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1.
Oecologia ; 188(3): 849-862, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30145700

RESUMO

Interspecific hybridization is an important and common evolutionary mechanism, but field-based evaluations of changes in realized niches and zonation patterns of native and exotic hybrids relative to those of their parental plant species are rare. Would native hybrids forming hybrid zones between their parental species show realized niches similar to that of their parents, whereas would exotic hybrids show larger realized niches than their parents, and alter zonation patterns of native species? To address these questions, we examined key sediment characteristics in plots representing realized niches of native Sarcocornia hybrids, invasive Spartina hybrids and parental species in 14 salt marshes from four estuaries in the Gulf of Cadiz, Southwest Iberian Peninsula. In one representative marsh, the presence of plant taxa relative to intertidal plant zonation was recorded. Results documented that native and fertile hybrids of Sarcocornia had similar realized niche dimensions as their parental species and co-occurred with other plant species, supporting community diversity. However, exotic sterile hybrids of Spartina had realized niche dimensions lower than those of their parental species and occurred in monocultures. The native hybrids played a community structuring role, whereas the exotic Spartina hybrids were a disruptive influence that changed native halophyte zonation pattern and decreased diversity. This negative functional role could intensify if the sterile hybrids evolve and become fertile. Our study suggests the ecological niche dimension concept is an important tool for understanding species roles in ecosystems, incorporating many ideas from the individual to ecosystem levels.


Assuntos
Ecossistema , Plantas Tolerantes a Sal , Hibridização Genética , Poaceae , Áreas Alagadas
2.
Epidemiol Infect ; 145(15): 3294-3302, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28942755

RESUMO

We compared the impact of a commercial chlorination product (brand name Air RahMat) in stored drinking water to traditional boiling practices in Indonesia. We conducted a baseline survey of all households with children 1000 MPN/100 ml (RR 1·86, 95% CI 1·09-3·19) in stored water than in households without detectable E. coli. Although results suggested that Air RahMat water treatment was associated with lower E. coli contamination and diarrhoeal rates among children <5 years than water treatment by boiling, Air RahMat use remained low.


Assuntos
Diarreia/prevenção & controle , Água Potável , Halogenação , Purificação da Água/métodos , Qualidade da Água , Adolescente , Adulto , Idoso , Pré-Escolar , Diarreia/epidemiologia , Água Potável/microbiologia , Água Potável/normas , Escherichia coli , Características da Família , Feminino , Humanos , Indonésia/epidemiologia , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Adulto Jovem
3.
J Water Health ; 9(3): 577-85, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21976204

RESUMO

In Indonesia, where diarrhea remains a major cause of mortality among children <5 years, the government promotes boiling of drinking water. We assessed the impact of boiling on water quality in South Sulawesi. We surveyed randomly selected households with at least one child <5 years old in two rural districts and tested source and stored water samples for Escherichia coli contamination. Among 242 households, 96% of source and 51% of stored water samples yielded E. coli. Unboiled water samples, obtained from 15% of households, were more likely to yield E. coli than boiled samples [prevalence ratios (PR) = 2.0, 95% confidence interval (CI) 1.7-2.5]. Water stored in wide-mouthed (PR = 1.4, 95% CI = 1.1-1.8) or uncovered (PR = 1.8, 95% CI = 1.3-2.4) containers, or observed to be touched by the respondent's hands (PR = 1.6, 95% CI = 1.3-2.1) was more likely to yield E. coli. A multivariable model showed that households that did not boil water were more likely to have contaminated stored water than households that did boil water (PR = 1.9, 95% CI = 1.5-2.3). Although this study demonstrated the effectiveness of boiling in reducing contamination, overall impact on water quality was suboptimal. Future studies are needed to identify factors behind the success of boiling water in Indonesia to inform efforts to scale up other effective water treatment practices.


