Biology subjects

Santos, S.

Publications and source records attributed to Santos, S..

9 recordsLinked to original sources

bioRxiv2024

Practice beyond performance stabilization increases the use of online adjustments to unpredictable perturbations in an interceptive task

In recent decades, research has focused on motor adjustments in interception tasks within predictable environments. However, emerging studies suggest that continued practice beyond performance stabilization enhances the ability to adapt to unpredictable events. The objective of this study was to investigate the effects of practicing until performance stabilization versus extended practice through superstabilization on the ability to adjust to unpredictable perturbations in intercepting a moving target. We hypothesized superstabilization would better facilitate motor adjustments in response to unpredictable perturbations. Forty participants engaged in an interception task until they achieved either performance stabilization or superstabilization. Subsequently, both stabilization and superstabilization groups were tested in an unpredictable environment, where, in certain trials, the targets velocity unexpectedly changed after the onset of the movement. The findings revealed that the superstabilization group made more adjustments in response to these perturbations than the stabilization group, attributed to their developed capacity to use online feedback as a control mechanism more efficiently. In contrast, the practice until performance stabilization did not foster this adaptive mechanism. These results support the notion that learning is a dynamic process that extends beyond the point of performance stabilization, emphasizing the benefits of continued practice for mastering complex motor tasks in variable contexts.

neuroscience↗

bioRxiv2024

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Small, gaseous molecules, known as gasotransmitters (NO, CO, H2S), are produced endogenously in mammalian cells and serve important biological roles. Hydrogen cyanide, traditionally considered a cytotoxic molecule in mammals, serves as an endogenous mediator in several plants and bacterial species. Here we show that low concentrations of cyanide are generated endogenously in mouse liver and human hepatocytes. Cyanide production is stimulated by glycine, occurs at the low pH of lysosomes and requires peroxidase activity. Cyanide, in turn, is detectable in several cellular compartments. Cyanide is also detectable basally in the blood of mice; its levels increase after treatment of the animals with glycine. Rhodanese activity regulates endogenous cyanide levels. Cyanide, when generated endogenously at an optimal level, exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism and cell proliferation. Dysregulation of endogenous cyanide, either below or above optimal levels, impairs cellular bioenergetics. The regulatory effects of cyanide are in part mediated by posttranslational modification of cysteine residues via protein cyanylation; cyanylated protein residues can be detected basally, and increase after treatment with glycine. Controlled low-dose cyanide supplementation exhibits cytoprotective effects, as demonstrated in hypoxia and reoxygenation models in vitro and in vivo. However, pathologically elevated cyanide production, as demonstrated in nonketotic hyperglycinemia - an autosomal recessive disease of glycine metabolism - is deleterious to the cells.

biochemistry↗

bioRxiv2022

BDNF and TRiC-inspired Reagents Rescue Cortical Synaptic Deficits in a Mouse Model of Huntington's Disease

Huntingtons disease (HD) results from a CAG repeat expansion in the gene for Huntington (HTT) resulting in expansion of the polyglutamine (Q) tract in the mutant protein (mHTT). Synaptic changes are early manifestations of neuronal dysfunction in HD. However, the mechanism(s) by which mHTT impacts synapse formation and function is not well defined. Herein we explored HD pathogenesis in the BACHD and the {Delta}N17-BACHD mouse models of HD by examining cortical synapse formation and function in primary cultures maintained for up to 35 days (DIV35). We identified synapses by immunostaining with antibodies against pre-synaptic (Synapsin 1) and a post-synaptic (PSD95) marker. Consistent with earlier studies, cortical neurons from both WT and the HD models began to form synapses at DIV14; at this age there were no genotypic differences in synapse numbers. However, from DIV21 through DIV35 BACHD neurons showed progressively smaller numbers of synapses relative to WT neurons. Remarkably, BACHD synaptic deficits were completely rescued by treating cultures with BDNF. Building on earlier studies using reagents inspired by the chaperonin TRiC, we found that addition of the recombinant apical domain of CCT1 partially rescued synapse number. Unexpectedly, unlike BACHD cultures, synapses in {Delta}N17-BACHD cultures showed a progressive increase in number as compared to WT neurons, thus distinguishing synaptic changes in these HD models. Using multielectrode arrays, we discovered age-related functional deficits in BACHD cortical cultures with significant differences present by DIV28. As for synapse number, BDNF treatment prevented most synaptic deficits, including mean firing rate, spikes per burst, inter-burst interval, and synchrony. The apical domain of CCT1 showed similar, albeit less potent effects. These data are evidence that deficits in HD synapse number and function can be replicated in vitro and that treatment with either BDNF or a TRiC-inspired reagent can prevent them. Our findings support the use of cellular models to further explicate HD pathogenesis and its treatments.

