Abstract. The abiotic synthesis of nucleotide oligomers via wet–dry cycling may have provided a source of nucleic acids necessary for the origin of primiti

Mouse experiments show that Alzheimer’s disease and corticobasal degeneration tau filaments retain their distinct structures during templated seeding, supporting strain-specific tau propagation a...

In this work, two ketone-containing pre-polyesters based on dimethyl 2-oxoglutarate (pDMOG) and dimethyl 1,3-acetonedicarboxylate (pDADC), were obtained via a solventless polymerization reaction in presence of Lipase B from Candida antarctica as the ...

Membrane pore-forming proteins (PFPs) form ring-shaped membrane-translocating oligomers on membranes, contributing to infection, immunity, and cell...

AbstractChiral 8-amino-2-carboxylic acid quinoline-based aromatic oligoamide foldamers with lengths up to circa 5 nm were synthesized to investigate their

Divalent zinc ions interact with amyloid β (Aβ) peptides and influence its Alzheimer disease-related aggregation, but the structural properties of Zn-induced Aβ oligomers remain underexplored. Here, t...

AbstractApolipoprotein E4 (ApoE4), one of the three common isoforms of ApoE, differs from ApoE3 and ApoE2 by just one amino acid substitution each. Yet these changes in ApoE4 profoundly impact protein structure and function to make it the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). ApoE4 exhibits a tendency to form oligomers (e.g., tetramers) that complicate high-resolution structural characterization in aqueous environments. Very little is known about the self-associated oligomeric structures. In this study, we employed ultracentrifugation, native mass spectrometry (MS), and fast photochemical oxidation of proteins (FPOP), a mass spectrometry-based protein footprinting approach, to investigate conformational differences among wild-type ApoE4 and two of its mutant variants ApoE4(V236E) (Jacksonville, JV) and ApoE4(V236E/L268E) (VL). These substitutions shift the oligomeric equilibrium toward dimeric and monomeric states, respectively, and allow the tetramer state to be compared with the dimer and monomer. Comparative footprinting reveals that conformational changes driven by these mutations result in altered solvent accessibility in key regions of the protein, suggesting disruption of interfaces responsible for oligomerization and altered access of lipid-binding regions. Given ApoE4’s central role in lipid metabolism and its altered interaction with lipid surfaces compared to other isoforms, these structural changes likely modulate lipid binding affinity and may contribute to its pathological role in AD. Our findings highlight the importance of conformational states in ApoE4 function and provide new insights into the structural basis of its disease-associated behavior.

From feeding bottles to formula and breast milk, researchers traced where plastic particles and oligomers appear and why reported exposure levels can vary so widely. Paper: Evidence, implications and mitigation of plastic-derived contaminants in infant food: a systematic review. Image Credit: Irina Gutyryak / Shutterstock Researchers recently conducted a systematic review, published in the journal NPJ Science of Food, to evaluate evidence on infant dietary exposure to plastic-derived contaminants, including nanoplastics and oligomers, and to assess the state of current research. Infant Exposure to Plastic-Derived Contaminants Plastics have become ubiquitous in manufacturing, packaging, and consumer products because of their cost-effectiveness and versatility. Their widespread use has also contributed to environmental contamination and human exposure to plastic-derived chemicals and particles. Infants may experience MNP exposure at least an order of magnitude higher than adults. Their potential exposure is increased by their smaller body size, greater food intake per kilogram of body weight, and frequent reliance on plastic-based feeding products. The detection of plastic-derived contaminants across breast milk, formula, solid infant foods, and feeding products, together with evidence of MNP contamination in the wider environment, points to multiple exposure pathways. Feeding products are often marketed as safe, but inconsistent testing and significant...

AbstractThe abiotic synthesis of nucleotide oligomers via wet–dry cycling may have provided a source of nucleic acids necessary for the origin of primitive forms of life. Mass spectrometry (MS) is an important analytical tool used to investigate such oligomers, but the products are surprisingly complex because of water molecules and salt ions adsorbed to ionic and polar groups on the molecules. There are also aggregates of monomers stabilized by noncovalent forces, and differentiating between covalent polymers and noncovalent aggregates remains a subject of technical debate. This study addresses methods for identifying peaks in mass spectra by investigating the adsorption of water and sodium during the ionization of uridine monophosphate and 3′,5′-cyclic guanosine monophosphate (UMP and cGMP). Using 18O-labeled water and increasing the temperature of the heated capillary inlet, we demonstrated that hydrogen-bonded water molecules persist even under high temperatures up to 450 °C. Furthermore, we identified the salt enrichment effect, where increasing chain length leads to a binomial accumulation of sodium ions even in an acidic (pH 2.5) environment. By employing field-asymmetric ion mobility MS, we successfully deconvoluted isobaric ions, distinguishing between massive noncovalent UMP 35-mer aggregates and true covalent 36-mer UMP polymers. These results confirm that water and salt involvement are intrinsic to the MS signature of nucleotide monomers and oligomers. Our findings provide a rigorous analytical framework for validating prebiotic polymerization and highlight the necessity of advanced separation techniques in the characterization of nucleic acid polymers synthesized nonenzymatically on the prebiotic Earth.

Acumen Pharmaceuticals is pressing its case for sabirnetug in Alzheimer's disease treatment by targeting toxic amyloid beta oligomers rather than amyloid plaques, laying out its clinical roadmap and biomarker data at the 12th Annual Cantor Fitzgerald Global Healthcare Conference.

Read the full paper: Microtubule end stabilisation by cooperative oligomers of Ska and Ndc80 complexes

Cable bacteria are filamentous microorganisms able to transport electrical currents over centimetre distances, giving them a survival advantage in aquatic sediments. The molecular basis of this conduc...

Background Parkinson’s disease (PD) is characterized by the progressive accumulation and spatio-temporal spread of α-synuclein (α-syn) oligomers and a progressive loss of dopaminergic neurons. Many st...