Biology subjects

Nasser, H.

Publications and source records attributed to Nasser, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Characterising sleep spindle emergence in infancy: Effects of prematurity and early locomotor intervention

Study objectives: Sleep spindles are thalamocortical oscillations evolving during early brain maturation. In adults, they support memory consolidation and are organised into rhythmic "trains" thought to support memory reactivation. How this temporal organisation emerges in infancy, and whether prematurity or early sensorimotor experience shapes it, remains unclear. This study characterised infant spindles and investigated how prematurity and early locomotor training affect their temporal and spatial organisation, providing insight into early brain maturation. Methods: Daytime high-density EEG sleep recordings were analysed in 50 infants born full-term (n=12) or very preterm (n=38, including 12 who received locomotor training) at 2 months corrected age. Spindle temporal organisation was analysed using a two-step Morlet wavelet transform to quantify slow modulations of spindle-band power (11-16Hz). Time-frequency decomposition around spindle onset was used to identify significant spindle-band scalp-wide activity, and topographical maps were statistically compared between groups. Results: All groups showed rhythmic spindle organisation, three times slower than in adults, with no group differences. Untrained preterm infants showed a more diffuse spindle-band activity than the distinct frontal and central clusters observed in full-term infants. Trained preterm infants exhibited a spatial distribution closely resembling that of full-term infants, although their frontal spindle density was lower than in both other groups. Conclusions: Spindle rhythmic organisation emerged early in infancy and remained unaffected by prematurity or locomotor training. Prematurity was associated with more diffuse spindle-band activity, suggesting reduced cortical specialisation, whereas trained preterm infants showed a spatial distribution resembling that of full-term infants, suggesting that early locomotor experience may influence thalamocortical organisation.

neuroscience↗

bioRxiv2026

Maternal preconception calorie restriction reprograms coping strategies, socio-sexual behaviour, and endocrine function in adult rat offspring

Maternal nutrition before conception is recognised as a determinant of offspring development; however, the behavioural and neuroendocrine consequences of preconception calorie restriction (CR) remain poorly understood. This study isolated the preconception window to examine how different CR patterns, stable (25% reduction; CR-25%), unpredictable deprivation (CR-A), and variable (25-75% fluctuation; CR-V), affect adult offspring outcomes. Male and female progeny from preconception CR female Wistar rats were assessed across domains sensitive to early-life programming, including anxiety- and depression-like behaviour, coping style, socio-sexual behaviour, and hypothalamic-pituitary-gonadal (HPG) axis activity. Preconception CR produced sex- and diet-specific effects. Females exhibited transient reductions in exploratory behaviour and more active coping styles, particularly CR-25% and CR-V animals. In males, all CR regimens enhanced copulatory behaviour and reduced aggression toward females. Endocrine profiling revealed divergent HPG responses: CR-A males showed elevated basal faecal testosterone metabolites (fTM) but reduced basal serum testosterone, whereas CR-V males exhibited blunted androgenic reactivity post-social provocation. These findings demonstrate that maternal preconception CR can program male offspring toward a prosocial, sexually motivated phenotype and female offspring toward an enhanced coping style, underscoring this period as a sensitive window for shaping behavioural and endocrine trajectories.

animal behavior and cognition↗

bioRxiv2025

Characterization of aperiodic and theta activity in preterm infants using EEG: Insights into cerebral maturation and inter-individual variability

Disrupting critical processes of brain development, preterm birth interferes with the maturation of brain networks and functional activity, including theta oscillations that are thought to play a key role in early network formation. Traditional EEG spectral analyses have indicated marked development of theta power in early infancy, but these approaches mix oscillatory and non-oscillatory activity, limiting insights into the mechanisms underlying the neural changes. Using spectral parameterization, we aimed to evaluate developmental changes in aperiodic activity and periodic theta power in infants born very preterm compared to full-terms, and to further explore whether clinical factors and brain microstructure could explain the inter-individual variability within preterms. High-density EEG was acquired during active/REM sleep at term-equivalent age (TEA) and 2 months corrected age (2mCA) in 41 very preterm infants (born <32 weeks gestational age [GA]; mean {+/-} standard deviation: 26.9{+/-}1.7 weeks) and 13 full-term controls (born [≥]37 weeks GA; 40.1{+/-}1 weeks). Spectral parameterization was used to extract aperiodic components (offset, exponent) and periodic theta power globally and across spatial clusters of electrodes (anterior, central, posterior). From TEA to 2mCA, offset, exponent, and theta power increased with no differences between preterm and full-term infants. At TEA, metrics of aperiodic activity were stronger in anterior compared with posterior areas, but this regional landscape shifted by 2mCA with pronounced increases in aperiodic offset and exponent in posterior areas from TEA to 2mCA. Within preterms, inter-individual variability in aperiodic and periodic activity at TEA was partly explained by clinical risk factors: male sex, lower gestational-age at birth, small weight at birth, and invasive ventilation were linked to alterations of aperiodic offset, exponent and theta power. Additionally, higher theta power at TEA correlated with lower cortical fractional anisotropy assessed with diffusion MRI at the same age, consistently with more advanced maturation of the brain. Collectively, these findings indicate that EEG spectral parameterization combined with spatial analysis provides a sensitive framework for characterizing the postnatal maturation of brain activity in infants, as well as early vulnerabilities associated with prematurity and perinatal adversity.

