The rational design of supramolecular polymers in water is imperative for their widespread use, but the design principles for these systems are not well understood. Herein, we employ a multi-scale ...(spatial and temporal) approach to differentiate two analogous water-soluble supramolecular polymers: one with and one without a stereogenic methyl. Initially aiming simply to understand the molecular behaviour of these systems in water, we find that while the fibres may look identical, the introduction of homochirality imparts a higher level of internal order to the supramolecular polymer. Although this increased order does not seem to affect the basic dimensions of the supramolecular fibres, the equilibrium dynamics of the polymers differ by almost an order of magnitude. This report represents the first observation of a structure/property relationship with regard to equilibrium dynamics in water-soluble supramolecular polymers.
Recent studies have shown that three-dimensional (3D) culture environments allow the study of cellular responses in a setting that more closely resembles the in vivo milieu. In this context, ...hydrogels have become popular scaffold options for the 3D cell culture. Because the mechanical and biochemical properties of culture matrixes influence crucial cell behavior, selecting a suitable matrix for replicating in vivo cellular phenotype in vitro is essential for understanding disease progression. Gelatin methacrylate (GelMA) hydrogels have been the focus of much attention because of their inherent bioactivity, favorable hydration and diffusion properties, and ease-of-tailoring of their physicochemical characteristics. Therefore, in this study we examined the efficacy of GelMA hydrogels as a suitable platform to model specific attributes of breast cancer. We observed increased invasiveness in vitro and increased tumorigenic ability in vivo in breast cancer cells cultured on GelMA hydrogels. Further, cells cultured on GelMA matrixes were more resistant to paclitaxel treatment, as shown by the results of cell-cycle analysis and gene expression. This study, therefore, validates GelMA hydrogels as inexpensive, cell-responsive 3D platforms for modeling key characteristics associated with breast cancer metastasis, in vitro.
The effect of active component addition and support modification of Ag/Al
O
has been reviewed to examine their contribution to HC-SCR of NOx. This review has depicted the possible mechanisms of ...reduction of NO by hydrocarbon using metal/metal oxide doped Ag/Al
O
. The addition of second metal results in the maximum formation of well dispersed Ag
clusters. Specifically, addition of Au improves the low-temperature activity of the catalyst. However, the role of second metal also depends on the pretreatment to the catalyst and nature of the reductants. The support modification of Ag/Al
O
by the addition of different metal oxides has also been reviewed. Modification by MgO showed improvement in activity besides sulfur tolerance. In situ DRIFT study demonstrates that the modification by MgO leads to the inhibition of sulfate formation of Ag and Al
O
. Enhancement in activity after second metal addition and support modification attributed to the synergistic effect and improved surface properties of Ag/Al
O
catalyst.
•EFSA’s OpenFoodTox database contains summary hazard data for 5000 chemicals in food and feed.•OpenFoodTox can be downloaded and visualised using a micro-strategy tool.•Current and future development ...include links to in silico models and integration of New Approach Methodologies.
Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA’s outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure–activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing.
