Trace_y: Software algorithms for structural analysis of individual helical filaments by three-dimensional contact point reconstruction atomic force microscopy.

Atomic force microscopy (AFM) is a powerful and increasingly accessible technology that has a wide range of bio-imaging applications. AFM is capable of producing detailed three-dimensional topographical images with high signal-to-noise ratio, which enables the structural features of individual molecules to be studied without the need for ensemble averaging. Here, a software tool Trace_y, designed to reconstruct the three-dimensional surface envelopes of individual helical filament structures from topographical AFM images, is presented.

A Support Vector Machine-Assisted Metabolomics Approach for Non-Targeted Screening of Multi-Class Pesticides and Veterinary Drugs in Maize.

The contamination risks of plant-derived foods due to the co-existence of pesticides and veterinary drugs (P&VDs) have not been fully understood. With an increasing number of unexpected P&VDs illegally added to foods, it is essential to develop a non-targeted screening method for P&VDs for their comprehensive risk assessment. In this study, a modified support vector machine (SVM)-assisted metabolomics approach by screening eligible variables to represent marker compounds of 124 multi-class P&VDs in maize was developed based on the results of high-performance liquid chromatography-tandem mass spectrometry.

Atomic force microscopy 3D structural reconstruction of individual particles in the study of amyloid protein assemblies.

Recent developments in atomic force microscopy (AFM) image analysis have made three-dimensional (3D) structural reconstruction of individual particles observed on 2D AFM height images a reality. Here, we review the emerging contact point reconstruction AFM (CPR-AFM) methodology and its application in 3D reconstruction of individual helical amyloid filaments in the context of the challenges presented by the structural analysis of highly polymorphous and heterogeneous amyloid protein structures. How individual particle-level structural analysis can contribute to resolving the amyloid polymorph structure-function relationships, the environmental triggers leading to protein misfolding and aggregation into amyloid species, the influences by the conditions or minor fluctuations in the initial monomeric protein structure on the speed of amyloid fibril formation, and the extent of the different types of amyloid species that can be formed, are discussed.

Geographical origin traceability of rice using a FTIR-based metabolomics approach.

Infrared spectroscopy is a crucial tool to achieve the origin traceability of rice, but it is constrained by data mining. In this study, a novel infrared spectroscopy-based metabolomics analytical method was proposed to discriminate rice products from 14 Chinese cities by seeking 'wave number markers'. Principal component analysis (PCA), cluster analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to separate all rice groups.

Tuning dynamic DNA- and peptide-driven self-assembly in DNA-peptide conjugates.

DNA-peptide conjugates offer an opportunity to marry the benefits of both biomolecular classes, combining the high level of programmability found with DNA, with the chemical diversity of peptides. These hybrid systems offer potential in fields such as therapeutics, nanotechnology, and robotics. Using the first DNA-β-turn peptide conjugate, we present three studies investigating the self-assembly of DNA-peptide conjugates over a period of 28 days.

An Additive-Free Model for Tau Self-Assembly.

Tau is a natively unfolded protein that contributes to the stability of microtubules. Under pathological conditions such as Alzheimer's disease (AD), tau protein misfolds and self-assembles to form paired helical filaments (PHFs) and straight filaments (SFs). Full-length tau protein assembles poorly and its self-assembly is enhanced with polyanions such as heparin and RNA in vitro, but a role for heparin or other polyanions in vivo remains unclear.

Metabolomics Approach on Non-Targeted Screening of 50 PPCPs in Lettuce and Maize.

The metabolomics approach has proved to be promising in achieving non-targeted screening for those unknown and unexpected (U&U) contaminants in foods, but data analysis is often the bottleneck of the approach. In this study, a novel metabolomics analytical method via seeking marker compounds in 50 pharmaceutical and personal care products (PPCPs) as U&U contaminants spiked into lettuce and maize matrices was developed, based on ultrahigh-performance liquid chromatography-tandem mass spectrometer (UHPLC-MS/MS) output results. Three concentration groups (20, 50 and 100 ng mL) to simulate the control and experimental groups applied in the traditional metabolomics analysis were designed to discover marker compounds, for which multivariate and univariate analysis were adopted.

Comparative Analysis of the Relative Fragmentation Stabilities of Polymorphic Alpha-Synuclein Amyloid Fibrils.

