Abstract in English:

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.

Abstract in English:

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.

Abstract in English:

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.

Abstract in English:

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.

Abstract in English:

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.

Abstract in English:

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.

Abstract in English:

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.

Abstract in English:

Abstract The breast microbiome presents a diverse microbial community that could affects health and disease states, in the context of breast cancer. Sequencing technologies have allowed describing the diversity and abundance of microbial communities among individuals. The complex tumoral microenvironment that includes the microbial composition could influence tumor growth. The imbalance of diversity and abundance inside the microbial community, known as dysbiosis plays a crucial role in this context. One the most prevalent bacterial genera described in breast invasive carcinoma are Bacillus, Pseudomonas, Brevibacillus, Mycobacterium, Thermoviga, Acinetobacter, Corynebacterium, Paenibacillus, Ensifer, and Bacteroides. Paenibacills genus shows a relation with patient survival. When the Paenibacills genus increases its abundance in patients with breast cancer, the survival probability decreases. Within this dysbiotic environment, various bacterial metabolites could play a pivotal role in the progression and modulation of breast cancer. Key bacterial metabolites, such as cadaverine, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), have been found to exhibit potential interactions within breast tissue microenvironments. Understanding the intricate relationships between dysbiosis and these metabolites in breast cancer may open new avenues for diagnostic biomarkers and therapeutic targets. Further research is essential to unravel the specific roles and mechanisms of these microbial metabolites in breast cancer progression.

Abstract in English:

Abstract Distinguishing between environmental adaptations and neutral processes poses a challenge in population genetics and evolutionary studies, particularly when phenomena can be explained by both processes. Clines are genotypic or phenotypic characters correlated with environmental variables, because of that correlation, they are used as examples of spatially varying selection. At the same time, many genotypic clines can be explained by demographic history, like isolation by distance or secondary contact zones. Clines have been extensively studied in Drosophila melanogaster, especially in North America and Australia, where they are attributed to both differential selection and various demographic processes. This review explores existing literature supporting this conclusion and suggests new approaches to better understand the influence of these processes on clines. These innovative approaches aim to shed light on the longstanding debate regarding the importance of natural selection versus neutral processes in maintaining variation in natural populations.

Abstract in English:

Abstract Animals adapt to the daily changes in their environmental conditions by means of genetically encoded circadian clocks. These clocks, found throughout the tree of life, regulate diverse biological functions, and allow periodical changes in physiology and behaviour. The molecular underpinnings of these clocks have been extensively studied across taxa, revealing a brain-based system that coordinates rhythmic activities through neuronal networks and signalling pathways. Entrainment, the alignment of internal rhythms with external cues or zeitgebers, is crucial for the adaptive value of these internal clocks. While the solar light-dark cycle is a primary zeitgeber for most animals, other relevant cues such as temperature, meal timing, predators, anxiety, fear, physical activity, and social interactions also play roles in entraining circadian clocks. The search of a detailed description of the circadian clocks is a goal for neurobiology and an area of growing societal interests. Moreover, as disruptions in circadian rhythms are implicated in various diseases, understanding the entrainment pathways contributes to developing interventions for improved wellbeing and health outcomes. This review focuses on socially relevant cues, examining their impact on animal physiology and behaviour, and explores the sensory pathways transmitting information to the central clock.

Abstract in English:

Abstract Oral squamous cell carcinoma (OSCC) has a poor prognosis and the treatment employed generates significant physical deformity in patients. In recent years, an increase in the incidence of cases of OSCC has been observed in adult patients up to 45 years old in several genetic underrepresented and underserved countries. The increase in OSCC cases in young people is very relevant because it shows that OSCC does not make exceptions and hereditarily must play an important role. This fact has not been associated with an evident biological basis, and a large majority of these patients do not present the classic principal risk factors association. OSCC is the result of accumulation of genetic and epigenetic alterations and this information is still fragmented in the literature, mainly in the young group. Conducting studies with a comprehensive analysis of genetic and epigenetic data is crucial, to provide greater understanding of the underlying biology of OSCC, because this information can be decisive to determine targets for therapeutic treatment. We review the main germline and somatic aspects of genetic and genomic variation in OSCC considering the absence of genomic data from developing countries such as Chile and the rest of Hispano-America.

