RESUMO
Crop landraces have unique local agroecological and societal functions and offer important genetic resources for plant breeding. Recognition of the value of landrace diversity and concern about its erosion on farms have led to sustained efforts to establish ex situ collections worldwide. The degree to which these efforts have succeeded in conserving landraces has not been comprehensively assessed. Here we modelled the potential distributions of eco-geographically distinguishable groups of landraces of 25 cereal, pulse and starchy root/tuber/fruit crops within their geographic regions of diversity. We then analysed the extent to which these landrace groups are represented in genebank collections, using geographic and ecological coverage metrics as a proxy for genetic diversity. We find that ex situ conservation of landrace groups is currently moderately comprehensive on average, with substantial variation among crops; a mean of 63% ± 12.6% of distributions is currently represented in genebanks. Breadfruit, bananas and plantains, lentils, common beans, chickpeas, barley and bread wheat landrace groups are among the most fully represented, whereas the largest conservation gaps persist for pearl millet, yams, finger millet, groundnut, potatoes and peas. Geographic regions prioritized for further collection of landrace groups for ex situ conservation include South Asia, the Mediterranean and West Asia, Mesoamerica, sub-Saharan Africa, the Andean mountains of South America and Central to East Asia. With further progress to fill these gaps, a high degree of representation of landrace group diversity in genebanks is feasible globally, thus fulfilling international targets for their ex situ conservation.
Assuntos
Produtos Agrícolas , Melhoramento Vegetal , Produtos Agrícolas/genética , Ásia Oriental , América do Sul , Triticum/genéticaRESUMO
The world population is expected to be larger and wealthier over the next few decades and will require more animal products, such as milk and beef. Tropical regions have great potential to meet this growing global demand, where pasturelands play a major role in supporting increased animal production. Better forage is required in consonance with improved sustainability as the planted area should not increase and larger areas cultivated with one or a few forage species should be avoided. Although, conventional tropical forage breeding has successfully released well-adapted and high-yielding cultivars over the last few decades, genetic gains from these programs have been low in view of the growing food demand worldwide. To guarantee their future impact on livestock production, breeding programs should leverage genotyping, phenotyping, and envirotyping strategies to increase genetic gains. Genomic selection (GS) and genome-wide association studies play a primary role in this process, with the advantage of increasing genetic gain due to greater selection accuracy, reduced cycle time, and increased number of individuals that can be evaluated. This strategy provides solutions to bottlenecks faced by conventional breeding methods, including long breeding cycles and difficulties to evaluate complex traits. Initial results from implementing GS in tropical forage grasses (TFGs) are promising with notable improvements over phenotypic selection alone. However, the practical impact of GS in TFG breeding programs remains unclear. The development of appropriately sized training populations is essential for the evaluation and validation of selection markers based on estimated breeding values. Large panels of single-nucleotide polymorphism markers in different tropical forage species are required for multiple application targets at a reduced cost. In this context, this review highlights the current challenges, achievements, availability, and development of genomic resources and statistical methods for the implementation of GS in TFGs. Additionally, the prediction accuracies from recent experiments and the potential to harness diversity from genebanks are discussed. Although, GS in TFGs is still incipient, the advances in genomic tools and statistical models will speed up its implementation in the foreseeable future. All TFG breeding programs should be prepared for these changes.
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The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP's role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.
Assuntos
Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Glioma/enzimologia , Glioma/genética , Purina-Núcleosídeo Fosforilase/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Criança , Pré-Escolar , Feminino , Edição de Genes , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/genética , Prognóstico , Purina-Núcleosídeo Fosforilase/genética , Transfecção , Adulto JovemRESUMO
Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC50 values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy.
Assuntos
Autofagia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Euphorbia/química , Glioblastoma/patologia , Lanosterol/análogos & derivados , Temozolomida/farmacologia , Antineoplásicos Alquilantes/farmacologia , Apoptose , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Movimento Celular , Proliferação de Células , Glioblastoma/tratamento farmacológico , Humanos , Lanosterol/farmacologia , Células Tumorais CultivadasRESUMO
Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I-IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN) Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Proteínas de Neoplasias/genética , Adolescente , Adulto , Idoso , Astrocitoma/diagnóstico , Astrocitoma/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Brasil , Criança , Hibridização Genômica Comparativa , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18/genética , Inibidor de Quinase Dependente de Ciclina p18/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Telomerase/genética , Telomerase/metabolismo , Análise Serial de Tecidos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Medula Espinal , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Deleção Cromossômica , Exoma/genética , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
The Amazon rainforest plays a crucial role in the climate system, helping to drive atmospheric circulations in the tropics by absorbing energy and recycling about half of the rainfall that falls on it. This region (Amazonia) is also estimated to contain about one-tenth of the total carbon stored in land ecosystems, and to account for one-tenth of global, net primary productivity. The resilience of the forest to the combined pressures of deforestation and global warming is therefore of great concern, especially as some general circulation models (GCMs) predict a severe drying of Amazonia in the twenty-first century. Here we analyse these climate projections with reference to the 2005 drought in western Amazonia, which was associated with unusually warm North Atlantic sea surface temperatures (SSTs). We show that reduction of dry-season (July-October) rainfall in western Amazonia correlates well with an index of the north-south SST gradient across the equatorial Atlantic (the 'Atlantic N-S gradient'). Our climate model is unusual among current GCMs in that it is able to reproduce this relationship and also the observed twentieth-century multidecadal variability in the Atlantic N-S gradient, provided that the effects of aerosols are included in the model. Simulations for the twenty-first century using the same model show a strong tendency for the SST conditions associated with the 2005 drought to become much more common, owing to continuing reductions in reflective aerosol pollution in the Northern Hemisphere.
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Aerossóis/análise , Desastres/estatística & dados numéricos , Ecossistema , Poluição Ambiental/estatística & dados numéricos , Efeito Estufa , Modelos Teóricos , Árvores/fisiologia , Oceano Atlântico , Dióxido de Carbono/análise , Desastres/história , História do Século XX , História do Século XXI , Oceano Pacífico , Probabilidade , Chuva , Estações do Ano , América do Sul , TemperaturaRESUMO
Modelling simulations of palaeoclimate and past vegetation form and function can contribute to global change research by constraining predictions of potential earth system responses to future warming, and by providing useful insights into the ecophysiological tolerances and threshold responses of plants to varying degrees of atmospheric change. We contrasted HadCM3LC simulations of Amazonian forest at the last glacial maximum (LGM; 21 kyr ago) and a Younger Dryas-like period (13-12 kyr ago) with predicted responses of future warming to provide estimates of the climatic limits under which the Amazon forest remains relatively stable. Our simulations indicate that despite lower atmospheric CO2 concentrations and increased aridity during the LGM, Amazonia remains mostly forested, and that the cooling climate of the Younger Dryas-like period in fact causes a trend toward increased above-ground carbon balance relative to today. The vegetation feedbacks responsible for maintaining forest integrity in past climates (i.e. decreased evapotranspiration and reduced plant respiration) cannot be maintained into the future. Although elevated atmospheric CO2 contributes to a positive enhancement of plant carbon and water balance, decreased stomatal conductance and increased plant and soil respiration cause a positive feedback that amplifies localized drying and climate warming. We speculate that the Amazonian forest is currently near its critical resiliency threshold, and that even minor climate warming may be sufficient to promote deleterious feedbacks on forest integrity.