The division of amyloid fibril particles through fragmentation is implicated in the progression of human neurodegenerative disorders such as Parkinson's disease. Fragmentation of amyloid fibrils plays a crucial role in the propagation of the amyloid state encoded in their three-dimensional structures and may have an important role in the spreading of potentially pathological properties and phenotypes in amyloid-associated diseases. However, despite the mechanistic importance of fibril fragmentation, the relative stabilities of different types or different polymorphs of amyloid fibrils toward fragmentation remain to be quantified.

Discrimination and Deaf Adolescents' Subjective Well-Being: The Role of Deaf Identity.

This study tested the influence of Deaf identity (cognitive identification and affective identification) on the association between perceived deaf discrimination and subjective well-being among Chinese adolescents who are deaf and hard-of-hearing (DHH), based on the rejection-identification model. Questionnaires on perceived deaf discrimination, subjective well-being, Deaf identity, and demographic information were completed by 246 DHH students (15-23 years old) from special residential schools in China. The results indicated that: (1) higher level of perceived deaf discrimination was significantly associated with lower level of subjective well-being (direct effect = -0.

Structural Identification of Individual Helical Amyloid Filaments by Integration of Cryo-Electron Microscopy-Derived Maps in Comparative Morphometric Atomic Force Microscopy Image Analysis.

The presence of amyloid fibrils is a hallmark of more than 50 human disorders, including neurodegenerative diseases and systemic amyloidoses. A key unresolved challenge in understanding the involvement of amyloid in disease is to explain the relationship between individual structural polymorphs of amyloid fibrils, in potentially mixed populations, and the specific pathologies with which they are associated. Although cryo-electron microscopy (cryo-EM) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy methods have been successfully employed in recent years to determine the structures of amyloid fibrils with high resolution detail, they rely on ensemble averaging of fibril structures in the entire sample or significant subpopulations.

Metabolomics-based non-targeted screening analysis of 34 PPCPs in bovine and piscine muscles.

The metabolomics-based analytical strategy has showed superiority on the non-targeted screening of contaminants, especially for unknown and unexpected (U&U) contaminants in the field of food safety, but data analysis is often the bottleneck of the strategy. In this study, a novel metabolomics-based analytical method searching for marker compounds was developed on the basis of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) results to accurately, rapidly and comprehensively achieve the non-targeted screening of 34 pharmaceutical and personal care products (PPCPs) as U&U contaminants spiked in bovine and piscine muscle matrices. Three concentration groups (20, 50 and 100 ng mL) were intentionally designed to simulate the control and experimental groups for the discovery of marker compounds, for which multivariate and univariate analyses were adopted.

Heterotypic Amyloid β interactions facilitate amyloid assembly and modify amyloid structure.

It is still unclear why pathological amyloid deposition initiates in specific brain regions or why some cells or tissues are more susceptible than others. Amyloid deposition is determined by the self-assembly of short protein segments called aggregation-prone regions (APRs) that favour cross-β structure. Here, we investigated whether Aβ amyloid assembly can be modified by heterotypic interactions between Aβ APRs and short homologous segments in otherwise unrelated human proteins.

Quantum chemical prediction of effects of temperature on hydrolysis rate of penicillin under weakly acidic condition.

Temperature and pH are important factors affecting the hydrolysis of β-lactam antibiotics in water environments. However, the determination of hydrolysis kinetics and pathways is experimentally challenging, particularly in low temperature aqueous solutions because of time and cost constraints. In this study, an equation was employed to correct the Gibbs energy calculated in aqueous solutions by density functional theory methods to predict the effect of temperature on the hydrolysis kinetics and pathways of penicillin G.

Metabolomics-based screening analysis of PPCPs in water pretreated with five different SPE columns.

The selection of solid phase extraction (SPE) columns in the pretreatment process plays a decisive role in the screening and quantification of pharmaceutical and personal care products (PPCPs). As growing PPCPs have frequently been detected in the aquatic environment, it is a burdensome task through one-by-one recovery comparison to judge which column presents relatively ideal pretreatment results for PPCPs. In view of this, we developed a novel metabolomics-based screening method based on ultrahigh-performance liquid chromatography-tandem mass spectrometer (UHPLC-MS/MS) results to accurately, rapidly and comprehensively choose a suitable column from 5 different kinds to handle 64 PPCPs in two water environments (50 μg L/pH ≅ 7.

Insights into the dynamic trajectories of protein filament division revealed by numerical investigation into the mathematical model of pure fragmentation.

