Turning regenerative technologies into treatment to repair myocardial injuries

Regenerative therapies including stem cell treatments hold promise to allow curing patients affected by severe cardiac muscle diseases. However, the clinical efficacy of stem cell therapy remains elusive, so far. The two key roadblocks that still need to be overcome are the poor cell engraftment into the injured myocardium and the limited knowledge of the ideal mixture of bioactive factors to be locally delivered for restoring heart function. Thus, therapeutic strategies for cardiac repair are directed to increase the retention and functional integration of transplanted cells in the damaged myocardium or to enhance the endogenous repair mechanisms through cell-free therapies. In this context, biomaterial-based technologies and tissue engineering approaches have the potential to dramatically impact cardiac translational medicine. This review intends to offer some consideration on the cell-based and cell-free cardiac therapies, their limitations and the possible future developments.     

Colonization history of Galapagos giant tortoises: Insights from mitogenomes support the progression rule

Galapagos giant tortoises (Chelonoidis spp.) are a group of large, long-lived reptiles that includes 14 species, 11 of which are extant and threatened by human activities and introductions of non-native species. Here, we evaluated the phylogenetic relationships of all extant and two extinct species (Chelonoidis abingdonii from the island of Pinta and Chelonoidis niger from the island of Floreana) using Bayesian and maximum likelihood analysis of complete or nearly complete mitochondrial genomes. We also provide an updated phylogeographic scenario of their colonization of the Galapagos Islands using chrono-phylogenetic and biogeographic approaches. The resulting phylogenetic trees show three major groups of species: one from the southern, central, and western Galapagos Islands; the second from the northwestern islands; and the third group from the northern, central, and eastern Galapagos Islands. The time-calibrated phylogenetic and ancestral area reconstructions generally align with the geologic ages of the islands. The divergence of the Galapagos giant tortoises from their South American ancestor likely occurred in the upper Miocene. Their diversification on the Galapagos adheres to the island progression rule, starting in the Pleistocene with the dispersal of the ancestral form from the two oldest islands (San Cristóbal and Española) to Santa Cruz, Santiago, and Pinta, followed by multiple colonizations from different sources within the archipelago. Our work provides an example of how to reconstruct the history of endangered taxa in spite of extinctions and human-mediated dispersal events and provides a framework for evaluating the contribution of colonization and in situ speciation to the diversity of other Galapagos lineages.     

An African bat in Europe,Plecotus gaisleri: Biogeographic and ecological insights from molecular taxonomy and Species Distribution Models

Because of the high risk of going unnoticed, cryptic species represent a major challenge to biodiversity assessments, and this is particularly true for taxa that include many such species, for example, bats. Long‐eared bats from the genus Plecotus comprise numerous cryptic species occurring in the Mediterranean Region and present complex phylogenetic relationships and often unclear distributions, particularly at the edge of their known ranges and on islands. Here, we combine Species Distribution Models (SDMs), field surveys and molecular analyses to shed light on the presence of a cryptic long‐eared bat species from North Africa, Plecotus gaisleri, on the islands of the Sicily Channel, providing strong evidence that this species also occurs in Europe, at least on the islands of the Western Mediterranean Sea that act as a crossroad between the Old Continent and Africa. Species Distribution Models built using African records of P. gaisleri and projected to the Sicily Channel Islands showed that all these islands are potentially suitable for the species. Molecular identification of Plecotus captured on Pantelleria, and recent data from Malta and Gozo, confirmed the species' presence on two of the islands in question. Besides confirming that P. gaisleri occurs on Pantelleria, haplotype network reconstructions highlighted moderate structuring between insular and continental populations of this species. Our results remark the role of Italy as a bat diversity hotspot in the Mediterranean and also highlight the need to include P. gaisleri in European faunal checklists and conservation directives, confirming the usefulness of combining different approaches to explore the presence of cryptic species outside their known ranges—a fundamental step to informing conservation.     