Abstract
In the Southern Ribeira Belt (Brazil), the Itatins Complex, composed of ortho- and para-derived migmatites record granulite facies metamorphism. Our work focuses on the ortho-derived ...migmatite, which displays features indicative of partial melting ranging from in-situ melting (cm-thick lenses and veins) to accumulations of melt as leucosomes and patches of diatexite. The unit comprises a biotite felsic granulite (metagranodiorite) with a residual neosome and a leucocratic neosome, generally referred to as leucosome. Phase equilibria modelling using a modified bulk composition from the geochemical standard JG-1 (granodiorite) was carried out to evaluate whether a protolith of granodiorite bulk composition could produce the mineral assemblages observed in the residual neosome and the compositions of melt and residue produced by the partial melting. Isopleth thermobarometry of plagioclase, biotite and orthopyroxene points to P-T conditions of 0.7–1.0 GPa and 845–872 ºC. The modified granodiorite bulk composition generated just 10 mol % melt at these conditions, far lower than the amount estimated from outcrops (around 32 %). A T-XH2O pseudosection shows that increasing H2O content enhances the fertility of the bulk composition and it can become capable of producing melt volumes similar to that observed in outcrop. The melt compositions determined for partial melting of the modified granodiorite bulk composition in open- and closed-systems using THERMOCALC are granitic, and peraluminous. The melts have SiO2 contents between 52.02 mol % and 77.27 mol. % and show XFe values of 0.68 and 0.86. In K2O vs. Na2O+CaO, K2O vs. XFe and K2O-(FeO+MgO)-(Na2O+CaO) space natural samples (5 from the residual neosome and 2 from leucosome) from the Itatins Complex plot in the direction of the trends for melt and residue compositions obtained from modelling of the modified granodiorite bulk composition. The differences between modeled compositions and real rocks are interpreted to result from the interaction of melt with its residual counterpart. Chondrite normalized REE patterns from the residual neosome shows considerably greater depletion of HREE than geochemical standard JG-1 (granodiorite), and the two analyzed leucosomes show lower HREE contents. Zircon rims have REE patterns interpreted to indicate metamorphic recrystallization. U-Pb zircon Concordia ages indicate that the protolith formed during the Paleoproterozoic (2137 Ma) but that metamorphic recrystallization is Neoproterozoic (between 632 and 601 Ma). The metamorphic age pre-dates the intense granitic magmatism that affected the Southern Ribeira Belt between 600 and 570 Ma.
Aims
Candida albicans is an important opportunistic pathogen, responsible for the majority of yeast infections in humans. Essential oils, extracted from aromatic plants, are well‐known antimicrobial ...agents, characterized by a broad spectrum of activities, including antifungal properties. The aim of this work was to assess the sensitivity of 30 different vaginal isolated strains of C. albicans to 12 essential oils, compared to the three main used drugs (clotrimazole, fluconazole and itraconazole).
Methods and Results
Thirty strains of C. albicans were isolated from vaginal swab on CHROMagar™ Candida. The agar disc diffusion method was employed to determine the sensitivity to the essential oils. The antifungal activity of the essential oils and antifungal drugs (clotrimazole, itraconazole and fluconazole) were investigated using a microdilution method. Transmission and scanning electron microscopy analyses were performed to get a deep inside on cellular damages. Mint, basil, lavender, tea tree oil, winter savory and oregano essential oils inhibited both the growth and the activity of C. albicans more efficiently than clotrimazole. Damages induced by essential oils at the cellular level were stronger than those caused by clotrimazole.
Conclusions
Candida albicans is more sensitive to different essential oils compared to the main used drugs. Moreover, the essential oil affected mainly the cell wall and the membranes of the yeast.
Significance and Impact of the Study
The results of this work support the research for new alternatives or complementary therapies against vaginal candidiasis.
Abstract
Nanocapsules that collapse in response to guanosine triphosphate (GTP) have the potential as drug carriers for efficiently curing diseases caused by cancer and RNA viruses because GTP is ...present at high levels in such diseased cells and tissues. However, known GTP-responsive carriers also respond to adenosine triphosphate (ATP), which is abundant in normal cells as well. Here, we report the elaborate reconstitution of microtubule into a nanocapsule that selectively responds to GTP. When the tubulin monomer from microtubule is incubated at 37 °C with a mixture of GTP (17 mol%) and nonhydrolysable GTP* (83 mol%), a tubulin nanosheet forms. Upon addition of photoreactive molecular glue to the resulting dispersion, the nanosheet is transformed into a nanocapsule. Cell death results when a doxorubicin-containing nanocapsule, after photochemically crosslinked for properly stabilizing its shell, is taken up into cancer cells that overexpress GTP.
