Valérie Mongrain's research while affiliated with Université de Montréal and other places

Publications (78)

Preprint
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MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmen...
Article
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Uncaria rhynchophylla is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing Uncaria ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions. Rhync...
Article
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Sleep is a vital part of our lives as it is required to maintain health and optimal cognition. In humans, sex differences are relatively well-established for many sleep phenotypes. However, precise differences in sleep phenotypes between male and female rodents are less documented. The main goal of this article is to review sex differences in sleep...
Article
The use of electrocorticographic (ECoG) recordings in rodents is relevant to sleep research and to the study of a wide range of neurological conditions. Adeno-associated viruses (AAVs) are increasingly used to improve understanding of brain circuits and their functions. The AAV-mediated manipulation of specific cell populations and/ or of precise m...
Chapter
This article will focus on age-related changes in the circadian timing system. It will present age-related changes in circadian regulation of the sleep–wake cycle and circadian entrainment in humans. It will then address non-visual effects of light, eye's characteristics, as well as plasticity and adaptative mechanisms in aging. Lastly, it will rep...
Article
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The fragile X autosomal homolog 1 (Fxr1) is regulated by lithium and has been GWAS-associated with schizophrenia and insomnia. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and involves both cell-autonomous and system-level processes such as sleep. We examined the contribution of Fxr1 to cell-autono...
Article
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Background: Disease severity is tremendously variable in tuberous sclerosis complex (TSC). In contrast with the detailed guidelines available for TSC diagnosis and management, clinical practice lacks adequate tools to evaluate the prognosis, especially in the case of in utero diagnosis. In addition, the correlation between genotypes and phenotypes...
Article
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Sleep-wake driven changes in non-rapid-eye-movement sleep (NREM) sleep (NREMS) EEG delta (δ-)power are widely used as proxy for a sleep homeostatic process. Here, we noted frequency increases in δ-waves in sleep-deprived mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We identified two classes of...
Article
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Synapse loss occurs early and correlates with cognitive decline in Alzheimer’s disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in t...
Article
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Correction to: Molecular Brain (2018) 11:52 https://doi.org/10.1186/s13041-018-0394-3 Following publication of the original article [1], the authors reported that the article was mistakenly submitted with the omission of two authors: Feng Cao and Zhengping Jia. The authors declare that this was an error made in good faith. The corrected author list...
Article
Study Objectives Aggregates of hyperphosphorylated tau protein are a hallmark of Alzheimer's disease (AD) and other tauopathies. Sleep disturbances are common in AD patients, and insufficient sleep may be a risk factor for AD. Recent evidence suggests that tau phosphorylation is dysregulated by sleep disturbances in mice. However, the physiological...
Article
Sleep and sleep loss are impacting protein synthesis in the brain but the contribution of translational control to wakefulness and sleep regulation remains poorly understood. Here, we studied the role of two suppressors of protein synthesis, the eukaryotic translation initiation factor 4E-binding protein 1 and 2 (4E-BP1 and 4E-BP2), in sleep archit...
Preprint
Full-text available
Sleep-wake driven changes in NREM sleep (NREMS) EEG delta (δ: ~0.75-4.5Hz) power are widely used as proxy for a sleep homeostatic process. We noted frequency increases in δ-waves in sleep-deprived (SD) mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We discovered two types of δ-waves; one respondi...
Article
Circadian rhythms are generated in mammals by a central clock located in the suprachiasmatic nucleus of the hypothalamus, which regulates the homeostasis of many biological processes. At the molecular level, the regulation of circadian rhythms is under the control of transcriptional‐translational feedback loops composed of clock factors, including...
Article
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Sleep disorders are comorbid with most psychiatric disorders, but the link between these is not well understood. Neuroligin-2 (NLGN2) is a cell adhesion molecule that plays roles in synapse formation and neurotransmission. Moreover, NLGN2 has been associated with psychiatric disorders, but its implication in sleep remains underexplored. In the pres...
Article
Full-text available
Scale-free analysis of brain activity reveals a complexity of synchronous neuronal firing which is different from that assessed using classic rhythmic quantifications such as spectral analysis of the electroencephalogram (EEG). In humans, scale-free activity of the EEG depends on the behavioral state and reflects cognitive processes. We aimed to ve...
Article
Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by progressive hippocampal-dependent explicit memory deficits that begin at the onset of the illness. An early hallmark of AD is the accumulation of amyloid-beta (Aß) proteins in brain structures involved in encoding and consolidation of memory, like the hippocampus...
