Dengue and Zika viruses : epidemiological history, potential therapies, and promising vaccines

© 2020 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 (http://creativecommons.org/licenses/by/4.0/).Dengue virus (DENV), which can lead to fatal hemorrhagic fever, affects 390 million people worldwide. The closely related Zika virus (ZIKV) causes microcephaly in newborns and Guillain-Barré syndrome in adults. Both viruses are mostly transmitted by Aedes albopictus and Aedes aegypti mosquitoes, which, due to globalization of trade and travel alongside climate change, are spreading worldwide, paving the way to DENV and ZIKV transmission and the occurrence of new epidemics. Local outbreaks have already occurred in temperate climates, even in Europe. As there are no specific treatments, these viruses are an international public health concern. Here, we analyze and discuss DENV and ZIKV outbreaks history, clinical and pathogenesis features, and modes of transmission, supplementing with information on advances on potential therapies and restraining measures. Taking advantage of the knowledge of the structure and biological function of the capsid (C) protein, a relatively conserved protein among flaviviruses, within a genus that includes DENV and ZIKV, we designed and patented a new drug lead, pep14-23 (WO2008/028939A1). It was demonstrated that it inhibits the interaction of DENV C protein with the host lipid system, a process essential for viral replication. Such an approach can be used to develop new therapies for related viruses, such as ZIKV.This research was supported by Fundação para a Ciência e a Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and Calouste Gulbenkian Foundation (FCG, Portugal) project Science Frontiers Research Prize 2010. N.M.S. acknowledges FCT-MCTES fellowship SFRH/BD/144585/2019. I.C.M. acknowledges FCT-MCTES program “Concurso de Estímulo ao Emprego Científico” (CEECIND/01670/2017).info:eu-repo/semantics/publishedVersio

The pseudo-circular genomes of Flaviviruses: structures, mechanisms, and functions of circularization

© 2021 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 (http://creativecommons.org/licenses/by/4.0/).The circularization of viral genomes fulfills various functions, from evading host defense mechanisms to promoting specific replication and translation patterns supporting viral proliferation. Here, we describe the genomic structures and associated host factors important for flaviviruses genome circularization and summarize their functional roles. Flaviviruses are relatively small, single-stranded, positive-sense RNA viruses with genomes of approximately 11 kb in length. These genomes contain motifs at their 5' and 3' ends, as well as in other regions, that are involved in circularization. These motifs are highly conserved throughout the Flavivirus genus and occur both in mature virions and within infected cells. We provide an overview of these sequence motifs and RNA structures involved in circularization, describe their linear and circularized structures, and discuss the proteins that interact with these circular structures and that promote and regulate their formation, aiming to clarify the key features of genome circularization and understand how these affect the flaviviruses life cycle.This research was supported by Fundação para a Ciência e a Tecnologia—Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) and the Calouste Gulbenkian Foundation (FCG, Portugal) project Science Frontiers Research Prize 2010. N.M.S. acknowledges FCT-MCTES fellowship SFRH/BD/144585/2019. I.C.M. acknowledges FCT-MCTES program “Concurso de Estímulo ao Emprego Científico” (CEECIND/01670/2017).info:eu-repo/semantics/publishedVersio

Manual de Instalação do Conector SQL Server 2008 para o intermediário Kafka

Este documento pretende auxiliar a instalação do conector SQL Server que permite obter dados do SGBD, convertê-los para JSON e publicá-los num intermediário Kafka usando o consumidor JSON Kafka-REST-Proxy [3]. O conector foi desenvolvido como parte de um sistema de integração de dados de uma multinacional de telecomunicações no âmbito de um projeto de mestrado do Departamento de Informática da Faculdade de Ciências da Universidade de Lisboa.info:eu-repo/semantics/submittedVersio

Manual de Instalação do Conector MySQL v5.7.6 para o intermediário Kafka

Este documento pretende auxiliar a instalação do conector MySQL que permite obter dados a partir do ficheiro de registo de alterações binário, convertê-los para JSON e publicá-los num intermediário Kafka usando o consumidor JSON Kafka-REST-Proxy [13]. O conector foi desenvolvido como parte de um sistema de integração de dados de uma multinacional de telecomunicações no âmbito de um projeto de mestrado do Departamento de Informática da Faculdade de Ciências da Universidade de Lisboa.info:eu-repo/semantics/submittedVersio

Effects of 'casoparan', a peptide isolated from casein hydrolysates with mastoparan-like properties.

