Biology subjects

Cross, N.

Publications and source records attributed to Cross, N..

11 recordsLinked to original sources

bioRxiv2026

Beyond Aging, Sex and Insomnia Disorder Shape NREM Brain Oscillations

ObjectivesChronic insomnia (INS) is particularly prevalent in older adults and females. Sex-and age-related differences in neurophysiological markers of sleep quality (sleep spindles and slow-wave activity [SWA]) may underlie differential vulnerability to INS. This study investigated the effects of sex and insomnia on spindle and SWA beyond aging, to better understand the mechanistic differences contributing to the higher prevalence of INS in females. MethodsAfter a habituation night, one night of sleep assessed with polysomnography was analyzed in 222 adults (aged 18-82) including 119 INS (71% female) and 103 healthy sleepers (HS; 61% female). Spindle density, slow oscillation (SO) density, relative sigma power and SWA were derived during NREM sleep. Age, group, sex, and group-by-sex interactions were examined, with age as a covariate. ResultsAge, insomnia, and sex each contributed uniquely to NREM oscillatory activity. INS primarily reduced spindle and SO density, while sex accounted for differences in SWA. While SWA was higher in females overall, sex differences were not significant within the INS or HS groups. Female INS reported highest rates of insomnia severity as well as lower sigma power than males in the INS group. Spindle and SO density deficits were also present in female INS relative to female HS, as well as male INS relative to male HS. ConclusionsThe combination of reduced sigma power in females with insomnia relative to their male counterparts, as well as less spindle and SO density compared to female healthy sleepers may contribute to greater insomnia severity in females. Statement of SignificanceInsomnia is a growing public health concern that is more commonly reported in females, yet the neural mechanisms underlying this sex difference remain poorly understood. Our findings suggest that specific markers of sleep quality are disproportionately disrupted in females with insomnia, potentially contributing to greater vulnerability and symptom severity. These results provide new insight into how sex influences the neurophysiology of insomnia disorder and identify oscillatory markers that could serve as targets for personalized interventions. Future research should investigate whether these alterations represent persistent dysfunction or reversible changes, which could advance understanding of the biological basis of insomnia and inform strategies to improve sleep health in at-risk populations.

neuroscience↗

bioRxiv2026

A Systematic Review and Meta-Analysis of Biological Sex Differences in Sleep Spindles and Slow Wave Activity in Adults with and without Insomnia

Mounting evidence shows sex-based differences in sleep experiences and outcomes, including the prevalence of insomnia disorder. However, the impact of biological sex on brain oscillations during sleep remains poorly understood, especially in the context of insomnia disorder. This is a notable gap, given that neurophysiological aspects of sleep are associated with brain health and overall sleep quality. We systematically reviewed and meta-analysed data from studies reporting spindle and slow wave activity in adults with and without insomnia disorder. We conducted systematic searches in PubMed, Embase, Scopus, and PsycInfo. Risk of bias was evaluated using the Cochrane Risk of Bias tool. Forty-three studies met our inclusion criteria, with thirteen studies of normal sleepers (N= 668) reporting sufficient data for random-effects meta-analyses. Compared with males, female normal sleepers had higher spindle density, sigma and delta power. Most studies recruited individuals with primary insomnia, and data pooling for insomnia and mixed groups was not possible due to insufficient statistical reporting. Moreover, group-by-sex interactions were limited, inconsistent, and varied across studies and sample characteristics. Further research is needed to explore sex-specific differences in sleep microarchitecture and their role in normal sleep and the manifestation of insomnia disorder.

neuroscience↗

bioRxiv2025

Sleep deprivation constrains dynamic configurations of integrated and segregated brain states impacting cognitive performance

The breakdown of cognitive control following sleep deprivation is widely recognised, but the physiological mechanisms and brain signatures that produce this vulnerability have not been resolved. Effective cognition relies on large-scale brain networks flexibly reconfiguring between states of integration and segregation. Here we combined functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and electrocardiography (ECG) collected during cognitive tasks under rested wakefulness, after sleep deprivation, and following a recovery nap to test the hypothesis that sleep deprivation constrains this dynamical repertoire and disrupts its physiological regulation. Using time-resolved functional connectivity and graph theory, we show that sleep deprivation increases the distribution of connections across networks, while reducing the temporal variability of between-network connectivity. Furthermore, dynamic fluctuations between integrated and segregated modes of network topology were dampened, with brain regions spending more time in intermediate configurations and showing greater instability of mode transitions. These alterations were tightly linked to behavioural impairment: participants who exhibited greater contraction toward intermediate topologies also showed poorer task accuracy and slower responses. Under well-rested conditions, thalamic activity peaked prior to transitions into integrated states and was suppressed during transitions into segregated states, consistent with a coordinating role in cortical dynamics. Sleep deprivation weakened and delayed this thalamic coupling. Finally, global and regional fMRI fluctuations were elevated after sleep loss, becoming decoupled from cardiac physiology while more strongly coupled to EEG delta power, further linking reduced arousal to constrained network flexibility. Together, these findings show that sleep deprivation narrows the brains dynamical repertoire, due to disrupted thalamic regulation and changes to the physiological integration with cortical networks.

