Protein Synthesis Attenuation by Phosphorylation of eIF2α Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms

Chagas' disease is a potentially life-threatening illness caused by the unicellular protozoan parasite Trypanosoma cruzi. It is transmitted to humans by triatomine bugs where T. cruzi multiplies and differentiates in the digestive tract. The differentiation of proliferative and non-infective epimastigotes into infective metacyclic trypomastigotes (metacyclogenesis) can be correlated to nutrient exhaustion in the gut of the insect vector. In vitro, metacyclic-trypomastigotes can be obtained when epimastigotes are submitted to nutritional stress suggesting that metacyclogenesis is triggered by nutrient starvation. The molecular mechanism underlying such event is not understood. Here, we investigated the role of one of the key signaling responses elicited by nutritional stress in all other eukaryotes, the inhibition of translation initiation by the phosphorylation of the eukaryotic initiation factor 2α (eIF2α), during the in vitro differentiation of T. cruzi. Monospecific antibodies that recognize the phosphorylated Tc-eIF2α form were generated and used to demonstrate that parasites subjected to nutritional stress show increased levels of Tc-eIF2α phosphorylation. This was accompanied by a drastic inhibition of global translation initiation, as determined by polysomal profiles. A strain of T. cruzi overexpressing a mutant Tc-eIF2α, incapable of being phosphorylated, showed a block on translation initiation, indicating that such a nutritional stress in trypanosomatids induces the conserved translation inhibition response. In addition, Tc-eIF2α phosphorylation is critical for parasite differentiation since the overexpression of the mutant eIF2α in epimastigotes abolished metacyclogenesis. This work defines the role of eIF2α phosphorylation as a key step in T. cruzi differentiation

Financial compensation due to municipalities that host radioactive waste deposits

This work aims to perform calculation about the financial compensation due to municipalities where there is viability for construction of radioactive waste deposits from low and medium activity. Were used like base structure de Resolution No. 96 of August, 10, 2010, entitled “Model of Calculation For Financial Compensation to Municipalities” where are determinate those principal characteristics by the waste and deposits, such as the half-life, activity level, type of deposits (initial, intermediate or final), costs for construction and maintenance of deposits, demography, between others. The calculation was made according to the temporally or definitive storage for solids waste like personal protection equipment (gloves, shoes, masks, etc) resins and filters used in wastewater treatment, between others, from of nuclear and radioactivity facilities. There are presented some countries that do the compensation, financial or not, for some municipalities for the construction of waste deposits and in some cases, the way that occurred the negotiation between the stakeholders, in other words, the local population and the companies. Also are presented others forms of financial compensation in Brazil in consequence of activities in large scale which result in potential risk for the surrounding population and for the environment, like compensation for oil and natural gas, hydropower plants and mining. Were used on methodology the inventory of waste presented on RMBN project (Repository of Waste of Low and Medium Activity) developed by the CDTN which present the implementation of a repository for final storage to radioactive waste. With this was possible to develop a case study with the creation of four scenarios. Values were found which initially range from R$2,6 mil to R$79,8 mil for month. Finally are analyzed the possible influences which that values may have on the municipality budget revenue and som

Design and construction of a didactic standalone photovoltaic plant

This paper proposes the design and construction of a standalone didactic photovoltaic (PV) plant. The system components are available as a didactic kit to the students of the Federal Institute of Education, Science and Technology of Ceará (IFCE), Brazil. Thus, contributing to the teaching-learning process and providing a system to be used in future researches. In addition, the system was designed for supplying electricity to the lighting circuit of the Energy Processing Laboratory, located at IFCE Fortaleza Campus. The PV system developed during the work has an autonomy of 900 Ah and the total installed power of 840 Wp. Using a data capture system, a generation generated by the PV microgeneration was registered in operation up to 647 W

Nanostructures as conveyors of functionality in foods: the case of cannabidiol-based nanostructured lipid carriers

Nanostructures incorporating functional compounds have earned their place as a very efficient means of conveying functionality in foods. They may be used to tackle malnutrition, reduce calorie density, reduce food digestibility, increase micronutrient bioavailability, control gut health, allow personalized nutrition and provide appropriate food for the elderly, among other potential uses. Building such nanostructures, particularly when considering that they need to be edible, is a challenging task. This keynote will address the latest developments made by our research group towards tackling some of these challenges, together with our vision on what still needs to be done and which partnerships are important to lead us to further improve their performance. The incorporation of cannabidiol (CBD) into nanostructured lipid carriers (NLC) will be given as an example of a potential solution to mitigate its low bioavailability, which represents a big challenge for the development of CBD-products. Some details regarding their development (e.g., using innovative emulsifiers) will be provided and the consequences in the stability of CBD will be analysed.info:eu-repo/semantics/publishedVersio

