Ausência da perda de heterozigose do PRKAR1A em células capturadas por microdissecção a laser de tecido de nódulo pigmentoso adrenocortical de um paciente com complexo de Carney causado por uma nova mutação nonsense

OBJECTIVE: Primary pigmented nodular adrenocortical disease (PPNAD) is the main endocrine manifestation of Carney complex, a multiple neoplasia syndrome caused by PRKAR1A gene mutations. The presence of PRKAR1A loss of heterozygosity (LOH) in adrenocortical tumorigenesis remains controversial. The aim of the present study is to investigate the presence of PRKAR1A LOH in adrenocortical cells in a patient with Carney complex. METHODS: The LOH was investigated using a PRKAR1A informative intragenic marker by GeneScan software analysis in DNA obtained from laser-captured microdissected cells of several adrenal nodules. Patients: A young adult male patient with Carney complex and his family were studied. RESULTS: A novel heterozygous mutation (p. Y21X) was identified at PRKAR1A in blood DNA of the male proband and his relatives. No PRKAR1A LOH was evidenced in the laser-captured microdissected cells from PPNAD tissue by different methodologies. CONCLUSION: We identified a new PRKAR1A nonsense mutation and in addition we did not evidence PRKAR1A LOH in laser-captured nodules cells, suggesting that adrenocortical tumorigenesis in PPNAD may occurs apart from the second hit.OBJETIVO: A doença adrenocortical nodular pigmentosa primária (PPNAD) é uma das manifestações do complexo de Carney, uma neoplasia endócrina múltipla causada por mutações no PRKAR1A. A perda de heterozigose (LOH) do PRKAR1A na tumorigenese adrenal permanece controversa dada à possibilidade de contaminação com o tecido normal. Nosso objetivo foi investigar a presença de LOH no PRKAR1A a partir de células do nódulo adrenal de um paciente com complexo de Carney. MÉTODOS: A pesquisa da LOH do PRKAR1A foi realizada através do estudo de um marcador intragênico em DNA de células do nódulo adrenal microdissecadas a laser, evitando contaminação com o tecido normal. Pacientes: Um paciente com PPNAD e cinco familiares foram estudados. RESULTADOS: A nova mutação (p. Y21X) foi identificada no PRKAR1A sem evidência de LOH no tecido adrenal. CONCLUSÃO: Identificamos uma nova mutação no PRKAR1A e não evidenciamos LOH nas células dos nódulos adrenocorticais, sugerindo que a PPNAD possa ocorrer na ausência de um segundo evento molecular

Aspectos clínicos e moleculares de tumor adrenocortical metacrônico pediátrico

The occurrence of metachronous adrenocortical carcinoma has rarely been described. We report a case of a child with virilizing adrenocortical metachronous tumors that, despite several metastases, presented long-term survival (15 years). We analyzed in this tumor IGF2, IGF1R and FGFR4 gene expression, and evaluated the presence of p.R337H germline p53 mutation and somatic CTNNB1 mutation. IGF2 gene was over-expressed in both left (Weiss score 5) and right (Weiss 7) adrenocortical tumors. IGF1R expression levels were higher in the right adrenocortical tumor. FGFR4 over-expression was also detected in the right adrenocortical tumor. In addition, this patient harbors the germline p.R337H p53 mutation and loss of heterozygosity (LOH) was detected in the tumors. No somatic CTNNB1 mutations were found in both tumors. In conclusion, we demonstrated in this unusual case the over-expression of growth signaling pathways, which are molecular mechanisms previously related to adrenocortical tumorigenesis. Furthermore, the absence of somatic CTNNB1 mutations, which is a molecular marker of poor prognosis in adults, might be related to the long-term survival of this patient.A ocorrência de carcinomas adrenocorticais metacrônicos é raramente relatada. Descrevemos o caso de uma criança portadora de tumor adrenocortical virilizante metacrônico que, apesar das inúmeras metástases, apresentou uma longa sobrevida (15 anos). Analisamos nesse tumor a expressão gênica de IGF2, IGF1R e FGFR4 e avaliamos a presença da mutação germinativa R337H no p53 e mutação somática no gene CTNNB1. O gene IGF2 foi hiperexpresso nos tumores adrenocorticais esquerdo (Weiss 5) e direito (Weiss 7). Os níveis de expressão de IGF1R foram maiores no tumor direito. Hiperexpressão do gene FGFR4 também foi observada no tumor adrenocortical direito. Esse paciente é portador da mutação germinativa R337H no p53, e perda de heterozigose (LOH) foi observada em ambos os tumores. Não foram encontradas mutações no gene CTNNB1 nos tumores. Em conclusão, demonstramos neste caso a hiperexpressão de vias moleculares de crescimento, que são mecanismos previamente relacionados à tumorigênese adrenocortical. Além disso, não encontramos mutações somáticas no gene CTNNB1, que é um marcador molecular de mau prognóstico em adultos e poderia estar relacionado à longa sobrevida desse paciente

Selection and validation of reference genes by RT-qPCR under photoperiodic induction of flowering in sugarcane ( Saccharum spp.)