neuroscience↗

bioRxiv2025

Development of an Intranasally- and Intramuscularly-Administrable Replicon Vaccine Efficacious Against H5N1 Influenza Virus

The risk of a respiratory viral pandemic is significant, including from the now widespread panzootic H5N1 influenza virus, highlighting the need for effective, stable, and inexpensive vaccine technologies that elicit strongly protective immunity. Intranasal vaccines can stimulate local immune responses at the site of natural respiratory viral infection, a key characteristic that can not only reduce morbidity and mortality caused by respiratory viruses but also potentially reduce viral transmissibility to limit outbreaks. Nucleic acid vaccines are now a valuable tool in pandemic responses, with high potency and rapid adaptability to target circulating or emerging viral strains; however, data are limited on which vaccine attributes are needed for efficient transmucosal delivery and immune stimulation following intranasal delivery. To demonstrate proof of concept, here we have developed a replicon vaccine expressing an H5 influenza antigen that uses a nanostructured lipid carrier (NLC) delivery system. A relationship was established between the molar ratio of positive charges on the NLC to the negative charges on the nucleic acid (N:P ratio) and the immunogenicity of the vaccine formulations, with higher N:P ratios resulting in an increase in vaccine immunogenicity. We demonstrated the ability of this replicon vaccine to be administered via intramuscular and intranasal routes with a singular vaccine formulation. The vaccine induced systemic immunity when dosed intramuscularly or intranasally in an immunocompetent mouse model, whereas intranasal dosing uniquely stimulated a strong mucosal immune response. Moreover, a mixed intramuscular/intranasal dosing strategy using this unified formulation stimulated a balanced systemic and mucosal immune response. Finally, we demonstrated the protective efficacy of this intranasally and intramuscularly/intranasally delivered H5 replicon-NLC vaccine against morbidity and mortality in a lethal H5N1 influenza challenge ferret model. This work establishes the replicon-NLC vaccine platform as a potential novel intranasal technology for rapid pandemic response.

immunology↗

bioRxiv2025

A bivalent self-amplifying RNA vaccine against yellow fever and Zika viruses

IntroductionYellow fever (YFV) and Zika (ZIKV) viruses cause significant morbidity and mortality, despite the existence of an approved YFV vaccine and the development of multiple ZIKV vaccine candidates to date. New technologies may improve access to vaccines against these pathogens. We previously described a nanostructured lipid carrier (NLC)-delivered self-amplifying RNA (saRNA) vaccine platform with excellent thermostability and immunogenicity, appropriate for prevention of tropical infectious diseases. MethodsYFV and ZIKV prM-E antigen-expressing saRNA constructs were created using a TC-83 strain Venezuelan equine encephalitis virus-based replicon and complexed with NLC by simple mixing. Monovalent and bivalent vaccine formulations were injected intramuscularly into C57BL/6 mice and Syrian golden hamsters, and the magnitude, durability, and protective efficacy of the resulting immune responses were then characterized. Results and discussionMonovalent vaccines established durable neutralizing antibody responses to their respective flaviviral targets, with little evidence of cross-neutralization. Both vaccines additionally elicited robust antigen-reactive CD4+ and CD8+ T cell populations. Notably, humoral responses to YFV saRNA-NLC vaccination were comparable to those in YF-17D-vaccinated animals. Bivalent formulations established humoral and cellular responses against both viral targets, commensurate to those established by monovalent vaccines, without evidence of saRNA interference or immune competition. Finally, both monovalent and bivalent vaccines completely protected mice and hamsters against lethal ZIKV and YFV challenge. We present a bivalent saRNA-NLC vaccine against YFV and ZIKV capable of inducing robust and efficacious neutralizing antibody and cellular immune responses against both viruses. These data support the development of other multivalent saRNA-based vaccines against infectious diseases.

