Toward Precision Medicine in Atopic Dermatitis Using Molecular-Based Approaches. / [Artículo traducido] Hacia una medicina de precisión en la dermatitis atópica mediante el uso de enfoques moleculares.

Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in developed countries. The pathophysiology of atopic dermatitis is complex and involves a strong genetic predisposition and T-cell driven inflammation. Although our understanding of the pathology and drivers of this disease has improved in recent years, there are still knowledge gaps in the immune pathways involved. Therefore, advances in new omics technologies in atopic dermatitis will play a key role in understanding the pathogenesis of this burden disease and could develop preventive strategies and personalized treatment strategies. In this review, we discuss the latest developments in genetics, transcriptomics, epigenomics, proteomics, and metagenomics and understand how integrating multiple omics datasets will identify potential biomarkers and uncover nets of associations between several molecular levels.

Toward Precision Medicine in Atopic Dermatitis Using Molecular-Based Approaches.

Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in developed countries. The pathophysiology of atopic dermatitis is complex and involves a strong genetic predisposition and T-cell driven inflammation. Although our understanding of the pathology and drivers of this disease has improved in recent years, there are still knowledge gaps in the immune pathways involved. Therefore, advances in new omics technologies in atopic dermatitis will play a key role in understanding the pathogenesis of this burden disease and could develop preventive strategies and personalized treatment strategies. In this review, we discuss the latest developments in genetics, transcriptomics, epigenomics, proteomics, and metagenomics and understand how integrating multiple omics datasets will identify potential biomarkers and uncover nets of associations between several molecular levels.

Toward an integrative molecular approach to wildlife disease.

Pathogens pose serious threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks. As such, wildlife managers are often tasked with mitigating the negative effects of disease. Yet, parasites form a major component of biodiversity that often persist. This is due to logistical challenges of implementing management strategies and to insufficient understanding of host-parasite dynamics. We advocate for an inclusive understanding of molecular diversity in driving parasite infection and variable host disease states in wildlife systems. More specifically, we examine the roles of genetic, epigenetic, and commensal microbial variation in disease pathogenesis. These include mechanisms underlying parasite virulence and host resistance and tolerance, and the development, regulation, and parasite subversion of immune pathways, among other processes. Case studies of devil facial tumor disease in Tasmanian devils (Sarcophilus harrisii) and chytridiomycosis in globally distributed amphibians exemplify the broad range of questions that can be addressed by examining different facets of molecular diversity. For particularly complex systems, integrative molecular analyses present a promising frontier that can provide critical insights necessary to elucidate disease dynamics operating across scales. These insights enable more accurate risk assessment, reconstruction of transmission pathways, discernment of optimal intervention strategies, and development of more effective and ecologically sound treatments that minimize damage to the host population and environment. Such measures are crucial when mitigating threats posed by wildlife disease to humans, domestic animals, and species of conservation concern.

Toward Precision Medicine in Atopic Dermatitis Using Molecular-Based Approaches / Hacia una medicina de precisión en la Dermatitis Atópica mediante el uso de enfoques moleculares

Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in developed countries. The pathophysiology of atopic dermatitis is complex and involves a strong genetic predisposition and T-cell driven inflammation. Although our understanding of the pathology and drivers of this disease has improved in recent years, there are still knowledge gaps in the immune pathways involved. Therefore, advances in new omics technologies in atopic dermatitis will play a key role in understanding the pathogenesis of this burden disease and could develop preventive strategies and personalized treatment strategies. In this review, we discuss the latest developments in genetics, transcriptomics, epigenomics, proteomics, and metagenomics and understand how integrating multiple omics datasets will identify potential biomarkers and uncover nets of associations between several molecular levels (AU)

La dermatitis atópica es el trastorno inflamatorio de la piel crónico más común. Afecta hasta a 20% de los niños y a 10% de los adultos en países desarrollados. La fisiopatología de la dermatitis atópica es compleja e implica una fuerte predisposición genética e inflamación impulsada por células T. Aunque nuestra comprensión de la patología y las causas de esta enfermedad ha mejorado en los últimos años, aún existen lagunas de conocimiento en las vías inmunológicas involucradas. En consecuencia, los avances en nuevas tecnologías ómicas en la dermatitis atópica desempeñarán un papel clave en la comprensión de la patogénesis de esta enfermedad y podrían desarrollar estrategias preventivas y tratamientos personalizados. En esta revisión se discuten los últimos avances en genética, transcriptómica, epigenómica, proteómica y metagenómica, y entendemos cómo la integración de múltiples conjuntos de datos ómicos identificará posibles biomarcadores y descubrirá redes de asociaciones entre varios niveles moleculares (AU)

