Despite its central importance for understanding the molecular basis of Alzheimer's disease (AD), high‐resolution structural information on amyloid β‐peptide (Aβ) fibrils, which are intimately linked with AD, is scarce. We report an atomic‐resolution fibril structure of the Aβ1‐40 peptide with the Osaka mutation (E22Δ), associated with early‐onset AD. The structure, which differs substantially from all previously proposed models, is based on a large number of unambiguous intra‐ and intermolecular solid‐state NMR distance restraints.

Marine invertebrates constantly interact with a wide range of microorganisms in their aquatic environment and possess an effective defense system that has enabled their existence for millions of years. Their lack of acquired immunity sets marine invertebrates apart from other marine animals. Invertebrates could rely on their innate immunity, providing the first line of defense, survival, and thriving. The innate immune system of marine invertebrates includes various biologically active compounds, and specifically, antimicrobial peptides. Nowadays, there is a revive of interest in these peptides due to the urgent need to discover novel drugs against antibiotic-resistant bacterial strains, a pressing global concern in modern healthcare. Modern technologies offer extensive possibilities for the development of innovative drugs based on these compounds, which can act against bacteria, fungi, protozoa, and viruses. This review focuses on structural peculiarities, biological functions, gene expression, biosynthesis, mechanisms of antimicrobial action, regulatory activities, and prospects for the therapeutic use of antimicrobial peptides derived from marine invertebrates.

In 2021, the fifth edition of the WHO classification of tumors of the central nervous system (WHO CNS5) was published. Molecular features of tumors were directly incorporated into the diagnostic decision tree, thus affecting both the typing and staging of the tumor. It has changed the traditional approach, based solely on histopathological classification. The Cancer Genome Atlas project (TCGA) is one of the main sources of molecular information about gliomas, including clinically annotated transcriptomic and genomic profiles. Although TCGA itself has played a pivotal role in developing the WHO CNS5 classification, its proprietary databases still retain outdated diagnoses which frequently appear incorrect and misleading according to the WHO CNS5 standards. We aimed to define the up-to-date annotations for gliomas from TCGA’s database that other scientists can use in their research. Based on WHO CNS5 guidelines, we developed an algorithm for the reclassification of TCGA glioma samples by molecular features. We updated tumor type and diagnosis for 828 out of a total of 1122 TCGA glioma cases, after which available transcriptomic and methylation data showed clustering features more consistent with the updated grouping. We also observed better stratification by overall survival for the updated diagnoses, yet WHO grade 3 IDH-mutant oligodendrogliomas and astrocytomas are still indistinguishable. We also detected altered performance in the previous diagnostic transcriptomic molecular biomarkers (expression of SPRY1, CRNDE and FREM2 genes and FREM2 molecular pathway) and prognostic gene signature (FN1, ITGA5, OSMR, and NGFR) after reclassification. Thus, we conclude that further efforts are needed to reconsider glioma molecular biomarkers.

Background: Amyloid fibrils formed by amyloid-β (Aβ) peptides are associated with Alzheimer's disease and can occur in a range of distinct morphologies that are not uniquely determined by the Aβ sequence. Whether distinct conformations of Aβ fibrils can be stably propagated over multiple cycles of seeding and fibril growth has not been established experimentally. Objective: The ability of the 40-residue peptide Aβ_1-40 to assemble into fibrils with the conformation of the mutant Aβ_1-40 peptide containing the ‘Osaka' mutation E22Δ was investigated. Methods: Fibril formation of highly pure, recombinant Aβ_1-40 in the presence of distinct, preformed seeds in vitro was recorded with thioflavin T fluorescence, and distinct fibrillar structures were identified and distinguished by fluorescence spectroscopy and electron microscopy. Results: We propagated the specific quaternary structure of Aβ_1-40 E22Δ fibrils with wild-type Aβ_1-40 over up to seven cycles of seeding and fibril elongation. As a result of a 10⁷-fold dilution of the initially present Aβ_1-40 E22Δ seeds, the vast majority of fibrils formed after the seventh propagation cycle with Aβ_1-40 did not contain a single molecule of Aβ_1-40 E22Δ, but still retained the conformation of the initial Aβ_1-40 E22Δ seeds. Increased critical concentrations of Aβ_1-40 fibrils formed in the presence of Aβ_1-40 E22Δ nuclei suggest that these fibrils are less stable than homologously seeded Aβ_1-40 fibrils, consistent with a kinetically controlled mechanism of fibril formation. Conclusion: The propagation of a distinct Aβ fibril conformation over multiple cycles of seeded fibril growth demonstrates the basic ability of the Aβ peptide to form amyloid strains that in turn may cause phenotypes in Alzheimer's disease.