immunology↗

bioRxiv2025

An intranasal, NLC-delivered self-amplifying RNA vaccine establishes protective immunity against pre-pandemic H5N1 and H7N9 influenza

Seasonal and pandemic influenzas are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. New RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent self-amplifying RNA (saRNA) vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/2013 H7N9. These saRNA vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The saRNA-NLC vaccines provided complete protection against morbidity and mortality in ferret challenge models, establishing this intranasally-administered saRNA-NLC vaccine platform as a potential pandemic response tool. ONE SENTENCE SUMMARYA self-amplifying RNA-NLC vaccine, delivered intranasally, induces robust mucosal immunity in mice and protects against H5N1 and H7N9 in ferrets

immunology↗

bioRxiv2024

NREM sleep brain networks modulate cognitive recovery from sleep deprivation

Decrease in cognitive performance after sleep deprivation and its recovery following sleep suggests the key role of sleep, especially non-rapid eye movement (NREM) sleep, in maintaining cognition. It remains unknown whether brain network reorganization in NREM sleep stages N2 and N3 can uniquely be mapped onto individual differences in cognitive performance after a recovery nap following sleep deprivation. Using resting state functional magnetic resonance imaging (fMRI), we quantified the integration and segregation of brain networks during N2 and N3 sleep in a 1-hour nap following 24-hour sleep deprivation, compared to well-rested wakefulness. Here, we introduce a new analytic framework called the hierarchical segregation index (HSI) to quantify network segregation across spatial scales, from whole-brain to the voxel level, by identifying spatio-temporally overlapping large-scale networks and the corresponding voxel-to-region hierarchy. We found that network segregation increased in the posterior cingulate cortex during both N2 and N3 sleep compared to wakefulness. In contrast, increased segregation in the visual cortex and decreased segregation in the posterior ventromedial prefrontal cortex during N2 returned to levels comparable to wakefulness during N3. More segregation during N3 sleep was associated with worse recovery of working memory, executive attention, and psychomotor vigilance after the nap. Sleep-related changes in network segregation emerged at different spatial scales, with regional- and voxel-level alterations being associated with different cognitive tasks. Finally, we demonstrated the sensitivity and reliability of voxel-level HSI to provide key insights into within-region variation, suggesting a mechanistic understanding of how NREM sleep replenishes cognition after sleep deprivation.

neuroscience↗

bioRxiv2023

Identification of B56alpha, B56gamma; and BAP1 as PRR14L binding partners

Truncating mutations have been previously described in PRR14L associated with acquired isodisomy of chromosome 22 in myeloid neoplasms. Very little is known about the function of PRR14L, but previous work showed localization to the midbody and binding to KIF4A. Here we confirm binding of PRR14L to PP2A components B56 and B56{gamma}. Similar to the related protein PRR14, PRR14L binds B56 via a conserved short linear motif within the C-terminal Tantalus domain. We also confirmed binding to BAP1, which forms the H2A deubiquinating complex PR-DUB with ASXL1, thereby linking PRR14L to a protein with established leukemogenic significance. AlphaFold data predicts PRR14L structure to be largely disordered, consistent with a possible role as a scaffold protein.

cancer biology↗

bioRxiv2022

An intranasal self-amplifying RNA SARS-CoV-2 vaccine produces durable respiratory and systemic immunity

While mRNA vaccines have been effective in combating SARS-CoV-2, waning of vaccine-induced antibody responses and lack of vaccine-induced respiratory tract immunity contribute to ongoing infection and transmission. In this work, we compare and contrast intranasal (i.n.) and intramuscular (i.m.) administration of a SARS-CoV-2 self-amplifying RNA (saRNA) vaccine delivered by a nanostructured lipid carrier (NLC). Both i.m. and i.n. vaccines induce potent systemic serum neutralizing antibodies, bone marrow-resident IgG-secreting cells, and splenic T cell responses. The i.n. vaccine additionally induces robust respiratory mucosal immune responses, including SARS-CoV-2-reactive lung-resident memory and lung-homing T cell populations. As a booster following previous i.m. vaccination, the i.n. vaccine also elicits the development of mucosal virus-specific T cells. Both the i.m. and i.n. administered vaccines durably protect hamsters from infection-associated morbidity upon viral challenge, significantly reducing viral loads and preventing challenged hamsters from transmitting virus to naive cagemates. This saRNA-NLC vaccines potent systemic immunogenicity, and additional mucosal immunogenicity when delivered i.n., may be key for combating SARS-CoV-2 and other respiratory pathogens.

