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This paper presents correlations derived by linear regression analysis of seismic velocities VP and VS and elastic moduli EP and ES with temperature in Los Humeros superhot (SHGS) and Acoculco enhanced (EGS) geothermal systems at depths down to 3 km below the surface and temperatures up to approximately 400 °C. In Los Humeros, the seismic velocity models were derived from the inversion of legacy active seismic survey data acquired in 1998, as well as from passive seismic monitoring and ambient seismic noise interferometry carried out during 2017–2019 by the GEMex consortium. In the Acoculco EGS, ambient seismic noise data were used. Steady-state formation temperatures were re-evaluated during and after the end of the GEMex project using measurements provided as a courtesy of the Federal Electricity Commission of Mexico (CFE). The density data needed for the calculation of elastic moduli were provided by the GEMex consortium, as derived from the inversion of regional and local gravity surveys. The analysis indicated that statistically significant correlations of seismic parameters to temperature exist in the vertical direction, namely exponential in Los Humeros superhot and logarithmic in Acoculco EGS, but no correlation was evident in the horizontal direction. This result suggests an indirect relationship among the considered variables due to interdependence on other parameters, such as pressure and vapor saturation. As the analysis was performed using only data obtained from sensing-at-surface methods, without direct geophysical calibration at depth, a distributed fiber-optic seismic and temperature sensing system at both surface and downhole is proposed for active-source and passive seismic monitoring, and seismic-while-drilling by the drill-bit source is considered for reverse vertical seismic profile (RVSP) recording whenever possible for future high-temperature geothermal applications.

Structural investigations of receptor-ligand interactions on living cells surface by high-resolution Nuclear Magnetic Resonance (NMR) are problematic due to their short lifetime, which often prevents the acquisition of experiments longer than few hours. To overcome these limitations, we developed an on-cell NMR-based approach for exploring the molecular determinants driving the receptor-ligand recognition mechanism under native conditions. Our method relies on the combination of high-resolution structural and dynamics NMR data with Molecular Dynamics simulations and Molecular Docking studies. The key point of our strategy is the use of Non Uniform Sampling (NUS) and T1ρ-NMR techniques to collect atomic-resolution structural and dynamics information on the receptor-ligand interactions with living cells, that can be used as conformational constraints in computational studies. In fact, the application of these two NMR methodologies allows to record spectra with high S/N ratio and resolution within the lifetime of cells. In particular, 2D NUS [1H–1H] trNOESY spectra are used to explore the ligand conformational changes induced by receptor binding; whereas T1ρ-based experiments are applied to characterize the ligand binding epitope by defining two parameters: T1ρ Attenuation factor and T1ρ Binding Effect. This approach has been tested to characterize the molecular determinants regulating the recognition mechanism of αvβ5-integrin by a selective cyclic binder peptide named RGDechi15D. Our data demonstrate that the developed strategy represents an alternative in-cell NMR tool for studying, at atomic resolution, receptor-ligand recognition mechanism on living cells surface. Additionally, our application may be extremely useful for screening of the interaction profiling of drugs with their therapeutic targets in their native cellular environment.

Abstract The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370–394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed. We show that AIF(370-394) interacts with CypA on the same surface recognized by AIF(Δ1-121) protein and that the region is very close to the CypA catalytic pocket. Such region partially overlaps with the binding site of cyclosporin A (CsA), the strongest catalytic inhibitor of CypA. Our data point toward distinct CypA structural determinants governing the inhibitor selectivity and the differential biological effects of AIF and CsA, and provide new structural insights for designing CypA/AIF selective inhibitors with therapeutic relevance in neurodegenerative diseases.