39 results on '"Van Gilst M"'
Search Results
2. Direct application of an ECG-based sleep staging algorithm on reflective photoplethysmography data decreases performance
- Author
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van Gilst, M. M., Wulterkens, B. M., Fonseca, P., Radha, M., Ross, M., Moreau, A., Cerny, A., Anderer, P., Long, X., van Dijk, J. P., and Overeem, S.
- Published
- 2020
- Full Text
- View/download PDF
3. The Burden of Narcolepsy in Adults: A Population Sampling Study Using Personal Media
- Author
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Quaedackers, L. (author), Van Gilst, M. M. (author), Van Den Brandt, I. (author), Vilanova Bartroli, A. (author), Lammers, G. J. (author), Markopoulos, P. (author), Overeem, S. (author), Quaedackers, L. (author), Van Gilst, M. M. (author), Van Den Brandt, I. (author), Vilanova Bartroli, A. (author), Lammers, G. J. (author), Markopoulos, P. (author), and Overeem, S. (author)
- Abstract
Objective: To obtain insight in the spectrum of narcolepsy symptoms and associated burden in a large cohort of patients. Methods: We used the Narcolepsy Monitor, a mobile app, to easily rate the presence and burden of 20 narcolepsy symptoms. Baseline measures were obtained and analyzed from 746 users aged between 18 and 75 years with a reported diagnosis of narcolepsy. Results: Median age was 33.0 years (IQR 25.0–43.0), median Ullanlinna Narcolepsy Scale 19 (IQR 14.0–26.0), 78% reported using narcolepsy pharmacotherapy. Excessive daytime sleepiness (97.2%) and lack of energy were most often present (95.0%) and most often caused a high burden (79.7% and 76.1% respectively). Cognitive symptoms (concentration 93.0%, memory 91.4%) and psychiatric symptoms (mood 76.8%, anxiety/panic 76.4%) were relatively often reported to be present and burdensome. Conversely, sleep paralysis and cataplexy were least often reported as highly bothersome. Females experienced a higher burden for anxiety/panic, memory, and lack of energy. Conclusions: This study supports the notion of an elaborate narcolepsy symptom spectrum. Each symptom’s contribution to the experienced burden varied, but lesser-known symptoms did significantly add to this as well. This emphasizes the need to not only focus treatment on the classical core symptoms of narcolepsy., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Computer Graphics and Visualisation
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- 2023
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4. The impact of healthy pregnancy on features of heart rate variability and pulse wave morphology derived from wrist-worn photoplethysmography
- Author
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Bester, M, Almario Escorcia, M J, Fonseca, P, Mollura, M, van Gilst, M M, Barbieri, R, Mischi, M, van Laar, J O E H, Vullings, R, Joshi, R, Bester, M, Almario Escorcia, M J, Fonseca, P, Mollura, M, van Gilst, M M, Barbieri, R, Mischi, M, van Laar, J O E H, Vullings, R, and Joshi, R
- Abstract
Due to the association between dysfunctional maternal autonomic regulation and pregnancy complications, tracking non-invasive features of autonomic regulation derived from wrist-worn photoplethysmography (PPG) measurements may allow for the early detection of deteriorations in maternal health. However, even though a plethora of these features-specifically, features describing heart rate variability (HRV) and the morphology of the PPG waveform (morphological features)-exist in the literature, it is unclear which of these may be valuable for tracking maternal health. As an initial step towards clarity, we compute comprehensive sets of HRV and morphological features from nighttime PPG measurements. From these, using logistic regression and stepwise forward feature elimination, we identify the features that best differentiate healthy pregnant women from non-pregnant women, since these likely capture physiological adaptations necessary for sustaining healthy pregnancy. Overall, morphological features were more valuable for discriminating between pregnant and non-pregnant women than HRV features (area under the receiver operating characteristics curve of 0.825 and 0.74, respectively), with the systolic pulse wave deterioration being the most valuable single feature, followed by mean heart rate (HR). Additionally, we stratified the analysis by sleep stages and found that using features calculated only from periods of deep sleep enhanced the differences between the two groups. In conclusion, we postulate that in addition to HRV features, morphological features may also be useful in tracking maternal health and suggest specific features to be included in future research concerning maternal health.
- Published
- 2023
5. Exploring the Parkinson patients’ perspective on home-based video recording for movement analysis: a qualitative study
- Author
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de Vries, N. M., Smilowska, K., Hummelink, J., Abramiuc, B., van Gilst, M. M., Bloem, B. R., de With, P. H. N., and Overeem, S.
- Published
- 2019
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6. Automated sleep staging in people with intellectual disabilities using heart rate and respiration variability.
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van den Broek, N., van Meulen, F., Ross, M., Cerny, A., Anderer, P., van Gilst, M., Pillen, S., Overeem, S., and Fonseca, P.
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STATISTICS ,SLEEP stages ,EPILEPSY ,RESPIRATORY measurements ,POLYSOMNOGRAPHY ,AUTOMATION ,HEART beat ,ELECTROCARDIOGRAPHY ,DESCRIPTIVE statistics ,RESEARCH funding ,DEMOGRAPHY ,ALGORITHMS ,COMORBIDITY - Abstract
Background: People with intellectual disabilities (ID) have a higher risk of sleep disorders. Polysomnography (PSG) remains the diagnostic gold standard in sleep medicine. However, PSG in people with ID can be challenging, as sensors can be burdensome and have a negative influence on sleep. Alternative methods of assessing sleep have been proposed that could potentially transfer to less obtrusive monitoring devices. The goal of this study was to investigate whether analysis of heart rate variability and respiration variability is suitable for the automatic scoring of sleep stages in sleep‐disordered people with ID. Methods: Manually scored sleep stages in PSGs of 73 people with ID (borderline to profound) were compared with the scoring of sleep stages by the CardioRespiratory Sleep Staging (CReSS) algorithm. CReSS uses cardiac and/or respiratory input to score the different sleep stages. Performance of the algorithm was analysed using input from electrocardiogram (ECG), respiratory effort and a combination of both. Agreement was determined by means of epoch‐per‐epoch Cohen's kappa coefficient. The influence of demographics, comorbidities and potential manual scoring difficulties (based on comments in the PSG report) was explored. Results: The use of CReSS with combination of both ECG and respiratory effort provided the best agreement in scoring sleep and wake when compared with manually scored PSG (PSG versus ECG = kappa 0.56, PSG versus respiratory effort = kappa 0.53 and PSG versus both = kappa 0.62). Presence of epilepsy or difficulties in manually scoring sleep stages negatively influenced agreement significantly, but nevertheless, performance remained acceptable. In people with ID without epilepsy, the average kappa approximated that of the general population with sleep disorders. Conclusions: Using analysis of heart rate and respiration variability, sleep stages can be estimated in people with ID. This could in the future lead to less obtrusive measurements of sleep using, for example, wearables, more suitable to this population. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. Sleep benefit in Parkinsonʼs disease: 220
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van Gilst, M.
