New frontiers in remediation of (micro)plastics

Plastic pollution is increasing daily, raising social, environ- mental, and economic concerns. Along with the reduction policies on plastic use and consumption, and improvement of waste management systems, it is of utmost importance to develop and implement remediation and emission control measures. Focused on the most recent literature, this article provides a critical overview and in-depth discussion on breakthrough technological and biotechnological research that may sustain an effective and efficient (micro)plastic remedia- tion in the near future.publishe

Calcific uraemic arteriolopathy - A mini-review

Calcific Uraemic Arteriolopathy (CUA) or calciphylaxis, is a thrombotic disorder of skin and subcutaneous tissue which typically presents with painful purpuric nodules that may progress to necrotic ulcers, and is a severe, life-threatening condition. CUA is an uncommon clinical entity that affects mostly haemodialysis (HD) patients. Although the process of vascular calcification was initially thought to be the result of a passive deposition of calcium-phosphate crystals, current knowledge suggests a distinct mechanism, including cellular activity with differentiation of vascular smooth muscle cells (VSMCs) into chondrocyte as well as osteoblast-like cellular phenotypes and deficiencies in calcification inhibitors. Although multiple studies suggest a potential relationship between warfarin and CUA, larger prospective studies are needed in order to better evaluate this association, and randomised controlled trials are needed to assess the benefit of distinct interventions in this setting. In this article the topic of CUA is reviewed based on a clinical case of a 65-year-old man undergoing haemodialysis, who underwent an aortic valve replacement one year earlier, receiving a mechanical heart valve, and who has been under warfarin therapy since the

A role for the small GTPases RAC1 and RAC1b in the modulation of NIS expression: potentiation of therapy with radioactive iodine in differentiated thyroid carcinoma

Introduction or Background: The Sodium Iodide Symporter (NIS) is responsible for active transport of iodide into thyroid follicular cells. The retention of its functional expression in most of the well-differentiated thyroid carcinomas (DTCs) enables the use of radioactive iodine (RAI) for treatment of metastatic disease. Still, about 30% of patients with advanced forms of DTC became refractory to RAI which makes their management very challenging. The main reason for impaired iodide uptake in refractory-DTC is the defective functional expression of NIS. Several molecular players have been described as critical for TSH-induced NIS expression, an example being the p38 mitogenic kinase. In breast cancer cells, the small GTPase RAC1 was shown to mediate the positive impact of p38 kinase activity on NIS expression. We, on the other hand, have previously shown that overexpression of RAC1b, a tumor-related splicing variant of RAC1, is associated with worse outcomes in DTC and correlates with the MAPK-activating BRAFV600E mutation, which has been related to the loss of NIS. Since RAC1 and RAC1b may act in an antagonistic fashion to regulate specific cellular responses, we asked if RAC1b would be implicated in NIS downregulation observed in DTCs. Methods Section: NIS expression levels were analyzed by RT-qPCR in a RAC1/RAC1b expression model system developed in non-transformed thyroid cell lines. A non-radioactive iodide influx assay was used to confirm the impact of RAC1-signaling on the efficacy of iodide uptake. Results Section: We demonstrate that ectopic overexpression of RAC1b is sufficient to decrease TSH-induced NIS expression, antagonizing the positive effect of RAC1 GTPase. Moreover, we clearly document, for the first time in thyroid cells, that both NIS expression and iodide uptake are downregulated upon RAC1 inhibition, supporting the role of canonical RAC1 signaling in promoting TSH-induced NIS expression. Conclusion: Our findings provide evidence that RAC1 and RAC1b signaling are implicated in the regulation of NIS expression in thyroid cells and suggest that RAC1b overexpression may be one of the mechanisms contributing to the low levels of NIS observed in some subgroups of DTCs, antagonizing RAC1 stimulatory effect on the TSH/cAMP-mediated induction of NIS expression.FCT - PTDC/BIAMOL/31787/2017N/

Atiya-Bott theory for orbifolds and Dedkind sums

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mathematics, 1994.Includes bibliographical references (leaf 17).by Ana M.L.G. Canas da Silva.M.S

Lipid-free Antigen B subunits from echinococcus granulosus: oligomerization, ligand binding, and membrane interaction properties

