-
Nature Genetics Aug 2023Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point...
Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods. Using this combined approach, we prioritize 10,642 unique gene-trait pairs across 113 complex traits and diseases with high precision, finding not only well-established gene-trait relationships but nominating new genes at unresolved loci, such as LGR4 for estimated glomerular filtration rate and CCR7 for deep vein thrombosis. Overall, we demonstrate that PoPS provides a powerful addition to the gene prioritization toolbox.
Topics: Humans; Multifactorial Inheritance; Quantitative Trait Loci; Genome-Wide Association Study; Genetic Predisposition to Disease; Phenotype; Polymorphism, Single Nucleotide
PubMed: 37443254
DOI: 10.1038/s41588-023-01443-6 -
Bioconjugate Chemistry Nov 2023Modified antibodies have essential roles in analytic, diagnostic, and therapeutic uses, and thus, these antibodies are required to have optimal physical and biological...
Modified antibodies have essential roles in analytic, diagnostic, and therapeutic uses, and thus, these antibodies are required to have optimal physical and biological properties. Consequently, the development of methods for site-selective antibody modification is crucial. Herein, we used epitope-based affinity labeling to introduce a Fab region-selective antibody modification method. Although labeling that exploits the high affinity between an antibody and its epitope may appear straightforward, it remains challenging probably because of the loss of target affinity caused by modification around the epitope-binding site. By thoroughly screening the modifying agent structure, reaction conditions, and purification methods, we developed an efficient method for the selective modification of the Fab region of the antibody while maintaining the high affinity for the epitope.
Topics: Epitopes; Antibodies, Monoclonal; Immunoglobulin Fab Fragments; Antibody Affinity
PubMed: 37861691
DOI: 10.1021/acs.bioconjchem.3c00340 -
Rheumatology (Oxford, England) Jan 2024Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well... (Review)
Review
Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies.
Topics: Humans; Leukocyte L1 Antigen Complex; Inflammation; Biomarkers; Feces; Neutrophils; Inflammatory Bowel Diseases
PubMed: 37603715
DOI: 10.1093/rheumatology/kead405 -
Critical Reviews in Food Science and... 2024Neural network (i.e. deep learning, NN)-based data analysis techniques have been listed as a pivotal opportunity to protect the integrity and safety of the global food... (Review)
Review
Neural network (i.e. deep learning, NN)-based data analysis techniques have been listed as a pivotal opportunity to protect the integrity and safety of the global food supply chain and forecast $11.2 billion in agriculture markets. As a general-purpose data analytic tool, NN has been applied in several areas of food science, such as food recognition, food supply chain security and omics analysis, and so on. Therefore, given the rapid emergence of NN applications in food safety, this review aims to provide a comprehensive overview of the NN application in food analysis for the first time, focusing on domain-specific applications in food analysis by introducing fundamental methodology, reviewing recent and notable progress, and discussing challenges and potential pitfalls. NN demonstrated that it has a bright future through effective collaboration between food specialist and the broader community in the food field, for example, superiority in food recognition, sensory evaluation, pattern recognition of spectroscopy and chromatography. However, major challenges impeded NN extension including void in the food scientist-friendly interface software package, incomprehensible model behavior, multi-source heterogeneous data, and so on. The breakthrough from other fields proved NN has the potential to offer a revolution in the immediate future.
Topics: Neural Networks, Computer; Humans; Food Analysis; Food Safety; Food Technology; Food Supply; Deep Learning
PubMed: 36322538
DOI: 10.1080/10408398.2022.2139217 -
Cardiovascular Diabetology Sep 2023Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated...
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease.
METHODS
The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes.
RESULTS
In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1β, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes.
CONCLUSION
Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets.
TRIAL REGISTRATION
The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).
Topics: Aged; Humans; Diabetes Mellitus, Type 2; C-Reactive Protein; Arachidonic Acid; Carotid Artery Diseases; Plaque, Atherosclerotic; Inflammation; Atherosclerosis
PubMed: 37710315
DOI: 10.1186/s12933-023-01979-1 -
Chemistry & Biodiversity Jun 2024This work lies in the growing concern over the potential impacts of pesticides on human health and the environment. Pesticides are extensively used to protect crops and...
