Characterization of the Lassa virus GP1 ectodomain shedding: implications for improved diagnostic platforms

<p>Abstract</p> <p>Background</p> <p>There is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of Lassa fever. In this regard, detection of early markers of Lassa virus (LASV) infection may improve diagnosis and ultimately successful treatment with antivirals. Characterization of LASV GP1 ectodomain shedding is an important step toward developing sensitive diagnostics to detect circulating levels of this viral glycoprotein in infected patient sera.</p> <p>Results</p> <p>Secretion of GP1 from mammalian cells expressing a native LASV GPC gene was not mediated by proteolytic cleavage, as determined by treatment with a panel of matrix metalloprotease (MMP) inhibitors. The shedding of GP1 was also not the result of over-expression of GPC under the control of a strong intron-A containing CMV promoter, as the soluble component could be immunoprecipitated from supernatants of cells expressing low levels of GPC under the control of an intronless promoter. Cells transfected with GPC retained surface membrane-associated expression of GP1 as determined by immunofluorescence assay, in addition to secreting the glycoprotein.</p> <p>Secreted GP1 derived from GPC expression has a higher content of high mannose N-linked glycosylation than sGP1 expressed independently from the GP2 portion of the protein. Neither GP1 isoform contains sialylated N-glycans, O-linked carbohydrate chains, or galactose-β(1-4)-N-acetylglucosamine commonly present in complex and hybrid N-glycan structures.</p> <p>Conclusion</p> <p>These results demonstrate the non-proteolytic secretory nature of GP1 shedding during expression of the arenaviral glycoprotein complex. This phenomenon parallels shedding of a secretory glycoprotein component in filovirus replication. The glycosylation pattern of soluble GP1 resulting from expression of GPC was different from that of a soluble GP1 construct (sGP1-RRAA-FLAG), highlighting the intricately orchestrated post translational processing of the LASV glycoprotein complex.</p

Robustness of timber structures in seismic areas

Major similarities between robustness assessment and seismic design exist, and significant information can be brought from seismic design to robustness design. As will be discussed, although some methods and limitations considered in seismic design can improve robustness, the capacity of the structure to sustain limited damage without disproportionate effects is significantly more complex. In fact, seismic design can either improve or reduce the resistance of structures to unforeseeable events, depending on the structural type, triggering event, structural material, among others. Based on a case study, the influence of redundancy and ductility on the seismic behavior and robustness of a long-span timber structure is assessed.COST E 5

Recent Advances in Sustainable Organocatalysis

The recent advances on green and sustainable organocatalysis are revised in this chapter. An important focus on one of the 12 principles of green chemistry, organocatalysis pursues to reduce energy consumption as well as to optimize the use of different resources, targeting to become a sustainable strategy in organic chemical transformations. In last decades, several experimental methodologies have been performed to make organocatalysis an even greener and sustainable alternative to stoichiometric approaches as well as non-catalytic conditions by the use of benign and friendlier reaction media. In this line, several approaches using water as preferential solvent, alternative solvents such as ionic liquids including chiral ones, deep eutectic solvents, polyethylene glycol (PEG), supercritical fluids and organic carbonates or solvent-free methodologies have been reported. In this chapter, we mainly focus on the recent remarkable advancements in organocatalysis using green and sustainable protocols

Photo-Organocatalysis, Photo-Redox, and Electro- Organocatalysis Processes

The research involving photo-organocatalysis, photoredox, and electro-organocatalysis processes is revised in this chapter. Modern synthetic processes enable the formation of large arrays of organic molecules with precise control over their three-dimensional structure, which is important in a variety of fields ranging from pharmaceutical to materials science. Photochemical reactions may have a substantial impact on these fields by affording direct access to specific structural motifs that are difficult to construct otherwise. The conjugate structural feature shown by most of the photo-organocatalysts seems to enable the production of free radicals or radical ions in an easy fashion. Electro-organocatalysis has also received recent interest from both academia and industry. In this chapter, we mainly review recent remarkable advancements in organocatalysis involving photo-, photoredox, and electrochemical processes with particular emphasis on asymmetric protocols

