RESUMEN

We are launching a series to celebrate the 40th anniversary of the first issue of Molecular Biology and Evolution. In 2024, we will publish virtual issues containing selected papers published in the Society for Molecular Biology and Evolution journals, Molecular Biology and Evolution and Genome Biology and Evolution. Each virtual issue will be accompanied by a perspective that highlights the historic and contemporary contributions of our journals to a specific topic in molecular evolution. This perspective, the first in the series, presents an account of the broad array of methods that have been published in the Society for Molecular Biology and Evolution journals, including methods to infer phylogenies, to test hypotheses in a phylogenetic framework, and to infer population genetic processes. We also mention many of the software implementations that make methods tractable for empiricists. In short, the Society for Molecular Biology and Evolution community has much to celebrate after four decades of publishing high-quality science including numerous important inferential methods.

Asunto(s)

RESUMEN

O carcinoma mioepitelial é uma doença incomum que tem origem majoritariamente nas glândulas salivares. A sua ocorrência no pulmão é um achado extremamente raro e acredita-se ter origem nas glândulas brônquicas submucosas do trato respiratório inferior. Marcado pela sua grande diversidade citológica e arquitetônica, que recapitula as características celulares e imunofenotípicas das células mioepiteliais, é uma neoplasia tipicamente de alto grau e comportamento agressivo, sendo facilmente confundida com outras neoplasias torácicas e representando um desafio diagnóstico. Não há diretrizes estabelecidas para o tratamento ­ a cirurgia parece ser a melhor alternativa, uma vez que o papel da quimioterapia e radioterapia é incerto. Este é um estudo observacional descritivo retrospectivo em modelo de relato de caso realizado através de avaliação do prontuário de um paciente com diagnóstico de carcinoma mioepitelial pulmonar matriculado no INCA no período de setembro a novembro de 2023. Para a discussão do tema, esse trabalho também contou com uma revisão da literatura médica utilizando os dados obtidos através das plataformas Pubmed, Scielo e Google acadêmico. Após extensa pesquisa, encontramos apenas 21 casos publicados de carcinoma mioepitelial pulmonar e acreditamos que a dificuldade técnica envolvida no diagnóstico, sobreposta as barreiras de tecnologia e conhecimento do passado, possam ter contribuído para subestimar o número de casos dessa neoplasia. Nesse contexto, o carcinoma mioepitelial pulmonar primário deve ser incluído no diagnóstico diferencial das neoplasias torácicas. Embora mais estudos sejam necessários para esclarecimento dos aspectos moleculares e estratégias terapêuticas, o tratamento individualizado é uma estratégia clínica promissora para neoplasias torácicas em geral e os eventos moleculares subjacentes devem ser investigados para encontrar os potenciais alvos terapêuticos

Myoepithelial carcinoma is an uncommon disease that originates mainly in the salivary glands. Its occurrence in the lung is an extremely rare finding and is believed to originate from the submucosal bronchial glands of the lower respiratory tract. Marked by its great histological and architectural diversity, which recapitulates the cellular and immunophenotypic characteristics of myoepithelial cells, it is a typically high-grade neoplasm with aggressive behavior, being easily confused with other thoracic neoplasms and representing a diagnostic challenge. There are no established guidelines for treatment ­ upfront surgery appears to be the best alternative, as the role of chemotherapy and radiotherapy is uncertain. This is a retrospective descriptive observational study using a case report model carried out by evaluating the medical records of a patient diagnosed with pulmonary myoepithelial carcinoma enrolled at INCA from september to november 2023. To discuss the topic, this work also included a review of the medical literature using data obtained from Pubmed, Scielo and Google Scholar. We found Only 21 published cases of pulmonary myoepithelial carcinoma on research platforms and we believe that the technical difficulty involved in diagnosis, combined with technology and knowledge barriers from the past, may have contributed to underestimating the number of cases of this neoplasm. In this context, primary pulmonary myoepithelial carcinoma should be included in the differential diagnosis of thoracic neoplasms. Although further studies are needed to clarify the molecular aspects and therapeutic strategies, individualized treatment is a promising clinical strategy for thoracic neoplasms in general and the underlying molecular events must be investigated to find potential therapeutic targets.

