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1.
Sensors (Basel) ; 22(3)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35161583

RESUMO

The impact of diet and digestive disorders in flatus composition remains largely unexplored. This is partially due to the lack of standardized sampling collection methods, and the easy atmospheric contamination. This paper describes a method to quantitatively determine the major gases in flatus and their application in a nutritional intervention. We describe how to direct sample flatus into Tedlar bags, and simultaneous analysis by gas chromatography-thermal conductivity detection (GC-TCD). Results are analyzed by univariate hypothesis testing and by multilevel principal component analysis. The reported methodology allows simultaneous determination of the five major gases with root mean measurement errors of 0.8% for oxygen (O2), 0.9% for nitrogen (N2), 0.14% for carbon dioxide (CO2), 0.11% for methane (CH4), and 0.26% for hydrogen (H2). The atmospheric contamination was limited to 0.86 (95% CI: [0.7-1.0])% for oxygen and 3.4 (95% CI: [1.4-5.3])% for nitrogen. As an illustration, the method has been successfully applied to measure the response to a nutritional intervention in a reduced crossover study in healthy subjects.


Assuntos
Flatulência , Metano , Dióxido de Carbono , Cromatografia Gasosa , Estudos Cross-Over , Dieta , Humanos , Condutividade Térmica
2.
Bioinformatics ; 36(9): 2943-2945, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31930381

RESUMO

SUMMARY: Nuclear magnetic resonance (NMR)-based metabolomics is widely used to obtain metabolic fingerprints of biological systems. While targeted workflows require previous knowledge of metabolites, prior to statistical analysis, untargeted approaches remain a challenge. Computational tools dealing with fully untargeted NMR-based metabolomics are still scarce or not user-friendly. Therefore, we developed AlpsNMR (Automated spectraL Processing System for NMR), an R package that provides automated and efficient signal processing for untargeted NMR metabolomics. AlpsNMR includes spectra loading, metadata handling, automated outlier detection, spectra alignment and peak-picking, integration and normalization. The resulting output can be used for further statistical analysis. AlpsNMR proved effective in detecting metabolite changes in a test case. The tool allows less experienced users to easily implement this workflow from spectra to a ready-to-use dataset in their routines. AVAILABILITY AND IMPLEMENTATION: The AlpsNMR R package and tutorial is freely available to download from http://github.com/sipss/AlpsNMR under the MIT license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Metabolômica , Software , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Fluxo de Trabalho
3.
Sensors (Basel) ; 21(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34577363

RESUMO

Gas chromatography-ion mobility spectrometry (GC-IMS) allows the fast, reliable, and inexpensive chemical composition analysis of volatile mixtures. This sensing technology has been successfully employed in food science to determine food origin, freshness and preventing alimentary fraud. However, GC-IMS data is highly dimensional, complex, and suffers from strong non-linearities, baseline problems, misalignments, peak overlaps, long peak tails, etc., all of which must be corrected to properly extract the relevant features from samples. In this work, a pipeline for signal pre-processing, followed by four different approaches for feature extraction in GC-IMS data, is presented. More precisely, these approaches consist of extracting data features from: (1) the total area of the reactant ion peak chromatogram (RIC); (2) the full RIC response; (3) the unfolded sample matrix; and (4) the ion peak volumes. The resulting pipelines for data processing were applied to a dataset consisting of two different quality class Iberian ham samples, based on their feeding regime. The ability to infer chemical information from samples was tested by comparing the classification results obtained from partial least-squares discriminant analysis (PLS-DA) and the samples' variable importance for projection (VIP) scores. The choice of a feature extraction strategy is a trade-off between the amount of chemical information that is preserved, and the computational effort required to generate the data models.


