Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

Evolutionary associations between sand seatrout (Cynoscion arenarius) and silver seatrout (C. nothus) inferred from morphological characters, mitochondrial DNA, and microsatellite markers

The evolutionary associations between closely related fish species, both contemporary and historical, are frequently assessed by using molecular markers, such as microsatellites. Here, the presence and variability of microsatellite loci in two closely related species of marine fishes, sand seatrout (Cynoscion arenarius) and silver seatrout (C. nothus), are explored by using heterologous primers from red drum (Sciaenops ocellatus). Data from these loci are used in conjunction with morphological characters and mitochondrial DNA haplotypes to explore the extent of genetic exchange between species offshore of Galveston Bay, TX. Despite seasonal overlap in distribution, low genetic divergence at microsatellite loci, and similar life history parameters of C. arenarius and C. nothus, all three data sets indicated that hybridization between these species does not occur or occurs only rarely and that historical admixture in Galveston Bay after divergence between these species was unlikely. These results shed light upon the evolutionary history of these fishes and highlight the genetic properties of each species that are influenced by their life history and ecology.

Spatial and seasonal abundance of sand seatrout (Cynoscion arenarius) and silver seatrout (C. nothus) off the coast of Texas, determined with twenty years of data (1987–200

Sand seatrout (Cynoscion arenarius) and silver seatrout (C. nothus) are both found within the immediate offshore areas of the Gulf of Mexico, especially around Texas; however information is limited on how much distributional overlap really occurs between these species. In order to investigate spatial and seasonal differences between species, we analyzed twenty years of bay and offshore trawl data collected by biologists of the Coastal Fisheries Division, Texas Parks and Wildlife Department. Sand seatrout and silver seatrout were distributed differently among offshore sampling areas, and salinity and water depth appeared to correlate with their distribution. Additionally, within the northernmost sampling area of the gulf waters, water depth correlated significantly with the presence of silver seatrout, which were found at deeper depths than sand seatrout. There was also an overall significant decrease in silver seatrout abundance during the summer season, when temperatures were at their highest, and this decrease may have indicated a migration farther offshore. Sand seatrout abundance had an inverse relationship with salinity and water depth offshore. In addition, sand seatrout abundance was highest in bays with direct passes to the gulf and correlated with corresponding abundance in offshore areas. These data highlight the seasonal and spatial differences in abundance between sand and silver seatrout and relate these differences to the hydrological and geological features found along the Texas coastline.

A estandardização dos contratos internacionais e o modelo FIDIC - Silver Book para contratos EPC

No presente trabalho acadêmico se apresentarão as principais características do processo de globalização, passando-se à exposição da relevância do Direito Comparado, até se chegar à análise da adoção de modelos internacionais de contratos como esforço uniformizador, de modo a reduzir riscos e a minorar custos de transação. Na sequência, investigar-se-á o modelo contratual EPC (acrônimo das palavras inglesas Engineering, Procurement and Construction - Engenharia, Gestão de Compra e Construção), originário da prática anglo-saxã, focando-se na análise e na qualificação tipológica do Contrato EPC, comparando-o com institutos existentes na legislação brasileira. Delinear-se-á o contexto de disseminação do Contrato EPC no exterior e sua consolidação no Brasil, amparadas, em larga medida, na necessidade de que - em vultosos projetos de infraestrutura, sobretudo em áreas de investimento em relação às quais os empreendedores desconheçam o ambiente regulatório e a realidade socioeconômica se tenha estatuto privado a transladar ao construtor a maior parte dos riscos atinentes a serviços complexos de engenharia. Enfrentar-se-ão as características essenciais deste modelo contratual, tomando-se como padrão o Conditions of Contract for EPC Turnkey Projects - general conditions, guidance for the preparation of particular conditions, forms of letter of tender, contract agreement and dispute adjudication agreement, recomendado pela Fédération Internationale des Ingénieurs Conseils - FIDIC. Apresentar-se-á como o direito estrangeiro equilibra a assunção dos riscos pelo construtor (Contractor ou Builder), inclusive aqueles, referentes a eventos não antecipáveis (unforeseen risks), inobstante a preservação pelo contratante (Owner) de lato poder de monitoramento e fiscalização (overseeing attributions, key personnel and contract manager approval, step-in rights).

Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

Two Glass Transitions Associated to Different Dynamic Disorders in the Nematic Glassy State of a Non-Symmetric Liquid Crystal Dimer Dopped with gamma-Alumina Nanoparticles

In the present work, the nematic glassy state of the non-symmetric LC dimer -(4-cyanobiphenyl-4-yloxy)--(1-pyrenimine-benzylidene-4-oxy) undecane is studied by means of calorimetric and dielectric measurements. The most striking result of the work is the presence of two different glass transition temperatures: one due to the freezing of the flip-flop motions of the bulkier unit of the dimer and the other, at a lower temperature, related to the freezing of the flip-flop and precessional motions of the cyanobiphenyl unit. This result shows the fact that glass transition is the consequence of the freezing of one or more coupled dynamic disorders and not of the disordered phase itself. In order to avoid crystallization when the bulk sample is cooled down, the LC dimer has been confined via the dispersion of -alumina nanoparticles, in several concentrations.

Monoculture of silver barb (Puntius gonionotus Bleeker) in rice floodwaters in Bangladesh

On-station and on-farm trials with silver barb (Puntius gonionotus) monoculture in rice floodwaters in Bangladesh are summarized and discussed in this article.