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Cell May 2023Phenotypic sex-based differences exist for many complex traits. In other cases, phenotypes may be similar, but underlying biology may vary. Thus, sex-aware genetic... (Review)
Review
Phenotypic sex-based differences exist for many complex traits. In other cases, phenotypes may be similar, but underlying biology may vary. Thus, sex-aware genetic analyses are becoming increasingly important for understanding the mechanisms driving these differences. To this end, we provide a guide outlining the current best practices for testing various models of sex-dependent genetic effects in complex traits and disease conditions, noting that this is an evolving field. Insights from sex-aware analyses will not only teach us about the biology of complex traits but also aid in achieving the goals of precision medicine and health equity for all.
Topics: Animals; Female; Male; Models, Genetic; Multifactorial Inheritance; Phenotype; Quality Control; Sex Characteristics; Genome-Wide Association Study; Guidelines as Topic; Gene-Environment Interaction; Humans
PubMed: 37172561
DOI: 10.1016/j.cell.2023.04.014 -
Metabolites Sep 2023Volumetric absorptive microsampling (VAMS) has arisen as a relevant tool in biological analysis, offering simplified sampling procedures and enhanced stability. Most of... (Review)
Review
Volumetric absorptive microsampling (VAMS) has arisen as a relevant tool in biological analysis, offering simplified sampling procedures and enhanced stability. Most of the attention VAMS has received in the past decade has been from pharmaceutical research, with most of the published work employing VAMS targeting drugs or other exogenous compounds, such as toxins and pollutants. However, biomarker analysis by employing blood microsampling has high promise. Herein, a comprehensive review on the applicability of VAMS devices for the analysis of endogenous metabolites/biomarkers was performed. The study presents a full overview of the analysis process, incorporating all the steps in sample treatment and validation parameters. Overall, VAMS devices have proven to be reliable tools for the analysis of endogenous analytes with biological importance, often offering improved analyte stability in comparison with blood under ambient conditions as well as a convenient and straightforward sample acquisition model.
PubMed: 37887363
DOI: 10.3390/metabo13101038 -
RSC Advances Sep 2020We report a novel bioluminescent aptasensor, which consists of 2'-F-RNA aptamer modules joined into a bi-specific aptamer construct. One aptamer module binds the...
We report a novel bioluminescent aptasensor, which consists of 2'-F-RNA aptamer modules joined into a bi-specific aptamer construct. One aptamer module binds the analyte, then after structural rearrangement the second module recruits non-covalently Ca-dependent photoprotein obelin from the solution, thus providing a bioluminescent signal. This concept allows using free protein as a reporter, which brings such advantages as no need for aptamer-protein conjugation, a possibility of thermal re-folding of aptamer component with no harm to a protein, and simpler detection protocol. We developed the new 2'-F-RNA aptamer for obelin, and proposed the strategy for engineering structure-switching bi-modular aptamer constructs which bind the analyte and the obelin in a sequential manner. With the use of hemoglobin as a model analyte, we showed the feasibility of utilizing the aptasensor in a fast and straightforward bioluminescent microplate assay. With a proper design of a secondary structure, this strategy of aptasensor engineering might be further extended to bi-specific aptamer-based bioluminescent sensors for other analytes of interest.
PubMed: 35516485
DOI: 10.1039/d0ra05117a -
Journal of Food and Drug Analysis Dec 2020In recent years, carbon dots (C-dots) have gained appreciable interest owing to their unique optical properties, including tunable fluorescence, stability against... (Review)
Review
In recent years, carbon dots (C-dots) have gained appreciable interest owing to their unique optical properties, including tunable fluorescence, stability against photobleaching and photoblinking, and strong fluorescence. Simple and low-cost hydrothermal and electrochemical approaches have been widely used in the preparation of biocompatible and high-quality C-dots. Various C-dots have been used for the quantitation of small analytes, mostly based on analyte induced fluorescence quenching. Depending on the nature of precursors, synthetic conditions (such as reaction temperature and time), and surface conjugation, multi-function C-dots can be prepared and used in diagnostics and therapeutics. Their strong fluorescence and photostability, enables use in cell imaging. Their biological activity from the surface residues and capability of generating reactive oxygen species, have allowed many C-dots to become candidates as antibacterial and anticancer reagents. After suitable conjugation, biocompatible and fluorescent C-dots can be used for diagnostics and therapeutics, thus, showing their great potential in the area of theranostics.
