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Antibody-functionalized MXene-based electrochemical biosensor for point-of-care detection of vitamin D deficiency
Clinical studies routinely show that individuals suffer from vitamin D deficiency, which can result in health complications that include cardiovascular disease, autoimmune disorders, neurodegenerative diseases, and different skeletal deformities. Given its integral role in homeostasis and connection to many pathologies, early diagnosis of vitamin D deficiency is crucial. However, monitoring vitamin D levels is challenging, particularly in remote regions, due to the cost, time, and complexity of existing methods. Here, we develop an electrochemical biosensor for vitamin D based on antibody-functionalized MXenes, offering clinically relevant sensitivity, specificity, and amenability for point-of-care testing. Ti3C2Tx MXene nanosheets are amine-functionalized by electrostatically-driven modification with polyethylenimine, whose functionalities are then used for covalent conjugation of anti-vitamin D antibodies via glutaraldehyde chemistry. This platform achieves a detection limit of 1 pg mL−1 with a dynamic range (0.1–500 ng mL−1) that covers clinically relevant deficiency, insufficiency, sufficiency, and toxicity.
Abundant ammonia and nitrogen-rich soluble organic matter in samples from asteroid (101955) Bennu
Organic matter in meteorites reveals clues about early Solar System chemistry and the origin of molecules important to life, but terrestrial exposure complicates interpretation. Samples returned from the B-type asteroid Bennu by the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer mission enabled us to study pristine carbonaceous astromaterial without uncontrolled exposure to Earth’s biosphere. Here we show that Bennu samples are volatile rich, with more carbon, nitrogen and ammonia than samples from asteroid Ryugu and most meteorites. Nitrogen-15 isotopic enrichments indicate that ammonia and other N-containing soluble molecules formed in a cold molecular cloud or the outer protoplanetary disk. We detected amino acids (including 14 of the 20 used in terrestrial biology), amines, formaldehyde, carboxylic acids, polycyclic aromatic hydrocarbons and N-heterocycles (including all five nucleobases found in DNA and RNA), along with ~10,000 N-bearing chemical species. All chiral non-protein amino acids were racemic or nearly so, implying that terrestrial life’s left-handed chirality may not be due to bias in prebiotic molecules delivered by impacts. The relative abundances of amino acids and other soluble organics suggest formation and alteration by low-temperature reactions, possibly in NH3-rich fluids. Bennu’s parent asteroid developed in or accreted ices from a reservoir in the outer Solar System where ammonia ice was stable.
A glycan foldamer that uses carbohydrate–aromatic interactions to perform catalysis
In nature, the ability to catalyse reactions is primarily associated with proteins and ribozymes. Inspired by these systems, peptide-based catalysts have been designed to accelerate chemical reactions and/or ensure regio- and stereoselective transformations. We wondered whether other biomolecules (such as glycans) could be designed to perform catalytic functions, expanding the portfolio of synthetic functional oligomers. Here we report a glycan foldamer inspired by the natural Sialyl Lewis X antigen that acts as catalyst in a chemical reaction. This glycan-based catalyst benefits from structural rigidity and modular adaptability, incorporating a substrate-recognition motif alongside a catalytic active site. Leveraging the inherent ability of carbohydrates to engage in CH–π interactions with aromatic substrates, we demonstrate the recruitment and functionalization of a tryptophan via a Pictet–Spengler transformation. Our modular glycan catalyst accelerates the reaction kinetics, enabling the modification of tryptophan-containing peptides in aqueous environments. Our findings pave the way for the development of glycan-based catalysts and suggest the possibility of catalytic capabilities of glycans in biological contexts.
B-cell receptor physical properties affect relative IgG1 and IgE responses in mouse egg allergy
Mutated and unmutated IgE and IgG play different and partly opposing roles in allergy development, but the mechanisms controlling their relative production are incompletely understood. Here, we analyzed the IgE-response in murine food allergy. Deep sequencing of the complementary-determining region (CDR) repertoires indicated that an ongoing unmutated extrafollicular IgE response coexists with a germinal center response, even after long-lasting allergen challenges. Despite overall IgG1-dominance, a significant proportion of clonotypes contained several-fold more IgE than IgG1. Clonotypes with differential bias to either IgE or IgG1 showed distinct hypermutation and clonal expansion. Hypermutation rates were associated with different physiochemical binding properties of individual B-cell receptors (BCR). Increasing BCR signaling strength inhibited class switching from IgG1 to IgE in vitro, preferentially constraining IgE formation. These data indicate that antigen-binding properties of individual BCRs determine differential IgE hypermutation and IgE versus IgG1 production on the level of single B-cell clones.
Upcycling of polyamides through chemical hydrolysis and engineered Pseudomonas putida
Aliphatic polyamides, or nylons, are widely used in the textile and automotive industry due to their high durability and tensile strength, but recycling rates are below 5%. Chemical recycling of polyamides is possible but typically yields mixtures of monomers and oligomers which hinders downstream purification. Here, Pseudomonas putida KT2440 was engineered to metabolize C6-polyamide monomers such as 6-aminohexanoic acid, ε-caprolactam and 1,6-hexamethylenediamine, guided by adaptive laboratory evolution. Heterologous expression of nylonases also enabled P. putida to metabolize linear and cyclic nylon oligomers derived from chemical polyamide hydrolysis. RNA sequencing and reverse engineering revealed the metabolic pathways for these non-natural substrates. To demonstrate microbial upcycling, the phaCAB operon from Cupriavidus necator was heterologously expressed to enable production of polyhydroxybutyrate (PHB) from PA6 hydrolysates. This study presents a microbial host for the biological conversion, in combination with chemical hydrolysis, of polyamide monomers and mixed polyamids hydrolysates to a value-added product.
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