/library/oar/handle/123456789/402 Tue, 04 Nov 2025 17:25:19 GMT 2025-11-04T17:25:19Z /library/oar/handle/123456789/140783 Title: The amyloid oligomer modulator anle138b has disease modifying effects in a human IAPP transgenic mouse model of type 2 diabetes mellitus (hIAPP Ob/Ob mice) Abstract: Cytotoxic aggregates of human islet amyloid polypeptide (hIAPP) contribute to type 2 diabetes mellitus (T2DM) pathogenesis by damaging pancreatic islet β cells and reducing insulin production. Anle138b is an amyloid oligomer modulator with disease modifying properties in mouse models of neurodegenerative diseases linked to protein aggregation and with favorable results in phase 1 clinical studies. We tested whether anle138b has disease modifying properties in a severe hIAPP transgenic mouse model of T2DM. Oral administration of anle138b in hIAPP Ob/Ob mice reduced hyperglycemia, decreased glycated hemoglobin levels, increased islet β-cell mass and improved islet function compared to non-treated mice. In contrast, anle138b administration did not affect these parameters in non-transgenic Ob/Ob mice, indicating that the anti-diabetic effects of anle138b are hIAPP-dependent. In vitro, anle138b inhibited hIAPP aggregation and toxic effects of hIAPP on mitochondria. These results indicate that anle138b is a promising drug candidate for treating and/or preventing T2DM -associated pathology [excerpt]. Mon, 01 Jan 2024 00:00:00 GMT /library/oar/handle/123456789/140783 2024-01-01T00:00:00Z /library/oar/handle/123456789/140740 Title: Processing neuroimaging data for research purposes : Open Science, FAIR data, and the GDPR Authors: Sant, Mireille M.; Bajada, Claude J. Abstract: Open Science and FAIR (Findable, Accessible, Interoperable, and Reusable) Science have emerged as two prominent, related, often conflated but actually distinct, frameworks supporting data sharing. The neuroimaging community has embraced the Open Science practice of sharing data with few, if any, restrictions. Neuroimaging data, in particular brain MRI data, is intrinsically personal data, and is, in most cases, impossible to adequately anonymize to the standards dictated by the General Data Protection Regulation (GDPR). As such, in the European Union, neuroimaging repositories are likely to process personal data as defined in the GDPR under all circumstances. The aims of open science are hampered by the GDPR’s requirements. European science is at a distinct disadvantage to its American and other global counterparts, due to the disproportionately high regulatory burden that is placed on research institutions and individual researchers who are often ill-equipped to comply. Wed, 01 Jan 2025 00:00:00 GMT /library/oar/handle/123456789/140740 2025-01-01T00:00:00Z /library/oar/handle/123456789/140717 Title: Auxetic systems fabricated using mycelia-based composites Authors: Cadinu, Claudia; Gatt, Ruben; Blundell, Renald; Grima, Joseph N.; Farrugia, Pierre-Sandre Abstract: In an era of increasingly problematic global waste management, innovative materials can hold the key to a circular economy. Within such a context, this work aimed at manufacturing, potentially for the first time, auxetic material (i.e., materials with a negative Poisson’s ratio) using mycelia-based composites (i.e., materials made by growing fungi on a biodegradable substrate). The fabrication of the auxetic biomaterials was undertaken using both direct growth methods in purposely designed molds and through subtractive manufacturing of commercially available mycelia panels. In the former case, various substrates were employed, differing in sawdust granulation and nutrient content. Furthermore, enhancements in the form of scaffolds and hay were considered with the aim of improving the cohesion and elastic properties of the end product. Mechanical testing of the samples produced showed that both manufacturing methods can produce structures capable of exhibiting a negative Poisson’s ratio. At the same time, the intrinsic brittle nature of mycelia-based composites limits the compactness and cohesion of the end products. In this context, the different methodologies employed to improve these properties yielded some promising results. Thus, while this work showed that indeed auxetic biomaterials can be fabricated, the manufacturing methods still require further improvement to produce better-performing specimens. Wed, 01 Jan 2025 00:00:00 GMT /library/oar/handle/123456789/140717 2025-01-01T00:00:00Z /library/oar/handle/123456789/140688 Title: Poration of mitochondrial membranes by amyloidogenic peptides and other biological toxins Authors: Vassallo, Neville Abstract: Mitochondria are essential organelles known to serve broad functions, including in cellular metabolism, calcium buffering, signaling pathways and the regulation of apoptotic cell death. Maintaining the integrity of the outer (OMM) and inner mitochondrial membranes (IMM) is vital for mitochondrial health. Cardiolipin (CL), a unique dimeric glycerophospholipid, is the signature lipid of energy-converting membranes. It plays a significant role in maintaining mitochondrial architecture and function, stabilizing protein complexes and facilitating efficient oxidative phosphorylation (OXPHOS) whilst regulating cytochrome c release from mitochondria. CL is especially enriched in the IMM and at sites of contact between the OMM and IMM. Disorders of protein misfolding, such as Alzheimer's and Parkinson's diseases, involve amyloidogenic peptides like amyloid-β, tau and α-synuclein, which form metastable toxic oligomeric species that interact with biological membranes. Electrophysiological studies have shown that these oligomers form ion-conducting nanopores in membranes mimicking the IMM's phospholipid composition. Poration of mitochondrial membranes disrupts the ionic balance, causing osmotic swelling, loss of the voltage potential across the IMM, release of pro-apoptogenic factors, and leads to cell death. The interaction between CL and amyloid oligomers appears to favour their membrane insertion and pore formation, directly implicating CL in amyloid toxicity. Additionally, pore formation in mitochondrial membranes is not limited to amyloid proteins and peptides; other biological peptides, as diverse as the pro-apoptotic Bcl-2 family members, gasdermin proteins, cobra venom cardiotoxins and bacterial pathogenic toxins, have all been described to punch holes in mitochondria, contributing to cell death processes. Collectively, these findings underscore the vulnerability of mitochondria and the involvement of CL in various pathogenic mechanisms, emphasizing the need for further research on targeting CL-amyloid interactions to mitigate mitochondrial dysfunction. Wed, 01 Jan 2025 00:00:00 GMT /library/oar/handle/123456789/140688 2025-01-01T00:00:00Z