Assuntos
Espectrometria de Mobilidade Iônica , Odorantes , Análise Discriminante , Cromatografia Gasosa-Espectrometria de Massas , Odorantes/análise , Fluxo de Trabalho
4.
Sensors (Basel) ; 19(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540524

RESUMO

Metal oxide (MOX) sensors are widely used for chemical sensing due to their low cost, miniaturization, low power consumption and durability. Yet, getting instantaneous measurements of fluctuating gas concentration in turbulent plumes is not possible due to their slow response time. In this paper, we show that the slow response of MOX sensors can be compensated by deconvolution, provided that an invertible, parametrized, sensor model is available. We consider a nonlinear, first-order dynamic model that is mathematically tractable for MOX identification and deconvolution. By transforming the sensor signal in the log-domain, the system becomes linear in the parameters and these can be estimated by the least-squares techniques. Moreover, we use the MOX diversity in a sensor array to avoid training with a supervised signal. The information provided by two (or more) sensors, exposed to the same flow but responding with different dynamics, is exploited to recover the ground truth signal (gas input). This approach is known as blind deconvolution. We demonstrate its efficiency on MOX sensors recorded in turbulent plumes. The reconstructed signal is similar to the one obtained with a fast photo-ionization detector (PID). The technique is thus relevant to track a fast-changing gas concentration with MOX sensors, resulting in a compensated response time comparable to that of a PID.

5.
Sensors (Basel) ; 19(3)2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30682827

RESUMO

This paper describes the development and validation of the currently smallest aerial platform with olfaction capabilities. The developed Smelling Nano Aerial Vehicle (SNAV) is based on a lightweight commercial nano-quadcopter (27 g) equipped with a custom gas sensing board that can host up to two in situ metal oxide semiconductor (MOX) gas sensors. Due to its small form-factor, the SNAV is not a hazard for humans, enabling its use in public areas or inside buildings. It can autonomously carry out gas sensing missions of hazardous environments inaccessible to terrestrial robots and bigger drones, for example searching for victims and hazardous gas leaks inside pockets that form within the wreckage of collapsed buildings in the aftermath of an earthquake or explosion. The first contribution of this work is assessing the impact of the nano-propellers on the MOX sensor signals at different distances to a gas source. A second contribution is adapting the 'bout' detection algorithm, proposed by Schmuker et al. (2016) to extract specific features from the derivative of the MOX sensor response, for real-time operation. The third and main contribution is the experimental validation of the SNAV for gas source localization (GSL) and mapping in a large indoor environment (160 m²) with a gas source placed in challenging positions for the drone, for example hidden in the ceiling of the room or inside a power outlet box. Two GSL strategies are compared, one based on the instantaneous gas sensor response and the other one based on the bout frequency. From the measurements collected (in motion) along a predefined sweeping path we built (in less than 3 min) a 3D map of the gas distribution and identified the most likely source location. Using the bout frequency yielded on average a higher localization accuracy than using the instantaneous gas sensor response (1.38 m versus 2.05 m error), however accurate tuning of an additional parameter (the noise threshold) is required in the former case. The main conclusion of this paper is that a nano-drone has the potential to perform gas sensing tasks in complex environments.

6.
Sensors (Basel) ; 19(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027330

RESUMO

This paper proposes the application of a low-cost gas sensor array in an assistant personal robot (APR) in order to extend the capabilities of the mobile robot as an early gas leak detector for safety purposes. The gas sensor array is composed of 16 low-cost metal-oxide (MOX) gas sensors, which are continuously in operation. The mobile robot was modified to keep the gas sensor array always switched on, even in the case of battery recharge. The gas sensor array provides 16 individual gas measurements and one output that is a cumulative summary of all measurements, used as an overall indicator of a gas concentration change. The results of preliminary experiments were used to train a partial least squares discriminant analysis (PLS-DA) classifier with air, ethanol, and acetone as output classes. Then, the mobile robot gas leak detection capabilities were experimentally evaluated in a public facility, by forcing the evaporation of (1) ethanol, (2) acetone, and (3) ethanol and acetone at different locations. The positive results obtained in different operation conditions over the course of one month confirmed the early detection capabilities of the proposed mobile system. For example, the APR was able to detect a gas leak produced inside a closed room from the external corridor due to small leakages under the door induced by the forced ventilation system of the building.

