Biology subjects

Cortes, N.

Publications and source records attributed to Cortes, N..

6 recordsLinked to original sources

bioRxiv2026

From mice to humans: A multi-omic predictive framework for translational immunology

Mice are key preclinical animal models in vaccine and immunological research, yet their predictive value for human immunity remains contested. Here, we evaluated the translatability of murine models across inactivated and subunit vaccination (influenza, hepatitis B), acute infection (S. aureus, E. coli), and injury (burns and trauma), integrating transcriptomic profiles with sequence evolution, cis-regulatory architecture, and functional annotation. Functional modules were more conserved between species than individual orthologous genes. Translational accuracy depended on stimulus intensity, as infections and injuries engaged conserved signatures, while single-dose vaccination diverged. We then built multilayer models to predict human expression rank and direction of change, and to classify shared leading-edge genes. Adding evolutionary and regulatory layers improved these predictions. We provide a step-by-step R Markdown notebook to apply the models to user data. The study code and datasets are available at https://github.com/wapsyed/mousetohuman_multilayer

bioinformatics↗

bioRxiv2021

Corticothalamic Projections Gate Alpha Rhythms in the Pulvinar

Two types of corticothalamic (CT) terminals reach the pulvinar nucleus of the thalamus, and their distribution varies according to the hierarchical level of the cortical area they originate from. While type 2 terminals are more abundant at lower hierarchical levels, terminals from higher cortical areas mostly exhibit type 1 axons. Such terminals also evoke different excitatory postsynaptic potential dynamic profiles, presenting facilitation for type 1 and depression for type 2. As the pulvinar is involved in the oscillatory regulation between intercortical areas, fundamental questions about the role of these different terminal types in the neuronal communication throughout the cortical hierarchy are yielded. Our theoretical results support that the co-action of the two types of terminals produces different oscillatory rhythms in pulvinar neurons. More precisely, terminal types 1 and 2 produce alpha-band oscillations at a specific range of connectivity weights. Such oscillatory activity is generated by an unstable transition of the balanced state networks properties that it is found between the quiescent state and the stable asynchronous spike response state. While CT projections from areas 17 and 21a are arranged in the model as the empirical proportion of terminals types 1 and 2, the actions of these two cortical connections are antagonistic. As area 17 generates low-band oscillatory activity, cortical area 21a shifts pulvinar responses to stable asynchronous spiking activity and vice-versa when area 17 produces an asynchronous state. To further investigate such oscillatory effects through corticothalamo-cortical projections, the transthalamic pathway, we created a cortical feedforward network of two cortical areas, 17 and 21a, with CT connections to a pulvinar-like network. With this model, the transthalamic pathway propagates alpha waves from the pulvinar to area 21a. This oscillatory transfer ceases when reciprocal connections from area 21a reach the pulvinar, closing the cortico-thalamic loop. Taken together, results of our model suggest that the pulvnar shows a bi-stable spiking activity, oscillatory or regular asynchronous spiking, whose responses are gated by the different activation of cortico-pulvinar projections from lower to higher-order areas such as areas 17 and 21a.

neuroscience↗

bioRxiv2021

Light-mediated planar polarization of cone photoreceptorcilia contributes to visual acuity in mammals

The coordinated spatial arrangement of organelles within a tissue plane, generally referred to as Planar Cell Polarity (PCP), is critical for various processes ranging from organogenesis to sensory detection. Mechanistically, planar cell polarity is typically set-up by gradients of morphogens and their receptors, but whether non-molecular cues, akin to phototropism in plants, might play a part in setting up PCP in animals remains unknown. Here we report that the basal body of newborn photoreceptor cells in the mouse retina is centrally positioned, but then moves laterally around the first post-natal week, thereby generating cell-intrinsic asymmetry. During the second postnatal week, when eyes open, the basal bodies of cone photoreceptor cilia, but not rods, become coordinated across the tissue plane to face the center of the retina. Mechanistically, we show that light is required during a critical window in development, triggering a non-canonical cascade whereby cone transducin interacts with the G- protein signaling modulator protein 2 (GPSM2), which is in turn necessary for cone PCP. This work uncovers a non-canonical PCP pathway initiated by light.

