| 1. |
- Bachi, Lorenzo, et al.
(författare)
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ECG Modeling for Simulation of Arrhythmias in Time-Varying Conditions
- 2023
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Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294. ; 70:12, s. 3449-3460
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Tidskriftsartikel (refereegranskat)abstract
- The present paper proposes an ECG simulator that advances modeling of arrhythmias and noise by introducing time-varying signal characteristics. The simulator is built around a discrete-time Markov chain model for simulating atrial and ventricular arrhythmias of particular relevance when analyzing atrial fibrillation (AF). Each state is associated with statistical information on episode duration and heartbeat characteristics. Statistical, time-varying modeling of muscle noise, motion artifacts, and the influence of respiration is introduced to increase the complexity of simulated ECGs, making the simulator well suited for data augmentation in machine learning. Modeling of how the PQ and QT intervals depend on heart rate is also introduced. The realism of simulated ECGs is assessed by three experienced doctors, showing that simulated ECGs are difficult to distinguish from real ECGs. Simulator usefulness is illustrated in terms of AF detection performance when either simulated or real ECGs are used to train a neural network for signal quality control. The results show that both types of training lead to similar performance.
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| 2. |
- Perez, Cristina, et al.
(författare)
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Evaluation of a QT Adaptation Time Estimator for ECG Exercise Stress Test in Controlled Simulation
- 2023
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Ingår i: Computing in Cardiology, CinC 2023. - 2325-8861 .- 2325-887X. - 9798350382525
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Konferensbidrag (refereegranskat)abstract
- Slowed adaptation of the QT interval to sudden abrupt heart rate (HR) changes has been identified as a marker of ventricular arrhythmic risk. However, abrupt HR changes are difficult to induce in patients. Quantifying the QT adaptation time in gradual HR changes, as observed in ECGs recording during an exercise stress test, has been recently proposed. The time lag between the QT series and an instantaneous memoryless HR-dependent QT series along stress test was computed as QT memory. Here, this method was evaluated in a control scenario using simulated exercise stress test ECG signals presenting different QT adaptation times. The method robustness was studied by contaminating the ECGs with muscular noise (MN) signals with different Signal-to-Noise ratio (SNR) values, either synthetic or extracted from real recordings. We found that delineation of the T-wave end point in the first transformed lead from Periodic Component Analysis offers the best performance for low SNR. Moreover, we confirmed that the estimator provides an unbiased estimate of the QT memory introduced in the simulations for the studied range of SNR values (25 to 50 dB).
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| 3. |
- Wilkes, Mark C., et al.
(författare)
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The active component of ginseng, ginsenoside Rb1, improves erythropoiesis in models of Diamond–Blackfan anemia by targeting Nemo-like kinase
- 2021
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 297:3
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Tidskriftsartikel (refereegranskat)abstract
- Nemo-like kinase (NLK) is a member of the mitogen-activated protein kinase family of kinases and shares a highly conserved kinase domain with other mitogen-activated protein kinase family members. The activation of NLK contributes to the pathogenesis of Diamond–Blackfan anemia (DBA), reducing c-myb expression and mechanistic target of rapamycin activity, and is therefore a potential therapeutic target. Unlike other anemias, the hematopoietic effects of DBA are largely restricted to the erythroid lineage. Mutations in ribosomal genes induce ribosomal insufficiency and reduced protein translation, dramatically impacting early erythropoiesis in the bone marrow of patients with DBA. We sought to identify compounds that suppress NLK and increases erythropoiesis in ribosomal insufficiency. We report that the active component of ginseng, ginsenoside Rb1, suppresses NLK expression and improves erythropoiesis in in vitro models of DBA. Ginsenoside Rb1–mediated suppression of NLK occurs through the upregulation of miR-208, which binds to the 30-UTR of NLK mRNA and targets it for degradation. We also compare ginsenoside Rb1–mediated upregulation of miR-208 with metformin-mediated upregulation of miR-26. We conclude that targeting NLK expression through miRNA binding of the unique 30-UTR is a viable alternative to the challenges of developing small-molecule inhibitors to target the highly conserved kinase domain of this specific kinase.
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| 4. |
- Padilla, Lorena, et al.
