Biology subjects

Campbell, I.

Publications and source records attributed to Campbell, I..

At least 19 recordsLinked to original sources

bioRxiv2026

Headbutting goats self-inflict traumatic brain injury

Traumatic brain injury (TBI) is a characteristic feature of neurodegenerative diseases such as Alzheimers disease and chronic traumatic encephalopathy. Small animal models have been used to establish clinically relevant biomarkers of neuropathology, however, they show significant anatomical differences from humans and are affected by artificial experimental manipulations, making them often unsuitable for longitudinal study of repetitive mild TBI. There is a need for more diverse and translationally relevant animal models to better understand disease onset and development. Building on a previous study of neuropathology in headbutting bovids in the wild, this pilot study investigated whether freely headbutting domestic goats, which naturally engage in low-intensity, high-frequency head impacts, accumulate measurable biomarkers of neurodegeneration in cerebrospinal fluid (CSF) and brain tissue. Over a six-month period, three male goats (Capra hircus) were allowed to freely headbutt under continuous video surveillance. Monthly CSF samples were collected, and concentrations of key neurodegeneration biomarkers were measured via multiplex immunoassays, including amyloid-{beta} peptides (A{beta}40, A{beta}42), total and phosphorylated tau (tTau and pTau), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and neurofilament M (NF-M). Imaging studies were completed for non-invasive assessment of glucose metabolism ([18F]-FDG) and neuroinflammation via translocator protein (TSPO, [18F]DPA-714). Postmortem immunohistochemistry was conducted on prefrontal cortical tissues using antibodies targeting pTau, GFAP, and S100B. Head impact kinematics were quantified using horn-mounted accelerometer and inclinometer sensors that recorded linear acceleration, rotational velocity, and head orientation during naturally occurring headbutting events. Several notable trends were observed. Phosphorylated tau as well as reactive astrocytes were detected in the brain tissue, mirrored by elevated GFAP detected in the CSF. PET TSPO did not illustrate a significant signal, however, PET FDG revealed frontal-dominant activity in all goats, and one with asymmetrical activation. Overall, the goats sustained 5,000-7,000 head impacts each over six months. Accelerometer measurements recorded forces up to 388 N and peak acceleration up to 16.5 g. This multi-modal observational study is the first to characterize neurodegeneration biomarkers and kinematics in headbutting goats. Even at one year old, the combination of pTau and gliosis in both the brain tissue and CSF indicates that the goats repetitive head impacts begin to show neurodegenerative consequences early in life. Likely, the severity of these consequences increases with headbutts and age, eventually resulting in chronic neurodegeneration. This system shows promise as a large-animal model for the longitudinal study of the onset and progression of neurodegenerative disease.

neuroscience↗

bioRxiv2026

In vivo modulation of locus coeruleus activity by light

Dysfunction of the Locus coeruleus (LC), a small brainstem nucleus which consists of the brains primary source of norepinephrine, is linked to various neurological and psychiatric disorders. Light exposure influences many non-image-forming (NIF) biological functions including those modulated by LC activity. Yet direct evidence of light-driven modulation of the LC has remained elusive due to the structures small size and deep location. Using ultra-high-field (7 Tesla) functional MRI during an emotional task under varying illuminances, we demonstrate that light modulates LC activity in an emotion-dependent manner. We show that increased illuminance dampens LC responses to negative emotional stimuli while enhancing responses to neutral stimuli. Furthermore, we provide tentative evidence that within an emotional context, light may affect LC activity through the basomedial nucleus of the amygdala as well as through a region of the hypothalamus encompassing the lateral hypothalamus. These findings open avenues for the development of targeted, non-pharmacological treatments leveraging light to modulate norepinephrine tone and/or LC activity in several neuropsychiatric disorders. Significance StatementDysfunction of the Locus Coeruleus (LC), a small nucleus of brain and the main source of norepinephrine, is linked to various brain disorders. Here we provide in vivo evidence that exposure to light can alter the activity of the LC with higher illuminance leading to dampened LC responses to negative emotional stimuli. These findings identify the LC as a key target for the therapeutic effects of light on emotion, offering a biological framework for using light to treat neuropsychiatric disorders.

