A mechanobiological model to study upstream cell migration guided by tensotaxis

Biomechanics and Modeling in Mechanobiology - Cell migration is a process of crucial importance for the human body. It is responsible for important processes such as wound healing and tumor...     

A serotonergic system in the brain of the Antarctic fish, Trematomus bernacchii

The immunohistochemical distribution of serotonin-containing nerve fibres and cells has been described in the brain of the Antarctic fish, Trematomus bernacchii. The largest serotonergic system was associated with the diencephalic and rhombencephalic ventricles. In particular, serotonin-positive cells have been found in the lateral recess and neuropile zone of the diencephalic ventricle, where we have identified the serotonergic portion of the paraventricular organ. Numerous serotonin cells were localized in the dorsal nucleus of the raphe, the dorsal tegmental nucleus and the central gray. Two large cell groups, arranged in a pair of well-defined columns and connecting the central gray with the dorsal reticular formation, were immunostained in the region of the trigeminal nuclei. In addition, few positive cells have been found in the preoptic area and the cerebellar valvula, and few serotonergic nerve fibres, probably belonging to the lateral lemniscus, have been identified. The distribution of serotonin elements in the brain of T. bernacchii has been compared with that described in other fish, where it showed some modifications in the immunoreactive pattern. Finally, the lack of a serotonergic system at the level of the reticular superior formation has been reported; however, it was not possible to rule out a phylogenetic or environmental explanation.     

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.     

Neuronal Basis of Innate Olfactory Attraction to Ethanol in Drosophila

The decision to move towards a mating partner or a food source is essential for life. The mechanisms underlying these behaviors are not well understood. Here, we investigated the role of octopamine – the invertebrate analogue of noradrenaline – in innate olfactory attraction to ethanol. We confirmed that preference is caused via an olfactory stimulus by dissecting the function of the olfactory co-receptor Orco (formally known as OR83b). Orco function is not required for ethanol recognition per se, however it plays a role in context dependent recognition of ethanol. Odor-evoked ethanol preference requires the function of Tbh (Tyramine β hydroxalyse), the rate-limiting enzyme of octopamine synthesis. In addition, neuronal activity in a subset of octopaminergic neurons is necessary for olfactory ethanol preference. Notably, a specific neuronal activation pattern of tyraminergic/octopaminergic neurons elicit preference and is therefore sufficient to induce preference. In contrast, dopamine dependent increase in locomotor activity is not sufficient for olfactory ethanol preference. Consistent with the role of noradrenaline in mammalian drug induced rewards, we provide evidence that in adult Drosophila the octopaminergic neurotransmitter functions as a reinforcer and that the molecular dissection of the innate attraction to ethanol uncovers the basic properties of a response selection system.     

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.     

Myotonia congenita (Thomsen's disease) excluded from the region of the myotonic dystrophy locus on chromosome 19

Summary Linkage analysis has been carried out in six German families with autosomal dominantly inherited myotonia congenita (Thomsen's disease) using five chromosome 19 markers known to be linked to the gene for myotonic dystrophy (DM). Two of the markers, APOC1 and APOC2, are tightly linked to DM. Close linkage between these markers and myotonia congenita (MC) has been excluded to a distance of 9cM (z=-2.158). These data support the clinical suggestion that MC and DM are non-allelic disorders.