(författare)
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Period of Boar Ejaculate Collection Contributes to the Yearly Intra-Male Variability of Seminal Plasma Cytokines
- 2020
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Ingår i: Biology. - : MDPI. - 2079-7737. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- The concentrations of cytokines in seminal plasma (SP) fluctuate over time in healthy males, weakening their practical usefulness as diagnostic tools. This study evaluated the relevance of intra-male variability in SP cytokines and to what extent the period of the year when ejaculate is collected contributes to such variability. Thirteen cytokines (GM-CSF, IFN gamma, IL-1 alpha, IL-1 beta, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, and TNF alpha) were measured using the Luminex xMAP(R) technology for 180 SP samples of ejaculate collected over a year from nine healthy and fertile boars. The SP samples were grouped into two annual periods according to decreasing or increasing daylight and ambient temperature. Intra-male variability was higher than inter-male variability for all cytokines. All SP cytokines showed concentration differences between the two periods of the year, showing the highest concentration during the increasing daylength/temperature period, irrespective of the male. Similarly, some cytokines showed differences between daylength/temperature periods when focusing on their total amount in the ejaculate. No strong relationship (explaining more than 50% of the total variance) was found between annual fluctuations in SP-cytokine levels and semen parameters. In conclusion, the period of the year during which ejaculates were collected helps explain the intra-male variability of SP-cytokine levels in breeding boars.
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| 5. |
- Roca, Jordi, et al.
(författare)
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Proteomics in fresh and preserved pig semen: Recent achievements and future challenges
- 2020
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Ingår i: Theriogenology. - : ELSEVIER SCIENCE INC. - 0093-691X .- 1879-3231. ; 150, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Proteins in semen, either in spermatozoa (SPZ) or seminal plasma (SP), are directly involved in molecular processes and biological pathways regulating sperm function, including fertilizing ability. Therefore, semen proteins are candidates of choice for biomarkers discovery for fertility and for sperm (dys)function. Mass spectrometry (MS)-based proteomics has opened up a new era for characterizing and quantifying the protein profile of SP and SPZ, as well as for unveiling the complex protein interactions involved in the activation of sperm functionality. This article overviews existing literature on MS-based proteomics regarding porcine semen, with a specific focus on the potential practical application of the results achieved so far. The weaknesses of current studies and the perspectives for future research in MS-based pig semen proteomics are also addressed. (C) 2020 Elsevier Inc. All rights reserved.
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| 6. |
- Wilkes, Mark C., et al.
(författare)
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Metformin-induced suppression of Nemo-like kinase improves erythropoiesis in preclinical models of Diamond–Blackfan anemia through induction of miR-26a
- 2020
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Ingår i: Experimental Hematology. - : Elsevier BV. - 0301-472X. ; 91, s. 65-77
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Tidskriftsartikel (refereegranskat)abstract
- Diamond–Blackfan anemia (DBA) results from haploinsufficiency of ribosomal protein subunits in hematopoietic progenitors in the earliest stages of committed erythropoiesis. Nemo-like kinase (NLK) is chronically hyperactivated in committed erythroid progenitors and precursors in multiple human and murine models of DBA. Inhibition of NLK activity and suppression of NLK expression both improve erythroid expansion in these models. Metformin is a well-tolerated drug for type 2 diabetes with multiple cellular targets. Here we demonstrate that metformin improves erythropoiesis in human and zebrafish models of DBA. Our data indicate that the effects of metformin on erythroid proliferation and differentiation are mediated by suppression of NLK expression through induction of miR-26a, which recognizes a binding site within the NLK 3′ untranslated region (3′UTR) to facilitate transcript degradation. We propose that induction of miR-26a is a potentially novel approach to treatment of DBA and could improve anemia in DBA patients without the potentially adverse side effects of metformin in a DBA patient population.
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| 7. |
- Barranco, Isabel, et al.
(författare)
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Extracellular vesicles isolated from porcine seminal plasma exhibit different tetraspanin expression profiles
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Seminal extracellular vesicles (EVs) include exosomes (phi 40-120 nm) and microvesicles (MVs, phi 120-1000 nm), which would be involved in multiple functional reproductive roles. The study aimed to establish which EV subtypes are present in pig semen, using a high-resolution flow cytometer to explore differences in their tetraspanin expression profile. The EVs were isolated from 12 pig ejaculates using serial ultracentrifugation and characterized by dynamic light scattering and electron microscopy for size and morphology as well as for tetraspanin expression using flow cytometry with Carboxyfluorescein succinimidyl ester (CFSE) and antibodies against CD9, CD63 and CD81. Pig semen contained a heterogeneous EV-population regarding size and morphology. Flow cytometric analysis demonstrated that the proportion of EVs expressing CD63 and CD9 was higher in MVs (P amp;lt; 0.001 and P amp;lt; 0.05, respectively) than in exosomes, while the opposite was true for CD81; higher (P amp;lt; 0.001) in exosomes than in MVs. In conclusion, (1) the new generation of flow cytometers are able to accurately identify EVs and to gate them in two size-different populations named exosomes and MVs. (2) Tetraspanins CD9, CD63 and CD81 are present in both seminal EVs, albeit with exosomes and MVs differing in expression profiles, suggesting dissimilar cargo and binding affinity.
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| 8. |
- Barranco, Isabel, et al.
