Physical energies to the rescue of damaged tissues

Rhythmic oscillatory patterns sustain cellular dynamics, driving the concerted action of regulatory molecules, microtubules, and molecular motors. We describe cellular microtubules as oscillators capable of synchronization and swarming,generating mechanical and electric patterns that impact biomolecular recognition.We consider the biological relevance of seeing the inside of cells populated by a network of molecules that behave as bioelectronic circuits and chromophores. We discuss the novel perspectives disclosed by mechanobiology,bioelectromagnetism, and photobiomodulation, both in term of fundamental basic science and in light of the biomedical implication of using physical energies to govern(stem) cell fate. We focus on the feasibility of exploiting atomic force microscopy and hyperspectral imaging to detect signatures of nanomotions and electromagnetic radiation(light), respectively, generated by the stem cells across the specification of their multilineage repertoire. The chance is reported of using these signatures and the diffusive features of physical waves to direct specifically the differentiation program of stem cells in situ, where they already are resident in all the tissues of the human body. We discuss how this strategy may pave the way to a regenerative and precision medicine without the needs for(stem) cell or tissue transplantation. We describe a novel paradigm based upon boosting our inherent ability for self-healing.     

Coexistence trend contingent to Mediterranean oaks with different leaf habits

In a previous work we developed a mathematical model to explain the co‐occurrence of evergreen and deciduous oak groups in the Mediterranean region, regarded as one of the distinctive features of Mediterranean biodiversity. The mathematical analysis showed that a stabilizing mechanism resulting from niche difference (i.e. different water use and water stress tolerance) between groups allows their coexistence at intermediate values of suitable soil water content. A simple formal derivation of the model expresses this hypothesis in a testable form linked uniquely to the actual evapotranspiration of forests community. In the present work we ascertain whether this simplified conclusion possesses some degree of explanatory power by comparing available data on oaks distributions and remotely sensed evapotranspiration (MODIS product) in a large‐scale survey embracing the western Mediterranean area. Our findings confirmed the basic assumptions of model addressed on large scale, but also revealed asymmetric responses to water use and water stress tolerance between evergreen and deciduous oaks that should be taken into account to increase the understating of species interactions and, ultimately, improve the modeling capacity to explain co‐occurrence.     

Analysis of DNA-damage response to ionizing radiation in serum-shock synchronized human fibroblasts

Many aspects of cellular physiology, including cellular response to genotoxic stress, are related to the circadian rhythmicity induced by the molecular clock. The current study investigated if the cellular response to DNA damage is in relation to endogenous expression levels of the PER2 protein, a key component of the molecular regulatory system that confers rhythmicity in mammalian cells. Human normal fibroblasts (CCD-34Lu) were subjected to serum shock to induce circadian oscillations of the PER2 protein and then irradiated with γ- rays at times corresponding to the trough and peak expression of the PER2 protein. To better examine cellular response to DNA damage, the experiments performed in this study were carried out in non-proliferating CCD-34Lu fibroblasts in order to maintain the cell and circadian cycles separated while they were being exposed to genotoxic stress. Study results demonstrated that clonogenic cell survival, double-strand break repair kinetics, and TP53 protein levels were affected in the cells irradiated at the trough than in those irradiated at peak expression of the PER2 protein.     

Design and synthesis of a novel inhibitor of T. Viride chitinase through an in silico target fishing protocol

In the last ten years, we identified and developed a new therapeutic class of antifungal agents, the macrocyclic amidinoureas. These compounds are active against several Candida species, including clinical isolates resistant to currently available antifungal drugs. The mode of action of these molecules is still unknown. In this work, we developed an in-silico target fishing procedure to identify a possible target for this class of compounds based on shape similarity, inverse docking procedure and consensus score rank-by-rank. Chitinase enzyme emerged as possible target. To confirm this hypothesis a novel macrocyclic derivative has been produced, specifically designed to increase the inhibition of the chitinase. Biological evaluation highlights a stronger enzymatic inhibition for the new derivative, while its antifungal activity drops probably because of pharmacokinetic issues. Collectively, our data suggest that chitinase represent at least one of the main target of macrocyclic amidinoureas.     

Landscape simplification weakens the association between terrestrial producer and consumer diversity in Europe

Land‐use change is one of the primary drivers of species loss, yet little is known about its effect on other components of biodiversity that may be at risk. Here, we ask whether, and to what extent, landscape simplification, measured as the percentage of arable land in the landscape, disrupts the functional and phylogenetic association between primary producers and consumers. Across seven European regions, we inferred the potential associations (functional and phylogenetic) between host plants and butterflies in 561 seminatural grasslands. Local plant diversity showed a strong bottom‐up effect on butterfly diversity in the most complex landscapes, but this effect disappeared in simple landscapes. The functional associations between plant and butterflies are, therefore, the results of processes that act not only locally but are also dependent on the surrounding landscape context. Similarly, landscape simplification reduced the phylogenetic congruence among host plants and butterflies indicating that closely related butterflies become more generalist in the resources used. These processes occurred without any detectable change in species richness of plants or butterflies along the gradient of arable land. The structural properties of ecosystems are experiencing substantial erosion, with potentially pervasive effects on ecosystem functions and future evolutionary trajectories. Loss of interacting species might trigger cascading extinction events and reduce the stability of trophic interactions, as well as influence the longer term resilience of ecosystem functions. This underscores a growing realization that species richness is a crude and insensitive metric and that both functional and phylogenetic associations, measured across multiple trophic levels, are likely to provide additional and deeper insights into the resilience of ecosystems and the functions they provide.     

Taste-active compounds in a traditional Italian food: 'lampascioni'

Nature is a rich source of taste-active compounds, in particular of plant origin, many of which have unusual tastes. Many of these are found in traditional food, where spontaneous plants are used as ingredients. Some taste-active compounds were identified in the bulbs of Muscari comosum, a spontaneous plant belonging to the family of the Liliaceae, very common in the Mediterranean area, and used in traditional gastronomy (called 'lampascioni' in South Italy). The bulbs were extracted with a series of solvents of different polarity. The different fractions were submitted to a preliminary sensory evaluation, and the most interesting ones, characterized by a strong bitter taste and some chemestetic properties, were submitted to further purification and structural analysis. From the ethereal extract, several 3-benzyl-4-chromanones and one stilbene derivative were isolated. Pure compounds were examined for their taste activity by means of sensory evaluation, and proved to be responsible for the characteristic taste of this food. Some of these compounds have been synthesized de novo to confirm their structure.