[Artículo traducido] Hacia una medicina de precisión en la dermatitis atópica mediante el uso de enfoques moleculares / Toward Precision Medicine in Atopic Dermatitis Using Molecular-Based Approaches

La dermatitis atópica es el trastorno inflamatorio de la piel crónico más común. Afecta hasta a 20% de los niños y a 10% de los adultos en países desarrollados. La fisiopatología de la dermatitis atópica es compleja e implica una fuerte predisposición genética e inflamación impulsada por células T. Aunque nuestra comprensión de la patología y las causas de esta enfermedad ha mejorado en los últimos años, aún existen lagunas de conocimiento en las vías inmunológicas involucradas. En consecuencia, los avances en nuevas tecnologías ómicas en la dermatitis atópica desempeñarán un papel clave en la comprensión de la patogénesis de esta enfermedad y podrían desarrollar estrategias preventivas y tratamientos personalizados. En esta revisión se discuten los últimos avances en genética, transcriptómica, epigenómica, proteómica y metagenómica, y entendemos cómo la integración de múltiples conjuntos de datos ómicos identificará posibles biomarcadores y descubrirá redes de asociaciones entre varios niveles moleculares (AU)

Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in developed countries. The pathophysiology of atopic dermatitis is complex and involves a strong genetic predisposition and T-cell driven inflammation. Although our understanding of the pathology and drivers of this disease has improved in recent years, there are still knowledge gaps in the immune pathways involved. Therefore, advances in new omics technologies in atopic dermatitis will play a key role in understanding the pathogenesis of this burden disease and could develop preventive strategies and personalized treatment strategies. In this review, we discuss the latest developments in genetics, transcriptomics, epigenomics, proteomics, and metagenomics and understand how integrating multiple omics datasets will identify potential biomarkers and uncover nets of associations between several molecular levels (AU)

Asthma Exacerbations: The Genes Behind the Scenes

The clinical and socioeconomic burden of asthma exacerbations (AEs) constitutes a major public health problem. In the last 4 years, there has been an increase in ethnic diversity in candidate-gene and genome-wide association studies of AEs, which in the latter case led to the identification of novel genes and underlying pathobiological processes. Pharmacogenomics, admixture mapping analyses, and the combination of multiple “omics” layers have helped to prioritize genomic regions of interest and/or facilitated our understanding of the functional consequences of genetic variation. Nevertheless, the field still lags behind the genomics of asthma, where a vast compendium of genetic approaches has been used (eg, gene–environment interactions, next-generation sequencing, and polygenic risk scores). Furthermore, the roles of the DNA methylome and histone modifications in AEs have received little attention, and microRNA findings remain to be validated in independent studies. Likewise, the most recent transcriptomic studies highlight the importance of the host–airway microbiome interaction in the modulation of risk of AEs. Leveraging -omics and deep-phenotyping data from subtypes or homogenous subgroups of patients will be crucial if we are to overcome the inherent heterogeneity of AEs, boost the identification of potential therapeutic targets, and implement precision medicine approaches to AEs in clinical practice (AU)

