Biology subjects

Hidalgo, C.

Publications and source records attributed to Hidalgo, C..

4 recordsLinked to original sources

bioRxiv2025

Glutamate and early functional NMDA Receptors promote axonal elongation modulating both actin cytoskeleton dynamics and H2O2 production dependent on Rac1 activity

NMDA Receptors (NMDARs) have essential functions in the nervous system, including neuronal maturation, neurotransmission, synaptic plasticity, learning, and memory. Following membrane depolarization and glutamate activation, NMDARs mediate Ca2+ influx into neurons, activating Ca2+ signaling cascades with key roles in neuronal function. However, no studies have been reported on the roles of glutamate and NMDARs during early neuronal development. Although NMDARs classically act at the postsynaptic membrane, the present results indicate that neurons express functional NMDARs during polarity acquisition and localize them in the axonal compartment early in development; at this stage, cultured neurons spontaneously release glutamate. In addition, pharmacological and genetic experiments for NMDARs loss- and gain-of-function modulated neuronal polarization and axonal elongation antagonistically. An intracellular mechanism involving Ca2+ release from the endoplasmic reticulum, activation of the Rho GTPase Rac1, and actin cytoskeleton rearrangements at the axonal growth cone couples these morphological changes. Moreover, NMDAR activity regulates the physiological intracellular production of hydrogen peroxide (H2O2) via a Rac1/NADPH oxidase complex to support neuronal development. Optogenetic Rac1 activation simultaneously promoted lamellipodia formation and H2O2 production suggesting functional coupling between these seemingly unconnected events. The mechanism presented here involves a dual function for the Rac1 protein that depends on glutamate and NMDAR activity. Based on these findings, we suggest that early physiological and spontaneous glutamate release activates NMDARs to promote early neuronal development before synapse formation, indicating that glutamate is necessary for neurotransmission, early neuronal development, and axonal growth.

cell biology↗

bioRxiv2023

The genetic architecture of protein stability

There are more ways to synthesize a 100 amino acid protein (20100) than atoms in the universe. Only a miniscule fraction of such a vast sequence space can ever be experimentally or computationally surveyed. Deep neural networks are increasingly being used to navigate high-dimensional sequence spaces. However, these models are extremely complicated and provide little insight into the fundamental genetic architecture of proteins. Here, by experimentally exploring sequence spaces >1010, we show that the genetic architecture of at least some proteins is remarkably simple, allowing accurate genetic prediction in high-dimensional sequence spaces with fully interpretable biophysical models. These models capture the non-linear relationships between free energies and phenotypes but otherwise consist of additive free energy changes with a small contribution from pairwise energetic couplings. These energetic couplings are sparse and caused by structural contacts and backbone propagations. Our results suggest that artificial intelligence models may be vastly more complicated than the proteins that they are modeling and that protein genetics is actually both simple and intelligible.

biophysics↗

bioRxiv2023

Perception of Speech Turn Dynamics is preserved in Congenitally Deaf children with Cochlear Implants

Perceptual and speech production abilities of children with cochlear implants (CI) are usually tested by word and sentence repetition or naming tests. However, in their daily life they show very heterogeneous language skills. Here, we describe a way of increasing the ecological validity of language assessment, promoting the use of close to real-life listening situations. The setup consists in watching the audio-visual conversation of two individuals. Childrens gaze-switches from one speaker to the other serve as a proxy of their prediction abilities. Moreover, to better understand the basis and the impact of anticipatory behaviour, we also measured childrens ability to understand the dialogue content, their speech perception and memory skills as well as their rhythmic skills. Importantly, we compared children with CI performances with those of an age-matched group of children with NH. While children with CI revealed poorer speech perception and verbal working memory abilities than NH children, there was no difference in gaze anticipatory behaviour. Interestingly, in children with CI only, we found a significant correlation between dialogue comprehension, perceptive skills and gaze anticipatory behaviour. Our results confirm and extend to a conversational context previous findings showing an absence of predictive deficits in children with CI. The current design seems an interesting avenue to provide an accurate and objective estimate of anticipatory language behaviour in a rather ecological conversational context also with young children.

neuroscience↗

bioRxiv2018

New insights of the local immune response against both fertile and infertile hydatid cysts

BackgroundCystic echinococcosis is caused by the metacestode of the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, the metacestode grows as a unilocular cyst known as hydatid cyst. This cyst is comprised of two layers of parasite origin: germinal and laminated layers, and one of host origin: the adventitial layer, that encapsulates the parasite. This adventitial layer is composed of collagen fibers, epithelioid cells, eosinophils and lymphocytes. To establish itself inside the host, the germinal layer produces the laminated layer, and to continue its life cycle, generates protoscoleces. Some cysts are unable to produce protoscoleces, and are defined as infertile cysts. The molecular mechanisms involved in cyst fertility are not clear, however, the host immune response could play a crucial role.\n\nMethodology/Principal fidingsWe collected hydatid cysts from both liver and lungs of slaughtered cattle, and histological sections of fertile, infertile and small hydatid cysts were stained with haematoxylin-eosin. A common feature observed in infertile cysts was the disorganization of the laminated layer by the infiltration of host immune cells. These infiltrating cells eventually destroy parts of laminated layer. Immunohistochemical analysis of both parasite and host antigens, identify these cells as cattle macrophages and are present inside the cysts associated to germinal layer.\n\nConclusions/SignificanceThis is the first report that indicates to cell from immune system present in adventitial layer of infertile bovine hydatid cysts could disrupt the laminated layer, infiltrating and probably causing the infertility of cyst.\n\nAuthor SummaryCystic echinococcosis is caused by the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, mainly liver and lungs of herbivores such as cows and sheep as well as human beings, the parasite grows as a unilocular cyst known as hydatid cyst. These cysts develop in their inner chamber a structure known as protoscolex, when consumed by the definitive host (e.g. dogs), it grows into a worm that resides in the small intestine and produces eggs that contaminate the environment. In cattle, most hydatid cysts are unable to produce protoscoleces, and thus are termed infertile hydatid cysts. The molecular mechanisms that explain the causes of hydatid cyst infertility remain unknown. We routinely collected cattle hydatid cysts from both liver and lugs and processed them for histological analysis. We found that there is a subset of fertile hydatid cysts that have low protoscolex viability and high immune infiltration surrounding the cyst. All infertile cysts have high immune infiltration, and many of them show disruption of the laminated layer and immune cells of host origin inside the cyst. This is the first report that shows that the cyst can be infiltrated by the host immune system.

immunology↗