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1.
Nature ; 614(7948): 564-571, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36755093

RESUMO

Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that have poorly defined functions1-3. Intrinsically disordered regions can mediate phase separation and the formation of biomolecular condensates, such as the nucleolus4,5. This suggests that mutations in disordered proteins may alter condensate properties and function6-8. Here we show that a subset of disease-associated variants in disordered regions alter phase separation, cause mispartitioning into the nucleolus and disrupt nucleolar function. We discover de novo frameshift variants in HMGB1 that cause brachyphalangy, polydactyly and tibial aplasia syndrome, a rare complex malformation syndrome. The frameshifts replace the intrinsically disordered acidic tail of HMGB1 with an arginine-rich basic tail. The mutant tail alters HMGB1 phase separation, enhances its partitioning into the nucleolus and causes nucleolar dysfunction. We built a catalogue of more than 200,000 variants in disordered carboxy-terminal tails and identified more than 600 frameshifts that create arginine-rich basic tails in transcription factors and other proteins. For 12 out of the 13 disease-associated variants tested, the mutation enhanced partitioning into the nucleolus, and several variants altered rRNA biogenesis. These data identify the cause of a rare complex syndrome and suggest that a large number of genetic variants may dysregulate nucleoli and other biomolecular condensates in humans.


Assuntos
Nucléolo Celular , Proteína HMGB1 , Humanos , Arginina/genética , Arginina/metabolismo , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Nucléolo Celular/patologia , Proteína HMGB1/química , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Síndrome , Mutação da Fase de Leitura , Transição de Fase
2.
Mycorrhiza ; 31(3): 395-401, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33782833

RESUMO

Rhizosphere microbiome is one of the main sources of plant protection against drought. Beneficial symbiotic microorganisms, such as ectomycorrhizal fungi (ECMF) and mycorrhiza helper bacteria (MHB), interact with each other for increasing or maintaining host plant fitness. This mutual support benefits all three partners and comprises a natural system for drought acclimation in plants. Cork oak (Quercus suber L.) tolerance to drought scenarios is widely known, but adaptation to climate changes has been a challenge for forest sustainability protection. In this work, ECMF and MHB communities from cork oak forests were cross-linked and correlated with climates. Cenococcum, Russula and Tuber were the most abundant ECMF capable of interacting with MHB (ECMF~MHB) genera in cork oak stands, while Bacillus, Burkholderia and Streptomyces were the most conspicuous MHB. Integrating all microbial data, two consortia Lactarius/Bacillaceae and Russula/Burkholderaceae have singled out but revealed a negative interaction with each other. Russula/Burkholderaceae might have an important role for cork oak forest sustainability in arid environments, which will be complemented by the lower drought adaptation of competitive Lactarius/Bacillaceae. These microbial consortia could play an essential role on cork oak forest resilience to upcoming climatic changes.


Assuntos
Micorrizas , Quercus , Bactérias , Secas , Florestas
3.
Int J Mol Sci ; 21(11)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32471127

RESUMO

Modifications of DNA and histones, including methylation and acetylation, are critical for the epigenetic regulation of gene expression during plant development, particularly during environmental adaptation processes. However, information on the enzymes catalyzing all these modifications in trees, such as Quercus suber L., is still not available. In this study, eight DNA methyltransferases (DNA Mtases) and three DNA demethylases (DDMEs) were identified in Q. suber. Histone modifiers involved in methylation (35), demethylation (26), acetylation (8), and deacetylation (22) were also identified in Q. suber. In silico analysis showed that some Q. suber DNA Mtases, DDMEs and histone modifiers have the typical domains found in the plant model Arabidopsis, which might suggest a conserved functional role. Additional phylogenetic analyses of the DNA and histone modifier proteins were performed using several plant species homologs, enabling the classification of the Q. suber proteins. A link between the expression levels of each gene in different Q. suber tissues (buds, flowers, acorns, embryos, cork, and roots) with the functions already known for their closest homologs in other species was also established. Therefore, the data generated here will be important for future studies exploring the role of epigenetic regulators in this economically important species.


