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Olsson, U.

Publications and source records attributed to Olsson, U..

7 recordsLinked to original sources

DNAJB6b: a complete amyloid inhibitor

In Alzheimer's disease (AD), the aggregation of amyloid {beta} (A{beta}) peptides has been linked to disease pathology. Once aggregates have formed, existing fibrils catalyze the formation of new fibrils in a runaway process associated with neuro degeneration. One component of the cellular defense system against amyloid formation is the molecular chaperone DNAJB6b (JB6). JB6 is known to suppress both primary nucleation and fibril-catalyzed secondary nucleation. However, the extent of JB6 binding to A{beta} fibrils and whether this interaction leads to inhibition of fibril elongation also, have not been established. Here, we combine well-characterized aggregation kinetics of A{beta}42 and the knowledge of JB6 self-assembly equilibrium and kinetics, with high-sensitivity HPLC measurements of free JB6 at nanomolar concentrations to determine the affinity of JB6 for A{beta}42 fibrils. We show that JB6 binds to A{beta}42 fibrils with high affinity and that this binding can quantitatively explain the observed elongation inhibition. Diffusion-based techniques reveal that JB6 binds to amyloid intermediates, resulting in potent suppression of amyloid nucleation until the pool of free JB6 is depleted, after which rapid bulk aggregation ensues. Our results provide a mechanistic link between chaperone-fibril binding and amyloid suppression, offering a quantitative framework for understanding how molecular chaperones regulate amyloid formation.

biochemistry↗

Errors in peptide synthesis are a source of discrepancies in Aβ42 studies

Amyloid-{beta}42 (A{beta}42) aggregation is highly sensitive to experimental conditions, making reproducibility a persistent challenge in Alzheimers disease research. Among the many variables that influence aggregation, the impact of peptide production remains poorly understood. Direct comparison of recombinant and chemically synthesised A{beta}42 prepared under carefully controlled conditions reveals that, despite following similar aggregation mechanism and forming the same predominant fibril structures, synthetic A{beta}42 aggregates more slowly and exhibits reduced seeding efficiency. Consequently, synthetic A{beta}42 produces fewer oligomeric species and displays lower cellular toxicity. Mass spectrometric analyses identify low-abundance sequence imperfections introduced during peptide synthesis as the origin of these differences. By linking synthesis-derived imperfections to variations in A{beta}42 behaviour, this work reveals a previously underappreciated source of discrepancies in amyloid studies. In addition, we provide a framework for evaluating the impact of sequence impurities on biophysical studies that are sensitive to peptide composition.

biochemistry↗

Genetic Diversity, Taxonomic Insights and Geographic Distribution of Bubo bubo Subspecies in Iran

The Eurasian Eagle Owl (Bubo bubo) exhibits a complex taxonomic structure with multiple subspecies across its broad geographic range, including southwestern Asia. While much is known about the species distribution in Europe and Asia, the taxonomic status and distribution of B. bubo subspecies in Iran remain poorly understood. This study aims to explore the genetic diversity and taxonomic relationships of B. bubo subspecies in Iran through mitochondrial gene analysis, focusing on nucleotide sequences of the cytochrome b (cytb) gene. A total of 36 samples collected from diverse localities across Iran, representing different ecological regions. Phylogenetic analysis revealed two distinct clades: one comprising western Iranian samples clustering with European (mostly from Germany) samples, and the other consisting of eastern and southern Iranian samples that shared haplotypes with populations from China. Notably, the western Iranian clade exhibited a minimal genetic distance from European populations, while the eastern Iranian clade was genetically similar to Chinese B. bubo subspecies, including B. bubo turkomanus. The genetic diversity indices for the Iranian population were relatively low, with three identified haplotypes and low nucleotide and haplotype diversity. Demographic analyses indicated a potential population expansion for the species, supported by a unimodal mismatch distribution and negative neutrality indices, although these results were not statistically significant for the Iranian population. The findings suggest that two subspecies, B. bubo nikolskii and B. bubo interpositus, are likely present in Iran, aligning with recent taxonomic assessments, but further investigation with additional genetic markers is needed to clarify the deeper evolutionary relationships among these populations. This study contributes new insights into the genetic landscape of B. bubo in Iran and the broader Palearctic region, with implications for conservation and future taxonomic revisions. Simple SummaryThis study examines the genetic diversity, taxonomic relationships, and geographic distribution of Bubo bubo subspecies in Iran, utilizing mitochondrial gene analysis, with a particular focus on the cytochrome b (cytb) gene. The research, based on 36 samples from various regions in Iran, reveals two distinct clades: one aligning with European populations and the other sharing haplotypes with Chinese subspecies. While genetic diversity in Iranian populations was relatively low, the findings highlight the presence of B. bubo nikolskii and B. bubo interpositus subspecies in Iran, emphasizing the importance of further genetic investigations for conservation and taxonomic revisions in the Palearctic region.

zoology↗

Supramolecular assembly of collagen mimetic peptide D-periodic fibrils and nanoassemblies

