Techniques, procedures, and applications in host genetic analysis.

This chapter overviews genetic techniques' fundamentals and methodological features, including different approaches, analyses, and applications that have contributed to advancing health and disease. The aim is to describe laboratory methodologies and analyses employed to understand the genetic landscape of different biological contexts, from conventional techniques to cutting-edge technologies. Besides describing detailed aspects of the polymerase chain reaction (PCR) and derived types as one of the principles for many novel techniques, we also discuss microarray analysis, next-generation sequencing, and genome editing technologies such as transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems. These techniques study several phenotypes, ranging from autoimmune disorders to viral diseases. The significance of integrating diverse genetic methodologies and tools to understand host genetics comprehensively and addressing the ethical, legal, and social implications (ELSI) associated with using genetic information is highlighted. Overall, the methods, procedures, and applications in host genetic analysis provided in this chapter furnish researchers and practitioners with a roadmap for navigating the dynamic landscape of host-genome interactions.

Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.

Performance in emotion recognition and theory of mind tasks in social anxiety and generalized anxiety disorders: a systematic review and meta-analysis.

Social cognition impairments may be associated with poor functional outcomes, symptoms, and disability in social anxiety disorder (SAD) and generalized anxiety disorder (GAD). This meta-analysis aims to determine if emotion recognition and theory of mind (ToM) are impaired in SAD or GAD compared to healthy controls. A systematic review was conducted in electronic databases (PubMed, PsycNet, and Web of Science) to retrieve studies assessing emotion recognition and/or ToM in patients with SAD or GAD, compared to healthy controls, up to March 2022. Meta-analyses using random-effects models were conducted. We identified 21 eligible studies: 13 reported emotion recognition and 10 ToM outcomes, with 585 SAD patients, 178 GAD patients, and 753 controls. Compared to controls, patients with SAD exhibited impairments in emotion recognition (SMD = -0.32, CI = -0.47 - -0.16, z = -3.97, p < 0.0001) and ToM (SMD = -0.44, CI = -0.83 -0.04, z = -2.18, p < 0.01). Results for GAD were inconclusive due to the limited number of studies meeting the inclusion criteria (two for each domain). Relevant demographic and clinical variables (age, sex, education level, and anxiety scores) were not significantly correlated with emotion recognition or ToM impairments in SAD and GAD. Further studies employing ecological measures with larger and homogenous samples are needed to better delineate the factors influencing social cognition outcomes in both SAD and GAD.

Methods in molecular biology and genetics: looking to the future.

In recent decades, advances in methods in molecular biology and genetics have revolutionized multiple areas of the life and health sciences. However, there remains a global need for the development of more refined and effective methods across these fields of research. In this current Collection, we aim to showcase articles presenting novel molecular biology and genetics techniques developed by scientists from around the world.

Current Evidence About the Role of Animais in the Transmission of Sars-Cov-2: Implications for Public Health / Evidencia Actual sobre el Papel de los Animales en la Transmisión del Sars-Cov-2: Implicaciones para la Salud Pública / Evidências Atuais sobre o Papel dos Animais na Transmissão do Sars-Cov-2: Implicações para a Saúde Pública

Abstract Introduction: The SARS-CoV-2 is the denomination of the new betacoronavirus, which was discovered and isolated for the first time in Wuhan, China, at the end of December 2019, and it is the causal agent of the sanitary emergency of the COVID-19 pandemic. Experimental studies have shown susceptibility to infection in pets (dogs and cats). Objective: To present the current information available on SARS-CoV-2 in animals under the care of humans that have been officially reported in the sanitary registries of the World Animal Health Information System (WAHIS) of the World Organization for Animal Health. Materials and methods: We conducted a narrative review using Medline/ PubMed, Scopus, and Web of Sciences, and official documents of the World Organisation for Animal Health. The search terms used were as follows: "coronavirus", "SARS coronavirus 2019", "SARS-CoV", "SARS-CoV-2 in dog and/or cat" "pets SARS-CoV-2". Results: The studies reviewed in this manuscript highlight those positive cases in cats and dogs for SARS-CoV-2 have been associated with an exposure to positive COVID-19 people. In the available evidence, 55.17 % of the total cases of animals that were positive for SARS-CoV-2 were associated with people with COVID-19 who had the disease at home, possibly due to maintaining a longer exposure to the humans. Conclusion: Regarding the zoonotic aspects, it is important to clarify that although several animal species have been infected by SARS-CoV-2, none of them has been scientifically proven to represent a risk of direct transmission between positive animals and other humans or to play an epidemiological role in the disease.

