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In the world of cultural heritage, a wide range of artefacts and buildings are made of wood and, therefore, are subjected to moisture-induced stress and strain cycles, owing to environmental fluctuations. Simultaneous action of moisture and mechanical loads lead to a mechanosorptive effect on wood. Therefore, an increase in time-dependent creep, due to mechanical loads, is observed. The assessment of these complex phenomena entails the use of advance and interdisciplinary approaches. Consequently, this article reviews experimental and mathematical methods to study these degradation mechanisms in wooden artefacts and timber elements in heritage buildings. The paper presents the results of a six-step descriptive literature review, providing an overall picture of the ongoing research. Experimental techniques need to be improved so that they are in line with the conservation principles. The combination of experiments and simulations is a reliable predictive approach for better assessing the potential risk damages due to temperature, humidity cycles, and mechanical loads in complex structures. Thus, advanced numerical simulations and mathematical modelling include climate data and experimental measurements. This work also provides an overview of research performed on different categories of cultural heritage characterised by multi-layer structures. The mechanical response to wood–moisture relation is affected by the level of complexity of these structures. Finally, the use of realistic models is limited by knowledge about the material properties and the behaviour of complex structures over time. In addition, research gaps, limitations, and possible future research directions are also provided. This review may represent a starting point for future research on the thermo-hygro-mechanical behaviour of wood heritage.

Peptidomimetic antimicrobials exhibit a selective interaction with bacterial cells over mammalian cells once they have achieved an optimum amphiphilic balance (hydrophobicity/hydrophilicity) in the molecular architecture.

Climate change is expected to significantly affect the interior climate of old, leaky buildings without HVAC systems. As a result, the items of cultural significance that are hosted indoors will experience new ambient conditions, which will affect their degradation. In the current research, the impact of climate change on the biological, mechanical, and chemical degradation of a cabinet and a storage trunk which are made of wood and have paintings on their outer surface is investigated. These two items are found in two different rooms of a historic timber building in Vestfold, Norway. Data from the REMO2015 driven by the global model MPI-ESM-LR are used in order to account for past, present, and future climate conditions. In addition, climate data from ERA5 reanalysis are used in order to assess the accuracy of the MPI-ES-LR_REMO2015 model results. Whole building hygrothermal simulations are employed to calculate the temperature and the relative humidity inside the rooms that host the items of interest. The transient hygrothermal condition and certain characteristics of the timber surfaces are used as inputs in models that describe their degradation. The biological degradation is examined by using i) the updated VTT mould model and ii) the Growing Degree Days (GDD) for temperature and humidity dependant insects. The mechanical deterioration is assessed by the method proposed by Mecklenburg et al. (1998). The concept of the Lifetime Multiplier (LM) is used in order to assess the chemical deterioration of the furniture. Results reveal a significant mechanical degradation risk and a very high chemical deterioration risk. The biodeterioration risk remains at acceptable levels. Moreover, it could be possible that the storage trunk would be damaged by certain insects in the future. It is then suggested that both items should be moved to a room with proper conditions in order to minimize their chemical and mechanical deterioration risk and extend their life span. Finally, the significance of implementing bias correction in the data from climate models is underlined.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic that broke out in 2020 and continues to be the cause of massive global upheaval. Coronaviruses are positive-strand RNA viruses with a genome of ~30 kb. The genome is replicated and transcribed by RNA-dependent RNA polymerase together with accessory factors. One of the latter is the protein helicase (NSP13), which is essential for viral replication. The recently solved helicase structure revealed a tertiary structure composed of five domains. Here, we investigated NSP13 from a structural point of view, comparing its RNA-free form with the RNA-engaged form by using atomistic molecular dynamics (MD) simulations at the microsecond timescale. Structural analyses revealed conformational changes that provide insights into the contribution of the different domains, identifying the residues responsible for domain–domain interactions in both observed forms. The RNA-free system appears to be more flexible than the RNA-engaged form. This result underlies the stabilizing role of the nucleic acid and the functional core role of these domains.

Theoretical work suggests that collective spatiotemporal behaviour of integral membrane proteins (IMPs) can be modulated by annular lipids sheathing their hydrophobic moiety. Here, we present evidence for this prediction in a natural membrane by investigating the mechanism that maintains steady amount of active isoform of Lck kinase (LckA) by Lck trans-autophosphorylation offset by the phosphatase CD45. We gauged experimental suitability by quantitation of CD45 and LckAsubcellular localisation, LckAgeneration as a function of Lck and pharmacological perturbation. Steady LckAwas challenged by swapping Lck membrane anchor with structurally divergent ones expected to substantially modify Lck annular lipids, such as that of Src or the transmembrane domains of LAT, CD4, palmitoylation-defective CD4 and CD45, respectively. The data showed only small alteration of LckA, except for CD45 hydrophobic anchor that thwarted LckA, due to excessive lateral proximity to CD45. The data are best explained by annular lipids facilitating or penalising IMPs’ lateral proximity, hence modulating IMPs protein-protein functional interactions. Our findings can contribute to improve the understanding of biomembranes’ organisation.

