Biology subjects

Santos, N.

Publications and source records attributed to Santos, N..

4 recordsLinked to original sources

bioRxiv2025

Homeostatic neuroimmune rhythms are linked to priming of olfactory bulb responses to an intranasal inflammatory challenge

The circadian and immune systems are important for tissue homeostasis, yet their integration in the brain remains understudied. The olfactory bulb, a brain region that exhibits robust circadian rhythms and is regularly exposed to inflammatory stimuli, provides an optimal locus to probe the interaction of these two systems. We found that the murine olfactory bulb rhythmically expresses immune-related transcripts, with antiviral transcripts peaking around dusk. This was accompanied by distinct transcriptional responses to intranasal poly(I:C) at dusk versus dawn, suggesting that time of day primes the olfactory bulbs response to inflammatory challenges. Using imaging flow cytometry, we detected two distinct populations of microglia, the resident macrophages of the brain, which differentially responded to intranasal poly(I:C) depending on time of day. This unveils a clear relationship between time of day and olfactory bulb immune processes, suggesting time is an important dimension to consider when studying the olfactory pathway into the brain.

immunology↗

bioRxiv2022

Superoxide Dismutase 1 translocates to the nucleus in spinal cord mixed cells from newborn rats

Superoxide dismutase 1 (SOD1) catalyzes the superoxide conversion to oxygen and hydrogen peroxide in general. SOD1 can translocate to the cell nucleus in response to oxidative stress in yeast and human fibroblasts. Here, we report the translocation of sod1 to the cell nucleus in primary co-cultures of neurons and astrocytes derived from newborn rats explants even in the absence of oxidative stress stimuli. The successful tissue explants from rats allowed simplistic and clean modeling of Amyotrophic lateral sclerosis (ALS)-simile tissue microenvironment. This mixed-cells-population was responsive to H2O2 (100 M) oxidative stress with a progressive dying process up to 6 h after stimuli. However, no differences in SOD1 nucleus translocation were observed in rat amyotrophic lateral sclerosis (ALS)-simile tissue microenvironment up to 6 hours under oxidative stress. These results altogether point to a robust cellular collaboration between neurons and astrocytes so that the tissue can equilibrate this SOD1 translocation during the oxidative stress response and in the early animal development.

biochemistry↗

bioRxiv2020

Evolution of lbx spinal cord expression and function

Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals. Amniotes have two Lbx genes, but only Lbx1 is expressed in spinal cord. In contrast, teleosts have three lbx genes and we show here that zebrafish lbx1a, lbx1b and lbx2 are expressed by distinct spinal cell types, and that lbx1a is expressed in dI4, dI5 and dI6 interneurons, as in amniotes. Our data examining lbx expression in Scyliorhinus canicula and Xenopus tropicalis suggest that the spinal interneuron expression of zebrafish lbx1a is ancestral, whereas lbx1b has acquired a new expression pattern in spinal cord progenitor cells. lbx2 spinal expression was probably acquired in the ray-finned lineage, as this gene is not expressed in the spinal cords of either amniotes or S. canicula. We also show that the spinal function of zebrafish lbx1a is conserved with mouse Lbx1. In zebrafish lbx1a mutants, there is a reduction in the number of inhibitory spinal interneurons and an increase in the number of excitatory spinal interneurons, similar to mouse Lbx1 mutants. Interestingly, the number of inhibitory spinal interneurons is also reduced in lbx1b mutants, although in this case the number of excitatory interneurons is not increased. lbx1a;lbx1b double mutants have a similar spinal interneuron phenotype to lbx1a single mutants. Taken together these data suggest that lbx1b and lbx1a may be required in succession for correct specification of dI4 and dI6 spinal interneurons, although only lbx1a is required for suppression of excitatory fates in these cells. Research Highlightslbx1 spinal expression and function is conserved in vertebrates. In contrast, zebrafish lbx1b and lbx2 have novel spinal expression patterns that probably evolved in the ray-finned vertebrate lineage (lbx2) or teleosts (lbx1b).

developmental biology↗

bioRxiv2020

CaMKII binds both substrates and effectors at the active site

Ca2+/calmodulin dependent protein kinase II (CaMKII) is a signaling protein required for long-term memory. Once activated by Ca2+/CaM, it sustains activity even after the Ca2+ dissipates. In addition to well-known autophosphorylation-mediated mechanism, interaction with specific binding partners also persistently activates CaMKII. A longstanding model invokes two distinct S- and T-sites. If an interactor binds at the T-site, it will preclude autoinhibition and allow substrates to be phosphorylated at the S-site. Here, we specifically test this model with X-ray crystallography, molecular dynamics simulations, and biochemistry. Our data are inconsistent with this model. Co-crystal structures of four different activators or substrates show that they all bind to a single continuous site across the kinase domain. We propose a mechanistic model that persistent CaMKII activity is facilitated by high affinity binding partners, which kinetically compete with autoinhibition by the regulatory segment to allow substrate phosphorylation.

biochemistry↗