Understanding the specificity of receptor tyrosine kinases signaling

Tyrosine kinase receptors (RTKs) represent a large family of transmembrane proteins,1,2 present in all metazoans, whose function is to transduce signals from the extracellular milieu to the inside of the cells. The common features of this protein family are: the extracellular domain, devoted to the binding to the specific receptor ligand, a single transmembrane region, and an intracellular chain featuring the conserved protein tyrosine kinase domain. RTKs control many aspects of cellular physiology both during development and in adult life, such as cell proliferation, migration, survival and differentiation.

Reciprocal control of cell proliferation and migration

In adult tissue the quiescent state of a single cell is maintained by the steady state conditions of its own microenvironment for what concern both cell-cell as well as cell-ECM interaction and soluble factors concentration. Physiological or pathological conditions can alter this quiescent state through an imbalance of both soluble and insoluble factors that can trigger a cellular phenotypic response. The kind of cellular response depends by many factors but one of the most important is the concentration of soluble cytokines sensed by the target cell. In addition, due to the intrinsic plasticity of many cellular types, every single cell is able, in response to the same stimulus, to rapidly switch phenotype supporting minimal changes of microenviromental cytokines concentration. Wound healing is a typical condition in which epithelial, endothelial as well as mesenchymal cells are firstly subjected to activation of their motility in order to repopulate the damaged region and then they show a strong proliferative response in order to successfully complete the wound repair process. This schema constitute the leitmotif of many other physiological or pathological conditions such as development vasculogenesis/angiogenesis as well as cancer outgrowth and metastasis

Geo-archaeology of the Roman palaeosurface of Sena Gallica (Senigallia, Italy)

ABSTRACTSena Gallica (Senigallia), in the northern Marche region, was the first Roman colony on the Adriatic coast founded at the beginning of the third century BC. This research adopted an integrated approach to different information sources that combines old and new data, archaeological excavations, topographic and geophysical surveys, and geological and geomorphological analyses. The data are managed within a GIS and supported by 3D modelling. One of the results of this work is a map which represents the geomorphological setting of the Roman colony, close to the mouth of the Misa river. The settlement exploited the top-surface of the uppermost Pleistocene–early Holocene coastal fan of the Misa river, now only preserved at the apex sector truncated seaward by wave erosion. The top-surface of the fan apex, in turn, was partly re-incised by stream erosion producing a series of slight topographic mounds, which were selected for the earliest human settlement (V-IV c. BC). Some of the mounds resulted in a pr..

Cysteinyl-glycine in the control of glutathione homeostasis in bovine lenses

PURPOSE: To define a possible metabolic and/or signaling role for Cys-Gly in glutathione homeostasis in bovine eye lenses. METHODS: Bovine lenses were cultured up to 24 h in a medium containing 0.5 mM reduced glutathione (GSH) under different conditions. The intracellular and the extracellular contents of thiol compounds were evaluated using a free zone capillary electrophoresis method. RESULTS: Culture of lenses in the presence of GSH and the gamma-glutamyl transferase inhibitor serine-borate demonstrated a 1.5 fold increase in the level of extra-lenticular glutathione with respect to the initial value. Cys-Gly exogenously added impaired the extra-lenticular accumulation of glutathione. Both cysteine and gamma-Glu-Cys were ineffective in reducing extra-lenticular glutathione accumulation. In all conditions no differences in reduced and total intra-lenticular glutathione levels were observed. CONCLUSIONS: The impairment of Cys-Gly generation correlated with inhibition of gamma-glutamyl transferase by serine/borate, resulting in high extra-lenticular concentration of glutathione effluxed from the bovine lens. The possibility that Cys-Gly may intervene either in the replenishment processes for cysteine in the GSH biosynthetic step or in the function of the efflux GSH-transporters is considered

Workflow of Digital Field Mapping and Drone-Aided Survey for the identification and Characterization of Capable Faults: The Case of a Normal Fault System in the Monte Nerone Area (Northern Apennines, Italy)

Field work on the search and characterization of ground effects of a historical earthquake (i.e., the Cagli earthquake in 1781) was carried out using terrestrial and aerial digital tools. The method of capturing, organizing, storing, and elaborating digital data is described herein, proposing a possible workflow starting from pre-field project organization, through reiteration of field and intermediate laboratory work, to final interpretation and synthesis. The case of one of the most important seismic events in the area of the northern Umbria–Marche Apennines provided the opportunity to test the method with both postgraduate students and researchers. The main result of this work was the mapping of a capable normal fault system with a great number of observations, as well as a large amount of data, from difficult outcrop areas. A GIS map and a three-dimensional (3D) model, with the integration of subsurface data (i.e., seismic profiles and recent earthquake distribution information), allowed for a new interpretation of an extensional tectonic regime of this Apennines sector, similar to one of the southernmost areas of central Italy where recent earthquakes occurred on 2016