Casein, a protein found in milk of several species, is divided into different chains from 19 to 25 kDa. Casein is also considered as a source of amino acids and generating peptides with biological activities such as opiate, immunostimulating, antibacterial, peptidase inhibitors, among others. In this work, Sephadex G-10 chromatography followed by high-performance liquid chromatography isolation purified NZCase TT, an industrial culture media for tetanus toxin production. In the first step, four pools were isolated and tested in different assays: isolated smooth muscle assay (guinea pig ileum, rat uterus), phagocytosis in vitro of opsonized sheep red blood cells, and hydrogen peroxide (H2O2) release from mouse peritoneal macrophages. Pool III was the main active pool being able to potentiate bradykinin action in guinea pig ileum, stimulating phagocitic activity by resident macrophages and increasing H2O2 release from macrophages previously activated with bacille Calmette Guérin. Using mass spectra the primary structure of the main peptide from pool III was obtained--INKKI, which corresponds to beta-casein fragment 26-30. The immunostimulating action is probably related to a direct action in macrophage cells

Towards a Cooperative Security System for Mobile-Health Applications

[EN] Mobile Health (m-Health) system architectures are typically based on mobile and wireless communications, and use mobile devices with data exchange supported by Web Services (WS). Although m-Health systems offer mobility as a potential and precious resource they also present several challenged issues and constraints, such as, battery and storage capacity, broadcast constraints, interferences, disconnections, noises, limited bandwidths, and network delays. Furthermore, constant mobility and often-required Internet connectivity also exposes and compromises the privacy and confidentiality of the m-Health system information. This paper proposes a novel data encryption solution for mobile health systems, considering a novel and early-proposed cooperation strategy. This encryption solution, called data encryption for mobile health applications (DE4MHA), tries to guarantee the best confidentiality, integrity, and authenticity of m-health systems users data. The paper also presents a performance evaluation study comparing the performance an m-Health application with and without the DE4MHA.This work has been partially supported by National Funding from the FCT - Fundacao para a Ciencia e a Tecnologia through the PEst-OE/EEI/LA0008/2013 Project; by the AAL4ALL (Ambient Assisted Living for All), project co-funded by COMPETE under FEDER via QREN Programme; by Brazilian National Council for Research and Development (CNPq) via Grant No. 309335/2017-5; and by FINEP, with resources from Funttel, Grant No. 01.14.0231.00, under the Centro de Referencia em Radiocomunicacoes - CRR project of the Instituto Nacional de Telecomunicacoes (Inatel), Brazil.Silva, BM.; Rodrigues, JJPC.; Canelo, F.; Lopes, IMC.; Lloret, J. (2019). Towards a Cooperative Security System for Mobile-Health Applications. Electronic Commerce Research and Applications. 19(3):629-654. https://doi.org/10.1007/s10660-014-9154-362965419

Structural and functional properties of the capsid protein of Dengue and related Flavivirus

© 2019 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 (http://creativecommons.org/licenses/by/4.0/).Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems. The capsid is a homodimeric protein that contains a disordered N-terminal region, an intermediate flexible fold section and a very stable conserved fold region. Since a better understanding of its structure can give light into its biological activity, here, first, we compared and analyzed relevant mosquito-borne Flavivirus capsid protein sequences and their predicted structures. Then, we studied the alternative conformations enabled by the N-terminal region. Finally, using dengue virus capsid protein as main model, we correlated the protein size, thermal stability and function with its structure/dynamics features. The findings suggest that the capsid protein interaction with host lipid systems leads to minor allosteric changes that may modulate the specific binding of the protein to the viral RNA. Such mechanism can be targeted in future drug development strategies, namely by using improved versions of pep14-23, a dengue virus capsid protein peptide inhibitor, previously developed by us. Such knowledge can yield promising advances against Zika, dengue and closely related Flavivirus.This work was supported by “Fundação para a Ciência e a Tecnologia–Ministério da Ciência, Tecnologia e Ensino Superior” (FCT-MCTES, Portugal) project PTDC/SAU-ENB/117013/2010, Calouste Gulbenkian Foundation (FCG, Portugal) project Science Frontiers Research Prize 2010. A.F.F., A.S.M. and J.C.R. also acknowledge FCT-MCTES fellowships SFRH/BD/77609/2011, PD/BD/113698/2015 and SFRH/BD/95856/2013, respectively. I.C.M. acknowledges FCT-MCTES Programs “Investigador FCT” (IF/00772/2013) and “Concurso de Estímulo ao Emprego Científico” (CEECIND/01670/2017). This work was also supported by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado.info:eu-repo/semantics/publishedVersio