neuroscience↗

bioRxiv2026

Transcriptomic timeseries links hepatic gene expression to an early and self-limited systemic response to enteric infection

The liver receives microbe and host signals from the intestine via the portal vein, thereby connecting the gut to systemic physiology. Homeostatic control of the timing of systemic responses is critical to prevent the expansion and dissemination of gut microbes and to mitigate untoward effects from prolonged systemic inflammation, however these mechanisms remain enigmatic. Here, to determine the role of the liver in coordinating systemic immune responses to enteric infection, matched measurements of global gene expression profiles were collected from the murine liver and intestinal epithelium throughout the course of enteric infection and clearance of Citrobacter rodentium, a mouse model of infectious colitis. These data revealed metabolic suppression in the liver during the peak of infection and a long-lived immune signaling pattern in the colon associated with CD4 and CD8 T cell infiltration that persisted beyond the clearance of infection. Furthermore, an early inflammatory signal was detected in the liver that resolved before the peak of disease and pathogen colonization. This self-limited, early signal depended on the pathogens virulence program and correlated with the timing of a corresponding systemic response, including circulating TNF- and IL-6, key mediators of acute-phase proteins. These results uncover the temporal pattern of hepatic changes in response to the course of intestinal infection and provide correlative evidence that an early pulse of gene expression in the liver coordinates and limits the duration of the systemic acute-phase protein response. Author summaryLocalized infections can trigger systemic inflammatory responses that help limit infection. However, prolonged systemic inflammation risks tissue damage and disease. Thus, the timing of systemic immune reactions is critical to the balance between immunity and damage. Yet, knowledge of the pathways that link gut-localized infections to systemic immune tone is limited. Since the liver is anatomically central to the connection between the gut and circulatory systems, we hypothesized that monitoring the kinetics of liver gene expression throughout the natural course of an intestinal bacterial infection would provide a valuable resource and yield insight into the control of systemic immune tone. Critically, we identified a burst of liver cytokine signaling that occurred and resolved before peak pathogen burden and disease in the colon and predicted the circulating inflammatory response. We propose that this early and self-limited signal from the liver coordinates the timing of the systemic response, ensuring it occurs early enough to promote immunity and resolve before causing tissue damage.

immunology↗

bioRxiv2026

Reconstituting Mouse Embryogenesis Ex Utero from Gastrulation to Fetal Development Reveals Maternally Independent Metabolic Programs

Mammalian development takes place inside the maternal uterus, creating technological constraints that make difficult the study of embryogenesis in live developing embryos. A central challenge for understanding the role of metabolism in mammalian development is discriminating placental and uterine-regulated signals from embryo-intrinsic processes independent of maternal influence, a process that until now has remained inseparable during gastrulation and organogenesis1-3. Ex utero culture systems allowing continuous growth of embryos during pre-gastrulation to organogenesis4,5 offer a promising solution to this challenge. Here, we present optimized ex utero culture platforms that support faithful development of mouse embryos from gastrulation (embryonic day 6.5/7.5) through the fetal period (embryonic day [~]12.5) and harnessed these platforms for dissecting metabolic transitions in vivo during embryogenesis independently of uterus and placenta. We characterized the metabolome of in utero and ex utero whole embryos, fetal organs and culture medium between embryonic days E6.5 and E12.5 by liquid chromatography mass-spectrometry (LC-MS) metabolomics, isotope tracing, and single cell transcriptomics. These datasets present a comprehensive overview of the dynamic embryonic metabolism during gastrulation and organogenesis in utero and ex utero. This analysis revealed that the midgestational metabolic switch occurring at E10.5-E11.5 is faithfully recapitulated ex utero, indicating that this transition is intrinsically programmed in embryonic tissues and does not require direct maternal or placental cues. Notably, oxygen availability modulated the extent of this transition, but elevated oxygen was insufficient to induce it prematurely, demonstrating that the switch is developmentally timed and only partially environmental-responsive. We further harnessed the ex utero platform for identifying and perturbing a mitochondrial redox shift at E7.5-E8.5 that is critical for developmental progress after gastrulation. These findings uncover the remarkable metabolic plasticity of the mammalian embryo, demonstrating its capacity to sustain growth independently of maternal inputs from the establishment of the body plan through the onset of the fetal period. Moreover, they highlight the use of long-term ex utero culture as a unique framework for dissecting the mechanisms that shape embryogenesis under physiological and experimentally perturbed conditions, while functionally uncoupling embryonic programs from maternal and placental influences.