- Published
- 2014
8. Within-subject variations of sleep (mis) perception in a placebo-controlled medication study
- Author
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Hermans, L., Regis, M., Fonseca, P., Overeem, S., Leufkens, T., Vermeeren, A., van Gilst, M., Section Psychopharmacology, and RS: FPN NPPP II
- Published
- 2020
9. Modelling sleep state misperception at sleep onset
- Author
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Hermans, L., Leufkens, T., van Gilst, M., Weysen, T., Ross, M., Anderer, P., Overeem, S., Vermeeren, A., Section Psychopharmacology, RS: FPN NPPP II, Signal Processing Systems, Biomedical Diagnostics Lab, and Future Everyday
- Published
- 2018
10. Social responsiveness in pediatric narcolepsy patients
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Quaedackers, L., van Gilst, M., van Mierlo, P., Lammers, G. J., Dhondt, K., Peeters, E., Hendriks, D., Vandenbussche, N., Pillen, S., Overeem, S., Future Everyday, Signal Processing Systems, and Biomedical Diagnostics Lab
- Published
- 2018
11. Validation of the Dutch translation of the Paris Arousal Disorder Severity Scale in a one-year and one-month version
- Author
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van Mierlo, P., van Gilst, M., Arnulf, I., Overeem, S., Pijpers, A., Signal Processing Systems, and Biomedical Diagnostics Lab
- Published
- 2018
12. The influence of the length of awakenings on sleep onset misperception
- Author
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Hermans, L., primary, van Gilst, M., additional, Langen, H., additional, van Mierlo, P., additional, Leufkens, T., additional, and Overeem, S., additional
- Published
- 2019
- Full Text
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13. Modelling sleep onset misperception in insomnia
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Hermans, L., primary, van Gilst, M., additional, Langen, H., additional, van Mierlo, P., additional, Leufkens, T., additional, and Overeem, S., additional
- Published
- 2019
- Full Text
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14. Stimulation and recording of dynamic pupillary reflex: the IRIS technique Part 2
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Reulen, J. P. H., Marcus, J. T., van Gilst, M. J., Koops, D., Bos, J. E., Tiesinga, G., de Vries, F. R., and Boshuizen, K.
- Published
- 1988
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15. Sleep-Wake Survival Dynamics in People with Insomnia
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Hermans LWA, Regis M, Fonseca P, Hoondert B, Leufkens TRM, Overeem S, and van Gilst MM
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insomnia ,survival analysis ,sleep fragmentation ,Psychiatry ,RC435-571 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Lieke WA Hermans,1 Marta Regis,2 Pedro Fonseca,1,3 Bertram Hoondert,4 Tim RM Leufkens,3 Sebastiaan Overeem,1,4 Merel M van Gilst1,4 1Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; 2Department of Mathematics and Computer Science, Eindhoven University of Technology, Eindhoven, the Netherlands; 3Philips Research, Eindhoven, the Netherlands; 4Sleep Medicine Center Kempenhaeghe, Heeze, the NetherlandsCorrespondence: Lieke WA HermansDepartment of Electrical Engineering, Eindhoven University of Technology, De Zaale, 5600, MB Eindhoven, the NetherlandsEmail l.w.a.hermans@tue.nlIntroduction: Assessing objective measures of sleep fragmentation could yield important features reflecting impaired sleep quality in people with insomnia. Survival analysis allows the specific examination of the stability of NREM sleep, REM sleep and wake. The objective of this study was to assess the differences between survival dynamics of NREM sleep, REM sleep and wake between people with insomnia and healthy controls.Methods: We analyzed retrospective polysomnography recordings from 86 people with insomnia and 94 healthy controls. For each participant, survival dynamics of REM sleep, NREM sleep and wake were represented using Weibull distributions. We used lasso penalized parameter selection in combination with linear regression to analyze the difference between participant groups with respect to the Weibull scale and shape parameters, while correcting for age, sex, total sleep time and relevant interaction effects.Results: Significant effects of group were found for the NREM scale parameter, and for the wake scale and shape parameters. Results indicated that people with insomnia had less stable NREM sleep and more stable wake after sleep onset compared to healthy controls. Additionally, the altered distribution of wake segment lengths indicated an increased difficulty to fall asleep after longer awakenings in the insomnia group. However, these differences were mainly observed in younger participants. Significant effects of group for the survival parameters of REM sleep were not found.Conclusion: As illustrated by our results, survival analysis can be very useful for disentangling different types of sleep fragmentation in people with insomnia. For instance, the current findings suggest that people with insomnia have an increased fragmentation of NREM sleep, but not necessarily of REM sleep. Additional research into the underlying mechanisms of NREM sleep fragmentation could possibly lead to a better understanding of impaired sleep quality in people with insomnia, and consequently to improved treatment.Keywords: insomnia, survival analysis, sleep fragmentation
- Published
- 2021
16. Model-Based Evaluation of Methods for Respiratory Sinus Arrhythmia Estimation
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John Morales, Carolina Varon, Pablo Armanac, Merel M. van Gilst, Sebastiaan Overeem, Michele Orini, Raquel Bailon, Johannes Van Dijk, Jonathan Moeyersons, Luca Faes, Sabine Van Huffel, MoralesTellez J.F., Moeyersons J., Armanac P., Orini M., Faes L., Overeem S., Van Gilst M., Van Dijk J., Huffel S.V., Bailon R., Varon C., Signal Processing Systems, Eindhoven MedTech Innovation Center, and Biomedical Diagnostics Lab
- Subjects
Scale (ratio) ,Computer science ,Biomedical Engineering ,Electrocardiography ,Heart Rate ,Heart rate ,Coherence (signal processing) ,Heart rate variability ,Humans ,Arrhythmia, Sinus ,respiratory sinus arrhythmia ,Vagal tone ,Respiratory system ,Estimation ,Cardiorespiratory coupling ,Modulation ,business.industry ,Respiration ,heart rate variability ,Pattern recognition ,Computational modeling ,Cardiorespiratory coupling, Computational modeling, Couplings, Electrocardiography, Heart rate variability, Modulation, Respiratory Sinus Arrhythmia ,Settore ING-INF/06 - Bioingegneria Elettronica E Informatica ,Couplings ,Artificial intelligence ,business - Abstract
OBJECTIVE: Respiratory sinus arrhythmia (RSA) refers to heart rate oscillations synchronous with respiration, and it is one of the major representations of cardiorespiratory coupling. Its strength has been suggested as a biomarker to monitor different conditions, and diseases. Some approaches have been proposed to quantify the RSA, but it is unclear which one performs best in specific scenarios. The main objective of this study is to compare seven state-of-the-art methods for RSA quantification using data generated with a model proposed to simulate, and control the RSA. These methods are also compared, and evaluated on a real-life application, for their ability to capture changes in cardiorespiratory coupling during sleep. METHODS: A simulation model is used to create a dataset of heart rate variability, and respiratory signals with controlled RSA, which is used to compare the RSA estimation approaches. To compare the methods objectively in real-life applications, regression models trained on the simulated data are used to map the estimates to the same measurement scale. Results, and conclusion: RSA estimates based on cross entropy, time-frequency coherence, and subspace projections showed the best performance on simulated data. In addition, these estimates captured the expected trends in the changes in cardiorespiratory coupling during sleep similarly. SIGNIFICANCE: An objective comparison of methods for RSA quantification is presented to guide future analyses. Also, the proposed simulation model can be used to compare existing, and newly proposed RSA estimates. It is freely accessible online. ispartof: Ieee Transactions On Biomedical Engineering vol:68 issue:6 ispartof: location:United States status: accepted
- Published
- 2021
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17. Estimating the Severity of Obstructive Sleep Apnea Using ECG, Respiratory Effort and Neural Networks.
