Resumo em Inglês:

Abstract Latin America (LatAm) has a rich and historically significant role in delineating both novel and well-documented genetic disorders. However, the ongoing advancements in the field of human genetics pose challenges to the relatively slow adaption of LatAm in the field. Here, we describe past and present contributions of LatAm to the discovery of novel genetic disorders, often referred as novel gene-disease associations (NGDA). We also describe the current methodologies for discovery of NGDA, taking into account the latest developments in genomics. We provide an overview of opportunities and challenges for NGDA research in LatAm considering the steps currently performed to identify and validate such associations. Given the multiple and diverse needs of populations and countries in LatAm, it is imperative to foster collaborations amongst patients, indigenous people, clinicians and scientists. Such collaborative effort is essential for sustaining and enhancing the LatAm´s contributions to the field of NGDA.

Resumo em Inglês:

Abstract Group I introns are small RNAs (250-500 nt) capable of catalyzing their own splicing from the precursor RNA. They are widely distributed across the tree of life and have intricate relationships with their host genomes. In this work, we review its basic structure, self-splicing and its mechanisms of gene mobility. As they are widely found in unicellular eukaryotes, especially fungi, we gathered information regarding their possible impact on the physiology of fungal cells and the possible application of these introns in medical mycology.

Resumo em Inglês:

Abstract Introducing new grass species into cultivation has long been proposed as beneficial to increase the sustainability and diversity of productive systems. However, wild species with potential tend to show high seed dormancy, causing slow, poor, and unsynchronized seedling emergence. Meanwhile, domesticated species, such as cereals, show lower seed dormancy, facilitating their successful establishment. In this work, we conduct a review of phenotypic variation on seed dormancy and its genetic and molecular basis. This quantitative and highly heritable trait shows phenotype plasticity which is modulated by environmental factors. The level of dormancy depends on the expression of genes associated with the metabolism and sensitivity to the hormones abscisic acid (ABA) and gibberellins (GA), along with other dormancy-specific genes. The genetic regulation of these traits is highly conserved across species. The low seed dormancy observed in cereals and some temperate forages was mostly unconsciously selected during various domestication processes. Emphasis is placed on selecting materials with low seed dormancy for warm-season forage grasses to improve their establishment and adoption. Finally, we review advances in the domestication of dallisgrass, where seed dormancy was considered a focus trait throughout the process.

Resumo em Inglês:

Abstract Senescence is a cellular state in which the cell loses its proliferative capacity, often irreversibly. Physiologically, it occurs due to a limited capacity of cell division associated with telomere shortening, the so-called replicative senescence. It can also be induced early due to DNA damage, oncogenic activation, oxidative stress, or damage to other cellular components (collectively named induced senescence). Tumor cells acquire the ability to bypass replicative senescence, thus ensuring the replicative immortality, a hallmark of cancer. Many anti-cancer therapies, however, can lead tumor cells to induced senescence. Initially, this response leads to a slowdown in tumor growth. However, the longstanding accumulation of senescent cells (SnCs) in tumors can promote neoplastic progression due to the enrichment of numerous molecules and extracellular vesicles that constitutes the senescence-associated secretory phenotype (SASP). Among other effects, SASP can potentiate or unlock the tumor plasticity and phenotypic transitions, another hallmark of cancer. This review discusses how SnCs can fuel mechanisms that underlie cancer plasticity, like cell differentiation, stemness, reprogramming, and epithelial-mesenchymal transition. We also discuss the main molecular mechanisms that make SnCs resistant to cell death, and potential strategies to target SnCs. At the end, we raise open questions and clinically relevant perspectives in the field.

Resumo em Inglês:

Abstract In the search for alternatives to overcome the challenge imposed by drug resistance development in cancer treatment, the modulation of autophagy has emerged as a promising alternative that has achieved good results in clinical trials. Nevertheless, most of these studies have overlooked a novel and selective type of autophagy: chaperone-mediated autophagy (CMA). Following its discovery, research into CMA’s contribution to tumor progression has accelerated rapidly. Therefore, we now understand that stress conditions are the primary signal responsible for modulating CMA in cancer cells. In turn, the degradation of proteins by CMA can offer important advantages for tumorigenesis, since tumor suppressor proteins are CMA targets. Such mutual interaction between the tumor microenvironment and CMA also plays a crucial part in establishing therapy resistance, making this discussion the focus of the present review. Thus, we highlight how suppression of LAMP2A can enhance the sensitivity of cancer cells to several drugs, just as downregulation of CMA activity can lead to resistance in certain cases. Given this panorama, it is important to identify selective modulators of CMA to enhance the therapeutic response.

Resumo em Inglês:

Abstract Leguminous plants can establish endosymbiotic relationships with nitrogen-fixing soil rhizobacteria. Bacterial infection and nodule organogenesis are two independent but highly coordinated genetic programs that are active during this interaction. These genetic programs can be regulated along all the stages of gene expression. Most of the studies, for both eukaryotes and prokaryotes, focused on the transcriptional regulation level determining the abundance of mRNAs. However, it has been demonstrated that mRNA levels only sometimes correlate with the abundance or activity of the coded proteins. For this reason, in the past two decades, interest in the role of translational control of gene expression has increased, since the subset of mRNA being actively translated outperforms the information gained only by the transcriptome. In the case of legume-rhizobia interactions, the study of the translatome still needs to be explored further. Therefore, this review aims to discuss the methodologies for analyzing polysome-associated mRNAs at the genome-scale and their contribution to studying translational control to understand the complexity of this symbiotic interaction. Moreover, the Dual RNA-seq approach is discussed for its relevance in the context of a symbiotic nodule, where intricate multi-species gene expression networks occur.

Resumo em Inglês:

Abstract Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and antidepressants, although useful and effective for some, do not have a high responsiveness rate across those with these conditions. One reason for low responsiveness to these drugs is patient heterogeneity, meaning there is diversity in patient characteristics relating to genetics, etiology, and environment affecting treatment. In the past two decades, novel induced pluripotent stem cell (iPSC) research and technology have enabled the use of human-derived brain cells as a new model to study human disease that can help account for patient variance. Human iPSC technology is an emerging tool to better understand the molecular mechanisms of these disorders as well as a platform to test novel treatments and existing pharmaceuticals. This literature review describes the use of iPSC technology to model bipolar and major depressive disorder, common medications used to treat these disorders, and novel patient-derived alternative treatment methods for non-responders stemming from past publications, as well as presenting new data derived from these models.