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We present a systematic investigation of muon-stopping states in superconductors that reportedly exhibit spontaneous magnetic fields below their transition temperatures due to time-reversal symmetry breaking. These materials include elemental rhenium, several intermetallic systems, and Sr_{2}RuO_{4}. We demonstrate that the presence of the muon leads to only a limited and relatively localized perturbation to the local crystal structure, while any small changes to the electronic structure occur several electron volts below the Fermi energy, leading to only minimal changes in the charge density on ions close to the muon. Our results imply that the muon-induced perturbation alone is unlikely to lead to the observed spontaneous fields in these materials, whose origin is more likely intrinsic to the time-reversal symmetry-broken superconducting state.
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The ground state of the simple Heisenberg nearest-neighbor quantum kagome antiferromagnetic model is a magnetically disordered spin liquid, yet various perturbations may lead to fundamentally different states. Here we disclose the origin of magnetic ordering in the structurally perfect kagome material YCu_{3}(OH)_{6}Cl_{3}, which is free of the widespread impurity problem. Ab initio calculations and modeling of its magnetic susceptibility reveal that, similar to the archetypal case of herbertsmithite, the nearest-neighbor exchange is by far the dominant isotropic interaction. Dzyaloshinskii-Moriya (DM) anisotropy deduced from electron spin resonance, susceptibility, and specific-heat data is, however, significantly larger than in herbertsmithite. By enhancing spin correlations within kagome planes, this anisotropy is essential for magnetic ordering. Our study isolates the effect of DM anisotropy from other perturbations and unambiguously confirms the predicted phase diagram.
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The energy landscape of carbon is exceedingly complex, hosting diverse and important metastable phases, including diamond, fullerenes, nanotubes, and graphene. Searching for structures, especially those with large unit cells, in this landscape is challenging. Here we use a combined stochastic search strategy employing two algorithms (ab initio random structure search and random sampling strategy combined with space group and graph theory) to apply connectivity constraints to unit cells containing up to 100 carbon atoms. We uncover three low energy carbon polymorphs (Pbam-32, P6/mmm, and I4[over ¯]3d) with new topologies, containing 32, 36, and 94 atoms in their primitive cells, respectively. Their energies relative to diamond are 96, 131, and 112 meV/atom, respectively, which suggests potential metastability. These three carbon allotropes are mechanically and dynamically stable, insulating carbon crystals with superhard mechanical properties. The I4[over ¯]3d structure possesses a direct band gap of 7.25 eV, which is the widest gap in the carbon allotrope family. Silicon, germanium, and tin versions of Pbam-32, P6/mmm, and I4[over ¯]3d also show energetic, dynamical, and mechanical stability. The computed electronic properties show that they are potential materials for semiconductor and photovoltaic applications.
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Cyclobutadiene has a four-membered carbon ring with two double bonds, but this highly strained molecular configuration is almost square and, via a coordinated motion, the nuclei quantum mechanically tunnels through the high-energy square state to a configuration equivalent to the initial configuration under a 90° rotation. This results in a square ground state, comprising a superposition of two molecular configurations, that is driven by quantum tunneling. Using a quantum mechanical model, and an effective nuclear potential from density functional theory, we calculate the vibrational energy spectrum and the accompanying wavefunctions. We use the wavefunctions to identify the motions of the molecule and detail how different motions can enhance or suppress the tunneling rate. This is relevant for kinematics of tunneling-driven reactions, and we discuss these implications. We are also able to provide a qualitative account of how the molecule will respond to an external perturbation and how this may enhance or suppress infra-red-active vibrational transitions.