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Fonseca P, Ross M, Cerny A, Anderer P, Schipper F, Grassi A, van Gilst M, and Overeem S
- Subjects
- Humans, Male, Middle Aged, Female, Adult, Aged, Algorithms, Severity of Illness Index, Sleep Stages physiology, Young Adult, Sleep Apnea, Obstructive physiopathology, Sleep Apnea, Obstructive diagnosis, Neural Networks, Computer, Electrocardiography methods, Signal Processing, Computer-Assisted, Polysomnography methods
- Abstract
Objective: wearable sensor technology has progressed significantly in the last decade, but its clinical usability for the assessment of obstructive sleep apnea (OSA) is limited by the lack of large and representative datasets simultaneously acquired with polysomnography (PSG). The objective of this study was to explore the use of cardiorespiratory signals common in standard PSGs which can be easily measured with wearable sensors, to estimate the severity of OSA., Methods: an artificial neural network was developed for detecting sleep disordered breathing events using electrocardiogram (ECG) and respiratory effort. The network was combined with a previously developed cardiorespiratory sleep staging algorithm and evaluated in terms of sleep staging classification performance, apnea-hypopnea index (AHI) estimation, and OSA severity estimation against PSG on a cohort of 653 participants with a wide range of OSA severity., Results: four-class sleep staging achieved a κ of 0.69 versus PSG, distinguishing wake, combined N1-N2, N3 and REM. AHI estimation achieved an intraclass correlation coefficient of 0.91, and high diagnostic performance for different OSA severity thresholds., Conclusions: this study highlights the potential of using cardiorespiratory signals to estimate OSA severity, even without the need for airflow or oxygen saturation (SpO2), traditionally used for assessing OSA., Significance: while further research is required to translate these findings to practical and unobtrusive sensors, this study demonstrates how existing, large datasets can serve as a foundation for wearable systems for OSA monitoring. Ultimately, this approach could enable long-term assessment of sleep disordered breathing, facilitating new avenues for clinical research in this field.
- Published
- 2024
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18. Performance of cardiorespiratory-based sleep staging in patients using beta blockers.
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Hermans L, van Meulen F, Anderer P, Ross M, Cerny A, van Gilst M, Overeem S, and Fonseca P
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- Humans, Retrospective Studies, Polysomnography methods, Sleep Stages physiology, Sleep physiology, Sleep Wake Disorders
- Abstract
Study Objectives: Automatic sleep staging based on cardiorespiratory signals from home sleep monitoring devices holds great clinical potential. Using state-of-the-art machine learning, promising performance has been reached in patients with sleep disorders. However, it is unknown whether performance would hold in individuals with potentially altered autonomic physiology, for example under the influence of medication. Here, we assess an existing sleep staging algorithm in patients with sleep disorders with and without the use of beta blockers., Methods: We analyzed a retrospective dataset of sleep recordings of 57 patients with sleep disorders using beta blockers and 57 age-matched patients with sleep disorders not using beta blockers. Sleep stages were automatically scored based on electrocardiography and respiratory effort from a thoracic belt, using a previously developed machine-learning algorithm (CReSS algorithm). For both patient groups, sleep stages classified by the model were compared to gold standard manual polysomnography scoring using epoch-by-epoch agreement. Additionally, for both groups, overall sleep parameters were calculated and compared between the two scoring methods., Results: Substantial agreement was achieved for four-class sleep staging in both patient groups (beta blockers: kappa = 0.635, accuracy = 78.1%; controls: kappa = 0.660, accuracy = 78.8%). No statistical difference in epoch-by-epoch agreement was found between the two groups. Additionally, the groups did not differ on agreement of derived sleep parameters., Conclusions: We showed that the performance of the CReSS algorithm is not deteriorated in patients using beta blockers. Results do not indicate a fundamental limitation in leveraging autonomic characteristics to obtain a surrogate measure of sleep in this clinically relevant population., Citation: Hermans L, van Meulen F, Anderer P, et al. Performance of cardiorespiratory-based sleep staging in patients using beta blockers. J Clin Sleep Med . 2024;20(4):575-581., (© 2024 American Academy of Sleep Medicine.)
- Published
- 2024
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19. The Burden of Narcolepsy in Adults: A Population Sampling Study Using Personal Media.
