Accumulating evidence from animal and human studies points to the involvement of the Ang/Tie system in vascular barrier dysfunction during critical illness. Many processes in injury and in repair act through this nonredundant system. Thus far, only preliminary studies in critically ill patients have been reported. Methods to manipulate this system are available but have not been tested in such patients. The response to treatment is difficult to predict because of the pleiotropic functions of the Ang/Tie system, because the balance among its components appears to be more important than the absolute levels, and because the sensitivity of the endothelium to disease-related stimuli varies, depending on the environment and the organ involved. To avoid disappointment, further experimental and translational research must be carried out, and Ang/Tie modulation must not be introduced into the clinic prematurely. Implementing the results of this research in critical care represents an opportunity to show what we have learned [2] . Ang/Tie signalling is a very promising target and must not be allowed to become lost in translation [179] .  Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu) influenza A virus strain neuraminidase for drug treatment and vaccination. We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas. Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site. The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu(®)), zanamivir (Relenza(®)) and peramivir; thus, the drugs should remain effective for treatment. However, the antigenic regions of the neuraminidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients. This article was reviewed by Sandor Pongor and L. Aravind. The recent epidemic of the "2009 H1N1" influenza A virus (also called swine or Mexican flu) has put the world on alert since a new swine flu strain (naturally hosted by pigs) has crossed the species barrier to human and, apparently, acquired the capability for human to human transmission [1, 2] . Given earlier experiences with risks of viral pandemics such as SARS and the avian flu [3] , global control and public health surveillance mechanisms provided sequences of the new flu strain in public sequence databases within weeks of the outbreak. Here, we analyze the protein sequence of its neuraminidase with respect to sim-ilarities and differences to known strains and implications on drug treatment and vaccination.