Surface modification of silica-based marine sponge bioceramics induce hydroxyapatite formation

Marine biomaterials are a new emerging area of research with significant applications. Recently, researchers are dedicating considerable attention to marine-sponge biomaterials for various applications. We have focused on the potential of biosilica from Petrosia ficidormis for novel biomedical/industrial applications. A bioceramic structure from this sponge was obtained after calcination at 750ºC for 6 hours in a furnace. The morphological characteristics of the 3D architecture were evaluated by scanning electron microscopy (SEM) and micro-computed tomography revealing a highly porous and interconnected structure. The skeleton of Petrosia ficidormis is a siliceous matrix composed of SiO2, which does not present inherent bioactivity. Induction of bioactivity was attained by subjecting the bioceramics structure to an alkaline treatment (KOH 2M) and acidic treatment (HCl 2M) for 1 and 3 hours. In vitro bioactivity of the bioceramics structure was evaluated in simulated body fluid (SBF), after 7 and 14 days. Observation of the structures by SEM, coupled with spectroscopic elemental analysis (EDS), has shown that the surface morphology presented a calcium-phosphate CaP coating, similar to hydroxyapatite (HA). The determination of the Ca/P ratio, together with the evaluation of the characteristic peaks of HA by infra-red spectroscopy and X-ray diffraction, have proven the existence of HA. In vitro biological performance of the structures was evaluated using an osteoblast cell line andthe acidic treatment has shown to be the most effective treatment. Cells were seeded on the bioceramics structures and their morphology, viability and growth was evaluated by SEM, MTS assay and DNA quantification, respectively, demonstrating that cells are able to grow and colonize the bioceramic structures.Alexandre Barros is grateful for financial support of FCT through Grant EXP/QEQ-EPS/0745/2012, SWIMS - Subcritical Water Isolation of compounds from Marine Sponges. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant REGPOT-CT2012-316331-POLARIS and under Grant no KBBE-2010-266033 (project SPECIAL). Funding from the project "Novel smart and biomimetic materials for innovative regenerative medicine approaches" RL1-ABMR-NORTE-01-0124-FEDER-000016) cofinanced by North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF) is also acknowledged

Water and carbon dioxide: green solvents for the extraction of collagen/gelatin from marine sponges

"Publication Date (Web): December 23, 2014"Marine sponges are extremely rich in natural products and are considered a promising biological resource. The major objective of this work is to couple a green extraction process with a natural origin raw material to obtain sponge origin collagen/gelatin for biomedical applications. Marine sponge collagen has unique physicochemical properties, but its application is hindered by the lack of availability due to inefficient extraction methodologies. Traditional extraction methods are time consuming as they involve several operating steps and large amounts of solvents. In this work, we propose a new extraction methodology under mild operating conditions in which water is acidified with carbon dioxide (CO2) to promote the extraction of collagen/gelatin from different marine sponge species. An extraction yield of approximately 50% of collagen/gelatin was achieved. The results of Fourier transformed infrared spectroscopy (FTIR), circular dichroism (CD), and differential scanning calorimetry (DSC) spectra suggest a mixture of collagen/gelatin with high purity, and the analysis of the amino acid composition has shown similarities with collagen from other marine sources. Additionally, in vitro cytotoxicity studies did not demonstrate any toxicity effects for three of the extracts.The authors are grateful for financial support of FCT through Grant EXP/QEQ:EPS/0745/2012, SWIMS (Subcritical Water Isolation of compounds from Marine Sponges). The funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement numbers REGPOT-CT2012-316331-POLARIS and KBBE-2010-266033 (project SPECIAL), as well as from ERDF under the project "Novel smart and biomimetic materials for innovative regenerative medicine approaches" RLI-ABMR-NORTE-01-0124-FEDER-000016), cofinanced by North Portugal Regional Operational Programme (ON.2,O Novo Norte), under the National Strategic Reference Framework (NSRF) are also gratefully ackowledged. The authors are also truly thankfull to Prof. Micha flan (Tel Aviv University, Israel), Dr. Ronald Osinga (Porifarma, The Netherlands), Dr. Antonio Sara and Dr. Martina Milanese (Studio Associato GAIA, Italy), and Dr. Joana Xavier (University of Azores) for the kind offer of marine sponges samples