7.
Anal Bioanal Chem ; 410(23): 5981-5992, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29959482

RESUMO

Advances in analytical instrumentation have provided the possibility of examining thousands of genes, peptides, or metabolites in parallel. However, the cost and time-consuming data acquisition process causes a generalized lack of samples. From a data analysis perspective, omics data are characterized by high dimensionality and small sample counts. In many scenarios, the analytical aim is to differentiate between two different conditions or classes combining an analytical method plus a tailored qualitative predictive model using available examples collected in a dataset. For this purpose, partial least squares-discriminant analysis (PLS-DA) is frequently employed in omics research. Recently, there has been growing concern about the uncritical use of this method, since it is prone to overfitting and may aggravate problems of false discoveries. In many applications involving a small number of subjects or samples, predictive model performance estimation is only based on cross-validation (CV) results with a strong preference for reporting results using leave one out (LOO). The combination of PLS-DA for high dimensionality data and small sample conditions, together with a weak validation methodology is a recipe for unreliable estimations of model performance. In this work, we present a systematic study about the impact of the dataset size, the dimensionality, and the CV technique used on PLS-DA overoptimism when performance estimation is done in cross-validation. Firstly, by using synthetic data generated from a same probability distribution and with assigned random binary labels, we have obtained a dataset where the true classification rate (CR) is 50%. As expected, our results confirm that internal validation provides overoptimistic estimations of the classification accuracy (i.e., overfitting). We have characterized the CR estimator in terms of bias and variance depending on the internal CV technique used and sample to dimensionality ratio. In small sample conditions, due to the large bias and variance of the estimator, the occurrence of extremely good CRs is common. We have found that overfitting peaks when the sample size in the training subset approaches the feature vector dimensionality minus one. In these conditions, the models are neither under- or overdetermined with a unique solution. This effect is particularly intense for LOO and peaks higher in small sample conditions. Overoptimism is decreased beyond this point where the abundance of noisy produces a regularization effect leading to less complex models. In terms of overfitting, our study ranks CV methods as follows: Bootstrap produces the most accurate estimator of the CR, followed by bootstrapped Latin partitions, random subsampling, K-Fold, and finally, the very popular LOO provides the worst results. Simulation results are further confirmed in real datasets from mass spectrometry and microarrays.


Assuntos
Biologia Computacional/métodos , Espectrometria de Massas/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise Discriminante , Humanos , Análise dos Mínimos Quadrados , Estudos de Validação como Assunto
8.
Sensors (Basel) ; 18(2)2018 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-29370092

RESUMO

Mobile applications based on gas sensing present new opportunities for low-cost air quality monitoring, safety, and healthcare. Metal oxide semiconductor (MOX) gas sensors represent the most prominent technology for integration into portable devices, such as smartphones and wearables. Traditionally, MOX sensors have been continuously powered to increase the stability of the sensing layer. However, continuous power is not feasible in many battery-operated applications due to power consumption limitations or the intended intermittent device operation. This work benchmarks two low-power, duty-cycling, and on-demand modes against the continuous power one. The duty-cycling mode periodically turns the sensors on and off and represents a trade-off between power consumption and stability. On-demand operation achieves the lowest power consumption by powering the sensors only while taking a measurement. Twelve thermally modulated SB-500-12 (FIS Inc. Jacksonville, FL, USA) sensors were exposed to low concentrations of carbon monoxide (0-9 ppm) with environmental conditions, such as ambient humidity (15-75% relative humidity) and temperature (21-27 °C), varying within the indicated ranges. Partial Least Squares (PLS) models were built using calibration data, and the prediction error in external validation samples was evaluated during the two weeks following calibration. We found that on-demand operation produced a deformation of the sensor conductance patterns, which led to an increase in the prediction error by almost a factor of 5 as compared to continuous operation (2.2 versus 0.45 ppm). Applying a 10% duty-cycling operation of 10-min periods reduced this prediction error to a factor of 2 (0.9 versus 0.45 ppm). The proposed duty-cycling powering scheme saved up to 90% energy as compared to the continuous operating mode. This low-power mode may be advantageous for applications that do not require continuous and periodic measurements, and which can tolerate slightly higher prediction errors.