Erythema multiforme induced by alendronate sodium in a geriatric patient : a case report and review of the literature

Erythema multiforme is an uncommon acute inflammatory disorder caused by exposure to microbes or drugs. Erythema multiforme minor typically affects only one mucosa and can be associated with symmetrical target skin lesions on the extremities. The disease usually occurs in patients in their 3rd and 4th decade of life, but can also affect children and adolescents. Alendronate sodium has been approved for the prevention and treatment of osteoporosis in postmenopausal women, but is associated with adverse events. This study reports and discusses a case of erythema multiforme minor. In addition, a literature search of articles published in PubMed-Medline was performed. The case was a 96-year-old woman who had taken alendronate. Intraoral clinical examination demonstrated hypersalivation and macrocheilia of the lower lip, associated with an ill-defined ulcer with erythematous borders measuring 20 mm in greatest diameter and covered with serofibrinous exudates. The aging of the population in developed and developing countries has increased the use of alendronate sodium to prevent osteoporosis and clinicians should be aware of possible oral adverse events associated with this drug

Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase

This work describes the synthesis of a series of sialylmimetic neoglycoconjugates represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives containing galactose modified at either C-1 or C-6 positions, glucose or gulose at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine-3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-functionalized sugars 1-N(3)-Gal (commercial), 6-N(3)-Gal, 3-N(3)-Glc and 3-N(3)-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N(3)-ThrOBn with 3-O-propynyl-GalOMe. the 1,2,3-triazole linked sialic acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma cruzi trans-sialidase (TcTS) inhibitory activity at 1.0 mM (approx. 90%), whilst only the former displayed relevant trypanocidal activity (IC(50) 260 mu M). These results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a prototype for further design of new neoglycoconjugates against Chagas' disease. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)USP, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP, BrazilUSP, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilWeb of Scienc

Development and characterization of nanostructured lipid carriers for cannabidiol delivery

Supplementary data to this article can be found online at https://doi.org/10.1016/j.foodchem.2023.138295.This study evaluated the physicochemical characteristics of nanostructured lipid carriers (NLCs) as a potential vehicle for cannabidiol (CBD), a lipophilic molecule with great potential to promote health benefits. NLCs were produced using hemp seed oil and fully-hydrogenated soybean oil at different proportions. The emulsifiers evaluated were soybean lecithin (SL), Tween 80 (T80) and a mixture of SL:T80 (50:50). CBD was tested in the form of CBD-rich extract or isolate CBD, to verify if it affects the NLCs characteristics. Based on particle size and polydispersity, SL was considered the most suitable emulsifier to produce the NLCs. All lipid proportions evaluated had no remarkable effect on the physicochemical characteristics of NLCs, resulting in CBD-loaded NLCs with particle size below 250 nm, high CBD entrapment efficiency and CBD retention rate of 100% for 30 days, demonstrating that NLCs are a suitable vehicle for both CBD-rich extract or isolate CBD.This study received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie SkłodowskaCurie grant agreement No 101062938 and was supported by Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, and by LABBELS – Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020. Fernanda L. Lüdtke thanks Iceland Liechtenstein Norway Grants (PT-INNOVATION-0105) for the fellowship

Perspectives of PV Microgeneration in Brazil: A Proposition of Regulation Enhancement Methodology

The solar photovoltaic (PV) generation is disseminating on multiple kinds of sites due to the energy market liberalization, the renewable energy sources subsidies policy, the decreasing of acquisition costs and the adaptability to different installation conditions. These factors allowed the growth of PV generation, especially in the distributed generation (DG) segment. Meanwhile, the development of a legal and regulatory apparatus became mandatory to assure benefits to DG-adopters, without causing damages to the utility grid, preventing technical failures and eventual excessive pricing to non-adopters. As the technology innovations impose new possibilities and the number of adopters grows exponentially, the challenges become more visible and a regulation update, urgent. In this context, this paper aims to review the current pricing model for DG in Brazil, focusing on PV microgeneration, and to propose a methodology based on the Delphi Method to enhance the most critical topics of the on-going regulation