- Author
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Quaedackers L, Van Gilst MM, Van Den Brandt I, Vilanova A, Lammers GJ, Markopoulos P, and Overeem S
- Subjects
- Adult, Female, Humans, Adolescent, Young Adult, Middle Aged, Aged, Sampling Studies, Anxiety, Narcolepsy diagnosis, Cataplexy diagnosis, Cataplexy epidemiology, Disorders of Excessive Somnolence
- Abstract
Objective: To obtain insight in the spectrum of narcolepsy symptoms and associated burden in a large cohort of patients., Methods: We used the Narcolepsy Monitor, a mobile app, to easily rate the presence and burden of 20 narcolepsy symptoms. Baseline measures were obtained and analyzed from 746 users aged between 18 and 75 years with a reported diagnosis of narcolepsy., Results: Median age was 33.0 years (IQR 25.0-43.0), median Ullanlinna Narcolepsy Scale 19 (IQR 14.0-26.0), 78% reported using narcolepsy pharmacotherapy. Excessive daytime sleepiness (97.2%) and lack of energy were most often present (95.0%) and most often caused a high burden (79.7% and 76.1% respectively). Cognitive symptoms (concentration 93.0%, memory 91.4%) and psychiatric symptoms (mood 76.8%, anxiety/panic 76.4%) were relatively often reported to be present and burdensome. Conversely, sleep paralysis and cataplexy were least often reported as highly bothersome. Females experienced a higher burden for anxiety/panic, memory, and lack of energy., Conclusions: This study supports the notion of an elaborate narcolepsy symptom spectrum. Each symptom's contribution to the experienced burden varied, but lesser-known symptoms did significantly add to this as well. This emphasizes the need to not only focus treatment on the classical core symptoms of narcolepsy.
- Published
- 2024
- Full Text
- View/download PDF
20. Hypoxia-induced mitochondrial stress granules.
- Author
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Sun CL, Van Gilst M, and Crowder CM
- Subjects
- Animals, Rats, Ethidium metabolism, Sodium Azide, Stress Granules, Hypoxia metabolism, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism, Caenorhabditis elegans metabolism, Protein Aggregates
- Abstract
Perturbations of mitochondrial proteostasis have been associated with aging, neurodegenerative diseases, and recently with hypoxic injury. While examining hypoxia-induced mitochondrial protein aggregation in C. elegans, we found that sublethal hypoxia, sodium azide, or heat shock-induced abundant ethidium bromide staining mitochondrial granules that preceded evidence of protein aggregation. Genetic manipulations that reduce cellular and organismal hypoxic death block the formation of these mitochondrial stress granules (mitoSG). Knockdown of mitochondrial nucleoid proteins also blocked the formation of mitoSG by a mechanism distinct from the mitochondrial unfolded protein response. Lack of the major mitochondrial matrix protease LONP-1 resulted in the constitutive formation of mitoSG without external stress. Ethidium bromide-staining RNA-containing mitochondrial granules were also observed in rat cardiomyocytes treated with sodium azide, a hypoxia mimetic. Mitochondrial stress granules are an early mitochondrial pathology controlled by LONP and the nucleoid, preceding hypoxia-induced protein aggregation., (© 2023. The Author(s).)
- Published
- 2023
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21. A computationally efficient algorithm for wearable sleep staging in clinical populations.
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Fonseca P, Ross M, Cerny A, Anderer P, van Meulen F, Janssen H, Pijpers A, Dujardin S, van Hirtum P, van Gilst M, and Overeem S
- Subjects
- Humans, Sleep physiology, Polysomnography, Algorithms, Sleep Stages physiology, Wearable Electronic Devices
- Abstract
This study describes a computationally efficient algorithm for 4-class sleep staging based on cardiac activity and body movements. Using an accelerometer to calculate gross body movements and a reflective photoplethysmographic (PPG) sensor to determine interbeat intervals and a corresponding instantaneous heart rate signal, a neural network was trained to classify between wake, combined N1 and N2, N3 and REM sleep in epochs of 30 s. The classifier was validated on a hold-out set by comparing the output against manually scored sleep stages based on polysomnography (PSG). In addition, the execution time was compared with that of a previously developed heart rate variability (HRV) feature-based sleep staging algorithm. With a median epoch-per-epoch κ of 0.638 and accuracy of 77.8% the algorithm achieved an equivalent performance when compared to the previously developed HRV-based approach, but with a 50-times faster execution time. This shows how a neural network, without leveraging any a priori knowledge of the domain, can automatically "discover" a suitable mapping between cardiac activity and body movements, and sleep stages, even in patients with different sleep pathologies. In addition to the high performance, the reduced complexity of the algorithm makes practical implementation feasible, opening up new avenues in sleep diagnostics., (© 2023. The Author(s).)
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- 2023
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22. Coordinate Regulation of Ribosome and tRNA Biogenesis Controls Hypoxic Injury and Translation.
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Itani OA, Zhong X, Tang X, Scott BA, Yan JY, Flibotte S, Lim Y, Hsieh AC, Bruce JE, Van Gilst M, and Crowder CM
- Published
- 2022
- Full Text
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23. Dissociative Symptoms are Highly Prevalent in Adults with Narcolepsy Type 1.
- Author
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Quaedackers L, Droogleever Fortuyn H, Van Gilst M, Lappenschaar M, and Overeem S
- Subjects
- Adult, Case-Control Studies, Dissociative Disorders complications, Dissociative Disorders epidemiology, Humans, Retrospective Studies, Cataplexy diagnosis, Cataplexy drug therapy, Narcolepsy complications, Narcolepsy diagnosis, Narcolepsy epidemiology
- Abstract
Introduction: The core symptoms of narcolepsy such as excessive daytime sleepiness and cataplexy are well known. However, there is mounting evidence for a much broader symptom spectrum, including psychiatric symptoms. Disordered sleep has previously been linked with dissociative symptoms, which may imply that patients with narcolepsy are more prone to develop such symptoms., Objectives: To investigate the frequency of dissociative symptoms in adult patients with narcolepsy type 1 compared to population controls., Methods: In a retrospective case control study, sixty adult patients fulfilling the criteria for narcolepsy type 1 and 120 matched population control subjects received a structured interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to assess dissociative symptoms and disorders., Results: A majority of narcolepsy patients reported dissociative symptoms, and even fulfilled the DSM-IV-TR criteria of a dissociative disorder (62% vs 1% in controls, p < .001). Most frequently reported symptoms were "dissociative amnesia" (37% vs 1%, p < .001) and "dissociative disorder of voluntary movement" (32% vs 1%, p < .001)., Conclusion: Dissociative symptoms are strikingly prevalent in adult patients with narcolepsy type 1. Although a formal diagnosis of dissociation disorder should not be made as the symptoms can be explained by narcolepsy as an underlying condition, the findings do illustrate the extent and severity of the dissociative symptoms. As for the pathophysiological mechanism, there may be symptom overlap between narcolepsy and dissociation disorder. However, there may also be a more direct link between disrupted sleep and dissociative symptoms. In either case, the high frequency of occurrence of dissociative symptoms should result in an active inquiry by doctors, to improve therapeutic management and guidance.
