RESUMO
The International Atomic Energy Agency (IAEA) has organised programmes on the development, comparison and testing of environmental assessment models and approaches for estimating the radiation exposure of humans and wildlife since the 1980s. The latest of these programmes was called MODARIA (Modelling and Data for Radiological Impact Assessment) and was run in two phases from 2012 to 2015 (MODARIA I) and 2016 to 2019 (MODARIA II). Both phases of the MODARIA programme had the overall objective to improve capabilities in the field of environmental transfer of radionuclides and public and non-human biota exposures assessment, by means of acquisition of improved data for model testing and comparison, reaching consensus on modelling philosophies, approaches and parameter values and building an international forum for the exchange of information. This paper provides an overview of the work undertaken during both phases of the MODARIA programme and its outputs. The overall aims and objectives of a new programme to follow on from MODARIA are described.
Assuntos
Energia Nuclear , Monitoramento de Radiação , Biota , Radioisótopos/análiseRESUMO
The International Commission on Radiological Protection (ICRP) recently reinforced the international system of radiological protection, initially focused on humans, by identifying principles of environmental protection and proposing a framework for assessing impacts of ionising radiation on non-human species, based on a reference flora and fauna approach. For this purpose, ICRP developed dosimetric models for a set of Reference Animals and Plants, which are representative of flora and fauna in different environments (terrestrial, freshwater, marine), and produced criteria based on information on radiation effects, with the aim of evaluating the level of potential or actual radiological impacts, and as an input for decision making. The approach developed by ICRP for flora and fauna is consistent with the approach used to protect humans. The International Atomic Energy Agency (IAEA) includes considerations on the protection of the environment in its safety standards, and is currently developing guidelines to assess radiological impacts based on the aforementioned ICRP approach. This paper presents the method developed by IAEA, in a series of meetings with international experts, to enable assessment of the radiological impact to the marine environment in connection with the Convention on the Prevention of Marine Pollution by Dumping of Wastes and Other Matter 1972 (London Convention 1972). This method is based on IAEA's safety standards and ICRP's recommendations, and was presented in 2013 for consideration by representatives of the contracting parties of the London Convention 1972; it was approved for inclusion in its procedures, and is in the process of being incorporated into guidelines.
Assuntos
Organismos Aquáticos/efeitos da radiação , Conservação dos Recursos Naturais , Ecossistema , Oceanos e Mares , Proteção Radiológica , Contaminação Radioativa da Água/análise , Contaminação Radioativa da Água/prevenção & controle , Organismos Aquáticos/fisiologia , Guias como Assunto , Agências Internacionais , Modelos Teóricos , Monitoramento de RadiaçãoRESUMO
An IAEA handbook presenting transfer parameter values for wildlife has recently been produced. Concentration ratios (CRwo-media) between the whole organism (fresh weight) and either soil (dry weight) or water were collated for a range of wildlife groups (classified taxonomically and by feeding strategy) in terrestrial, freshwater, marine and brackish generic ecosystems. The data have been compiled in an on line database, which will continue to be updated in the future providing the basis for subsequent revision of the Wildlife TRS values. An overview of the compilation and analysis, and discussion of the extent and limitations of the data is presented. Example comparisons of the CRwo-media values are given for polonium across all wildlife groups and ecosystems and for molluscs for all radionuclides. The CRwo-media values have also been compared with those currently used in the ERICA Tool which represented the most complete published database for wildlife transfer values prior to this work. The use of CRwo-media values is a pragmatic approach to predicting radionuclide activity concentrations in wildlife and is similar to that used for screening assessments for the human food chain. The CRwo-media values are most suitable for a screening application where there are several conservative assumptions built into the models which will, to varying extents, compensate for the variable data quality and quantity, and associated uncertainty.