Resumen Introducción: El SARS-CoV-2 es el nombre para el nuevo betacoronavirus, que fue descubierto y aislado por primera vez en Wuhan, China, a fines de diciembre de 2019, y es el agente causal de la emergencia sanitaria del COVID-19. Estudios experimentales han demostrado susceptibilidad a la infección en mascotas (perros y gatos). Objetivo: Presentar la información actual sobre el SARS-CoV-2 en animales bajo el cuidado de humanos que han sido oficialmente reportados en los registros sanitarios del Sistema Mundial de Información Sanitaria Animal (WAHIS) de la Organización Mundial de Sanidad Animal. Materiales y métodos: Se realizó una revisión narrativa utilizando Medline/PubMed, Scopus y Web of Sciences, y documentos oficiales de la Organización Mundial de Sanidad Animal. Los términos de búsqueda utilizados fueron los siguientes: "coronavirus", "SARS coronavirus 2019", "SARS-CoV", "SARS-CoV-2 en perro y/o gato" "mascotas SARS-CoV-2". Resultados: Los estudios revisados en este manuscrito destacan que los casos positivos en gatos y perros para SARS-CoV-2 se han asociado con una exposición a personas positivas para COVID-19. En la evidencia disponible, el 55,17 % del total de casos de animales positivos para SARS-CoV-2 estaban asociados a personas con COVID-19 que tenían la enfermedad en casa, posiblemente por mantener una mayor exposición a los humanos. Conclusión: En cuanto a los aspectos zoonóticos, es importante aclarar que si bien varias especies animales han sido infectadas por el SARS-CoV-2, ninguna de ellas ha demostrado científicamente que represente un riesgo de transmisión directa entre animales positivos y otros humanos o que juegue un papel epidemiológico en la enfermedad.

Resumo Introdução: SARS-CoV-2 é o nome do novo betacoronavírus, que foi descoberto e isolado pela primeira vez em Wuhan, China, no final de dezembro de 2019, e é o agente causal da emergência sanitária COVID-19. Estudos experimentais mostraram suscetibilidade à infecção em animais de estimação (cães e gatos). Objetivo: Apresentar as informações atuais sobre SARS-CoV-2 em animais sob cuidados humanos que foram oficialmente notificados nos registros sanitários do World Animal Health Information System (WAHIS) da Organização Mundial de Saúde Animal. Materiais e métodos: Foi realizada uma revisão narrativa utilizando Medline/PubMed, Scopus e Web of Sciences e documentos oficiais da Organização Mundial de Saúde Animal. Os termos de pesquisa utilizados foram os seguintes: "coronavírus", "SARS coronavirus 2019", "SARS-CoV", "SARS-CoV-2 in dogs and/ or cats" "SARS-CoV-2 pets". Resultados: Os estudos revisados neste manuscrito destacam que casos positivos em gatos e cães para SARS-CoV-2 foram associados à exposição a pessoas positivas para COVID-19. Nas evidências disponíveis, 55,17 % do total de casos animais positivos para SARS-CoV-2 foram associados a pessoas com COVID-19 que tiveram a doença em casa, possivelmente devido à maior exposição a humanos. Conclusão: Em relação aos aspectos zoonóticos, é importante esclarecer que, embora várias espécies animais tenham sido infectadas pelo SARS-CoV-2, nenhuma de las foi cientificamente comprovada como representando risco de transmissão direta entre animais positivos e outros humanos ou que desempenhe um papel papel epidemiológico da doença.

