Ena-DATASET-DKFZ-Epigenomics-06-10-2021-17:00:39:371-42 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001008199 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Description not provided
| EGAD00001008198 | EGA
Project description:Recently, certain C-terminal fragments (CTFs) of A?42 have been shown to be effective inhibitors of A?42 toxicity. Here, we examine the interactions between the shortest CTF in the original series, A?(39-42), and full-length A?. Mass spectrometry results indicate that A?(39-42) binds directly to A? monomers and to the n = 2, 4, and 6 oligomers. The A?42:A?(39-42) complex is further probed using molecular dynamics simulations. Although the CTF was expected to bind to the hydrophobic C-terminus of A?42, the simulations show that A?(39-42) binds at several locations on A?42, including the C-terminus, other hydrophobic regions, and preferentially in the N-terminus. Ion mobility-mass spectrometry (IM-MS) and electron microscopy experiments indicate that A?(39-42) disrupts the early assembly of full-length A?. Specifically, the ion-mobility results show that A?(39-42) prevents the formation of large decamer/dodecamer A?42 species and, moreover, can remove these structures from solution. At the same time, thioflavin T fluorescence and electron microscopy results show that the CTF does not inhibit fibril formation, lending strong support to the hypothesis that oligomers and not amyloid fibrils are the A? form responsible for toxicity. The results emphasize the role of small, soluble assemblies in A?-induced toxicity and suggest that A?(39-42) inhibits A?-induced toxicity by a unique mechanism, modulating early assembly into nontoxic hetero-oligomers, without preventing fibril formation.
| S-EPMC3271797 | biostudies-literature
Project description:Description not provided
| EGAD00001003419 | EGA
Project description:B*38:01 and B*39:06 are present with phenotypic frequencies <2% in the general population, but are of interest as B*39:06 is the B allele most associated with type 1 diabetes susceptibility and 38:01 is most protective. A previous study derived putative main anchor motifs for both alleles based on peptide elution data. The present study has utilized panels of single amino acid substitution peptide libraries to derive detailed quantitative motifs accounting for both primary and secondary influences on peptide binding. From these analyses, both alleles were confirmed to utilize the canonical position 2/C-terminus main anchor spacing. B*38:01 preferentially bound peptides with the positively charged or polar residues H, R, and Q in position 2 and the large hydrophobic residues I, F, L, W, and M at the C-terminus. B*39:06 had a similar preference for R in position 2, but also well-tolerated M, Q, and K. A more dramatic contrast between the two alleles was noted at the C-terminus, where the specificity of B*39:06 was clearly for small residues, with A as most preferred, followed by G, V, S, T, and I. Detailed position-by-position and residue-by-residue coefficient values were generated from the panels to provide detailed quantitative B*38:01 and B*39:06 motifs. It is hoped that these detailed motifs will facilitate the identification of T cell epitopes recognized in the context of two class I alleles associated with dramatically different dispositions towards type 1 diabetes, offering potential avenues for the investigation of the role of CD8 T cells in this disease.
| S-EPMC4760861 | biostudies-literature
Project description:Description not provided
| EGAD00001003778 | EGA
Project description:The ability of the infectious bronchitis H120 (a Massachusetts strain) and CR88 (a 793B strain) live attenuated vaccine viruses to protect from two Middle East infectious bronchitis virus isolates, IS/885/00-like (IS/885) and IS/1494/06-like (IS/1494) in broiler chicks was investigated. Day-old chicks were separated into three groups, (I) vaccinated with H120 at day-old followed by CR88 at 14 days-old, (II) vaccinated with H120 and CR88 simultaneously at day-old and again with CR88 at 14 days-old, (III) control unvaccinated. At 30 days-old, each of the groups was challenged with virulent IS/885 or IS/1494. Protection was evaluated based on the clinical signs, tracheal and kidney gross lesions and tracheal ciliostasis. Results showed that administering combined live H120 and CR88 vaccines simultaneously at day-old followed by CR88 vaccine at 14 days-old gave more than 80 per cent tracheal ciliary protection from both of the Middle East isolates. In addition, this programme conferred 100 per cent protection from clinical signs and tracheal or kidney lesions. The other vaccination programme, H120 at day-old followed by CR88 at 14 days-old, the tracheal ciliary protection conferred were 60 per cent and 80 per cent from IS/885/00-like and IS/1494/06-like, respectively.
| S-EPMC4567785 | biostudies-literature
Project description:Since the introduction of acetyl cholinesterase inhibitors as the first approved drugs by the US Food and Drug Administration for Alzheimer's disease (AD) in clinics, less than satisfactory success in the design of anti-AD agents has impelled the scientists to also focus toward inhibition of Aβ aggregation. Considering the specific binding of fragments for their parent peptide, herein, we synthesized more than 40 new peptides based on a C-terminus tetrapeptide fragment of Aβ1-42. Initial screening by MTT cell viability assay and supportive results by ThT fluorescence assay led us to identify a tetrapeptide showing complete inhibition for Aβ1-42 aggregation. Peptide 20 displayed 100% cell viability at 20 μM concentration, while at lower concentrations of 10 and 2 μM 76.6 and 70% of cells were viable. Peptide 20 was found to restrict the conformational transition of Aβ1-42 peptide toward β-sheet structure. Inhibitory activity of tetrapeptide 20 was further evidenced by the absence of Aβ1-42 aggregates in electron microscopy. Peptide 20 and other significantly active tetrapeptide analogues could prove imperative in the future design of anti-AD agents.
| S-EPMC6645473 | biostudies-literature
Project description:Clostridium ganghwense strain:HY-42-06 Genome sequencing and assembly
| PRJNA907154 | ENA
Project description: Not available
| S-EPMC9239722 | biostudies-literature