immunology↗

bioRxiv2020

Altered functional integration of brain activity is a marker of impaired cognitive performance following sleep deprivation

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of sleep deprivation, and a recovery nap containing non-rapid eye movement (NREM) sleep. Overall, sleep deprivation was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within vs between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex toward a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamo-cortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bi-directional effect. These results demonstrate that intra- and inter-individual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep deprived state. Significance StatementSleep deprivation has significant negative consequences for cognitive function. Understanding how changes in brain activity underpin changes in cognition is important not only to discover why performance declines following extended periods of wakefulness, but also for answering the fundamental question of why we require regular and recurrent sleep for optimal performance. Finding neural correlates that predict performance following sleep deprivation also has the potential to understand which individuals are particularly vulnerable to sleep deprivation, and what aspects of brain function may protect them from these negative consequences on performance. Finally, understanding how perturbations to regular (well-rested) brain functioning affect cognitive performance, will provide important insight into how underlying principles of information processing in the brain may support cognition generally.

neuroscience↗

bioRxiv2020

Data-driven beamforming techniques to attenuate ballistocardiogram (BCG) artefacts in EEG-fMRI without detecting cardiac pulses in electrocardiography (ECG) recordings

Simultaneous recording of EEG and fMRI is a very promising non-invasive neuroimaging technique, providing a wide range of complementary information to characterize underlying mechanisms associated with brain functions. However, EEG data obtained from the simultaneous EEG-fMRI recordings are strongly influenced by MRI related artefacts, namely gradient artefacts (GA) and ballistocardiogram (BCG) artefacts. The GA is induced by temporally varying magnetic field gradients used for MR imaging, whereas the BCG artefacts are produced by cardiac pulse driven head motion in the strong magnetic field of the MRI scanner, so that this BCG artefact will be present when the subject is lying in the scanner, even when no fMRI data are acquired. When compared to corrections of the GA, the BCG artefact corrections are more challenging to remove due to its inherent variabilities and dynamic changes over time. Typically, the BCG artefacts obscure the EEG signals below 20Hz, and this remains problematic especially when the frequency of interest of EEG signals is below 20Hz, such as Alpha (8-13Hz) and Beta (13-30Hz) band EEG activity, or sleep spindle (11-16Hz) and slow-wave oscillations (<1 Hz) during sleep. The standard BCG artefact corrections, as for instance Average Artefact Subtraction method (AAS), require detecting cardiac pulse (R-peak) events from simultaneous electrocardiography (ECG) recordings. However, ECG signals in the MRI scanner are sometimes distorted and will become problematic for detecting reliable R-peaks. In this study, we focused on a beamforming technique, which is a spatial filtering technique to reject sources of signal variance that do not appear dipolar in the source space. This technique attenuates all unwanted source activities outside of a presumed region of interest without having to specify the location or the configuration of these underlying source signals. Specifically, in this study, we revisited the advantages of the beamforming technique to attenuate the BCG artefact in EEG-fMRI, and also to recover meaningful task-based induced neural signals during an attentional network task (ANT) which required participants to identify visual cues and respond as accurately and quickly as possible. We analysed EEG-fMRI data in 20 healthy participants when they were performing the ANT, and compared four different BCG correction approaches (non-BCG corrected, AAS BCG corrected, beamforming+AAS BCG corrected, beamforming BCG corrected). We demonstrated that beamforming BCG corrected data did not only significantly reduce the BCG artefacts, but also significantly recovered the expected task-based induced brain activity when compared to the standard AAS BCG corrections. Without detecting R-peak events from the ECG, this data-driven beamforming technique appears promising especially for longer data acquisition of sleep and resting EEG-fMRI. Our findings extend previous work regarding the recovery of meaningful EEG signals by an optimized suppression of MRI related artefacts. HighlightsO_LIBeamforming spatial filtering technique attenuates ballistocardiogram (BCG) artefacts in EEG-fMRI without detecting cardiac pulses in electrocardiography (ECG) recordings. C_LIO_LIBeamforming BCG denoising technique recovers expected task-based induced visual alpha and motor beta event-related desynchronization (ERD). C_LIO_LIBeamforming technique improves signal-noise ratios (SNR) of neural activities as compared to sensor level signals. C_LIO_LIData-driven beamforming technique appears promising for longer data acquisition of sleep and resting EEG-fMRI without relying on ECG signals. C_LI

neuroscience↗