Finally, if À1 RF is widely used to regulate gene expression, then it should be well conserved. The major problem associated with attempting a phylogenetic analysis of À1 RF signals is the inherent limitations of the software used to predict them. In short, it is not well enough developed to automatically identify matching motifs. In an attempt to begin to address this issue, the orthologous Bub3p, Est2p, Spr6p and Tbf1p's in six closely related yeast species were identified, their nucleotide sequences extracted from the Yeast Gene Order Browser (28) , and analyzed for the presence of potential À1 RF signals. These analyses revealed that while specific À1 RF signals do not appear to be evolutionarily conserved, À1 RF itself may be relatively well-enough conserved as a mechanism to post-transcriptionally regulate the expression of these genes across many but not all species examined (see Supplementary Table S4 ). Importantly, the control experiment showed that putative À1 RF signals were not detected in any of the orthologs of six S. cerevisiae genes that themselves were not predicted to contain À1 RF signals. These observations are in agreement with current evolutionary theory based on analyses of 5 0 UTR sequences of Drosophila species proposing that rapid rates of mutation in cis-acting regulatory elements drives speciation because they confer very specific effects on gene expression, as opposed to mutations affecting protein structure, the pleiotrophic effects of which impose very high penalties on fitness (58) (59) (60) . The findings presented in this work, i.e. that while À1 RF signals are not conserved in orthologs from other yeasts, these ORFs contain generically contain À1 RF signals, and that the absence of À1 RF signals in other orthologous ORFs, agrees very well with this theory of molecular evolution. Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide. The present paradigm is that hantaviruses in the Americas cause hantavirus pulmonary syndrome (HPS), while hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses present in Eurasia [1] [2] [3] . Hantaviruses associated with HFRS and HPS are primarily transmitted by inhalation of viral particles shed by infected rodents [4, 5] . In both syndromes there is a local immune reaction in the lungs, mainly in terms of a CD8 + T lymphocyte response [2, 6, 7] . Another important feature is endothelial dysfunction and capillary leakage [1] [2] [3] 8] . After the prodromal phase, including fever, nausea, myalgia and headache, patients with HFRS commonly develop renal failure whereas in HPS the kidneys are often spared and instead the patient frequently presents with severe cardiopulmonary dysfunction [1, 3, 9] .