- Published
- 2022
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24. Effect of the mitochondrial unfolded protein response on hypoxic death and mitochondrial protein aggregation.
- Author
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Yan J, Sun CL, Shin S, Van Gilst M, and Crowder CM
- Subjects
- Animals, Animals, Genetically Modified, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Cell Hypoxia, Mitochondria genetics, Mitochondria pathology, Mitochondrial Proteins genetics, Protein Aggregates, Protein Aggregation, Pathological, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins metabolism, Mitochondria metabolism, Mitochondrial Proteins metabolism, Unfolded Protein Response
- Abstract
Mitochondria are the main oxygen consumers in cells and as such are the primary organelle affected by hypoxia. All hypoxia pathology presumably derives from the initial mitochondrial dysfunction. An early event in hypoxic pathology in C. elegans is disruption of mitochondrial proteostasis with induction of the mitochondrial unfolded protein response (UPR
mt ) and mitochondrial protein aggregation. Here in C. elegans, we screen through RNAis and mutants that confer either strong resistance to hypoxic cell death or strong induction of the UPRmt to determine the relationship between hypoxic cell death, UPRmt activation, and hypoxia-induced mitochondrial protein aggregation (HIMPA). We find that resistance to hypoxic cell death invariantly mitigated HIMPA. We also find that UPRmt activation invariantly mitigated HIMPA. However, UPRmt activation was neither necessary nor sufficient for resistance to hypoxic death and vice versa. We conclude that UPRmt is not necessarily hypoxia protective against cell death but does protect from mitochondrial protein aggregation, one of the early hypoxic pathologies in C. elegans., (© 2021. The Author(s).)- Published
- 2021
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25. Model-Based Evaluation of Methods for Respiratory Sinus Arrhythmia Estimation.
- Author
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Morales J, Moeyersons J, Armanac P, Orini M, Faes L, Overeem S, Van Gilst M, Van Dijk J, Van Huffel S, Bailon R, and Varon C
- Subjects
- Arrhythmia, Sinus diagnosis, Electrocardiography, Heart Rate, Humans, Respiration, Respiratory Sinus Arrhythmia
- Abstract
Objective: Respiratory sinus arrhythmia (RSA) refers to heart rate oscillations synchronous with respiration, and it is one of the major representations of cardiorespiratory coupling. Its strength has been suggested as a biomarker to monitor different conditions, and diseases. Some approaches have been proposed to quantify the RSA, but it is unclear which one performs best in specific scenarios. The main objective of this study is to compare seven state-of-the-art methods for RSA quantification using data generated with a model proposed to simulate, and control the RSA. These methods are also compared, and evaluated on a real-life application, for their ability to capture changes in cardiorespiratory coupling during sleep., Methods: A simulation model is used to create a dataset of heart rate variability, and respiratory signals with controlled RSA, which is used to compare the RSA estimation approaches. To compare the methods objectively in real-life applications, regression models trained on the simulated data are used to map the estimates to the same measurement scale. Results, and conclusion: RSA estimates based on cross entropy, time-frequency coherence, and subspace projections showed the best performance on simulated data. In addition, these estimates captured the expected trends in the changes in cardiorespiratory coupling during sleep similarly., Significance: An objective comparison of methods for RSA quantification is presented to guide future analyses. Also, the proposed simulation model can be used to compare existing, and newly proposed RSA estimates. It is freely accessible online.
- Published
- 2021
- Full Text
- View/download PDF
26. Coordinate Regulation of Ribosome and tRNA Biogenesis Controls Hypoxic Injury and Translation.
- Author
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Itani OA, Zhong X, Tang X, Scott BA, Yan JY, Flibotte S, Lim Y, Hsieh AC, Bruce JE, Van Gilst M, and Crowder CM
- Subjects
- Animals, Animals, Genetically Modified, Caenorhabditis elegans genetics, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism, Feedback, Physiological, Homeostasis genetics, Mutation, RNA Helicases genetics, RNA Helicases metabolism, Cell Hypoxia genetics, Gene Expression Regulation, Protein Biosynthesis genetics, RNA, Transfer biosynthesis, Ribosomes metabolism
- Abstract
The translation machinery is composed of a myriad of proteins and RNAs whose levels must be coordinated to efficiently produce proteins without wasting energy or substrate. However, protein synthesis is clearly not always perfectly tuned to its environment, as disruption of translation machinery components can lengthen lifespan and stress survival. While much has been learned from bacteria and yeast about translational regulation, much less is known in metazoans. In a screen for mutations protecting C. elegans from hypoxic stress, we isolated multiple genes impacting protein synthesis: a ribosomal RNA helicase gene, tRNA biosynthesis genes, and a gene controlling amino acid availability. To define better the mechanisms by which these genes impact protein synthesis, we performed a second screen for suppressors of the conditional developmental arrest phenotype of the RNA helicase mutant and identified genes involved in ribosome biogenesis. Surprisingly, these suppressor mutations restored normal hypoxic sensitivity and protein synthesis to the tRNA biogenesis mutants, but not to the mutant reducing amino acid uptake. Proteomic analysis demonstrated that reduced tRNA biosynthetic activity produces a selective homeostatic reduction in ribosomal subunits, thereby offering a mechanism for the suppression results. Our study uncovers an unrecognized higher-order-translation regulatory mechanism in a metazoan whereby ribosome biogenesis genes communicate with genes controlling tRNA abundance matching the global rate of protein synthesis with available resources., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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27. Multilevel Interval Coded Scoring to Assess the Cardiovascular Status of Sleep Apnea Patients Using Oxygen Saturation Markers.
