The importance of lipid conjugation on anti-fusion peptides against Nipah virus

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Nipah virus (NiV) is a recently emerging zoonotic virus that belongs to the Paramyxoviridae family and the Henipavirus genus. It causes a range of conditions, from asymptomatic infection to acute respiratory illness and fatal encephalitis. The high mortality rate of 40 to 90% ranks these viruses among the deadliest viruses known to infect humans. Currently, there is no antiviral drug available for Nipah virus disease and treatment is only supportive. Thus, there is an urgent demand for efficient antiviral therapies. NiV F protein, which catalyzes fusion between the viral and host membranes, is a potential target for antiviral drugs, as it is a key protein in the initial stages of infection. Fusion inhibitor peptides derived from the HRC-domain of the F protein are known to bind to their complementary domain in the protein's transient intermediate state, preventing the formation of a six-helix bundle (6HB) thought to be responsible for driving the fusion of the viral and cell membranes. Here, we evaluated the biophysical and structural properties of four different C-terminal lipid-tagged peptides. Different compositions of the lipid tags were tested to search for properties that might promote efficacy and broad-spectrum activity. Fluorescence spectroscopy was used to study the interaction of the peptides with biomembrane model systems and human blood cells. In order to understand the structural properties of the peptides, circular dichroism measurements and molecular dynamics simulations were performed. Our results indicate a peptide preference for cholesterol-enriched membranes and a lipid conjugation-driven stabilization of the peptide α-helical secondary structure. This work may contribute for the development of highly effective viral fusion against NiV inhibitors.This work was financially supported by Fundação para a Ciência e a Tecnologia—Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), through projects PTDC/BBB-BQB/3494/2014, PTDC/QUI-BIQ/114774/2009, PTDC/CCI-BIO/28200/2017 and Pest-OE/EQB/LA0004/2011, and by National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), project R01AI114736, lead by Anne Moscona (Columbia University Medical Center, NY, USA). This work was also financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT-MCTES. MCM, PMS and DL were supported by FCT-MCTES fellowships SFRH/BPD/118731/2016, SFRH/BD/118413/2016 and SFRH/BPD/92537/2013, respectively.info:eu-repo/semantics/publishedVersio

A biorefinery from Nannochloropsis sp. microalga – Energy and CO2 emission and economic analyses

Are microalgae a potential energy source for biofuel production? This paper presents the laboratory results from a Nannochloropsis sp. microalga biorefinery for the production of oil, high-value pigments, and biohydrogen (bioH2). The energy consumption and CO2 emissions involved in the whole process (microalgae cultivation, harvest, dewater, mill, extraction and leftover biomass fermentation) were evaluated. An economic evaluation was also performed. Oil was obtained by soxhlet (SE) and supercritical fluid extraction (SFE). The bioH2 was produced by fermentation of the leftover biomass. The oil production pathway by SE shows the lowest value of energy consumption, 177-245 MJ/MJprod, and CO2 emissions, 13–15 kgCO2/MJprod. Despite consuming and emitting c.a. 20% more than the SE pathway, the oil obtained by SFE, proved to be more economically viable, with a cost of 365€/kgoil produced and simultaneously extracting high-value pigments. The bioH2 as co-product may be advantageous in terms of product yield or profit

Procura-PALavras (P-PAL): a new measure of word frequency for contemporary European Portuguese

Neste trabalho apresentamos as estratégias e os procedimentos adoptados na constituição de uma nova medida de frequência lexical do Português Europeu contemporâneo, o Procura-PALavras (P- -PAL). Baseado num corpus de mais de 227 milhões de palavras, o P-PAL é uma aplicação web que oferece, por defeito, valores de frequência lexical para todas as suas entradas lexicais (lemas e formas) e que permite a computação de uma grande diversidade de outras medidas objectivas (lexicais e sublexicais) e subjectivas. Descrevemos ainda o processo de defi nição das suas entradas lexicais e da extracção dos respectivos valores de frequência. O elevado número de índices e de entradas lexicais tornam o P-PAL numa aplicação web avançada e indispensável à promoção e internacionalização da investigação em Portugal. O P-PAL encontra-se disponível em http://p-pal.di.uminho.pt/toolsIn this paper we present the strategies and procedures undertaken in the development of a new measure of lexical frequency of the contemporary European Portuguese – Procura-PALavras (P-PAL). Based on a corpus of over 227 million words, P-PAL offers the default frequency per million words (lemmas and wordforms), and the computation of several other objective (lexical and sublexical) and subjective word metrics. We also describe lexical entry integration and word frequency extraction. The high number of indices and lexical entries makes P-PAL an advanced and indispensable web application for the promotion and internationalization of Portuguese research. P-PAL is available at http://p-pal.di.uminho.pt/toolsFundação para a Ciência e a Tecnologia (FCT

