Secondary Nucleation of Aβ Revealed by Single-Molecule and Computational Approaches.

Understanding the mechanisms underlying amyloid-β (Aβ) aggregation is pivotal in the context of Alzheimer's disease. This study aims to elucidate the secondary nucleation process of Aβ42 peptides by combining experimental and computational methods. Using a newly developed nanopipette-based amyloid seeding and translocation assay, confocal fluorescence spectroscopy, and molecular dynamics simulations, the influence of the seed properties on Aβ aggregation is investigated.

Demonstration of event position reconstruction based on diffusion in the NEXT-white detector.

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored.

Characterizing Prion-Like Protein Aggregation: Emerging Nanopore-Based Approaches.

Prion-like protein aggregation is characteristic of numerous neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. This process involves the formation of aggregates ranging from small and potentially neurotoxic oligomers to highly structured self-propagating amyloid fibrils. Various approaches are used to study protein aggregation, but they do not always provide continuous information on the polymorphic, transient, and heterogeneous species formed.

Ultrasensitive Detection of Aβ42 Seeds in Cerebrospinal Fluid with a Nanopipette-Based Real-Time Fast Amyloid Seeding and Translocation Assay.

In this work, early-stage Aβ42 aggregates were detected using a real-time fast amyloid seeding and translocation (RT-FAST) assay. Specifically, Aβ42 monomers were incubated in buffer solution with and without preformed Aβ42 seeds in a quartz nanopipette coated with L-DOPA. Then, formed Aβ42 aggregates were analyzed on flyby resistive pulse sensing at various incubation time points.

Aβ42 fibril and non-fibril oligomers characterization using a nanopipette.

The Aβ42 aggregates with different structures and morphology was investigated through a single molecule label-free technique. To this end, the quartz nanopipettes were functionalized with polyethylene glycol. The set of Aβ42- epigallocatechin-3-gallate fibrils with length (from 85 nm to 250 nm) obtained by sonication was detected.

Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial.

Background: Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear.

Investigation of α-Synuclein and Amyloid-β(42)-E22Δ Oligomers Using SiN Nanopore Functionalized with L-Dopa.

Solid-state nanopores are an emerging technology used as a high-throughput, label-free analytical method for the characterization of protein aggregation in an aqueous solution. In this work, we used Levodopamine to coat a silicon nitride nanopore surface that was fabricated through a dielectric breakdown in order to reduce the unspecific adsorption. The coating of inner nanopore wall by investigation of the translocation of heparin.

Reg-1α, a New Substrate of Calpain-2 Depending on Its Glycosylation Status.

Reg-1α/lithostathine, a protein mainly associated with the digestive system, was previously shown to be overexpressed in the pre-clinical stages of Alzheimer's disease. In vitro, the glycosylated protein was reported to form fibrils at physiological pH following the proteolytic action of trypsin. However, the nature of the protease able to act in the central nervous system is unknown.

Loss of glucocorticoid receptor phosphorylation contributes to cognitive and neurocentric damages of the amyloid-β pathway.

Aberrant cortisol and activation of the glucocorticoid receptor (GR) play an essential role in age-related progression of Alzheimer's disease (AD). However, the GR pathways required for influencing the pathobiology of AD dementia remain unknown. To address this, we studied an early phase of AD-like progression in the well-established APP/PS1 mouse model combined with targeted mutations in the BDNF-dependent GR phosphorylation sites (serines 134/267) using molecular, behavioral and neuroimaging approaches.

Environmental implications of interaction between humic substances and iron oxide nanoparticles: A review.

Goethite, hematite, ferrihydrite, and other iron oxides bind through various sorption reactions with humic substances (HS) in soils creating nano-, micro-, and macro-aggregates with a specific nature and stability. Long residence times of soil organic matter (SOM) have been attributed to iron-humic substance (Fe-HS) complexes due to physical protection and chemical stabilization at the organic-mineral interface. Humic acids (HA) and fulvic acids (FA) contain many acidic functional groups that interact with Fe oxides through different mechanisms.

Real-Time Fast Amyloid Seeding and Translocation of α-Synuclein with a Nanopipette.

The detection to α-synuclein (αS) assemblies as a biomarker of synucleinopathies is an important challenge for further development of an early diagnosis tool. Here, we present proof of concept real-time fast amyloid seeding and translocation (RT-FAST) based on a nanopipette that combines in one unique system a reaction vessel to accelerate the seed amplification and nanopore sensor for single-molecule αS assembly detection. RT-FAST allows the detection of the presence αS seeds WT and A53T variant in a given sample in only 90 min by adding a low quantity (35 μL at 100 nM) of recombinant αS for amplification.

Solid-state and polymer nanopores for protein sensing: A review.

In two decades, the solid state and polymer nanopores became attractive method for the protein sensing with high specificity and sensitivity. They also allow the characterization of conformational changes, unfolding, assembly and aggregation as well the following of enzymatic reaction. This review aims to provide an overview of the protein sensing regarding the technique of detection: the resistive pulse and ionic diodes.

Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1-42) peptides and dimeric splitting phenomena.

The Aβ(1-42) aggregation is a key event in the physiopathology of Alzheimer's disease (AD). Exogenous factors such as environmental pollutants, and more particularly pesticides, can corrupt Aβ(1-42) assembly and could influence the occurrence and pathophysiology of AD. However, pesticide involvement in the early stages of Aβ(1-42) aggregation is still unknown.

Detection of Amyloid-β Fibrils Using Track-Etched Nanopores: Effect of Geometry and Crowding.

Several neurodegenerative diseases have been linked to proteins or peptides that are prone to aggregate in different brain regions. Aggregation of amyloid-β (Aβ) peptides is recognized as the main cause of Alzheimer's disease (AD) progression, leading to the formation of toxic Aβ oligomers and amyloid fibrils. The molecular mechanism of Aβ aggregation is complex and still not fully understood.

Deconstructing Alzheimer's Disease: How to Bridge the Gap between Experimental Models and the Human Pathology?

Discovered more than a century ago, Alzheimer's disease (AD) is not only still present in our societies but has also become the most common dementia, with 50 million people worldwide affected by the disease. This number is expected to double in the next generation, and no cure is currently available to slow down or stop the disease progression. Recently, some advances were made due to the approval of the aducanumab treatment by the American Food and Drug Administration.

Walnuts, Long-Chain Polyunsaturated Fatty Acids, and Adolescent Brain Development: Protocol for the Walnuts Smart Snack Dietary Intervention Trial.

Adolescence, when the most complex behaviors are refined to adult sophistication, represents a major window of opportunity and vulnerability for neuropsychological development. To support and protect this complex and active brain growth, different nutritional components considered essential need to be acquired from the diet. For instance, omega-3 fatty acids are mainly obtained from seafood, seeds, and walnuts.

Open vs Minimally Invasive Scarf Osteotomy for Hallux Valgus Correction: A Randomized Controlled Trial.

Background: Minimally invasive (MI) surgery is becoming increasingly popular in the treatment of hallux valgus (HV). The scarf osteotomy is an effective procedure with a track record in open HV surgery. We adapted this effective osteotomy to MI surgery as a novel technique never reported before.

Combining P and Zn fertilization to enhance yield and grain quality in maize grown on Mediterranean soils.

The main aim of this study was to elucidate the effect of individual and joint fertilization with P and Zn on maize plants grown on typical Mediterranean soils with a limited Zn availability. For this purpose, we examined the effects of P and Zn fertilization individually and in combination on growth, yield and grain protein content in maize grown in pots filled with three different Mediterranean soils (LCV, FER and INM). Phosphorus and Zn translocation to grain was impaired, and aboveground dry matter and yield at harvest reduced by 8-85% (LCV and FER), in plants treated with Zn or P alone relative to unfertilized (control) plants.

Prenatal exposure to low doses of fungicides corrupts neurogenesis in neonates.

Neurogenesis plays a crucial role during neurodevelopment and its dysfunction can lead to neurodevelopmental disorders. A recent hypothesis stipulates that exogenous factors could corrupt this process and predispose to neurodegenerative disorders later in life. The presence of pesticide residues in the diet represents a threat of which we have recently become aware of.

Optimum Olsen Phosphorus/Zinc ratio for the initial growth of maize in agricultural soils of the Mediterranean region.

Background: Zinc (Zn) deficiency in crops is commonly aggravated by high levels of phosphorus (P) in soil. In this work, the initial performance of pot-growing maize in response to the available P and Zn in soils with low available Zn and to the application of P and Zn fertilizers was investigated.

Results: The soils (six non-calcareous and 14 calcareous) ranged widely in available P (Olsen P: 5.

Machine Learning to Improve the Sensing of Biomolecules by Conical Track-Etched Nanopore.

Single nanopore is a powerful platform to detect, discriminate and identify biomacromolecules. Among the different devices, the conical nanopores obtained by the track-etched technique on a polymer film are stable and easy to functionalize. However, these advantages are hampered by their high aspect ratio that avoids the discrimination of similar samples.

Current practice of pressurized intraperitoneal aerosol chemotherapy (PIPAC): Still standardized or on the verge of diversification?

Background: PIPAC is a new treatment modality for peritoneal cancer which has been practiced and evaluated until very recently by few academic centers in a highly standardized manner. Encouraging oncological outcomes and the safety profile have led to widespread adoption. The aim of this study was to assess current PIPAC practice in terms of technique, treatment and safety protocol, and indications.

Effects of functional oils on the growth, carcass and meat characteristics, and intestinal morphology of commercial turkey toms.

Two experiments were conducted to evaluate the effects of functional oils containing cashew nutshell and castor oil on turkey performance and intestinal morphology. In experiment 1, 585 hatchlings were randomly placed in 15 replicate floor pens, (13 poults/pen) with recycled litter and provided feed and water ad libitum. Birds were randomly assigned to 3 dietary treatments from 1 to 12 wk: nonmedicated control, 0.