Membrane interactions of the anuran antimicrobial peptide HSP1-NH2: Different aspects of the association to anionic and zwitterionic biomimetic systems

Studies have suggested that antimicrobial peptides act by different mechanisms, such as micellisation, self-assembly of nanostructures and pore formation on the membrane surface. This work presents an extensive investigation of the membrane interactions of the 14 amino-acid antimicrobial peptide hylaseptin P1-NH₂ (HSP1-NH₂), derived from the tree-frog Hyla punctata, which has stronger antifungal than antibacterial potential. Biophysical and structural analyses were performed and the correlated results were used to describe in detail the interactions of HSP1-NH₂ with zwitterionic and anionic detergent micelles and phospholipid vesicles. HSP1-NH₂ presents similar well-defined helical conformations in both zwitterionic and anionic micelles, although NMR spectroscopy revealed important structural differences in the peptide N-terminus. ²H exchange experiments of HSP1-NH₂ indicated the insertion of the most N-terminal residues (1–3) in the DPC-d₃₈ micelles. A higher enthalpic contribution was verified for the interaction of the peptide with anionic vesicles in comparison with zwitterionic vesicles. The pore formation ability of HSP1-NH₂ (examined by dye release assays) and its effect on the size and surface charge as well as on the lipid acyl chain ordering (evaluated by Fourier-transform infrared spectroscopy) of anionic phospholipid vesicles showed membrane disruption even at low peptide-to-phospholipid ratios, and the effect increases proportionately to the peptide concentration. On the other hand, these biophysical investigations showed that a critical peptide-to-phospholipid ratio around 0.6 is essential for promoting disruption of zwitterionic membranes. In conclusion, this study demonstrates that the binding process of the antimicrobial HSP1-NH₂ peptide depends on the membrane composition and peptide concentration.     

Aerobic training prevents cardiometabolic changes triggered by myocardial infarction in ovariectomized rats

This study aimed to evaluate the impact of aerobic training (AT) on autonomic, cardiometabolic, ubiquitin‐proteasome activity, and inflammatory changes evoked by myocardial infarction (MI) in ovariectomized rats. Female Wistar rats were ovariectomized and divided into four groups: sedentary + sham (SS), sedentary + MI (SI), AT + sham surgery (TS), AT + MI (TI). AT was performed on a treadmill for 8 weeks before MI. Infarcted rats previously subjected to AT presented improved physical capacity, increased interleukin‐10, and decreased pro‐inflammatory cytokines. Metabolomic analysis identified and quantified 62 metabolites, 9 were considered significant by the Vip Score. SS, SI, and TS groups presented distinct metabolic profiles; however, TI could not be distinguished from the SS group. MI dramatically increased levels of dimethylamine, and AT prevented this response. Our findings suggest that AT may be useful in preventing the negative changes in functional, inflammatory, and metabolic parameters related to MI in ovariectomized rats.     

A molecular phylogeny of the lizard genus Phymaturus (Squamata,Liolaemini): Implications for species diversity and historical biogeography of southern South America

The lizard genus Phymaturus is widely distributed in Argentina and along the eastern edge of Chile between 25° and 45° south. We sampled 27 of the 38 currently recognized species plus 22 candidate species using two mitochondrial genes (cytb and 12S), four protein coding nuclear genes and seven anonymous nuclear loci, and present the first comprehensive molecular phylogenetic hypothesis for the clade. We recovered two large clades (the palluma or northern group and patagonicus or southern group) previously recognized on the basis of morphological and mitochondrial sequence evidence, and compared results obtained from concatenated-gene analyses with results of a coalescent-based species-tree approach (BEST). With both methods we identified four main clades within the palluma group (mallimaccii, roigorum, verdugo, and vociferator) and five main clades within the patagonicus group (calcogaster, indistinctus, payuniae, somuncurensis, and spurcus). We found several instances of non-monophyly with cytb and cases of incongruence between mitochondrial vs nuclear data for which we discuss alternative hypotheses. Although with lower support values, combined BEST results are more congruent with concatenated nuclear data than with combined concatenated analyses, suggesting that BEST is less influenced by demographic processes than combined concatenated analyses. We discuss the taxonomic, biogeographic and conservation implications of these results and how the future integration of phylogeographic and morphological approaches will allow the further testing of demographic and biogeographic hypotheses.