The dynamics by which polymeric protein filaments divide in the presence of negligible growth, for example due to the depletion of free monomeric precursors, can be described by the universal mathematical equations of 'pure fragmentation'. The rates of fragmentation reactions reflect the stability of the protein filaments towards breakage, which is of importance in biology and biomedicine for instance in governing the creation of amyloid seeds and the propagation of prions. Here, we devised from mathematical theory inversion formulae to recover the division rates and division kernel information from time-dependent experimental measurements of filament size distribution.

Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles.

Amyloid seeds are nanometer-sized protein particles that accelerate amyloid assembly as well as propagate and transmit the amyloid protein conformation associated with a wide range of protein misfolding diseases. However, seeded amyloid growth through templated elongation at fibril ends cannot explain the full range of molecular behaviors observed during cross-seeded formation of amyloid by heterologous seeds. Here, we demonstrate that amyloid seeds can accelerate amyloid formation via a surface catalysis mechanism without propagating the specific amyloid conformation associated with the seeds.

On the Structural Diversity and Individuality of Polymorphic Amyloid Protein Assemblies.

The prediction of highly ordered three-dimensional structures of amyloid protein fibrils from the amino acid sequences of their monomeric self-assembly precursors constitutes a challenging and unresolved aspect of the classical protein folding problem. Because of the polymorphic nature of amyloid assembly whereby polypeptide chains of identical amino acid sequences under identical conditions are capable of self-assembly into a spectrum of different fibril structures, the prediction of amyloid structures from an amino acid sequence requires a detailed and holistic understanding of its assembly free energy landscape. The full extent of the structure space accessible to the cross-β molecular architecture of amyloid must also be resolved.

Thermodynamics of amyloid fibril formation from non-equilibrium experiments of growth and dissociation.

Amyloid fibrils are ordered, non-covalent polymers of proteins that are linked to a range of diseases, as well as biological functions. Amyloid fibrils are often considered thermodynamically so stable that they appear to be irreversible, explaining why very few quantitative thermodynamic studies have been performed on amyloid fibrils, compared to the very large body of kinetic studies. Here we explore the thermodynamics of amyloid fibril formation by the protein PI3K-SH3, which forms amyloid fibrils under acidic conditions.

The Division of Amyloid Fibrils: Systematic Comparison of Fibril Fragmentation Stability by Linking Theory with Experiments.

The division of amyloid protein fibrils is required for the propagation of the amyloid state and is an important contributor to their stability, pathogenicity, and normal function. Here, we combine kinetic nanoscale imaging experiments with analysis of a mathematical model to resolve and compare the division stability of amyloid fibrils. Our theoretical results show that the division of any type of filament results in self-similar length distributions distinct to each fibril type and the conditions applied.

Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly.

Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism are not understood due to lack of structural insights at the single-fibril level.

Three-dimensional reconstruction of individual helical nano-filament structures from atomic force microscopy topographs.

Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs.

Romantic Love and Attentional Biases Toward Attractive Alternatives and Rivals: Long-Term Relationship Maintenance Among Female Chinese College Students.

Studies about heterosexual individuals' long-term relationship maintenance have indicated that committed individuals possess evolved psychological mechanisms that help protect their ongoing romantic relationships against threats from attractive others during early stage attentional processing when mating-related motivation is activated. In this study, two experiments tested the relationship maintenance mechanism among committed female college students in the Chinese cultural context under different love priming conditions. Committed Chinese women displayed inattention to attractive alternatives in positive love-scenario priming (Study 1: 114 female undergraduates, age range = 18-26 years), subliminal semantic love priming (Study 2: 110 female undergraduates, age range = 18-25 years), and baseline conditions (Studies 1 and 2).

Modeling flood susceptibility using data-driven approaches of naïve Bayes tree, alternating decision tree, and random forest methods.

Floods are one of the most devastating types of disasters that cause loss of lives and property worldwide each year. This study aimed to evaluate and compare the prediction capability of the naïve Bayes tree (NBTree), alternating decision tree (ADTree), and random forest (RF) methods for the spatial prediction of flood occurrence in the Quannan area, China. A flood inventory map with 363 flood locations was produced and partitioned into training and validation datasets through random selection with a ratio of 70/30.

Tau (297-391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer's disease brain.

The constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimer's disease (AD) and other tauopathies. Full-length tau requires the addition of anionic cofactors such as heparin to enhance assembly. We have shown that a fragment from the proteolytically stable core of the PHF, tau 297-391 known as 'dGAE', spontaneously forms cross-β-containing PHFs and straight filaments under physiological conditions.