Assuntos
Bases de Dados Factuais , Exposição Ambiental , Monitoramento de Radiação/métodos , Poluentes Radioativos , Radioisótopos , Animais , Ecossistema , Cadeia Alimentar , Água Doce , Trato Gastrointestinal/efeitos da radiação , Agências Internacionais , Modelos Teóricos , Moluscos , Raízes de Plantas , Plantas/efeitos da radiação , Polônio/análise , Radioisótopos/análise , SoloAssuntos
Epigênese Genética/genética , Mutação/genética , Feocromocitoma/genética , Adolescente , Adulto , Idoso , Sequência de Bases , Ilhas de CpG/genética , Metilação de DNA , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteínas Oncogênicas/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases/genéticaAssuntos
Deleção de Genes , Mutação em Linhagem Germinativa/genética , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/patologia , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas , Adulto , Análise Mutacional de DNA , Feminino , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , EspanhaAssuntos
Neoplasias das Glândulas Suprarrenais/genética , Análise Mutacional de DNA/métodos , Mutação em Linhagem Germinativa/genética , Proteínas Ferro-Enxofre/genética , Feocromocitoma/genética , Adulto , Arginina/genética , Códon de Terminação/genética , Feminino , Humanos , Masculino , Subunidades Proteicas , Succinato Desidrogenase/genéticaAssuntos
Substituição de Aminoácidos/genética , Glutamina/genética , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Mutação/genética , Sequência de Aminoácidos/genética , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Perda Auditiva Neurossensorial/congênito , Humanos , Masculino , Dados de Sequência Molecular , Núcleo Familiar , Linhagem , Espanha/epidemiologia , SíndromeRESUMO
Abstract Abnormalities in adrenal and/or ovarian steroidogenesis are found in most patients with hirsutism. The rate-limiting step in the synthesis of steroids in the ovary and the adrenal is the conversion of cholesterol into pregnenolone by cholesterol side-chain cleavage enzyme (P450scc), encoded by the gene CYP11A, after cholesterol is introduced into the mitochondria by the steroidogenic acute regulatory protein (StAR). DAX-1 is a repressor of StAR gene expression, and steroidogenic factor-1 (SF-1) is a regulator of CYP11A, DAX-1, and StAR gene. Mutations in any of these factors resulting in gain of function, or loss of repression, of StAR or P450scc might contribute to the steroidogenic abnormalities present in hirsute patients. In the present study we have screened, using heteroduplex analysis, the genes encoding StAR and SF-1 as well as DAX-1 and CYP11A for mutations in genomic DNA from 19 women presenting with hirsutism and increased serum androgen levels. When variants were found, analysis was extended to a larger group of hyperandrogenic patients and nonaffected women. Two variants were identified in the SF-1 gene. A G-->C change in exon 6, resulting in an Arg(365)Pro mutation, was found in 1 of 45 patients, but not in controls. Also, a Gly(146)Ala missense mutation, resulting from a G-->C change in exon 4, was found in 2 of 48 patients and in 2 of 50 nonaffected individuals. We identified a C-->T base pair change at position -33 of the StAR gene. Three of 48 patients and 3 of 43 controls presented this variant. No mutations were found in coding regions of the StAR gene. Analysis of CYP11A-coding regions identified a G-->A change in exon 3, resulting in a Val(179)Ile missense mutation. This mutation was found in 1 of 29 patients studied and was not present in 50 controls. Finally, analysis of DAX-1 showed no variant in any of the women studied. In conclusion, mutations in StAR, SF-1, CYP11A, and DAX-1 are seldom found in hirsute patients and do not explain the steroidogenic abnormalities found in these women.
Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Proteínas de Ligação a DNA/genética , Hirsutismo/genética , Hiperandrogenismo/genética , Mutação , Fosfoproteínas/genética , Receptores do Ácido Retinoico/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Cromossomo X/genética , Glândulas Suprarrenais/anormalidades , Adulto , Anormalidades Congênitas/genética , Receptor Nuclear Órfão DAX-1 , Transtornos do Desenvolvimento Sexual , Feminino , Fatores de Transcrição Fushi Tarazu , Dosagem de Genes , Testes Genéticos , Proteínas de Homeodomínio , Humanos , Receptores Citoplasmáticos e Nucleares , Fator Esteroidogênico 1RESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is caused by mutations in at least two different genes: PKD1 and PKD2. The study of mutations in these genes is very difficult nowadays. In this study we have analyzed the non reiterated region of the PKD1 gene and all the exons and intron exon boundaries of the PKD2 gene. The technique used to study these genes have been single strand conformation analysis and heteroduplex. We have found 25 differences within the DNA sequence of the PKD1 gene with respect to the published sequence. Seven of these changes correspond to nonsense, missense, frameshifting and splicing mutations. The rest of changes correspond to polymorphisms or rare DNA variants. In the PKD2 gene we have identified 8 new mutations and one polymorphism. Six of these mutations are frameshifting, one is missense and the other one is a large deletion of the PKD2 gene. The rate of mutation detection within the PKD1 gene has been 4% and the rate for PKD2 has been 100%. We have not observed any correlation between genotype and phenotype either in the PKD1 nor in the PKD2 gene. The mutation analysis of ADPKD genes is very difficult, specially for the PKD1 gene. The rate of mutation detection is higher in the PKD2 gene but the global efficacy of the technique is very low as PKD2 represents only 15% of ADPKD patients. Nowadays linkage analysis is still the most useful technique for the molecular diagnosis of ADPKD patients.
Assuntos
Proteínas de Membrana/genética , Rim Policístico Autossômico Dominante/genética , Proteínas/genética , Análise Mutacional de DNA , Humanos , Canais de Cátion TRPPRESUMO
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder that can be caused by mutations in at least three different genes. Several mutations have been identified in PKD1 and PKD2 genes. Most of the mutations found in PKD2 gene are predicted to cause premature termination of the protein. METHODS: We analysed an Argentinian family characterized previously as PKD2. The PKD2 gene was amplified from genomic DNA using 17 primer pairs and the products were analysed by heteroduplex analysis. PCR products that showed a variation by heteroduplex analysis were sequenced directly. The mutation was confirmed by sequencing relatives. The segregation of the mutation in this family was verified by restriction endonuclease digestion of PCR products obtained from genomic DNA of all family members. Results and conclusions. Here, we report a novel mutation present in an Argentinian family characterized as PKD2 by linkage analysis. The mutation, shared by all affected members of the family, is a thymidine insertion at position 2436 of the gene, which results in a translation frameshift and creates an immediate stop codon. This mutation is expected to lead to a truncated protein that lacks the interacting domain with the PKD1 gene product. The thymidine insertion abolished a Ddel restriction site, allowing a rapid test for detection of PKD2 carriers in the family.
Assuntos
Canais de Cálcio/genética , Códon de Terminação/genética , Mutação da Fase de Leitura , Proteínas de Membrana/genética , Rim Policístico Autossômico Dominante/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA/análise , Primers do DNA/química , Éxons , Ligação Genética/genética , Predisposição Genética para Doença , Genótipo , Humanos , Linhagem , Rim Policístico Autossômico Dominante/metabolismo , Reação em Cadeia da Polimerase , Prognóstico , Canais de Cátion TRPPRESUMO