Central and Peripheral Immune Dysregulation in Posttraumatic Stress Disorder: Convergent Multi-Omics Evidence.

Posttraumatic stress disorder (PTSD) is a chronic and multifactorial disorder with a prevalence ranging between 6-10% in the general population and ~35% in individuals with high lifetime trauma exposure. Growing evidence indicates that the immune system may contribute to the etiology of PTSD, suggesting the inflammatory dysregulation as a hallmark feature of PTSD. However, the potential interplay between the central and peripheral immune system, as well as the biological mechanisms underlying this dysregulation remain poorly understood. The activation of the HPA axis after trauma exposure and the subsequent activation of the inflammatory system mediated by glucocorticoids is the most common mechanism that orchestrates an exacerbated immunological response in PTSD. Recent high-throughput analyses in peripheral and brain tissue from both humans with and animal models of PTSD have found that changes in gene regulation via epigenetic alterations may participate in the impaired inflammatory signaling in PTSD. The goal of this review is to assess the role of the inflammatory system in PTSD across tissue and species, with a particular focus on the genomics, transcriptomics, epigenomics, and proteomics domains. We conducted an integrative multi-omics approach identifying TNF (Tumor Necrosis Factor) signaling, interleukins, chemokines, Toll-like receptors and glucocorticoids among the common dysregulated pathways in both central and peripheral immune systems in PTSD and propose potential novel drug targets for PTSD treatment.

A Bioinformatics-Assisted Review on Iron Metabolism and Immune System to Identify Potential Biomarkers of Exercise Stress-Induced Immunosuppression.

The immune function is closely related to iron (Fe) homeostasis and allostasis. The aim of this bioinformatics-assisted review was twofold; (i) to update the current knowledge of Fe metabolism and its relationship to the immune system, and (ii) to perform a prediction analysis of regulatory network hubs that might serve as potential biomarkers during stress-induced immunosuppression. Several literature and bioinformatics databases/repositories were utilized to review Fe metabolism and complement the molecular description of prioritized proteins. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to build a protein-protein interactions network for subsequent network topology analysis. Importantly, Fe is a sensitive double-edged sword where two extremes of its nutritional status may have harmful effects on innate and adaptive immunity. We identified clearly connected important hubs that belong to two clusters: (i) presentation of peptide antigens to the immune system with the involvement of redox reactions of Fe, heme, and Fe trafficking/transport; and (ii) ubiquitination, endocytosis, and degradation processes of proteins related to Fe metabolism in immune cells (e.g., macrophages). The identified potential biomarkers were in agreement with the current experimental evidence, are included in several immunological/biomarkers databases, and/or are emerging genetic markers for different stressful conditions. Although further validation is warranted, this hybrid method (human-machine collaboration) to extract meaningful biological applications using available data in literature and bioinformatics tools should be highlighted.

The importance of adherence to international standards for depositing open data in public repositories.

There has been an important global interest in Open Science, which include open data and methods, in addition to open access publications. It has been proposed that public availability of raw data increases the value and the possibility of confirmation of scientific findings, in addition to the potential of reducing research waste. Availability of raw data in open repositories facilitates the adequate development of meta-analysis and the cumulative evaluation of evidence for specific topics. In this commentary, we discuss key elements about data sharing in open repositories and we invite researchers around the world to deposit their data in them.

Sarcopenia: Etiology, Nutritional Approaches, and miRNAs.

Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the quality of life. Although there is a consensus that sarcopenia is a multifactorial syndrome, the etiology and underlying mechanisms are not yet delineated. Moreover, research about nutritional interventions to prevent the development of sarcopenia is mainly focused on the amount and quality of protein intake. The impact of several nutrition strategies that consider timing of food intake, anti-inflammatory nutrients, metabolic control, and the role of mitochondrial function on the progression of sarcopenia is not fully understood. This narrative review summarizes the metabolic background of this phenomenon and proposes an integral nutritional approach (including dietary supplements such as creatine monohydrate) to target potential molecular pathways that may affect reduce or ameliorate the adverse effects of sarcopenia. Lastly, miRNAs, in particular those produced by skeletal muscle (MyomiR), might represent a valid tool to evaluate sarcopenia progression as a potential rapid and early biomarker for diagnosis and characterization.