International audience; Theoretical work suggests that collective spatiotemporal behaviour of integral membrane proteins (IMPs) should be modulated by boundary lipids sheathing their membrane anchors. Here, we show evidence for this prediction whilst investigating the mechanism for maintaining a steady amount of the active form of IMP Lck kinase (LckA) by Lck trans-autophosphorylation regulated by the phosphatase CD45. We used super-resolution microscopy, flow cytometry, and pharmacological and genetic perturbation to gain insight into the spatiotemporal context of this process. We found that LckA is generated exclusively at the plasma membrane, where CD45 maintains it in a ceaseless dynamic equilibrium with its unphosphorylated precursor. Steady LckA shows linear dependence, after an initial threshold, over a considerable range of Lck expression levels. This behaviour fits a phenomenological model of trans-autophosphorylation that becomes more efficient with increasing LckA. We then challenged steady LckA formation by genetically swapping the Lck membrane anchor with structurally divergent ones, such as that of Src or the transmembrane domains of LAT, CD4, palmitoylation-defective CD4 and CD45 that were expected to drastically modify Lck boundary lipids. We observed small but significant changes in LckA generation, except for the CD45 transmembrane domain that drastically reduced LckA due to its excessive lateral proximity to CD45. Comprehensively, LckA formation and maintenance can be best explained by lipid bilayer critical density fluctuations rather than liquid-ordered phase-separated nanodomains, as previously thought, with "like/unlike" boundary lipids driving dynamical proximity and remoteness of Lck with itself and with CD45.

The COVID-19 pandemic is caused by SARS-CoV-2. Currently, most of the research efforts towards the development of vaccines and antibodies against SARS-CoV-2 were mainly focused on the spike (S) protein, which mediates virus entry into the host cell by binding to ACE2. As the virus SARS-CoV-2 continues to spread globally, variants have emerged, characterized by multiple mutations of the S glycoprotein. Herein, we employed microsecond-long molecular dynamics simulations to study the impact of the mutations of the S glycoprotein in SARS-CoV-2 Variant of Concern 202012/01 (B.1.1.7), termed the “UK variant”, in comparison with the wild type, with the aim to decipher the structural basis of the reported increased infectivity and virulence. The simulations provided insights on the different dynamics of UK and wild-type S glycoprotein, regarding in particular the Receptor Binding Domain (RBD). In addition, we investigated the role of glycans in modulating the conformational transitions of the RBD. The overall results showed that the UK mutant experiences higher flexibility in the RBD with respect to wild type, this behavior might be correlated with the increased transmission reported for this variant. Our work also adds useful structural information on antigenic “hotspots” and epitopes targeted by neutralizing antibodies.

Warehouses are big architectonical structures mostly made of spruce wood and utilized as storage buildings principally by food traders in Northern Countries. Trondheim’s warehouses currently observable along the river Nidelva, date back between the 17th and half of the 19th century were mostly used to stock and process fish. Therefore, where the food goods were stored, residuals are expected to be still present and/or to be responsible for the formation of alteration products on the wooden surfaces as well as inside the wooden structure. Here we propose a characterization of residual and neo-formed compounds inside and on the surface of wooden logs by means of vacuum microbalance that allowed both to individuate the type of salts, as well as, to estimate the maximum water film thickness adsorbed on the wooden samples at 93% of RH. These data have been related to variations in the acoustic emission (AE) intensity detected at the log surface and to the wood moisture content measured with capacitive and resistance operating moisture meters. The application of three independent techniques have allowed obtaining interestingly information indicating their potentiality as decay assessment techniques in the field of historical materials and specifically in the study of salts weathering on wood. The methodology allowed identifying a clear relationship between the amount of water in logs as a function of their distance from the ground and variations in the amplitude of the acoustic emission signals.

Background and AimsThe aim of this study was to apply machine learning models and a nomogram to differentiate critically ill from non-critically ill COVID-19 pneumonia patients.MethodsClinical symptoms and signs, laboratory parameters, cytokine profile, and immune cellular data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Outcomes were followed up until Mar 12, 2020. A logistic regression function (LR model), Random Forest, and XGBoost models were developed. The performance of these models was measured by area under receiver operating characteristic curve (AUC) analysis.ResultsUnivariate analysis revealed that there was a difference between critically and non-critically ill patients with respect to levels of interleukin-6, interleukin-10, T cells, CD4+ T, and CD8+ T cells. Interleukin-10 with an AUC of 0.86 was most useful predictor of critically ill patients with COVID-19 pneumonia. Ten variables (respiratory rate, neutrophil counts, aspartate transaminase, albumin, serum procalcitonin, D-dimer and B-type natriuretic peptide, CD4+ T cells, interleukin-6 and interleukin-10) were used as candidate predictors for LR model, Random Forest (RF) and XGBoost model application. The coefficients from LR model were utilized to build a nomogram. RF and XGBoost methods suggested that Interleukin-10 and interleukin-6 were the most important variables for severity of illness prediction. The mean AUC for LR, RF, and XGBoost model were 0.91, 0.89, and 0.93 respectively (in two-fold cross-validation). Individualized prediction by XGBoost model was explained by local interpretable model-agnostic explanations (LIME) plot.ConclusionsXGBoost exhibited the highest discriminatory performance for prediction of critically ill patients with COVID-19 pneumonia. It is inferred that the nomogram and visualized interpretation with LIME plot could be useful in the clinical setting. Additionally, interleukin-10 could serve as a useful predictor of critically ill patients with COVID-19 pneumonia.