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Insect pests can reduce wheat yield by direct feeding and transmission of plant viruses. Here we report results from laboratory and field phenotyping studies on a wide range of wheat, including landraces from the Watkins collection deriving from before the green revolution, more modern cultivars from the Gediflux collection (north-western Europe) and modern UK Elite varieties, for resistance to the bird cherry-oat aphid, Rhopalosiphum padi (Homoptera: Aphididae) and the English grain aphid, Sitobion avenae (Homoptera: Aphididae). A total of 338 lines were screened for R. padi and 340 lines for S. avenae. Field trials were also conducted on 122 Watkins lines to identify wheat bulb fly, Delia coarctata, preference on these landraces. Considerable variation was shown in insect performance among and within different wheat collections, with reduced susceptibility in a number of varieties, but phenotyping did not identify strong resistance to aphids or wheat bulb fly. Field trials showed within collection differences in aphid performance, with fewer aphids populating lines from the Watkins collection. This differs from development data in laboratory bioassays and suggests that there is a pre-alighting cue deterring aphid settlement and demonstrates differences in aphid preference and performance on older plants in the field compared with seedlings in the laboratory, highlighting the need for phenotyping for aphid resistance at different plant growth stages. No association was identified between performance of the different insect species on individual varieties, potentially suggesting different nutritional requirements or resistance mechanisms.
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Honey bees, Apis mellifera, are markedly less sensitive to neonicotinoid insecticides containing a cyanoimino pharmacophore than to those with a nitroimino group. Although previous work has suggested that this results from enhanced metabolism of the former by detoxification enzymes, the specific enzyme(s) involved remain to be characterized. In this work, a pretreatment of honey bees with a sublethal dose of thiacloprid resulted in induced insensitivity to the same compound immediately following thiacloprid feeding. A longer pretreatment time resulted in no, or increased, sensitivity. Transcriptome profiling, using microarrays, identified a number of genes encoding detoxification enzymes that were over-expressed significantly in insecticide-treated bees compared with untreated controls. These included five P450s, CYP6BE1, CYP305D1, CYP6AS5, CYP315A1, CYP301A1, and a carboxyl/cholinesterase (CCE) CCE8. Four of these P450s were functionally expressed in Escherichia coli and their ability to metabolize thiacloprid examined by liquid chromatography-mass spectrometry (LC-MS) analysis.
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Abelhas/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Inativação Metabólica/genética , Anabasina/farmacologia , Animais , Abelhas/metabolismo , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inseticidas/farmacologia , Neonicotinoides , Piridinas/farmacologia , Tiazinas/farmacologia , Ativação Transcricional/efeitos dos fármacosRESUMO
Crop protection is an integral part of establishing food security, by protecting the yield potential of crops. Cereal aphids cause yield losses by direct damage and transmission of viruses. Some wild relatives of wheat show resistance to aphids but the mechanisms remain unresolved. In order to elucidate the location of the partial resistance to the bird cherry-oat aphid, Rhopalosiphum padi, in diploid wheat lines of Triticum monococcum, we conducted aphid performance studies using developmental bioassays and electrical penetration graphs, as well as metabolic profiling of partially resistant and susceptible lines. This demonstrated that the partial resistance is related to a delayed effect on the reproduction and development of R. padi. The observed partial resistance is phloem based and is shown by an increase in number of probes before the first phloem ingestion, a higher number and duration of salivation events without subsequent phloem feeding and a shorter time spent phloem feeding on plants with reduced susceptibility. Clear metabolic phenotypes separate partially resistant and susceptible lines, with the former having lower levels of the majority of primary metabolites, including total carbohydrates. A number of compounds were identified as being at different levels in the susceptible and partially resistant lines, with asparagine, octopamine and glycine betaine elevated in less susceptible lines without aphid infestation. In addition, two of those, asparagine and octopamine, as well as threonine, glutamine, succinate, trehalose, glycerol, guanosine and choline increased in response to infestation, accumulating in plant tissue localised close to aphid feeding after 24 h. There was no clear evidence of systemic plant response to aphid infestation.
