Biology subjects

Ibarra, C.

Publications and source records attributed to Ibarra, C..

7 recordsLinked to original sources

bioRxiv2022

The cognitive and neural correlates of irony

It has been suggested that irony is one of the most challenging forms of communication, consequently, it can be a valuable indicator of communication abilities. An ironic statement transmits the opposite meaning of its literal counterpart. The cognitive processes that may support the interpretation of irony include the Theory of Mind (ToM), executive functions, and processing style. The brain areas associated with irony detection are the medial prefrontal cortex, inferior frontal gyrus (IFG), posterior superior temporal gyrus (pSTG), precuneus, and inferior parietal lobule, among others. This study aims to analyze the cognitive processes and neural correlates involved in irony detection in Mexican adults. Forty-five participants underwent a cognitive assessment and performed a contextual discrepancy task during fMRI acquisition. The behavioral results showed that the detection of nonliteral statements (irony, unrelated, and white lies) requires ToM and verbal abilities. In addition, white lies detection seemed to involve inhibitory control. Ironic statements were the hardest intention to detect, having the lowest percentage of classification and the slowest latency of classification. Irony detection involved brain areas associated with the ToM (i.e., precuneus) and language (i.e., IFG and pSTG) as was expected based on the results of previous studies. The detection of literal and unrelated statements recruited motor areas. No differential activation pattern was found for detection of white lies. Finally, a global perceptual processing style predicted the percent change in the BOLD signal in the IFG for all the nonliteral and literal statements.

neuroscience↗

bioRxiv2022

Opposing effects of calcium stress in human muscle: defective glucose utilization leading to diabetes vs. stress-adaptive effects of a junctophilin fragment

Calcium ion movements between cellular stores and the cytosol govern muscle contraction, the most energy-consuming function in mammals, which confers skeletal myofibers a pivotal role in glycemia regulation. Chronic myoplasmic calcium elevation, found in malignant hyperthermia-susceptible (MHS) patients and multiple myopathies, has been suggested to underlie the progression from hyperglycemia to insulin resistance. What drives such progression remains elusive. We find that muscle cells derived from MHS patients have increased an activated fragment of GSK3{beta} -- a specialized kinase that inhibits glycogen synthase, impairing glucose utilization and delineating a path to hyperglycemia. We also find decreased content of junctophilin1, an essential structural protein that colocalizes in the couplon with the voltage-sensing CaV1.1, the calcium channel RyR1 and calpain1, accompanied by an increase in a 44-kDa junctophilin1 fragment (JPh44) that moves into nuclei. We trace these changes to activated proteolysis by calpain1, secondary to increased myoplasmic calcium. We demonstrate that a JPh44-like construct induces transcriptional changes predictive of increased glucose utilization in myoblasts, including less transcription and translation of GSK3{beta} and decreased transcription of proteins that reduce utilization of glucose. These effects reveal a stress-adaptive response, mediated by the novel regulator of transcription JPh44.

cell biology↗

bioRxiv2022

Detection and characterization of circulating microvesicles containing Shiga toxin type 2 (Stx2) in a rat model of Hemolytic Uremic Syndrome

Shiga toxin (Stx) producing Escherichia coli (STEC) are foodborne pathogens that release Stx and may develop Hemolytic Uremic Syndrome (HUS). Stx causes endothelial cell damage and leads to platelets deposition and thrombi formation within the microvasculature. It has been described that Stx activates blood cells and induces the shedding of proinflammatory and prothrombotic microvesicles (MVs) containing the toxin. In this sense, it has been postulated that MVs containing Stx2 (MVs-Stx2+) can contribute to the physiopathology of HUS, allowing Stx to reach the target organs and evading the immune system. In this work, we propose that circulating MVs-Stx2+ can be a potential biomarker for the diagnosis and prognosis of STEC infections and HUS progression. In this regard, we developed a rat HUS model by the intreperitoneal injection of a sublethal dose of Stx2 and observed: decrease in body weight, increase of creatinine and urea levels, decrease of creatinine clearance and histological renal damages. After characterization of renal damages we investigated circulating total MVs and MVs-Stx2+ by flow cytometry at different times after Stx2 injection. Additionally, we evaluated the correlation of biochemical parameters such as creatinine and urea in plasma with MVs-Stx2+. As a result, we found a significant circulation of Mvs-Stx2+ at 96 hours after Stx2 injection, nevertheless no correlation with creatinine and urea plasma levels were detected. Our results suggest that MVs-Stx2+ may be an additional biomarker for the characterization and diagnosis of HUS progression. Further analysis is required in order to validate MVs-Stx2+ as biomarker of the disease.

pathology↗

bioRxiv2021

Arabidopsis ROOT UV-B SENSITIVE 1 and 2 Interact with Aminotransferases to Regulate Vitamin B6 Homeostasis