9.
Sensors (Basel) ; 18(2)2018 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-29439490

RESUMO

Indoor fire detection using gas chemical sensing has been a subject of investigation since the early nineties. This approach leverages the fact that, for certain types of fire, chemical volatiles appear before smoke particles do. Hence, systems based on chemical sensing can provide faster fire alarm responses than conventional smoke-based fire detectors. Moreover, since it is known that most casualties in fires are produced from toxic emissions rather than actual burns, gas-based fire detection could provide an additional level of safety to building occupants. In this line, since the 2000s, electrochemical cells for carbon monoxide sensing have been incorporated into fire detectors. Even systems relying exclusively on gas sensors have been explored as fire detectors. However, gas sensors respond to a large variety of volatiles beyond combustion products. As a result, chemical-based fire detectors require multivariate data processing techniques to ensure high sensitivity to fires and false alarm immunity. In this paper, we the survey toxic emissions produced in fires and defined standards for fire detection systems. We also review the state of the art of chemical sensor systems for fire detection and the associated signal and data processing algorithms. We also examine the experimental protocols used for the validation of the different approaches, as the complexity of the test measurements also impacts on reported sensitivity and specificity measures. All in all, further research and extensive test under different fire and nuisance scenarios are still required before gas-based fire detectors penetrate largely into the market. Nevertheless, the use of dynamic features and multivariate models that exploit sensor correlations seems imperative.

10.
Sensors (Basel) ; 18(6)2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29899257

RESUMO

The quality and composition of bitter orange essential oils (EOs) strongly depend on the ripening stage of the citrus fruit. The concentration of volatile compounds and consequently its organoleptic perception varies. While this can be detected by trained humans, we propose an objective approach for assessing the bitter orange from the volatile composition of their EO. The method is based on the combined use of headspace gas chromatography⁻mass spectrometry (HS-GC-MS) and artificial neural networks (ANN) for predictive modeling. Data obtained from the analysis of HS-GC-MS were preprocessed to select relevant peaks in the total ion chromatogram as input features for ANN. Results showed that key volatile compounds have enough predictive power to accurately classify the EO, according to their ripening stage for different applications. A sensitivity analysis detected the key compounds to identify the ripening stage. This study provides a novel strategy for the quality control of bitter orange EO without subjective methods.

11.
Sensors (Basel) ; 17(4)2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28425926

RESUMO

We present the estimation of a likelihood map for the location of the source of a chemical plume dispersed under atmospheric turbulence under uniform wind conditions. The main contribution of this work is to extend previous proposals based on Bayesian inference with binary detections to the use of concentration information while at the same time being robust against the presence of background chemical noise. For that, the algorithm builds a background model with robust statistics measurements to assess the posterior probability that a given chemical concentration reading comes from the background or from a source emitting at a distance with a specific release rate. In addition, our algorithm allows multiple mobile gas sensors to be used. Ten realistic simulations and ten real data experiments are used for evaluation purposes. For the simulations, we have supposed that sensors are mounted on cars which do not have among its main tasks navigating toward the source. To collect the real dataset, a special arena with induced wind is built, and an autonomous vehicle equipped with several sensors, including a photo ionization detector (PID) for sensing chemical concentration, is used. Simulation results show that our algorithm, provides a better estimation of the source location even for a low background level that benefits the performance of binary version. The improvement is clear for the synthetic data while for real data the estimation is only slightly better, probably because our exploration arena is not able to provide uniform wind conditions. Finally, an estimation of the computational cost of the algorithmic proposal is presented.