The thyroid-stimulating hormone receptor (TSHR) has been indicated as a putative domestication gene in chicken. Comparison of WGS identified a variant in residue 558 of the transmembrane domain (TM) of TSHR, where the domestic chicken (GGD) presents an arginine, whereas the red jungle fowl (RJF) shares a conserved glycine with other vertebrates. This variant has been demonstrated to be associated with phenotypes that are important for domestication and related to thyroid regulation, such as less fearful behavior, reduced aggressive behavior and reduced dependence on seasonal reproduction in GGD as compared with RJF. By means of molecular dynamics simulations, we highlighted the structural and dynamic differences of variant Gly558Arg in the TSHR TM domain. Alterations in TM helix flexibility, structure and protein overall motion are described. The so-called 'arginine snorkeling' of residue 568 in GGD is observed and we hypothesize it as the originating force that produces the observed whole-protein perturbation in the helix bundle dynamics, capable of altering the TSHR signal transduction. The results are discussed in the context of their implications for a better understanding of biological mechanisms in chicken under control of the thyroid, such as body metabolism, as well as for their usefulness in biomedical research.

Cocaine abuse is rising in the young population, triggering uncommon and potentially life-threatening causes of acute abdomen in this age group. The authors present the case of a 30-year-old man with emergency admission due to abdominal pain, with no history of drug abuse. Several signs and symptoms elicited toxicologic blood screening, which disclosed high serum levels of cocaine and its metabolites. Twelve hours after admission, the onset of acute abdomen with signs of diffuse peritonitis prompted surgical exploration through a minimally invasive approach. Two segmental small bowel ischemic loops and diffuse peritonitis, but no bowel perforation, were identified and treated by laparoscopic peritoneal lavage with 5 l of heated saline and intravenous administration of sodium heparin, 10 000 IU. Postoperative course was uneventful with home discharge on postoperative day 5. High index of suspicion is required to establish a prompt diagnosis and treatment of this uncommon cocaine abuse-related disease.

The conformational state of the activation loop (A-loop) is pivotal for the activity of most protein kinases. Hence, the characterization of the conformational dynamics of the A-loop is important to increase our understanding of the molecular processes related to diseases and to support the discovery of small molecule kinase inhibitors. Here, we carry out a combination of molecular dynamics (MD) and essential dynamics (ED) analyses to fully map the effects of phosphorylation, ADP, and conformation disrupting (CD) inhibitors (i.e., CD532 and MLN8054) on the dynamics of the A-loop of Aurora-A. MD revealed that the stability of the A-loop in an open conformation is enhanced by single phospho-Thr-288, while paradoxically, the presence of a second phosphorylation at Thr-287 decreases such stability and renders the A-loop more fluctuant in time and space. Moreover, we found that this post-translational modification has a significant effect on the direction of the A-loop motions. ED analysis suggests that the presence of the phosphate moiety induces the dynamics of Aurora-A to sample two distinct energy minima, instead of a single large minimum, as in unphosphorylated Aurora-A states. This observation indicates that the conformational distributions of Aurora-A with both single and double phospho-threonine modifications are remarkably different from the unphosphorylated state. In the closed states, binding of CD532 and MLN8054 inhibitors has the effect of increasing the distance of the N- and C-lobes of the kinase domain of Aurora-A, and the angle analysis between those two lobes during MD simulations showed that the N- and C-lobes are kept more open in presence of CD532, compared to MLN8054. As the A-loop is a common feature of Aurora protein kinases, our studies provide a general description of the conformational dynamics of this structure upon phosphorylation and different ligands binding.

Given the enormous social and health impact of the pandemic triggered by severe acute respiratory syndrome 2 (SARS-CoV-2), the scientific community made a huge effort to provide an immediate response to the challenges posed by Coronavirus disease 2019 (COVID-19). One of the most important proteins of the virus is an enzyme, called 3CLpro or main protease, already identified as an important pharmacological target also in SARS and Middle East respiratory syndrome virus (MERS) viruses. This protein triggers the production of a whole series of enzymes necessary for the virus to carry out its replicating and infectious activities. Therefore, it is crucial to gain a deeper understanding of 3CLpro structure and function in order to effectively target this enzyme. All-atoms molecular dynamics (MD) simulations were performed to examine the different conformational behaviors of the monomeric and dimeric form of SARS-CoV-2 3CLpro apo structure, as revealed by microsecond time scale MD simulations. Our results also shed light on the conformational dynamics of the loop regions at the entry of the catalytic site. Studying, at atomic level, the characteristics of the active site and obtaining information on how the protein can interact with its substrates will allow the design of molecules able to block the enzymatic function crucial for the virus.