Recent advances of metallocenes for medicinal chemistry

This work was supported by LAQV-REQUIMTE; Fundacao para a Ciencia e Tecnologia (FCT, Portugal), through projects and the IF researcher consolidator contract (IF/0041/2013/CP1161/CT005), and Solchemar Company.Background: The recent advances for the synthesis and application of different metallocenes for Medicinal Chemistry is reviewed. Objective: This manuscript presents the different metallocene scaffolds, with special emphasis on ferrocene derivatives, and their potential pharmaceutical application. Over the last years, the synthesis of new metallocene compounds and their biological and medicinal effects against some types of diseases (e.g. anti-tumoral, antibiotics, anti-viral) have been reported. From the medicinal point of view, the attractive properties of metallocene derivatives, such as their high stability, low toxicity and appealing redox behaviors are particularly relevant. Results: This area has attracted many researchers as well as the pharmaceutical industry due to the promising results of some metallocenes, in particular ferrocene compounds, in breast cancer and malaria.authorsversionpublishe

Crescimento e qualidade da carcaça de suinos Landrace X Large White submetidos a acabamento intensivo até elevado peso de abate

Ao longo dos últimos anos, em muitos países, e como já é habitual em Itália, o peso vivo de abate de suínos tem registado um progressivo aumento, o que tem sido possível devido ao melhoramento genético de raças industriais, com potencial para produzir mais carne magra. Utilizaram-se 30 suínos, F1 cruzados de Landrace x Large White, castrados, submetidos a acabamento intensivo com alimento composto (Energia Bruta 3833 kcal / kg MS), distribuído ad libitum, até um peso elevado ao abate (90-160 kg de PV). Avaliou-se o desempenho produtivo dos animais, espessura da gordura e profundidade do Longissimus dorsi, in vivo, e peso de carcaça. Os animais foram pesados semanalmente e a ingestão de alimento controlada, individual e diariamente, permitindo calcular os GMD e IC. Efetuaram-se diversas medições, in vivo, da espessura da gordura (P1 - linha média da última vertebra torácica, P2 - a 6 cm da linha média ao nível da última vertebra torácica e P3 - linha média da última vertebra lombar) e da profundidade do Longissimus dorsi, por ultra-sonografia, aos 90, 120 e 160 kg PV. Os animais foram abatidos em matadouro experimental, registando-se o peso de carcaça, a quente e a frio (24 h post mortem), bem como o total das gorduras rejeitadas e miudezas. Os GMD dos animais foram de 828,3 ± 110,3 g e de 673,1 ± 112,2 g, nos períodos 90-120 kg e 120- 160 kg, respetivamente, o que representa um decréscimo de 19% do GMD, entre os períodos considerados. Nos mesmos períodos, os IC foram de 4,27 ± 0,32 e de 4,99 ± 0,49, representando um incremento de 17%. O consumo médio de alimento foi de 3,34 kg / dia. Para as três medições de espessura da gordura efetuadas e da profundidade do Longissimus dorsi, registou-se um crescimento constante ao longo do ensaio, no total de 1,1 cm, e de 1,2 cm, respetivamente. Observou-se apenas uma diferenciação do crescimento do P2, menos acentuado entre os 90 e os 120 kg, mas recuperando, no período 120-160 Kg. Os pesos médios da carcaça, a quente e a frio, foram respectivamente 132,1 Kg e 130 kg, representando 82,4% e 81% do peso vivo ao abate. Obteve-se um peso médio da perna (com chispe) de 19 kg. Os resultados obtidos indiciam uma possível utilização deste cruzamento na produção de suínos em sistema intensivo com objetivo de produção de pernas para presunto e com aproveitamento das restantes peças cárneas.info:eu-repo/semantics/publishedVersio

Protic ionic liquids as electrolyte for electrochemical CO2 reduction [Resumo]

ABSTRACT: Ionic liquids have been considered a promising material under investigation for integration of CO2 capture and electrochemical reduction, due to their recognized sustainability and tunable properties. During previous works, the development of an electrochemical process to produce syngas (CO+H2) using electrolytes based on 1-ethyl-3-methyl-imidazolium trifluoromethanosulfate [EMIM][OTf] was reported [1-2]. A more recent work reported the effect of replacing the 1-ethyl-3-methyl-imidazolium cation [EMIM] by 1-ethyl-3-picolinium [C2-3-pic] and 1-ethyl-4-picolinium [C2-4-pic] cations as electrolyte for electrochemical reduction of CO2 at pressures higher than atmospheric [3]. The objective of this work is to study the influence of protic ionic liquids-based electrolytes in electrochemical CO2 reduction. In this context, protic ionic liquids prepared by direct protonation of different imidazolium compounds using suitable organic acids have been investigated. All electrolytes are characterized by cyclic voltammetry and electrochemical impedance spectroscopy to evaluate their electrochemistry behavior for CO2 electroreduction processes. Productivities of gaseous products resulting from the co-electrolysis of CO2 and water together with their faradaic efficiencies have been also determined.info:eu-repo/semantics/publishedVersio