A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation.

Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose-response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review.

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl--dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4-]2- and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3-]-. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.

Molecular genetics of substance use disorders: An umbrella review.

BACKGROUND: Substance use disorders (SUD) are a category of psychiatric disorders with a large epidemiological and societal impact around the world. In the last decades, a large number of genetic studies have been published for SUDs. METHODS: With the objective of having an overview and summarizing the evidence published up to date, we carried out an umbrella review of all the meta-analyses of genetic studies for the following substances: alcohol, tobacco, cannabis, cocaine, opioids, heroin and methamphetamines. Meta-analyses for candidate gene studies and genome-wide association studies (GWAS) were included. RESULTS: Alcohol and tobacco were the substances with the largest number of meta-analyses, and cannabis, opioids and cocaine the least studied. The following genes were associated with two or more SUDs: OPRM1, DRD2, DRD4, BDNF and SL6A4. The only genes that had an OR higher than two were the SLC6A4 for all addictions, the ADH1B for alcohol dependence, and BDNF for methamphetamine dependence. GWAS confirmed the possible role of CHRNA5 gene in nicotine dependence and identified novel candidate genes in other SUDs, such as FOXP2, PEX and, AUTS2, which need further functional analyses. CONCLUSIONS: This umbrella review summarizes the evidence of 16 years of research on the genetics of SUDs and provides a broad and detailed overview of results from more than 150 meta-analyses for SUD. The results of this umbrella review will guide the need for future genetic studies geared toward understanding, preventing and treating SUDs.

Common genes and pathways involved in the response to stressful stimuli by astrocytes: A meta-analysis of genome-wide expression studies.

Astrocytes play pivotal roles in the brain and they become reactive under stress conditions. Here, we carried out, for the first time, an integrative meta-analysis of genome-wide expression profiling of astrocytes from human and mouse exposed to different stressful stimuli (hypoxia, infections by virus and bacteria, cytokines, ethanol, among others). We identified common differentially expressed genes and pathways in human and murine astrocytes. Our results showed that astrocytes induce expression of genes associated with stress response and immune system regulation when they are exposed to stressful stimuli, whereas genes related to neurogenesis are found as downregulated. Several of the identified genes showed to be important hubs in the protein-protein interaction analysis (TRAF2, CDC37 and PAX6). This work demonstrates that despite astrocytes are highly heterogeneous and complex, there are common gene expression signatures that can be triggered under distinct detrimental stimuli, which opens an opportunity for exploring other possible markers of reactivity.

Functional Genomics of Epileptogenesis in Animal Models and Humans.

It has been estimated that epilepsies are among the top five neurological diseases with the highest burden of disease. In recent years, genome-wide expression studies (GWES) have been carried out in experimental models of epilepsy and in samples from human patients. In this study, I carried out meta-analyses and analyses of convergence for available GWES for epileptogenesis in humans and in mouse, rat, zebrafish and fruit fly models. Multiple lines of evidence (such as genome-wide association data and known druggable genes) were integrated to prioritize top candidate genes for epileptogenesis and a functional enrichment analysis was carried out. Several top candidate genes, which are supported by multiple lines of genomic evidence, such as GRIN1, KCNAB1 and STX1B, were identified. Druggable genes of potential interest (such as GABRA2, GRIK1, KCNAB1 and STX4) were also identified. An enrichment of genes regulated by the MEF2 and SOX5 transcription factors and the miR-106b-5p and miR-101-3p miRNAs was found. The current work is the first meta-analysis and convergent analysis of GWES for epileptogenesis in humans and in multiple animal models, integrating results from several genomic studies. Novel candidate genes and pathways for epileptogenesis were identified in this analysis.

A brief guide to the science and art of writing manuscripts in biomedicine.