Article
NEUROLIGIN-1 (NLGN1) is a postsynaptic adhesion molecule involved in the regulation of glutamatergic transmission. It has been associated with several features of sleep and psychiatric disorders. Our previous work suggested that transcription of the Nlgn1 gene could be regulated by the transcription factors CLOCK and BMAL1 because they bind to the...
Article
Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some ver...
Article
Aim: The goal of this study was to test the state of methylation of transcription start positions in DNA that are actively involved in transcription. Materials & methods: We used sequential ChIP-bisulfite-sequencing with an antibody to RNpolII-PS5 to map the state of methylation of actively transcribing transcription start sites (TSS). Results:...
Article
Slow waves occurring during non-rapid eye movement sleep have been associated with neurobehavioural performance and memory. In addition, the duration of previous wakefulness and sleep impacts characteristics of these slow waves. However, molecular mechanisms regulating the dynamics of slow-wave characteristics remain poorly understood. The EphA4 re...
Article
Circadian (~24 h) rhythms of cellular network plasticity in the central circadian clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal network in the SCN regulates photic resetting of the circadian clock as well as stability of the circadian system during both entrained and constant conditions. EphA4, a cell adhesion molecule...
Article
Full-text available
The suprachiasmatic nucleus (SCN) is the central circadian clock in mammals. It is entrained by light but resistant to temperature shifts that entrain peripheral clocks [1-5]. The SCN expresses many functionally important neuropeptides, including vasoactive intestinal peptide (VIP), which drives light entrainment, synchrony, and amplitude of SCN ce...
Article
Cell adhesion molecules (CAM) play essential roles in the central nervous system, where some families are involved in synaptic development and function. These synaptic adhesion molecules (SAMs) are involved in the regulation of synaptic plasticity, and the formation of neuronal networks. Recent findings from studies examining the consequences of sl...
Article
Unlabelled: It is hypothesized that a fundamental function of sleep is to restore an individual's day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met...
Article
Full-text available
Sleep disturbances are common in psychiatric disorders, but the causal relationship between the two and the underlying genetic factors is unclear. The DISC1 gene is strongly linked to mood disorders and schizophrenia in a Scottish pedigree. In an earlier study we found a sleep homeostasis disturbance in a Drosophila model overexpressing wild-type h...
Article
Full-text available
Study objectives: Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of Ep...
Article
Neuroligin 1 (NLGN1) is a postsynaptic adhesion molecule that determines N-methyl-D-aspartate receptor (NMDAR) function and cellular localization. Our recent work showed that Nlgn1 knockout (KO) mice cannot sustain neuronal activity occurring during wakefulness for a prolonged period of time. Since NMDAR-dependent neuronal activity drives an import...
Article
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Traumatic brain injury (TBI), including mild TBI (mTBI), is importantly associated with vigilance and sleep complaints. Because sleep is required for learning, plasticity and recovery, we here evaluated the bidirectional relationship between mTBI and sleep with two specific objectives: (1) Test that mTBI rapidly impairs sleep–wake architecture and...
Article
Introduction: Medication-induced sleep disturbances are a major concern in drug development as a multitude of prescription drugs alter sleep patterns, often negatively. Polysomnography is used in clinical diagnostics but is also applicable to animal models. Rodent sleep architecture (nocturnal) differs from larger diurnal mammals, including humans...
Article
Full-text available
L’occurrence d’un traumatisme craniocérébral (TCC) est un problème de santé publique majeure. Les troubles du sommeil et de l’éveil sont parmi les symptômes les plus persistants et les plus déshabilitants à la suite d’un TCC. Or, les études empiriques portant sur l’apparition de ces symptômes, leur chronicisation et leur traitement demeurent non co...
Article
Cynomolgus monkeys are widely used as models of diseases and in pre-clinical studies to assess the impact of new pharmacotherapies on brain function and behaviour. However, the time course of electroencephalographic delta activity during sleep, which represents the main marker of sleep intensity associated with recovery during sleep, has never been...
Conference Paper
Relationships between sleep and epilepsy have been described since antiquity. Notably, epileptic seizures interfere with normal sleep patterns whereas specific sleep-wake stages have been associated with the occurrence of epileptic seizures (ES) and of interictal epileptiform discharges (IEDs). Moreover, sleep deprivation (SD) facilitates the onset...