La carga clínica y socioeconómica de las exacerbaciones asmáticas (EA) representa un importante problema de salud pública. En los últimos cuatro años, ha aumentado la diversidad étnica en los estudios de asociación de genes candidatos y del genoma completo (GWAS) de las EA, lo que, en este último caso, ha llevado a la identificación de nuevos genes y procesos fisiopatológicos subyacentes. La farmacogenómica, los análisis de mapeo por mezcla y la combinación de múltiples capas "ómicas" han contribuido a priorizar regiones genómicas de interés y/o comprender las consecuencias funcionales de la variación genética. A pesar de esto, el campo todavía está en desarrollo en comparación con la genómica del asma, donde se ha utilizado un amplio compendio de enfoques genéticos (por ejemplo: interacciones gen-ambiente, secuenciación de nueva generación o puntuaciones de riesgo poligénico). Además, el papel de la metilación del ADN y las modificaciones de las histonas en las EA se ha explorado escasamente, y los hallazgos relacionados con los microARNs aún no se han validado en estudios independientes. Asimismo, los estudios transcriptómicos más recientes destacan la importancia de la interacción entre el microbioma de las vías respiratorias y el huésped en la modulación del riesgo de las EA. La integración de datos ómicos y de fenotipado profundo de subtipos o subgrupos homogéneos de pacientes será crucial para superar la heterogeneidad inherente de las EA e impulsar la identificación de dianas terapéuticas potenciales y la implementación de la medicina de precisión para las EA en la práctica clínica (AU)

Imaginando el futuro / Looking to the future

Presentamos la visión futurista que de su especialidad tienen 7 líderes de opinión estrechamente comprometidos con la patología mamaria. Las especialidades incluidas fueron radiología, patología, cirugía, cirugía plástica, medicina nuclear, oncología médica y oncología radioterápica. Los autores plasman, en este artículo, sus opiniones y criterios respecto a los avances que vislumbran en su futuro profesional.Conceptos clave como sistemas de cribado sin radiación, transcriptómica clínica, diagnóstico funcional del tumor, inteligencia artificial, navegación intraoperatoria, biopsia líquida, ADN tumoral circulante, reconstrucción con técnicas microquirúrgicas avanzadas, hipofraccionamiento extremo o teragnosis, son algunos de los conceptos presentados y discutidos.Los autores justifican sus puntos de vista, abriendo líneas de trabajo a tener en cuenta para optimizar esfuerzos y el conocimiento futuro. (AU)

We present the futuristic vision of their specialty of seven opinion leaders closely involved in breast pathology. The specialties were radiology, pathology, surgery, plastic surgery, nuclear medicine, medical oncology, and radiation oncology. In this article, the authors express their opinions and criteria regarding the advances they foresee for their professional future.Key concepts such as radiation-free screening systems, clinical transcriptomics, functional tumor diagnosis, artificial intelligence, intraoperative navigation, liquid biopsy, circulating tumor DNA, reconstruction with advanced microsurgical techniques, extreme hypofractionation or theragnosis are some of the concepts presented and discussed.The authors justify their points of view, suggesting lines of work to optimize efforts and future knowledge. (AU)

Cuantificación de la expresión del gen amo-A en poblaciones bacterianas y archaeales presentes en muestras de suelos de un lote arrocero caracterizado por ambientes

El ciclo del nitrógeno representa uno de los procesos biogeoquímicos más importantes para los ecosistemas terrestres y acuáticos. Las comunidades microbianas desempeñan un papel crucial en los procesos de transformación del nitrógeno en el suelo, ya que participan en diversas etapas como la nitrificación, de gran importancia para la producción agrícola. Dentro de los marcadores moleculares más utilizados para evaluar la actividad de poblaciones microbianas oxidantes de amonio se han considerado ampliamente los genes que codifican enzimas claves como la subunidad A de la actividad amonio monooxigenasa (AMO). Sin embargo, no se comprende completamente si la expresión de esta enzima tiene relación directa con el rendimiento de los cultivos. En este contexto, se evaluó la expresión del gen amo-A de comunidades bacterianas y archaeales presentes en un lote arrocero previamente caracterizado por ambientes. Para cuantificar la abundancia de arqueas y bacterias oxidantes de amonio, (AOA y AOB, respectivamente) se emplearon las técnicas de PCR en tiempo real (RT-qPCR) y PCR digital (RT-dPCR). En este trabajo se encontró a través del análisis de datos metagenómicos que hubo una mayor presencia de AOB en las muestras de suelo rizosférico mientras que las AOA fueron predominantes en las muestras de suelo de soporte "bulk", sin embargo, no se detectó la expresión del gen amo-A asociada a la comunidad de bacterias en las muestras de suelo analizadas. Por otra parte, no se presentaron diferencias entre los transcritos del gen amo-A asociados a la comunidad de AOA de los ambientes caracterizados. Además, la expresión de transcritos no estuvo relacionada con alguna de las propiedades químicas evaluadas. Finalmente, las estrategias de cuantificación para RT-qPCR (plásmido y templete) resultaron ser homólogas y funcionales para identificar la expresión del gen amo-A de AOA, mientras que la técnica de RT-dPCR fue más precisa para el análisis de la comunidad de AOB y AOA.

