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.

Contribution of Resource-Based View and Entrepreneurial Orientation on Small Firm Growth

[EN] This research provides a useful framework for identifying a small firms’ propensity to engage in entrepreneurial orientation. We examine the impact of the Entrepreneurial Orientation (EO) as a main resource and capability on small firm’ growth. The growth seems to come out as an important demonstration of the entrepreneurial orientation of small firms (Davidsson, 1989; Green and Brown, 1997; Janney and Gregory, 2006). Thus, this research builds on prior conceptual research that suggests a positive integration between entrepreneurial orientation and resource-based view. In the first instance, the research will focus on reviewing literature in the emerging area of entrepreneurial orientation as it applies to growth oriented small firms and resource-based view of the firm. Secondly, an empirical study was developed based on a stratified sample of small firms of manufacturing industry. Data were submitted to a multivariate statistical analysis and a linear regression model was performed in order to predict the influence of the resources and capabilities on small firms’ growth. In this sense, we consider the construct growth as a dependent variable and the ones relates with resources and capabilities (entrepreneur resources, firm resources, networks and EO) as independent variables. The research results suggest a set of resources and capabilities that promote the growth of the small firms. Also, the EO seems to have a predictive value on growth. Explaining variables related with resources and capabilities and EO were identified as essential in growth oriented small firms. It was still possible to conclude that the entrepreneurial firms which grew seem to have resources and develop more capabilities and take advantage in the search for those competences. This attitude reflects on the EO of the firm. This study has important implication for both researchers and practitioners. It highlights the necessity of firms to develop superior EO of all their members and also to invest on better resources and consequently superior capabilities as a way of reaching higher levels of growth. While previous authors have attempted to analyse certain aspects of this process (linkage between entrepreneurial orientation and growth), this research developed a framework that combines these and others factors (resource-based view) pertinent to growth oriented small firms. The results support the necessity to identify explicative variables of multiple levels to explain the growth of small firms. The adoption of an entrepreneurial orientation as an indispensable variable to the growth oriented small firms seems pertinent.

A predictive model of the export behaviour of small and medium sized firms: an application to the case of Castilla-La Mancha

[EN] Based on an extensive theoretical review, the aim of this paper is to carry out a closer examination of the differences between exporters according to their commitment to the international market. Once the main disparities are identified by means of a non-parametric test, a logistic analysis based upon data collected from small and medium sized manufacturing firms is conducted in order to construct a classificatory model.

Retroviral Infections in Sheep and Goats: Small Ruminant Lentiviruses and Host Interaction

Small ruminant lentiviruses (SRLV) are members of the Retrovirus family comprising the closely related Visna/Maedi Virus (VMV) and the Caprine Arthritis-Encephalitis Virus (CAEV), which infect sheep and goats. Both infect cells of the monocyte/macrophage lineage and cause lifelong infections. Infection by VMV and CAEV can lead to Visna/Maedi (VM) and Caprine Arthritis-Encephalitis (CAE) respectively, slow progressive inflammatory diseases primarily affecting the lungs, nervous system, joints and mammary glands. VM and CAE are distributed worldwide and develop over a period of months or years, always leading to the death of the host, with the consequent economic and welfare implications. Currently, the control of VM and CAE relies on the control of transmission and culling of infected animals. However, there is evidence that host genetics play an important role in determining Susceptibility/Resistance to SRLV infection and disease progression, but little work has been performed in small ruminants. More research is necessary to understand the host-SRLV interaction.

Streamflow response of a small forested catchment on different timescales

The hydrological response of a catchment to rainfall on different timescales is result of a complex system involving a range of physical processes which may operate simultaneously and have different spatial and temporal influences. This paper presents the analysis of streamflow response of a small humid-temperate catchment (Aixola, 4.8 km(2)) in the Basque Country on different timescales and discusses the role of the controlling factors. Firstly, daily time series analysis was used to establish a hypothesis on the general functioning of the catchment through the relationship between precipitation and discharge on an annual and multiannual scale (2003-2008). Second, rainfall-runoff relationships and relationships among several hydrological variables, including catchment antecedent conditions, were explored at the event scale (222 events) to check and improve the hypothesis. Finally, the evolution of electrical conductivity (EC) during some of the monitored storm events (28 events) was examined to identify the time origin of waters. Quick response of the catchment to almost all the rainfall events as well as a considerable regulation capacity was deduced from the correlation and spectral analyses. These results agree with runoff event scale data analysis; however, the event analysis revealed the non-linearity of the system, as antecedent conditions play a significant role in this catchment. Further, analysis at the event scale made possible to clarify factors controlling (precipitation, precipitation intensity and initial discharge) the different aspects of the runoff response (runoff coefficient and discharge increase) for this catchment. Finally, the evolution of EC of the waters enabled the time origin (event or pre-event waters) of the quickflow to be established; specifically, the conductivity showed that pre-event waters usually represent a high percentage of the total discharge during runoff peaks. The importance of soil waters in the catchment is being studied more deeply.