Article
Full-text available
Sleep is critical for normal brain function and mental health. However, the molecular mechanisms mediating the impact of sleep loss on both cognition and the sleep electroencephalogram remain mostly unknown. Acute sleep loss impacts brain gene expression broadly. These data contributed to current hypotheses regarding the role for sleep in metabolis...
Article
Sleep parallels brain functioning and mental health. Neuronal activity during wakefulness leads to a subsequent increase in sleep intensity as measured using electroencephalographic slow-wave activity (SWA; index of neuronal synchrony in the low-frequency range). Wakefulness, and particularly prolonged wakefulness, also drives important changes in...
Article
Full-text available
Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here h...
Data
Time-dependent effect of TURP injection on cytokine levels. Animals were treated with either TURP or saline at ZT14, ZT20, ZT2, or ZT8 (time of injection, TOI) and sacrificed 10 h later at ZT0, ZT6, ZT12 and ZT18 (time of sacrifice, TOS), respectively. (A) IL-1Ra and (B) TNFα levels in serum at sacrifice were measured by ELISA. Closed boxes represe...
Data
Cytokine induction over time after TURP treatment at ZT2. Animals were treated with either saline or TURP at ZT2 (0 hours) and sacrificed at 6 different time points ZT4, ZT8, ZT12, ZT16, ZT20, and ZT0 (time after sacrifice, TOS) corresponding to 2, 6, 10, 14, 18, and 22 h after injection (HAI), respectively. (A) IL-1Ra and (B) TNFα levels in serum...
Data
Full-text available
Primer sequences used in the SYBR Green quantitative PCR assays. (PDF)
Data
IL-Ra induction after TURP treatment with or without hrIL-1Ra co-treatment. All animals were treated with either saline or TURP at ZT2 and sacrificed at either ZT12 or ZT16 time of sacrifice (TOS) with additional IL-1Ra treatment at 0, 4, and 8 h (ZT12 TOS) and 0, 4, 8 and 12 h (ZT16 TOS) after the initial treatment. One-way ANOVA for the four grou...
Article
Full-text available
Many aspects of the immune system, including circulating cytokine levels as well as counts and function of various immune cell types, present circadian rhythms. Notably, the mortality rate of animals subjected to high doses of lipopolysaccharide is dependent on the time of treatment. In addition, the severity of symptoms of various inflammatory con...
Data
Full-text available
Controls genes selected by GeNorm for each in vivo experiment. (PDF)
Article
Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes and increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated slee...
Article
Aging produces major changes in sleep structure and intensity which might be linked to cognitive impairment in the elderly. In this study, the genetic contribution to age-related changes in sleep was assessed in three inbred mouse strains of various ages. Baseline sleep and the response to 6 hours sleep deprivation (SD) achieved by gentle handling...
Article
Full-text available
We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) c...
Data
BMAL1 and CLOCK binding onto the promoter of 4 clock genes in the mouse cerebral cortex. Mice were sacrificed every 6 hours for 24 hours, and brain cortices were rapidly processed. Chromatin immunoprecipitation (ChIP) was performed using antibodies against BMAL1 and CLOCK or no antibody (negative control), and enrichment of putative promoter sequen...
Data
BMAL1 and CLOCK binding onto the promoter of 4 clock genes in the mouse liver. Mice were sacrificed every 6 hours for 24 hours, and livers were rapidly processed. Chromatin immunoprecipitation (ChIP) was performed using antibodies against BMAL1 and CLOCK or no antibody (negative control), and enrichment of putative promoter sequences of Cry1, Dbp,...
Article
Full-text available
Orexins (OX-A, OX-B) are neuropeptides involved in the regulation of the sleep-wake cycle, feeding and reward, via activation of orexin receptors 1 and 2 (OX1R, OX2R). The loss of orexin peptides or functional OX2R has been shown to cause the sleep disorder, narcolepsy. Since the regulation of orexin receptors remains largely undefined, we searched...
Article
Full-text available
Brain recovery after prolonged wakefulness is characterized by increased density, amplitude and slope of slow waves (SW, <4 Hz) during non-rapid eye movement (NREM) sleep. These SW comprise a negative phase, during which cortical neurons are mostly silent, and a positive phase, in which most neurons fire intensively. Previous work showed, using EEG...
Data
SW density and characteristics per sleep cycle in chronotypes. SW density, amplitude, slope (left panels), frequency, negative and positive phases duration (right panels) are shown per sleep cycle for M-types (open diamonds) and E-types (black squares) for the firsts 4 sleep cycles of baseline and recovery nights. SW properties were compared using...