The nitrogen cycle represents one the most important biogeochemical process for terrestrial and aquatic ecosystems. Microbial communities play a crucial role in the processes of transformation of soil nitrogen in the, since they participate in various stages such as nitrification, which is of great importance for agricultural production. Among the most used molecular markers to assess ammonium oxidizing microbial populations activity have been considered widely the genes encoding key enzymes such as ammonium monooxygenase (AMO) subunit A. However, it is not fully understood whether the expression of this enzyme is directly related to the crop yield. In this context, this research work evaluated the expression of the amo-A gene of bacterial and archaeal communities present in a rice field previously characterized by environments. Real-time PCR (RT-qPCR) and digital PCR (RT-dPCR) techniques were used to quantify the abundance of archaea and ammonium-oxidizing bacteria (AOA and AOB, respectively). In this work it was found that in the analysis of metagenomic data there was a greater presence of AOB in rhizospheric soil samples while AOA were predominant in bulk soil samples, however, the expression of the amo-A gene was not detected. associated with the community of bacteria in the soil samples analyzed. On the other hand, it was found that the transcripts of the amo-A gene of the AOA community did not present differences between the characterized environments. Furthermore, the expression of transcripts is not related to any of the chemical properties evaluated. Finally, the quantification strategies for RT-qPCR (plasmid and quenching) turned out to be homologous and functional to identify the expression of the AOA amo-A gene, while the RT-dPCR technique was more precise for the analysis of the community of AOB and AOA.

A peep into the transcriptome studies of the industrially important brown algae with special focus on Macrocystis genus / Una mirada a los estudios de transcriptoma en algas pardas de importancia industrial, en especial del género Macrocystis

Abstract Brown algae are a commercial source of different polysaccharides/hydrocolloids that has been used to produce food, pharmaceutical, and several other useful biotechnological stuff. Nevertheless, transcriptomics has become a tool that not only provides valuable information for the understanding of the physiological processes of a species but also allows the identification of industrially important candidate genes. This study describes the transcriptome of brown algae and their industrial application with a special focus on Macrocystis integrifolia.

Resumen Las algas pardas son una fuente comercial de diferentes polisacáridos / hidrocoloides utilizados para producir alimentos, productos farmacéuticos y otros productos biotecnológicos útiles. Por otra parte, la transcriptómica se ha convertido en una herramienta que no solo proporciona información valiosa para la comprensión de los procesos fisiológicos de una especie, sino que también permite la identificación de genes candidatos industrialmente importantes. Este estudio describe el transcriptoma de algas pardas y su aplicación industrial con un enfoque especial en Macrocystis integrifolia.

Co-Expression Network Analysis Identifies Possible Hub Genes in Aging of the Human Prefrontal Cortex / Análisis de redes de coexpresión identifica posibles genes clave en el envejecimiento de la corteza prefrontal humana / Análise de redes de co-expressão identifica possíveis genes chave no envelhecimento do córtex pré-frontal humano

Abstract Introduction : Aging is the main risk factor for the development of chronic diseases such as cancer, diabetes, Parkinson's disease, and Alzheimer's disease. The central nervous system is particularly susceptible to progressive functional deterioration associated with age, among the brain regions the prefrontal cortex (PFC) has one of the highest involvements. Transcriptomics studies of this brain region have identified the decrease in synaptic function and activation of neuroglia cells as fundamental characteristics of the aging process. The aim of this study was to identify hub genes in the transcriptomic deregulation in the PFC aging to advance in the knowledge of this process. Materials and methods : A gene co-expression analysis was carried out for 45 people 60 to 80 years old compared with 38 people 20 to 40 years old. The networks were visualized and analyzed using Cytoscape; citoHubba was used to determine which genes had the best topological characteristics in the co-expression networks. Results : Five genes with high topological characteristics were identified. Four of them -HPCA, CACNG3, CA10, PLPPR4- were repressed and one was over-expressed -CRYAB-. Conclusion: The four repressed genes are expressed preferentially in neurons and regulate the synaptic function and the neuronal plasticity, while the overexpressed gene is typical of glial cells and is expressed as a response to neuronal damage, facilitating myelination and neuronal regeneration.