Asunto(s)

RESUMEN

Brazilian mammarenavirus, or Sabiá virus (SABV), is a New World (NW) arenavirus associated with fulminant hemorrhagic disease in humans and the sole biosafety level 4 microorganism ever isolated in Brazil. Since the isolation of SABV in the 1990s, studies on viral biology have been scarce, with no available countermeasures against SABV infection or disease. Here we provide a comprehensive review of SABV biology, including key aspects of SABV replication, and comparisons with related Old World and NW arenaviruses. SABV is most likely a rodent-borne virus, transmitted to humans, through exposure to urine and feces in peri-urban areas. Using protein structure prediction methods and alignments, we analyzed shared and unique features of SABV proteins (GPC, NP, Z, and L) that could be explored in search of therapeutic strategies, including repurposing intended application against arenaviruses. Highly conserved catalytic activities present in L protein could be targeted for broad-acting antiviral activity among arenaviruses, while protein-protein interactions, such as those between L and the matrix protein Z, have evolved in NW arenaviruses and should be specific to SABV. The nucleoprotein (NP) also shares targetable interaction interfaces with L and Z and exhibits exonuclease activity in the C-terminal domain, which may be involved in multiple aspects of SABV replication. Envelope glycoproteins GP1 and GP2 have been explored in the development of promising cross-reactive neutralizing antibodies and vaccines, some of which could be repurposed for SABV. GP1 remains a challenging target in SABV as evolutive pressures render it the most variable viral protein in terms of both sequence and structure, while antiviral strategies targeting the Z protein remain to be validated. In conclusion, the prediction and analysis of protein structures should revolutionize research on viruses such as SABV by facilitating the rational design of countermeasures while reducing dependence on sophisticated laboratory infrastructure for experimental validation.

Asunto(s)

RESUMEN

Objective: The aim of this study is to investigate the molecular genetic causes of non-syndromic primary ovarian insufficiency (POI) cases with the gene panel basedon next generation sequencing analysis and to establish the relationship between genotype and phenotype. Materials and methods: Twenty three cases aged 14-40 years followed up with POI were included. Patients with a karyotype of 46, XX, primary or secondary amenorrhea before the age of 40, with elevated FSH (>40 IU/mL) and low AMH levels (<0.03 ng/mL) were included in the study. Molecular genetic analyzes were performed by the next generation sequencing analysis method targeted with the TruSight TM Exome panel. Results: Median age of the cases was 17.8 (14.0-24.3) years, and 12 (52%) cases admitted before the age of 18. Fifteen (65%) patients had consanguineous parents. In2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene. Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype. Conclusion: Genetic panels based on next generation sequencing analysis technologies can be used to determine the molecular genetic diagnosis of POI, which has a highly heterogeneous genetic basis.

Asunto(s)

Asunto(s)

RESUMEN

Background and Objectives: Recently, complementary resources and equipment have emerged to improve prevention of healthcare-associated infections (HAIs). Our aim is to verify availability and use of different resources/ equipment by infection controllers. Methods: We conducted a survey with infection controllers from the State of Rio de Janeiro, Brazil, by invitation using a social media group, in August 2022. Nine different resources and equipment were evaluated. Categorical and continuous variables were evaluated by the chi-square test and Mann­Whitney U test, respectively. A p value of less than 0.05 was considered statistically significant. Results: One hundred and eight persons answered the questionnaire. The mean age was 42.8 years (SD +/- 8.5 years) and 53 (49.1%) reported most of their workload in public hospitals, 45 (41.7%) in private hospitals and 10 (9.2%) reported the same workload in public and private hospitals. Sixty-there percent reported teaching activities in their institutions. There was no correlation between the existence of teaching activities and hospital profile (p=0.42). The most common resource available was molecular biology (PCR) for microbiological samples research for 73 (67.6%) participants. The second resource most available was applications (Apps) for HAIs prevention and control for 33 (30.6%), 19 (17.6%) reported no availability of resource/equipment technology. Conclusion: Molecular biology (PCR) for microbiological samples research was the most common resource available for infection controllers of an important state of Brazil.(AU)