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BACKGROUND: Glutathione S-transferase 1 (GSTP1) inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). This study assessed whether the level of circulating methylated GSTP1 (mGSTP1) in plasma DNA is associated with chemotherapy response and overall survival (OS). METHODS: Plasma samples were collected prospectively from a Phase I exploratory cohort of 75 men with castrate-resistant PC (CRPC) and a Phase II independent validation cohort (n=51). mGSTP1 levels in free DNA were measured using a sensitive methylation-specific PCR assay. RESULTS: The Phase I cohort identified that detectable baseline mGSTP1 DNA was associated with poorer OS (HR, 4.2 95% CI 2.1-8.2; P<0.0001). A decrease in mGSTP1 DNA levels after cycle 1 was associated with a PSA response (P=0.008). In the Phase II cohort, baseline mGSTP1 DNA was a stronger predictor of OS than PSA change after 3 months (P=0.02). Undetectable plasma mGSTP1 after one cycle of chemotherapy was associated with PSA response (P=0.007). CONCLUSIONS: We identified plasma mGSTP1 DNA as a potential prognostic marker in men with CRPC as well as a potential surrogate therapeutic efficacy marker for chemotherapy and corroborated these findings in an independent Phase II cohort. Prospective Phase III assessment of mGSTP1 levels in plasma DNA is now warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Metilação de DNA , DNA de Neoplasias/genética , Epigenômica , Glutationa S-Transferase pi/genética , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ilhas de CpG , DNA de Neoplasias/sangue , Seguimentos , Glutationa S-Transferase pi/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Reação em Cadeia da Polimerase , Prognóstico , Regiões Promotoras Genéticas/genética , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Taxa de Sobrevida , Estudos de Validação como AssuntoRESUMO
BACKGROUND: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are â¼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. METHODS: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients. RESULTS: Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together. CONCLUSIONS: Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.
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Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Biomarcadores Tumorais/sangue , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/sangue , Neoplasias da Próstata/tratamento farmacológico , RNA Neoplásico/sangue , Taxoides/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Docetaxel , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Curva ROC , Fatores de Risco , Taxoides/farmacologia , Resultado do TratamentoRESUMO
In vertebrate DNA, 3% to 5% of cytosine residues are present as 5-methylcytosine, and it is generally accepted that essentially all of this methylation occurs at cytosines which are contained in the symmetrical dinucleotide CpG. In this report we demonstrate, using bisulphite genomic sequencing, that the methylation machinery of mammalian cells is capable of both maintenance and de novo methylation at CpNpG sites. The existence of inherited CpNpG methylation in mammalian cells has important implications in gene regulation and in the aetiology of disease.
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Citosina/análogos & derivados , Citosina/metabolismo , DNA/metabolismo , Células 3T3 , 5-Metilcitosina , Animais , Sequência de Bases , Linhagem Celular , DNA/química , Enzimas de Restrição do DNA/metabolismo , Metilação , Metiltransferases/metabolismo , Camundongos , Dados de Sequência Molecular , Mutagênicos/química , Plasmídeos , Análise de Sequência/métodos , Sulfitos/química , TransfecçãoRESUMO
This paper develops a simple diagnostic for the investigation of uncertainty within genetic linkage maps using a Bayesian procedure. The method requires only the genotyping data and the proposed genetic map, and calculates the posterior probability for the possible orders of any set of three markers, accounting for the presence of genotyping error (mistyping) and for missing genotype data. The method uses a Bayesian approach to give insight into conflicts between the order in the proposed map and the genotype scores. The method can also be used to assess the accuracy of a genetic map at different genomic scales and to assess alternative potential marker orders. Simulation and two case studies were used to illustrate the method. In the first case study, the diagnostic revealed conflicts in map ordering for short inter-marker distances that were resolved at a distance of 8-12 cM, except for a set of markers at the end of the linkage group. In the second case study, the ordering did not resolve as distances increase, which could be attributed to regions of the map where many individuals were untyped.