Resumen Introducción : el envejecimiento es el principal factor de riesgo para el desarrollo de enfermedades crónicas como el cáncer, la diabetes, el Parkinson y el Alzheimer. El sistema nervioso central es particularmente susceptible al deterioro funcional progresivo asociado con la edad, entre las regiones cerebrales con mayor compromiso se encuentra la corteza prefrontal (CPF). Estudios de transcriptómica de esta región han identificado como características fundamentales del proceso de envejecimiento la disminución de la función sináptica y la activación de las células de la neuroglia. No es claro cuáles son las causas iniciales, ni los mecanismos moleculares subyacentes a estas alteraciones. El objetivo de este estudio fue identificar genes clave en la desregulación transcriptómica en el envejecimiento de la CPF para avanzar en el conocimiento de este proceso. Materiales y métodos : se hizo un análisis de coexpresión de genes de los transcriptomas de 45 personas entre 60 y 80 años con el de 38 personas entre 20 y 40 años. Las redes fueron visualizadas y analizadas usando Cytoscape, se usó citoHubba para determinar qué genes tenían las mejores características topológicas en las redes de coexpresión. Resultados : se identificaron cinco genes con características topológicas altas. Cuatro de ellos -HPCA, CACNG3, CA10, PLPPR4- reprimidos y uno sobreexpresado -CRYAB-. Conclusión : los cuatro genes reprimidos se expresan preferencialmente en neuronas y regulan la función sináptica y la plasticidad neuronal, mientras el gen sobreexpresado es típico de células de la glía y se expresa como respuesta a daño neuronal facilitando la mielinización y la regeneración neuronal.

Resumo Introdução : o envelhecimento é o principal fator de risco pra o desenvolvimento de doenças crónicas como o câncer, a diabetes, o Parkinson e o Alzheimer. O sistema nervoso central é particularmente susceptível ao deterioro funcional progressivo associado à idade, uma das regiões do cérebro com maior compromisso é o pré-frontal (CPF). Estudos de transcritoma desta região têm identificado como características fundamentais do processo de envelhecimento a diminuição da função sináptica e ativação das células da neuroglia. Não é claro quais são as causas iniciais, nem os mecanismos moleculares subjacentes a estas alterações. O objetivo deste estudo foi identificar genes chave na desregulação transcritoma no envelhecimento da CPF para avançar no conhecimento deste processo. Materiais e métodos : se fez uma análise de co-expressão de genes dos transcritomas de 45 pessoas entre 60 e 80 anos com o de 38 pessoas entre 20 e 40 anos. As redes foram visualizadas e analisadas usando Cytoscape, usou-se citoHubba para determinar que genes tinham as melhores características topológicas nas redes de co-expressão. Resultados : identificaram-se cinco genes com características topológicas altas. Quatro deles -HPCA, CACNG3, CA10, PLPPR4- reprimidos e um superexpresso -CRYAB-. Conclusão : os quatro genes reprimidos se expressam preferencialmente em neurônios e regulam a função sináptica e plasticidade neuronal, enquanto o gene superexpresso é típico de células da glia e se expressa como resposta ao dano neuronal facilitado a mielinização e a regeneração neuronal.

Expresión diferencial de genes involucrados en la respuesta al estrés por helada en Solanum tuberosum subsp. andigena