Desenvolvimento, produção e caracterização de nanocristais de fármacos pouco solúveis

Poorly soluble drugs have low bioavailability, representing a major challenge for the pharmaceutical industry. Processing drugs into the nanosized range changes their physical properties, and these are being used in pharmaceutics to develop innovative formulations known as Nanocrystals. Use of nanocrystals to overcome the problem of low bioavailability, and their production using different techniques such as microfluidization or high pressure homogenization, was reviewed in this paper. Examples of drugs, cosmetics and nutraceutical ingredients were also discussed. These technologies are well established in the pharmaceutical industry and are approved by the Food and Drug Administration

Exploring Scenedesmus obliquus and nannochloropsis sp. potential as a sustianable raw material for biofuels amd high added value compounds

In this work, the authors propose a microalga-based integrated system, where optimization of several energy vectors (biodiesel, bioethanol and bioH2) is highlighted under the concept of biorefinery (Project PTDC/AAC-AMB/100354/2008). This involves the integration of different processes such as oil and sugar extraction from microalgae for biodiesel and bioethanol production respectively, and bioH2 production from the whole and/or biomass leftovers. The extraction of high value added compounds, such as carotenoids, contributes to the economic viability of the overall process

Untargeted Metabolomics Reveals Antidepressant Effects in a Marine Photosynthetic Organism: The Diatom Phaeodactylum tricornutum as a Case Study

The increased use of antidepressants, along with their increased occurrence in aquatic environments, is of concern for marine organisms. Although these pharmaceutical compounds have been shown to negatively affect marine diatoms, their mode of action in these non-target, single-cell phototrophic organisms is yet unknown. Using a Fourier-transform ion cyclotron-resonance mass spectrometer (FT-ICR-MS) we evaluated the effects of fluoxetine in the metabolomics of the model diatom Phaeodactylum tricornutum, as well as the potential use of the identified metabolites as exposure biomarkers. Diatom growth was severely impaired after fluoxetine exposure, particularly in the highest dose tested, along with a down-regulation of photosynthetic and carbohydrate metabolisms. Notably, several mechanisms that are normally down-regulated by fluoxetine in mammal organisms were also down-regulated in diatoms (e.g., glycerolipid metabolism, phosphatidylinositol signalling pathway, vitamin metabolism, terpenoid backbone biosynthesis and serotonin remobilization metabolism). Additionally, the present work also identified a set of potential biomarkers of fluoxetine exposure that were up-regulated with increasing fluoxetine exposure concentration and are of high metabolic significance following the disclosed mode of action, reinforcing the use of metabolomics approaches in ecotoxicology.info:eu-repo/semantics/publishedVersio

Dental Informatics: an emerging discipline

Este trabalho de revisão de literatura pretende demonstrar não só a importância da introdução da disciplina de Informática Odontológica no currículo das Faculdades de Odontologia mas também no cotidiano do médico-dentista ou cirurgião-dentista. Nos últimos anos houve um rápido desenvolvimento da Informática aplicada à Odontologia, sobretudo em áreas dedicadas ao exame do paciente, ao diagnóstico e ao plano de tratamento. Os sistemas CAD-CAM, as sondas periodontais computadorizadas, os aparelhos de radiologia digital, as câmaras intra-orais são exemplos da aplicação da Informática em Odontologia. É neste sentido que surge a disciplina de Informática Odontológica, uma área em constante desenvolvimento, que tem por base a aplicação de computadores e ciências de informação para melhorar a prática clínica, a pesquisa, a educação e a gestão. É importante que simultaneamente com a formação em Odontologia haja também adequada formação em Informática Odontológica. Atualmente os avanços tecnológicos e as pesquisas científicas requerem interdisciplinaridade e integração de uma grande quantidade de informação, muitas vezes proveniente de fontes díspares, havendo necessidade de compilar a informação em bases de dados. Os meios informáticos podem aumentar significativamente a velocidade de integração e correlação dessa informação, tornando o diagnóstico médico-odontológico mais rápido e a implementação da terapêutica mais eficaz. Palavras-chave: Informática Odontológica; bioinformática; base de dados; formação odontológica; diagnósticoThis literature review aimed to present the importance of the discipline of Dental Informatics for the curriculum of dental schools and daily dental practice. In the last years there was a fast development of Informatics applied to Dentistry, especially in areas related to patient exam, diagnosis, and treatment plan. CAD-CAM systems, computerized periodontal probes, digital radiography, and intraoral cameras are examples of the application of Informatics in Dentistry. Dental Informatics is a discipline showing constant development and is based on the application of computers and information science to improve clinical practice, research, education, and management. Therefore, it is important that Dental Informatics is included in the dental curriculum. At present the technological advances and scientific research require interdisciplinary approach and integration of large amount of information. This information usually comes from several sources, which requires its compilation in databases. Informatics media can significantly increase the velocity of integration and correlation of necessary information to speed up the medical-dental diagnosis and improve treatment efficacy. Key words: Dental informatics; bioinformatics, databases; dental education; diagnosisinfo:eu-repo/semantics/publishedVersio