Assuntos
Epigênese Genética , Genoma de Planta , Quercus/genética , DNA (Citosina-5-)-Metiltransferases/química , DNA (Citosina-5-)-Metiltransferases/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Filogenia , Desenvolvimento Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Domínios Proteicos , Quercus/enzimologia , Quercus/crescimento & desenvolvimento
4.
J Phys Chem A ; 123(38): 8188-8199, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31453699

RESUMO

The inner space of carbon nanotubes has already been proven to provide a type of confinement, which can dramatically alter the energetics of chemical reactions when compared to the gas phase. Moreover, BN doping can be used to fine-tune electronic properties, which might influence the enthalpy and activation energy of chemical reactions that take place inside their inner space. The energy profile of the prototype Menshutkin SN2 reaction between ammonia and chloromethane has been analyzed in a variety of carbon-based materials at the DFT (density functional theory) level. Pristine zigzag (9,0) and (12,0) single-walled carbon nanotubes and graphene sheets have been doped with boron and nitrogen at different stoichiometries, namely, BN, BNC, BNC2, and BNC4, that resulted in remarkable variations of their catalytic effects. Graphene has revealed to be the support material, which depends less on doping in terms of enthalpy and energy barrier of the reaction. However, when graphene is rolled up into tubular forms, the influence of doping becomes increasingly stronger as the nanotube radius decreases. In the case of BNC4 doping of (9,0) nanotubes, the activation energy drops 10 kcal/mol when compared to the pristine case, and the reaction became even exothermic by more than 15 kcal/mol.

5.
Int J Sport Nutr Exerc Metab ; 27(4): 361-369, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28253032

RESUMO

We aimed to assess the validity of a single question to evaluate leisure-time physical activity (PA) in adolescents. We included 209 participants (57.4% girls) aged 14-18 years from Porto, Portugal, evaluated as part of the SALTA project. A self-reported question with four answer options, designed for the EPITeen study, was used to classify the intensity level of usual leisure-time activities. Actigraph accelerometers were used to objectively measure total PA during 7 consecutive days. Since the accelerometers measured PA as a continuous variable, hierarchical cluster analysis was used to identify clusters of individuals with similar level of objectively measured PA. Correlations between self-reported and objective measures were evaluated through polychoric correlations. In girls, we found higher mean time on sedentary activities among those describing their leisure-time PA as "sitting", and an increase on the time spent on light and moderate activities with increasing intensity of PA on self-reported classification. A similar trend was found in boys, but not reaching statistical significance. The correlation between the two measures of PA was 0.42 for girls and 0.46 for boys. We found an acceptable correlation between our single question and the objectively measured PA, showing that, although the single question is not adequate to quantify the intensity of the physical activity, it allows to rank adolescents according to leisure-time physical activity.


Assuntos
Exercício Físico , Inquéritos e Questionários , Actigrafia , Adolescente , Feminino , Humanos , Masculino , Portugal
6.
Plant Cell Physiol ; 56(12): 2297-311, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26468507

RESUMO

Post-translational modification mechanisms function as switches that mediate the balance between optimum growth and the response to environmental stimuli, by regulating the activity of key proteins. SUMO (small ubiquitin-like modifier) attachment, or sumoylation, is a post-translational modification that is essential for the plant stress response, also modulating hormonal circuits to co-ordinate developmental processes. The Arabidopsis SUMO E3 ligase SAP and Miz 1 (SIZ1) is the major SUMO conjugation enhancer in response to stress, and is implicated in several aspects of plant development. Here we report that known SUMO targets are over-represented in multiple carbohydrate-related proteins, suggesting a functional link between sumoylation and sugar metabolism and signaling in plants. We subsequently observed that SUMO-conjugated proteins accumulate in response to high doses of sugar in a SIZ1-dependent manner, and that the null siz1 mutant displays increased expression of sucrose and starch catabolic genes and shows reduced starch levels. We demonstrated that SIZ1 controls germination time and post-germination growth via osmotic and sugar-dependent signaling, respectively. Glucose was specifically linked to SUMO-sugar interplay, with high levels inducing root growth inhibition and aberrant root hair morphology in siz1. The use of sugar analogs and sugar marker gene expression analysis allowed us to implicate SIZ1 in a signaling pathway dependent on glucose metabolism, probably involving modulation of SNF1-related kinase 1 (SnRK1) activity.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Metabolismo dos Carboidratos , Ligases/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Metabolismo dos Carboidratos/efeitos dos fármacos , Metabolismo dos Carboidratos/genética , Carboidratos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Germinação/efeitos dos fármacos , Germinação/genética , Glucose/farmacologia , Hexoquinase/metabolismo , Ligases/genética , Modelos Biológicos , Peso Molecular , Mutação/genética , Fenótipo , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Amido/metabolismo , Sacarose/metabolismo , Sumoilação
7.
J Sex Med ; 12(11): 2141-52, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26556180

RESUMO

INTRODUCTION: Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that other sirtuins could also be expressed in the CC. Expression of these enzymes in tissues is affected by aging, the main independent risk factor for erectile dysfunction besides other cardiovascular disease risk factors (CVDRF), such as diabetes or obesity. AIM: The aim of this study was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC relatively to age and CVDRF. METHODS: Samples of CC collected from patients submitted to programmed surgeries or organ donors were divided in three groups according to age and presence of CVDRF. Expression of SIRT1-3 and SIRT5-7 mRNAs was assessed by real-time polymerase chain reaction. Cellular localization and semi-quantification of sirtuins proteins were performed by immunofluorescence and Western blotting (WB), respectively. Nuclear factor kappa B (NFkB)-p65, inducible (iNOS) and endothelial nitric oxide synthase (eNOS) levels were also assayed by WB. MAIN OUTCOME MEASURES: The main outcome measure was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC. RESULTS: SIRT1-3 and SIRT5-7 mRNAs were detected in all individuals, without statistical differences among groups, excepting SIRT7 that decreased four times in aged groups relatively to young (P = 0.013). WB analysis demonstrated that aged individuals with CVDRF presented higher levels of SIRT7 protein relatively to young (P = 0.0495) and lower levels of SIRT3 protein relatively to healthy aged (P = 0.0077). Expression of NFkB-p65 and iNOS were higher in aged than in young individuals (P = 0.0185; P = 0.004, respectively). No differences in other sirtuins or total eNOS were seen among groups although phospho eNOS Ser(1177) levels decreased in groups of aged men relatively to young (P = 0.0043; P = 0.0099). CONCLUSIONS: Our results demonstrate for the first time expression of SIRT2-3 and SIRT5-7 in the human CC. Aged individuals with CVDRF presented an increase in SIRT7 protein levels and a decrease in mitochondrial SIRT3. This finding suggests that CVDRF induces the loss of antioxidant defense mechanisms leading to endothelial injury.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/fisiopatologia , Disfunção Erétil/fisiopatologia , Pênis/fisiopatologia , Sirtuínas/metabolismo , Adulto , Idoso , Western Blotting , Doenças Cardiovasculares/metabolismo , Endotélio/metabolismo , Disfunção Erétil/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/metabolismo , Pênis/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Sirtuína 1 , Regulação para Cima
8.
J Sex Med ; 12(4): 876-86, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25487286

RESUMO

INTRODUCTION: Erectile dysfunction is highly prevalent in patients with advanced age or cardiovascular disease risk factors (CVDRFs). These conditions interfere on expression of vascular growth factors and respective receptors causing disturbance in endothelial function. AIM: This study aims to assess the effect of aging and CVDRF on the expression of tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie) 1 in human corpus cavernosum (CC). METHODS: CC fragments obtained from programmed surgeries or organ donors were divided into three groups: young, healthy aged, and aged with CVDRF. Angiopoietin (Ang) 1, Ang2, Tie1, and Tie2 mRNA and protein levels were assessed by real-time polymerase chain reaction and Western blotting, respectively. Dual-immunolabeling of Tie1 with specific markers of endothelium and smooth muscle and Ang1 and Ang2 was performed. MAIN OUTCOME MEASURES: To characterize the expression of Tie1 in human CC and elucidate its potential inhibitory effect in Ang-Tie2 system. RESULTS: Analysis of mRNAs demonstrated a decrease in Tie1 expression in CVDRF individuals compared with aged or young healthy individuals. No variation for Tie2, Ang1, or Ang2 expression was observed among the studied groups. In all analyzed CC fragments, a 125 kDa band, Tie1, was detected. This protein presented a significant age-related decrease, specially in individuals with CVDRF. Immunofluorescence study revealed Tie1 expression in the endothelium of samples of all experimental groups. CONCLUSIONS: Employing different methodological approaches, we show for the first time that Tie1 is expressed in human CC endothelium, and its level of expression diminishes in aged individuals, particularly those with CVDRF. This finding reinforces the view that delivery of Ang1 to the CC of erectile dysfunction affected CVDRF patients is able to activate a beneficial Tie2 response.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/fisiopatologia , Pênis/metabolismo , Receptor de TIE-1/biossíntese , Adulto , Fatores Etários , Idoso , Angiopoietina-1/biossíntese , Angiopoietina-2/biossíntese , Western Blotting , Endotélio/metabolismo , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor TIE-2/biossíntese , Fatores de Risco
9.
J Org Chem ; 80(1): 281-9, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-25418452