Structural study of CUG-repeating small RNAs complexed with silencing suppressor P19

The study is focused on structural aspects of interaction between silencing suppressor p19 and CUG-repeating small RNAs. The work involves crystal structure determination of a protein-unbound RNA form and RNA fragments of various lengths (19, 20, 21 nucleotides) complexed with p19-suppressor. Results prove the ability of silencing suppressor p19 to bind CUG-repeating small RNAs, as well as reveal features of U•U mismatches flanked by Watson-Crick C•G base pairs in p19-bound and p19-unbound states. In addition, structural data reveal a p19 specific site for anchoring extra nucleotides in small RNAs. In general, the study extends our knowledge about the mechanism of small RNA recognition by silencing suppressor p19.

Delivery of small nucleic acids by conjugation to carbohydrates and lipids as novel research and therapeutic tools

399 p. : il., graf.

The basque ecological debt: global socioecological impacts of a small open economy

4 p.

Warsaw Conference: “Small steps forward while awaiting major decisions at the 2015 Paris Conference”

6 p.

Viral metagenomic analysis of feces of wild small carnivores

Background: Recent studies have clearly demonstrated the enormous virus diversity that exists among wild animals. This exemplifies the required expansion of our knowledge of the virus diversity present in wildlife, as well as the potential transmission of these viruses to domestic animals or humans. Methods: In the present study we evaluated the viral diversity of fecal samples (n = 42) collected from 10 different species of wild small carnivores inhabiting the northern part of Spain using random PCR in combination with next-generation sequencing. Samples were collected from American mink (Neovison vison), European mink (Mustela lutreola), European polecat (Mustela putorius), European pine marten (Martes martes), stone marten (Martes foina), Eurasian otter (Lutra lutra) and Eurasian badger (Meles meles) of the family of Mustelidae; common genet (Genetta genetta) of the family of Viverridae; red fox (Vulpes vulpes) of the family of Canidae and European wild cat (Felis silvestris) of the family of Felidae. Results: A number of sequences of possible novel viruses or virus variants were detected, including a theilovirus, phleboviruses, an amdovirus, a kobuvirus and picobirnaviruses. Conclusions: Using random PCR in combination with next generation sequencing, sequences of various novel viruses or virus variants were detected in fecal samples collected from Spanish carnivores. Detected novel viruses highlight the viral diversity that is present in fecal material of wild carnivores.

Effects of Small-Sided Games vs. Interval Training in Aerobic Fitness and Physical Enjoyment in Young Elite Soccer Players

The purpose of this study was to compare the effects of Small-Sided Games (SSG) vs. Interval Training (IT) in soccer training on aerobic fitness and physical enjoyment in youth elite soccer players during the last 8 weeks of the season. Seventeen U-16 male soccer players (age = 15.5 +/- 0.6 years, and 8.5 years of experience) of a Spanish First Division club academy were randomized to 2 different groups for 6 weeks: SSG group (n = 9) and IT group (n = 8). In addition to the usual technical and tactical sessions and competitive games, the SSG group performed 11 sessions with different SSGs, whereas the IT group performed the same number of sessions of IT. Players were tested before and after the 6-week training intervention with a continuous maximal multistage running field test and the counter movement jump test (CMJ). At the end of the study, players answered the physical activity enjoyment scale (PACES). During the study, heart rate (HR) and session perceived effort (sRPE) were assessed. SSGs were as effective as IT in maintaining the aerobic fitness in elite young soccer players during the last weeks of the season. Players in the SSG group declared a greater physical enjoyment than IT (P = 0.006; ES = 1.86 +/- 1.07). Coaches could use SSG training during the last weeks of the season as an option without fear of losing aerobic fitness while promoting high physical enjoyment.

System architecture and deployment scenarios for SESAME: Small cEllS coordinAtion for Multi-tenancy and Edge services

The surge of the Internet traffic with exabytes of data flowing over operators mobile networks has created the need to rethink the paradigms behind the design of the mobile network architecture. The inadequacy of the 4G UMTS Long term Evolution (LTE) and even of its advanced version LTE-A is evident, considering that the traffic will be extremely heterogeneous in the near future and ranging from 4K resolution TV to machine-type communications. To keep up with these changes, academia, industries and EU institutions have now engaged in the quest for new 5G technology. In this paper we present the innovative system design, concepts and visions developed by the 5G PPP H2020 project SESAME (Small cEllS coordinAtion for Multi-tenancy and Edge services). The innovation of SESAME is manifold: i) combine the key 5G small cells with cloud technology, ii) promote and develop the concept of Small Cellsas- a-Service (SCaaS), iii) bring computing and storage power at the mobile network edge through the development of nonx86 ARM technology enabled micro-servers, and iv) address a large number of scenarios and use cases applying mobile edge computing. Topics: