Evidence for the formation of linearo ligopeptides with nonrandoms equences from mixtures of amino acids coadsorbed on silica ands ubmitted to as imple thermal activation is presented. The amino acid couples (glutamic acid + leucine)a nd (aspartic acid + valine) were deposited on a fumed silica and submitted to as ingle heating step at moderate temperature. The evolution of the systemsw as characterized by X-ray diffraction, infrared spectroscopy,t hermosgravimetric analysis, HPLC, and electrospray ionizationm ass spectrometry (ESI-MS). Evidence for the formation of amide bonds was found in all systemss tudied. Whilet he products of single aminoa cids activation on silica could be consid-ered as evolutionary dead ends, (glutamic acid + leucine) and, at to somee xtent, (aspartic acid + valine) gave rise to the high yield formation of linear peptides up to the hexamers. Oligopeptides of such length have not been observed beforei ns urface polymerization scenarios (unless the amino acids had been depositedb yc hemical vapor deposition, which is not realistic in ap rebiotic environment). Furthermore,n ot all possible amino acid sequences werep resent in the activation products,w hich is indicative of polymerization selectivity.These resultsare promisingf or origins of life studies because they suggest the emergence of nonrandom biopolymers in as imple prebiotic scenario.

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The prominent impact that coronary microcirculation disease (CMD) exerts on heart failure symptoms and prognosis, even in the presence of macrovascular atherosclerosis, has been recently acknowledged. Experimental delivery of pericytes in non-revascularized myocardial infarction improves cardiac function by stimulating angiogenesis and myocardial perfusion.Aim of this work is to verify if pericytes (Pc) residing in ischemic failing human hearts display altered mechano-transduction properties and to assess which alterations of the mechano-sensing machinery are associated with the observed impaired response to mechanical cues. Results: Microvascular rarefaction and defects of YAP/TAZ activation characterize failing human hearts. Although both donor (D-) and explanted (E-) heart derived cardiac Pc support angiogenesis, D-Pc exert this effect significantly better than E-Pc. The latter are characterized by reduced focal adhesion density, decreased activation of the focal adhesion kinase (FAK)/ Crk-associated substrate (CAS) pathway, low expression of caveolin-1, and defective transduction of extracellular stiffness into cytoskeletal stiffening, together with an impaired response to both fibronectin and lysophosphatidic acid. Importantly, Mitogen-activated protein kinase kinase inhibition restores YAP/TAZ nuclear translocation. Conclusion: Heart failure impairs Pc mechano-transduction properties, but this defect could be reversed pharmacologically.

Thymosin β4 (Tβ4) is a small, 44-amino acid polypeptide. It has been implicated in multiple processes, including cell movement, angiogenesis, and stemness. Previously, we reported that melanoma cell lines differ in Tβ4 levels. Studies on stable clones with silenced TMSB4X expression showed that Tβ4 impacted adhesion and epithelial-mesenchymal transition progression. Here, we show that the cells with silenced TMSB4X expression exhibited altered actin cytoskeleton’s organization and subcellular relocalization of two intermediate filament proteins: Nestin and Vimentin. The rearrangement of the cell cytoskeleton resulted in changes in the cells’ topology, height, and stiffness defined by Young’s modulus. Simultaneously, only for some A375 clones with a lowered Tβ4 level, we observed a decreased ability to initiate colony formation in soft agar, tumor formation in vivo, and alterations in Nanog’s expression level transcription factor regulating stemness. Thus, we show for the first time that in A375 cells, biomechanical properties are not directly coupled to stemness features, and this cell line is phenotypically heterogeneous.