Recent advances in language modeling have had a tremendous impact on how we handle sequential data in science. Language architectures have emerged as a hotbed of innovation and creativity in natural ...language processing over the last decade, and have since gained prominence in modeling proteins and chemical processes, elucidating structural relationships from textual/sequential data. Surprisingly, some of these relationships refer to three-dimensional structural features, raising important questions on the dimensionality of the information encoded within sequential data. Here, we demonstrate that the unsupervised use of a language model architecture to a language representation of bio-catalyzed chemical reactions can capture the signal at the base of the substrate-binding site atomic interactions. This allows us to identify the three-dimensional binding site position in unknown protein sequences. The language representation comprises a reaction-simplified molecular-input line-entry system (SMILES) for substrate and products, and amino acid sequence information for the enzyme. This approach can recover, with no supervision, 52.13% of the binding site when considering co-crystallized substrate-enzyme structures as ground truth, vastly outperforming other attention-based models.
In response to the environmental problems, we propose herein to use a common base of formulation leading to a set of galenic systems such as ethanol-free hydrogels, surfactant-free and silica-free ...Pickering emulsions and microcapsules. All of the systems are developed from the self-assembly of α-cyclodextrin (α-CD) and polyethylene glycol (PEG) using the colloidal tectonics approach. Firstly, α-CD and PEG were mixed to obtain stable hydrogels loaded with antifungal drugs in the form of complexes with 2-hydroxypropyl-β-CD to increase the drugs solubility in the gels. Secondly, oil-in-water Pickering emulsions were prepared from the unloaded hydrogels by adding paraffin oil containing antifungals in their native forms. Thirdly, these emulsions were dried to obtain loaded microcapsules. The different systems were characterized by means of physicochemical measurements (microscopy, pH, rheology and stability) and anti-pathogen activities. Their properties are close to those of commercially available ones but superior for their stability, with even a clear enhancement of the anti-pathogen activity (up to 1.6). All formulations reduce the potential drawbacks of the commonly used excipients and are in line with the current trend of simplifying formulas in terms of ingredients.
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Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel ...habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis then termed postinfectious IBS (PI-IBS), the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field.
The metabolome is the biochemical basis of plant form and function, but we know little about its macroecological variation across the plant kingdom. Here, we used the plant functional trait concept ...to interpret leaf metabolome variation among 457 tropical and 339 temperate plant species. Distilling metabolite chemistry into five metabolic functional traits reveals that plants vary on two major axes of leaf metabolic specialization—a leaf chemical defense spectrum and an expression of leaf longevity. Axes are similar for tropical and temperate species, with many trait combinations being viable. However, metabolic traits vary orthogonally to life-history strategies described by widely used functional traits. The metabolome thus expands the functional trait concept by providing additional axes of metabolic specialization for examining plant form and function.
Leaf metabolic traits describe additional dimensions of plant life-history variation that expand the functional trait concept.
Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this ...risk is not understood. Here, we report that serum levels of CD95 ligand (CD95L) are higher in patients with TNBC than in other patients with breast cancer. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility due to the formation of an unconventional CD95-containing receptosome called the motility-inducing signaling complex. The formation of this complex was instrumental for Nox3-driven reactive oxygen species generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a prometastatic function for metalloprotease-cleaved CD95L in TNBCs, revisiting its role in carcinogenesis.
