FE-SEM, HR-TEM, DRS, TCSPC, and BET surface area techniques. The studies revealed a high dispersion of AgBr in the g-C3N4 matrix. The nanocomposites have been found to exhibit remarkable antimicrobial properties over a drought-resistant bacterial strain of Pseudomonas putida under both dark and light conditions compared with similar compositions obtained through other methods reported so far. The present study offers a new approach for synthesizing highly dispersed and efficient nanocomposites.The human nuclear membrane is composed of a double bilayer, the inner membrane being linked to the protein lamina network and the outer nuclear membrane continuous with the endoplasmic reticulum. Nuclear membranes can form large invaginations inside the nucleus; their specific roles still remain unknown. Although much of the protein identification has been determined, their lipid composition remains largely undetermined. In order to understand the mechanical and dynamic properties of nuclear membranes we investigated their lipid composition by two quantitative methods, namely, 31P and 1H multidimensional NMR and mass spectrometry, using internal standards. We also developed a nondetergent nuclei extraction protocol allowing to produce milligram quantities of nuclear membrane lipids. We found that the nuclear membrane lipid extract is composed of a complex mixture of phospholipids with different phosphatidylcholine species present in large amounts. Negatively charged lipids, with elevated amounts of phosphatidylinositol (PI), were also present.
Here's my website: https://www.selleckchem.com/products/e-64.html