Mechanism of inhibition of rat liver bilirubin UDP-glucuronosyltransferase by triphenylalkyl derivatives

A series of potent and competitive inhibitors of UDP-glucuronosyltransferase derived from 7,7,7-triphenylheptanoic acid has been synthesized in order to probe the active site of the isozyme involved in the glucuronidation of the endogenous toxic compound, bilirubin IXα. Like triphenylalkylcarboxylic acids, triphenyl alcohols were found to be very effective competitive inhibitors of the reaction (K_i 12 to 180 μM). Superimposition of the best inhibitors with bilirubin by computer modeling showed a marked spatial similarity, which accounts for the observed competitive-type inhibition. The bulky triphenylmethyl moiety of the inhibitor superimposed well on the part of the bilirubin molecule containing three of the four pyrrole rings. In agreement, substitution of the triphenylmethyl moiety by planar structures such as fluorenyl or indenyl rings completely suppressed the inhibition. In addition, the weak inhibition exerted by the shortest carboxylic acids could be related to the higher acidity of these molecules. The inhibition potency depended on the acidity of the molecules; the more acidic, the less inhibitory, suggesting that the presence of a negative charge on the inhibitor molecule prevents bilirubin glucuronidation. Based on these results, a reaction mechanism for bilirubin glucuronidation is postulated. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 19–27, 1998     

Dual treatment with kynurenine pathway inhibitors and NAD+ precursors synergistically extends life span in Drosophila

Tryptophan catabolism is highly conserved and generates important bioactive metabolites, including kynurenines, and in some animals, NAD⁺. Aging and inflammation are associated with increased levels of kynurenine pathway (KP) metabolites and depleted NAD⁺, factors which are implicated as contributors to frailty and morbidity. Contrastingly, KP suppression and NAD⁺ supplementation are associated with increased life span in some animals. Here, we used DGRP_229 Drosophila to elucidate the effects of KP elevation, KP suppression, and NAD⁺ supplementation on physical performance and survivorship. Flies were chronically fed kynurenines, KP inhibitors, NAD⁺ precursors, or a combination of KP inhibitors with NAD⁺ precursors. Flies with elevated kynurenines had reduced climbing speed, endurance, and life span. Treatment with a combination of KP inhibitors and NAD⁺ precursors preserved physical function and synergistically increased maximum life span. We conclude that KP flux can regulate health span and life span in Drosophila and that targeting KP and NAD⁺ metabolism can synergistically increase life span.     

Efficient screening of potential cellulases and hemicellulases produced by <Emphasis Type="Italic">Bosea</Emphasis> sp. FBZP-16 using the combination of enzyme assays and genome analysis

Identification of bacteria that produce carbohydrolytic enzymes is extremely important given the increased demand for these enzymes in many industries. Twenty lignocellulose-degrading bacterial isolates from Algerian compost and different soils were screened for their potential to produce different enzymes involved in biomass deconstruction. Based on 16S rRNA gene sequencing, the isolates belonged to Proteobacteria and Actinobacteria. Differences among species were reflected both as the presence/absence of enzymes or at the level of enzyme activity. Among the most active species, Bosea sp. FBZP-16 demonstrated cellulolytic activity on both amorphous cellulose (CMC) and complex lignocellulose (wheat straw) and was selected for whole-genomic sequencing. The genome sequencing revealed the presence of a complex enzymatic machinery required for organic matter decomposition. Analysis of the enzyme-encoding genes indicated that multiple genes for endoglucanase, xylanase, β-glucosidase and β-mannosidase are present in the genome with enzyme activities displayed by the bacterium, while other enzymes, such as certain cellobiohydrolases, were not detected at the genomic level. This indicates that a combination of functional screening of bacterial cultures with the use of genome-derived information is important for the prediction of potential enzyme production. These results provide insight into their possible exploitation for the production of fuels and chemicals derived from plant biomass.     

Improving Interfacial Charge Recombination in Planar Heterojunction Perovskite Photovoltaics with Small Molecule as Electron Transport Layer

Although perovskite solar cells (PSCs) have emerged as a promising alternative to widely used fossil fuels, the involved high‐temperature preparation of metal oxides as a charge transport layer in most state‐of‐the‐art PSCs has been becoming a big stumbling block for future low‐temperature and large‐scale R2R manufacturing process. Such an issue strongly encourages scientists to find new type of materials to replace metal oxides. Except for expensive PC₆₁BM with unmanageable morphology and electrical properties, the past investigation on the development of low‐temperature‐processed and highly efficient electron transport layers (ETLs) has met some mixed success. In order to further enhance the performance of all‐solution‐processed PSCs, we propose a novel n‐type sulfur‐containing small molecule hexaazatrinaphtho[2,3‐c][1,2,5]thiadiazole (HATNT) with high electron mobility up to 1.73 × 10^?2 cm² V^?1 s^?1 as an ETL in planar heterojunction PSCs. A high power conversion efficiency of 18.1% is achieved, which is fully comparable with the efficiency from the control device fabricated with PC₆₁BM as ETL. This superior performance mainly attributes from more effective suppression of charge recombination at the perovskite/HATNT interface than that between the perovskite and PC₆₁ BM. Moreover, high electron mobility and strong interfacial interaction via S? I or S? Pb bonding should be also positive factors. Significantly, our results undoubtedly enable new guidelines in exploring n‐type organic small molecules for high‐performance PSCs.     