12.
BMC Bioinformatics ; 16: 377, 2015 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-26553056

RESUMO

BACKGROUND: The detection of regulatory regions in candidate sequences is essential for the understanding of the regulation of a particular gene and the mechanisms involved. This paper proposes a novel methodology based on information theoretic metrics for finding regulatory sequences in promoter regions. RESULTS: This methodology (SIGMA) has been tested on genomic sequence data for Homo sapiens and Mus musculus. SIGMA has been compared with different publicly available alternatives for motif detection, such as MEME/MAST, Biostrings (Bioconductor package), MotifRegressor, and previous work such Qresiduals projections or information theoretic based detectors. Comparative results, in the form of Receiver Operating Characteristic curves, show how, in 70% of the studied Transcription Factor Binding Sites, the SIGMA detector has a better performance and behaves more robustly than the methods compared, while having a similar computational time. The performance of SIGMA can be explained by its parametric simplicity in the modelling of the non-linear co-variability in the binding motif positions. CONCLUSIONS: Sequence Information Gain based Motif Analysis is a generalisation of a non-linear model of the cis-regulatory sequences detection based on Information Theory. This generalisation allows us to detect transcription factor binding sites with maximum performance disregarding the covariability observed in the positions of the training set of sequences. SIGMA is freely available to the public at http://b2slab.upc.edu.


Assuntos
Algoritmos , Genoma , Genômica/métodos , Motivos de Nucleotídeos/genética , Software , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação/genética , Humanos , Camundongos , Dinâmica não Linear , Ligação Proteica/genética , Curva ROC
13.
Anal Bioanal Chem ; 406(16): 3941-56, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24817347

RESUMO

Over the last two decades, electronic nose research has produced thousands of research works. Many of them were describing the ability of the e-nose technology to solve diverse applications in domains ranging from food technology to safety, security, or health. It is, in fact, in the biomedical field where e-nose technology is finding a research niche in the last years. Although few success stories exist, most described applications never found the road to industrial or clinical exploitation. Most described methodologies were not reliable and were plagued by numerous problems that prevented practical application beyond the lab. This work emphasizes the need of external validation in machine olfaction. I describe some statistical and methodological pitfalls of the e-nose practice and I give some best practice recommendations for researchers in the field.


Assuntos
Técnicas Biossensoriais/normas , Nariz Eletrônico/normas , Odorantes/análise , Humanos , Olfato
14.
Sensors (Basel) ; 14(9): 17331-52, 2014 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-25232911

RESUMO

In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources.


Assuntos
Técnicas de Química Analítica/instrumentação , Técnicas de Química Analítica/métodos , Gases/análise , Robótica/instrumentação , Robótica/métodos , Software , Interface Usuário-Computador , Misturas Complexas/análise , Desenho de Equipamento , Análise de Falha de Equipamento , Movimento (Física) , Integração de Sistemas
15.
Sensors (Basel) ; 14(4): 6045-55, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24681671

RESUMO

This paper proposes the use of an autonomous assistant mobile robot in order to monitor the environmental conditions of a large indoor area and develop an ambient intelligence application. The mobile robot uses single high performance embedded sensors in order to collect and geo-reference environmental information such as ambient temperature, air velocity and orientation and gas concentration. The data collected with the assistant mobile robot is analyzed in order to detect unusual measurements or discrepancies and develop focused corrective ambient actions. This paper shows an example of the measurements performed in a research facility which have enabled the detection and location of an uncomfortable temperature profile inside an office of the research facility. The ambient intelligent application has been developed by performing some localized ambient measurements that have been analyzed in order to propose some ambient actuations to correct the uncomfortable temperature profile.