Highly water soluble room temperature superionic liquids of APIs

Fundacao para a Ciencia e a Tecnologia through project (PEst-C/LA0006/2013). The authors also thank Prof. Madalena Dionisio and Dr Natalia Correia for their support with the DSC analyses.Herein a straightforward approach for the enhancement of the water solubility of common antibiotic and NSAID active pharmaceutical ingredients (APIs) is presented. The APIs are converted into ionic liquids (API-ILs) and molten salts by combination with the organic superbases TMG, DBU and DBN. The prepared superionic liquids were characterized by 1H and 13C NMR as well as FTIR spectroscopy and elemental analysis. Most products are amorphous non-polymorphic room temperature ionic liquids with very high solubility in water, which may enhance the bioavailability of the API-ILs in comparison with the parent drugs.authorsversionpublishe

Imidazolium and picolinium-based electrolytes for electrochemical reduction of CO2 at high pressure

ABSTRACT: Ionic liquids (ILs) have been considered among one of the most promising materials under investigation for integration of CO2 capture and electrochemical reduction (ECR). In the design of an IL-based electrolyte that can be employed industrially, the understanding of the influence of IL structure on ECR was considered essential. In this context, electrolytes with trifluoromethanosulfonate (OTf) anion were investigated as aqueous electrolytes for electrochemical reduction of CO2 at high pressure and near room temperature with zinc electrodes. The effect of replacing the 1-ethyl-3-methyl-imidazolium cation [EMIM] by 1-ethyl-3-picolinium [C2(3)pic] and by 1-ethyl-4-picolinium [C2(4)pic] cations was studied. The use of picolinium-based electrolytes in ECR is for the first time reported. A high-pressure single compartment test bed was used for electrolyte screening. Carbon monoxide productivities and selectivities were determined for the several electrolytes with different water contents. The electrolytes were characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Electrolyte conductivities and diffusion coefficients were estimated. The effect of the cations is complex as it affects conductivity, double layer structure, reaction reversibility and even the ionic liquid physical state. Notwithstanding, it is possible to tune these properties to achieve similar CO productions with reduced IL amounts, considering the nature of the cation and the water content, leading to the design of more cost effective electrolytes for efficient ECR process.info:eu-repo/semantics/publishedVersio

Advances in electrochemical reduction of CO2 in ionic liquid-based electrolytes [Resumo]

ABSTRACT: Electrochemical reduction of CO2 was for the first time reported in 1870 [1], but it was only after 2010 that this field was the subject of intense research efforts. The use of renewable electricity to convert CO2 into products that are currently derived from fossil products and have high carbon footprint will certainly make this technology one pillar of a sustainable chemical industry. The scepticism towards the availability of cost effective products derived from CO2 electro-reduction that customers will be willing to buy has shifted to the belief that they can be commercially viable. Turning electrochemical CO2 reduction into a commercial technology will depend on economics, on the price of electricity, efficiency of the process and the value of the products. One way to improve the economics and improve the efficiency of the process is to integrate CO2 capture with conversion [2,3]. In this way the energy intensive regeneration step of the capture media can be eliminated and also CO2 transportation and storage. Ionic liquids are ideal media to achieve this integration, due to high CO2 adsorption capacity, high selectivity, wide electrochemical windows and nearly zero vapour pressure. The present work reports the progress of electrochemical reduction of CO2 in ionic liquids and the work of the authors in this field. It has been recognized that ionic liquids promote CO2 electro-reduction through lowering the reduction potential, the suppression of the competing hydrogen evolution reaction and by increasing the selectivity towards the target products. However, the understanding of the interactions between ionic liquids, CO2 and catalyst is still quite limited, but fundamental for synthetizing more efficient electrolytes for CO2 electro-reduction [4]. Thus, current cation and anion effects will be analysed and an overview of the current performance of heterogeneous electro-catalysts in ionic liquid- based electrolytes for CO2 electro-reduction will be provided.N/