RESUMO

The first direct epoxidation of acridine on the edge positions is reported. The reaction proceeds under mild conditions using a biomimetic catalytic system based on a Mn(III) porphyrin. The successive oxyfunctionalization to mono-, di-, and tetraepoxy derivatives is accomplished using hydrogen peroxide as a green oxidant at room temperature. Computed optimized geometries showed only slight shifts to the base planarity upon dearomatization by epoxidation, which is an important feature for DNA intercalation and bioactivity. NMR studies and comparison with theoretical values allowed the assignment of the stereochemistry of the anti- and syn-diepoxy and -tetraepoxy derivatives as well as compounds resulting from epoxide ring opening, exemplified by epoxydiol. The diepoxide is formed in an anti:syn ratio of ∼4, and the attack by nucleophiles, exemplified by ethylaniline, occurs selectively and with full conversion, using a microwave process with acetonitrile reflux for 10 min. Finally, studies of the electrostatic potential allowed the mechanisms of the formation of 4-hydroxyacridine and the regioselective reaction of diepoxyacridine with nucleophiles to be rationalized.


Assuntos
Acridinas/química , Materiais Biomiméticos/química , Compostos de Epóxi/síntese química , Manganês/química , Metaloporfirinas/química , Catálise , Compostos de Epóxi/química , Estrutura Molecular , Teoria Quântica
10.
Chem Sci ; 15(25): 9793-9805, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38939148

RESUMO

Secreted phospholipase A2 (sPLA2) is a Ca2+-dependent, widely distributed enzyme superfamily in almost all mammalian tissues and bacteria. It is also a critical component of the venom of nearly all snakes, as well as many invertebrate species. In non-venomous contexts, sPLA2 assumes significance in cellular signaling pathways by binding cell membranes and catalyzing ester bond hydrolysis at the sn-2 position of phospholipids. Elevated levels of GIIA sPLA2 have been detected in the synovial fluid of arthritis patients, where it exhibits a pro-inflammatory function. Consequently, identifying sPLA2 inhibitors holds promise for creating highly effective pharmaceutical treatments. Beyond arthritis, the similarities among GIIA sPLA2s offer an opportunity for developing treatments against snakebite envenoming, the deadliest neglected tropical disease. Despite decades of study, the details of PLA2 membrane-binding, substrate-binding, and reaction mechanism remain elusive, demanding a comprehensive understanding of the sPLA2 catalytic mechanism. This study explores two reaction mechanism hypotheses, involving one or two water molecules, and distinct roles for the Ca2+ cofactor. Our research focuses on the human synovial sPLA2 enzyme bound to lipid bilayers of varying phospholipid compositions, and employing adiabatic QM/MM and QM/MM MD umbrella sampling methods to energetically and geometrically characterize the structures found along both reaction pathways. Our studies demonstrate the higher frequency of productive conformations within the single-water pathway, also revealing a lower free energy barrier for hydrolyzing POPC. Furthermore, we observe that the TS of this concerted one-step reaction closely resembles transition state geometries observed in X-ray crystallography complexes featuring high-affinity transition state analogue inhibitors.