Assuntos
Inteligência Artificial , Meio Ambiente , Movimento (Física) , Robótica/métodos , Gases/análise , Decoração de Interiores e Mobiliário , Temperatura , Vento
16.
Int J Surg ; 110(3): 1493-1501, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38116682

RESUMO

BACKGROUND: Early detection of postoperative complications after colorectal cancer (CRC) surgery is associated with improved outcomes. The aim was to investigate early metabolomics signatures capable to detect patients at risk for severe postoperative complications after CRC surgery. MATERIALS AND METHODS: Prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before and after surgery, and analyzed by mass spectrometry obtaining 188 metabolites and 21 ratios. Postoperative complications were registered with Clavien-Dindo Classification and Comprehensive Complication Index. RESULTS: One hundred forty-six patients were included. Surgery substantially modified metabolome and metabolic changes after surgery were quantitatively associated with the severity of postoperative complications. The strongest positive relationship with both Clavien-Dindo and Comprehensive Complication Index (ß=4.09 and 63.05, P <0.001) corresponded to kynurenine/tryptophan, against an inverse relationship with lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs). Patients with LPC18:2/PCa36:2 below the cut-off 0.084 µM/µM resulted in a sevenfold higher risk of major complications (OR=7.38, 95% CI: 2.82-21.25, P <0.001), while kynurenine/tryptophan above 0.067 µM/µM a ninefold (OR=9.35, 95% CI: 3.03-32.66, P <0.001). Hexadecanoylcarnitine below 0.093 µM displayed a 12-fold higher risk of anastomotic leakage-related complications (OR=11.99, 95% CI: 2.62-80.79, P =0.004). CONCLUSION: Surgery-induced phospholipids and amino acid dysregulation is associated with the severity of postoperative complications after CRC surgery, including anastomotic leakage-related outcomes. The authors provide quantitative insight on metabolic markers, measuring vulnerability to postoperative morbidity that might help guide early decision-making and improve surgical outcomes.


Assuntos
Fístula Anastomótica , Neoplasias Colorretais , Humanos , Estudos Prospectivos , Triptofano , Cinurenina , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Estudos Retrospectivos
17.
Bioinformatics ; 28(10): 1328-35, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22467907

RESUMO

MOTIVATION: The identification of the sites at which transcription factors (TFs) bind to Deoxyribonucleic acid (DNA) is an important problem in molecular biology. Many computational methods have been developed for motif finding, most of them based on position-specific scoring matrices (PSSMs) which assume the independence of positions within a binding site. However, some experimental and computational studies demonstrate that interdependences within the positions exist. RESULTS: In this article, we introduce a novel motif finding method which constructs a subspace based on the covariance of numerical DNA sequences. When a candidate sequence is projected into the modeled subspace, a threshold in the Q-residuals confidence allows us to predict whether this sequence is a binding site. Using the TRANSFAC and JASPAR databases, we compared our Q-residuals detector with existing PSSM methods. In most of the studied TF binding sites, the Q-residuals detector performs significantly better and faster than MATCH and MAST. As compared with Motifscan, a method which takes into account interdependences, the performance of the Q-residuals detector is better when the number of available sequences is small.


Assuntos
Algoritmos , Motivos de Nucleotídeos , Matrizes de Pontuação de Posição Específica , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Humanos , Ligação Proteica , Análise de Sequência de DNA/métodos , Fatores de Transcrição/química , Fatores de Transcrição/genética
18.
Front Mol Biosci ; 10: 1125582, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333016