Justificativas e Objetivos: Recentemente, recursos e equipamentos complementares têm surgido para melhorar a prevenção de infecções relacionadas à assistência à saúde. O objetivo deste artigo é verificar a disponibilidade e o uso de diferentes recursos e equipamentos pelos controladores de infecção. Métodos: Realizamos uma pesquisa do tipo survey com controladores de infecção do estado do Rio de Janeiro, por meio de convite pela mídia social, em agosto de 2022. Nove diferentes recursos e equipamentos foram avaliados quanto à disponibilidade e ao uso. Variáveis categóricas e contínuas foram avaliadas pelo teste qui-quadrado e Mann-Whitney, respectivamente. Um valor de p menor que 0,05 foi considerado estatisticamente significativo. Resultados: Cento e oito pessoas responderam ao questionário. A média de idade foi de 42,8 anos (DP +/- 8,5 anos), e 53(49,1%) relataram maior carga de trabalho em hospitais públicos, 45 (41,7%) em hospitais privados e 10(9,2%) carga horária similar nos dois tipos de hospitais. Dos 108, 63% relataram a existência de atividades de ensino nas instituições. Não houve correlação entre existência de atividades de ensino e tipo de hospital (p=0,42). O recurso mais disponível foi o uso de biologia molecular (reação em cadeia de polimerase) por 73 (67,6%) participantes. A segunda ferramenta mais encontrada foi o uso de aplicativos para prevenção e controle de infecção para 33 (30,6%) desses participantes. Dezenove deles (17,6%) relataram ausência de todos os recursos/equipamentos. Conclusão: O uso de biologia molecular para pesquisa de amostras biológicas foi o recurso mais disponível para controladores de infecção de um importante estado brasileiro.(AU)

Antecedentes y objetivos: Recientemente han surgido recursos y equipos complementarios para mejorar la prevención de las infecciones asociadas a la atención de la salud. El objetivo es verificar la disponibilidad y el uso de diferentes recursos/equipos por los controladores de infecciones. Métodos: Realizamos una encuesta entre los controladores de infecciones del estado de Rio de Janeiro, Brasil, por invitación en redes sociales, en agosto de 2022. Se evaluó la disponibilidad y uso de nueve recursos y equipos diferentes. Las variables categóricas y continuas se evaluaron mediante las pruebas de chi-cuadrado y Mann-Whitney, respectivamente. Se consideró estadísticamente significativo un valor de p < 0.05. Resultados: Ciento ocho personas respondieron al cuestionario. La edad media fue de 42,8 años (DE +/- 8,5 años) y 53 (49,1%) reportaron mayor carga de trabajo en hospitales públicos, 45 (41,7%) en privados y 10 (9,2%) reportaron la misma carga en hospitales públicos y privados. De los 108, el 63% reportó actividades docentes en sus instituciones. No hubo correlación entre la existencia de actividades docentes y el tipo de hospital (p=0,42). El recurso más disponible fue el uso de la biología molecular (reacción en cadena de la polimerasa) por 73 (67,6%) participantes. El segundo más común fue el uso de aplicaciones de prevención y control de infecciones por 33 (30,6%) participantes. Diecinueve participantes (17,6%) señalaron la ausencia de todos los recursos/equipos. Conclusiones: El uso de la biología molecular para investigar muestras microbiológicas fue el recurso/equipo más disponible para los controladores de infecciones de un importante estado brasileño.(AU)

Asunto(s)

RESUMEN

Human-driven plant selection, a practice as ancient as agriculture itself, has laid the foundations of plant breeding and contemporary farming [...].