neuroscience↗

bioRxiv2025

A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity

The global circulation of SARS-CoV-2 in human populations has driven the emergence of Omicron subvariants, which have become highly diversified through recombination. In late 2024, SARS-CoV-2 Omicron XEC variant emerged from the recombination of two JN.1 progeny, KS.1.1 and KP.3.3, and became predominant worldwide. Here, we investigated virological features of the XEC variant. Epidemic dynamics modeling suggested that spike substitutions in XEC mainly contribute to its increased viral fitness. Additionally, four licensed antivirals were effective against XEC. Although the fusogenicity of XEC spike is comparable to that of the JN.1 spike, the intrinsic pathogenicity of XEC in hamsters was significantly higher than that of JN.1. Notably, we found that the nucleocapsid R204P mutation of XEC enhanced inflammation through NF-{kappa}B activation. Recent studies suggest that the evolutionary potential of spike protein is reaching its limit. Indeed, our findings highlight the critical role of non-spike mutations in the future evolution of SARS-CoV-2.

microbiology↗

bioRxiv2024

Novel Exploration Growth Quantifies Anxiety-like Behaviour in the Elevated Plus Maze

The elevated plus maze is intended to provoke anxiety-like behaviour, which is primarily measured by the degree to which the rodent explores or avoids the risker, unenclosed arms. Measures such as arm entries and total time spent within the arm are conventionally used, but their analysis often produces inconsistent inferences about the level of anxiety-like behaviour being observed. This inconsistency occurs because the measures do not correlate with one another, raising the question of how validly they capture both the exploratory and avoidance motivations that typify anxiety-like behaviour. Given this inconsistency, we propose a new measure, novel exploration growth, that captures avoidance and exploratory behaviours within the maze. The growth of novel exploration tracks the first visit to discrete areas of the maze over time. The absolute amount of novel exploration, combined with the phasic nature of the exploration, reveals behavioural phenotypes with both avoidance and exploration quantified in a single time series. By addressing both motivations evoked by the maze through a single coherent measure, we provide a superior estimation of anxiety-like behaviour and resolve inconsistencies that arise when applying conventional measures alone.

animal behavior and cognition↗

bioRxiv2024

Temporal dynamics and maturation of resting-state activity in preterm infants

By interfering with the normal sequence of mechanisms serving the brain maturation, premature birth and related stress can alter perinatal experiences, with potential long-term consequences on a childs neurodevelopment. The early characterization of brain functioning and maturational changes is thus of critical interest in premature infants who are at high risk of atypical outcomes and could benefit from early diagnosis and dedicated interventions. Using high-density electroencephalography (HD-EEG), we recorded brain activity in extreme and very preterm infants at the equivalent age of pregnancy term (n=43), and longitudinally 2-months later (n=33), compared with full-term born infants (n=14). We characterized the maturation of brain activity by using a dedicated microstate analysis to quantify the spatio-temporal dynamics of the spontaneous transient network activity while controlling for vigilance states. The comparison of premature and full-term infants first showed slower dynamics as well as altered spatio-temporal properties of brain activity in preterm infants. Maturation of functional networks between term-equivalent age and 2 months later in preterms was linked to the emergence of faster dynamics, manifested in part by shorter duration of microstates, as well as an evolution in the spatial organization of the dominant microstates. The inter-individual differences in the temporal dynamics of brain activity at term-equivalent age were further impacted by sex (with slower microstate dynamics in boys) and by gestational age at birth for some microstate dynamics but not by other considered risk factors. This study highlights the potential of the microstate approach to reveal maturational properties of the emerging brain network activity in premature infants.

neuroscience↗

bioRxiv2023

Virological characteristics of the SARS-CoV-2 BA.2.86 variant

In late 2023, a lineage of SARS-CoV-2 emerged and was named the BA.2.86 variant. BA.2.86 is phylogenetically distinct from other Omicron sublineages identified so far, displaying an accumulation of over 30 amino acid mutations in its spike protein. Here, we performed multiscale investigations to reveal the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Experimental studies showed that four clinically-available antivirals were effective against BA.2.86. Although the fusogenicity of BA.2.86 spike is similar to that of the parental BA.2 spike, the intrinsic pathogenicity of BA.2.86 in hamsters was significantly lower than that of BA.2. Since the growth kinetics of BA.2.86 is significantly lower than that of BA.2 in both in vitro cell cultures and in vivo, it is suggested that the attenuated pathogenicity of BA.2.86 is due to its decreased replication capacity.

microbiology↗

bioRxiv2023

Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant

In middle-late 2023, a sublineage of SARS-CoV-2 Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. Here, we performed multiscale investigations to reveal virological features of newly emerging EG.5.1 variant. Our phylogenetic-epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T, are critical to the increased viral fitness. Experimental investigations addressing the growth kinetics, sensitivity to clinically available antivirals, fusogenicity and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 is comparable to that of XBB.1.5. However, the cryo-electron microscopy reveals the structural difference between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible at least in our experimental setup. Our multiscale investigations provide the knowledge for understanding of the evolution trait of newly emerging pathogenic viruses in the human population.

microbiology↗

bioRxiv2023

Virological characteristics correlating with SARS-CoV-2 spike protein fusogenicity

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike (S) protein is essential in mediating membrane fusion of the virus with the target cells. Several reports demonstrated that SARS-CoV-2 S protein fusogenicity is reportedly closely associated with the intrinsic pathogenicity of the virus determined using hamster models. However, the association between S protein fusogenicity and other virological parameters remains elusive. In this study, we investigated the virological parameters of eleven previous variants of concern (VOCs) and variants of interest (VOIs) correlating with S protein fusogenicity. S protein fusogenicity was found to be strongly correlated with S1/S2 cleavage efficiency and plaque size formed by clinical isolates. However, S protein fusogenicity was less associated with pseudoviral infectivity, pseudovirus entry efficiency, and viral replication kinetics. Taken together, our results suggest that S1/S2 cleavage efficiency and plaque size could be potential indicators to predict the intrinsic pathogenicity of newly emerged SARS-CoV-2 variants.

microbiology↗

bioRxiv2023

Virological characteristics of the SARS-CoV-2 XBB.1.5 variant

Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the F486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determined the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. The intrinsic pathogenicity of XBB.1.5 in hamsters is lower than that of XBB.1. Importantly, we found that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC expression. In vivo experiments using recombinant viruses revealed that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, these data suggest that the mutations in ORF8 and S could enhance spreading of XBB.1.5 in humans.

microbiology↗

bioRxiv2023

APOBEC3 degradation is the primary function of HIV-1 Vif for virus replication in the myeloid cell line THP-1

HIV-1 must overcome multiple innate antiviral mechanisms to replicate in CD4+ T lymphocytes and macrophages. Previous studies have demonstrated that the APOBEC3 (A3) family of proteins (at least A3D, A3F, A3G, and stable A3H haplotypes) contribute to HIV-1 restriction in CD4+ T lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this antiviral activity by degrading A3 enzymes allowing HIV-1 replication in infected cells. In addition to A3 proteins, Vif also targets other cellular proteins in CD4+ T lymphocytes, including PPP2R5 proteins. However, whether Vif primarily degrades only A3 proteins or has additional essential targets during viral replication is currently unknown. Herein, we describe the development and characterization of A3F-, A3F/A3G-, and A3A-to-A3G-null THP-1 cells. In comparison to Vif-proficient HIV-1, Vif-deficient viruses have substantially reduced infectivity in parental and A3F-null THP-1 cells, and a more modest decrease in infectivity in A3F/A3G-null cells. Remarkably, disruption of A3A-A3G protein expression completely restores the infectivity of Vif-deficient viruses in THP-1 cells. These results indicate that the primary function of Vif during HIV-1 replication in THP-1 cells is the targeting and degradation of A3 enzymes. ImportanceHIV-1 Vif neutralizes the HIV-1 restriction activity of A3 proteins. However, it is currently unclear whether Vif has additional essential cellular targets. To address this question, we disrupted A3A to A3G genes in the THP-1 myeloid cell line using CRISPR and compared the infectivity of wildtype HIV-1 and Vif mutants with the selective A3 neutralization activities. Our results demonstrate that the infectivity of Vif-deficient HIV-1 and the other Vif mutants is fully restored by ablating the expression of cellular A3A to A3G proteins. These results indicate that A3 proteins are the only essential target of Vif that is required for HIV-1 replication in THP-1 cells.

microbiology↗

bioRxiv2022

Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

In late 2022, the SARS-CoV-2 Omicron subvariants have highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged by recombination of two co-circulating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022 around India. In vitro experiments revealed that XBB is the most profoundly resistant variant to BA.2/5 breakthrough infection sera ever and is more fusogenic than BA.2.75. Notably, the recombination breakpoint is located in the receptor-binding domain of spike, and each region of recombined spike conferred immune evasion and augmented fusogenicity to the XBB spike. Finally, the intrinsic pathogenicity of XBB in hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provided evidence suggesting that XBB is the first documented SARS-CoV-2 variant increasing its fitness through recombination rather than single mutations.

microbiology↗

bioRxiv2022

Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

In late 2022, although the SARS-CoV-2 Omicron subvariants have highly diversified, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein. Here, we illuminated the evolutionary rules underlying the convergent evolution of Omicron subvariants and the properties of one of the latest lineages of concern, BQ.1.1. Our phylogenetic and epidemic dynamics analyses suggest that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. Particularly, BQ.1.1, which harbors all five convergent substitutions, shows the highest fitness among the viruses investigated. Neutralization assays show that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. The BQ.1.1 spike exhibits enhanced binding affinity to human ACE2 receptor and greater fusogenicity than the BA.5 spike. However, the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5. Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants.

microbiology↗

bioRxiv2022

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75

SARS-CoV-2 Omicron BA.2.75 emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically different from BA.5, the currently predominant BA.2 descendant. Here, we showed that the effective reproduction number of BA.2.75 is greater than that of BA.5. While the sensitivity of BA.2.75 to vaccination- and BA.1/2 breakthrough infection-induced humoral immunity was comparable to that of BA.2, the immunogenicity of BA.2.75 was different from that of BA.2 and BA.5. Three clinically-available antiviral drugs were effective against BA.2.75. BA.2.75 spike exhibited a profound higher affinity to human ACE2 than BA.2 and BA.5 spikes. The fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were comparable to those of BA.5 but were greater than those of BA.2. Our multiscale investigations suggest that BA.2.75 acquired virological properties independently of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.

microbiology↗

bioRxiv2022

Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2. HighlightsO_LISpike L452R/Q/M mutations increase the effective reproduction number of BA.2 C_LIO_LIBA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infections C_LIO_LIBA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2 C_LIO_LIBA.4/5 is more pathogenic than BA.2 in hamsters C_LI

microbiology↗

bioRxiv2022

SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant

Recent studies have revealed the unique virological characteristics of Omicron, the newest SARS-CoV-2 variant of concern, such as pronounced resistance to vaccine-induced neutralizing antibodies, less efficient cleavage of the spike protein, and poor fusogenicity. However, it remains unclear which mutation(s) in the spike protein determine the virological characteristics of Omicron. Here, we show that the representative characteristics of the Omicron spike are determined by its receptor-binding domain. Interestingly, the molecular phylogenetic analysis revealed that the acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidate that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue in another protomer in the spike trimer, which confers the attenuated spike cleavage efficiency and fusogenicity of Omicron. Our data shed light on the evolutionary events underlying Omicron emergence at the molecular level. HighlightsO_LIOmicron spike receptor binding domain determines virological characteristics C_LIO_LISpike S375F mutation results in the poor spike cleavage and fusogenicity in Omicron C_LIO_LIAcquisition of the spike S375F mutation triggered the explosive spread of Omicron C_LIO_LIF375-H505-mediated {pi}-{pi} interaction in the spike determines the phenotype of Omicron C_LI

microbiology↗

bioRxiv2022

Virological characteristics of SARS-CoV-2 BA.2 variant

Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron lineage, BA.1 (ref1, 2), another Omicron lineage, BA.2, has initiated outcompeting BA.1. Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1. Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.

microbiology↗

bioRxiv2021

SARS-CoV-2 spike P681R mutation enhances and accelerates viral fusion

During the current SARS-CoV-2 pandemic, a variety of mutations have been accumulated in the viral genome, and currently, four variants of concerns (VOCs) are considered as the hazardous SARS-CoV-2 variants to the human society1. The newly emerging VOC, the B.1.617.2/Delta variant, closely associates with a huge COVID-19 surge in India in Spring 20212. However, its virological property remains unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic, and notably, more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates the spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than the parental virus. Our data suggest that the P681R mutation is a hallmark that characterizes the virological phenotype of the B.1.617.2/Delta variant and is closely associated with enhanced pathogenicity.

microbiology↗