With the utilization of a novel synergistic approach, we constrain the vertical distribution of water vapor on Mars with measurements from nadir‐pointing instruments. Water vapor column abundances ...were retrieved simultaneously with PFS (sensing the thermal infrared range) and SPICAM (sensing the near‐infrared range) on Mars Express, yielding distinct yet complementary sensitivity to different parts of the atmospheric column. We show that by exploiting a spectral synergy retrieval approach, we obtain more accurate water vapor column abundances compared to when only one instrument is used, providing a new and highly robust reference climatology from Mars Express. We present a composite global data set covering all seasons and latitudes, assembled from colocated observations sampled from seven Martian years. The synergy also offers a way to study the vertical partitioning of water, which has remained out of the scope of nadir observations made by single instruments covering a single spectral interval. Special attention is given to the north polar region, with extra focus on the sublimation of the seasonal polar cap during the late spring and summer seasons. Column abundances from the Mars Climate Database were found to be significantly higher than synergistically retrieved values, especially in the summer Northern Hemisphere. Deviations between synergy and model in both magnitude and meridional variation of the vertical confinement were also discovered, suggesting that certain aspects of the transport and dynamics of water vapor are not fully captured by current models.
Plain Language Summary
Water vapor plays an important role in the weather and climate on Mars, even though little of it remains today. The behavior of water vapor has been studied for decades, yet how water vapor varies with altitude, especially close to the surface, remains an open question. In this study, we use measurements from two instruments on the Mars Express satellite to learn about the near‐surface water vapor. By combining measurements from the SPICAM and PFS spectrometers, a composite full‐year climatology is assembled. We measure the total amount of water vapor with great accuracy, and also obtain information about the vertical distribution. The north polar cap is studied in detail during early summer, when part of the polar ice cap sublimates into water vapor and is transported south. The results are compared to model data from the Mars Climate Database, and significant differences between the observations and the model are identified. The total water content is found to be smaller than model estimates, while observations indicate that more water than expected is confined near the surface. This suggests that some aspects of the atmospheric transport processes are not currently fully understood.
Key Points
Using a spectral synergy retrieval method on nadir observations from SPICAM and PFS to obtain a highly accurate water vapor climatology
The synergy method is sensitive to the vertical distribution of H2O, and can distinguish near‐surface water from the rest of the column
Discrepancies in meridional and seasonal behavior of vertical confinement are revealed between the synergy and the Mars Climate Database
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► Nonionic surfactants inhibit the biocidal activity of quaternary ammonium surfactants. ► Co-micellization decreases the concentration of unimers of the biocidal surfactant. ► ...Cationic unimers exhibit a biocidal activity unlike micellized cationic surfactants. ► The biocidal activity of cationic surfactants is maintained when mixed with C10Ej. ► The biocidal activity of cationic surfactants is strongly inhibited with C12Ej.
Mixed aggregate formation and synergistic interactions of binary surfactant mixtures of di-n-decyldimethylammonium chloride, DiC10Cl, with polyoxyethylene alkyl ethers, CiEj (i=10, 12, j=4, 6, 8), have been investigated for various DiC10Cl/CiEj ratios. The critical aggregation concentration of the binary mixtures has been determined by tensiometry, and the aggregate characteristics (i.e., size and composition, free ammonium concentration) have been estimated using the pulsed field gradient NMR spectroscopy and a DiC10-selective electrode. Diffusion coefficient measurements of micelles confirmed the synergistic interaction between the surfactants. It is thus shown that the formation of surface monolayers and mixed aggregates from DiC10Cl/C10Ej mixtures is driven by both tail/tail and head/head interactions, whereas DiC10Cl/C12Ej co-aggregation is mainly driven by tail/tail interactions. As a consequence, the co-aggregation phenomenon notably influences the biocidal activity of DiC10Cl on the Candida albicans fungi. In the presence of C12Ej, the biocidal activity of the ammonium salt is inhibited due to the trapping of the cationic surfactants in the mixed aggregates, whereas in the presence of C10Ej, the biocidal activity of the surfactant mixture is maintained. The mode of action is also confirmed by a faster increase in the zeta potential of a C. albicans suspension in the presence of DiC10Cl/C10E8 than in the presence of DiC10Cl/C12E8. Therefore, a judicious adjustment of the alkyl (i) and polyoxyethylene (j) chain lengths of CiEj avoids its antagonistic effect on the biocidal activity of DiC10Cl.
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