Biology subjects

Phillips, C.

Publications and source records attributed to Phillips, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Cognitive Fitness in Ageing (COFITAGE): A Multimodal and Longitudinal Neuroimaging Dataset

Purpose: Brain aging involves interrelated changes in molecular processes, neuroinflammatory mechanisms, brain macro- and microstructure, sleep physiology, and cognition. The 50 to 70 years age range represents a critical transition period, in which these subtle alterations may precede measurable cognitive decline and the onset of clinical neurodegenerative disease. To allow systematic investigation of these early alterations and the subsequent progression in brain aging, we provide an open-access data resource from a multidisciplinary longitudinal study integrating neuroimaging, genetics, sleep, and neuropsychological phenotyping with assessments at baseline and at 2-year follow-up. Acquisition and Validation Methods: The baseline cohort comprises 101 community-dwelling participants (50-69 years old) who underwent magnetic resonance imaging (MRI) using a 3T protocol that included high-resolution structural imaging (T1- and T2-weighted), quantitative multi-parametric acquisitions with B1 mapping, and multi-shell diffusion-weighted imaging. Moreover, positron emission tomography (PET) imaging was performed using [18F]Flutemetamol or [18F]Florbetapir (amyloid-beta tracers) in all participants, with a subset also undergoing [18F]THK-5351 PET (tau-related/neuroinflammation). The dataset was complemented by extensive phenotypic data, including sleep and neuropsychological assessments, and by genotype data through genetic analysis. 66 participants underwent a 2-year cognitive follow-up, enabling longitudinal analyses of cognitive trajectories. Data acquisition and curation were performed using standardized procedures, with systematic quality control to support reliable cross-sectional and longitudinal analyses. Data Format and Usage Notes: All data are distributed in a BIDS-compliant format, and released in open-access (EBRAINS). Potential Applications: This dataset supports multimodal analyses, allowing the identification of interpretable patterns characterizing brain aging from multiple perspectives. It enables the comparison of different models to derive (semi)quantitative MRI parameters, the discovery of imaging biomarkers associated with early cognitive decline, and the monitoring or prediction of brain aging progression. In addition, it offers focused coverage of adults aged 50-70 years, which is often underrepresented in existing healthy subjects public datasets.

neuroscience↗

bioRxiv2026

Quantitative MRI Preprocessing: Effects of Tissue-Specific Smoothing Approaches on Statistical inference

Background: Quantitative MRI (qMRI) provides voxel-wise measurements of tissue properties related to myelin, iron and water content, making it a powerful tool for studying brain aging and microstructural alterations in vivo. However, conventional spatial smoothing can introduce partial-volume effects and blur tissue boundaries, potentially affecting both statistical sensitivity and anatomical specificity. Several tissue-specific smoothing strategies have been proposed to address these limitations, yet their relative impact on voxel-wise statistical analyses remains insufficiently characterized. The present study aims (i) to systematically compare three tissue-specific smoothing strategies: a linear tissue-weighted compensated approach (TWS), a generalized version of nonlinear tissue-masked compensated smoothing approach (gTSPOON), and an intensity-weighted edge-preserving approach based on the Smallest Univalue Segment Assimilating Nucleus smoothing (SUSANs), and (ii) to investigate how smoothing approaches interact with statistical inference frameworks by comparing parametric and non-parametric voxel-wise analyse. Methods: Analyses were performed on a publicly available lifespan qMRI dataset comprising 138 healthy participants (19-75 years) and quantitative maps of MTsat, PD, R1, and R2*. The generalized TSPOON (gTSPOON) method was implemented using tissue-specific masks derived from probabilistic tissue segmentation. All three smoothing approaches (TWS, gTSPOON and SUSANs) were parameterized to achieve comparable nominal spatial smoothing. Age-related effects were investigated separately in GM and WM using voxel-wise general linear models following a previously published framework. Statistical inference was assessed using multiple complementary approaches, including parametric Random Field Theory (RFT), under both stationarity and non-stationarity assumptions, as well as non-parametric permutation-based inference. In addition to conventional thresholded statistical parametric maps, voxel-wise log-likelihood (LL) maps were computed to quantify general linear model (GLM) goodness-of-fit independently of statistical thresholding. Bland-Altman analyses and spatial agreement metrics were subsequently used to compare smoothing strategies. Results: TWS and gTSPOON produced highly similar spatial distributions of age-related effects across all qMRI parameters and tissue classes. However, TWS consistently yielded a larger number of significant voxels and clusters, reflecting slightly higher sensitivity, from slightly wider effective smoothness and reduced RESEL counts. By contrast, SUSANs generated substantially fewer significant voxels and clusters, associated with approximately half the effective smoothness and a markedly larger number of RESELs. Despite these differences in statistical sensitivity, voxel-wise LL analyses revealed distinct anatomical preferences for each smoothing strategy. TWS provided the best model fit predominantly within GM, whereas gTSPOON showed superior performance in homogeneous WM regions. Conversely, SUSANs achieved the highest LL values at GM-WM interfaces, particularly within sulcal and gyral transitions, indicating improved preservation of sharp anatomical gradients. These spatial patterns were consistently observed across MTsat, PD, R1 and R2* maps. Comparisons across stationary and non-stationary RFT assumptions revealed only minor differences, while non-parametric inference produced highly concordant results, indicating that the primary source of variability originated from the smoothing procedure itself rather than the inference framework. Conclusions: Tissue-specific smoothing strategies substantially influence both statistical sensitivity and voxel-wise model fitting in qMRI analyses. While TWS and gTSPOON provide highly consistent results, the edge-preserving SUSANs approach preferentially enhances model fit at tissue boundaries. Importantly, voxel-wise log-likelihood mapping revealed that no smoothing strategy is uniformly optimal throughout the brain; instead, each method exhibits anatomically preferential regions where model fit is maximized. These findings suggest that smoothing should be viewed as a region-dependent optimization problem and highlight voxel-wise LL mapping as a principled framework for selecting or developing adaptive smoothing strategies tailored to specific neuroanatomical structures and biological processes, including age-related brain changes.