Background: The hydatid disease parasite Echinococcus granulosus has a restricted lipid metabolism, and needs to harvest essential lipids from the host. Antigen B (EgAgB), an abundant lipoprotein of the larval stage (hydatid cyst), is thought to be important in lipid storage and transport. It contains a wide variety of lipid classes, from highly hydrophobic compounds to phospholipids. Its protein component belongs to the cestode-specific Hydrophobic Ligand Binding Protein family, which includes five 8-kDa isoforms encoded by a multigene family (EgAgB1-EgAgB5). How lipid and protein components are assembled into EgAgB particles remains unknown. EgAgB apolipoproteins self-associate into large oligomers, but the functional contribution of lipids to oligomerization is uncertain. Furthermore, binding of fatty acids to some EgAgB subunits has been reported, but their ability to bind other lipids and transfer them to acceptor membranes has not been studied.<p></p> Methodology/Principal Findings: Lipid-free EgAgB subunits obtained by reverse-phase HPLC were used to analyse their oligomerization, ligand binding and membrane interaction properties. Size exclusion chromatography and cross-linking experiments showed that EgAgB8/2 and EgAgB8/3 can self-associate, suggesting that lipids are not required for oligomerization. Furthermore, using fluorescent probes, both subunits were found to bind fatty acids, but not cholesterol analogues. Analysis of fatty acid transfer to phospholipid vesicles demonstrated that EgAgB8/2 and EgAgB8/3 are potentially capable of transferring fatty acids to membranes, and that the efficiency of transfer is dependent on the surface charge of the vesicles.<p></p> Conclusions/Significance: We show that EgAgB apolipoproteins can oligomerize in the absence of lipids, and can bind and transfer fatty acids to phospholipid membranes. Since imported fatty acids are essential for Echinococcus granulosus, these findings provide a mechanism whereby EgAgB could engage in lipid acquisition and/or transport between parasite tissues. These results may therefore indicate vulnerabilities open to targeting by new types of drugs for hydatidosis therapy.<p></p&gt

Oxidative damage and decreased aerobic energy production due to ingestion of polyethylene microplastics by Chironomus riparius (Diptera) larvae

Riverine sediments are major sinks of microplastics from inland anthropogenic activities, imposing a threat to freshwater benthic invertebrates. This study investigated the ingestion of three size-classes (SC) of irregularly shaped polyethylene microplastics (PE-MPs; SC I: 32-63 μm; II: 63-250 μm; III: 125-500 μm) after 48 h by dipteran larvae (detritivore/collector) Chironomus riparius, and the consequent effects on neurotransmission, energy allocation and oxidative stress. The tested PE-MPs concentrations (1.25; 5; 20 g kg-1) were within the range of concentrations reported in riverbanks from highly urbanised areas (1 - 9 g kg-1), except for 20 g kg-1 representing the worst-case scenario. After exposure to SC I, larvae presented high amounts (up to ∼2400 particles/organism) of PE-MPs in their guts, with an average size-range of 30-60 μm. In the SC II and III, larvae presented PE-MPs of higher diameter (up to 125 μm) and a visible gut obstruction. The high number of particles in the larval gut (SC I) and/or difficulties for their egestion (SC I, II and III) induced oxidative damage and reduced aerobic energy production. In addition, larvae exposed to SC II and III revealed depletion in their total lipid reserves as a consequence of lacking nutrients, and the ones exposed to SC III presented a decrease in their detoxification capacity. These results highlight that freshwater detritivores with low selective feeding behaviour (e.g., chironomids) are more prone to ingest microplastics, with potentially adverse effects on cellular metabolism, redox status and antioxidant-detoxification defences. These harmful effects at lower levels of the biological organisation may ultimately affect organisms' physiology and fitness.publishe

Menthol-based deep eutectic systems as antimicrobial and anti-inflammatory agents for wound healing

Funding Information: This work received funding from Foundation for Science and Technology (FCT) , through project PTDC/BBB- 490 EBB/1676/2014 – Des.Zyme and ERC-2016-CoG 725034 (ERC Consolidator Grant Des.solve). E.S. and J.S. would also like to acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through the doctoral grant with reference number SFRH/BD/143902/2019 and postdoctoral contract CEECIND/01026/2018 , respectively. Publisher Copyright: © 2022Effective antimicrobial treatment has been identified as a serious and unmet medical need. Herein, we present a strategy based on deep eutectic systems (DES) to overcome current limitations, answering the need not only to effectively kill bacterial agents but also to avoid their adhesion and proliferation, which is associated with biofilm formation and have a crucial impact on bacterial virulence. To achieve such a goal, natural deep eutectic systems (NADES) based on menthol (Me) and saturated free fatty acids (FFA) were produced, fully physicochemical characterized, and its bioactive properties were described. The antimicrobial potential of menthol-based NADES with FFA, namely, myristic acid (MA), lauric acid (LA), and stearic acid (SA) were investigated towards a broad panel of microorganisms. The obtained data indicates that NADES possess effective antimicrobial properties towards the Gram-positive bacterial and fungal strains tested. Among the tested formulations, Me:LA at a molar ratio of 4:1 molar was used to carry out a biofilm detachment/removal assay due to is superior microbiological properties. This formulation was able to effectively lead to biofilm removal/dispersion of not only methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans, but also Escherichia coli, without the need of any additional physical force or antibiotic. Furthermore, since microbial invasion and biofilm formation is highly undesired in wound healing, namely in chronic wound healing, the wound healing properties of these eutectic formulations was also investigated. The results suggest that these NADES can cope with microbial invasion and biofilm detachment while not compromising normal keratinocyte proliferation and migration verified in wound healing and epidermis repair, while also contributing to the reduction of cell stress and inflammation via the control of ROS production. In conclusion, these results provide the indication that NADES based on Me and FFA holds great interest as antimicrobial agents for preventive and therapeutic applications in various clinical settings, including wound healing.publishersversionpublishe