La helada es un fenómeno meteorológico caracterizado por la disminución de la temperatura del aire por debajo de cero grados centígrados que provocan estrés térmico en las plantas, es uno de los problemas de mayor incidencia e impacto en la agricultura andina. Por otro lado, estudios morfológicos y fisiológicos señalan a las papas nativas como fuentes de tolerancia genética a las bajas temperaturas. Sin embargo, las bases moleculares de los mecanismos de tolerancia en papa, aún son desconocidas. La tecnología del secuenciamiento de ARN (RNA-seq) es una excelente herramienta que permite identificar cambios en los perfiles de expresión génica tras el estrés por helada. En este trabajo, el transcriptoma de una variedad de papa tolerante y otra variedad susceptible a helada fueron secuenciados y comparados después de la exposición al estrés por helada (-8 °C) durante una hora, utilizando la técnica del RNA-seq para identificar diferencias en la expresión de genes entre ambas variedades. Se observó que más de 199 millones de lecturas de RNA-seq fueron alineadas al genoma de referencia ( Solanum tuberosum Grupo Phureja), lo que corresponde al 82.1% del total de las lecturas obtenidas tras el secuenciamiento. En cuanto a la modulación en la expresión de genes, la variedad tolerante presentó el mayor número de genes expresados diferencialmente ( Differentially Expressed Genes, DEGS) sobreexpresados (262 DEGs) y la variedad susceptible presentó el mayor número de DEGs reprimidos (37 DEGs) tras el estrés por helada.

Freezing is abiotic stress characterized by a decrease air temperature below zero degrees Celsius. It is one of the highest incidence and impact problems in Andean´s agriculture. Morphological and physiological studies indicate that native potatoes are sources of genes related to plant frost tolerance. However, the molecular bases of tolerance mechanisms in potato are still unknown. RNA sequencing technology (RNA-seq) is an excellent tool to identify genes expression profile changes after freezing stress. In this work, the transcriptome of a freezing tolerant and another susceptible variety of potato were sequenced and compared after exposition to freezing stress (-8 °C) for an hour, using the RNA-seq technique to identify differences in the genes expression between both varieties. It was observed that more than 199 million reads were aligned against the reference genome (Solanum tuberosum Group Phureja), which correspond to 82.1% of the total reads obtained after sequencing. The tolerant variety showed the highest number of Differentially Expressed Genes (DEGs) upexpressed (262 DEGs), while the susceptible variety showed the highest number of down-expressed DEGs (37 DEGs).

Caracterização de adaptações do repertório molecular de serpentes das tribos Xenodontini e Pseudoboini relacionadas à sua ecologia de predação

Among the wide spectrum of food ecologies, some groups of snakes have become ophiophagous, feeding mainly on other snakes. Due to the relationship between diet and venom composition, these ophiophagous groups probably needed to develop specific toxins targeting snakes and some type of resistance to the venoms of the snakes they preyed on, associating these characteristics with the development of ophiophagy. In the Neotropics, more precisely in the Dipsadidae family, there are several ophiophagous species. The genus Erythrolamprus (Tribe Xenodontini) and the genera Clelia and Boiruna (Tribe Pseudoboini) contain species that are specialists in snakes. However, due to their relatively low medical relevance, they have been poorly studied and there is scarce information about their venoms and possible resistance factors or mechanisms. In the present work, the toxin composition of the venom gland transcriptome of 8 genera and 19 species of the tribe Pseudoboini and 3 genera and 8 species of the tribe Xenodontini was analyzed. In addition to being the first compositional analysis of the venom of the two tribes, a new type of enzymatic toxins exclusive to the Dipsadidae family (the svMMPs) was identified and characterized in the analyzed samples, as well as high expression levels of a type of phospholipases A2 in some species of the Pseudoboini tribe was detected. On the other hand, comparisons between liver transcriptomes and plasma proteomes of ophiophagous and non-ophiophagous species of the tribe Pseudoboini allowed identifying high expression levels of several types of toxin inhibitors. However, the occurrence of overexpression of these inhibitors in ophiophagous species was not detected. The analyzes revealed, in a broad scale, the evolutionary novelties present in the compositional profile of the venoms of the two tribes and verified the occurrence of plasma toxin inhibitors in the analyzed species.

