α-GalCer sp-iminoglycolipid analogs as CD1d-dependent iNKT modulators: Evaluation of their immunotherapeutic potential in murine models of asthma and autoimmune hepatitis.

Invariant natural killer T (iNKT) cells are a subset of innate T cells displaying powerful immunomodulatory functions. Despite extensive preclinical research on the use of iNKT agonist and antagonist for various diseases, translating these findings into successful clinical applications has proven challenging, leaving no approved treatments to date. Efforts to optimize therapeutic outcomes by developing alternative glycolipids to α-galactosylceramide (α-GalCer or KRN7000), the prototypical iNKT antigen, have shown improved preclinical results.

Fluorinated trehalose analogues for cell surface engineering and imaging of .

The sensitive, rapid and accurate diagnosis of () infection is a central challenge in controlling the global tuberculosis (TB) pandemic. Yet the detection of mycobacteria is often made difficult by the low sensitivity of current diagnostic tools, with over 3.6 million TB cases missed each year.

Fast Quantitative Validation of 3D Models of Low-Affinity Protein-Ligand Complexes by STD NMR Spectroscopy.

Low-affinity protein-ligand interactions are important for many biological processes, including cell communication, signal transduction, and immune responses. Structural characterization of these complexes is also critical for the development of new drugs through fragment-based drug discovery (FBDD), but it is challenging due to the low affinity of fragments for the binding site. Saturation transfer difference (STD) NMR spectroscopy has revolutionized the study of low-affinity receptor-ligand interactions enabling binding detection and structural characterization.

Differential Solvent DEEP-STD NMR and MD Simulations Enable the Determinants of the Molecular Recognition of Heparin Oligosaccharides by Antithrombin to Be Disentangled.

The interaction of heparin with antithrombin (AT) involves a specific sequence corresponding to the pentasaccharide GlcNAc/NS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S (AGA*IA). Recent studies have revealed that two AGA*IA-containing hexasaccharides, which differ in the sulfation degree of the iduronic acid unit, exhibit similar binding to AT, albeit with different affinities. However, the lack of experimental data concerning the molecular contacts between these ligands and the amino acids within the protein-binding site prevents a detailed description of the complexes.

Fluorinated Man as a High Mannose Mimetic to Unravel Its Recognition by DC-SIGN Using NMR.

Lectins are capable of reading out the structural information contained in carbohydrates through specific recognition processes. Determining the binding epitope of the sugar is fundamental to understanding this recognition event. Nuclear magnetic resonance (NMR) is a powerful tool to obtain this structural information in solution; however, when the sugar involved is a complex oligosaccharide, such as high mannose, the signal overlap found in the NMR spectra precludes an accurate analysis of the interaction.

Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers.

Antifungal drugs such as amphotericin B (AmB) interact with lipids and phospholipids located on fungal cell membranes to disrupt them and create pores, leading to cell apoptosis and therefore efficacy. At the same time, the interaction can also take place with cell components from mammalian cells, leading to toxicity. AmB was selected as a model antifungal drug due to the complexity of its supramolecular chemical structure which can self-assemble in three different aggregation states in aqueous media: monomer, oligomer (also known as dimer) and poly-aggregate.

Molecular Recognition of Natural and Non-Natural Substrates by Cellodextrin Phosphorylase from Ruminiclostridium Thermocellum Investigated by NMR Spectroscopy.

β-1→4-Glucan polysaccharides like cellulose, derivatives and analogues, are attracting attention due to their unique physicochemical properties, as ideal candidates for many different applications in biotechnology. Access to these polysaccharides with a high level of purity at scale is still challenging, and eco-friendly alternatives by using enzymes in vitro are highly desirable. One prominent candidate enzyme is cellodextrin phosphorylase (CDP) from Ruminiclostridium thermocellum, which is able to yield cellulose oligomers from short cellodextrins and α-d-glucose 1-phosphate (Glc-1-P) as substrates.

Chemoenzymatic Synthesis of Fluorinated Cellodextrins Identifies a New Allomorph for Cellulose-Like Materials*.

Understanding the fine details of the self-assembly of building blocks into complex hierarchical structures represents a major challenge en route to the design and preparation of soft-matter materials with specific properties. Enzymatically synthesised cellodextrins are known to have limited water solubility beyond DP9, a point at which they self-assemble into particles resembling the antiparallel cellulose II crystalline packing. We have prepared and characterised a series of site-selectively fluorinated cellodextrins with different degrees of fluorination and substitution patterns by chemoenzymatic synthesis.

Structural heterogeneities in starch hydrogels.

Hydrogels have a complex, heterogeneous structure and organisation, making them promising candidates for advanced structural and cosmetics applications. Starch is an attractive material for producing hydrogels due to its low cost and biocompatibility, but the structural dynamics of polymer chains within starch hydrogels are not well understood, limiting their development and utilisation. We employed a range of NMR methodologies (CPSP/MAS, HR-MAS, HPDEC and WPT-CP) to probe the molecular mobility and water dynamics within starch hydrogels featuring a wide range of physical properties.

Conformational dynamics of a G protein-coupled receptor helix 8 in lipid membranes.

G protein-coupled receptors (GPCRs) are the largest and pharmaceutically most important class of membrane proteins encoded in the human genome, characterized by a seven-transmembrane helix architecture and a C-terminal amphipathic helix 8 (H8). In a minority of GPCR structures solved to date, H8 either is absent or adopts an unusual conformation. The controversial existence of H8 of the class A GPCR neurotensin receptor 1 (NTS1) has been examined here for the nonthermostabilized receptor in a functionally supporting membrane environment using electron paramagnetic resonance, molecular dynamics simulations, and circular dichroism.