Article
Full-text available
The sleep-deprivation-induced changes in delta power, an electroencephalographical correlate of sleep need, and brain transcriptome profiles have importantly contributed to current hypotheses on sleep function. Because sleep deprivation also induces stress, we here determined the contribution of the corticosterone component of the stress response t...
Article
Full-text available
Accumulating evidence indicate that molecular mechanisms generating circadian rhythms display some degree of tissue-specificity. More specifically, distinct patterns of expression for nuclear receptors of the ROR family indicate that the transcriptional control of the clock gene Bmal1 differs among tissues. This study aims to investigate the expres...
Article
Vigilance levels of 12 morning types (M-types) and 12 evening types (E-types) were investigated after a baseline night, 2 nights of sleep fragmentation (5 min of forced awakening every half-hour) and a recovery night. Sleep timing was adjusted to the preferred sleep schedule of each subject. Daytime vigilance levels were assessed with test series i...
Article
To present a longitudinal overview of the sleep schedules during weekdays and the weekend in a large sample of children and to examine the sleep-wake schedules in relation to nocturnal sleep duration and birth season. Longitudinal survey design. Data were collected by home interviews and questionnaires. Data for sleep schedules at the ages of 4, 5,...
Article
Sleep and vigilance disorders are among the most commonly reported symptoms following a concussion. The aim of the study was thus to investigate the effects of sport-related concussions on subjective and objective sleep quality. Ten concussed athletes and 11 non-concussed athletes were included. Concussed athletes had a history of 4.6+/-2.1 concuss...
Article
To evaluate the influence of chronotype on sleep stages and quantitative sleep EEG when sleep pressure is increased and sleep schedule remains constant. A 5-day session comprising an adaptation night, a baseline night, two nights of sleep fragmentation, and a recovery night. Chronobiology laboratory. Twenty-four healthy subjects aged 19-34 years: 1...
Article
Morning-type individuals (M-types) have earlier sleep schedules than do evening types (E-types) and therefore differ in their exposure to the external light-dark cycle. M-types and E-types usually differ in their endogenous circadian phase as well, but whether this is the cause or the consequence of the difference in light exposure remains controve...
Article
The aim of the present study was to evaluate the influence of season of birth and photoperiod at birth on diurnal preference in young adults. Participants were 1591 volunteers aged 17-35 years (69% women). The scores obtained on the Morningness-Eveningness Questionnaire (MEQ) of Horne and Ostberg were first assessed as a function of gender and seas...
Article
Morningness-eveningness has been associated with the entrained circadian phase. However, we recently identified morning and evening types having similar circadian phases. In this paper, we compared parameters of slow-wave activity (SWA) decay in non-rapid-eye-movement (NREM) sleep between these two subgroups to test the hypothesis that differences...
Article
Circadian types classify individuals according to their preferred timing for activity and sleep, morning and evening types showing, respectively, early or late preferences. This characteristic has been associated with corresponding differences in circadian sleep propensity. In this study, quantitative analysis of the sleep EEG in antero-posterior d...
Article
From the earliest interest in sleep research, sleep has been perceived as a recovery process and this function is easily understandable because sleep is needed to feel refreshed and to be able to perform optimally. Accordingly, Nathaniel Kleitman, the “father” of modern sleep research, emphasized the necessity of sleep [1]. The essential nature of...
Article
Full-text available
To evaluate the influence of chronotype (morning types and evening types) on sleep stages and quantitative sleep electroencephalograms when constraints on the sleep schedule are minimal and when sex difference is taken into account. A 48-hour session in the laboratory, including 2 nights of polysomnography, preceded by 7 days of ambulatory actigrap...
Article
Full-text available
A shorter phase angle between habitual wake time and underlying circadian rhythms has been reported in evening types (E types) compared to morning-types (M types). In this study, phase angles were compared between 12 E types and 12 M types to verify if this difference was observed when the sleep schedule was relatively free from external social con...

Citations

... Fourth, we only used male mice for sleep analysis in the present study since RBD is generally more common in males than in females. The previous study analyzing WT mice inoculated with α-syn PFFs into the CNS reported that male PFFsinjected mice developed more severe α-syn pathology than female ones [19], while there was no significant difference in REM sleep amounts between the sexes [20]. Future research should be done on both sexes to understand the disease in future studies. ...