Dentre o amplo espectro de ecologias alimentares, alguns grupos de serpentes tornaram-se ofiófagos, alimentando-se principalmente de outras serpentes. Devido à relação entre a dieta e a composição do veneno, esses grupos ofiófagos provavelmente precisaram desenvolver toxinas específicas para serpentes e algum tipo de resistência aos venenos das serpentes que predavam, associando essas características ao desenvolvimento da ofiofagia. Nos neotrópicos, mais precisamente na família Dipsadidae, ocorrem diversas espécies ofiófagas. O gênero Erythrolamprus (Tribo Xenodontini) e os gêneros Clelia e Boiruna (Tribo Pseudoboini) contêm espécies especialistas em serpentes. No entanto, devido à sua relevância médica relativamente baixa, foram pouco estudados e existem poucas informações sobre seus venenos e possíveis fatores ou mecanismos de resistência. No presente trabalho foi analisada a composição de toxinas do transcriptoma da glândula de veneno de 8 gêneros e 19 espécies da tribo Pseudoboini e de 3 gêneros e 8 espécies da tribo Xenodontini. Além de ser a primeira análise composicional do veneno das duas tribos, permitiu a identificação e caracterização de um novo tipo de toxinas enzimáticas exclusivo da família Dipsadidae (as svMMPs), assim como revelou níveis de expressão elevados de um tipo de fosfolipases A2 em algumas espécies da tribo Pseudoboini. Por outro lado, as comparações entre os transcriptomas do fígado e os proteomas do plasma de espécies ofiófagas e não ofiófagas da tribo Pseudoboini indicaram níveis de expressão elevados de vários tipos de inibidores de toxinas. Porém, não foi detectada a ocorrência de sobre expressão destes inibidores nas espécies ofiófagas. As análises revelaram, em escala abrangente, as novidades evolutivas presentes no perfil composicional dos venenos das duas tribos e verificaram a ocorrência de inibidores de toxinas plasmáticos nas espécies analisadas.

Proteômica e transcriptômica aplicadas ao estudo da variabilidade do veneno Bothrops jararaca ( Serpentes Viperidae) / A proteomics and transcriptomics applied to the study of Bothrops jararaca venom variability ( Serpentes viperidae)

Estudos prévios demonstram que as atividades biológicas do veneno da serpente Bothrops jararaca sofrem significantes modificações ontogenéticas. Neste estudo é apresentada uma análise comparativa do proteoma, peptidoma e transcriptoma da glândula de veneno de filhotes e adultos de B. jararaca, correlacionando os resultados obtidos com algumas catacterísticas funcionais dos venenos...

Previous studies have demonstrated that the biological activities displayed by the venom of snake Bothrops jararaca undergo a significant ontogenic shift. In this investigation, we performed comparative proteomic, peptidomic and transcriptomic analyses of venoms and venom glands from newborn and adult specimens of B. jararaca and correlated the results with the evaluation of functional venom features...

Proteômica e transcriptômica aplicadas ao estudo da variabilidade do veneno de Bothrops jararaca (serpentes:viperidae) / Proteomics and transcriptomics applied to the study of Bothrops jararaca venom variability (Serpentes: Viperidae)

Estudos prévios demonstraram que as atividades biológicas do veneno da serpente Bothrops jararaca sofrem significantes modificações ontogenéticas. Neste estudo é apresentada uma análise comparativa do proteoma, peptidoma e transcriptoma da glândula de veneno de filhotes e adultos de B. jararaca, correlacionando os resultados obtidos com algumas características funcionais dos venenos. Venenos de 694 filhotes de até duas semanas de idade e 110 adultos, provenientes do Estado de São Paulo foram extraídos e liofilizados para as análises proteômicas/peptidômicas e funcionais. O mRNA de glândulas de veneno de 20 filhotes e 10 adultos foi obtido para a contrução de bibliotecas de cDNA e a análise de Expressed Sequence Tag (ESTs). Demonstramos que a atividade hemorrágica é similar para os venenos de filhotes e adultos, enquanto que o veneno de adultos é discretamente mais letal para camundongos; entretanto, o veneno de filhotes mostrou-se extremamente mais letal para aves, uma característica que pode garantir proteção contra potenciais predadores nas fases iniciais de vida da espécie. A atividade coagulante do veneno de filhotes é cerca de 10 vezes mais alta que aquela verificada para o veneno de adultos e é atribuída sobretudo à atividade de metaloproteinases. Essas diferenças nas atividades funcionais se refletiram nos diferentes perfis verificados por eletroforese bidimensional e identificação de spots de proteínas por digestão tripsínica in-gel seguida de análise por cromatografia líquida acoplada à espectrometria de massas em tandem, zimografia com gelatina, imunocoloração utilizando anticorpos específicos anti-proteinases, e glicoproteínas com afinidade pela concanavalina -A. A comparação dos venenos por derivatização com tags isóbaros (iTRAQ) e a análise das ESTs revelaram diferenças claras entre os níveis de toxinas presentes nos venenos e as metaloproteinases foram a classe de toxinas mais expressa, além de serem as toxinas cujos perfis estruturais ...