PubMed: 35696139
DOI: 10.38212/2224-6614.1154 -
Analytical and Bioanalytical Chemistry Jan 2024The development and expansion of analytical methods for per- and polyfluoroalkyl substances (PFAS) in food are essential for the continued monitoring of the United...
The development and expansion of analytical methods for per- and polyfluoroalkyl substances (PFAS) in food are essential for the continued monitoring of the United States (US) food supply and assessments of dietary exposure. In March 2022, the European Union Reference Laboratory for Halogenated Persistent Organic Pollutants in Feed and Food (EURL POPs) released a guidance document covering priority PFAS of interest, including analytical method parameters and limits of quantification (LOQs). As a result, the Food and Drug Administration (FDA) began method extension work to incorporate ten new additional analytes to method C-010.02 including long-chain perfluorosulfonic acids, fluorotelomer sulfonates, and perfluorooctane sulfonamide. Four long-chain carboxylic acids were also validated across all foods, which were previously added to C-010.02 but only validated in seafood. In December 2022, the European Union published Commission Regulation 2022/2388, establishing maximum levels for perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) in certain foodstuffs, primarily fish, molluscs, crustaceans, and eggs. As a result, the FDA method was evaluated for performance in reaching LOQs defined in Commission Regulation (EU) 2022/1431. The FDA method was found to be able to reach all required LOQs for analytes in matrices with established maximum levels. Currently, method detection limits (MDLs), which are used by the FDA as the lower limit for reporting PFAS in surveillance samples, were in the same range as defined indicative levels. With further method modifications, required LOQs could be met in fruits, vegetables, and milk. Reaching the lower targeted LOQs for these food matrices will require moving the method to an instrument that can provide increased signal:noise gains at the lower limits of quantification.
Topics: Animals; United States; Alkanesulfonic Acids; Fluorocarbons; Vegetables; Dietary Exposure; Environmental Pollutants
PubMed: 37528269
DOI: 10.1007/s00216-023-04833-1 -
Biochimica Et Biophysica Acta Jul 2015Technologies to assay single cells and their extracellular microenvironments are valuable in elucidating biological function, but there are challenges. Sample volumes... (Review)
Review
Technologies to assay single cells and their extracellular microenvironments are valuable in elucidating biological function, but there are challenges. Sample volumes are low, the physicochemical parameters of the analytes vary widely, and the cellular environment is chemically complex. In addition, the inherent difficulty of isolating individual cells and handling small volume samples complicates many experimental protocols. Here we highlight a number of mass spectrometry (MS)-based measurement approaches for characterizing the chemical content of small volume analytes, with a focus on methods used to detect intracellular and extracellular metabolites and peptides from samples as small as individual cells. MS has become one of the most effective means for analyzing small biological samples due to its high sensitivity, low analyte consumption, compatibility with a wide array of sampling approaches, and ability to detect a large number of analytes with different properties without preselection. Having access to a flexible portfolio of MS-based methods allows quantitative, qualitative, untargeted, targeted, multiplexed, and spatially resolved investigations of single cells and their similarly scaled extracellular environments. Combining MS with on-line and off-line sample conditioning tools, such as microfluidic and capillary electrophoresis systems, significantly increases the analytical coverage of the sample's metabolome and peptidome, and improves individual analyte characterization/identification. Small volume assays help to reveal the causes and manifestations of biological and pathological variability, as well as the functional heterogeneity of individual cells within their microenvironments and within cellular populations. This article is part of a Special Issue entitled: Neuroproteomics: Applications in Neuroscience and Neurology.
Topics: Animals; Humans; Mass Spectrometry; Peptides
PubMed: 25617659
DOI: 10.1016/j.bbapap.2015.01.008 -
Annales de Biologie Clinique Aug 2018Salivary cortisol assay, described for the first time almost forty years ago, has not been expanding until the last decade. Its simplicity, non-invasiveness and the easy... (Review)
Review
Salivary cortisol assay, described for the first time almost forty years ago, has not been expanding until the last decade. Its simplicity, non-invasiveness and the easy repetition of sampling make it an analytical matrix of interest. Since the publication of the recommendations of the American endocrinology society in 2008, salivary cortisol is recognized as one of the three main tests to screen for Cushing's syndrome. In addition, salivary cortisone, the major metabolite of salivary cortisol, still represents a severe potential interferent but could also be a complementary analyte for indications where evaluation of cortisol secretion is sought. Moreover, in the current context of practices and methods harmonization, the problem of lack of standardization presents also for salivary cortisol. This review briefly develops the three main tests of Cushing's syndrome screening to explain the reasons for integrating the saliva test into this screening. Then we will develop the variables that can influence salivary cortisol from a pre-analytic, physiopathological and finally analytical point of view.
