Resumo em Inglês:

Abstract The ultraconserved regions (UCRs) are 481 genomic elements, longer than 200 bp, 100% conserved in human, mouse, and rat genomes. Usually, coding regions are more conserved, but more than 80% of UCRs are either intergenic or intronic, and many of them produce long non-coding RNAs (lncRNAs). Recently, the deregulated expression of transcribed UCRs (T-UCRs) has been associated with pathological conditions. But, differently from many lncRNAs with recognized crucial effects on malignant cell processes, the role of T-UCRs in the control of cancer cell networks is understudied. Furthermore, the potential utility of these molecules as molecular markers is not clear. Based on this information, the present review aims to organize information about T-UCRs with either oncogenic or tumor suppressor role associated with cancer cell signaling, and better describe T-UCRs with potential utility as prognosis markers. Out of 481 T-UCRs, 297 present differential expression in cancer samples, 23 molecules are associated with tumorigenesis processes, and 12 have more clear potential utility as prognosis markers. In conclusion, T-UCRs are deregulated in several tumor types, highlighted as important molecules in cancer networks, and with potential utility as prognosis markers, although further investigation for translational medicine is still needed.

Resumo em Inglês:

Abstract Genetically antimicrobial resistance in Mycobacterium tuberculosis is currently one of the most important aspects of tuberculosis, considering that there are emerging resistant strains for almost every known drug used for its treatment. There are multiple antimicrobials used for tuberculosis treatment, and the most effective ones are the first-line drugs, which include isoniazid, pyrazinamide, rifampicin, and ethambutol. In this context, understanding the mechanisms of action and resistance of these molecules is essential for proposing new therapies and strategies of treatment. Additionally, understanding how and where mutations arise conferring a resistance profile to the bacteria and their effect on bacterial metabolism is an important requisite to be taken in producing safer and less susceptible drugs to the emergence of resistance. In this review, we summarize the most recent literature regarding novel mutations reported between 2017 and 2022 and the advances in the molecular mechanisms of action and resistance against first-line drugs used in tuberculosis treatment, highlighting recent findings in pyrazinamide resistance involving PanD and, additionally, resistance-conferring mutations for novel drugs such as bedaquiline, pretomanid, delamanid and linezolid.

Resumo em Inglês:

Abstract The role of steroid hormones against infectious diseases has been extensively studied. From immunomodulatory action to direct inhibition of microorganism growth, hormones D3 (VD3) and 17β-estradiol (E2), and the genetic pathways modulated by them, are key targets for a better understanding pathogenesis of infectious respiratory diseases (IRD) such as tuberculosis (TB) and the coronavirus disease-19 (COVID-19). Currently, the world faces two major public health problems, the outbreak of COVID-19, accounting for more than 6 million so far, and TB, more than 1 million deaths per year. Both, although resulting from different pathogens, the Mtb and the SARS-CoV-2, respectively, are considered serious and epidemic. TB and COVID-19 present similar infection rates between men and women, however the number of complications and deaths resulting from the two infections is higher in men when compared to women in childbearing age, which may indicate a role of the sex hormone E2 in the context of these diseases. E2 and VD3 act upon key gene pathways as important immunomodulatory players and supporting molecules in IRDs. This review summarizes the main roles of these hormones (VD3 and E2) in modulating immune and inflammatory responses and their relationship with TB and COVID-19.

Resumo em Inglês:

Abstract Bacteria live in polymicrobial communities and constantly compete for resources. These organisms have evolved an array of antibacterial weapons to inhibit the growth or kill competitors. The arsenal comprises antibiotics, bacteriocins, and contact-dependent effectors that are either secreted in the medium or directly translocated into target cells. During bacterial antagonistic encounters, several cellular components important for life become a weak spot prone to an attack. Nucleic acids and the machinery responsible for their synthesis are well conserved across the tree of life. These molecules are part of the information flow in the central dogma of molecular biology and mediate long- and short-term storage for genetic information. The aim of this review is to summarize the diversity of antibacterial molecules that target nucleic acids during antagonistic interbacterial encounters and discuss their potential to promote the emergence antibiotic resistance.

Resumo em Inglês:

Abstract Repeated phenotypes, often referred to as ‘homoplasies’ in cladistic analyses, may evolve through changes in developmental processes. Genetic bases of recurrent evolution gained attention and have been studied in the past years using approaches that combine modern analytical phylogenetic tools with the stunning assemblage of new information on developmental mechanisms. In this review, we evaluated the topic under an integrated perspective, revisiting the classical definitions of convergence and parallelism and detailing comparative methods used to evaluate evolution of repeated phenotypes, which include phylogenetic inference, estimates of evolutionary rates and reconstruction of ancestral states. We provide examples to illustrate how a given methodological approach can be used to identify evolutionary patterns and evaluate developmental mechanisms associated with the intermittent expression of a given trait along the phylogeny. Finally, we address why repeated trait loss challenges strict definitions of convergence and parallelism, discussing how changes in developmental pathways might explain the high frequency of repeated trait loss in specific lineages.

Resumo em Inglês:

Abstract We present a concept that explains the pattern of occurrence of widely distributed organisms with large chromosomal diversity, large or small molecular divergence, and the insufficiency or absence of morphological identity. Our model is based on cytogenetic studies associated with molecular and biological data and can be applied to any lineage of sister species, chronospecies, or cryptic species. Through the evaluation of the karyotypic macrostructure, as the physical location of genes e satellites DNAs, in addition to phylogenetic reconstructions from mitochondrial and nuclear genes, per example, we have observed morphologically indistinguishable individuals presenting different locally fixed karyomorphs with phylogeographic discontinuity. The biological process behind this pattern is seen in many groups of cryptic species, in which variation lies mainly in the organization of their genomes but not necessarily in the ecosystems they inhabit or in their external morphology. It’s similar to the processes behind other events observed in the distribution of lineages. In this work, we explore the hypothesis of a process analogous to ecological-evolutionary radiation, which we called Chromosomal Radiation. Chromosomal Radiation can be adaptive or non-adaptive and applied to different groups of organisms.