Assuntos
Água Potável/microbiologia , Escherichia coli/isolamento & purificação , Microbiologia da Água , Purificação da Água/métodos , Qualidade da Água , Adolescente , Adulto , Estudos Transversais , Água Potável/normas , Feminino , Manipulação de Alimentos , Inocuidade dos Alimentos , Temperatura Alta , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos e Questionários , Abastecimento de Água , Adulto Jovem
4.
Food Chem ; 352: 129370, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33652199

RESUMO

As the worldwide population continues to rise, so does global demand for agricultural production. This scenario of uncertain food supply is exacerbated by the high salinization of soils worldwide, a serious constraint to crop productivity. In this context, there is an increasing need for alternative sustainable crops. Halophytes are thought to be a promising alternative food source due to their natural ability to grow in saline soils and their multiple potential uses in the food industry. In this study, the protein and fatty acid content of the halophyte Halimione (Atriplex) portulacoides (L.) was studied in different saline conditions. Although more studies are needed to explore the nutritional properties of H. portulacoides, the data presented here suggest that this halophyte should be considered as a promising food crop for saline agriculture.


Assuntos
Chenopodiaceae/química , Ácidos Graxos/análise , Proteínas de Plantas/análise , Salinidade , Plantas Tolerantes a Sal/química , Solo/química
5.
Science ; 161(3847): 1255-6, 1968 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-4299806

RESUMO

By utilizing the kinetics of neutralization, it was found that an antibody response to type 1 (oral) and type 2 (genital) herpesvirus infection could be independently measured and correlated with type of virus isolated from the patient. The presence of antibodies to type 1 and type 2 herpesvirus was examined in patients with carcinoma of the cervix, in matched controls, random controls, and patients with other types of malignancy. Antibodies to type 2 were found with greater frequency in patients with carcinoma of the cervix (83 percent) than in the other groups tested (0 to 20 percent). The data suggest an association of genital herpesvirus and carcinoma of the cervix.


Assuntos
Infecções por Herpesviridae/imunologia , Neoplasias do Colo do Útero/microbiologia , Adulto , Criança , Pré-Escolar , Circuncisão Masculina , Feminino , Gengivite/microbiologia , Herpesviridae/isolamento & purificação , Infecções por Herpesviridae/complicações , Humanos , Lactente , Cinética , Lábio/microbiologia , Masculino , Pessoa de Meia-Idade , Boca/microbiologia , Testes de Neutralização , Pênis/microbiologia , Pele/microbiologia , Fatores Socioeconômicos , Estomatite/microbiologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/epidemiologia , Vagina/microbiologia
6.
Ecotoxicol Environ Saf ; 72(6): 1694-700, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19577295

RESUMO

The south-American cordgrass, Spartina densiflora, has become the dominant plant species on recent tidal marsh restorations in the Doñana National Park (SW Spain). We examined the effect of different doses of glyphosate (720-7200 g a.i. ha(-1)) and imazamox (20-68 g a.i. ha(-1)) on growth and photosynthetic apparatus of S. densiflora. Imazamox had no effect on neither on growth nor photosynthetic apparatus of S. densiflora. On the contrary, glyphosate inhibited photochemical efficiency of photosynthesis from day one. Net photosynthetic rate, stomatal conductance and photosynthetic pigments and the number of new tillers were reduced. Glyphosate at high doses (ca. 7200 g a.i. ha(-1)) could be an appropriate method of control, since it has a negative effect over the photosynthetic apparatus and growth of S. densiflora. Furthermore, glyphosate and its main metabolite, AMPA, were not extracted from the soil, since they were retained by the very high iron and aluminum oxide content of this soil.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Imidazóis/toxicidade , Poaceae/efeitos dos fármacos , Clorofila/metabolismo , Fluorescência , Glicina/toxicidade , Fotossíntese/efeitos dos fármacos , Poaceae/crescimento & desenvolvimento , Poaceae/metabolismo , Solo/análise , Glifosato
7.
Plant Biol (Stuttg) ; 10(6): 754-62, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18950433