Genetic population diversity of European eel <Emphasis Type="Italic">Anguilla anguilla</Emphasis> elvers in two Egyptian water bodies,Rosetta (Rachid) estuary and Burullus Lake

The European eel Anguilla anguilla is a species of great economic importance for Egypt. Its long trans-Atlantic migrations for semelparous spawning then larval homing provides a possible way for worldwide mixing of populations. Its natural habitats in Egypt, as in other Mediterranean countries, are under heavy load of pollution due to anthropogenic activities. Hence, a major priority should be given to assess the genetic diversity within/among eels’ populations as a step towards revealing populations’ status, identification of possible conservation units, and, subsequently, implementation of proper conservation and management strategies for them. For this, A. anguilla elvers were collected from Rosetta estuary and Burullus coastal lagoon in the North of Egypt. Sequencing of the barcode region of the cytochrome c oxidase subunit 1 gene (COI) was carried out for all collected elvers. The sequences were analyzed using various genetic, phylogenetic, and population analyses to assess their variability. A total of 33 haplotypes were identified, 14 of which were unique to Burullus Lake, and 11 to Rosetta estuary. Very low fixation (F _st ?=?0–0.04) was found for A. anguilla populations in Egypt and worldwide, except for the Turkish and Czech ones (F _st ?=?0.47–0.62 and 0.18–0.41, respectively). Both Egyptian populations showed signs of recent populations’ expansion, besides low, non-significant raggedness values. The results suggested Burullus Lake and Rosetta estuary as separate conservation units for A. anguilla in Egypt. These units require special attention for proper protection and management of the existing eel diversity and permitting sustainability in the activities dealing with eel’s fishing and aquaculture.     

Expression and purification of the recombinant membrane protein YidC: a case study for increased stability and solubility

YidC is an inner membrane protein from Escherichia coli and is an essential component in insertion, translocation and assembly of membrane proteins in the membranes. Previous purification attempts resulted in heavy aggregates and precipitated protein at later stages of purification. Here we present a rapid and straightforward stability screening strategy based on gel filtration chromatography, which requires as little as 10 microg of protein and takes less than 15 min to perform. With this technique, we could rapidly screen several buffers in order to identify an optimum condition that stabilizes purified YidC. After optimization we could obtain several milligrams of purified YidC that could be easily prepared at high concentrations and that was stable for weeks at +4 degrees C. The isolated protein is thus well suited for structural studies.     

Formation of potential titanium antigens based on protein binding to titanium dioxide nanoparticles

Degradation products of titanium implants include free ions, organo-metallic complexes, and particles, ranging from nano to macro sizes. The biological effects, especially of nanoparticles, is yet unknown. The main objective of this study was to develop Ti-protein antigens in physiological solutions that can be used in testing of cellular responses. For this purpose, 0.1% TiO2 nanoparticles less than 100 nm were mixed with human serum albumin (HSA), 0.1% and 1%, in cell culture medium (DMEM, pH 7.2). The Ti concentrations in the resulting solutions were analyzed by inductively coupled plasma mass spectrometry. The stability of the nanoparticles in suspension was analyzed by UV-vis spectrophotometer and Dynamic Light Scattering. The concentration of Ti in suspension was dependent on the presence and concentration of HSA. Albumin prevented high aggregation rate of TiO2 nanoparticles in cell culture medium. It is shown that nano TiO2-protein stable aggregates can be produced under physiological conditions at high concentrations, and are candidates for use in cellular tests.     

Molecular characterization of larval anisakid nematodes from marine fishes off the Moroccan and Mauritanian coasts

A total of 242 larval forms of Anisakis collected from marine fishes at different sites off the Moroccan and Mauritanian coasts, recognised as belonging to Type I and Type II larvae, were identified by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphisms) of the ITS (Internal Transcribed Spacers) region (ITS-1, 5.8 subunit rRNA gene and ITS-2), using a previously established molecular key. The Type I larvae were found with a frequency of 98.34% and were identified as belonging to the following species: A. simplex s.str., A. pegreffii, A. simplex s.str/A. pegreffii heterozygote genotypes, A. typica, A. ziphidarum and Anisakis sp. A. The Type II larvae were found to belong to A. physeteris, with the frequency of 1.65%. The results reported in the present study provide further epizootiological and biological data on the Anisakis spp. in marine fishes off the Moroccan and Mauritanian coasts, improving the picture of the occurrence of these species in the central Atlantic coasts.