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Arabidopsis/genética , Brassica napus/genética , Mapeamento Cromossômico/métodos , Ligação Genética , Cromossomos de Plantas/genética , Simulação por Computador , Cruzamentos Genéticos , Bases de Dados Genéticas , Ecótipo , Marcadores Genéticos , ProbabilidadeRESUMO
The electronic structure of the single component molecular crystal [Ni(ptdt)(2)] (ptdt = propylenedithiotetrathiafulvalenedithiolate) is determined at ambient and high pressure using density functional theory. The electronic structure of this crystal is found to be of the "crossing bands" type with respect to the dispersion of the HOMO and LUMO, resulting in a small, non-zero density of states at the Fermi energy at ambient pressure, indicating that this crystal is a "poor quality" metal, and is consistent with the crystal's resistivity exhibiting a semiconductor-like temperature dependence. The ambient pressure band structure is found to be predominantly one-dimensional, reflecting enhanced intermolecular interactions along the [100] stacking direction. Our calculations indicate that the band structure becomes two-dimensional at high pressures and reveals the role of shortened intermolecular contacts in this phenomenon. The integrity of the molecular structure is found to be maintained up to at least 22 GPa. The electronic structure is found to exhibit a crossing bands nature up to 22 GPa, where enhanced intermolecular interactions increase the Brillouin zone centre HOMO-LUMO gap from 0.05 eV at ambient pressure to 0.15 eV at 22 GPa; this enhanced HOMO-LUMO interaction ensures that enhancement of a metallic state in this crystal cannot be simply achieved through the application of pressure, but rather requires some rearrangement of the molecular packing. Enhanced HOMO-LUMO interactions result in a small density of states at the Fermi energy for the high pressure window 19.8-22 GPa, and our calculations show that there is no change in the nature of the electronic structure at the Fermi energy for these pressures. We correspondingly find no evidence of an electronic semiconducting-metal insulator transition for these pressures, contrary to recent experimental evidence [Cui et al., J. Am. Chem. Soc. 131, 6358 (2009)].
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Although considerable research on the development of agri-environment schemes has focussed on the value of managed field margins as reservoirs for arthropod natural enemies, their potential as reservoirs of entomopathogenic fungi has received less attention. Whether field margins that are most beneficial for arthropod natural enemies are the same as those for entomopathogenic fungi is unknown. Here, within glasshouse mesocosms, we assessed the reproductive success of the aphid-specific entomopathogenic fungus Pandora neoaphidis on aphids in a 'simple margin' containing one plant species and on the same species of aphid in a 'mixed margin' containing seven plant species. These assessments were done in the presence of Aphidius ervi, a hymenopteran parasitoid of aphids regarded as being a key species to conserve in agri-environment schemes in the UK. When only the plants initially infested with aphids were assessed, transmission of P. neoaphidis was significantly greater (p<0.001) in the mixed margin as was parasitisation by A. ervi (p<0.05). However, when all of the plants in the mesocosms were assessed, transmission of P. neoaphidis remained greater in the mixed margin (p<0.05) whereas parasitisation by A. ervi was greater in the simple margin (p<0.05). This difference may be due to aphid dispersal which was greater in the simple margin thereby benefitting the actively foraging parasitoid whereas clustering of aphids in the mixed margin benefited the passively dispersed fungus. In a second mesocosm experiment, the movement of P. neoaphidis over the crop-margin interface was similar to that of A. ervi despite the fungus only being passively dispersed in contrast to the actively foraging parasitoid. The results presented here indicate that, although the optimal plant composition of field margins may differ for P. neoaphidis and A. ervi, both species can co-exist and reproduce in field margins and will move over the crop-margin interface. Managed field margins that benefit both key arthropod and key microbial enemies have potential for enhancing pest control in associated crops.
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Afídeos , Produtos Agrícolas , Entomophthorales , Controle Biológico de Vetores/métodos , Doenças das Plantas , Animais , Sistemas Ecológicos FechadosRESUMO
Rat T cells and thymocytes were induced to proliferate by a pair of mAbs, MRC OX-54 and MRC OX-55, directed against rat CD2. Accessory cells were required but their role was not simply for crosslinking of the two mAbs, as neither MRC OX-54 nor MRC OX-55 alone, in the presence of a crosslinking second antibody, caused T cell mitogenesis. Nor could the phorbol ester PMA replace either antibody. The two mAbs recognized distinct epitopes on rat CD2; however, MRC OX-54 could partially block MRC OX-55 binding whereas the reverse situation was not seen. A further CD2 epitope was recognized by two mutually competitive mAbs, MRC OX-34 and MRC OX-53, which were not mitogenic. Neither MRC OX-34 nor MRC OX-53 affected the binding of MRC OX-54 or MRC OX-55, yet they prevented the mitogenic effect induced by these mAbs. The presence of mAbs against CD4 and the IL-2-R also abrogated this mitogenesis, whereas an anti-CD5 mAb augmented the CD2-induced proliferation.