Publishing articles in international scientific journals is the primary method for the communication of validated research findings and ideas. Journal articles are commonly used as a major input for evaluations of researchers and institutions. Few articles have been published previously about the different aspects needed for writing high-quality articles. In this manuscript, we provide an updated and brief guide for the multiple dimensions needed for writing manuscripts in the health and biological sciences, from current, international and interdisciplinary perspectives and from our expertise as authors, peer reviewers and editors. We provide key suggestions for writing major sections of the manuscript (e.g. title, abstract, introduction, methods, results and discussion), for submitting the manuscript and bring an overview of the peer review process and  of the post-publication impact of the articles.

Association between resilience and a functional polymorphism in the serotonin transporter (SLC6A4) gene: A meta-analysis.

Resilience is a mechanism used by humans to adapt to adverse situations. It is a protective factor against mental health problems. This process can be influenced by environmental and genetic factors. Several genes have been associated with interindividual differences in resilience levels, but the results are inconclusive. Therefore, the aim of this meta-analysis was to evaluate the effect of a functional polymorphism (5-HTTLPR) in the SLC6A4 gene on resilience levels. A search in PubMed, HugeNavigator and Google Scholar databases was carried out and 16 studies about the association of 5-HTTLPR polymorphism and resilience in humans were identified. The OpenMeta[Analyst] program was employed to perform statistical analysis using a random-effects model. The final analysis included 9 studies, for a total of 4,080 subjects. Significant results were found when the standardized mean differences (SMD) of LL and SL carriers were compared, (SMD: -0.087 (confidence interval: -0.166 to -0.008; I 2 : 0 %); P value: 0.031). A significant result was also found in an analysis comparing SS/SL versus LL genotypes (SMD: -0.231; confidence interval: -0.400 to -0.061, P value: 0.008; I 2 : 0 %). This is the first meta-analysis performed to identify the pooled association of a functional polymorphism in the serotonin transporter gene and resilience. The current results suggest that the L/L genotype is associated with resilience. Further studies are necessary to elucidate the role of genetics on the resilience mechanisms.

Recommendations for working from home during the COVID-19 pandemic (and beyond).

BACKGROUND: There is a growing trend around the globe for having more people working from home, particularly in the current COVID-19 pandemic. Although it is widely implemented in a number of countries and types of companies, it has shown to have multiple challenges. METHODS: In this article, we provide several recommendations on how to work from home, incorporating information from several publications. RESULTS: The suggestions are: create routines, be organized, have an adequate home office, enhance your productivity, be responsible, avoid extreme multitasking, facilitate communication and networking, be balanced, use available computer programs and platforms, be creative with remote teaching, explore options for remote research and learn from the challenges. CONCLUSIONS: These recommendations would help students, professors and researchers around the globe during the current COVID-19 pandemic, and beyond.

Integrative In Silico Analysis of Genome-Wide DNA Methylation Profiles in Schizophrenia.

Schizophrenia (SZ) is a complex and severe psychiatric disorder, which has a global lifetime prevalence of 0.4% and a heritability of around 0.81. A number of epigenome-wide association studies (EWAS) have been carried out for SZ, with discordant results. The main aim of this study was to carry out an integrative in silico analysis of available genome-wide DNA methylation profiles in schizophrenia. In this work, an integration of multiple lines of evidence (top candidate genes from several EWAS and genome-wide expression and association data) was carried out, in order to identify top differentially methylated (DM) genes for SZ. In addition, functional enrichment and protein-protein interaction analyses were carried out. Several top differentially methylated genes, such as APC, CACNB2, and PRKN, were found, and an enrichment of binding sites for brain-expressed transcription factors, such as FOXO1, MYB, and ZIC3, was also observed. Moreover, a protein-protein interaction network showed a central role for DISC1 and ZNF688 genes, and experimentally validated targets of MIR-137, such as and KCNB2, NRXN1, and SYN2, were identified among DM genes. This is the first integrative in silico analysis of available genome-wide DNA methylation profiles in schizophrenia. This work identified novel candidate genes and pathways for SZ and provides the basis to explore their role in the pathogenesis of SZ in future studies.