Release dynamics of nanodiamonds created by laser-driven shock-compression of polyethylene terephthalate.

Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states. Analysing the structural integrity along different release paths via molecular dynamic simulations, we found substantial disintegration rates upon shock release, increasing with the on-Hugnoiot shock temperature. We also find that recrystallization can occur after the expansion and hence during the release, depending on subsequent cooling mechanisms. Our study suggests higher ND recovery rates from off-Hugoniot states, e.g., via double-shocks, due to faster cooling. Laser-driven shock compression experiments of polyethylene terephthalate (PET) samples with in situ X-ray probing at the simulated conditions found diamond signal that persists up to 11 ns after breakout. In the diffraction pattern, we observed peak shifts, which we attribute to thermal expansion of the NDs and thus a total release of pressure, which indicates the stability of the released NDs.

Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry.

INTRODUCTION: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors. METHODS: Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models. RESULTS: Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV-2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5-7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections. CONCLUSION: VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.

Improving Antibiotic Prescribing for Dentistry in France Using an Ontology.

Antibiotic overprescribing in dentistry is a major concern that contributes to the emergence of antimicrobial resistance. It is due in part to the misuse of antibiotics by dentists but also by other practitioners who see patients in emergency for dental care. We used the Protégé software to create an ontology regarding the most common dental diseases and the most used antibiotics to treat them. It is an easy shareable knowledge base that could be used directly as decision support tool to improve the use of antibiotics in dental care.

Diamond formation kinetics in shock-compressed C─H─O samples recorded by small-angle x-ray scattering and x-ray diffraction.

Extreme conditions inside ice giants such as Uranus and Neptune can result in peculiar chemistry and structural transitions, e.g., the precipitation of diamonds or superionic water, as so far experimentally observed only for pure C─H and H2O systems, respectively. Here, we investigate a stoichiometric mixture of C and H2O by shock-compressing polyethylene terephthalate (PET) plastics and performing in situ x-ray probing. We observe diamond formation at pressures between 72 ± 7 and 125 ± 13 GPa at temperatures ranging from ~3500 to ~6000 K. Combining x-ray diffraction and small-angle x-ray scattering, we access the kinetics of this exotic reaction. The observed demixing of C and H2O suggests that diamond precipitation inside the ice giants is enhanced by oxygen, which can lead to isolated water and thus the formation of superionic structures relevant to the planets' magnetic fields. Moreover, our measurements indicate a way of producing nanodiamonds by simple laser-driven shock compression of cheap PET plastics.

Stability of high-temperature salty ice suggests electrolyte permeability in water-rich exoplanet icy mantles.

Electrolytes play an important role in the internal structure and dynamics of water-rich satellites and potentially water-rich exoplanets. However, in planets, the presence of a large high-pressure ice mantle is thought to hinder the exchange and transport of electrolytes between various liquid and solid deep layers. Here we show, using first-principles simulations, that up to 2.5 wt% NaCl can be dissolved in dense water ice at interior conditions of water-rich super-Earths and mini-Neptunes. The salt impurities enhance the diffusion of H atoms, extending the stability field of recently discovered superionic ice, and push towards higher pressures the transition to the stiffer ice X phase. Scaling laws for thermo-compositional convection show that salts entering the high pressure ice layer can be readily transported across. These findings suggest that the high-pressure ice mantle of water-rich exoplanets is permeable to the convective transport of electrolytes between the inner rocky core and the outer liquid layer.

Fast-ion conduction and local environments in BIMEVOX.

The energy landscape of the fast-ion conductor Bi4V2O11 is studied using density functional theory. There are a large number of energy minima, dominated by low-lying thermally accessible configurations in which there are equal numbers of oxygen vacancies in each vanadium-oxygen layer, a range of vanadium coordinations and a large variation in Bi-O and V-O distances. By dividing local minima in the energy landscape into sets of configurations, we then examine diffusion in each different layer using ab initio molecular dynamics. These simulations show that the diffusion mechanism mainly takes place in the 〈110〉 directions in the vanadium layers, involving the cooperative motion of the oxide ions between the O(2) and O(3) sites in these layers, but not O(1) in the Bi-O layers, in agreement with experiment. O(1) vacancies in the Bi-O layers are readily filled by the migration of oxygens from the V-O layers. The calculated ionic conductivity is in reasonable agreement with the experiment. We compare ion conduction in δ-Bi4V2O11 with that in δ-Bi2O3. This article is part of the Theo Murphy meeting issue 'Understanding fast-ion conduction in solid electrolytes'.

Analyzing Melts and Fluids from Ab Initio Molecular Dynamics Simulations with the UMD Package.