Although reference genes have previously been used in the expression analysis of genes involved in sugarcane flowering they had not been experimentally validated for stability and consistency of expression between different samples over a wide range of experimental conditions. Here we report the analysis of candidate reference genes in different tissue types, at different temporal time-points, in both short and long day photoperiodic treatments. The stability of the candidate reference genes in all conditions was evaluated with NormFinder, BestKeeper, and RefFinder algorithms that complement each other for a more robust analysis. As the Normfinder algorithm was more appropriate for our experimental conditions, greater emphasis was placed on Normfinder when choosing the most stable genes. UBQ1 and TUB were shown to be the most stable reference genes to use for normalizing RT-qPCR gene expression data during floral induction, whilst 25SrRNA1 and GAPDH were the least stable. Their use as a reference gene pair was validated by analyzing the expression of two differentially expressed target genes (PIL5 and LHP1). The UBQ1/TUB reference genes combination was able to reveal small significant differences in gene expression of the two target genes that were not detectable when using the least stable reference gene combination. These results can be used to inform the choice of reference genes to use in the study of the sugarcane floral induction pathway. Our work also demonstrates that both PIL5 and LHP1 are significantly up-regulated in the initial stages of photoperiodic induction of flowering in sugarcane

ACIDENTES COM ANIMAIS PEÇONHENTOS EM UM ESTADO DO NORTE DO BRASIL

Accidents by venomous animals are an important public health problem, due to the high frequency with which they occur and the lethality they cause. This study aimed to analyze epidemiological aspects of accidents with venomous animals in the state of Tocantins. Cross-sectional, retrospective study with a quantitative and descriptive approach by consulting the database of the Ministry of Health's Notification Disclosure Information System from January 2009 to December 2019. There were 31,289 reported cases, of which (31, 40%) were caused by scorpions and (29.35%) by snakes. The highest death rates were caused by snakes (0.33%). Regarding gender, the highest percentage was found in males (60.52%). Regarding the age group, there was a progressive increase in the incidence of involvement during the evolution of the age group until reaching the largest number of cases between 20 and 39 years of age, corresponding to (35.81%). It was concluded that the state of Tocantins presented an increase in the number of reported cases during the study period. With a profile of accidents with venomous animals, mostly affecting young people and adults in the economically active age group, with a male prevalence. And the main types of accidents are with scorpions and snakes. It was observed in this study, important data for the public power to outline the improvement of strategies and actions in order to guarantee the adequate diagnosis, treatment and prevention for the population of the state. In addition, the need for further studies on the subject is stated, in order to obtain a more refined analysis of the data presented.  Los accidentes de animales venenosos son un importante problema de salud pública, debido a la alta frecuencia con que ocurren y la letalidad que causan. Este estudio tuvo como objetivo analizar los aspectos epidemiológicos de los accidentes con animales venenosos en el estado de Tocantins. Estudio transversal y retrospectivo con un enfoque cuantitativo y descriptivo consultando la base de datos del Sistema de Información de Divulgación de Notificación del Ministerio de Salud desde enero de 2009 hasta diciembre de 2019. Hubo 31,289 casos reportados, de los cuales (31, 40%) fueron causados ??por escorpiones y (29.35%) por serpientes. Las tasas de mortalidad más altas fueron causadas por serpientes (0,33%). En cuanto al género, el mayor porcentaje se encontró en hombres (60.52%). En cuanto al grupo de edad, hubo un aumento progresivo en la incidencia de afectación durante la evolución del grupo de edad hasta alcanzar el mayor número de casos entre 20 y 39 años, correspondiente a (35.81%). Se concluyó que el estado de Tocantins presentó un aumento en el número de casos reportados durante el período de estudio. Con un perfil de accidentes con animales venenosos, que afecta principalmente a jóvenes y adultos en el grupo de edad económicamente activo, con una prevalencia de machos. Y los principales tipos de accidentes son con escorpiones y serpientes. Se observó en este estudio, datos importantes para el poder público para delinear la mejora de las estrategias y acciones con el fin de garantizar el diagnóstico, tratamiento y prevención adecuados para la población del estado. Además, se establece la necesidad de realizar más estudios sobre el tema, a fin de obtener un análisis más refinado de los datos presentados.  Os acidentes por animais peçonhentos são um importante problema de Saúde Pública, pela alta frequência com que ocorrem e pela letalidade que ocasionam. Este estudo teve por objetivo analisar aspectos epidemiológicos dos acidentes com animais peçonhentos no estado do Tocantins. Estudo transversal, retrospectivo com abordagem quantitativa e descritiva por meio da consulta à base de dados do Sistema de Informação de Agravo de Notificação do Ministério da Saúde no período de janeiro de 2009 a dezembro de 2019. Foram 31.289 casos notificados, dos quais (31,40%) foram ocasionados por escorpiões e (29,35%) por serpentes. As maiores taxas de óbito foram ocasionadas por serpentes (0,33%). Em relação ao sexo o maior percentual foi verificado no sexo masculino (60,52%). Em relação à faixa etária, observou-se um aumento progressivo da incidência de acometimento durante a evolução da faixa etária até atingir o maior número de casos entre 20 a 39 anos de idade correspondendo a (35,81%). Concluí-se que o estado do Tocantins apresentou um aumento no número de casos notificados ao longo do período de estudo. Com um perfil de acidentes com animais peçonhentos atingindo em sua maioria jovens e adultos na faixa etária economicamente ativa, com prevalência do sexo masculino. E os principais tipos de acidentes são com escorpiões e serpentes. Observou-se nesse estudo, dados importantes para o poder público delinear o aperfeiçoamento de estratégias e ações a fim de garantir o diagnóstico, tratamento e prevenção adequados para a população do estado. Em adição, afirma-se a necessidade de mais estudos a respeito do tema, no intuito de se obter uma análise mais refinada dos dados apresentados