11.
Nat Cell Biol ; 26(8): 1309-1321, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38969762

RESUMO

Transcription factors (TFs) control specificity and activity of gene transcription, but whether a relationship between these two features exists is unclear. Here we provide evidence for an evolutionary trade-off between the activity and specificity in human TFs encoded as submaximal dispersion of aromatic residues in their intrinsically disordered protein regions. We identified approximately 500 human TFs that encode short periodic blocks of aromatic residues in their intrinsically disordered regions, resembling imperfect prion-like sequences. Mutation of periodic aromatic residues reduced transcriptional activity, whereas increasing the aromatic dispersion of multiple human TFs enhanced transcriptional activity and reprogramming efficiency, promoted liquid-liquid phase separation in vitro and more promiscuous DNA binding in cells. Together with recent work on enhancer elements, these results suggest an important evolutionary role of suboptimal features in transcriptional control. We propose that rational engineering of amino acid features that alter phase separation may be a strategy to optimize TF-dependent processes, including cellular reprogramming.


Assuntos
Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/química , Mutação , Ligação Proteica , Transcrição Gênica , DNA/metabolismo , DNA/genética , Células HEK293 , Reprogramação Celular/genética , Regulação da Expressão Gênica
12.
Methods Mol Biol ; 2581: 367-383, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36413331

RESUMO

ABSTACT: Plant sumoylation research has seen significant advances in recent years, particularly since high-throughput proteomic strategies have enabled the discovery of more than one thousand SUMO targets. In the present chapter, we update the previously reported SUMO (small ubiquitin-related modifier) gene network (SGN) to its v4 iteration. SGN is a curated assembly of Arabidopsis thaliana genes that have been functionally associated with sumoylation, from SUMO pathway components to targets and interactors. The enclosed tutorial helps interpret and manage these datasets and details bioinformatic tools that can be used for in silico-based hypothesis generation. The latter include tools for sumoylation site prediction, comparative genomics, and gene network analysis.


Assuntos
Arabidopsis , Redes Reguladoras de Genes , Biologia Computacional , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Proteômica , Arabidopsis/genética , Arabidopsis/metabolismo
13.
J Phys Chem B ; 127(2): 557-566, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36282235

RESUMO

Graphene oxide (GO), a nanomaterial with promising applications that range from water purification to enzyme immobilization, is actively present in scientific research since its discovery. GO studies with computational methodologies such as molecular dynamics are frequently reported in the literature; however, the models used often rely on approximations, such as randomly placing functional groups and the use of generalized force fields. Therefore, it is important to develop new MD models that provide a more accurate description of GO structures and their interaction with an aqueous solvent and other adsorbate molecules. In this paper, we derived new force field non-bonded parameters from linear-scaling density functional theory calculations of nanoscale GO sheets with more than 10,000 atoms through an atoms-in-molecules (AIM) partitioning scheme. The resulting GAFF2-AIM force field, derived from the bonded terms of GAFF2 parameterization, reproduces the solvent structure reported in ab initio MD simulations better than the force field nowadays widely used in the literature. Additionally, we analyzed the effect of the ionic strength of the medium and of the C/O ratio on the distribution of charges surrounding the GO sheets. Finally, we simulated the adsorption of natural amino acid molecules to a GO sheet and estimated their free energy of binding, which compared very favorably to their respective experimental values, validating the force field presented in this work.


Assuntos
Simulação de Dinâmica Molecular , Água , Adsorção , Água/química , Solventes
14.
Porto Biomed J ; 7(2): e144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38304155

RESUMO

Background: We studied if proximity of urban green spaces to residences reduces the socioeconomic inequalities in sports practice, evaluating 17-year-old girls (n = 722) from EPITeen cohort, Porto, Portugal. Methods: The shortest routes from residences to urban green spaces were calculated using the street network from Geographic Information System. Distances were classified as: ≤400, >400 to ≤800, and >800 m. Parental education was used as a proxy of socioeconomic status (SES). We used chi-square test to compare proportions of teenagers practicing sports per SES, stratified by classes of distances to urban green spaces and logistic regression to estimate the association between sports practice and SES through odds ratio (OR) and 95% confidence intervals. Results: Strong inequalities were found. Girls from low SES have ≥75% less odds of sports practice (reference: high SES), regardless of the distance to urban green spaces. As distances are lowering the socioeconomic inequalities in the sports practice between girls from high and medium SES diminishes, being the OR 0.42 (0.22-0.80) at ≥800 m, 0.51 (0.24-1.09) at ≥400 to ≤800 m, and 0.63 (0.29-1.37) at ≤400 m. Conclusion: At closer distances inequalities in the proportion of sports practice between high and medium SES vanishes, but remain to low SES.