RESUMO

Spartina densiflora Brongn. is found in coastal marshes of southwest Spain, growing over sediments containing 100-4800 ppm Zn. A glasshouse experiment was designed to investigate the effect of Zn from 0 to 100 mmol.l(-1) on the growth and photosynthetic apparatus of S. densiflora, by measuring relative growth rate, leaf elongation rate, number of tillers, height of tillers, chlorophyll fluorescence parameters, gas exchange and photosynthetic pigment concentrations. We also determined total ash, Zn, calcium, magnesium and phosphorus concentrations, and the C/N ratio. At 100 mmol.l(-1) Zn, S. densiflora showed a 48% biomass reduction after 1 month of treatment. Long-term effects of Zn on growth of S. densiflora consisted mainly of variations in net photosynthesis. Modification of the Zn/Mg ratio was linked to a strong decrease in RuBP carboxylase (Zn was favoured in local competition with Mg, so that the affinity of RuBisCO for CO(2) decreased), oxygenase activity of RuBisCO acting as a substitute for the photosynthetic function. Also, Zn had a marked overall effect on the photochemical (PSII) apparatus and the synthesis of photosynthetic pigments. However, the results indicate that S. densiflora is capable of tolerating very high and continued exposure to Zn, as this species lowers the translocation of Zn from the nutrient solution to roots and controls Zn ion transport into leaves. Therefore, S. densiflora could be useful in the phytostabilization of soils.


Assuntos
Fotossíntese , Poaceae/crescimento & desenvolvimento , Poaceae/metabolismo , Zinco/farmacologia , Análise de Variância , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Poaceae/efeitos dos fármacos , Ribulose-Bifosfato Carboxilase/metabolismo
8.
Mar Pollut Bull ; 56(12): 2037-42, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18805558

RESUMO

In the joint estuary of the Odiel and Tinto rivers (SW Spain), the invasive Spartina densiflora Brongn. and the native Spartina maritima (Curtis) Fernald are growing over sediments with extreme concentrations of heavy metals. The contents of As, Cu, Fe, Mn, Pb and Zn were determined in sediments, rhizosediments and different tissues of both species, from Odiel and Tinto marshes. S. densiflora showed a higher capability to retain metals around their roots and to control the uptake or transport of metals, mediated by a higher formation of plaques of Fe/Mn (hydro) oxides on the roots. At the Tinto marsh, there were no differences between the metal concentrations of the sediment and those of the rhizosediment, a fact that could be explained by the extremely high concentrations of metals which can pass over a threshold value, altering the properties of root cells and preventing roots from acting as a 'barrier' to the uptake or transport of metals.


Assuntos
Biodegradação Ambiental , Sedimentos Geológicos/química , Metais/metabolismo , Poaceae/metabolismo , Poluentes Químicos da Água/metabolismo , Conservação dos Recursos Naturais , Rios/química
9.
Leukemia ; 31(11): 2479-2490, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28321121

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises ~15% and 25% of pediatric and adult ALL cases, respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects. A finer detailed understanding of the genetic and molecular mechanisms underlying T-ALL is required identify patients at increased risk for treatment failure and the development of precision medicine strategies. Generation of genetic models that more accurately reflect the normal developmental history of T-ALL are necessary to identify new avenues for treatment. The DNA methyltransferase enzyme DNMT3A is also recurrently mutated in T-ALL patients, and we show here that inactivation of Dnmt3a combined with Notch1 gain-of-function leads to an aggressive T-ALL in mouse models. Moreover, conditional inactivation of Dnmt3a in mouse hematopoietic cells leads to an accumulation of immature progenitors in the thymus, which are less apoptotic. These data demonstrate that Dnmt3a is required for normal T-cell development, and acts as a T-ALL tumor suppressor.


Assuntos
DNA (Citosina-5-)-Metiltransferases/fisiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Linfócitos T/citologia , Animais , Apoptose , Linhagem Celular , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , DNA Metiltransferase 3A , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
10.
Mater Sci Eng C Mater Biol Appl ; 74: 36-46, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28254305

