Communication: Role of explicit water models in the helix folding/unfolding processes

In the last years, it has become evident that computer simulations can assume a relevant role in modelling protein dynamical motions for their ability to provide a full atomistic image of the processes under investigation. The ability of the current protein force-fields in reproducing the correct thermodynamics and kinetics systems behaviour is thus an essential ingredient to improve our understanding of many relevant biological functionalities. In this work, employing the last developments of the metadynamics framework, we compare the ability of state-of-the-art all-atom empirical functions and water models to consistently reproduce the folding and unfolding of a helix turn motif in a model peptide. This theoretical study puts in evidence that the choice of the water models can influence the thermodynamic and the kinetics of the system under investigation, and for this reason cannot be considered trivial

Integrating Superconductive and Optical Circuits

We have integrated on oxidized silicon wafers superconductive films and Josephson junctions along with sol-gel optical channel waveguides. The fabrication process is carried out in two steps that result to be solid and non-invasive. It is demonstrated that 660 nm light, coupled from an optical fibre into the channel sol-gel waveguide, can be directed toward superconducting tunnel junctions whose current-voltage characteristics are affected by the presence of the radiation. The dependence of the change in the superconducting energy gap under optical pumping is discussed in terms of a non-equilibrium superconductivity model.Comment: Document composed of 7 pages of text and 3 figure

The Italian fund for Alzheimer's and other dementias: strategies and objectives to face the dementia challenge

The Italian Fund for Alzheimer's and other dementias was approved and signed in December 2021. The Fund is financed with 15 million euros in three years. The main goal is to provide new strategies in the field of dementia with a Public Health perspective. The Fund includes eight main activities that will be monitored and supervised by the Italian National Institute of Health: 1) development of a guideline for the assessment, management and support for people with dementia and their families/carers; 2) updating of the Dementia National Plan (DNP); 3) implementation of the documents of the DNP; 4) conducting surveys dedicated to the Italian Dementia Services; 5) promotion of dementia prevention strategies; 6) training strategies for healthcare professionals, families and caregivers; 7) creation of a National Electronic Record for Dementia; 8) evaluation and monitoring of activities promoted by Regions and Autonomous Provinces in the field of dementia, together with the dementia National Permanent Table. These activities are outlined in detail in the present paper

A practical guide to the simultaneous determination of protein structure and dynamics using metainference

Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of uncertainty and errors as well as with system heterogeneity. Furthermore, metainference can be implemented using the metadynamics approach, which enables the computational study of complex biological systems requiring extensive conformational sampling. In this chapter, we provide a step-by-step guide to perform and analyse metadynamic metainference simulations using the ISDB module of the open-source PLUMED library, as well as a series of practical tips to avoid common mistakes. Specifically, we will guide the reader in the process of learning how to model the structural ensemble of a small disordered peptide by combining state-of-the-art molecular mechanics force fields with nuclear magnetic resonance data, including chemical shifts, scalar couplings and residual dipolar couplings.Comment: 49 pages, 9 figure

Methods of probing the interactions between small molecules and disordered proteins

It is generally recognized that a large fraction of the human proteome is made up of proteins that remain disordered in their native states. Despite the fact that such proteins play key biological roles and are involved in many major human diseases, they still represent challenging targets for drug discovery. A major bottleneck for the identification of compounds capable of interacting with these proteins and modulating their disease-promoting behaviour is the development of effective techniques to probe such interactions. The difficulties in carrying out binding measurements have resulted in a poor understanding of the mechanisms underlying these interactions. In order to facilitate further methodological advances, here we review the most commonly used techniques to probe three types of interactions involving small molecules: (1) those that disrupt functional interactions between disordered proteins; (2) those that inhibit the aberrant aggregation of disordered proteins, and (3) those that lead to binding disordered proteins in their monomeric states. In discussing these techniques, we also point out directions for future developments.Gabriella T. Heller is supported by the Gates Cambridge Trust Scholarship. Francesco A. Aprile is supported by a Senior Research Fellowship award from the Alzheimer’s Society, UK (grant number 317, AS-SF-16-003)

Latest Cretaceous climatic and environmental change in the South Atlantic region

Latest Maastrichtian climate change caused by Deccan volcanism has been invoked as a cause of mass extinction at the Cretaceous-Paleogene (K-Pg) boundary (~66.0 Ma). Yet late Maastrichtian climate and ecological changes are poorly documented, in particular on the Southern Hemisphere. Here we present upper Maastrichtian-lower Danian climate and biotic records from the Bajada del Jagüel (BJ) shelf site (Neuquén Basin, Argentina), employing the TEX86 paleothermometer, marine palynology (dinoflagellate cysts), and micropaleontology (foraminifera). These records are correlated to the astronomically tuned Ocean Drilling Program Site 1262 (Walvis Ridge). Collectively, we use these records to assess climatic and ecological effects of Deccan volcanism in the Southern Atlantic region. Both the TEX86-based sea surface temperature (SST) record at BJ and the bulk carbonate δ18O-based SST record of Site 1262 show a latest Maastrichtian warming of ~2.5-4°C, at 450 to 150 kyr before the K-Pg boundary, coinciding with the a large Deccan outpouring phase. Benthic foraminiferal and dinocyst assemblage changes indicate that this warming resulted in enhanced runoff and stratification of the water column, likely resulting from more humid climate conditions in the Neuquén Basin. These climate conditions could have been caused by an expanding and strengthening thermal low over the South American continent. Biotic changes in response to late Maastrichtian environmental changes are rather limited, when compared to the major turnovers observed at many K-Pg boundary sites worldwide. This suggests that environmental perturbations during the latest Maastrichtian warming event were less severe than those following the K-Pg boundary impact

Bragg grating optical filters by UV nanoimprinting

Results on an optical waveguide filter operating in the near IR region are reported. The device consists of a hybrid sol-gel -based grating loaded waveguide, obtained through the merging of conventional photolithography and UV-nanoimprinting. Starting from submicrometric gratings, fabricated by electron beam lithography, a soft mould has been produced and the original structures were replicated onto sol-gel photosensitive films. A final photolithographic step allowed the production of grating-loaded channel waveguides. The devices were optically characterized by transmission measurements in the telecom range 1450–1590 nm. The filter extinction ratio is −11 dB and the bandwidth is 1.7 nm