Unrest at Campi Flegrei: A contribution to the magmatic versus hydrothermal debate from inverse and finite element modeling

[ 1] We present results from the modeling of ground deformation and microgravimetric data recorded at Campi Flegrei in order to assess the causative phenomena of caldera unrest between 1981 and 2001. We find that residual gravity changes during ground uplift ( 1982 - 1984) are indicative of mass changes in a hybrid of magmatic and hydrothermal sources. During deflation between 1985 and 2001, the inversion of gravity residuals for a single source does not provide convincing results. We then performed the joint inversion of gravity and deformation data for multiple spherical sources and refined source parameters by finite element modeling in order to mitigate against limitations of the analytical solutions. The data recorded during inflation and rapid deflation may be best explained by mass and pressure changes in a deep magmatic source at about 5 km depth and a shallow ( 2 km deep) hydrothermal source. Both sources contribute equally to the gravity changes observed between 1982 and 1984; the contemporary uplift appears to be mainly caused by the shallow source. The subsequent deflation is dominated by a pressure decrease in the hydrothermal source; the magmatic source contributes chiefly to the observed gravity changes. Pressure and density variations within multiple shallow-seated hydrothermal sources provide acceptable fits to the deflation and accompanying gravity changes recorded since 1988. These shallow level dynamics also appear to trigger spatially and temporarily random short-term reversals of the overall mode of ground subsidence since 1985. Our analysis does not support the idea of magmatic contributions to these short-lived periods of inflation

4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors

In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2. © 2021 Elsevier Inc

Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice

Summary: Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca2+ signaling, vesicle cycling, and AMPA-receptor exocytosis, thus suggesting a role in long-term potentiation (LTP). Finally, we show that, in the CA1 hippocampal region, the attenuation of CS56 glycoepitopes, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in mice. These findings show that activity-dependent remodeling of the peri-synaptic ECM regulates the induction and consolidation of LTP, contributing to hippocampal-dependent memory

An Experimental Investigation of Emotions and Reasoning in the Trolley Problem

experiments, intuition, moral emotions, moral judgement, moral reasoning, trolley problem,