RESUMO

Application of polymers cross-linked by gamma irradiation on cutaneous wounds has resulted in the improvement of healing. Chitosan (CH) and poloxamer 407 (P407)-based hydrogels confer different advantages in wound management. To combine the properties of both compounds, a gamma-irradiated mixture of 0.75/25% (w/w) CH and P407, respectively, was obtained (CH-P), and several physical, chemical, and biological analyses were performed. Notably, gamma radiation induced changes in the mixture's thermal behavior, viscosity, and swelling, and exhibited stability at neutral pH. The thermal reversibility provided by P407 and the bacteriostatic effect of CH were maintained. Mice full-thickness wounds treated with CH-P diminished the wound area during the first days. Consequently, with this treatment, increased levels of macrophages, α-SMA, and collagen deposition in wounds were observed, indicating a more mature scar tissue. In conclusion, the new hydrogel CH-P, at physiologic pH, combined the beneficial characteristics of both polymers and produced new properties for wound management.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Poloxâmero/química , Actinas/metabolismo , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/farmacologia , Varredura Diferencial de Calorimetria , Candida albicans/efeitos dos fármacos , Quitosana/química , Escherichia coli/efeitos dos fármacos , Raios gama , Hidrogéis/efeitos da radiação , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Microscopia de Fluorescência , Reologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Temperatura , Viscosidade , Cicatrização/efeitos dos fármacos
11.
Chemosphere ; 120: 171-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25025740

RESUMO

We evaluate copper tolerance and accumulation in Vitis vinifera ssp. sylvestris in populations from a copper contaminated site and an uncontaminated site, and in the grapevine rootstock "41B", investigating the effects of copper (0-23 mM) on growth, photosynthetic performance and mineral nutrient content. The highest Cu treatment induced nutrient imbalances and inhibited photosynthetic function, causing a drastic reduction in growth in the three study plants. Effective concentration was higher than 23 mM Cu in the wild grapevines and around 9 mM in the "41B" plants. The wild grapevine accessions studied controlled root Cu concentration more efficiently than is the case with the "41B" rootstock and must be considered Cu-tolerant. Wild grapevines from the Cu-contaminated site present certain physiological characteristics that make them relatively more suitable for exploitation in the genetic improvement of vines against conditions of excess Cu, compared to wild grapevine populations from uncontaminated sites.


Assuntos
Cobre/metabolismo , Cobre/toxicidade , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Vitis/efeitos dos fármacos , Vitis/metabolismo , Espanha
12.
Am J Clin Pathol ; 95(4 Suppl 1): S8-21, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2008886

RESUMO

The authors have reviewed and described molecular methods for the detection of etiologic agents or genetic sequences involved in the pathogenesis of various diseases. Molecular probes are now available for the rapid diagnosis of diseases caused by a large number of viruses, bacteria, fungi, spirochetes, rickettsia, and other infectious agents. Since nucleic acid probes can distinguish minute differences indicative of genetic mutations or alternations, specific probes also can be developed even for those diseases with unknown causative agents or etiologies. Further, using these techniques, specific drug-resistant and pathogenic strains associated with epidemics in widely separated areas of a country or a town have been identified. Thus, the sensitivity and specificity of molecular detection methods using both radioactive and nonradioactive probes are at a point that clinical specimens can be tested for rapid diagnosis and identification of etiologic agent(s) that may be responsible for the pathogenesis of a wide variety of diseases.


Assuntos
Doenças Transmissíveis/diagnóstico , Técnicas de Sonda Molecular , Patologia , Doenças Transmissíveis/genética , Humanos
13.
Water Sci Technol ; 45(10): 243-8, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12188552

RESUMO

The performance of a sewage treatment system consisting of a settler followed by an Upflow Anaerobic Sludge Bed (UASB) reactor is described. Mean ambient and sewage temperature were 16.5 and 21.6 degrees C, respectively. Total Chemical Oxygen Demand (CODt) concentration averaged 224.2 and 152.6 mg/L, for raw and settled sewage, respectively. The effluent concentration was 68.5 mgCODt/L. Total and suspended COD removal efficiencies of approximately 70 and 80%, respectively, have been observed in the system at a mean Hydraulic Retention Time (HRT) of 2 + 5 h. Maximum COD removal efficiency was achieved in the UASB reactor when upflow velocity (Vup) was 0.43 m/h (HRT = 6 h). Mean Specific Methanogenic Activity (SMA) and Volatile Suspended Solids (VSS) concentration in the granular sludge bed were 0.11 gCOD-CH4/gVSS.d and 30.0 gVSS/Lsludge, respectively. SMA was inversely related to VSS concentration, and both parameters varied along the sludge bed height. The Solids Retention Time (SRT) in the reactor was 450 days. Sludge characteristics have not been affected by changes of up to one month in Vup in the range 0.28-0.85 m/h (HRT 3-9 h). This system or two UASB reactors in series could be an alternative for sewage treatment under moderate temperature conditions.