cell biology↗

bioRxiv2021

Dynamical processing of orientation precision in the primary visual cortex

In our daily visual environment, the primary visual cortex (V1) processes distributions of oriented features as the basis of our visual computations. Changes of the global, median orientation of such inputs form the basis of our canonical knowledge about V1. However, another overlooked but defining characteristic of these sensory variables is their precision, which characterizes the level of variance in the input to V1. Such variability is an intrinsic part of natural images, yet it remains unclear if and how V1 accounts for the changes in orientation precision to achieve its robust orientation recognition performances. Here, we used naturalistic stimuli to characterize the response of V1 neurons to quantified variations of orientation precision. We found that about thirty percent of the recorded neurons showed a form of invariant responses to input precision. While feedforward mechanisms failed to account for the existence of these resilient neurons, neuronal competition within V1 explained the extent to which a neuron is invariant to precision. Using a decoding algorithm, we showed that the existence of such neurons in the population response of V1 can serve to encode both the orientation and its precision in the V1 population activity, which improves the robustness of the overall neural code. These precision-specific neurons operate with slow recurrent cortical dynamics, which supports the notion of predictive precisionweighted processes in V1.

neuroscience↗

bioRxiv2020

SARS-CoV-2 genomics beyond the consensus sequence: evidence for circulating mixed viral populations

Extensive global sampling and whole genome sequencing of the pandemic virus SARS-CoV-2 have enabled researchers to characterise its spread, and to identify mutations that may increase transmission or enable the virus to escape therapies or vaccines. Two important components of viral spread are how frequently variants arise within individuals, and how likely they are to be transmitted. Here, we characterise the within-host diversity of SARS-CoV-2, and the extent to which genetic diversity is transmitted, by quantifying variant frequencies in 1390 clinical samples from the UK, many from individuals in known epidemiological clusters. We show that SARS-CoV-2 infections are characterised by low levels of within-host diversity across the entire viral genome, with evidence of strong evolutionary constraint in Spike, a key target of vaccines and antibody-based therapies. Although within-host variants can be observed in multiple individuals in the same phylogenetic or epidemiological cluster, highly infectious individuals with high viral load carry only a limited repertoire of viral diversity. Most viral variants are either lost, or occasionally fixed, at the point of transmission, consistent with a narrow transmission bottleneck. These results suggest potential vaccine-escape mutations are likely to be rare in infectious individuals. Nonetheless, we identified Spike variants present in multiple individuals that may affect receptor binding or neutralisation by antibodies. Since the fitness advantage of escape mutations in highly-vaccinated populations is likely to be substantial, resulting in rapid spread if and when they do emerge, these findings underline the need for continued vigilance and monitoring.

genomics↗

bioRxiv2019

Spring-loaded inverted pendulum goes through two contraction-extension cycles during the single stance phase of walking

Despite the overall complexity of legged locomotion, the motion of the center of mass (COM) itself is relatively simple, and can be qualitatively described by simple mechanical models. The spring-loaded inverted pendulum (SLIP) is one such model, and describes both the COM motion and the ground reaction forces (GRFs) during running. Similarly, walking can be modeled by two SLIP-like legs (double SLIP or DSLIP). However, DSLIP has many limitations and is unlikely to serve as a quantitative model for walking. As a first step to obtaining a quantitative model for walking, we explored the ability of SLIP to model the single stance phase of walking across the entire range of walking speeds. We show that SLIP can be employed to quantitatively model the single stance phase except for two exceptions: first, it predicts larger horizontal GRFs than empirically observed. A new model - angular and radial spring-loaded inverted pendulum (ARSLIP) can overcome this deficit. Second, even the single stance phase has active elements, and therefore a quantitative model of locomotion would require active elements. Surprisingly, the leg spring undergoes a contraction-extension-contraction-extension (CECE) during walking; this cycling is partly responsible for the M-shaped GRFs produced during walking. The CECE cycle also lengthens the stance duration allowing the COM to travel passively for a longer time, and decreases the velocity redirection between the beginning and end of a step. A combination of ARSLIP along with active mechanisms during transition from one step to the next is necessary to describe walking.

bioengineering↗