We have developed a Python-based open-source package to analyze the results stemming from ab initio molecular-dynamics simulations of fluids. The package is best suited for applications on natural systems, like silicate and oxide melts, water-based fluids, and various supercritical fluids. The package is a collection of Python scripts that include two major libraries dealing with file formats and with crystallography. All the scripts are run at the command line. We propose a simplified format to store the atomic trajectories and relevant thermodynamic information of the simulations, which is saved in UMD files, standing for Universal Molecular Dynamics. The UMD package allows the computation of a series of structural, transport and thermodynamic properties. Starting with the pair-distribution function it defines bond lengths, builds an interatomic connectivity matrix, and eventually determines the chemical speciation. Determining the lifetime of the chemical species allows running a full statistical analysis. Then dedicated scripts compute the mean-square displacements for the atoms as well as for the chemical species. The implemented self-correlation analysis of the atomic velocities yields the diffusion coefficients and the vibrational spectrum. The same analysis applied on the stresses yields the viscosity. The package is available via the GitHub website and via its own dedicated page of the ERC IMPACT project as open-access package.

Lactation and gestation controls on calcium isotopic compositions in a mammalian model.

Lactation and gestation are among the physiological events that trigger the most intense changes in body calcium (Ca) fluxes. Along with the composition of the animal 2021 diet, these events are suspected to impact the Ca isotopic composition of Ca body reservoirs but their dynamics are poorly understood. In this study, we monitored a group of domestic sows across a full reproduction cycle. We collected tissues and fluids (blood, urine, milk, colostrum, umbilical blood, adult and piglet bones) at different steps of gestation and lactation, and analyzed their Ca isotopic compositions (i.e. δ44/42Ca) by means of multi-collector inductively coupled plasma mass spectrometry. Among other results, we report the first observations of Ca isotopic fractionation between maternal and umbilical blood (Δ44/42Caumbilical blood-sow blood = -0.18 ± 0.11‰, n = 3). Our data also highlight that gestation and lactation periods are characterized by small diet-bone Ca isotopic offsets (Δ44/42Cabone-diet = -0.28 ± 0.11‰, n = 3), with 44Ca-enriched blood compositions during nursing (Δ44/42Canursing blood-gestation blood = $+ 0.42{\rm{\,\,}}_{ - 0.12}^{ + 0.11}$‰, n = 3). Under the light of an up-to-date mammalian box model, we explored different scenarios of gestation and lactation Ca fluxes experienced by a sow-like animal. These simulations suggest that gestation changes on body δ44/42Ca values may result from the intensification of Ca absorption by the animal, whereas the production of 44Ca-depleted milk is the main driver for the 44Ca enrichment in blood during lactation. In addition, our results also support that bone mineralization could be associated with a more restricted Ca isotopic fractionation than previously envisioned. Together, these results refine the framework of Ca isotope applications, notably regarding the monitoring of human bone balance and the study of species and ecosystems from the present and the past.

Safety and efficacy of a novel home-use device for light-potentiated (LED) skin treatment.

Skin structure and function results from a dynamic interplay between dermal and epidermal cell types. Optimizing skin health through an effective and long-lasting skin care regime therefore requires a global approach, encompassing various mechanisms to stimulate this interplay beyond the action scope of a classical topical solution. This study evaluates the impact of a novel home-use device combining a topical serum, light-emitting diodes and massage on the clinical signs of extrinsic skin aging. The innovative principle relies on potentiating the effect of active ingredients contained in the topical serum with visible and near infra-red photons to prevent extracellular matrix degradation and promote its reconstruction. After in vitro and ex vivo investigations, a clinical study assessed the safety and efficacy of a daily treatment with the home-use device for 28 days. A significant increases in skin density and radiance while reducing the wrinkles was obtained with no side effects.

In situ X-ray diffraction of silicate liquids and glasses under dynamic and static compression to megabar pressures.

Properties of liquid silicates under high-pressure and high-temperature conditions are critical for modeling the dynamics and solidification mechanisms of the magma ocean in the early Earth, as well as for constraining entrainment of melts in the mantle and in the present-day core-mantle boundary. Here we present in situ structural measurements by X-ray diffraction of selected amorphous silicates compressed statically in diamond anvil cells (up to 157 GPa at room temperature) or dynamically by laser-generated shock compression (up to 130 GPa and 6,000 K along the MgSiO3 glass Hugoniot). The X-ray diffraction patterns of silicate glasses and liquids reveal similar characteristics over a wide pressure and temperature range. Beyond the increase in Si coordination observed at 20 GPa, we find no evidence for major structural changes occurring in the silicate melts studied up to pressures and temperatures exceeding Earth's core mantle boundary conditions. This result is supported by molecular dynamics calculations. Our findings reinforce the widely used assumption that the silicate glasses studies are appropriate structural analogs for understanding the atomic arrangement of silicate liquids at these high pressures.

