Reverse Engineering of the Pediatric Sepsis Regulatory Network and Identification of Master Regulators.

Sepsis remains a leading cause of death in ICUs all over the world, with pediatric sepsis accounting for a high percentage of mortality in pediatric ICUs. Its complexity makes it difficult to establish a consensus on genetic biomarkers and therapeutic targets. A promising strategy is to investigate the regulatory mechanisms involved in sepsis progression, but there are few studies regarding gene regulation in sepsis. This work aimed to reconstruct the sepsis regulatory network and identify transcription factors (TFs) driving transcriptional states, which we refer to here as master regulators. We used public gene expression datasets to infer the co-expression network associated with sepsis in a retrospective study. We identified a set of 15 TFs as potential master regulators of pediatric sepsis, which were divided into two main clusters. The first cluster corresponded to TFs with decreased activity in pediatric sepsis, and GATA3 and RORA, as well as other TFs previously implicated in the context of inflammatory response. The second cluster corresponded to TFs with increased activity in pediatric sepsis and was composed of TRIM25, RFX2, and MEF2A, genes not previously described as acting in a coordinated way in pediatric sepsis. Altogether, these results show how a subset of master regulators TF can drive pathological transcriptional states, with implications for sepsis biology and treatment.

Ionotropic Receptors as a Driving Force behind Human Synapse Establishment.

The origin of nervous systems is a main theme in biology and its mechanisms are largely underlied by synaptic neurotransmission. One problem to explain synapse establishment is that synaptic orthologs are present in multiple aneural organisms. We questioned how the interactions among these elements evolved and to what extent it relates to our understanding of the nervous systems complexity. We identified the human neurotransmission gene network based on genes present in GABAergic, glutamatergic, serotonergic, dopaminergic, and cholinergic systems. The network comprises 321 human genes, 83 of which act exclusively in the nervous system. We reconstructed the evolutionary scenario of synapse emergence by looking for synaptic orthologs in 476 eukaryotes. The Human-Cnidaria common ancestor displayed a massive emergence of neuroexclusive genes, mainly ionotropic receptors, which might have been crucial to the evolution of synapses. Very few synaptic genes had their origin after the Human-Cnidaria common ancestor. We also identified a higher abundance of synaptic proteins in vertebrates, which suggests an increase in the synaptic network complexity of those organisms.

Analysis of Arabidopsis thaliana Redox Gene Network Indicates Evolutionary Expansion of Class III Peroxidase in Plants.

Reactive oxygen species (ROS) are byproducts of aerobic metabolism and may cause oxidative damage to biomolecules. Plants have a complex redox system, involving enzymatic and non-enzymatic compounds. The evolutionary origin of enzymatic antioxidant defense in plants is yet unclear. Here, we describe the redox gene network for A. thaliana and investigate the evolutionary origin of this network. We gathered from public repositories 246 A. thaliana genes directly involved with ROS metabolism and proposed an A. thaliana redox gene network. Using orthology information of 238 Eukaryotes from STRINGdb, we inferred the evolutionary root of each gene to reconstruct the evolutionary history of A. thaliana antioxidant gene network. We found two interconnected clusters: one formed by SOD-related, Thiol-redox, peroxidases, and other oxido-reductase; and the other formed entirely by class III peroxidases. Each cluster emerged in different periods of evolution: the cluster formed by SOD-related, Thiol-redox, peroxidases, and other oxido-reductase emerged before opisthokonta-plant divergence; the cluster composed by class III peroxidases emerged after opisthokonta-plant divergence and therefore contained the most recent network components. According to our results, class III peroxidases are in expansion throughout plant evolution, with new orthologs emerging in each evaluated plant clade divergence.

Sex-biased gene expression in the frontal cortex of common marmosets (Callithrix jacchus) and potential behavioral correlates.

INTRODUCTION: The common marmoset (Callithrix jacchus), a small New World monkey, has been widely used as a biological model in neuroscience to elucidate neural circuits involved in cognition and to understand brain dysfunction in neuropsychiatric disorders. In this regard, the availability of gene expression data derived from next-generation sequencing (NGS) technologies represents an opportunity for a molecular contextualization. Sexual dimorphism account for differences in diseases prevalence and prognosis. Here, we explore sex differences on frontal cortex of gene expression in common marmoset's adults. METHODS: Gene expression profiles in six different tissues (cerebellum, frontal cortex, liver, heart, and kidney) were analyzed in male and female marmosets. To emphasize the translational value of this species for behavioral studies, we focused on sex-biased gene expression from the frontal cortex of male and female in common marmosets and compared to humans (Homo sapiens). RESULTS: In this study, we found that frontal cortex genes whose expression is male-biased are conserved between marmosets and humans and enriched with "house-keeping" functions. On the other hand, female-biased genes are more related to neural plasticity functions involved in remodeling of synaptic circuits, stress cascades, and visual behavior. Additionally, we developed and made available an application-the CajaDB-to provide a friendly interface for genomic, expression, and alternative splicing data of marmosets together with a series of functionalities that allow the exploration of these data. CajaDB is available at cajadb.neuro.ufrn.br. CONCLUSION: The data point to differences in gene expression of male and female common marmosets in all tissues analyzed. In frontal cortex, female-biased expression in synaptic plasticity, stress, and visual processing might be linked to biological and behavioral mechanisms of this sex. Due to the limited sample size, the data here analyzed are for exploratory purposes.