Influenza A Gradual and Epochal Evolution: Insights from Simple Models

The recurrence of influenza A epidemics has originally been explained by a “continuous antigenic drift” scenario. Recently, it has been shown that if genetic drift is gradual, the evolution of influenza A main antigen, the haemagglutinin, is punctuated. As a consequence, it has been suggested that influenza A dynamics at the population level should be approximated by a serial model. Here, simple models are used to test whether a serial model requires gradual antigenic drift within groups of strains with the same antigenic properties (antigenic clusters). We compare the effect of status based and history based frameworks and the influence of reduced susceptibility and infectivity assumptions on the transient dynamics of antigenic clusters. Our results reveal that the replacement of a resident antigenic cluster by a mutant cluster, as observed in data, is reproduced only by the status based model integrating the reduced infectivity assumption. This combination of assumptions is useful to overcome the otherwise extremely high model dimensionality of models incorporating many strains, but relies on a biological hypothesis not obviously satisfied. Our findings finally suggest the dynamical importance of gradual antigenic drift even in the presence of punctuated immune escape. A more regular renewal of susceptible pool than the one implemented in a serial model should be part of a minimal theory for influenza at the population level.     

Dispersal vs. vicariance in the Mediterranean: historical biogeography of the Palearctic Pachydeminae (Coleoptera, Scarabaeoidea)

Aim The geological evolution of the Mediterranean region is largely the result of the Tertiary collision of the African and Eurasian Plates, but also a mosaic of migrating island arcs, fragmenting tectonic belts, and extending back‐arc basins. Such complex paleogeography has resulted in a ‘reticulate’ biogeographical history, in which Mediterranean biotas repeatedly fragmented and merged as dispersal barriers appeared and disappeared through time. In this study, dispersal‐vicariance analysis (DIVA) is used to assess the relative role played by dispersal and vicariance in shaping distribution patterns in the beetle subfamily Pachydeminae Reitter, 1902 (Scarabaeoidea), an example of east–west Mediterranean disjunction. Location The Mediterranean region, including North Africa, the western Mediterranean, Balkans–Anatolia, Middle East, Caucasus, the Iranian Plateau, and Central Asia. Methods A phylogenetic hypothesis of the Palearctic genera of Pachydeminae in conjunction with distributional data was analysed using DIVA. This method reconstructs the ancestral distribution in a given phylogeny based on the vicariance model, while allowing dispersal and extinction to occur. Unlike other methods, DIVA does not enforce area relationships to conform to a hierarchical ‘area cladogram’, so it can be used to reconstruct ‘reticulate’ biogeographical scenarios. Results Optimal reconstructions, requiring 23 dispersal events, suggest that the ancestor of Pachydeminae was originally present in the south‐east Mediterranean region. Basal splitting within the subfamily was caused by vicariance events related to the late Tertiary collision of the African microplates Apulia and Arabia with Eurasia, and the resultant arise of successive dispersal barriers (e.g. the Red Sea, the Zagros Mountains). Subsequent diversification in Pachydeminae involved multiple speciation events within the Middle East and Iran–Afghanistan regions, which gave rise to the least speciose genera of Pachydeminae (e.g. Otoclinius Brenske, 1896). Finally, the presence of Pachydeminae in the western Mediterranean region seems to be the result of a recent dispersal event. The ancestor of the Iberian genera Ceramida Baraud, 1987 and Elaphocera Gené, 1836 probably dispersed from the Middle East to the Iberian Peninsula across North Africa and the Gibraltar Strait during the ‘Messinian salinity crisis’ at the end of the Miocene. Main conclusions Although the basal diversification of Pachydeminae around the Mediterranean appears to be related to vicariance events linked to the geological formation of the Mediterranean Basin, dispersal has also played a very important role. Nearly 38% of the speciation events in the phylogeny resulted from dispersal to a new area followed by allopatric speciation between lineages. Relationships between western and eastern Mediterranean disjuncts are usually explained by dispersal through Central Europe. The biogeographical history of the Pachydeminae corroborates other biogeographical studies that consider North Africa to be an alternative dispersal route by which Mediterranean taxa could have achieved circum‐Mediterranean distributions.     

Stability of the Transthyretin Molecule as a Key Factor in the Interaction with A-Beta Peptide - Relevance in Alzheimer's Disease

Transthyretin (TTR) protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/A-Beta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenyl)amino] (DCPA) and [4-(3,5-difluorophenyl)] (DFPB) were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this interaction, which may be relevant in AD pathogenesis and for the design of therapeutic TTR-based therapies.     

Cell adhesion molecule in the hexactinellid Aphrocallistes vastus

Abstract. The Hexactinellida sponge Aphrocallistes vastus contains a soluble aggregation factor (AF) whose purification has been described in this communication. It is characterized by a S°_20.w value of 37 and a buoyant density of 1.45 g/cm³. The AF is a glycoporteinaceous particle composed of three major protein species; no core structure could be visualized. In the presence of Ca²⁺, the AF causes secondary aggregation of single cells. The aggregation process is temperature, pH, and ionic strength independent within a broad range. Evidence is presented indicating that two (or more) AF molecules are required for the establishment of a stable cell: cell interaction. In contrast to the AFs from demosponges, the hexactinellid AF functions species-unspecifically.     

Hydrolysis of nucleic acids by sepharose-micrococcal endonuclease

Initial reaction rates for the hydrolysis of nucleic acids with micrococcal endonuclease (EC 3.1.31.1) insolubilized on Sepharose are strongly influenced by diffusional limitations. Although the absolute values are low, they can be increased substantially by changing particle and pore size of the support, or enzyme concentration in the insoluble derivative. As a result of steric and diffusional limitations, the course of the reaction and selectivity to hydrolysis products for the insoluble derivatives are different to those of the native enzyme; the former produces mainly large and small fragments but few of intermediate size. Because of these differences in course and selectivity of the reaction, diffusional limitations become less important when high initial reaction rates are not required.     

Photosynthetic electron transport interaction of xanthorrhizol isolated from Iostephane heterophylla and its derivatives

A bioactivity-guided chemical study of Iostephane heterophylla (Asteraceae) led to the isolation of xanthorrhizol (1) as the compound that causes inhibition of ATP synthesis, H⁺-uptake and electron flow from water to methylviologen (basal, phosphorylating and uncoupled) in freshly lysed spinach chloroplasts, thus acting as an inhibitor of the Hill reaction. Acetyl (2), dihydro (3) and acetyl-dihydro (4) derivatives were synthesized. It was found that 4 was less active than 1 and 2 in ATP synthesis, whereas 3 was the most potent inhibitor of the Hill reaction and was also an inhibitor of H⁺-ATPase. Studies of the photosynthetic partial redox reactions from PQ to MV indicated that 1 partially inhibited the PQ pool, but that 3 did not. However, both inhibited the uncoupled electron transport in PSII from water to DCBQ. Uncoupled electron flow from water to silicomolybdate was completely inhibited by 3 and partially by 1. The reaction from DPC to DCPIP was inhibited by both 1 and 3. These results indicate that the inhibition site is located within PSII for 1 and 3 as was corroborated by fluorescence decay data.