The collagen triple helix assembles hierarchically into bundled oligomers, solvated networks and fibers. Synthetic peptide assemblies, driven by supramolecular interactions, can form single triple helices through intrahelical amino acid pairs, but the principles guiding interhelical associations into higher-order structures remain unclear. Here, we incorporate cation-{pi} and electrostatic charge pairs to probe interhelical interactions and elucidate the mechanisms driving triple helix assembly into fibrils, nanotubes, and nanosheets. Introducing cation-{pi} pairs into a fibrillating collagen mimetic resulted in D-periodic fibrils with pH-sensitive gelation. Modifying the presentation of interhelical interactions also enabled the characterization of another D-periodic fibril resembling cartilage collagens, featuring inner and outer triple helix layers. Enhancing electrostatic charge pairs promoted antiparallel assembly, leading to the formation of nanotubes and nanosheets. The packing behavior of triple helices correlates with the interhelical interactions, where parallel associations favor fibril formation, and antiparallel interactions drive nanotube and nanosheet assembly.

biochemistry↗

Covalent Stabilization of Collagen Mimetic Triple Helices and Assemblies by Dopa Crosslinking

Creating thermally stable collagen mimetic peptides (CMPs) is a persistent challenge. Nature leverages covalent crosslinkings to stabilize collagens signature triple helical tertiary structure and higher-order assemblies. Herein, we demonstrate that crosslinkings between levodopa (Dopa) and lysine, amino acids present in native collagen, can covalently stabilize the triple helix in collagen mimetic peptides. Since alkaline conditions catalyze the oxidation of the catechol on Dopa to a benzoquinone, while being in proximity to the nucleophilic lysine, we hypothesized that this reaction could be a facile method to covalently capture the supramolecular structure of CMPs by simply increasing the pH of the aqueous solvent with the addition of sodium hydroxide. This covalent capture strategy successfully stabilizes CMP homotrimers and a de novo designed ABC-type heterotrimer demonstrating that the Lysine-Dopa covalent bond is best templated by a supramolecular, axial cation-{pi} pairwise interaction. In nature, collagen can hierarchically assemble into fibers. This behavior can be mimicked with the self-assembly of CMPs, but the resulting nanofibers typically exhibit thermal stability below body temperature. In a final application, we demonstrate that Dopa-Lysine covalent capture also enhances the thermal stability of CMP nanofibers well above 37 {degrees}C. This biomimetic covalent capture strategy can stabilize a wide variety of CMP systems and potentially enable the biomedical application of these materials.

biochemistry↗

Population genomics of the island thrush elucidates one of earth's great archipelagic radiations

Tropical islands are renowned as natural laboratories for evolutionary study. Lineage radiations across tropical archipelagos are ideal systems for investigating how colonization, speciation, and extinction processes shape biodiversity patterns. The expansion of the island thrush across the Indo-Pacific represents one of the largest yet most perplexing island radiations of any songbird species. The island thrush exhibits a complex mosaic of pronounced plumage variation across its range, and is arguably the worlds most polytypic bird. It is a sedentary species largely restricted to mountain forests, yet it has colonized a vast island region spanning a quarter of the globe. We conducted comprehensive sampling of island thrush populations and obtained genome-wide SNP data, which we used to reconstruct its phylogeny, population structure, gene flow, and demographic history. The island thrush evolved from migratory Palearctic ancestors and radiated explosively across the Indo-Pacific during the Pleistocene, with numerous instances of gene flow between populations. Its bewildering plumage variation masks a biogeographically intuitive stepping stone colonization path from the Philippines through the Greater Sundas, Wallacea and New Guinea to Polynesia. The island thrushs success in colonizing Indo-Pacific mountains can be understood in light of its ancestral mobility and adaptation to cool climates; however, shifts in elevational range, degree of plumage variation and apparent dispersal rates in the eastern part of its range raise further intriguing questions about its biology.

evolutionary biology↗

Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements

Advances in high-throughput sequencing techniques now allow relatively easy and affordable sequencing of large portions of the genome, even for non-model organisms. Many phylogenetic studies reduce costs by focusing their sequencing efforts on a selected set of targeted loci, commonly enriched using sequence capture. The advantage of this approach is that it recovers a consistent set of loci, each with high sequencing depth, which leads to more confidence in the assembly of target sequences. High sequencing depth can also be used to identify phylogenetically informative allelic variation within sequenced individuals, but allele sequences are infrequently assembled in phylogenetic studies.\n\nInstead, many scientists perform their phylogenetic analyses using contig sequences which result from the de novo assembly of sequencing reads into contigs containing only canonical nucleobases, and this may reduce both statistical power and phylogenetic accuracy. Here, we develop an easy-to-use pipeline to recover allele sequences from sequence capture data, and we use simulated and empirical data to demonstrate the utility of integrating these allele sequences to analyses performed under the Multispecies Coalescent (MSC) model. Our empirical analyses of Ultraconserved Element (UCE) locus data collected from the South American hummingbird genus Topaza demonstrate that phased allele sequences carry sufficient phylogenetic information to infer the genetic structure, lineage divergence, and biogeographic history of a genus that diversified during the last three million years. The phylogenetic results support the recognition of two species, and suggest a high rate of gene flow across large distances of rainforest habitats but rare admixture across the Amazon River. Our simulations provide evidence that analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences.

evolutionary biology↗