Asunto(s)

RESUMEN

The current millennium brought up a revolutionary paradigm shift in molecular biology: many operative proteins, rather than being quasi-rigid polypeptide chains folded into unique configurations - as believed throughout most of the past century - are now known to be intrinsically disordered, dynamic, pleomorphic, and multifunctional structures with stochastic behaviors. Yet, part of this knowledge, including suggestions about possible mechanisms and plenty of evidence for the same, became available by the 1950s and 1960s to remain then nearly forgotten for over 40 years. Here, we review the main steps toward the classic notions about protein structures, as well as the neglected precedents of present views, discuss possible explanations for such long oblivion, and offer a sketch of the current panorama in this field.

Asunto(s)

RESUMEN

Las técnicas de Biología Molecular de última generación, como es la secuenciación masiva en paralelo o NGS (Next Generation Sequencing), permite obtener gran cantidad de información genómica, la cual muchas veces va más allá de la detección de una variante patogénica en un gen que explique la patología (hallazgo primario). Es así como surgió desde hace años la discusión internacional respecto a la decisión a tomar frente a los hallazgos secundarios accionables, es decir, aquellos hallazgos de variantes clasificadas como patogénicas o probablemente patogénicas que no están relacionadas con el fenotipo del paciente, pero que tiene alguna medida preventiva o tratamiento posible y, por lo tanto, podría ser de utilidad para la salud del paciente. Luego de revisar la bibliografía internacional y debatir entre los expertos del Hospital de Pediatría Garrahan, se logró establecer una política institucional y reforzar el hecho de que se trata de una disciplina multidisciplinaria. Así, fue posible definir que solo se atenderá las cuestiones relacionadas con la edad pediátrica, dejando para un tratamiento posterior aquellas variantes detectadas en genes que sean accionables en edad adulta. En el Hospital Garrahan, ha sido posible definir claramente cómo proceder frente a los hallazgos secundarios, al adaptar el consentimiento informado a esta necesidad, definiendo cuándo serán informados, y sabiendo que serán buscados intencionalmente en los genes clínicamente accionables enlistados en la última publicación del American College of Medical Genetics and Genomics, siempre y cuando el paciente/padre/tutor lo consienta (AU)

The latest generation of molecular biology techniques, including massive parallel sequencing or NGS (Next Generation Sequencing), allows us to obtain a whealth of genomic information, which often goes beyond the detection of a pathogenic variant in a gene that explains the pathology (primary finding). As a result, an international discussion has arisen over the years regarding the decision-making concerning actionable secondary findings, it means, those findings of variants classified as pathogenic or probably pathogenic that are not related to the patient's phenotype, but which have some possible preventive measure or treatment and, therefore, could be useful for the patient's health. After reviewing the international literature and discussing among the experts of the Hospital de Pediatría Garrahan, an institutional policy was established and the concept that this is a multidisciplinary discipline was reinforced. Consequently, it has been defined that only issues related to children will be addressed, reserving those variants detected in genes that are actionable in adulthood for later treatment. At Garrahan Hospital, we were able to clearly define how to proceed with secondary findings by adapting the informed consent to this need, defining when they will be reported, and knowing that they will be intentionally searched for in the clinically actionable genes listed in the latest publication of the American College of Medical Genetics and Genomics, as long as the patient/parent/guardian consents (AU)

Asunto(s)

RESUMEN

This Editorial highlights the various observations made in the Special Issue of the International Journal of Molecular Sciences on "Recent Advances in Biochemistry and Molecular Biology of Infectious Diseases" [...].