neuroscience↗

bioRxiv2026

Structural Basis for Dimeric Genome Selection by HIV-1

HIV-1 packages a dimeric RNA genome into assembling virions, a requirement for replication. To understand the mechanism of dimer selection, we conducted cryogenic electron microscopy (cryoEM) studies of nascent assemblies formed between HIV-1 Gag protein constructs and genomic RNA elements that promote dimerization and packaging. CryoEM maps revealed structural architectures in which the helical dimer initiation signal (DIS) of the RNA packaging signal bridges two 6-helix bundles (6HBs) that protrude from adjacent Gag hexamers. Conserved guanosines that sandwich the DIS are located beneath the 6HBs and poised to interact with clusters of nucleocapsid domains. Mutation of these guanosines severely impairs RNA packaging into virus-like particles. Our findings suggest that DIS functions as a molecular ruler, organizing Gag hexamers into structures optimized for Gag lattice expansion.

molecular biology↗

bioRxiv2026

Active transcriptome remodeling and epigenetic adaptations underlie persistence in Leishmania parasites

Persistence - characterized by the transient ability of subpopulations of drug-susceptible parasites to survive exposure to drug - is a major driver of treatment failure and clinical relapses in leishmaniasis. Persisters are characterized by non-dividing or slow-growing state and increased drug tolerance. However, the molecular mechanisms governing formation of persisters remain poorly understood in Leishmania parasites. Here, we developed a model to explore persistence in Leishmania mexicana. Viable promastigote persister-like subpopulations were enriched using Ficoll density gradient centrifugation following lethal exposure to antimonial drugs that killed 80% of parasites. The surviving parasites exhibited delayed growth in drug-free medium that is characteristic for persisters, and significantly higher tolerance to drug upon rechallenge. Transcriptomic profiling across acute stress, drug-free recovery, and rechallenge phases revealed a global remodeling in persisters under all tested conditions. Induction phase in Leishmania persisters was characterized by downregulation of several biological processes and a robust upregulation of nucleolar pathways, supporting epitranscriptomic changes during formation of persisters. Upon drug removal, this profile rapidly reverted, initiating ribosomal biogenesis to exit latency and resume cellular proliferation. Resuscitation phase exhibited activated protein synthesis and upregulation in many biological processes associated with metabolic and mitochondrial functions. Furthermore, comparative analysis of drug responses in rechallenged drug-tolerant persisters and parental parasites exposed to the drug for the first time, revealed that persisters exhibit distinct drug response profiles compared to parental parasites by rapidly implementing a highly conserved, coordinated survival reprogramming, where 316 genes were uniquely downregulated, and 241 genes were upregulated. The distinct features of the drug response in rechallenged persister cells were characterized by the downregulation of mitochondrial function and protein synthesis machinery to induce a dormant, idling state, and the upregulation of drug-response and stress-tolerance genes to survive immediate toxicity. In contrast, parental parasites displayed a broad and disorganized drug response. Additionally, rechallenged persisters exhibited a distinct transcriptomic memory that transiently phenocopies stable genetic resistance. This pre-adapted state is characterized by the targeted upregulation of epigenetic modulators, heavy metal transporters, and catabolic enzymes to maintain viability. These findings demonstrate that drug persistence in Leishmania is not merely a metabolic collapse, but rather a sophisticated survival strategy involving active transcriptome remodeling, downregulation of translation and epigenetic adaptations. This transient state constitutes an initial evolutionary step toward permanent drug resistance and highlights new molecular vulnerabilities for therapeutic interventions aimed at preventing clinical relapse. Author summaryThe efficacy of leishmaniasis chemotherapy is often fails because Leishmania parasites survive the drugs by entering a dormant state, causing relapses in patients. In this study, however, we discovered that these parasites are not simply quiescent. On the contrary, they orchestrate a highly active survival response: they shut down energy-consuming functions while keeping their cellular alert mechanisms active. Remarkably, upon re-exposure to antileishmanial drugs, the parasites recall previous stress events and transiently activate defensive pathways characteristic of stable drug resistance. Understanding how Leishmania employs this temporary adaptive strategy provides critical targets for developing therapies designed to eradicate the infection and avert relapses.