Topics: Addison Disease; Circadian Rhythm; Cushing Syndrome; Humans; Hydrocortisone; Pre-Analytical Phase; Saliva; Specimen Handling
PubMed: 29952304
DOI: 10.1684/abc.2018.1355 -
Biochemia Medica 2015This systematic review presents the latest trends in salivary research and its applications in health and disease. Among the large number of analytes present in saliva,... (Review)
Review
This systematic review presents the latest trends in salivary research and its applications in health and disease. Among the large number of analytes present in saliva, many are affected by diverse physiological and pathological conditions. Further, the non-invasive, easy and cost-effective collection methods prompt an interest in evaluating its diagnostic or prognostic utility. Accumulating data over the past two decades indicates towards the possible utility of saliva to monitor overall health, diagnose and treat various oral or systemic disorders and drug monitoring. Advances in saliva based systems biology has also contributed towards identification of several biomarkers, development of diverse salivary diagnostic kits and other sensitive analytical techniques. However, its utilization should be carefully evaluated in relation to standardization of pre-analytical and analytical variables, such as collection and storage methods, analyte circadian variation, sample recovery, prevention of sample contamination and analytical procedures. In spite of all these challenges, there is an escalating evolution of knowledge with the use of this biological matrix.
Topics: Animals; Biomarkers; Clinical Laboratory Techniques; Humans; Reagent Kits, Diagnostic; Saliva; Sensitivity and Specificity; Specimen Handling; Systems Biology
PubMed: 26110030
DOI: 10.11613/BM.2015.018 -
Annals of Biomedical Engineering Oct 2020Molecular diagnostics have traditionally relied on discrete biological substances as diagnostic markers. In recent years however, advances in on-chip biomarker screening... (Review)
Review
Molecular diagnostics have traditionally relied on discrete biological substances as diagnostic markers. In recent years however, advances in on-chip biomarker screening technologies and data analytics have enabled signature-based diagnostics. Such diagnostics aim to utilize unique combinations of multiple biomarkers or diagnostic 'fingerprints' rather than discrete analyte measurements. This approach has shown to improve both diagnostic accuracy and diagnostic specificity. In this review, signature-based diagnostics enabled by microfluidic and micro-/nano- technologies will be reviewed with a focus on device design and data analysis pipelines and methodologies. With increasing amounts of data available from microfluidic biomarker screening, isolation, and detection platforms, advanced data handling and analytics approaches can be employed. Thus, current data analysis approaches including machine learning and recent advances with image processing, along with potential future directions will be explored. Lastly, the needs and gaps in current literature will be elucidated to inform future efforts towards development of molecular diagnostics and biomarker screening technologies.
Topics: Animals; Biomarkers; Humans; Lab-On-A-Chip Devices; Machine Learning; Microfluidic Analytical Techniques; Molecular Diagnostic Techniques
PubMed: 32816167
DOI: 10.1007/s10439-020-02593-y -
PloS One 2019The maximum entropy model, a commonly used species distribution model (SDM) normally combines observations of the species occurrence with environmental information to...
The maximum entropy model, a commonly used species distribution model (SDM) normally combines observations of the species occurrence with environmental information to predict the geographic distributions of animal or plant species. However, it only produces point estimates for the probability of species existence. To understand the uncertainty of the point estimates, we analytically derived the variance of the outputs of the maximum entropy model from the variance of the input. We applied the analytic method to obtain the standard deviation of dengue importation probability and Aedes aegypti suitability. Dengue occurrence data and Aedes aegypti mosquito abundance data, combined with demographic and environmental data, were applied to obtain point estimates and the corresponding variance. To address the issue of not having the true distributions for comparison, we compared and contrasted the performance of the analytical expression with the bootstrap method and Poisson point process model which proved of equivalence of maximum entropy model with the assumption of independent point locations. Both Dengue importation probability and Aedes aegypti mosquito suitability examples show that the methods generate comparatively the same results and the analytic method we introduced is dramatically faster than the bootstrap method and directly apply to maximum entropy model.
Topics: Aedes; Algorithms; Animals; Biodiversity; Dengue; Dengue Virus; Ecosystem; Entropy; Models, Theoretical; Mosquito Vectors; Uncertainty
PubMed: 31120909
DOI: 10.1371/journal.pone.0214190