Transcriptomic analysis of changes in gene expression during flowering induction in sugarcane under controlled photoperiodic conditions

Flowering is of utmost relevance for the agricultural productivity of the sugarcane bioeconomy, but data and knowledge of the genetic mechanisms underlying its photoperiodic induction are still scarce. An understanding of the molecular mechanisms that regulate the transition from vegetative to reproductive growth in sugarcane could provide better control of flowering for breeding. This study aimed to investigate the transcriptome of +1 mature leaves of a sugarcane cultivar subjected to florally inductive and non-inductive photoperiodic treatments to identify gene expression patterns and molecular regulatory modules. We identified 7,083 differentially expressed (DE) genes, of which 5,623 showed significant identity to other plant genes. Functional group analysis showed differential regulation of important metabolic pathways involved in plant development, such as plant hormones (i.e., cytokinin, gibberellin, and abscisic acid), light reactions, and photorespiration. Gene ontology enrichment analysis revealed evidence of upregulated processes and functions related to the response to abiotic stress, photoprotection, photosynthesis, light harvesting, and pigment biosynthesis, whereas important categories related to growth and vegetative development of plants, such as plant organ morphogenesis, shoot system development, macromolecule metabolic process, and lignin biosynthesis, were downregulated. Also, out of 76 sugarcane transcripts considered putative orthologs to flowering genes from other plants (such as Arabidopsis thaliana, Oryza sativa, and Sorghum bicolor), 21 transcripts were DE. Nine DE genes related to flowering and response to photoperiod were analyzed either at mature or spindle leaves at two development stages corresponding to the early stage of induction and inflorescence primordia formation. Finally, we report a set of flowering-induced long non-coding RNAs and describe their level of conservation to other crops, many of which showed expression patterns correlated against those in the functionally grouped gene network

RETRACTED ARTICLE: Fatal factitious Cushing\ud syndrome (Münchhausen’s syndrome) in a patient with macroprolactinoma and silent\ud corticotrophinoma: case report and literature review

Abstract\ud Münchhausen’s syndrome (MS) is a chronic factitious disorder\ud characterized by the intentional production of clinical symptoms without external\ud incentive. One type of MS is factitious Cushing syndrome, an extremely rare clinical\ud situation in which the diagnosis is challenging mainly due to interference of the\ud exogenous medication in cortisol immunoassays. We described a 26-year-old woman who\ud was originally diagnosed with a macroprolactinoma and during follow-up developed\ud clinical and laboratorial hypercortisolism. A transsphenoidal surgery was performed\ud and immunohistochemistry revealed positive and diffuse staining for both hormones.\ud Four years later, her hypercortisolism recurred and the confirmation of factitious\ud Cushing syndrome was delayed due to conflicting laboratorial results.\ud There are few cases in the literature of factitious Cushing syndrome,\ud and only one had a fatal outcome. The diagnosis of this condition is complex and\ud includes cyclic Cushing syndrome in the differential diagnosis. These patients have\ud high morbidity and increased mortality risk and are likely to have other psychiatric\ud disorders. Prednisone was identified as the culprit in the majority of the\ud cases.We would like to thank Dr. Wagner Farid Gattaz and Dr. Jose Gallucci Neto,\ud from the Psychiatric Division, for providing assistance during hospitalization.\ud This work was partially supported by grants from Conselho Nacional de\ud Desenvolvimento Científico e Tecnológico – CNPq (301339/2008-9 to B.B.M.)

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016