La poliquistosis renal autosómica dominante (PQRAD) es la enfermedad renal hereditaria más frecuente. Es causada por mutaciones en al menos 2 genes: PKD1 y PKD2. El estudio molecular directo, mediante el análisis de mutaciones resulta actualmente complejo. En el presente trabajo hemos analizado una región de la zona no repetida del gen PKD1 y todos los exones y regiones intrónicas flanqueantes del gen PKD2. Las técnicas utilizadas han sido SSCA (single strand conformation analysis) y heteroduplex. Durante el presente estudio se han hallado 25 diferencias en la secuencia de ADN del gen PKD1 respecto a la secuencia publicada. Siete de ellas corresponden a mutaciones de tipo sin sentido, de sentido erróneo, cambio de pauta de lectura o de splicing y el resto son polimorfismos. Por lo que respecta al gen PKD2 hemos hallado 8 nuevas mutaciones y un polimorfismo, todos ellos no descritos previamente. Seis de las mutaciones modifican la pauta de lectura, una es de tipo sentido erróneo y otra es una gran deleción del gen PKD2. La tasa de detecciones para PKD1 ha sido del 4 por ciento mientras que para PKD2 ha sido del 100 por ciento. No se ha observado correlación genotipo-fenotipo para PKD1 ni para PKD2.El análisis mutación el de la PQRAD es complejo, sobre todo el del gen PKD1. El rendimiento del estudio de mutaciones es superior en el gen PKD2 pero la eficacia global es baja pues la prevalencia de la forma PKD2 es tan sólo de un 15 por ciento del total de poliquistosis. En la actualidad el análisis de ligamiento continúa sien-do la principal herramienta a utilizar para realizar el diagnóstico molecular de la enfermedad (AU)
Assuntos
Humanos , Rim Policístico Autossômico Dominante , Proteínas de Membrana , Proteínas , Análise Mutacional de DNARESUMO
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci accounting for the disease. Mutations in the PKD2 gene on the long arm of chromosome 4 are expected to be responsible for approximately 15% of cases of ADPKD. METHODS: We report a systematic screening for mutations covering the 15 exons of the PKD2 gene in eight unrelated families with ADPKD type 2, using the heteroduplex technique. RESULTS: Seven novel mutations were identified and characterized that, together with the previously described changes, amount to a detection rate of 85% in the population studied. The newly described mutations are two nonsense mutations, a 1 bp deletion, a 1 bp insertion, a mutation that involves both a substitution and a deletion (2511AG-->C), a complex mutation in exon 6 consisting of a simultaneous 7 bp inversion and a 4 bp deletion, and the last one is a G-->C transversion that may be a missense mutation. Most of these mutations are expected to lead to the formation of shorter truncated proteins lacking the carboxyl terminus of PKD2. We have also characterized a frequent polymorphism, Arg-Pro, at codon 28 in this gene. The clinical features of these PKD2 patients are similar to the previously described, with the mean age of end-stage renal disease being 75.5 years (SE +/- 3.8 years). CONCLUSIONS: Our results confirm that many different mutations are likely to be responsible for the disease and that most pathogenic defects probably are point or small changes in the coding region of the gene.
Assuntos
Proteínas de Membrana/genética , Mutação/genética , Rim Policístico Autossômico Dominante/genética , Sequência de Aminoácidos/genética , Sequência de Bases/genética , Éxons/genética , Mutação da Fase de Leitura/genética , Humanos , Mutação de Sentido Incorreto/genética , Polimorfismo Genético/genética , Análise de Sobrevida , Canais de Cátion TRPPRESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent inherited disorders. The majority of cases are due to mutation of the PKD1 gene, on 16p13.3, while in most of the remainder the disease maps to the PKD2 locus, at chromosome 4q21-q23. Recently, the PKD2 gene has been positionally cloned and three nonsense mutations within the coding sequence of the gene identified. Here we report a systematic mutation screening of all 15 exons of the PKD2 gene in chromosome 4-linked ADPKD families, using heteroduplex and SSCP analyses. We have identified and characterized seven novel mutations, with a detection rate of approximately 90% in the population studied. All of the mutations result in the premature stop of translation: four nonsense changes and three deletions. The deletions are all frameshifting, of four T nucleotides in one case and one G nucleotide in the other two. All mutations are unique and are distributed throughout the gene without evidence of clustering. Comparison of specific mutations with the clinical profile in ADPKD2 families shows no clear correlation.
Assuntos
Proteínas de Membrana/genética , Mutação , Rim Policístico Autossômico Dominante/genética , Cromossomos Humanos Par 4 , Códon de Terminação , Éxons , Feminino , Mutação da Fase de Leitura , Testes Genéticos , Humanos , Masculino , Polimorfismo Conformacional de Fita Simples , Deleção de Sequência , Canais de Cátion TRPPRESUMO
A new polymorphic CA repeat sequence was identified within the candidate region for the autosomal dominant polycystic kidney disease-type 2 (PKD2) locus. It should be a useful marker in the localization of this gene.