A Simple Algorithm to Suppress Diagonal Peaks in High-Resolution Homonuclear Chemical Shift Correlation NMR Spectra.

Previous experimental strategies aimed at completely suppressing diagonal peaks in NMR homonuclear correlation spectra often resulted in reduced sensitivity for cross peaks. In this work, we report a spectral shearing approach that transforms diagonal peaks along the diagonal axis of a homonuclear correlation spectrum into a zero-frequency line in the indirect dimension. This allows for effective extraction and substantial suppression of diagonal peaks using a recently proposed data processing algorithm based on quadrature-detected spin-echo diagonal peak suppression.

Anionic Lipid Catalyzes the Generation of Cytotoxic Insulin Oligomers.

The misfolding and aggregation of proteins into amyloidogenic assemblies are key features of several metabolic and neurodegenerative diseases. Human insulin has long been known to form amyloid fibrils under various conditions, which affects its bioavailability and function. Clinically, insulin aggregation at recurrent injection sites poses a challenge for diabetic patients who rely on insulin therapy.

Anionic lipid catalyzes the generation of cytotoxic insulin oligomers.

Misfolding and aggregation of proteins into amyloidogenic assemblies are key features of several metabolic and neurodegenerative diseases. Human insulin has long been known to form amyloid fibrils under various conditions, which affects its bioavailability and function. Clinically, insulin aggregation at recurrent injection sites poses a challenge for diabetic patients who rely on insulin therapy.

Sugar distributions on gangliosides guide the formation and stability of amyloid-β oligomers.

Aggregation of Aβ peptides is a key contributor to the etiology of Alzheimer's disease. Being intrinsically disordered, monomeric Aβ is susceptible to conformational excursions, especially in the presence of important interacting partners such as membrane lipids, to adopt specific aggregation pathways. Furthermore, components such as gangliosides in membranes and lipid rafts are known to play important roles in the adoption of pathways and the generation of discrete neurotoxic oligomers.

amyloid peptides with subtle sequence variations differ in their self-assembly and nanomechanical properties.

Proteinaceous amyloids are well known for their widespread pathological roles but lately have emerged also as key components in several biological functions. The remarkable ability of amyloid fibers to form tightly packed conformations in a cross β-sheet arrangement manifests in their robust enzymatic and structural stabilities. These characteristics of amyloids make them attractive for designing proteinaceous biomaterials for various biomedical and pharmaceutical applications.

Sugar distributions on gangliosides guide the formation and stability of amyloid-β oligomers.

Aggregation of Aβ peptides has been known as a key contributor to the etiology of Alzheimer's disease. Being intrinsically disordered, the monomeric Aβ is susceptible to conformational excursions, especially in the presence of key interacting partners such as membrane lipids, to adopt specific aggregation pathways. Furthermore, key components such as gangliosides in membranes and lipid rafts are known to play important roles in the adoption of pathways and the generation of discrete neurotoxic oligomers.

αS Oligomers Generated from Interactions with a Polyunsaturated Fatty Acid and a Dopamine Metabolite Differentially Interact with Aβ to Enhance Neurotoxicity.

It is increasingly becoming clear that neurodegenerative diseases are not as discrete as originally thought to be but display significant overlap in histopathological and clinical presentations. For example, nearly half of the patients with Alzheimer's disease (AD) and synucleinopathies such as Parkinson's disease (PD) show symptoms and pathological features of one another. Yet, the molecular events and features that underlie such comorbidities in neurodegenerative diseases remain poorly understood.

Biophysical characteristics of lipid-induced Aβ oligomers correlate to distinctive phenotypes in transgenic mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects cognition and memory. Recent advances have helped identify many clinical sub-types in AD. Mounting evidence point toward structural polymorphism among fibrillar aggregates of amyloid-β (Aβ) to being responsible for the phenotypes and clinical manifestations.

Effects of Stereochemistry and Hydrogen Bonding on Glycopolymer-Amyloid-β Interactions.

Saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition processes and protein binding. Synthetic glycopolymers with pendant saccharides of controlled stereochemistry provide an attractive approach for the design of polysaccharide-inspired biomaterials. Acrylamide-based polymers containing either β,d-glucose or β,d-galactose pendant groups, designed to mimic GM1 ganglioside saccharides, and their small-molecule analogues were used to evaluate the effect of stereochemistry on glycopolymer solution aggregation processes alone and in the presence of Aβ42 peptide using dynamic light scattering, gel permeation chromatography-multiangle laser light scattering, and fluorescence assays.

A game-theoretic approach to deciphering the dynamics of amyloid- aggregation along competing pathways.

Aggregation of amyloid- (A) peptides is a significant event that underpins Alzheimer's disease (AD). A aggregates, especially the low-molecular weight oligomers, are the primary toxic agents in AD pathogenesis. Therefore, there is increasing interest in understanding their formation and behaviour.