Pyridoxal-5-phosphate (PLP), the enzymatic cofactor form of Vitamin B6 (vitB6), is a versatile compound that has essential roles in metabolism. Cellular PLP homeostasic regulation is currently not well understood. Here we report that in Arabidopsis, biosynthesized PLP is sequestered by specific aminotransferases (ATs), and that the proteins ROOT UV-B SENSITIVE 1 (RUS1) and RUS2 function with ATs to regulate PLP homeostasis. The stunted growth phenotypes of rus1 and rus2 mutants were previously shown to be rescuable by exogenously supplied vitB6. Specific residue changes near the PLP-binding pocket in ASPARTATE AMINOTRANSFERASE2 (ASP2) also rescued rus1 and rus2 phenotypes. In this study, saturated suppressor screens identified 14 additional suppressor of rus (sor) alleles in four aminotransferase genes (ASP1, ASP2, ASP3, or ALANIN AMINOTRANSFERASE1 (AAT1)), which suppressed the rus phenotypes to varying degrees. Each of the sor mutations altered an amino acid in the PLP-binding pocket of the protein, and sor proteins were found to have reduced levels of PLP conjugation. Genetic data revealed that the availability of PLP normally requires both RUS1 and RUS2, and that increasing the number of sor mutants additively enhanced the suppression of rus phenotypes. Biochemical results showed that RUS1 and RUS2 physically interacted with ATs. Our studies suggest a mechanism in which RUS1, RUS2 and specific ATs work together to regulate PLP homeostasis in Arabidopsis.

genetics↗

bioRxiv2021

Sleep problems in preschoolers with autism spectrum disorders are associated with sensory sensitivities and thalamocortical overconnectivity

Projections between the thalamus and sensory cortices are established early in development and play an important role in sleep regulation as well as in relaying sensory information to cortex. Atypical thalamocortical functional connectivity frequently observed in children with autism spectrum disorders (ASD) might therefore be linked to sensory and sleep problems common in ASD. Here we investigated the relationship between auditory-thalamic functional connectivity measured during natural sleep fMRI, sleep problems, and sound sensitivities in 70 toddlers and preschoolers (1.5 to 5-year-olds) with ASD compared to a matched group of 46 typically developing (TD) children. In children with ASD, sleep problems and sensory sensitivities were positively correlated, and increased sleep latency was associated with overconnectivity between the thalamus and auditory cortex in a subsample with high quality MRI data (n=29). Additionally, auditory cortex BOLD signal amplitude was elevated in children with ASD, potentially reflecting reduced sensory gating or a lack of auditory habituation during natural sleep. These findings indicate that atypical thalamocortical functional connectivity can be detected early in development and may play a crucial role in sleep problems and sensory sensitivities in ASD.

neuroscience↗

bioRxiv2019

Genome-wide Analysis In Response to N and C Identifies New Regulators for root AtNRT2 Transporters

In Arabidopsis thaliana, the High-Affinity Transport System (HATS) for root NO3- uptake depends mainly on four NRT2 transporters, namely NRT2.1, NRT2.2, NRT2.4 and NRT2.5. The HATS is the target of many regulations to coordinate nitrogen (N) acquisition with the N status of the plant and with carbon (C) assimilation through photosynthesis. At the molecular level, C and N signaling pathways have been shown to control gene expression of the NRT2 transporters. Although several regulators of these transporters have been identified in response to either N or C signals, the response of NRT2 genes expression to the interaction of these signals has never been specifically investigated and the underlying molecular mechanisms remain largely unknown. To address this question we used an original systems biology approach to model a regulatory gene network targeting NRT2.1, NRT2.2, NRT2.4 and NRT2.5 in response to N/C signals. Our systems analysis of the data highlighted the potential role of three putative transcription factors, TGA3, MYC1 and bHLH093. Functional analysis of mutants combined with yeast one hybrid experiments confirmed that all 3 transcription factors are regulators of NRT2.4 or NRT2.5 in response to N or C signals.\n\nOne sentence summaryIdentification of three transcription factors involved in the regulation of NRT2s transporters using a systems biology approach and NRT2.1 as target gene in response to combinations of N/C treatments

plant biology↗

bioRxiv2018

A non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease

Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted for example in pulmonary hypertension. Its dysregulation in disease is incompletely understood. Here we show in pulmonary artery endothelial cells that feedback inhibition by NO of the NO receptor, the cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous NO from endothelial NO synthase or exogenous NO from NO donor compounds decreased sGC protein and activity. This was not mediated by cGMP as the NO-independent sGC stimulator or direct activation of cGMP-dependent protein kinase did not mimic it. Thiol-sensitive mechanisms were also not involved as the thiol-reducing agent, N-acetyl-L-cysteine did not prevent this feedback. Instead, both in-vitro and in-vivo and in health and acute respiratory lung disease, chronically elevated NO led to the inactivation and degradation of sGC whilst leaving the heme-free isoform, apo-sGC, intact or even increasing its levels. Thus, NO regulates sGC in a bimodal manner, acutely stimulating and chronically inhibiting, as part of self-limiting direct feedback that is cGMP-independent. In high NO disease conditions, this is aggravated but can be functionally recovered in a mechanism-based manner by apo-sGC activators that re-establish cGMP formation.

pharmacology and toxicology↗