Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads.

The aim of this exploratory study was to determine heart rate and the levels of oxytocin, cortisol, and insulin in dogs and their owners in response to a short-term interaction. In addition, the dogs' behavior was studied. The owners' responses were compared with those obtained from a control group. Ten female volunteers and their own male Labrador dogs participated in an experiment during which the owner stroked, petted, and talked with her dog during the first 3 minutes. Blood samples were collected from both dog and owner before (0) and at 1, 3, 5, 15, 30, and 60 minutes after the start of the interaction. Blood samples were analyzed by EIA. Heart rate was monitored telemetrically. The data were analyzed using linear mixed models and paired t-tests. The dogs' oxytocin levels were significantly increased 3 minutes after the start of the interaction (p = 0.027). Cortisol levels were significantly increased after 15 and 30 minutes (p = 0.004 and p = 0.022, respectively), and heart rate was significantly decreased after 55 minutes (p = 0.008). The dogs displayed normal behaviors during the experiment. The owners' oxytocin levels peaked between 1 and 5 minutes after interaction (p = 0.026). No such effect was seen in the controls. Cortisol levels displayed a significant decrease at 15 or 30 minutes in both owners and controls, and insulin levels did so at 60 minutes (p = 0.030, p = 0.002 and p = 0.002, 301 Anthrozoös Anthrozoös Short-Term Interaction between Dogs and Their Owners… p < 0.0001, respectively). Heart rate decreased significantly in the owners at 55 and 60 minutes (p = 0.0008) but not in the controls. In conclusion, short-term sensory interaction between dogs and their owners influences hormonal levels and heart rate. However, further studies need to be performed in order to better understand the effects of interaction between dogs and their owners.

Serum OPG is strongly predictive of long-term mortality and HF development in patients with ACS, independent of conventional risk markers.

The greater microbial stability and reduction in LAB and members of the Streptococcus bovis/equinus complex on diet F indicate an opportunity to develop feeding strategies that support equine health and welfare. Novel changes identified in the faecal microbiota that resulted from carbohydrate inclusion merit further investigation.