Populations of short self-replicating RNA variants have been confined to one side of a reaction-diffusion traveling wave front propagating along thin capillary tubes containing the Qfi viral enzyme. The propagation speed is accurately measurable with a magnitude ofabout 1 pm/sec, and the wave persists for hundreds of generations (of duration less than 1 min). Evolution of RNA occurs in the wavefront, as established by front velocity changes and gel electrophoresis of samples drawn from along the capillary. The hih population numbers (.0"11), their well-characterized biochemistry, their short generation time, and the constant conditions make the system ideal for evolution experiments. Growth is monitored continuously by excitation of an added RNA-sensitive fluorescent dye, ethidium bromide. An analytic expression for the front velocity is derived for the multicomponent kinetic scheme that reduces, for a high RNA-enzyme binding constant, to the Fisher form v = 2VcD, whereD isthe diffusion constant ofthe complex and Kc is the low-concentration overall replication rate coefficient. The latter is confirmed as the selective value-determining parameter by numerical solution of a two-species system.It is difficult to provide a constant set of conditions for an explosive reaction over long periods. In a chemical traveling wave, constant reaction conditions are maintained in spite of an intrinsic stability in the homogeneous kinetics (1). The stirred flow reactor (2) and serial transfer method (3) represent laboratory techniques for establishing homogeneous constant chemical conditions. Studies in a constant environment are particularly important to an elementary understanding of molecular evolution. In this work we establish that a constant environment for RNA replication can be attained for a thousand generations or more (corresponding to a day-long experiment) in a traveling concentration wave. The usual difficulties of confinement (1014 molecules, with the reaction catalyzed by a single molecule) are resolved by the physical seal of a fluid-filled capillary.

BackgroundNon-hereditary angioedema (non-HAE) is characterized by local swelling due to self-limiting, subcutaneous or submucosal extravasation of fluid, and can be divided into three subtypes. These subtypes are believed to have different pathophysiological backgrounds and are referred to in recent guidelines as bradykinin-mediated (e.g. caused by angiotensin-converting-enzyme-inhibitors), mast cell-mediated (e.g. angioedema with wheals) or idiopathic (cause unknown). Bradykinin-mediated subtypes are more closely related to hereditary angioedema than the other forms. Because clinical features of these non-HAE subtypes have not been studied in detail, we have looked at the clinical characteristics of symptoms and potential differences in clinical presentation of bradykinin-mediated and mast cell-mediated angioedema (AE) subtypes.MethodsA questionnaire was sent to patients presenting with AE at our tertiary outpatient clinic to document clinical characteristics, potential triggers and location of AE. The severity of AE attacks was analysed using visual analogue scales (VAS).ResultsThe questionnaire was returned by 106 patients, of which 104 were included in the analysis. AE with wheals, idiopathic AE, and drug-associated AE occurred in 64 (62%), 25 (24%) and 15 patients (14%) respectively. Most patients (62%) reported prodromal symptoms while 63% reported multiple locations for an attack. Face and oropharynx were the main locations of AE attacks of any subtype while swelling was the symptom most frequently reported as severe. Overall severity of the last attack was indicated as severe by 68% of the patients. There were no differences between the subgroups.ConclusionThis similarity in clinical presentation raises the possibility that ACEi-induced, mast cell-mediated and idiopathic AE share common pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s13601-015-0049-8) contains supplementary material, which is available to authorized users.

CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.

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