- Author
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Deviaene M, Borzee P, van Gilst M, van Dijk J, Overeem S, Buyse B, Testelmans D, Van Huffel S, and Varon C
- Subjects
- Humans, Oxygen, Polysomnography, Risk Assessment, Sleep Apnea Syndromes, Sleep Apnea, Obstructive diagnosis
- Abstract
Objective: Studies have shown an increased cardiovascular risk in obstructive sleep apnea (OSA) patients. In order to prioritize treatment of high risk patients, there is a need for improved cardiovascular OSA phenotyping. This study investigates the use of oxygen saturation (SpO
2 ) parameters for cardiovascular risk assessment of OSA patients. To this end, a novel multilevel interval coded scoring (mICS) algorithm is proposed., Methods: The study includes SpO2 recordings from 1987 overnight polysomnographies, of which 974 are from patients suspected to have OSA, 931 from the general population based Sleep Heart Health Study and 83 from healthy controls. The minimal SpO2 value, SpO2 upslope and amplitude ratio of desaturation over resaturation are extracted for all oxygen desaturations and averaged per patient. These three SpO2 parameters are used together with patient demographics to develop a mICS model to predict the probability that a patient had a cardiovascular condition, or had already experienced a cardiovascular event, at the time of the polysomnography., Results: Including the SpO2 parameters in the mICS together with age and BMI improves the model's performance by 2.7% and leads to a test area under the curve (AUC) of 69.5% for the detection of any cardiovascular comorbidity. Moreover, an increase in AUC of 5% was obtained for the detection of cardiovascular events, resulting in an AUC of 93.5%., Conclusions: This study shows that parameters based on SpO2 and the mICS model are useful to predict the cardiovascular comorbidity status of OSA patients., Significance: The proposed model could be used to assist in prioritizing OSA patients for treatment.- Published
- 2020
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28. A time to grow and a time to pause.
- Author
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Van Gilst M
- Subjects
- Animals, Polycomb-Group Proteins, Vertebrates, Diapause
- Published
- 2020
- Full Text
- View/download PDF
29. A Mobile App for Longterm Monitoring of Narcolepsy Symptoms: Design, Development, and Evaluation.
- Author
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Quaedackers L, De Wit J, Pillen S, Van Gilst M, Batalas N, Lammers GJ, Markopoulos P, and Overeem S
- Subjects
- Humans, Sleep, Surveys and Questionnaires, Cataplexy diagnosis, Mobile Applications, Narcolepsy diagnosis
- Abstract
Background: Narcolepsy is a chronic sleep disorder with a broad variety of symptoms. Although narcolepsy is primarily characterized by excessive daytime sleepiness and cataplexy (loss of muscle control triggered by emotions), patients may suffer from hypnagogic hallucinations, sleep paralysis, and fragmented night sleep. However, the spectrum of narcolepsy also includes symptoms not related to sleep, such as cognitive or psychiatric problems. Symptoms vary greatly among patients and day-to-day variance can be considerable. Available narcolepsy questionnaires do not cover the whole symptom spectrum and may not capture symptom variability. Therefore, there is a clinical need for tools to monitor narcolepsy symptoms over time to evaluate their burden and the effect of treatment., Objective: This study aimed to describe the design, development, implementation, and evaluation of the Narcolepsy Monitor, a companion app for long-term symptom monitoring in narcolepsy patients., Methods: After several iterations during which content, interaction design, data management, and security were critically evaluated, a complete version of the app was built. The Narcolepsy Monitor allows patients to report a broad spectrum of experienced symptoms and rate their severity based on the level of burden that each symptom imposes. The app emphasizes the reporting of changes in relative severity of the symptoms. A total of 7 patients with narcolepsy were recruited and asked to use the app for 30 days. Evaluation was done by using in-depth interviews and user experience questionnaire., Results: We designed and developed a final version of the Narcolepsy Monitor after which user evaluation took place. Patients used the app on an average of 45.3 (SD 19.2) days. The app was opened on 35% of those days. Daytime sleepiness was the most dynamic symptom, with a mean number of changes of 5.5 (SD 3.7) per month, in contrast to feelings of anxiety or panic, which was only moved 0.3 (SD 0.7) times per month. Mean symptom scores were highest for daytime sleepiness (1.8 [SD 1.0]), followed by lack of energy (1.6 [SD 1.4]) and often awake at night (1.5 [SD 1.0]). The personal in-depth interviews revealed 3 major themes: (1) reasons to use, (2) usability, and (3) features. Overall, patients appreciated the concept of ranking symptoms on subjective burden and found the app easy to use., Conclusions: The Narcolepsy Monitor appears to be a helpful tool to gain more insight into the individual burden of narcolepsy symptoms over time and may serve as a patient-reported outcome measure for this debilitating disorder., (©Laury Quaedackers, Jan De Wit, Sigrid Pillen, Merel Van Gilst, Nikolaos Batalas, Gert Jan Lammers, Panos Markopoulos, Sebastiaan Overeem. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 07.01.2020.)
- Published
- 2020
- Full Text
- View/download PDF
30. Reactivation of RNA metabolism underlies somatic restoration after adult reproductive diapause in C. elegans .
- Author
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Burnaevskiy N, Chen S, Mailig M, Reynolds A, Karanth S, Mendenhall A, Van Gilst M, and Kaeberlein M
- Subjects
- Animals, Caenorhabditis elegans genetics, Caenorhabditis elegans growth & development, DNA, Mitochondrial drug effects, DNA, Mitochondrial genetics, Deoxyuridine administration & dosage, Deoxyuridine analogs & derivatives, Germ Cells drug effects, Germ Cells growth & development, Longevity drug effects, RNA drug effects, Reproduction drug effects, Stem Cells drug effects, Diapause genetics, Longevity genetics, RNA genetics, Reproduction genetics
- Abstract
The mechanisms underlying biological aging are becoming recognized as therapeutic targets to delay the onset of multiple age-related morbidities. Even greater health benefits can potentially be achieved by halting or reversing age-associated changes. C. elegans restore their tissues and normal longevity upon exit from prolonged adult reproductive diapause, but the mechanisms underlying this phenomenon remain unknown. Here, we focused on the mechanisms controlling recovery from adult diapause. Here, we show that functional improvement of post-mitotic somatic tissues does not require germline signaling, germline stem cells, or replication of nuclear or mitochondrial DNA. Instead a large expansion of the somatic RNA pool is necessary for restoration of youthful function and longevity. Treating animals with the drug 5-fluoro-2'-deoxyuridine prevents this restoration by blocking reactivation of RNA metabolism. These observations define a critical early step during exit from adult reproductive diapause that is required for somatic rejuvenation of an adult metazoan animal., Competing Interests: NB, SC, MM, AR, SK, AM, MV No competing interests declared, MK Reviewing editor, eLife, (© 2018, Burnaevskiy et al.)
- Published
- 2018
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31. Recurrent Neural Network for Classification of Snoring and Non-Snoring Sound Events.