15.
Langmuir ; 26(13): 10842-53, 2010 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-20476725

RESUMO

A novel multilayer film containing a cationic phosphonium-derivatized Ni(salen)-type complex and poly(sodium-4-styrenesulfonate (NaPSS) was assembled onto quartz, mica, and metal surfaces using the layer-by-layer (LbL) technique. Spectroscopic (UV-vis) and gravimetric (QCM) responses for the multilayer films show regular stepwise growth and the signature of strong electrostatic interactions between the component layers. The gravimetric responses indicate the presence of substantial additional (net neutral) material in the PSS layers, which XPS shows is not polyelectrolyte or salt, so charge compensation is intrinsic; we deduce the presence of space-filling solvent. Direct electrostatic interaction of the two-component layers is enhanced by a secondary noncovalent interaction between the delocalized pi-systems of the two components. Permeability of the film to the redox probe [Fe(CN)(6)](3-/4-) was studied by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Qualitatively similar results were obtained in the absence and presence of a precursor PSS/PAH multilayer, but with a general shift in kinetic and diffusional processes to longer time scales (lower frequencies) in the presence of the precursor layer and with increasing numbers of PSS/[Ni(salen)] bilayers. Quantitatively, the EIS data were interpreted using a capillary membrane model (CMM) to yield values of coverage, apparent charge transfer resistance, double-layer capacitance, pore size, and diffusion coefficient. The coverage values were consistent with a model in which there are no preferential growth sites and the surface charge density is independent of the number of bilayers.

16.
J Phys Chem A ; 114(45): 12016-20, 2010 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-20979403

RESUMO

Controlling the selectivity between H(2)+CO and H+HCO in the S(1)/S(0) nonadiabatic photodissociation of formaldehyde has been investigated using direct quantum dynamics. Simulations started from the S(1) transition state have suggested that a key feature for controlling the branching ratio of ground-state products is the size of the momentum given to the wavepacket along the transition vector. Our results show that letting the wavepacket fall down from the barrier to the conical intersection with no initial momentum leads to H(2)+CO, while extra momentum toward products favors the formation of H+HCO through the same conical intersection. Quantum dynamics results are interpreted in semiclassical terms with the aid of a Mulliken-like analysis of the final population distribution among both products and the reactant on each electronic state.

17.
J Theor Biol ; 257(2): 303-11, 2009 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-19111559

RESUMO

The cancer diagnostic is a complex process and, sometimes, the specific markers can interfere or produce negative results. Thus, new simple and fast theoretical models are required. One option is the complex network graphs theory that permits us to describe any real system, from the small molecules to the complex genetic, neural or social networks by transforming real properties in topological indices. This work converts the protein primary structure data in specific Randic's star networks topological indices using the new sequence to star networks (S2SNet) application. A set of 1054 proteins were selected from previous works and contains proteins related or not with two types of cancer, human breast cancer (HBC) and human colon cancer (HCC). The general discriminant analysis method generates an input-coded multi-target classification model with the training/predicting set accuracies of 90.0% for the forward stepwise model type. In addition, a protein subset was modified by single amino acid mutations with higher log-odds PAM250 values and tested with the new classification if can be related with HBC or HCC. In conclusion, we shown that, using simple input data such is the primary protein sequence and the simples linear analysis, it is possible to obtain accurate classification models that can predict if a new protein related with two types of cancer. These results promote the use of the S2SNet in clinical proteomics.


