Heterotropic and homotropic cooperativity by a drug-metabolising mutant of cytochrome P450 BM3

Recently, we described a triple mutant of the bacterial cytochrome P450 BM3 as the first mutant with affinity for drug-like compounds. In this paper, we show that this mutant, but not wild-type BM3, is able to metabolise testosterone and several drug-like molecules such as amodiaquine, dextromethorphan, acetaminophen, and 3,4-methylenedioxymethylamphetamine that are known substrates of human P450s. Interestingly, the metabolism of 3,4-methylenedioxymethylamphetamine and acetaminophen could be stimulated up to 70-fold by the addition of caffeine, a known activator of rat P450 3A2. With testosterone metabolism, homotropic cooperativity was observed. This shows that heterotropic and homotropic cooperativity, known to occur in the P450 3A family, can also take place in BM3. BM3 therefore can be used as a model system to study atypical kinetics in mammalian P450s. Second, this study shows that BM3 can be engineered to a drug-metabolising enzyme, making it a promising candidate to use as biocatalyst in drug discovery and synthesis.     

Microbial Community Changes Elicited by Exposure to Cyanobacterial Allelochemicals

An increasing body of evidence points out that allelopathy may be an important process shaping microbial communities in aquatic ecosystems. Cyanobacteria have well-documented allelopathic properties, mainly derived from the evaluation of the activity of allelopathic extracts or pure compounds towards monocultures of selected target microorganisms. Consequently, little is known regarding the community dynamics of microorganisms associated with allelopathic interactions. In this laboratory-based study, a Microcystis spp.-dominated microbial community from a freshwater lake was exposed, for 15 days, to exudates from the cyanobacterium Oscillatoria sp. strain LEGE 05292 in laboratory conditions. This cyanobacterium is known to produce the allelochemicals portoamides, which were among the exuded compounds. The community composition was followed (by means of polymerase chain reaction followed by denaturing gradient gel electrophoresis and microscopic analyses) and compared to that of a non-exposed situation. Following exposure, clear differences in the community structure were observed, in particular for cyanobacteria and unicellular eukaryotic taxa. Interestingly, distinct Microcystis genotypes present in the community were differentially impacted by the exposure, highlighting the fine-scale dynamics elicited by the exudates. These results support a role for cyanobacterial allelochemicals in the structuring of aquatic microbial communities.     

Enhancement of fruit byproducts through bioconversion by Hermetia illucens (Diptera: Stratiomyidae)

Bioconversion is a biological process by which organic materials are converted into products with higher biological and commercial value. During its larval stage the black soldier fly Hermetia illucens is extremely voracious and can feed on a wide variety of organic materials. To study the impact of different fruit byproducts on the insect's growth, final larval biomass, substrate reduction, bioconversion parameters, and larval nutritional composition, 10 000 black soldier fly larvae (BSFL) were reared on 7.0 kg of one of three substrates (strawberry, tangerine, or orange) or on a standard diet as a control. The results highlight that BSFL can successfully feed and grow on each of these diets, though their development time, growth rate, and final biomass were differently impacted by the substrates, with strawberry being the most suitable. The lipid and protein contents of BSFL were similar among larvae fed on different substrates; however, major differences were detected in ash, micronutrient, fiber, fatty acid, and amino acid contents. Overall, the results indicate that fruit waste management through the BSFL bioconversion process represents a commercially promising resource for regional and national agrifood companies. Our study offers new perspectives for sustainable and environmentally friendly industrial development by which fruit byproducts or waste might be disposed of or unconventionally enhanced to create secondary products of high biological and economic value, including BSFL biomass as animal feed or, in perspective, as alternative protein source for human nutrition.     

Identification and seasonal distribution of airborne fungi in three horse stables in Italy

Fungal agents are responsible for a variety of respiratory diseases both in humans and animals. The nature and seasonal variations of fungi have been investigated in many environments with wide ranging results. The aims of the present report were (i) to evaluate the quality and magnitude of exposure to airborne fungi in three differently structured equine stalls (open air, partially and completely enclosed buildings) during a one-year period, using an air sampling technique and (ii) to compare the distribution and frequency of fungal species, with regards to these different environments. Air samples were collected monthly from December 2001 to November 2002 by means of a surface air sampler (SAS) Super-90, (PBI International, Milan, Italy). Penicillium and Aspergillus spp. were cultured from all the stables in all seasons. Mucoraceae were also recovered in all seasons in stalls 1 and 2, while they were not isolated in spring and fall in stall 3. These fungi were detected in 28.4%, 72.9% and 60.5% of the total number of samples, respectively. Other fungal genera such as Alternaria, Cladosporium, Fusarium, Beauveria and Drechslera were also occasionally recovered.Viable fungal concentrations varied greatly, ranging from below the limit of detection to more than 3000 CFU/m³ for stables 1 and 2, and 1750 CFU/m³ for stable 3. The median fungal concentration was approximately 178 CFU/m³. Total fungal concentration appeared to be highest in summer, winter and spring, and lowest in the fall.     

New therapies for the treatment of Parkinson's disease: adenosine A2A receptor antagonists

The development of non-dopaminergic therapies for the treatment of Parkinson's disease (PD) has attracted much interest in recent years. Among new different classes of drugs, adenosine A2A receptor antagonists have emerged as best candidates. The present review will provide an updated summary of the results reported in literature concerning the effects of adenosine A2A antagonists in rodent and primate models of PD. These results show that A2A receptor antagonists improve motor deficits without inducing dyskinesia and counteract parkinsonian tremor. In progress clinical trials have shown that a low dose of L-DOPA plus KW-6002 produced symptomatic relief no different from that produced by an optimal dose of L-DOPA alone, whereas dyskinesias were reduced rendering this class of compounds particularly attractive.     

A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline

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Scalable Triple Cation Mixed Halide Perovskite–BiVO4 Tandems for Bias‐Free Water Splitting

Strong interest exists in the development of organic–inorganic lead halide perovskite photovoltaics and of photoelectrochemical (PEC) tandem absorber systems for solar fuel production. However, their scalability and durability have long been limiting factors. In this work, it is revealed how both fields can be seamlessly merged together, to obtain scalable, bias‐free solar water splitting tandem devices. For this purpose, state‐of‐the‐art cesium formamidinium methylammonium (CsFAMA) triple cation mixed halide perovskite photovoltaic cells with a nickel oxide (NiO_x) hole transport layer are employed to produce Field's metal‐epoxy encapsulated photocathodes. Their stability (up to 7 h), photocurrent density (–12.1 ± 0.3 mA cm^?2 at 0 V versus reversible hydrogen electrode, RHE), and reproducibility enable a matching combination with robust BiVO₄ photoanodes, resulting in 0.25 cm² PEC tandems with an excellent stability of up to 20 h and a bias‐free solar‐to‐hydrogen efficiency of 0.35 ± 0.14%. The high reliability of the fabrication procedures allows scaling of the devices up to 10 cm², with a slight decrease in bias‐free photocurrent density from 0.39 ± 0.15 to 0.23 ± 0.10 mA cm^?2 due to an increasing series resistance. To characterize these devices, a versatile 3D‐printed PEC cell is also developed.