β-cyclodextrin/isopentyl caffeate inclusion complex: synthesis, characterization and antileishmanial activity

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in -cyclodextrin (-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.This research was funded by Banco do Nordeste (grant FUNDECI/2016.0015), Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017-00 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019) and from the Portuguese Science and Technology Foundation (FCT) project UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

P-PAL: uma base lexical com índices psicolinguístico do português europeu

Neste trabalho apresentamos o projecto Procura-PALvras (P-PAL) cujo principal objectivo é desenvolver uma ferramenta electrónica que disponibilize informação sobre índices psicolinguísticos objectivos e subjectivos de palavras do Português Europeu (PE). O P-PAL será disponibilizado gratuitamente à comunidade científica num formato user-friendly a partir de um website a construir para o efeito. Ao utilizar o P-PAL, o investigador poderá fazer uma utilização personalizada do programa ao seleccionar, da ampla variedade de análises oferecidas, os índices que se adequam aos propósitos da sua investigação e numa dupla funcionalidade de utilização: pedir ao programa para analisar listas de palavras previamente constituídas nos índices considerados relevantes para a investigação ou para obter listas de palavras que obedeçam aos parâmetros definidos. O P-PAL assume-se assim como uma ferramenta fundamental à promoção e internacionalização da investigação em Portugal.Fundação para a Ciência e a Tecnologia (FCT)Fundo Europeu de Desenvolvimento Regional (FEDER

Percutaneous vs. surgical treatment of patent ductus arteriosus in children and adolescents

INTRODUÇÃO: Estudos comparando os métodos percutâneo e cirúrgico no tratamento da persistência do canal arterial (PCA) são raros na literatura. Nosso objetivo foi realizar análise comparativa entre os dois métodos de tratamento da PCA, enfatizando os aspectos de eficácia e morbidade. MÉTODOS: Estudo observacional com 2 coortes de crianças e adolescentes &gt; 5 kg e < 14 anos, portadores de PCA, tratados durante um projeto de avaliação de incorporação de novas tecnologias ao Sistema Único de Saúde (SUS), realizado em um hospital cardiológico de excelência, em parceria com o Ministério da Saúde do Brasil. Foi feita análise prospectiva no grupo percutâneo entre 2009 e 2011 e retrospectiva no grupo cirúrgico entre 2006 e 2011. RESULTADOS: Foram incluídos 80 pacientes no grupo percutâneo (60% do sexo feminino) e 39 no grupo cirúrgico (51% do sexo feminino; P = 0,37). A mediana de idade e de peso dos grupos percutâneo e cirúrgico foi de 39,4 meses vs. 25,5 meses (P = 0,04) e de 14 kg vs. 11,1 kg (P = 0,052), respectivamente. No grupo percutâneo, 78 pacientes (92%) tinham PCA do tipo A e o diâmetro mínimo do canal à angiografia foi de 2,5 ± 1,2 mm. As próteses mais utilizadas foram Amplatzer®, molas de Gianturco e CeraTM. A técnica cirúrgica mais utilizada foi a clipagem. A taxa de sucesso dos procedimentos foi de 100% nos dois grupos. O grupo cirúrgico apresentou maiores taxas de complicação, incluindo quilotórax, infecções, necessidade de hemoderivados, hipertensão arterial sistêmica e uso de opioides, como também maior necessidade de terapia intensiva. A mediana do tempo de internação foi de 1,3 dia no grupo percutâneo e de 7,9 dias no grupo cirúrgico (P < 0,01). À alta hospitalar, as taxas de oclusão foram semelhantes nos dois grupos (91% no grupo percutâneo e 87% no grupo cirúrgico; P = 0,71). CONCLUSÕES: Em decorrência da menor morbidade, do menor tempo de internação e da igual eficácia, o tratamento percutâneo da PCA deve ser considerado a modalidade terapêutica de escolha para pacientes selecionados