- Author
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Arsenali B, van Dijk J, Ouweltjes O, den Brinker B, Pevernagie D, Krijn R, van Gilst M, and Overeem S
- Subjects
- Humans, Neural Networks, Computer, Sleep Apnea, Obstructive, Sound, Sound Spectrography, Snoring
- Abstract
Obstructive sleep apnea (OSA) is a disorder that affects up to 38% of the western population. It is characterized by repetitive episodes of partial or complete collapse of the upper airway during sleep. These episodes are almost always accompanied by loud snoring. Questionnaires such as STOP-BANG exploit snoring to screen for OSA. However, they are not quantitative and thus do not exploit its full potential. A method for automatic detection of snoring in whole-night recordings is required to enable its quantitative evaluation. In this study, we propose such a method. The centerpiece of the proposed method is a recurrent neural network for modeling of sequential data with variable length. Mel-frequency cepstral coefficients, which were extracted from snoring and non-snoring sound events, were used as inputs to the proposed network. A total of 20 subjects referred to clinical sleep recording were also recorded by a microphone that was placed 70 cm from the top end of the bed. These recordings were used to assess the performance of the proposed method. When it comes to the detection of snoring events, our results show that the proposed method has an accuracy of 95%, sensitivity of 92%, and specificity of 98%. In conclusion, our results suggest that the proposed method may improve the process of snoring detection and with that the process of OSA screening. Follow-up clinical studies are required to confirm this potential.
- Published
- 2018
- Full Text
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32. Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network.
- Author
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Arda HE, Taubert S, MacNeil LT, Conine CC, Tsuda B, Van Gilst M, Sequerra R, Doucette-Stamm L, Yamamoto KR, and Walhout AJ
- Subjects
- Animals, Gene Expression Regulation, Models, Genetic, Promoter Regions, Genetic, RNA Interference, Two-Hybrid System Techniques, Yeasts, Caenorhabditis elegans genetics, Caenorhabditis elegans metabolism, Gene Regulatory Networks genetics, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Cytoplasmic and Nuclear metabolism
- Abstract
Gene regulatory networks (GRNs) provide insights into the mechanisms of differential gene expression at a systems level. GRNs that relate to metazoan development have been studied extensively. However, little is still known about the design principles, organization and functionality of GRNs that control physiological processes such as metabolism, homeostasis and responses to environmental cues. In this study, we report the first experimentally mapped metazoan GRN of Caenorhabditis elegans metabolic genes. This network is enriched for nuclear hormone receptors (NHRs). The NHR family has greatly expanded in nematodes: humans have 48 NHRs, but C. elegans has 284, most of which are uncharacterized. We find that the C. elegans metabolic GRN is highly modular and that two GRN modules predominantly consist of NHRs. Network modularity has been proposed to facilitate a rapid response to different cues. As NHRs are metabolic sensors that are poised to respond to ligands, this suggests that C. elegans GRNs evolved to enable rapid and adaptive responses to different cues by a concurrence of NHR family expansion and modular GRN wiring.
- Published
- 2010
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33. Diversity and function of orphan nuclear receptors in nematodes.
- Author
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Van Gilst M, Gissendanner CR, and Sluder AE
- Subjects
- Amino Acid Sequence, Animals, DNA metabolism, DNA-Binding Proteins chemistry, DNA-Binding Proteins classification, DNA-Binding Proteins metabolism, DNA-Binding Proteins physiology, Ligands, Molecular Sequence Data, Receptors, Cytoplasmic and Nuclear chemistry, Receptors, Cytoplasmic and Nuclear classification, Receptors, Cytoplasmic and Nuclear metabolism, Caenorhabditis elegans metabolism, Receptors, Cytoplasmic and Nuclear physiology
- Abstract
Nuclear receptors (NRs) have key regulatory functions in a wide range of biological processes and are one of the most abundant classes of transcriptional regulators in metazoans. NRs are particularly numerous in nematodes, in which the NR gene family has undergone extensive expansion and diversification, providing an evolutionary structure function experiment that is yielding new perspectives on the mechanisms of NR function and on nematode biology. The genome sequence of the free-living nematode Caenorhabditis elegans reveals 270 predicted NR genes, more than fivefold more than observed for any other species to date, though existing data suggest that NR genes are similarly abundant in other nematodes. Most of the currently available information regarding the functions of nematode NRs comes from ongoing studies with C. elegans, and we review here what has been learned thus far in three key areas: the relationships of C. elegans NRs to those in other species; the biochemical consequences of nematode NR sequence diversity.
- Published
- 2002
- Full Text
- View/download PDF
34. Quantitative dissection of transcriptional control system: N-dependent antitermination complex of phage lambda as regulatory paradigm.
- Author
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Van Gilst MR and von Hippel PH
- Subjects
- Bacteriophage lambda physiology, Escherichia coli virology, Gene Expression Regulation, Viral, Genetic Techniques, Kinetics, Models, Genetic, Terminator Regions, Genetic, Thermodynamics, Bacteriophage lambda genetics, Escherichia coli genetics, Transcription, Genetic
- Published
- 2000
- Full Text
- View/download PDF
35. Assembly of the N-dependent antitermination complex of phage lambda: NusA and RNA bind independently to different unfolded domains of the N protein.
- Author
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Van Gilst MR and von Hippel PH
- Subjects
- Binding Sites genetics, Circular Dichroism, DNA-Binding Proteins metabolism, Escherichia coli Proteins, Fluorescent Dyes metabolism, Gene Expression Regulation, Viral, Mutation genetics, Nucleic Acid Conformation, Peptide Fragments chemistry, Peptide Fragments genetics, Peptide Fragments metabolism, Protein Binding, Protein Conformation, RNA chemistry, RNA-Binding Proteins metabolism, Spectrometry, Fluorescence, Transcription, Genetic, Transcriptional Elongation Factors, Viral Regulatory and Accessory Proteins chemistry, Bacterial Proteins metabolism, Peptide Elongation Factors, Protein Folding, RNA metabolism, Transcription Factors metabolism, Viral Regulatory and Accessory Proteins metabolism
- Abstract
The N protein of bacteriophage lambda activates expression of the delayed early genes of this phage by modifying RNA polymerase (RNAP) into a form that is resistant to termination signals. N binds to the boxB hairpin that forms in the nascent RNA transcript upon transcription of the nut regulatory element, and then interacts with RNAP by RNA looping. The binding of the N-boxB subassembly to the transcription complex is further stabilized by interaction with the Escherichia coli NusA protein. N, free in solution, exists as an unfolded protein that becomes partially structured upon binding specifically to boxB RNA. Because NusA does not assist in antitermination unless N is specifically bound to boxB, we have asked whether the structural change induced by binding to boxB affects the interaction of N with NusA. Using fluorescence spectroscopy, we have measured the affinity of N for NusA in the presence and absence of boxB RNA. We find that NusA binds to the unfolded N protein with a dissociation constant (Kd) of approximately 70 nM, and although N undergoes a significant structural change upon binding to boxB, the binding affinity of NusA for a N protein complexed with boxB is not altered. We have also shown that the boxA element of nut does not affect NusA binding to N-boxB. These results demonstrate that the interaction of N with NusA is independent of RNA binding, arguing that NusA must interact with an unfolded region of the polypeptide that remains unstructured even when N binds to boxB RNA. To further establish this point we isolated a truncated peptide containing the amino-terminal 36 residues of the N protein. Binding of boxB RNA to this peptide showed that all of the structural change in N that occurs upon binding to boxB RNA is localized within the amino-terminal 36 residues of N, therefore the C terminus of N, including the regions necessary for NusA binding and RNAP activation, remains unfolded when the full length N binds to boxB RNA. Thus it appears that N can be described as an unfolded multi-domain protein that becomes ordered in a modular fashion as it encounters its various binding partners within the N-dependent antitermination complex., (Copyright 1997 Academic Press Limited.)