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Antígenos de Diferenciação de Linfócitos T/imunologia , Ativação Linfocitária , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais/imunologia , Reações Antígeno-Anticorpo , Células Apresentadoras de Antígenos/imunologia , Células Cultivadas , Relação Dose-Resposta Imunológica , Linfonodos/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ratos , Receptores Imunológicos/imunologia , Receptores de Interleucina-2 , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
The MRC OX-34 antigen of rat T lymphocytes was purified and peptide sequences were obtained. Oligonucleotide probes were synthesized and cDNA clones coding for the antigen were isolated and sequenced to yield a predicted protein sequence for the molecule that fitted the peptide data. Comparison of this sequence with that for human CD2 determined by Sewell et al. showed that OX-34 is rat CD2. The primary structure of the molecule was notable for a moderately large cytoplasmic domain of unusual sequence and also for its highly significant relationship to CD4 antigen in the membrane proximal extracellular region and the transmembrane sequence. A relationship to the Ig superfamily can be argued for the two extra cellular domains of CD2, even though neither fits the standard pattern for Ig-related domains. Within the T lymphocyte lineage, rat CD2 seemed to be present on all stages with the exception of approximately 50% of the thymic CD4-,CD8- cells. In addition, the antigen was prominent on most macrophages in the spleen but not found on peritoneal or liver macrophages. CD4 antigen is also expressed on T lymphocytes and macrophages, and thus CD2 and CD4 appear similar in their cellular expression as well as structural characteristics.
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Antígenos de Superfície/imunologia , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Antígenos de Diferenciação de Linfócitos T , Antígenos de Superfície/isolamento & purificação , Sequência de Bases , Clonagem Molecular , DNA/genética , Humanos , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Ratos , Ratos Endogâmicos , Baço/imunologia , Timo/imunologiaRESUMO
The CD4 antigen is expressed on T cells of all mammalian species examined and appears to play an important role in the response of T cells to antigen. In humans, the molecule acts as a receptor for the AIDS virus. Previous studies have demonstrated that M phi in the rat and human also express the CD4 antigen, which is indistinguishable from that on T cells. In this paper we demonstrate by FACS analysis, Northern blot hybridization, and immunoperoxidase labeling that, in striking contrast to the rat and human, mouse M phi do not express the CD4 (L3T4) antigen. This species heterogeneity indicates that T cells and M phi regulate CD4 antigen expression independently and that CD4 may not be essential for M phi function.
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Antígenos de Superfície/imunologia , Macrófagos/imunologia , Animais , Anticorpos Monoclonais , Antígenos de Diferenciação de Linfócitos T , Camundongos , Camundongos Endogâmicos C57BL , Especificidade da EspécieRESUMO
BACKGROUND: Collagen and calcium-binding EGF domains 1 (CCBE1) is an uncharacterised gene that has down-regulated expression in breast cancer. As CCBE1 maps to 18q21.32, a region frequently exhibiting loss of heterozygosity in ovarian cancer, the aim of this study was to determine the expression and function of CCBE1 in ovarian cancer. METHODS: Expression and methylation patterns of CCBE1 were determined in ovarian cancer cell lines and primary tumours. CCBE1 contains collagen repeats and an aspartic acid/asparagine hydroxylation/EGF-like domain, suggesting a function in extracellular matrix remodelling and migration, which was determined using small-interfering RNA (siRNA)-mediated knockdown and over-expression of CCBE1 in cell lines. RESULTS: CCBE1 is expressed in normal ovary, but is reduced in ovarian cancer cell lines and primary carcinomas. Pharmacological demethylation/deacetylation in ovarian cancer cell lines re-induced CCBE1 expression, indicating that epigenetic mechanisms contribute to its silencing in cancer. CCBE1 promoter hypermethylation was detected in 6/11 (55%) ovarian cancer cell lines and 38/81 (41%) ovarian carcinomas. siRNA-mediated knockdown of CCBE1 in ovarian cancer cell lines enhanced their migration; conversely, re-expression of CCBE1 reduced migration and survival. Hence, loss of CCBE1 expression may promote ovarian carcinogenesis by enhancing migration and cell survival. CONCLUSIONS: These data suggest that CCBE1 is a new candidate tumour suppressor in ovarian cancer.