Assuntos
Bactérias Anaeróbias/fisiologia , Reatores Biológicos , Euryarchaeota/fisiologia , Esgotos/microbiologia , Oxigênio/química , Projetos Piloto , Esgotos/química , Temperatura , Clima Tropical , Eliminação de Resíduos Líquidos/métodos
14.
Chemosphere ; 93(2): 294-301, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23746388

RESUMO

The present study evaluates the tolerance and accumulation potential of Vitis vinifera ssp. sylvestris under moderate and high external Cu levels. A greenhouse experiment was conducted in order to investigate the effects of a range of external Cu concentrations (0-23mmolL(-1)) on growth and photosynthetic performance by measuring gas exchange, chlorophyll fluorescence parameters and photosynthetic pigments. We also measured the total copper, nitrogen, phosphorus, sulphur, calcium, magnesium, iron, potassium and sodium concentrations in the plant tissues. All the experimental plants survived even with external Cu concentrations as high as 23mmolL(-1) (1500mg Cu L(-1)), although the excess of metal resulted in a biomass reduction of 35%. The effects of Cu on growth were linked to a reduction in net photosynthesis, which may be related to the effect of the high concentration of the metal on photosynthetic electron transport. V. vinifera ssp. sylvestris survived with leaf Cu concentrations as high as 80mgkg(-1) DW and growth parameters were unaffected by leaf tissue concentrations of 35mg Cu kg(-1) DW. The results of our study indicate that plants of V. vinifera ssp. sylvestris from the studied population are more tolerant to Cu than the commercial varieties of grapevine that have been studied in the literature, and could constitute a basis for the genetic improvement of Cu tolerance in grapevine.


Assuntos
Cobre/farmacologia , Poluentes Ambientais/farmacologia , Fotossíntese/efeitos dos fármacos , Vitis/efeitos dos fármacos , Vitis/crescimento & desenvolvimento , Clorofila/metabolismo , Relação Dose-Resposta a Droga , Complexo de Proteína do Fotossistema II/metabolismo , Pigmentos Biológicos/metabolismo , Vitis/metabolismo
15.
Mar Pollut Bull ; 75(1-2): 28-32, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24018174

RESUMO

The halophytic shrub Halimione portulacoides demonstrates a high tolerance to heavy metal contamination and a capacity for accumulating metals within its tissues. On the Iberian Peninsula, this species has colonized habitats with high levels of metal pollution. The aim of this study is to analyze the response of H. portulacoides stem cuttings to this pollution. Growth, photosynthesis and metal uptake were examined in H. portulacoides through an experiment in which stem cuttings were replanted in metal-contaminated soil. This condition decreased growth and lowered both photosynthetic rate and stomatal conductance. Reduced photosynthetic performance was largely due to the reduced concentration of photosynthetic pigments. Despite these responses, there was some important evidence suggesting the phytoremediatory potential of Halimione stem cuttings. The results of our study indicate that this salt-marsh shrub may represent a biotool of value in the restoration of polluted areas.


Assuntos
Amaranthaceae/fisiologia , Metais Pesados/toxicidade , Poluentes do Solo/toxicidade , Adaptação Fisiológica , Amaranthaceae/crescimento & desenvolvimento , Amaranthaceae/metabolismo , Biodegradação Ambiental , Clorofila/metabolismo , Metais Pesados/análise , Fotossíntese/fisiologia , Plantas Tolerantes a Sal/fisiologia , Solo/química , Poluentes do Solo/análise , Áreas Alagadas
16.
Environ Sci Pollut Res Int ; 20(12): 8839-47, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23744160

RESUMO

A glasshouse study of the coastal shrub Limoniastrum monopetalum was carried out to evaluate its tolerance and capacity to accumulate copper. We investigate the effects of Cu from 0 to 60 mmol l(-1) on the growth, photosynthetic apparatus, and nutrient uptake of L. monopetalum, by measuring gas exchange, chlorophyll fluorescence parameters, photosynthetic pigments, and total copper, nitrogen, phosphorus, sulfur, calcium, and magnesium content in the plant tissues. Although L. monopetalum did not survive at 60 mmol l(-1) Cu, the species demonstrated a high tolerance to Cu-induced stress, since all plants survived external Cu concentrations of up to 35 mmol l(-1) and displayed similar growth in the Cu-enriched medium as in the control treatment of up to the external level of 15 mmol Cu l(-1) (1,000 mg Cu l(-1)). The reduced growth registered in plants exposed to 35 mmol Cu l(-1) can be attributed to reduced photosynthetic carbon assimilation associated with the adverse effect of the metal on the photochemical apparatus and a reduction in the absorption of essential nutrients. Copper tolerance was associated with the capacity of the plant to accumulate the metal in its roots and effectively prevent its translocation to photosynthetic tissues. L. monopetalum has the characteristics of a Cu-excluder plant and could be used in the revegetation of Cu-contaminated soils.


Assuntos
Sulfato de Cobre/toxicidade , Fotossíntese/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Poluentes do Solo/toxicidade , Traqueófitas/fisiologia , Adaptação Fisiológica , Biodegradação Ambiental , Cálcio/metabolismo , Magnésio/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo , Fotossíntese/fisiologia , Raízes de Plantas/metabolismo
17.
Leukemia ; 27(4): 852-60, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23235717

RESUMO

Mixed lineage leukemia (MLL)-fusion proteins can induce acute myeloid leukemias (AMLs) from either hematopoietic stem cells (HSCs) or granulocyte-macrophage progenitors (GMPs), but it remains unclear whether the cell of origin influences the biology of the resultant leukemia. MLL-AF9-transduced single HSCs or GMPs could be continuously replated, but HSC-derived clones were more likely than GMP-derived clones to initiate AML in mice. Leukemia stem cells derived from either HSCs or GMPs had a similar immunophenotype consistent with a maturing myeloid cell (LGMP). Gene expression analyses demonstrated that LGMP inherited gene expression programs from the cell of origin including high-level Evi-1 expression in HSC-derived LGMP. The gene expression signature of LGMP derived from HSCs was enriched in poor prognosis human MLL-rearranged AML in three independent data sets. Moreover, global 5'-mC levels were elevated in HSC-derived leukemias as compared with GMP-derived leukemias. This mirrored a difference seen in 5'-mC between MLL-rearranged human leukemias that are either EVI1 positive or EVI1 negative. Finally, HSC-derived leukemias were more resistant to chemotherapy than GMP-derived leukemias. These data demonstrate that the cell of origin influences the gene expression profile, the epigenetic state and the drug response in AML, and that these differences can account for clinical heterogeneity within a molecularly defined group of leukemias.


Assuntos
Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Adulto , Animais , Antineoplásicos/farmacologia , Citarabina/farmacologia , Perfilação da Expressão Gênica , Histona-Lisina N-Metiltransferase , Humanos , Camundongos , Camundongos Endogâmicos C57BL
18.
Mar Pollut Bull ; 64(4): 721-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22364950

RESUMO

The present study evaluated the tolerance and accumulation potential in the salt-marsh shrub Halimione portulacoides under moderate and high external Cu levels. A greenhouse experiment was conducted in order to investigate the effects of a range of external Cu concentrations (0 to 60 mmol l(-1)) on growth and photosynthetic performance by measuring gas exchange, chlorophyll fluorescence parameters and photosynthetic pigments. We also determined total copper, nitrogen, phosphorus and sulfur concentrations in the plant tissues. H. portulacoides survived with external Cu concentrations of up to 35 mmol Cu l(-1), although the excess of metal resulted in a biomass reduction of 48%. The effects of Cu on growth were linked to a drastic reduction in net photosynthesis. However, H. portulacoides tolerated Cu levels of up to 15 mmol Cu l(-1) without suffering adverse physiological effects. Our results indicate that this species could play an important role in the restoration of Cu-contaminated soils.