This work lies in the growing concern over the potential impacts of pesticides on human health and the environment. Pesticides are extensively used to protect crops and control pests, but their interaction with essential biomolecules like haemoglobin remains poorly understood. Spectrofluorometric, electrochemical, and simulations investigations have been chosen as potential methods to delve into this issue, as they offer valuable insights into the molecular-level interactions between pesticides and haemoglobin. The research aims to address the gaps in knowledge and contribute to the development of safer and more sustainable pesticide practices. The interaction was studied by spectroscopic techniques (UV-Visible & Fluorescence), in silico studies (molecular docking & molecular dynamics simulations) and electrochemical techniques (cyclic voltammetry and tafel). The studies showed effective binding of dinotefuran with the Hb and will cause toxicity to human. The formation of a stable molecular complex between ofloxacin and hemoglobin was shown via molecular docking and the binding energy was found to -5.37 kcal/mol. Further, molecular dynamics simulations provide an insight for the stability of the complex (Hb-dinotefuran) for a span of 250 ns with a binding free energy of -53.627 kJ/mol. Further, cyclic voltammetry and tafel studies for the interaction of dinotefuran with Hb effectively.
PubMed: 38838069
DOI: 10.1002/cbdv.202400495 -
Nature Communications Jan 2024To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in... (Meta-Analysis)
Meta-Analysis
To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.
Topics: Humans; Thyroid Gland; Thyroxine; Genome-Wide Association Study; Triiodothyronine; Thyrotropin
PubMed: 38291025
DOI: 10.1038/s41467-024-44701-9 -
Analytical and Bioanalytical Chemistry Jul 2023
Topics: Chemistry, Analytic; Chemistry Techniques, Analytical
PubMed: 37328579
DOI: 10.1007/s00216-023-04777-6 -
Journal of Agricultural and Food... Dec 2023The presence of multiple conjugated double bonds and chiral carbon atoms endows astaxanthin with geometric and optical isomers, and these isomers widely exist in... (Review)
Review
The presence of multiple conjugated double bonds and chiral carbon atoms endows astaxanthin with geometric and optical isomers, and these isomers widely exist in biological sources, food processing, and absorption. However, there remains no systematic summary of astaxanthin isomers regarding isomerization methods and analytic techniques. To address this need, this Review focuses on a comprehensive analysis of -isomerization methods of astaxanthin, including solvent system, catalyst, and heat treatment. Comparatively, high-efficiency and health-friendly methods are more conducive to put into practical use, such as food-grade solvents and food-component catalysts. In addition, we outline the recent advances in analysis techniques of astaxanthin isomers, as well as the structural characteristics reflected by various methods (e.g., HPLC, NMR, FTIR, and RS). Furthermore, we summarized the related research on the safety evaluation of astaxanthin isomers. Finally, future trends and barriers in transformation and analysis of astaxanthin isomers are also discussed.
Topics: Isomerism; Xanthophylls; Chemical Phenomena; Catalysis; Solvents
PubMed: 37924299
DOI: 10.1021/acs.jafc.3c06863 -
Faraday Discussions Jul 2023The viability of using ammonia as a hydrogen storage vector is contingent on the development of catalytic systems active for ammonia decomposition at low temperatures....
The viability of using ammonia as a hydrogen storage vector is contingent on the development of catalytic systems active for ammonia decomposition at low temperatures. Zeolite-supported metal catalysts, unlike systems based on supports like MgO or carbon nanotubes (CNTs), are crystalline and lend themselves to analytic techniques like synchrotron X-ray powder diffraction (SXRD) and Rietveld refinement, allowing precise characterisation of catalytic active sites, and therefore mechanistic elucidation. This study focuses on characterising and optimising novel zeolite-supported Ru catalysts for ammonia decomposition, with a focus on the effects of N-substitution on catalyst structure and activity. Characterisation focuses on an unsubstituted and N-substituted Ru-zeolite Y pair with NMR, FTIR, TEM, XRD, XAS, ICP, and BET, demonstrating the successful incorporation of N into the zeolite framework and an enhancement in metal dispersion upon N-substitution. A series of 18 monometallic and bimetallic catalysts is then synthesised on X and USY supports and screened for catalytic activity. Ru is identified as the most active metal for ammonia decomposition. Observed trends suggest catalyst dispersion can be increased with substantially lower metal loadings, and in particular the formation of stably anchored oligonuclear metal clusters within the zeolite framework, as opposed to much larger nanoparticles (NPs) on its exterior, following N-substitution of the framework. DFT modelling proposes a prismatic RuN cluster fitted to XAS data. High-activity catalyst Ru-β (N) 2.4% demonstrates comparable or better ammonia conversion by Ru wt% than recently reported catalysts in the literature at 450 °C and 30 000 WHSV.
PubMed: 37186100
DOI: 10.1039/d2fd00175f