neuroscience↗

bioRxiv2021

Carnivores cross irrigation canals more often through overpasses than through culverts

As rainfall becomes scarcer or more erratic, we rely more on irrigation systems for water provision. Impacts of irrigation canals such as the barrier effect on wildlife movements are poorly documented. Although canal culverts and overpasses can be used by wildlife, little is known about their crossing patterns to guide barrier effect mitigation efforts. Over 7 years, we recorded medium-sized carnivore crossings by video-surveillance through 30 culverts and 28 overpasses in a large irrigation project in south-central Portugal. We examined the influence of the structures features and landscape context on the likelihood of canal crossing. Culvert crossings were positively influenced by the proportion of nearby montado, a high nature value farming system. Overpass crossings were more likely in areas away from paved roads and with more nearby wetlands. Overpasses increased the crossing rates by about 11 % relative to culverts and both were crossed more often in landscapes with evenly distributed land uses. In the project area, 20% of the montado has recently transitioned to irrigated agriculture, and wetlands have increased by 43%. It is therefore plausible that the increase in the crossing rate of overpasses relative to culverts will be accentuated. Our study produced the first evidence of a contrast in crossing rates among irrigation canal crossing structures. We have shown that the landscape can be a driver of animal crossings but irrigation projects can in turn be transformative of the landscape. Broadly, the fact that the deployment of irrigation canals may favor some land uses over others creates a conundrum that needs careful consideration when planning barrier effect mitigation interventions.

ecology↗

bioRxiv2020

A FGF2-mediated incoherent feedforward loop inducesErk inhibition and promotes naive pluripotency

Naive pluripotency is a transient state during mammalian development that can be recapitulated indefinitely in vitro by inhibition of the mitogen-activated protein kinase (MAPK/Erk) signalling and activation of STAT and Wnt pathways. How Erk is inhibited in vivo to promote naive pluripotency remains largely unknown. By combining live cell imaging and quantitative proteomics we found that FGF2, a known Erk activator and pro-differentiation cue, induces instead long-term Erk inhibition in both ES cells and mouse embryos. We show that Erk inhibition results from a FGF2-induced incoherent feedforward loop. Importantly, we see that FGF2 induces up-regulation of naive pluripotency factors, down-regulation of DNA methylation by suppression of de novo DNA methylases thereby helping maintain naive pluripotency. We show that FGF2 is expressed maternally and propose that integration of signals from the embryos niche may contribute to the generation of embryonic lineages with the right cell proportions. We suggest that feedforward regulation may play a role driving transient, reversible developmental transitions.

developmental biology↗

bioRxiv2020

Genomic approach for conservation and the sustainable management of endangered species of the Amazon

A broad panel of potentially amplifiable microsatellite loci and a multiplex system were developed for the Amazonian symbol fish species Arapaima gigas, which is currently in high danger of extinction due to the disorderly fishing exploitation. Several factors have contributed to the increase of this threat, among which we highlight the lack of genetic information about the structure and taxonomic status of the species, as well as the lack of accurate tools for evaluation of the effectivity of current management programs. Based on Arapaima gigas whole genome, available at the NCBI database (ID: 12404), a total of 95,098 unique perfect microsatellites were identified, including their proposed primers. From this panel, a multiplex system containing 12 tetranucleotide microsatellite markers was validated. These tools are valuable for research in as many areas as bioinformatics, ecology, genetics, evolution and comparative studies, since they are able to provide more accurate information for fishing management, conservation of wild populations and genetic management of aquaculture.

genomics↗

bioRxiv2020

MAPS integrates overlooked regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT

A full understanding of the contribution of small RNAs (sRNAs) to bacterial virulence demands knowledge of their target suites under infection-relevant conditions. Here, we take an integrative approach to capturing targets of the Hfq-associated sRNA PinT, a known post-transcriptional timer of the two major virulence programs of Salmonella enterica. Using MS2 affinity purification and RNA-sequencing (MAPS), we identify PinT ligands in bacteria under in-vitro conditions mimicking specific stages of the infection cycle, and in bacteria growing inside macrophages. This reveals PinT-mediated translational inhibition of the secreted effector kinase SteC, which had gone unnoticed in previous target searches. Using genetic, biochemical, and microscopic assays, we provide evidence for PinT-mediated repression of steC mRNA, eventually preventing actin rearrangements in infected host cells. Our findings support the role of PinT as a central post-transcriptional regulator in Salmonella virulence and illustrate the need for complementary methods to reveal the full target suites of sRNAs.

microbiology↗

bioRxiv2019

The apparent requirement for protein synthesis during G2 phase is due to checkpoint activation

Protein synthesis inhibitors (e.g. cycloheximide) prevent cells from entering mitosis, suggesting that cell cycle progression requires protein synthesis until right before mitotic entry. However, cycloheximide is also known to activate p38 MAPK, which can delay mitotic entry through a G2/M checkpoint. Here we asked whether checkpoint activation or a requirement for protein synthesis is responsible for the cycloheximide effect. We found that p38 inhibitors prevent cycloheximide-treated cells from arresting in G2 phase, and that G2 duration is normal in about half of these cells. The Wee1/Myt1 inhibitor PD0166285 also prevents cycloheximide from blocking mitotic entry, raising the possibility that Wee1 and/or Myt1 mediate the cycloheximide-induced G2 arrest. Thus, the ultimate trigger for mitotic entry appears not to be the continued synthesis of mitotic cyclins or other proteins. However, M-phase progression was delayed in cycloheximide-plus-kinase-inhibitor-treated cells, emphasizing the different requirements of protein synthesis for timely entry and completion of mitosis. Impact statementCycloheximide arrests cells in G2 phase due to activation of p38 MAPK, not inhibition of protein synthesis, arguing that protein synthesis in G2 phase is not required for mitotic entry.

cell biology↗

bioRxiv2017

chewBBACA: A complete suite for gene-by-gene schema creation and strain identification

Gene-by-gene approaches are becoming increasingly popular in bacterial genomic epidemiology and outbreak detection. However, there is a lack of open-source scalable software for schema definition and allele calling for these methodologies. The chewBBACA suite was designed to assist users in the creation and evaluation of novel whole-genome or core-genome gene-by-gene typing schemas and subsequent allele calling in bacterial strains of interest. The software can run in a laptop or in high performance clusters making it useful for both small laboratories and large reference centers. ChewBBACA is available at https://github.com/B-UMMI/chewBBACA or as a docker image at https://hub.docker.com/r/ummidock/chewbbaca/.\n\nDATA SUMMARYO_LIAssembled genomes used for the tutorial were downloaded from NCBI in August 2016 by selecting those submitted as Streptococcus agalactiae taxon or sub-taxa. All the assemblies have been deposited as a zip file in FigShare (https://figshare.com/s/9cbe1d422805db54cd52), where a file with the original ftp link for each NCBI directory is also available.\nC_LIO_LICode for the chewBBACA suite is available at https://github.com/B-UMMI/chewBBACA while the tutorial example is found at https://github.com/B-UMMI/chewBBACA_tutorial.\nC_LI\n\nI/We confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. {boxtimes}\n\nIMPACT STATEMENTThe chewBBACA software offers a computational solution for the creation, evaluation and use of whole genome (wg) and core genome (cg) multilocus sequence typing (MLST) schemas. It allows researchers to develop wg/cgMLST schemes for any bacterial species from a set of genomes of interest. The alleles identified by chewBBACA correspond to potential coding sequences, possibly offering insights into the correspondence between the genetic variability identified and phenotypic variability. The software performs allele calling in a matter of seconds to minutes per strain in a laptop but is easily scalable for the analysis of large datasets of hundreds of thousands of strains using multiprocessing options. The chewBBACA software thus provides an efficient and freely available open source solution for gene-by-gene methods. Moreover, the ability to perform these tasks locally is desirable when the submission of raw data to a central repository or web services is hindered by data protection policies or ethical or legal concerns.

bioinformatics↗