microbiology↗

bioRxiv2026

Pooling quantitative MRI data: A multi-protocol study of healthy subcortical ageing

Quantitative MRI (qMRI) measures relaxation rates, exchange rates and proton densities that reflect biophysical properties of tissue and are ideally free from protocol- and scanner-dependence. In practice, qMRI has not yet achieved this level of independence from sequence and hardware choice, and quantitative estimates often differ across sites and acquisition schemes. At the same time pooling data across different sources can be beneficial to statistical power of longitudinal, cross-sectional or case-control studies. Here we investigate how protocol and hardware differences can affect pooling data from different sources in large ultra high field (UHF) qMRI studies in the context of healthy aging. We combine the openly available ageing UHF qMRI MP2RAGEME-based dataset with two different MPM-based sets of qMRI data. We evaluate how pooling affects age dependence of qMRI parameters and investigate protocol-related biases, with a particular focus on subcortical structures. We focus the analysis, first, on replication and expansion of the reference qMRI dataset on normative aging, second, the examination of the protocol influence on the estimated qMRI values, and third, on detecting the protocol effect on the age dependence inferred from the data. We find that the age-related changes for R1 measure around 4-17% of the lifespan mean in different structures. Similarly, age-related R2* variation in different structures constitutes around 6-30%. Subcortical structure volume change is on the order of 5-27%. We further observe larger relative difference between protocols for R1 and volume, while R2* remains more consistent for most regions. We show how pooling the UHF qMRI data from different sites and collected with different quantitative protocols can be both detrimental and beneficial for the analysis outcomes.

neuroscience↗

bioRxiv2026

Regional Hypothalamic Responses to Light Vary Across Developmental Stages but Remain Stable with Time of Day

Background: Light plays a significant role in regulating various non-visual biological processes, such as stimulating alertness and cognition. However, the precise subcortical neural pathways are not fully established, including within the hypothalamus. In particular, how the hypothalamus processes are modulated by time-of-day and developmental stages, remains poorly understood. Methods: In this study, we used 7 Tesla functional magnetic resonance imaging to examine in vivo the impact of different light illuminance (0.16, 37, 92, and 190 melanopic equivalent daylight illuminance: mel-EDI lux) on the activity of the hypothalamus of healthy young adults (N=33; 20 women; 24.3 {+/-}3.2y) and adolescents (N=16; 5 women; 16.8 {+/-}1.1y) while they completed an auditory executive task, in the morning or in the evening. Results: Performance to the task improved with increasing illuminance irrespective of time of day and age group. When focusing on time-of-day differences in young adults, we found that the regional impact of light illuminance on the activity of the hypothalamus was consistent between the morning and the evening, with the posterior and anterior hypothalamus, respectively, showing increased and decreased activity with increasing illuminance. When focusing on developmental stages differences, during the evening session only, we found similar regional patterns in adolescents and young adult. The magnitude of the response at the highest illuminance was, however, larger in adolescents, with a larger deactivation of the superior-anterior and inferior-tubular hypothalamus. Conclusions: These findings reveal a complex and non-uniform impact of light on hypothalamus activity and provide novel insights into how light influences vary with developmental stages.