Ti-6Al-4V (Ti64) plates were subjected to rolling at 600°C and 800°C, respectively, for reductions up to 90% reduction in thickness. The mechanism of texture and microstructure evolution during ...rolling was studied in the present study. Extension twins of coherent nature were observed in the samples rolled up to 50% of reduction. The deformation was relatively inhomogeneous in the samples rolled at 600°C compared to that at 800°C. Visco-plastic self-consistent (VPSC) simulation showed that relative activity of pyramidal <c+a> slip was higher during rolling at 800°C compared to that at 600°C. The average activity of slip systems per grain was less than five for the samples rolled at 600°C and this might be responsible for the strain heterogeneity in the large grains. Further, twinning activity was found to be limited to a true strain of 0.5, as supported by the microstructural observation. VPSC simulation also showed the presence of contraction twins in the samples which was further supported by X-ray texture measurement. Dominant basal texture was observed in the samples irrespective of the temperature of rolling.
The opening-angle of quartz c-axis fabrics (OA) is strongly temperature dependent and has proven to be a powerful deformation thermometer for natural metamorphic rocks. Previous considerations of ...empirical data have identified a linear correlation between OA and temperature between 250 and 650°C, and no correlation above 650°C. However, possible effects of pressure have not been investigated. We expanded the data set of OA versus temperature, including data from rocks deformed over 300–1050°C and 2.5–15kbar. Disregarding possible effects of pressure, the OA–temperature relationship can be described by two linear correlations for the intervals ~250–650°C and ~650–1050°C:T°C=6.9OAdegrees+48250°C≤T≤650°CandOA≤87°T°C=4.6OAdegrees+258650°C≤T≤1050°CandOA≥87°
The change on the curve slope of the OA–temperature relationship correlates approximately to the low- to high-quartz transition and to changes in the dynamic recrystallization mechanism from subgrain rotation to grain boundary migration. The available data suggest that pressure has a secondary effect accompanying the major temperature dependence of OA, which is particularly important for temperatures above 650°C, where the correlation between OA and temperature is less pronounced. For fixed pressures, the OA has logarithmic relationships with temperature over the range 250–1050°C. The following thermometer equation is formulated from a multiple regression:T°C=410.44lnOAdegrees+14.22Pkbar−1272
An uncertainty of ±50°C is inherited from the petrological temperature estimates of the natural samples. The data suggest the gradual increasing importance of prism c slip relative to slip in quartz with rising temperature. Under conditions of ‘average’ geological strain rate and water weakening, prism c slip dominates for deformation above ~700°C.
•We improved the quartz c-axis fabric opening-angle deformation thermometer.•We extended the thermometer to higher deformation temperatures (up to 1050°C).•The opening-angle has logarithmic relationships with temperature for fixed pressures.•Pressure has a secondary effect on the opening-angle over the range of 2.5–15kbar.•The data yielded the fit: T (°C)=410.44 ln (opening-angle)+14.22 P (kbar)−1272.
This paper reports the application of molecular dynamics methods to understand the interactions between dendritic molecules with spermine surface groups and double-helical DNA. Importantly, we are ...able to reproduce the binding effects observed experimentally, indicating that this type of modeling is robust and reliable. The energetic effects were deconvoluted in order to quantify the binding of each spermine unit to the DNA double helix. Importantly, for the first-generation dendron G1, DNA binding was adversely affected by increasing levels of NaCl (>10% of the interaction energy is lost). For second-generation G2 however, we observed a compensation effect, in which some ligands “sacrifice” themselves, losing large amounts of binding energy with DNA. However, these ligands screen the complex, which enables the other spermine residues to bind more effectively to DNA. In this way, the multivalent array is able to maintain its high affinity binding, even as the salt concentration increases (only ca. 1% of the interaction energy is lost). These modeling studies are in agreement with, and provide a unique insight into, the experimental results. Clearly, ligand flexibility and ability to reorganize the interactions with DNA are important, demonstrating that high levels of preorganization and ligand framework rigidity are not always beneficial for multivalent recognition. The concept suggested by this modeling study, in which ligand “sacrifice” and binding site screening combine to enable high-affinity binding, is a new paradigm in multivalency.
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