Assuntos
Neoplasias da Mama/classificação , Neoplasias do Colo/classificação , Simulação por Computador , Modelos Estatísticos , Proteínas de Neoplasias/classificação , Sequência de Aminoácidos , Neoplasias da Mama/metabolismo , Neoplasias do Colo/metabolismo , Análise Discriminante , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Proteínas de Neoplasias/genética , Reconhecimento Automatizado de Padrão
18.
J Theor Biol ; 256(3): 458-66, 2009 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-18992259

RESUMO

The importance of the promoter sequences in the function regulation of several important mycobacterial pathogens creates the necessity to design simple and fast theoretical models that can predict them. This work proposes two DNA promoter QSAR models based on pseudo-folding lattice network (LN) and star-graphs (SG) topological indices. In addition, a comparative study with the previous RNA electrostatic parameters of thermodynamically-driven secondary structure folding representations has been carried out. The best model of this work was obtained with only two LN stochastic electrostatic potentials and it is characterized by accuracy, selectivity and specificity of 90.87%, 82.96% and 92.95%, respectively. In addition, we pointed out the SG result dependence on the DNA sequence codification and we proposed a QSAR model based on codons and only three SG spectral moments.


Assuntos
DNA Bacteriano/genética , Mycobacterium/genética , Regiões Promotoras Genéticas/genética , Códon , Cadeias de Markov , Modelos Biológicos , Estrutura Secundária de Proteína , Relação Quantitativa Estrutura-Atividade
19.
J Chem Phys ; 131(14): 144301, 2009 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-19831435

RESUMO

The mechanisms of radiationless decay involved in the photodissociation of formaldehyde into H(2) and CO have been investigated using complete active space self-consistent field (CASSCF) calculations and direct dynamics variational multiconfiguration Gaussian (DD-vMCG) quantum dynamics in the S(1), T(1), and S(0) states. A commonly accepted scheme involves Fermi Golden Rule internal conversion from S(1) followed by dissociation of vibrationally hot H(2)CO in S(0). We recently proposed a novel mechanism [M. Araujo et al., J. Phys. Chem. A 112, 7489 (2008)] whereby internal conversion and dissociation take place in concert through a seam of conical intersection between S(1) and S(0) after the system has passed through an S(1) transition barrier. The relevance of this mechanism depends on the efficiency of tunneling in S(1). At lower energy, an alternative scheme to internal conversion involves intersystem crossing via T(1) to regenerate the reactant before the S(0) barrier to dissociation. We propose here a previously unidentified mechanism leading directly to H(2) and CO products via T(1). This channel opens at medium energies, near or above the T(1) barrier to dissociation and still lower than the S(1) barrier, thus making T(1) a possible shortcut to molecular dissociation.

20.
J Theor Biol ; 254(2): 476-82, 2008 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-18606172

RESUMO

The huge amount of new proteins that need a fast enzymatic activity characterization creates demands of protein QSAR theoretical models. The protein parameters that can be used for an enzyme/non-enzyme classification includes the simpler indices such as composition, sequence and connectivity, also called topological indices (TIs) and the computationally expensive 3D descriptors. A comparison of the 3D versus lower dimension indices has not been reported with respect to the power of discrimination of proteins according to enzyme action. A set of 966 proteins (enzymes and non-enzymes) whose structural characteristics are provided by PDB/DSSP files was analyzed with Python/Biopython scripts, STATISTICA and Weka. The list of indices includes, but it is not restricted to pure composition indices (residue fractions), DSSP secondary structure protein composition and 3D indices (surface and access). We also used mixed indices such as composition-sequence indices (Chou's pseudo-amino acid compositions or coupling numbers), 3D-composition (surface fractions) and DSSP secondary structure amino acid composition/propensities (obtained with our Prot-2S Web tool). In addition, we extend and test for the first time several classic TIs for the Randic's protein sequence Star graphs using our Sequence to Star Graph (S2SG) Python application. All the indices were processed with general discriminant analysis models (GDA), neural networks (NN) and machine learning (ML) methods and the results are presented versus complexity, average of Shannon's information entropy (Sh) and data/method type. This study compares for the first time all these classes of indices to assess the ratios between model accuracy and indices/model complexity in enzyme/non-enzyme discrimination. The use of different methods and complexity of data shows that one cannot establish a direct relation between the complexity and the accuracy of the model.


Assuntos
Simulação por Computador , Modelos Moleculares , Proteínas/classificação , Algoritmos , Sequência de Aminoácidos , Animais , Sequência de Bases , Enzimas/classificação , Dados de Sequência Molecular , Reconhecimento Automatizado de Padrão , Conformação Proteica , Relação Quantitativa Estrutura-Atividade , Análise de Sequência de Proteína
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