neuroscience↗

bioRxiv2025

Sampling Microbial Dynamics in the Salish Sea Estuary: Evaluating Methods to Capture Cyanobacteria and Cyanophage

Picocyanobacteria from the genera Prochlorococcus and Synechococcus thrive across the globe in aqueous environments, have relatively small genomes, and have growth dynamics regulated by both viral interactions and abiotic conditions, making them excellent model organisms for exploring host-pathogen coevolution. The Salish Sea, located in the Western coastal waters bordering the USA and Canada, is at the current northern boundary (defined by Prochlorococcus versus Synechococcus prevalence ratios) of the range of Prochlorococcus. Predictions suggest that this boundary will shift northward as warmer waters move northward, providing an excellent system to study host-pathogen dynamics and coevolution in a changing environmental context. In preparation for such studies, we developed and refined methods to sample and sequence cyanobacteria, cyanophages, and their abiotic environment. In addition to basic methodological questions focused on the physical sampling, filtering, viral precipitation, DNA extraction, and technical replicability, we explored how well our filtering and extraction protocols enrich for our main target, picocyanobacteria. The protocol described herein can successfully discriminate large-cell eukaryotic organisms, but size fractionation of picocyanobacteria appears to be affected by the presence of free DNA, multicellular structures, and abundant tycheposons. Our preferred final protocol at the conclusion of these experiments based on yield and processing time is presented. We recovered substantial Prochlorococcus, Synechococcus and amoeba-like sequences in most samples, and preliminary exploration of relative taxon sequence read recoveries across locations, over time, and tidal conditions are also discussed. Approaches described here may be useful to other efforts such as harmful algal bloom monitoring, species isolation and enrichment, water quality assessments, anti-viral discovery, and understanding picocyanobacterial population changes over space and time.

microbiology↗

bioRxiv2025

The specificity of fatigue cerebral substrates in early Multiple Sclerosis - An fMRI study

ContextThe cerebral substrates of fatigue in patients with Multiple Sclerosis (pwMS) are not elucidated yet. This study aims at exploring the disease-specific functional brain substrates of fatigue in pwMS with a recent disease history MethodsSixteen pwMS (disease history < 5 years) and 17 matched Healthy Controls (HC) performed a N-Back task with three difficulty levels during fMRI acquisitions following high vs. low fatigue induction. Measures of subjective trait and state fatigue were also recorded. Behavioral performance at n-back task and evolution of subjective fatigue states were analyzed by means of Bayesian repeated measures analyses of variance. Functional MRI data were analyzed to determine between-group differences (1) in task-related brain activity, independently of trait fatigue score; (2) in the association between trait fatigue and brain activity ResultsA similar trajectory was observed in the two groups for subjective and task-related measures following fatigue induction. No between-group difference was observed in brain activity unrelated to fatigue score. However, negative associations between trait fatigue score and brain activity were observed in pwMS, while the associations are positive in HC. Specifically, interactions between group and task difficulty were observed in regions belonging to the Striato-Thalamo-Cortical (STC) network and the fronto-parietal cortex ConclusionGroup-specific patterns of brain activity related to fatigue were identified in pwMS and HC in the STC circuitry, despite similar behavioral performance and subjective fatigue level. This confirms the implication of the STC loops in fatigue pathophysiology, occurring from the early stages of the disease.

neuroscience↗

bioRxiv2025

Napping alters Functional Brain Responses in the Aged

Circadian rhythms shape the temporal organization of sleep and wakefulness and evolve throughout the adult lifespan, leading to higher sleep-wake cycle fragmentation with ageing. The increasing prevalence of daytime napping represents a visible manifestation of such fragmentation and has been suggested to forecast age-related cognitive decline. Here, we assessed the impact of napping on functional brain correlates of performance on a Sternberg working memory (WM) task using functional magnetic resonance imaging in 60 healthy older individuals, prospectively recruited with respect to their napping habits (39 females, age: 59-82y). As compared to non-nappers, nappers showed reduced hemispheric asymmetry in the dorsolateral prefrontal cortex (DLPFC, p< 0.001) and decreased performance at high WM load levels. Only in non-nappers was increased ipsilateral activation in the DLPFC associated with better performance at high WM load levels (p < 0.05), while contralateral activation across all WM load levels was not associated with better performance. These findings indicate that functional brain compensation and dedifferentiation processes vary according to an individuals napping phenotype, potentially serving as a marker of inter-individual differences in cognitive and brain aging.