- Published
- 1997
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- View/download PDF
36. Complexes of N antitermination protein of phage lambda with specific and nonspecific RNA target sites on the nascent transcript.
- Author
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Van Gilst MR, Rees WA, Das A, and von Hippel PH
- Subjects
- Amino Acid Sequence, Binding Sites, Models, Molecular, Molecular Sequence Data, Spectrometry, Fluorescence, Viral Regulatory and Accessory Proteins metabolism, RNA metabolism, Viral Regulatory and Accessory Proteins chemistry
- Abstract
The mechanisms that control N protein dependent antitermination in phage lambda have counterparts in many eukaryotic systems, including specific regulatory interactions of the antitermination protein with the nascent RNA transcript. Here we describe the specific and nonspecific RNA binding modes of antitermination protein N. These modes differ markedly in RNA binding affinity and in structure. N protein, either free in solution or as a complex with nonspecific RNA, lacks observable secondary and tertiary structure and binds RNA sequences indiscriminately with a dissociation constant (Kd) of approximately 10(-6) M. In contrast N becomes partially folded with at least 16-18 amino acids of ordered alpha-helical structure and binds much more tightly (Kd approximately 10(-9) M) on forming a highly specific 1:1 complex with its cognate boxB RNA hairpin. These observations and others are used to help define a bipartite model of N-dependent antitermination in which these specific and nonspecific interactions control the binding of N to the nascent transcript. Finally the role of RNA looping in delivering the bound N to the transcription complex and determining the stability (and thus the terminator specificity) of the resulting antitermination interaction of N with the RNA polymerase is considered in quantitative terms.
- Published
- 1997
- Full Text
- View/download PDF
37. Histidine-tryptophan interactions in T4 lysozyme: 'anomalous' pH dependence of fluorescence.
- Author
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Van Gilst M and Hudson BS
- Subjects
- Fluorescence, Hydrogen-Ion Concentration, Models, Molecular, Mutagenesis genetics, Tryptophan genetics, Histidine metabolism, Muramidase metabolism, T-Phages enzymology, Tryptophan metabolism
- Abstract
A variant of T4 lysozyme which contains only a single tryptophan residue (at position 138) has been prepared (W126Y/W158Y designated 'YWY'). Two additional mutations to YWY have been prepared involving replacement of glutamine 105, which hydrogen bonds to the indole N-H of trp 138 in wild type, with either a histidine (YWY/Q105H) or an alanine (YWY/Q105A). The fluorescence properties of these two species are investigated as a function of pH. YWY/Q105A exhibits essentially a single exponential fluorescence decay (5% tau = 0.35 ns 95% tau = 5 ns) and almost no pH dependence in steady state or time resolved fluorescence behavior. In contrast, YWY/Q105H exhibits complex fluorescence decay over the entire pH range used in these experiments. As the pH is lowered from 8 to 4, there is an increase in the quantum yield and a change in the average lifetime (from 2.0 to 3.1 ns). Using this data, the pKa of histidine 105 has been determined to be 5.9. These results are contrasted to those from other proteins which show a pH dependent tryptophan fluorescence associated with a neighboring histidine or other residue. Quenching behavior in terms of the stereochemistry of the tryptophan-histidine interaction and implications of these results for current models of complex fluorescence behavior of single tryptophan proteins are also discussed.
- Published
- 1996
- Full Text
- View/download PDF
38. Structural and thermodynamic characteristics of the binding of the lambda N protein to a RNA hairpin.
- Author
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Van Gilst M, Rees WA, and von Hippel PH
- Subjects
- Bacteriophage lambda genetics, Bacteriophage lambda metabolism, Base Sequence, Binding Sites, Molecular Sequence Data, Molecular Structure, Nucleic Acid Conformation, Protein Binding, RNA, Viral genetics, Thermodynamics, Viral Regulatory and Accessory Proteins chemistry, RNA, Viral chemistry, RNA, Viral metabolism, Viral Regulatory and Accessory Proteins metabolism
- Abstract
The specific binding of the lambda N protein to a 15 nucleotide RNA oligomer that forms a hairpin structure has been investigated by biophysical methods. Using fluorescence spectroscopy and equilibrium ultra-centrifugation, it was found that the N protein binds specifically to this RNA hairpin as a monomer. Circular dichroism experiments show that both the N protein and the RNA hairpin undergo structural change upon association of the complex.
- Published
- 1995
39. Quenching interactions and nonexponential decay: tryptophan 138 of bacteriophage T4 lysozyme.
- Author
-
Van Gilst M, Tang C, Roth A, and Hudson B
- Abstract
Site-directed mutagenesis has been used to prepare variants of bacteriophage T4 lysozyme that contain only one tryptophan residue at position 138 and to change the residues in the immediate environment of this buried residue. Replacement of glutamine-105 by alanine results in a 2.7-fold increase in fluoresence quantum yield and converts the fluorescence decay from a highly nonexponential form to a single-exponential decay. This is atributed to electron transfer quenching of tryptophan-138 fluorescence by glutamine-105. Replacemeent of alanine-146 by threonine results in a 1.6-fold decrease in fluorescence intensity, indicating enhanced quenching by glutamine-105; replacement of glutamine-105 by alanine in this species results in a 5-fold in crease in fluorescence intensity. The interpretation of the nonexponential decay of the glutamine-105-containing species is discussed in terms of reversibility of the quenching process.
- Published
- 1994
- Full Text
- View/download PDF
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