developmental biology↗

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

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

Capsule-Based Single-Cell Genome Sequencing

Single-cell genomics methods have unveiled the heterogeneity present in seemingly homogenous populations of cells, however, these techniques require meticulous optimization. How exactly does one handle and manipulate the biological contents from a single cell? Here, we introduce and characterize a novel semi-permeable capsule (SPC), capable of isolating single cells and their contents while facilitating biomolecular exchange based on size-selectivity. These capsules maintain stability under diverse physical and chemical conditions and allow selective diffusion of biomolecules, effectively retaining larger biomolecules including genomic DNA, and cellular complexes, while permitting the exchange of smaller molecules, including primers and enzymes. We demonstrate the utility of SPCs for single cell assays by performing the simultaneous culture of over 500,000 cellular colonies, demonstrating efficient and unbiased nucleic acid amplification, and performing combinatorial indexing-based single-cell whole genome sequencing (sc-WGS). Notably, SPC-based sc-WGS facilitates uniform genome coverage and minimal cross-contamination allowing for the detection of genomic variants with high sensitivity and specificity. Leveraging these properties, we conducted a proof-of-concept lineage tracing experiment using cells harboring the hypermutator polymerase {varepsilon} allele (POLE P286R). Sequencing of 1000 single cell genomes at low depth facilitated the capture of lineage marks deposited throughout the genome during each cell division and the subsequent reconstruction of cellular genealogies. Capsule-based sc-WGS expands the single-cell genomics toolkit and will facilitate the investigation of somatic variants, resolved to single cells at scale.

genomics↗

bioRxiv2024

Florigen and antiflorigen gene expression correlates with reproductive state in a marine angiosperm, Zostera marina

O_LIFlorigen and antiflorigen genes within the phosphatidylethanolamine-binding protein (PEBP) family regulate flowering in angiosperms. In eelgrass (Zostera marina), a marine foundation species threatened by climate change, flowering and seed production are crucial for population resilience. Yet, the molecular mechanism underpinning flowering remains unknown. C_LIO_LIUsing phylogenetic analysis and functional assays in Arabidopsis, we identified thirteen PEBP genes in Z. marina (ZmaPEBP) and showed that four genes altered flowering phenotypes when overexpressed. We used quantitative RT-PCR on Z. marina shoots from perennial and annual populations in Willapa Bay, USA to assess expression of these four genes in different tissue and expression changes throughout the growth season. C_LIO_LIWe demonstrated that ZmaFT2 and ZmaFT4 promote flowering, and ZmaFT9 and ZmaTFL1a repress flowering in Arabidopsis. Across five natural sites exhibiting different degrees of population genetic structure, ZmaFT2 and ZmaFT4 were expressed in leaves of vegetative and reproductive shoots and in stems and rhizomes of reproductive shoots. ZmaFT9 was distinctively expressed in leaves of vegetative and juvenile shoots, while ZmaTFL1a levels increased after flowering shoots emerged. C_LIO_LIOur results suggest that ZmaFT2 and ZmaFT4 may promote flowering, while ZmaFT9 may inhibit a floral transition in eelgrass. We speculate that ZmaTFL1a may be involved in flowering shoot architecture. C_LI

plant biology↗

bioRxiv2024

A robust unsupervised clustering approach for high-dimensional biological imaging data reveals shared drug-induced morphological signatures

Modern biology increasingly relies on large-scale screening to generate high dimensional datasets with potential to accelerate discovery. However, analysing these complex datasets remains challenging, particularly in applications where the underlying structure and groupings are unknown, and high dimensionality introduces noise and artifacts that make follow up studies difficult to prioritise. Here, we present an unsupervised consensus clustering tool that quantifies biologically meaningful patterns based on multi-scale data organisation to guide decision-making in high-throughput screening. Using large-scale drug screening data in cancer cell lines and bacterium model, we demonstrate its ability to use diverse data inputs to prioritize robust drug clusters with shared biological mechanisms and conserved drug responses. This method addresses key limitations associated with prioritising robust, actionable hits from scalable screening data.