Asunto(s)

RESUMEN

As it spread through time and into distinct areas of science-from comparative anatomy to evolutionary biology, cladistics, developmental and molecular biology-the homology concept has changed considerably, presenting various meanings. Despite many attempts at developing a comprehensive understanding of the concept, this context-sensitive notion of homology has been a subject of an ongoing debate. Inspired by that and following Kevin de Queiroz and Richard Mayden's view on species concept and delimitation, we presented in this article an attempt to systematize and advance the understanding of the homology problem. Our main goals were: (i) to present a comprehensive checklist of 'concepts of homology'; (ii) to identify which are really concepts with ontological definitions (theoretically rooted in structural correspondence and common ancestry), and which are, in fact, not concepts, but epistemological (empirical and methodological) criteria of homology delimitation; (iii) to provide a synonymy of the concepts and criteria of homology delimitation; (iv) to present a hierarchy of homology concepts within Hennig's hologenetic system; and (v) to endorse the adoption of a unified view of homology by treating homology as a correspondence of spatio-temporal properties (genetic, epigenetic, developmental and positional) at the level of the individual, species or monophyletic group. We found 59 'concepts of homology' in the literature, from which 34 were categorically treated as concepts, 17 as criteria of homology delimitation, Four were excluded from our treatment, and Müller's five concepts were rather treated as approaches to homology. Homology concepts and criteria were synonymized based on structural correspondence, replicability, common ancestry, genetic and epigenetic developmental causes, position and optimization. Regarding the synonymy, we conclusively recognized 21 different concepts of homology, and five empirical and four methodological criteria. Hierarchical ontological aspects of homology were systematized under Hennig's hologenetic system, based on the existence of ontogenetic, tokogenetic and phylogenetic levels of homology. The delimitation of tokogenetic and phylogenetic homologies depends on optimization criteria. The unified view of homology is discussed in the context of the ancestral angiosperm flower.

Asunto(s)

RESUMEN

SUMMARY: Obesity is commonly associated with chronic tissue inflammation and skeletal muscle dysfunction. The study aimed to investigate the effects of High-Intensity Interval training (HIIT) on myokines and endoplasmic reticulum (ER) stress of diet- induced obese (DIO) mice. Three-month-old C57BL/6 male mice were fed a control (C) diet (n=20) or a high-fat (HF) diet (n=20) for 16 weeks. Then, half of the groups underwent HIIT (treadmill running) for an additional four weeks. HIIT increased calf muscles' contribution to BW (+24 %) and reduced weight gain in HF/HIIT than in HF (-120 %). Intramuscular fat accumulation was observed in HF and HF/ HIIT. Peak velocity was higher in HF/HIIT compared to HF (+26 %). Plasma insulin did not change, but glycemia was lower in HF/HIIT than in HF (-30 %). Fndc5 (+418 %) and Irisin (+72 %) were higher in HF/HIIT than in HF. Muscle Fgf21 was higher in HF/HIIT compared to HF (+30 %). In addition, NfKb (-53 %) and Tnfa (-63 %) were lower in HF/HIIT than in HF. However, Il1b (-86 %), Il6 (- 48 %), Il7 (-76 %), and Il15 (-21 %) were lower in HF/HIIT than in HF. Finally, HIIT reduced ER stress in HF/HIIT compared to HF: Atf4, -61 %; Chop, -61 %; Gadd45, -95 %. In conclusion, HIIT leads to weight loss and avoids muscle depletion. HIIT improves blood glucose, Irisin-Fndc5, and peak velocity. In addition, HIIT mitigates muscle inflammation and ER stress.