neuroscience↗

bioRxiv2025

The relationships among alkaloid production, fungal biomass, and host genetics in the Tall Fescue-Epichloe symbiosis

Tall fescue (Lolium arundinaceum) is an important forage and turf grass that covers 35 million acres (140,000 square kilometers) in the transition zone of the southeastern United States. Most tall fescue in the US is infected with a symbiotic fungus, Epichloe coenophiala, which confers biotic and abiotic stress tolerance for the plant but also produces toxic alkaloids that harm livestock. Although there has been prior evidence that the grass host can influence alkaloid production levels, these have never been precisely quantified. Here, we report on testing alkaloid production and relative fungal biomass on >1000 genetically distinct tall fescue plants. We find that these two traits are weakly correlated, and that both show evidence of moderate to high influence by the host genome. Genome-wide association find only a single marginally significant hit, however, implying that any genetic control by the host is spread among a large number of genes. These results indicate that the host plant exerts moderate influence on these endophytic traits, that the two are largely independent of each other, and that the hosts influence is likely due to a large number of genes of small effect. These results have relevance for breeding tall fescue for forage and turf production, and especially for optimizing the endophyte relationship for tall fescue management.

plant biology↗

bioRxiv2025

The crosstalk between the anterior hypothalamus and the locus coeruleus during wakefulness is associated with low frequency oscillations power during sleep

Study ObjectivesAnimal research has demonstrated that sleep regulation heavily depends on a network of subcortical nuclei. In particular, whether the crosstalk between the Locus Coeruleus (LC) and hypothalamic nuclei influences sleep variability and age-related changes in humans remains unexplored. This study investigated whether the effective connectivity between the LC and subparts of the hypothalamus is associated with the electrophysiology of rapid eye movement sleep (REMS). MethodsThirty-three healthy younger ([~]22y, 27 women) and 18 older ([~]61y, 14 women) individuals underwent 7-Tesla functional magnetic resonance imaging during wakefulness to investigate the effective connectivity between LC and distinct hypothalamus subparts encompassing several nuclei. Additionally, we recorded their sleep electroencephalogram (EEG) to explore relationships between effective connectivity measures and REMS theta energy and sigma power prior to REMS episodes. ResultsThe effective connectivity analysis revealed robust evidence of a mutual positive influence between the LC and the anterior-superior and posterior hypothalamus, supporting the idea that the connectivity patterns observed in animal models are also present in humans. Furthermore, our results suggest that in older adults, stronger effective connectivity from the anterior-superior hypothalamus, including the preoptic area, to the LC is associated with reduced REM theta energy. Specificity analysis showed that this association was not limited to REM theta energy but also extended to specific lower-frequency bands during REMS and NREMS. ConclusionsThese findings highlight the complex age-dependent modulation of the LC circuitry and its role in sleep regulation. Understanding these neural interactions offers valuable insight into the mechanisms driving age-related sleep changes.

neuroscience↗

bioRxiv2025

Light Impact on Thalamo-Cortical Connectivity During an Executive Cognitive Task: Effects of Time of Day and Specificities of Teenagers

BackgroundLight affects not only vision but also attention, alertness, and cognition, primarily through intrinsically photosensitive retinal ganglion cells sensitive to blue-wavelength light. While previous research has shown that light influences brain regional activity, its impact on brain connectivity remains unclear. MethodsUsing 7-Tesla fMRI, this study examined how light illuminance modulates canonical left-lateralized verbal thalamo-prefrontal-parietal network connectivity during an auditory executive task. Fifty-five participants, including young adults (19-30 y, 23 Females: scanned in the morning or evening) and adolescents (15-18 y, 6 Females: scanned only in the evening), were studied. ResultsWe first found that across all the groups, moderate blue-enriched light strengthened parietal-to-frontal connectivity, while low-illuminance orange light enhanced thalamus-to-parietal connectivity. When focusing on time-of-day differences in young adults, we found that higher-illuminance blue-enriched light strengthened thalamus-to-prefrontal connectivity in the morning compared to the evening. When focusing on developmental stages differences, during the evening session only, we observe that moderate blue-enriched light enhanced thalamus-to-parietal connectivity in adolescents compared to young adults. ConclusionThese findings reinforce the view that the thalamus plays a key role in mediating the impact of light on cognition and the impact of light depends on the context of light administration, i.e. with timing and age.