RESUMO

Introduction: There is evidence that sample treatment of blood-based biosamples may affect integral signals in nuclear magnetic resonance-based metabolomics. The presence of macromolecules in plasma/serum samples makes investigating low-molecular-weight metabolites challenging. It is particularly relevant in the targeted approach, in which absolute concentrations of selected metabolites are often quantified based on the area of integral signals. Since there are a few treatments of plasma/serum samples for quantitative analysis without a universally accepted method, this topic remains of interest for future research. Methods: In this work, targeted metabolomic profiling of 43 metabolites was performed on pooled plasma to compare four methodologies consisting of Carr-Purcell-Meiboom-Gill (CPMG) editing, ultrafiltration, protein precipitation with methanol, and glycerophospholipid solid-phase extraction (g-SPE) for phospholipid removal; prior to NMR metabolomics analysis. The effect of the sample treatments on the metabolite concentrations was evaluated using a permutation test of multiclass and pairwise Fisher scores. Results: Results showed that methanol precipitation and ultrafiltration had a higher number of metabolites with coefficient of variation (CV) values above 20%. G-SPE and CPMG editing demonstrated better precision for most of the metabolites analyzed. However, differential quantification performance between procedures were metabolite-dependent. For example, pairwise comparisons showed that methanol precipitation and CPMG editing were suitable for quantifying citrate, while g-SPE showed better results for 2-hydroxybutyrate and tryptophan. Discussion: There are alterations in the absolute concentration of various metabolites that are dependent on the procedure. Considering these alterations is essential before proceeding with the quantification of treatment-sensitive metabolites in biological samples for improving biomarker discovery and biological interpretations. The study demonstrated that g-SPE and CPMG editing are effective methods for removing proteins and phospholipids from plasma samples for quantitative NMR analysis of metabolites. However, careful consideration should be given to the specific metabolites of interest and their susceptibility to the sample treatment procedures. These findings contribute to the development of optimized sample preparation protocols for metabolomics studies using NMR spectroscopy.

19.
J Cell Biol ; 222(9)2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37378613

RESUMO

Autonomous circadian clocks exist in nearly every mammalian cell type. These cellular clocks are subjected to a multilayered regulation sensitive to the mechanochemical cell microenvironment. Whereas the biochemical signaling that controls the cellular circadian clock is increasingly well understood, mechanisms underlying regulation by mechanical cues are largely unknown. Here we show that the fibroblast circadian clock is mechanically regulated through YAP/TAZ nuclear levels. We use high-throughput analysis of single-cell circadian rhythms and apply controlled mechanical, biochemical, and genetic perturbations to study the expression of the clock gene Rev-erbα. We observe that Rev-erbα circadian oscillations are disrupted with YAP/TAZ nuclear translocation. By targeted mutations and overexpression of YAP/TAZ, we show that this mechanobiological regulation, which also impacts core components of the clock such as Bmal1 and Cry1, depends on the binding of YAP/TAZ to the transcriptional effector TEAD. This mechanism could explain the impairment of circadian rhythms observed when YAP/TAZ activity is upregulated, as in cancer and aging.


Assuntos
Relógios Circadianos , Fatores de Transcrição de Domínio TEA , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP , Animais , Relógios Circadianos/genética , Ritmo Circadiano/genética , Mamíferos , Transdução de Sinais , Proteínas de Sinalização YAP/genética , Fatores de Transcrição de Domínio TEA/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/genética
20.
Chem Senses ; 37(7): 639-53, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22459165

RESUMO

In an effort to deepen our understanding of mammalian olfactory coding, we have used an objective method to analyze a large set of odorant-evoked activity maps collected systematically across the rat olfactory bulb to determine whether such an approach could identify specific glomerular regions that are activated by related odorants. To that end, we combined fuzzy c-means clustering methods with a novel validity approach based on cluster stability to evaluate the significance of the fuzzy partitions on a data set of glomerular layer responses to a large diverse group of odorants. Our results confirm the existence of glomerular response clusters to similar odorants. They further indicate a partial hierarchical chemotopic organization wherein larger glomerular regions can be subdivided into smaller areas that are rather specific in their responses to particular functional groups of odorants. These clusters bear many similarities to, as well as some differences from, response domains previously proposed for the glomerular layer of the bulb. These data also provide additional support for the concept of an identity code in the mammalian olfactory system.


Assuntos
Bulbo Olfatório/fisiologia , Olfato , Animais , Análise por Conglomerados , Desoxiglucose/farmacologia , Bulbo Olfatório/efeitos dos fármacos , Análise de Componente Principal , Ratos
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