bioinformatics↗

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↗

bioRxiv2024

Exposure to light supresses the activity of the medial and superior amygdala during emotional processing

The brain mechanisms through which changes in season and light exposure modulate mood may involve different nuclei of the amygdala. We aimed to test this hypothesis using 7 Tesla functional magnetic resonance imaging in 29 healthy young adults. We first considered time-of-year changes in activity that are related to the slow change in photoperiod. We find that the response to emotional stimuli of selected medial and superior nuclei of the amygdala peaked around the start of winter or increased with worse mood status. We further assessed how alternating short exposures to light of different illuminance acutely affected the regional activity of the amygdala. We show that the same areas showed a linear reduction of activity when exposed to increasing light illuminance, specifically when processing emotional stimuli. Importantly, the impact of light on part of these nuclei peaked around the start of summer or decreased with worse mood. These findings provide new evidence that humans show seasonality and that, for mood, it involves parts of the amygdala. The results bring novel insights into the mechanisms that underlie the long-term and acute impact of light on mood and that may contribute to the benefits of light therapy in the treatment of mood disorders.

neuroscience↗

bioRxiv2023

Regional response to light illuminance across the human hypothalamus

Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.3 {+/-} 2.9y) were completing two auditory cognitive tasks. We find that, during both the executive and emotional tasks, higher illuminance triggered an activity increase over the posterior part of the hypothalamus, which includes part of the tuberomamillary nucleus and the posterior part of the lateral hypothalamus. In contrast, increasing illuminance evoked a decrease in activity over the anterior and ventral parts of the hypothalamus, encompassing notably the suprachiasmatic nucleus and another part of the tuberomammillary nucleus. Critically, the performance of the executive task was improved under higher illuminance and was negatively correlated with the activity of the posterior hypothalamus area. These findings reveal the distinct local dynamics of different hypothalamus regions that underlie the impact of light on cognition.

neuroscience↗

bioRxiv2023

Light modulates task-dependent thalamo-cortical connectivity during an auditory attentional task

Exposure to blue wavelength light stimulates alertness and performance by modulating a widespread set of task-dependent cortical and subcortical areas. How light affects the crosstalk between brain areas to trigger this stimulating effect is not established. We recorded the brain activity of 19 healthy young participants (24.05{+/-}2.63; 12 women) while they completed an auditory attentional task in darkness or under an active (blue-enriched) or a control (orange) light, in an ultra-high-field 7 Tesla MRI scanner. We tested if light modulated the effective connectivity between an area of the posterior associative thalamus, encompassing the pulvinar, and the intraparietal sulcus (IPS), key areas in the regulation of attention. We found that only the blue-enriched light strengthened the connection from the posterior thalamus to the IPS. Our results provide the first empirical data supporting that blue wavelength light affects ongoing non-visual cognitive activity by modulating task-dependent information flow from subcortical to cortical areas.

neuroscience↗

bioRxiv2023

Impact of light on task-evoked pupil responses during cognitive tasks.

Light has many non-image-forming functions including modulation of pupil size and stimulation of alertness and cognition. Part of these non-image-forming effects may be mediated by the brainstem locus coeruleus. The processing of sensory inputs can be associated with a transient pupil dilation that is likely driven in part by the phasic activity of the locus coeruleus. Here, we aimed to characterise the task-evoked pupil response associated with auditory inputs under different light levels and across two cognitive tasks. We continuously monitored the pupil of 20 young healthy participants (24.05y {+/-}4.0; 14 women) while they completed an attentional and an emotional auditory task whilst exposed to repeated 30-to-40s-blocks of light interleaved with darkness periods. Blocks could either consist of monochromatic orange light [0.16 melanopic Equivalent Daylight Illuminance (EDI) lux] or blue-enriched white light of three different levels [37, 92, 190 melanopic EDI lux; 6500K]. For the analysis 15 and then 14 participants were included in the attentional and emotional tasks respectively. Generalized Linear Mixed Models showed a significant main effect of light level on the task-evoked pupil responses triggered by the attentional and emotional tasks (p[≤].0001). The impact of light was different for the target vs. non-target stimulus of the attentional task but was not different for the emotional and neutral stimulus of the emotional task. Despite a smaller sustained pupil size during brighter light blocks, a higher light level triggers a stronger task-evoked pupil response to auditory stimulation, presumably through the recruitment of the locus coeruleus.