neuroscience↗

bioRxiv2025

Diurnal dynamics of multilayer brain networks predict cognitive trajectories in aging

ObjectivesResting-state functional connectivity (rsFC) is a highly dynamic process that varies across different times of the day within each individual. Although this variability was long considered to be noise, recent evidence suggests it may allow for an optimal adaptation to changes in the environment. However, the way rsFC is shaped on a circadian scale and its association with cognition are still unclear. MethodsWe analyzed data from 90 late-middle-age participants from the Cognitive Fitness in Aging study (61 women; 50-69y). Participants completed five electroencephalographic (EEG) recordings of spontaneous resting-state activity spread over 20h of prolonged wakefulness. Using a temporal multilayer network approach, we characterized the diurnal variations of the dynamic recruitment and integration of resting-state brain networks. We focused on the theta and gamma frequency bands within the default mode network (DMN), central executive network (CEN), and salience network (SN). Additionally, we investigated the relationship recruitment and integration of these network with baseline cognitive performance and at 7-year longitudinal follow-up, as well as with positron emission tomography (PET) early neuropathological markers of Alzheimers disease such as {beta}-amyloid and tau/neuroinflammation. ResultsDiurnal changes in theta and gamma dynamics were associated with distinct cognitive aspects. Specifically, higher baseline memory performance was associated with higher theta dynamic integration of the SN and the CEN, as well as higher theta dynamic recruitment of the DMN. Moreover, lower longitudinal memory decline at 7-year was associated with higher theta dynamic integration of the SN, CEN, and DMN. In contrast, higher gamma diurnal dynamic integration of the SN and the CEN was associated with lower executive and attentional performance, as well as higher early {beta}-amyloid accumulation, at baseline. DiscussionThese findings suggest that maintaining a balance between network flexibility and stability throughout the diurnal phase of the circadian cycle may play a crucial role in cognitive aging, with stable theta-band connectivity supporting memory, whereas excessive gamma-band stability in the SN and CEN may contribute to executive decline and early amyloid accumulation. These insights highlight the importance of considering time-of-day in brain rsFC studies, calling for a temporal multilayer approach to capture these dynamic patterns more effectively.

neuroscience↗

bioRxiv2025

Linker histone H1 functions as a liquid-like glue to organize chromatin in living human cells

Linker histone H1, the most abundant chromatin protein, condenses chromatin, modulates DNA transactions such as transcription and DNA replication/repair, and participates in differentiation, development and tumorigenesis. While recent studies indicate that nucleosomes are clustered as condensed chromatin domains in higher eukaryotic cells, how histone H1 mechanically condenses chromatin remains unclear. Here, using a combination of direct visualization of single-H1 molecules in living human cells and multiscale molecular dynamics simulations, we demonstrate that the majority of H1 behaves like a liquid inside chromatin domains, rather than binding stably to nucleosomes as suggested by the traditional model. H1 functions as a liquid-like "glue", mediating dynamic multivalent electrostatic interactions between nucleosomes within chromatin domains. Consistently, rapid-depletion of H1.2 leads to decondensed chromatin domains both in cells and in silico. Our findings suggest that the H1 "glue" condenses chromatin domains while keeping them fluid and accessible, thereby supporting essential DNA transactions.

cell biology↗

bioRxiv2025

Age-related differences in the association between REM sleep and the polygenic risk for Parkinson's disease

ObjectiveParkinsons disease (PD) is one of the rare diseases for which sleep alteration is a true marker of disease outcome. Yet, how the association between sleep and PD emerges over the healthy lifetime is not established. We examined association between the polygenic risk score (PRS) for PD and the variability in the electrophysiology of Rapid Eye Movement (REM) sleep in 433 younger (18-31y) and 85 late-midlife (50-69y) healthy individuals. MethodsIn this prospective cross-sectional study, in-lab EEG recordings of sleep were recorded to extract REM sleep metrics. PRS was computed using SBayesR approach. ResultsGeneralized Additive Model for Location, Scale and Shape (GAMLSS) analysis showed significant association of REM duration (pcorr=0.03) and theta energy in REM (pcorr=0.004) with PRS for PD in interaction with age group. In the younger sub-sample, REM duration and theta energy were positively associated with PD PRS. In contrast, in the late-midlife sub-sample, the same associations were negative (though only qualitatively for REM theta energy) and may differ between men and women. InterpretationREM sleep is associated with the PRS for PD in early adulthood, 2 to 5 decades prior to typical symptoms onset. The association changes from positive in younger individuals, presumably free of alpha-synuclein, to negative in late-midlife individuals, possibly because of the progressive presence of alpha-synuclein aggregates or of the repeated increased oxidative metabolism imposed by REM sleep. Our findings may unravel core associations between PD and sleep and may contribute to novel intervention targets to prevent or delay PD.