La obesidad es asociada comúnmente con inflamación tisular crónica y disfunción del músculo esquelético. El estudio tuvo como objetivo investigar los efectos del entrenamiento de intervalos de alta intensidad (HIIT) en las mioquinas y el estrés del retículo endoplásmico (ER) de ratones obesos inducidos por dieta (DIO). Se alimentó a ratones macho C57BL/6 de tres meses de edad con una dieta control (C) (n=20) o una dieta rica en grasas (HF) (n=20) durante 16 semanas. Luego, la mitad de los grupos se sometieron a HIIT (carrera en una trotadora) durante cuatro semanas más. HIIT aumentó la contribución de los músculos de la pantorrilla al BW (+24 %) y redujo el aumento de peso en HF/HIIT en HF (-120 %). Se observó acumulación de grasa intramuscular en HF y HF/HIIT. La velocidad máxima fue mayor en HF/HIIT en comparación con HF (+26 %). La insulina plasmática no cambió, pero la glucemia fue menor en HF/HIIT que en HF (-30 %). Fndc5 (+418 %) e Irisin (+72 %) fueron mayores en HF/HIIT que en HF. El Fgf21 muscular fue mayor en HF/ HIIT en comparación con HF (+30 %). Además, NfKb (-53 %) y Tnfa (-63 %) fueron menores en HF/HIIT que en HF. Sin embar- go, Il1b (-86 %), Il6 (-48 %), Il7 (-76 %) e Il15 (-21 %) fueron más bajos en HF/HIIT que en HF. Finalmente, HIIT redujo el estrés de RE en HF/HIIT en comparación con HF: Atf4, -61 %; Picar, - 61 %; Gadd45, -95 %. En conclusión, HIIT conduce a la pérdida de peso y evita el agotamiento muscular. HIIT mejora la glucosa en sangre, Irisin-Fndc5 y la velocidad máxima. Además, HIIT mitiga la inflamación muscular y el estrés ER.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Significant scientific advances to elucidate the Moniliophthora perniciosa pathosystem have been achieved in recent years, but the molecular biology of this pathogen-host interaction is still a field with many unanswered questions. In order to present insights at the molecular level, we present the first systematic review on the theme. All told, 1118 studies were extracted from public databases. Of these, 109 were eligible for the review, based on the inclusion and exclusion criteria. The results indicated that understanding the transition from the biotrophic-necrotrophic phase of the fungus is crucial for control of the disease. Proteins with strong biotechnological potential or that can be targets for pathosystem intervention were identified, but studies regarding possible applications are still limited. The studies identified revealed important genes in the M. perniciosa-host interaction and efficient molecular markers in the search for genetic variability and sources of resistance, with Theobroma cacao being the most common host. An arsenal of effectors already identified and not explored in the pathosystem were highlighted. This systematic review contributes to the understanding of the pathosystem at the molecular level, offering new insights and proposing different paths for the development of new strategies to control witches' broom disease.

Asunto(s)

Asunto(s)

RESUMEN

Abstract: CRISPR/Cas genes evolved in prokaryotic organisms as a mechanism of defense designed to identify and destroy genetic material from threatening viruses. A breakthrough discovery is that CRISPR/Cas system can be used in eukaryotic cells to edit almost any desired gene. This comprehensive review addresses the most relevant work in the CRISPR/Cas field, including its history, molecular biology, gene editing capability, ongoing clinical trials, and bioethics. Although the science involved is complex, we intended to describe it in a concise manner that could be of interest to diverse readers, including anyone dedicated to the treatment of patients who could potentially benefit from gene editing, molecular biologists, and bioethicists. CRISPR/Cas has the potential to correct inherited diseases caused by single point mutations, to knock-in the promoter of a gene whose expression is highly desirable or knockout the gene coding for a deleterious protein. CRISPR/Cas technique can also be used to edit ex vivo immune cells and reinsert them in patients, improving their efficiency in attacking malignant cells, limiting the infectious potential of viruses or modulating xenotransplant rejection. Very important bioethical considerations on this topic include the need to internationally regulate its use by ad hoc expert committees and to limit its use until safety and bioethical issues are satisfactorily resolved.

Asunto(s)

Asunto(s)

RESUMEN

In their natural environments, microorganisms usually live in organized communities. Profiling analysis of microbial communities has recently assumed special relevance as it allows a thorough understanding of the diversity of the microbiota, its behavior over time, and the establishment of patterns associated with health and disease. The application of molecular biology approaches holds the advantage of including culture-difficult and as-yet-uncultivated phylotypes in the profiles, providing a more comprehensive picture of the microbial community. This chapter focuses on two particular techniques, namely terminal restriction fragment length polymorphism (T-RFLP) and denaturing gradient gel electrophoresis (DGGE), both of which have been widely used in environmental studies and have been recently successfully used by the authors in the study of the oral microbial communities associated with conditions of health and disease.

Asunto(s)