The release of pro-inflammatory cytokines is mediated via mitogen-activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes.

Toll-like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the 3-D structures of pathogen-associated molecules and are therefore useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides and monosodium urate (MSU) crystals in the activation of the TLR and NOD-like receptor (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NOD-like receptor P3 and TLR4, both of which are components of inflammasome complexes involved in the activation of interleukin (IL)-1ß, were not expressed in keratinocytes. Transcriptomic analysis showed that the combination of MSU and lipopolysaccharide priming did not elicit significant results compared to MSU treatment, which induced the expression of TLR2, IL-6 and IL-8/chemokine (C-X-C motif) ligand 8 CXCL8 in the keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of extracellular signal-regulated kinase 1/2 and MAPK14/p38α mitogen-activated protein kinases. We concluded that MSU stimulates a pro-inflammatory response in keratinocytes via mitogen-activated protein kinase pathway to induce production of IL-8/CXCL8 chemokine (C-X-C motif) ligand 8 and TLR2.

Superionic-Superionic Phase Transitions in Body-Centered Cubic H_{2}O Ice.

From first-principles molecular dynamics, we investigate the relation between the superionic proton conduction and the behavior of the O─H⋯O bond (ice VII^{'} to ice X transition) in body-centered-cubic (bcc) H_{2}O ice between 1300 and 2000 K and up to 300 GPa. We bring evidence that there are three distinct phases in the superionic bcc stability field. A first superionic phase characterized by extremely fast diffusion of highly delocalized protons (denoted VII^{''} hereinafter) is stable at low pressures. A first-order transition separates this phase from a superionic VII^{'}, characterized by a finite degree of localization of protons along the nonsymmetric O─H⋯O bonds. The transition is identified in structural, energetic, and elastic analysis. Upon further compression a second-order phase transition leads to the superionic ice X with symmetric O─H─O bonds.

Assessment of cellular actin dynamics by measurement of fluorescence anisotropy.

To study cellular actin dynamics, a cell-free assay based on fluorescence anisotropy was developed. Using G-actin-Alexa as a probe, we found that anisotropy enhancement reflects F-actin elongation. Anisotropy enhancement varies with the concentration of magnesium and calcium cations and with ethylenediaminetetraacetate or well-known effectors of the polymerization. This assay gives the overall status of actin dynamics in cell extracts which are the closest conditions to in vivo, implying most of the regulating proteins that are missing in purified actin measurements. It can be used in a large-scale screening for chemical compounds which modulate actin polymerization.

The human biological resource centres network. A key infrastructure for biomedical research in Europe.

Continuing advances in life sciences and medical research are the result of the remarkable achievements of cell and molecular biology. In the post-sequencing era, the quality of the huge amount of data continuously generated by biotechnology, i.e. genomics, proteomics and high-throughput screening, depends on the quality assurance and the traceability of the original biological materials, including the annotations linked to these materials. Thus, biological resource centres are key infrastructures supporting biotechnology, bioprocessing and the development of new approaches in the prevention, diagnosis and treatment of diseases.

Specific triazine resistance in bacterial reaction centers induced by a single mutation in the QA protein pocket.

We report here the first example of a reaction center mutant from Rhodobacter sphaeroides, where a single mutation (M266His --> Leu) taking place in the primary quinone protein pocket confers selective resistance to triazine-type inhibitors (terbutryn, ametryn, and atrazine), which bind in the secondary quinone protein pocket, at about 13 A from the mutation site. The M266His --> Leu mutation involves one of the iron atom ligands. Interestingly, neither the secondary quinone nor the highly specific inhibitor stigmatellin binding affinities are affected by the mutation. It is noticeable that in the M266His --> Ala mutant a nativelike behavior in observed. We suggest that the long side chain of Leu in position M266 may lack space to accommodate in the Q(A) pocket therefore transferring its hindrance to the Q(B) pocket. This may occur via the structural feature formed by the Q(A)-M219His-Fe-L190His-inhibitor (or Q(B)) connection, pushing L189Leu and/or L229Ile in closer contact to the triazine molecules, therefore decreasing their bindings. This opens the possibility to finely tune, in reaction center proteins, the affinity for herbicides by designing mutations distant from their binding sites.

Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy

This investigation was performed to verify the effect of specific chemotherapy (Benznidazole or MK-346) on the inflammatory and fibrotic cardiac alterations in mice chronically infected with the strains 21 SF (Type II) and Colombian (Type III) of Trypanosoma cruzi. To obtain chronically infected mice, two groups of 100 Swiss mice each, were infected with either the 21 SF or the Colombian strain (2x 10***4 and 5x 10***4 blood forms respectively). The rate of morality in the acute phase was of 80% for both groups. Twenty surviving mice chronically infected with the 21 SF strain and 20 with the Colombian strain were then divided in treated and untreated groups. Excluding those that died during the course of treatment, 14 mice chronically infected with the 21 SF strain and 15 with the Colombian strain were evaluated in the present study. Chemotherapy was performed with Benznidazole (N-benzil-2-nitro-1-imidazolacetamide) in the dose of 100mg/k.b.w/day, for 60 days, or with the MK-436(3(1-methyl-5 nitroimidazol-2-yl) in two daily doses of 250 mg/k.b.w, for 20 days. Parasitological cure tests were performed (xenodiagnosis, haemoculture, subinovulation of the blood into newborn mice), and serological indirect immunofluorescence test. The treated and untreated mice as well as intact controls were killed at different periods after treatment and the heart were submitted to histopathological study with hematoxilineosin and picrosirius staining; ultrastructural study; collagen immunotyping, fibronectin and laminin identification by immunofluorescence tests. Results: the untreated controls either infected with 21 SF or Colombian strain, showed inflammatory and fibrotic alterations that were mild to moderate with the 21 SF strain and intense with the Colombian strain. Redpicrosirius staining showed bundles of collagen in the interstitial space and around cardiac fibers. Increased deposits of mitritial components and collagen fibers, macrophages and fibroblasts appeared at the ultrastructural examination. Deposits of fibronectin, laminin, pro-III and IV collagens were seen, most intense in those infected with the Colombian strain. Treated mice, parasitologically cured, presented clear-cut regression of the inflamatory lesions and of the interstitial matrix thickening. Mice infected with the Colombian strain and treated with MK-436, was parasitologically cured in 5/6 cases and showed mild inflammatory infiltration and fibrosis. The mice treated with Benznidazole (Colombia

Cell-matrix interactions in Schistosomal portal fibrosis: a dynamic event

In recent years, one of the most significant progress in the understanding of liver diseases was the demonstration that liver fibrosis is a dynamic process resulting from a balance between synthesis and degradation of several matrix components, collagen in particular. Thus, fibrosis has been found to be a very early event during liver diseases, be it of toxic, viral or parasitic origin, and to be spontaneously reversible, either partially or totally. In liver fibrosis cell matrix interactions are dependent on the existence of the many factors (sometimes acting in combination) which produce the same events at the cellular and molecular levels. These events are: (i) the recruitment of fiber-producing cells, (ii) their proliferation, (iii) the secretion of matrix constituents of the extracellular matrix, and (iv) the remodeling and degradation of the newly formed matrix. All these events represent, at least in principle, a target for a therapeutic intervention aimed at influencing the experimentally induced hepatic fibrosis. In this context, hepatosplenic schistosomiasis is of particular interest, being an immune cell-mediated granulomatous disease and a model of liver fibrosis allowing extensive studies in human and animals as well as providing original in vitro models.

Chronic murine myocarditis due to Trypanosoma cruzi: an ultrastructural study and immunochemical characterization of cardiac interstitial matrix

Utilizando o modelo experimental do camundongo, foi realizado um estudo sorológico, histopatológico e ultraestrutural bem como a imunotipagem do colágeno na matriz conjuntiva do miocárdio em camundongos suiços cronicamente infectados com as cepas 21 SF e Mambaí (Tipo II) PMN e Bolívia (Tipo III) por períodos de 154 a 468 dias. Os testes sorológicos e de imunofluorescência indireta mostraram altos títulos de anticorpos específicos. O estudo estrutural definiu melhor a constituiçäo celular do infiltrado inflamatório, mostrando a predominância de monócitos e de macrófagos com intensa atividade fagocítica, fibroblastos em atividade de síntese e miofibroblastos bem como abundante matriz colagênica sugerindo uma associaçäo entre o processo inflamatório e fibrogênese na cardiomiopatia chagásica crônica. A imunotipagem do colágeno mostrou a predominância dos tipos III e IV. Alteraçöes dos capilares sangüíneos e de arteríolas e sua dissociaçäo das miocélulas, pelo infiltrado inflamatório, se relacionam com alteraçöes ultraestruturais em miocélulas cardíacas näo parasitadas. Havia intensificaçäo do processo inflamatório em áreas focais correspondentes à rotura de fibras cardíacas parasitadas. Os achados do presente trabalho sugerem que o modelo do camundongo é adequado para o estudo dos mecanismos patogênicos na doença de Chagas, pela utilizaçäo de cepas do T. cruzi com baixa virulência e alta patogenicidade