Abstract in English:

Abstract Regulated cell death by a non-apoptotic pathway known as parthanatos is increasingly recognised as a central player in pathological processes, including ischaemic tissue damage and neurodegenerative diseases. Parthanatos is activated under conditions that induce high levels of DNA damage, leading to hyperactivation of the DNA damage sensor PARP1. While this strict dependence on PARP1 activation is a defining feature of parthanatos that distinguishes it from other forms of cell death, the molecular events downstream of PARP1 activation remain poorly understood. In this mini-review, we highlight a number of important questions that remain to be answered about this enigmatic form of cell death.

Abstract in English:

Abstract The catalytic, regulatory and structural properties of RNA, combined with their extraordinary ubiquity in cellular processes, are consistent with the proposal that this molecule played a much more conspicuous role in heredity and metabolism during the early stages of biological evolution. This review explores the pivotal role of RNA in the earliest life forms and its relevance in modern biological systems. It examines current models that study the early evolution of life, providing insights into the primordial RNA world and its legacy in contemporary biology.

Abstract in English:

Abstract The genetic architecture of complex diseases affecting populations with Indigenous American ancestries is poorly understood due to their underrepresentation in genomics studies. While most of the genetic diversity associated with disease trait variation is shared among worldwide populations, a fraction of this component is expected to be unique to each continental group, including Indigenous Americans. Here, I describe the current state of knowledge from genome-wide association studies on Indigenous populations, as well as non-Indigenous populations with partial Indigenous ancestries from the American continent, focusing on disease susceptibility and anthropometric traits. While some studies identified risk alleles unique to Indigenous populations, their effects on trait variation are mostly small. I suggest that the associations rendered by many inter-population studies are probably inflated due to the absence of socio-cultural-economic covariates in the association models. I encourage the inclusion of admixed individuals in future GWAS studies to control for inter-ancestry differences in environmental factors. I suggest that some complex diseases might have arisen as trade-off costs of adaptations to past evolutionary selective pressures. Finally, I discuss how expanding panels with Indigenous ancestries in GWAS studies is key to accurately assess genetic risk in populations from the American continent, thus decreasing global health disparities.

Abstract in English:

Abstract The review explores parasitic plants’ evolutionary success and adaptability, highlighting their widespread occurrence and emphasizing the role of an invasive organ called haustorium in nutrient acquisition from hosts. It discusses the genetic and physiological adaptations that facilitate parasitism, including horizontal gene transfer, and the impact of environmental factors like climate change on these relationships. It addresses the need for further research into parasitic plants’ genomes and interactions with their hosts to better predict environmental changes’ impacts.

Abstract in English:

Abstract Here we reassess available evidence for the long-held misconception of amoebae possessing exceptionally large genomes. Traditionally, estimates relied on inaccurate methods like DNA weight measurements, leading to inflated sizes. These methods failed to account for contaminating DNA from prey, endosymbionts, and intrinsic genomic features like ribosomal operon amplification. Modern sequencing techniques unveil a different picture. Fully sequenced amoebozoa genomes range from 14.4 to 52.37 mega basepairs, well within the typical single-celled eukaryote expectation. While the whole genome of the historically relevant Amoeba proteus has not yet been fully sequenced, we provide here a statistical analysis using protein-coding genes from transcriptomic data, suggesting that the genome size is consistent with this range, far smaller than previously claimed. The misconception likely originated in the early 21st century and perpetuated through popular science materials. We conclude that there is no longer reason to reaffirm that amoeba genomes are giant.

Abstract in English:

Abstract Aging is a significant risk factor for male fertility and can lead to severe developmental disorders in offspring. It disrupts testicular function and spermatogenesis, resulting in sperm abnormalities and DNA fragmentation. Male aging alters the genome and epigenome of germ cells due to persistent oxidative stress caused by the cumulative effects of environmental factors over a lifetime. At the molecular level, DNA damage occurs and is poorly repaired due to impaired DNA repair pathways, leading to unrepaired lesions and de novo mutations. Aging also creates distinct epigenetic landscapes that modify gene expression in germ cells, affect the DNA damage response, and generate de novo DNA and epigenetic mutations that are transmitted to the sperm and inherited by the offspring. This review discusses current knowledge on the age-associated effects on male germ cells and the genomic and epigenomic mechanisms contributing to altered male reproductive health and outcomes in progeny. We propose a male reproductive aging threshold, where cumulative exposure to risk factors leads to oxidative stress, impaired spermatogenesis, and altered reproductive outcomes. Finally, we discuss novel interventions to prevent premature testicular aging and emphasize the need for public health policies and counseling guidelines for men seeking paternity.