Defining plastic pollution hotspots.

Plastic pollution in the natural environment poses a growing threat to ecosystems and human health, prompting urgent needs for monitoring, prevention and clean-up measures, and new policies. To effectively prioritize resource allocation and mitigation strategies, it is key to identify and define plastic hotspots. UNEP's draft global agreement on plastic pollution mandates prioritizing hotspots, suggesting a potential need for a defined term. Yet, the delineation of hotspots varies considerably across plastic pollution studies, and a definition is often lacking or inconsistent without a clear purpose and boundaries of the term. In this paper, we applied four common definitions of hotspot locations to plastic pollution datasets ranging from urban areas to a global scale. Our findings reveal that these hotspot definitions encompass between 0.8 % to 93.3 % of the total plastic pollution, covering <0.1 % to 50.3 % of the total locations. Given this wide range of results and the possibility of temporal inconsistency in hotspots, we emphasize the need for fit-for-purpose criteria and a unified approach to defining plastic hotspots. Therefore, we designed a step-wise framework to define hotspots by determining the purpose, units, spatial scale, temporal scale, and threshold values. Incorporating these steps in research and policymaking yields a harmonized definition of hotspots, facilitating the development of effective plastic pollution prevention and reduction measures.

Pan-neuronal expression of human mutant SOD1 in Drosophila impairs survival and motor performance, induces early neuroinflammation and chromosome aberrations.

Several mutations in the SOD1 gene encoding for the antioxidant enzyme Superoxide Dismutase 1, are associated with amyotrophic lateral sclerosis, a rare and devastating disease characterized by motor neuron degeneration and patients' death within 2-5 years from diagnosis. Motor neuron loss and related symptomatology manifest mostly in adult life and, to date, there is still a gap of knowledge on the precise cellular and molecular events preceding neurodegeneration. To deepen our awareness of the early phases of the disease, we leveraged two Drosophila melanogaster models pan-neuronally expressing either the mutation A4V or G85R of the human gene SOD1 (hSOD1A4V or hSOD1G85R). We demonstrate that pan-neuronal expression of the hSOD1A4V or hSOD1G85R pathogenic construct impairs survival and motor performance in transgenic flies. Moreover, protein and transcript analysis on fly heads indicates that mutant hSOD1 induction stimulates the glial marker Repo, up-regulates the IMD/Toll immune pathways through antimicrobial peptides and interferes with oxidative metabolism. Finally, cytological analysis of larval brains demonstrates hSOD1-induced chromosome aberrations. Of note, these parameters are found modulated in a timeframe when neurodegeneration is not detected. The novelty of our work is twofold: we have expressed for the first time hSOD1 mutations in all neurons of Drosophila and confirmed some ALS-related pathological phenotypes in these flies, confirming the power of SOD1 mutations in generating ALS-like phenotypes. Moreover, we have related SOD1 pathogenesis to chromosome aberrations and antimicrobial peptides up-regulation. These findings were unexplored in the SOD1-ALS field.

Delineating Purinergic Signaling in Drosophila.

Simplistic models can aid in discovering what is important in the context of normal and pathological behavior. First recognized as a genetic model more than 100 years ago, to date, fruit flies (Drosophila melanogaster) still remain an astonishingly good laboratory stand-in for scientists to study development and physiology and to investigate the molecular mechanisms of human diseases. This is because fruit flies indeed represent a simplistic model. Furthermore, about 75% of human disease-related genes have their counterparts in the Drosophila genome, added to the fact that fruit flies are inexpensive and extremely easy to maintain, being invertebrates and, moreover, lacking any ethical concern issues. Purinergic signaling is, by definition, mediated by extracellular purinergic ligands, among which ATP represents the prototype molecule. A key feature that has progressively emerged when dissecting the purinergic mechanisms is the multilayer and dynamic nature of the signaling sustained by purinergic ligands. Indeed, these last are sequentially metabolized by several different ectonucleotidases, which generate the ligands that simultaneously activate several different purinergic receptors. Since significant purinergic actions have also been described in Drosophila, the aim of the present work is to provide a comprehensive picture of the purinergic events occurring in fruit flies.

Influence of synthetic isoflavones on selected urinary steroid biomarkers: Relevance to doping control.

In this work we have investigated the influence of the intake of two synthetic isoflavones, methoxyisoflavone and ipriflavone, on the urinary concentration of endogenous steroids, and on their relative ratios, of doping relevance. Specifically, the concentrations of testosterone (T), epitestosterone (E), androsterone (A), etiocholanolone (Etio), 5α-androstan-3α,17α-diol (5αAdiol), 5ß-androstan-3α,17α-diol (5ßAdiol), and the ratios T/E, A/T, A/Etio, 5αAdiol/5ßAdiol, 5αAdiol/E, were considered, in the framework of the Steroidal Module of the Athlete Biological Passport (ABP). The above set of parameters were complemented by the urinary levels of luteinizing hormone (total LH) and the ratio between T and LH (T/total LH), to assess the possible effects on the biosynthesis of the mentioned steroids. Five healthy Caucasian male volunteers were selected for the study. Urine samples were collected before and during the administration of (i) methoxyisoflavone (Methoxyisoflavone, MyProtein) and (ii) ipriflavone (Osteofix ®, Chiesi Farmaceutici). For the analysis of the urinary steroid profile, after enzymatic hydrolysis with ß-glucuronidase from Escherichia Coli (E. Coli) and liquid-liquid extraction with tert-buthylmethyl ether, all samples were analyzed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS), while for the determination of total LH all urine samples were directly analyzed by a chemiluminescent immunometric assay technique (Siemens Immulite 2000 LH). Our results show that the administration of either methoxyisoflavone or ipriflavone causes an alteration of the urinary concentrations and concentration ratios of the investigated steroids, in the range 55-80% from the baseline values. Furthermore, an oversecretion of LH after the daily intake of methoxyisoflavone or ipriflavone was also recorded in all volunteers, corresponding to an increase in the biosynthesis and excretion of T and some of its metabolites. These changes trigger a disregulation in the pattern of urinary excretion of the steroids included in the Steroidal Module of the ABP, which makes more difficult the interpretation of the longitudinal steroid profile based on the definition of individual normality ranges for each athlete. Our data are also consistent with previous evidence regarding the in vitro effects of natural and synthetic isoflavones, suggesting that their monitoring in doping control routine analysis would be very beneficial for the result management activities.