(författare)
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Seminal Plasma Cytokines Are Predictive of the Outcome of Boar Sperm Preservation
- 2019
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media S.A.. - 2297-1769. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Boar seminal plasma is rich in cytokines, which could influence the capability of spermatozoa to tolerate preservation.Objectives: To evaluate the involvement of boar seminal plasma cytokines in the changes experienced by boar spermatozoa during their storage, either in liquid or frozen state.Materials and Methods: In two separated experiments, semen samples from healthy and fertile boars were split in two aliquots, one centrifuged twice (1,500 ×g for 10 min) to harvest seminal plasma, whereas the other was either commercially extended (3 × 107 sperm/mL) and liquid-stored at 17°C during 144 h (n = 28, Experiment 1) or frozen-thawed using a standard 0.5 mL protocol (n = 27, Experiment 2). Sixteen cytokines were quantified using Luminex xMAP®. Sperm attributes (CASA-evaluated total and progressive motility; flow cytometry-evaluated sperm viability, production of intracellular H2O2 and O2•-" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">O∙−2O2•- and levels of lipid peroxidation in viable spermatozoa) were evaluated either at 0, 72, or 144 h of liquid storage (Experiment 1) or before freezing and at 30- and 150-min post-thawing (Experiment 2).Results: Multiple linear regression models, with Bayesian approach for variable selection, revealed that the anti-inflammatory TGF-β2, TGF-β3, IL-1Ra, and IL-4 and the pro-inflammatory IL-8 and IL-18, predicted changes in sperm motility for liquid-stored semen while the anti-inflammatory IFN-γ was included in the models predicting changes in all sperm attributes for cryopreserved semen.Conclusion: Specific boar seminal plasma cytokines would contribute to modulate the structural and metabolic changes shown by spermatozoa during preservation, either in liquid or frozen state.
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| 9. |
- Perez-Patino, Cristina, et al.
(författare)
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Cryopreservation Differentially Alters the Proteome of Epididymal and Ejaculated Pig Spermatozoa
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 20:7
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Tidskriftsartikel (refereegranskat)abstract
- Cryopreservation induces differential remodeling of the proteome in mammalian spermatozoa. How these proteome changes relate to the loss of sperm function during cryopreservation remains unsolved. The present study aimed to clarify this issue evaluating differential changes in the proteome of fresh and frozen-thawed pig spermatozoa retrieved from the cauda epididymis and the ejaculate of the same boars, with clear differences in cryotolerance. Spermatozoa were collected from 10 healthy, sexually mature, and fertile boars, and cryopreserved using a standard 0.5 mL-straw protocol. Total and progressive motility, viability, and mitochondria membrane potential were higher and membrane fluidity and reactive oxygen species generation lower in frozen-thawed (FT) epididymal than ejaculated spermatozoa. Quantitative proteomics of fresh and FT spermatozoa were analyzed using a LC-ESI-MS/MS-based Sequential Window Acquisition of All Theoretical Spectra approach. Cryopreservation quantitatively altered more proteins in ejaculated than cauda epididymal spermatozoa. Differential protein-protein networks highlighted a set of proteins quantitatively altered in ejaculated spermatozoa, directly involved in mitochondrial functionality which would explain why ejaculated spermatozoa deteriorate during cryopreservation.
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| 10. |
- Perez-Patino, Cristina, et al.
(författare)
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The proteome of frozen-thawed pig spermatozoa is dependent on the ejaculate fraction source
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The preservation of sperm functional parameters and fertility post-cryopreservation largely varies in the porcine, a species with a fractionated ejaculate. Although intrinsic individual differences have primarily been linked to this variation, differences in protein abundance among frozen-thawed (FT)-spermatozoa are far more relevant. This study, performed in two experiments, looked for proteomic quantitative differences between FT-sperm samples differing in post-thaw viability, motility, apoptosis, membrane lipid peroxidation and nuclear DNA fragmentation. The spermatozoa were either derived from the sperm-rich ejaculate fraction (SRF) or the entire ejaculate (Experiment 1) or from the first 10 mL of the SRF, the remaining SRF and the post-SRF (Experiment 2). Quantitative sperm proteomic differences were analysed using a LC-ESI-MS/MS-based SWATH approach. In Experiment 1, FT-spermatozoa from the SRF showed better preservation parameters than those from the entire ejaculate, with 26 Sus scrofa proteins with functional sperm relevance showing relative quantitative differences (FC amp;gt;= 1.5) between sperm sources. In Experiment 2, FT-spermatozoa from the first 10 mL of the SRF and the remaining SRF were qualitatively better than those from the post-SRF, and 187 proteins showed relative quantitative differences among the three ejaculate sources. The results indicate that quantitative proteome differences are linked to sperm cryosurvival.
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