neuroscience↗

bioRxiv2023

Impact of repeated short light exposures on sustained pupil responses in an fMRI environment

Light triggers numerous non-image forming (NIF), or non-visual, biological effects. The brain correlates of these NIF effects have been investigated, notably using Magnetic Resonance Imaging (MRI) and short light exposures varying in irradiance and spectral quality. However, it is not clear whether having light in subsequent blocks may induce carry over effects of one light block onto the next, thus biasing the study. We reasoned that pupil light reflex (PLR) was an easy readout of one of the NIF effects of light that could be used to address this issue. We characterized the sustained PLR in 13 to 16 healthy young individuals under short light exposures during three distinct cognitive processes (executive, emotional and attentional). Light conditions pseudo-randomly alternated between monochromatic orange light [0.16 melanopic Equivalent Daylight Illuminance (mel EDI) lux] and polychromatic blue-enriched white light of three different levels [37, 92, 190 mel EDI lux]. As expected, higher melanopic irradiance was associated with larger sustained PLR in each cognitive domain. This result was stable over the light block sequence under higher melanopic irradiance levels as compared to lower ones. Exploratory frequency-domain analyses further revealed that PLR was more variable within a light block under lower melanopic irradiance levels. Importantly, PLR varied across tasks independently of the light condition pointing to a potential impact of the light history and/or cognitive context on PLR. Together, our results emphasize that the distinct contribution and adaptation of the different retinal photoreceptors influence the NIF effects of light and therefore potentially their brain correlates.

neuroscience↗

bioRxiv2023

Laboratory evolution identifies elongated flavodoxins that support electron transfer to sulfite reductases

Flavodoxins (Flds) mediate the flux of electrons between oxidoreductases in diverse metabolic pathways. While dozens of Fld-partner oxidoreductases have been discovered, these only represent a subset of the oxidoreductases that couple with ferredoxin (Fd) protein electron carriers. To investigate whether Flds can support electron transfer to a sulfite reductase (SIR) that evolved to couple with a Fd, we evaluated the ability of Flds to transfer electrons from a Fd-NADP reductase (FNR) to a Fd-dependent SIR using growth complementation of a microbe with a sulfur metabolism defect. We show that Flds from cyanobacteria complement the growth of this microbe when coexpressed with an FNR and an SIR that evolved to couple with a plant Fd. To better understand the interaction of Fld with these partner oxidoreductases, we evaluated the effect of peptide insertion on Fld-mediated electron transfer. We observe a high insertion sensitivity within regions predicted to be proximal to the cofactor and partner binding sites and a high insertion tolerance within the loop that is used to differentiate short- and long-chain flavodoxins. These results represent the first evidence that Flds can support electron transfer to assimilatory SIRs, and they suggest that the pattern of peptide-insertion tolerance is influenced by interactions with oxidoreductase partners in electron transfer pathways.

biochemistry↗

bioRxiv2023

In vivo Locus Coeruleus activity while awake is associated with REM sleep quality in healthy older individuals

The locus coeruleus (LC) is the primary source of norepinephrine (NE) in the brain, and the LC-NE system is involved in regulating arousal and sleep. It plays key roles in the transition between sleep and wakefulness, and between slow wave sleep (SWS) and rapid eye movement sleep (REMS). However, it is not clear whether the LC activity during the day predicts sleep quality and sleep properties during the night, and how this varies as a function of age. Here, we used 7 Tesla functional Magnetic Resonance Imaging (7T fMRI), sleep electroencephalography (EEG) and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 52 healthy younger (N=33; ~22y; 28 women) and older (N=19; ~61y; 14 women) individuals. We find that, in older, but not in younger participants, higher LC activity, as probed during an auditory mismatch negativity task, is associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS (4-8Hz), which are two sleep parameters significantly correlated in our sample of older individuals. The results remain robust even when accounting for the age-related changes in the integrity of the LC. These findings suggest that the activity of the LC may contribute to the perception of the sleep quality and to an essential oscillatory mode of REMS, and that the LC may be an important target in the treatment of sleep disorders and age-related diseases.

neuroscience↗