... Spiro-fused indole motifs have been identified as a divergent chemical scaffold with promising biological activities. They are also found in several plant products including spirogamaenzine A, 1 fluorocurine, 2 peteropodine, 3 isopeteropodine, 3 mitraphylline, 4 mitragynine, 5 rauniticine, 6 rhynchophylline, 7 welwitindolinone A, 8 and spirotryprostatin A.9 Some of spiro-fused indoles have been reported as pharmaceutical significant compounds as shown in Figure 1. 3,[10][11][12][13] Several synthetic methods have been reported in various studies, including intermolecular alkylation, 14 cycloaddition, 15 palladium catalyzed reactions, 16 Cu/TEMPO catalyzed, 17 and sigmatropic rearrangement. ...
... In rodents the evidence for an overall increase in synaptic strength during wake and a net decrease during sleep comes from multiple sources. Electrophysiologically, experiments in mice and rats found that the slope and amplitude of cortical evoked responses, as well as the amplitude and/or frequency of miniature excitatory postsynaptic currents, are higher after wake than after sleep (Vyazovskiy et al., 2008;Liu et al., 2010;Bjorness et al., 2020;Bridi et al., 2020;Khlghatyan et al., 2020). The molecular evidence was provided by studies in synapse-rich preparations obtained from cortex, hippocampus, and the whole forebrain. ...
... TSC patients have been reported at 4, 11, and 26 years of age. Patients were diagnosed after unexplained seizures, skin lesions, or unexplained mental retardation [14][15][16]. Further medical work-up was completed, and patients had the required two major criteria or one major criteria plus two minor criteria. ...
... In other words, sleep is triggered by modest error around the true set point. This evident in traditional indicators of Process S: SWA is an effective indicator of sleep deprivation, but its value in free behavior has been questioned (Hubbard et al., 2020). Third, Process S is traditionally queried in the frontal cortices of adult animals. ...
... Indeed, TSP-1 could induce the expression of α2δ-1, a voltage-activated Ca2 + channel subunit, and the synaptic adhesion molecule neuroligin-1 (NLGN1), leading to potentiated synaptogenesis in animal models [213]. Neuroligins adjust synapse formation and function, and down-regulation of their activation results in synaptic and memory deficits, as shown in AD mice [215,216]. Thereby, restoration of their expression and function as facilitated by administration of MSCs-derived exosome may attenuate AD-associated pathological symptoms. On the other hand, it appears that iNOS may serve as the initiator of Aβ deposition and AD progression [217]. ...
... In addition to amyloidopathy, the pathogenesis of AD also involves an accumulation of hyperphosphorylated tau proteins that form intracellular neurofibrillary tangles [176]. Tau phosphorylation also follows a circadian rhythm driven by sleep and circadian induced changes in body temperature [177]. A study on a Tg4510 mouse model of pathological tau physiology, taupathy, found alterations in circadian rhythm at both the molecular and behavioral level. ...
... forms two functionally distinct protein complexes mTORC (mTOR complex) 1 and mTORC2 (Fig. 3). Recent work has found it regulates various neuronal processes including neural progenitor cell growth and differentiation, synaptic plasticity, learning and memory, hormone secretion, food uptake, and sleep [67][68][69][70][71][72]. mTORC1 activity has been extensively studied in the SCN [16,18,19,47,73]. ...
... Another neglected sleep-related research area concerns the potential for effects of Rhy on circadian functions. Many of the pathways presented in this review have been linked to the circadian timing system [290]. For instance, NMDARs (including the GluN2B subunit), TrkB receptors, and D2Rs show circadian rhythms of mRNA or protein levels in specific brain regions [291][292][293][294][295][296]. ...
... Based on the above retina-brain similarities, the rsERG signal will be analyzed using methodologies previously applied to the EEG, such as that detailed in Donoghue et al.'s (2020) study which showed the importance of disentangling the periodic (which emphasizes frequency peaks in the spectrum) and the aperiodic (or scale-free activity) components of neuronal signals. In the present study, we also analyzed these two components, where the periodic component was assessed by means of a spectral analysis of the data and the aperiodic component was modeled with a power law relationship that organizes the various temporal scales as 1/f α , an approach also used in EEG (Donoghue et al., 2020;Lina et al., 2019;Gadhoumi et al., 2015). Of note, the aperiodic component was previously shown to yield valuable information as it reveals the spectral organization of the EEG signal, without having to rely on a specific scale or frequency (Ma et al., 2005;He et al., 2010;Zorick and Mandelkern, 2013). ...
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