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Proteínas de Ligação ao Cálcio/fisiologia , Carcinoma/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Proteínas de Neoplasias/fisiologia , Neoplasias Ovarianas/genética , Regiões Promotoras Genéticas/genética , Proteínas Supressoras de Tumor/fisiologia , Mama/citologia , Neoplasias da Mama/patologia , Proteínas de Ligação ao Cálcio/genética , Carcinoma/patologia , Linhagem Celular Transformada/metabolismo , Linhagem Celular Tumoral/citologia , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas/metabolismo , Ilhas de CpG/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/patologia , Estrutura Terciária de Proteína , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , RNA Interferente Pequeno/farmacologia , Proteínas Recombinantes de Fusão/fisiologia , Ensaio Tumoral de Célula-Tronco , Proteínas Supressoras de Tumor/genéticaRESUMO
The UK Farm-Scale Evaluations (FSE) compared the effects on biodiversity of management of genetically modified herbicide-tolerant (GMHT) spring-sown crops with conventional crop management. The FSE reported larger weed abundance under GMHT management for fodder maize, one of three crops studied. Increased seed production may be important for the long-term persistence of these arable weeds and may benefit invertebrates, small mammals and seed-eating birds. In three-quarters of FSE maize fields, growers used atrazine on the conventionally managed half, reflecting contemporary commercial practice. Withdrawal of the triazine herbicides atrazine, simazine and cyanazine from approved lists of EU chemicals could therefore reduce or even reverse the reported benefits of GMHT maize. Here we analyse effects of applications of triazine herbicides in conventional maize regimes on key indicators, using FSE data. Weed abundances were decreased greatly relative to all other regimes whenever atrazine was applied before weeds emerged. Here, we forecast weed abundances in post-triazine herbicide regimes. We predict weed abundances under future conventional herbicide management to be considerably larger than that for atrazine used before weeds emerged, but still smaller than for the four FSE sites analysed that used only non-triazine herbicides. Our overall conclusion is that the comparative benefits for arable biodiversity of GMHT maize cropping would be reduced, but not eliminated, by the withdrawal of triazines from conventional maize cropping.
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Herbicidas/farmacologia , Plantas/efeitos dos fármacos , Zea mays/fisiologia , Atrazina/farmacologia , Biodiversidade , Biomassa , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Desenvolvimento Vegetal , Plantas Geneticamente Modificadas , Reino Unido , Zea mays/efeitos dos fármacos , Zea mays/genéticaRESUMO
We present results of first principles density functional theory calculations of the electronic and atomic structural properties of model Z-type Langmuir-Blodgett (LB) layers comprising amphiphilic quinolinium tricyanoquinodimethanide (Q3CNQ) chromophores. We find that the chromophore electronic ground state is not as clearly "zwitterionic" as required by models to explain electrical rectification purportedly seen in such systems. The computed visible region transitions are not what have been assumed to be the intervalence charge transfer bands seen in the visible region of molecules in Z-type LB films. Our own LB deposition and spectroscopic studies suggest that almost all visible region features previously seen may be ascribed to aggregates. The calculated lowest energy electronic excitation between HOMO and LUMO levels, which is located in the near infrared region, has a transition moment aligned approximately 9° off the molecular long axis, and has a normalized oscillator strength of 1 order of magnitude higher than those of the visible region transitions. This most dominant feature has been neglected from discussions of Langmuir-Blodgett layer rectification but our own deposition studies show no sign of this feature, indicating that the structure of the modeled system differs from that of typical experimental structures. The model indicates that such idealized LB layer structures cannot confidently be invoked to explain their experimental optical or electrical properties.
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Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease.