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Biology subjects

Moghimi, S.

Publications and source records attributed to Moghimi, S..

6 recordsLinked to original sources

Neural categorisation of rhythm in human newborns

Music is ubiquitous across cultures, and humans engage in social interactions through music from early in life. A cornerstone of these interactions is rhythm categorisation, allowing the sheer diversity of rhythmic inputs to be mapped onto internal rhythm categories. The pervasiveness of certain rhythm categories across cultures suggests that rhythm categorisation may be partially rooted in neurobiological predispositions constraining the internal representations of rhythm. However, this view appears to conflict with the diversity of music practices across cultures, which points to a role of experience in rhythm categorisation. To assess the relative contributions of neurobiological predispositions and experience, we tested 0- to 3-day-old newborns, capitalising on their minimal postnatal experience with music. Using electroencephalography (EEG), we recorded, in newborns and adults, brain responses to drum sounds whose pattern of relative interval duration ranged from isochronous to long-short rhythms (1:1 - 2:1 interval ratio). Results indicate significant categorisation in newborns's neural responses, with a representational structure that correlate with those of adults, yet with a greater degree of differentiation across rhythms. These findings reveal neurobiological predispositions enabling rhythm categorisation to be present at birth and further shaped across the lifespan, highlighting the evolutionary roots and plasticity supporting this human cultural practice.

neuroscience↗

A touch that lingers: synchronized patting strengthens neural tracking of auditory rhythm in newborns

Rhythmic auditory stimulation in early life rarely occurs in isolation. Caregivers naturally combine singing and speech with rhythmic touch, rocking, and visual cues. Newborns are sensitive to auditory rhythm from birth, yet little is known about how temporally aligned information across sensory modalities shapes the neural encoding of auditory rhythmic structure. Here, we tested whether rhythmic touch can alter how the newborn brain tracks an ongoing auditory signal beyond the period of tactile stimulation. We recorded high-density electroencephalography from full-term newborns (N = 40), 1-3 days after birth, while they were exposed to recorded French lullabies presented either alone or accompanied by gentle patting synchronized with the metrically strong beat. Patting was delivered intermittently, allowing us to compare neural responses to lullabies across conditions, notably during periods without concurrent tactile stimulation. We quantified neural tracking of the lullabies using brain-stimulus coherence and temporal response function modeling. Newborns' neural activity synchronized with the rhythmic structure of the lullabies at frequencies corresponding to both the beat and the metrically accented strong beat. Critically, neural tracking was stronger when the lullabies had been accompanied by synchronized touch than when they were presented alone, and this enhancement persisted during subsequent periods in which no touch was delivered. Although rhythmic touch enhanced tracking in newborns with both weaker and stronger auditory-only tracking, there was a larger gain in those who initially showed weaker auditory tracking. Together, our findings reveal that the newborn brain exploits rhythmic touch to strengthen its encoding of auditory rhythm, and that this benefit outlasts the touch itself. This provides neural evidence that patting an infant in time with a song, a caregiving practice shared across cultures, does more than simply provide a tactile stimulation. It shapes how the newborn brain encodes the song's rhythm.

neuroscience↗

Effect of tempo on newborns' neural processing of auditory rhythm: Emergence of sensitivity to metrical structure

Rhythm perception ability underpins music and language processing, and its developmental origins trace back to the earliest periods of life. While most rhythm patterns contain a variety of inter-onset intervals, listeners typically extract a steady underlying beat periodicity, as well as beat grouping periodicities (groups of two or three beats will be at frequencies 1/2 or 1/3, respectively, of that of the primary beat), forming a metrical hierarchy. While the developing brain can track auditory rhythm before birth, a previous study found that neural sensitivity to faster beat-related periodicities emerges early in third trimester of gestation, whereas encoding of slower metrical structure periodicities only appears closer to term birth. However, as rhythm patterns were only presented at one tempo, neural sensitivity to metrical structure could not be disentangled from sensitivity to tempo during early development. Thus, here we presented auditory rhythmic sequences at two different tempi and used high-resolution electroencephalography to measure neural sensitivity to their encoding in full-term newborns and young adults. Adults demonstrated a similar sensitivity to metrical structure across tempi, with greatest response at the duple metrical frequency regardless of tempo. Newborn neural responses, by contrast, were tempo-dependent, displaying markedly different response patterns across beat and meter frequencies at the different tempi. Together, these results reveal that tempo and metrical structure interact in shaping how the neonatal brain encodes auditory rhythm, suggesting that early neural processing may be constrained in its ability to track slower periodicities, and highlighting a developmental shift in the relative contributions of tempo and metrical structure to rhythmic processing. Research HighlightsO_LIAdults show stable sensitivity to metrical structure across tempi, with peak responses at the duple level. C_LIO_LINewborns neural responses are tempo-dependent, showing distinct patterns across beat and metrical frequencies. C_LIO_LITempo and metrical structure jointly shape neural encoding of rhythm in the brain, revealing a developmental shift in their relative contributions. C_LI

neuroscience↗

Viral vector-driven trans-encapsidation of replicon RNAs as a rapid approach for the development of safe and economically attractive anti-enterovirus vaccines

Multiple enteroviruses are associated with life-threatening and economically important diseases, yet licensed vaccines are available only against poliovirus (worldwide) and enterovirus A71 (China). Both live attenuated and inactivated anti-poliovirus vaccines, while highly successful in preventing the disease, have important shortcomings. Live vaccine strains are inherently genetically unstable and can regain virulence, leading to re-emergence of paralytic disease. Inactivated vaccine does not induce the mucosal immunity sufficient to interrupt viral transmission and is made from virulent strains, presenting a biosafety challenge. Recent alternatives, such as new vaccine strains with improved genetic stability and VLP-based vaccines, only partially address these concerns. Here, we investigated another approach to the development of anti-enterovirus vaccines based on efficient trans-encaspidation of replication-competent enterovirus RNAs coding for only the non-structural proteins (replicons) by Newcastle Disease virus vectors expressing enterovirus capsid proteins. Thus, the encapsidated replicon production is driven by effectively replicating enterovirus RNA and the NDV vector. This system is easily scalable and can be adapted to any cell culture provided it can be infected by both the enterovirus and NDV. Unlike the empty VLPs, the encapsidated replicons recapitulate the stability and antigenicity of native enterovirus particles, but cannot propagate beyond the originally infected cell. The protective efficacy of an encapsidated poliovirus replicon immunization was similar to that of the licensed Sabin vaccine strain in a murine model. This approach can easily be adapted to any enterovirus, allowing the rapid development of new, affordable vaccine candidates.

microbiology↗

The Development of Resistance to an Inhibitor of a Cellular Protein Reveals a critical interaction between the enterovirus protein 2C and a small GTPase Arf1

The cellular protein GBF1, an activator of Arf GTPases (ArfGEF: Arf guanine nucleotide exchange factor), is recruited to the replication organelles of enteroviruses through interaction with the viral protein 3A, and its ArfGEF activity is required for viral replication. Here, we investigated the development of resistance of poliovirus, a prototype enterovirus, to increasing concentrations of brefeldin A (BFA), an inhibitor of GBF1. High level of resistance required a gradual accumulation of multiple mutations in the viral protein 2C. The 2C mutations conferred BFA resistance even in the context of a 3A mutant previously shown to be defective in the recruitment of GBF1 to replication organelles, and in cells depleted of GBF1, suggesting a GBF1-independent replication mechanism. Still, activated Arfs accumulated on the replication organelles of this mutant even in the presence of BFA, its replication was inhibited by a pan-ArfGEF inhibitor LM11, and the BFA-resistant phenotype was compromised in Arf1-knockout cells. Importantly, the mutations strongly increased the interaction of 2C with the activated form of Arf1. Analysis of other enteroviruses revealed a particularly strong interaction of 2C of human rhinovirus 1A with activated Arf1. Accordingly, the replication of this virus was significantly less sensitive to BFA than that of poliovirus. Thus, our data demonstrate that enterovirus 2Cs may behave like Arf1 effector proteins and that GBF1 but not Arf activation can be dispensable for enterovirus replication. These findings have important implications for the development of host-targeted anti-viral therapeutics.

microbiology↗

A Proximity Biotinylation Assay with a Host Protein Bait Reveals Multiple Factors Modulating Enterovirus Replication

As ultimate parasites, viruses depend on host factors for every step of their life cycle. On the other hand, cells evolved multiple mechanisms of detecting and interfering with viral replication. Yet, our understanding of the complex ensembles of pro- and anti-viral factors is very limited in virtually every virus-cell system. Here we investigated the proteins recruited to the replication organelles of poliovirus, a representative of the genus Enterovirus of the Picornaviridae family. We took advantage of a strict dependence of enterovirus replication on a host protein GBF1, and established a stable cell line expressing a truncated GBF1 fused to APEX2 peroxidase that effectively supported viral replication upon inhibition of the endogenous GBF1. This construct biotinylated multiple host and viral proteins on the replication organelles. Among the viral proteins, the polyprotein cleavage intermediates were overrepresented, arguing that the GBF1 environment is linked to the viral polyprotein processing. The proteomics characterization of biotinylated host proteins identified those previously associated with the enterovirus replication, as well as more than 200 new factors recruited to the replication organelles. RNA metabolism proteins many of which normally localize in the nucleus constituted the largest group, underscoring the massive release of nuclear factors in the cytoplasm of infected cells and their involvement in the viral replication. Analysis of several newly identified proteins revealed both pro- and anti-viral factors, including a novel component of infection-induced stress granules. Depletion of these proteins similarly affected the replication of diverse enteroviruses indicating broad conservation of the replication mechanisms. Thus, our data significantly increase the knowledge about the organization of enterovirus replication organelles and may provide new targets for anti-viral interventions.

microbiology↗