Fulvic acid increases forage legume growth inducing preferential up-regulation of nodulation and signalling-related genes.

The use of potential biostimulants is of broad interest in plant science for improving yields. The application of a humic derivative called fulvic acid (FA) may improve forage crop production. FA is an uncharacterized mixture of chemicals and, although it has been reported to increase growth parameters in many species including legumes, its mode of action remains unclear.

Mapping analysis to predict EQ-5D-5 L utility values based on the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires in the Spanish population suffering from lower limb osteoarthritis.

Background: The EQ-5D-5 L is a quality-of-life questionnaire based on individuals' preferences that is widely employed for cost-effectiveness analysis. Given the current demand for mapping algorithms to directly assign "utilities", this study aimed to generate different mapping models for predicting EQ-5D-5 L utility values based on scores of the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires provided by patients suffering from hip and knee osteoarthritis (OA), respectively, and to assess the predictive capability of these functions.

Methods: This was a prospective, observational study.

Hydrophobization of Cellulose Nanocrystals for Aqueous Colloidal Suspensions and Gels.

Surface hydrophobization of cellulose nanomaterials has been used in the development of nanofiller-reinforced polymer composites and formulations based on Pickering emulsions. Despite the well-known effect of hydrophobic domains on self-assembly or association of water-soluble polymer amphiphiles, very few studies have addressed the behavior of hydrophobized cellulose nanomaterials in aqueous media. In this study, we investigate the properties of hydrophobized cellulose nanocrystals (CNCs) and their self-assembly and amphiphilic properties in suspensions and gels.

Detergent-free extraction of a functional low-expressing GPCR from a human cell line.

Dopamine receptors (DRs) are class A G-Protein Coupled Receptors (GPCRs) prevalent in the central nervous system (CNS). These receptors mediate physiological functions ranging from voluntary movement and reward recognition to hormonal regulation and hypertension. Drugs targeting dopaminergic neurotransmission have been employed to treat several neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, Huntington's disease, attention deficit hyperactivity disorder (ADHD), and Tourette's syndrome.

High Molecular Weight Mixed-Linkage Glucan as a Mechanical and Hydration Modulator of Bacterial Cellulose: Characterization by Advanced NMR Spectroscopy.

Bacterial cellulose (BC) consists of a complex three-dimensional organization of ultrafine fibers which provide unique material properties such as softness, biocompatibility, and water-retention ability, of key importance for biomedical applications. However, there is a poor understanding of the molecular features modulating the macroscopic properties of BC gels. We have examined chemically pure BC hydrogels and composites with arabinoxylan (BC-AX), xyloglucan (BC-XG), and high molecular weight mixed-linkage glucan (BC-MLG).

Understanding heat driven gelation of anionic cellulose nanofibrils: Combining saturation transfer difference (STD) NMR, small angle X-ray scattering (SAXS) and rheology.

A novel mechanism of heat-triggered gelation for oxidised cellulose nanofibrils (OCNF) is reported. We demonstrate that a synergistic approach combining rheology, small-angle X-ray scattering (SAXS) and saturation transfer difference NMR (STD NMR) experiments enables a detailed characterisation of gelation at different length scales. OCNF dispersions experience an increase in solid-like behaviour upon heating as evidenced by rheological studies, associated with enhanced interfibrillar interactions measured using SAXS.

Surfactant controlled zwitterionic cellulose nanofibril dispersions.

Zwitterionic cellulose nanofibrils (ZCNFs) with an isoelectric point of 3.4 were obtained by grafting glycidyltrimethylammonium chloride onto TEMPO/NaBr/NaOCl-oxidised cellulose nanofibrils. The ZCNF aqueous dispersions were characterized via transmission electron microscopy, rheology and small angle neutron scattering, revealing a fibril-bundle structure with pronounced aggregation at pH 7.

Mechanically Robust Gels Formed from Hydrophobized Cellulose Nanocrystals.

Cellulose nanocrystals (CNCs) that bind to each other through associative hydrophobic interactions have been synthesized by modifying sulfated CNCs (sCNCs) with hydrophobic moieties. These octyl-CNCs form gels at significantly lower concentrations than parent sCNCs, producing extremely strong hydrogels. Unlike sCNCs, these octyl-CNCs do not form ordered liquid crystalline phases indicating a random association into a robust network driven by hydrophobic interactions.

Dynamic tuneable G protein-coupled receptor monomer-dimer populations.

G protein-coupled receptors (GPCRs) are the largest class of membrane receptors, playing a key role in the regulation of processes as varied as neurotransmission and immune response. Evidence for GPCR oligomerisation has been accumulating that challenges the idea that GPCRs function solely as monomeric receptors; however, GPCR oligomerisation remains controversial primarily due to the difficulties in comparing evidence from very different types of structural and dynamic data. Using a combination of single-molecule and ensemble FRET, double electron-electron resonance spectroscopy, and simulations, we show that dimerisation of the GPCR neurotensin receptor 1 is regulated by receptor density and is dynamically tuneable over the physiological range.

Nanodisc-Targeted STD NMR Spectroscopy Reveals Atomic Details of Ligand Binding to Lipid Environments.

Saturation transfer difference (STD) NMR spectroscopy is one of the most popular ligand-based NMR techniques for the study of protein-ligand interactions. This is due to its robustness and the fact that it is focused on the signals of the ligand, without any need for NMR information on the macromolecular target. This technique is most commonly applied to systems involving different types of ligands (e.