neuroscience↗

bioRxiv2024

Aerial root formation in Oaxacan maize (Zea mays) landraces persists into the adult phase and is minimally affected by soil nitrogen and ambient humidity.

Maize (Zea mays) is the most widely produced crop in the world, and conventional production requires significant amounts of synthetic nitrogen fertilizer, which has negative economic and environmental consequences. Maize landraces from Oaxaca, Mexico, can acquire nitrogen from nitrogen-fixing bacteria that live in a mucilage secreted by aerial nodal roots. The development of these nodal roots is a characteristic traditionally associated with the juvenile vegetative stage of maize plants. However, mature Oaxacan landraces develop many more nodes with aerial roots than commercial maize varieties. Our study shows that Oaxacan landraces develop aerial roots during both the juvenile and adult vegetative phases and even during early flowering under greenhouse and field conditions. Surprisingly, the development of these roots was only minimally affected by soil nitrogen and ambient humidity. These findings are an important first step in developing maize varieties that can reduce fertilizer needs in maize production across different environmental conditions.

plant biology↗

bioRxiv2024

Cortical Excitability is Affected by Light Exposure- Distinct Effects in Adolescents and Young Adults

Light, particularly blue-wavelength light exerts a broad range of non-image forming (NIF) effects including the stimulation of cognition and alertness and the regulation of mood, sleep and circadian rhythms. However, its underlying brain mechanisms are not fully elucidated. Likewise, whether adolescents show a different NIF sensitivity to light compared to adults is not established. Here, we investigated whether cortical excitability, a basic aspect of brain function that depends on sleep-wake regulation, is affected by blue light and whether the effect is similar in young adults and adolescents. We used transcranial magnetic stimulation coupled to high-density electroencephalography (TMS-EEG) in healthy young adults (N=13, 24.2 {+/-} 3.4 y) and in adolescents (N=15, 16.9 {+/-} 1.1 y). Our results showed that, in young adults, blue light affected cortical excitability following an apparent inverted-U relationship, while adolescents cortical excitability was not significantly different under blue light compared to orange light. In addition, although light did not affect performance on a visuomotor vigilance task completed during the TMS-EEG recordings, cortical excitability was positively correlated to task performance in both age groups. This study provides valuable insights into the complex interplay between light, cortical excitability, and behavior. Our findings highlight the role of age in NIF effects of light, suggesting that brain responses to light differ during developmental periods.

neuroscience↗

bioRxiv2024

REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness

BackgroundAnimal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to sleep variability in humans is not yet established. Here, we investigated if the in vivo activity of the LC is related to the variability in the quality of Rapid Eye Movement (REM) sleep. MethodsWe assessed the LC activity of 34 healthy younger ([~]22y) and 18 older ([~]61y) individuals engaged in bottom-up and top-down cognitive tasks using 7-Tesla functional Magnetic Resonance Imaging (fMRI). We further recorded their sleep electroencephalogram (EEG) to evaluate associations between LC fMRI measures and REM sleep EEG metrics. ResultsTheta oscillation energy during REM sleep was positively associated with LC response in the top-down task. In contrast, REM sleep theta energy was negatively associated with LC activity in older individuals during the bottom-up task. Importantly, sigma oscillations power immediately preceding a REM sleep episode was positively associated with LC activity in the top-down task. ConclusionsLC activity during wakefulness was related to REM sleep intensity and to a transient EEG change preceding REM sleep, a feature causally related to LC activity in animal studies. The associations depend on the cognitive task, suggesting that a balanced level of LC tonic activity during wakefulness is required for optimal expression of REM sleep. The findings may have implications for the high prevalence of sleep complaints reported in aging and for disorders such as insomnia, Alzheimers, and Parkinsons disease, for which the LC may play pivotal roles through sleep.

neuroscience↗