Previous studies have demonstrated that the biological activities displayed by the venom of the snake Bothrops jararaca undergo a significant ontogenetic shift. In this investigation, we performed comparative proteomic, peptidomic and transcriptomic analyses of venoms and venom glands from newborn and adult specimens of B. jararaca and correlated the results with the evaluation of functional venom features. Venoms from 694 two-week old newborns and 110 adults from São Paulo state were milked and lyophilized for functional and proteomic/peptidomic analyses. Additionally, mRNA was obtained from the venom glands of 20 newborns and 10 adults and used for the construction of cDNA libraries and Expressed Sequence Tag (ESTs). We demonstrate that newborn and adult venoms have similar hemorrhagic activities, while the adult venom has a slightly higher lethal activity upon mice; however, the newborn venom is extremely more potent to kill chicks, a feature that might ensure protection against potential predators in early stages of B. jararaca life. Interestingly, the coagulant activity of the newborn venom upon human plasma is ten times higher than that of the adult venom and is contributed mainly by metalloproteinases. Differences in functional activities were clearly reflected in the venom different profiles of two-dimensional gel electrophoresis (2D-PAGE) and protein spot identification by in-gel trypsin digestion followed by liquid chromatography and tandem mass spectrometry (LC-MS/MS), gelatin zimography, immunostaining using specific anti-proteinase antibodies, and concanavalin A-binding proteins. The venom comparison by isobaric tag peptide labeling (iTRAQ) and ESTs analysis revealed clear differences in toxin levels. The metalloproteinases were detected as the toxin class most expressed in the venoms in addition to being the toxins whose structural profile most changed, as illustrated by the ratio P-III/P-I class being higher in newborn venoms. Sexual ...

Contribuição das ômicas na saúde humana: avanços e desafios / Contribution of the omics siences to human health: advances and challenges

O seqüenciamento do genoma humano abriu portas para uma era de descrições holísticas sobre a saúde humana. Hoje, é possível estudar os mecanismos biológicos humanos em relação a dietas e fatores ambientais como drogas e poluentes. Nopassado, as pesquisas científicas estiveram muito focadas nas doenças e em como restabelecer a saúde humana após estas enfermidades. Atualmente, a prevenção das doenças vem ganhando maior atenção e reconhecimento. Para que se possa entender a relação do ambiente com a saúde, as pesquisas devem abranger uma ampla faixa de áreas, desde níveis moleculares até o estudo do corpo como um todo. Ultimamente, têm sido revistas as implicações do sistema biológico no entendimento da saúde humana e é sabido que a descrição mecanicista completa do organismo humano ainda não é possível. Entretanto, recentes avanços no estudo da biologia dos sistemas determinam uma trajetória para as pesquisas futuras garantindo melhora das condições de saúde individuais e das populações. A prevenção de doenças se tornará mais importante, sendo vista como o caminho óbvio para pesquisas em ciências da vida. Além disso, mais ênfase será dada nesses caminhos naturais. Novas disciplinas mediarão recentes percepções sobre a saúde humana que, sem dúvida, terão significante impacto positivo em nossa qualidade de vida.

The sequencing of the human genome has opened the door to the most exciting new era of the holistic system description of human health. It is now possible to study the mechanisms of human health in relation to diet and other environmental factors such as drugs and toxic pollutants. Life-Science research has in the past much focused on diseases and how to reestablish human health after illness. Today, prevention of illness is gaining recognition. To understand the link between environment and health, research must cover a broad range of areas, from the molecular level to whole body studies. The current state and implications of systems biology in the understanding of human health are reviewed. It becomes clear that a complete mechanistic description of the human organism is not possible yet. However, recent advances in systems biology provide a trajectory for future research in order to improve health of individuals and populations. Disease prevention will become more important as the obvious path of research in life sciences and more focus will need to be put in those natural ways. The new disciplines, will mediate new insights into human health that will finally have significant positive impact on our quality of life.