Assuntos
Amaranthaceae/efeitos dos fármacos , Amaranthaceae/metabolismo , Cobre/metabolismo , Cobre/toxicidade , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Amaranthaceae/crescimento & desenvolvimento , Recuperação e Remediação Ambiental , Fotossíntese/efeitos dos fármacos
19.
Chemosphere ; 86(9): 867-74, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22099539

RESUMO

The halophytic shrub Halimione portulacoides is known to be capable of growth in soils containing extremely high concentrations of Zn. This study evaluated in detail the tolerance and accumulation potential of H. portulacoides under moderate and high external Zn levels. A greenhouse experiment was conducted in order to investigate the effects of a range of Zn concentrations (0-130 mmol L(-1)) on growth and photosynthetic performance by measuring relative growth rate, total leaf area, specific leaf area, gas exchange, chlorophyll fluorescence parameters and photosynthetic pigment concentrations. We also determined the total zinc, nitrogen, phosphorus, calcium, magnesium, sodium, potassium, iron and copper concentrations in the plant tissues. H. portulacoides demonstrated hypertolerance to Zn stress, since it survived with leaf concentrations of up to 2300 mg Zn kg(-1)dry mass, when treated with 130 mmol Zn L(-1). Zinc concentrations greater than 70 mmol L(-1) in the nutrient solution negatively affected plant growth, in all probability due to the recorded decline in net photosynthesis rate. Our results indicate that the Zn-induced decline in the photosynthetic function of H. portulacoides may be attributed to the adverse effect of the high concentration of the metal on photosynthetic electron transport. Growth parameters were virtually unaffected by leaf tissue concentrations as high as 1500 mg Zn kg(-1)dry mass, demonstrating the strong capability of H. portulacoides to protect itself against toxic Zn concentrations. The results of our study indicate that this salt-marsh shrub may represent a valuable tool in the restoration of Zn-polluted areas.


Assuntos
Amaranthaceae/metabolismo , Zinco/metabolismo , Amaranthaceae/fisiologia , Cálcio/metabolismo , Clorofila/metabolismo , Cobre/metabolismo , Ferro/metabolismo , Magnésio/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo , Fotossíntese , Potássio/metabolismo , Sódio/metabolismo , Solo/química , Áreas Alagadas
20.
Leukemia ; 26(5): 893-901, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22033493

RESUMO

Acute myeloid leukemia (AML) is a disease of the elderly. Poor outcomes with standard therapies necessitate novel approaches. Outpatient regimens sufficiently potent and well tolerated to induce remissions and enable continuation therapy may be beneficial. In this phase-1 study, we determined the maximum tolerated dose (MTD) and the efficacy for sequential azacitidine and lenalidomide as remission induction and continuation therapy in elderly, previously untreated patients. We investigated the impact on global DNA methylation and bone marrow cytokines, and sought biological predictors of response. Eighteen patients were enrolled. The MTD was not reached. Median follow-up was 8.2 months (10.3 months for survivors). Common adverse events included fatigue, injection site reactions, constipation, nausea, pruritus and febrile neutropenia. Ten patients responded (56%), and the rate of complete remissions (CRs) or CRs with incomplete recovery of blood counts for evaluable patients was 44% (7/16). The median response duration was 6.2 months. DNA demethylation and changes in bone marrow cytokines were observed; responders had a unique cytokine profile and a trend towards lower methylation levels. Sequential azacitidine and lenalidomide was well tolerated with encouraging clinical and biological activity in previously untreated elderly AML patients. This trial is registered at ClinicalTrials.gov (NCT00890929).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Estudos de Coortes , Citocinas/genética , Citocinas/metabolismo , Metilação de DNA , Feminino , Perfilação da Expressão Gênica , Humanos , Lenalidomida , Leucemia Mieloide Aguda/genética , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mutação , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do Tratamento
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