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The electron-hole plasma in charge-neutral graphene is predicted to realize a quantum critical system in which electrical transport features a universal hydrodynamic description, even at room temperature1,2. This quantum critical 'Dirac fluid' is expected to have a shear viscosity close to a minimum bound3,4, with an interparticle scattering rate saturating1 at the Planckian time, the shortest possible timescale for particles to relax. Although electrical transport measurements at finite carrier density are consistent with hydrodynamic electron flow in graphene5-8, a clear demonstration of viscous flow at the charge-neutrality point remains elusive. Here we directly image viscous Dirac fluid flow in graphene at room temperature by measuring the associated stray magnetic field. Nanoscale magnetic imaging is performed using quantum spin magnetometers realized with nitrogen vacancy centres in diamond. Scanning single-spin and wide-field magnetometry reveal a parabolic Poiseuille profile for electron flow in a high-mobility graphene channel near the charge-neutrality point, establishing the viscous transport of the Dirac fluid. This measurement is in contrast to the conventional uniform flow profile imaged in a metallic conductor and also in a low-mobility graphene channel. Via combined imaging and transport measurements, we obtain viscosity and scattering rates, and observe that these quantities are comparable to the universal values expected at quantum criticality. This finding establishes a nearly ideal electron fluid in charge-neutral, high-mobility graphene at room temperature4. Our results will enable the study of hydrodynamic transport in quantum critical fluids relevant to strongly correlated electrons in high-temperature superconductors9. This work also highlights the capability of quantum spin magnetometers to probe correlated electronic phenomena at the nanoscale.
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OBJECTIVE: To determine whether alcohol consumption is associated with the risk of periodontitis. BASIC RESEARCH DESIGN: Systematic review and meta-analysis of observational studies performed using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. METHOD: PubMed and Scopus were searched for eligible articles published in English from inception till November 2018. The quality of studies was assessed by the Newcastle Ottawa Scale. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated for the risk of periodontitis associated with highest versus lowest/non-alcohol in a random effects meta-analysis model. Heterogeneity and sensitivity were investigated in meta regression analysis. A funnel plot was used to assess publication bias. RESULTS: Twenty-nine observational studies were included. One study with two separate datasets was considered as two separate studies for analysis. Alcohol consumption was significantly associated with the presence of periodontitis (OR = 1.26, 95% CI= 1.11-1.41). Significant heterogeneity (I2=71%) was present in the overall analysis, primarily attributable to sampling cross-sectional studies (I2=76.6%). A funnel plot and Egger tests (p=0.0001) suggested the presence of publication bias. CONCLUSION: Alcohol consumption was associated with increased occurrence of periodontitis and should be considered as a parameter in periodontal risk assessment. Publication bias should be explored in future studies.
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Consumo de Bebidas Alcoólicas , Periodontite , Estudos Transversais , Humanos , Estudos Observacionais como Assunto , Razão de Chances , Medição de RiscoRESUMO
Domain walls separating regions of AB and BA interlayer stacking in bilayer graphene have attracted attention as novel examples of structural solitons, topological electronic boundaries, and nanoscale plasmonic scatterers. We show that strong coupling of domain walls to surface plasmons observed in infrared nanoimaging experiments is due to topological chiral modes confined to the walls. The optical transitions among these chiral modes and the band continua enhance the local conductivity, which leads to plasmon reflection by the domain walls. The imaging reveals two kinds of plasmonic standing-wave interference patterns, which we attribute to shear and tensile domain walls. We compute the electronic structure of both wall varieties and show that the tensile wall contains additional confined bands which produce a structure-specific contrast of the local conductivity, in agreement with the experiment. The coupling between the confined modes and the surface plasmon scattering unveiled in this work is expected to be common to other topological electronic boundaries found in van der Waals materials. This coupling provides a qualitatively new pathway toward controlling plasmons in nanostructures.
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Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR) = 0.54, 95 % confidence interval (CI) = 0.35-0.83, p = 0.005; OR = 0.26, 95 % CI = 0.18-0.39, p < 0.001; and OR = 0.19, 95 % CI = 0.10-0.35, p < 0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR = 1.70, 95 % CI = 1.20-2.40, p = 0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR = 0.22, 95 % CI = 0.14-0.33, p trend < 0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT + TT) genotypes were significantly lower in the older (OR = 0.31, 95 % CI = 0.15-0.65, p = 0.002) and female (OR = 0.30, 95 % CI = 0.17-0.52, p < 0.001) subgroups, and rs13170556 (TC + CC) genotypes exhibited the same effect in all subgroups (all p < 0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC + CC) genotypes were significantly more frequent in the younger (OR = 1.86, 95 % CI = 1.18-2.94, p = 0.007) and female (OR = 2.38, 95 % CI = 1.48-3.83, p < 0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.
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Receptor Celular 2 do Vírus da Hepatite A/genética , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas do Core Viral/imunologia , Adulto , Anticorpos Antivirais/sangue , Feminino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Interações Hospedeiro-Patógeno/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Plant-based meat analogs are food products that mimic the appearance, texture, and taste of real meat. The development process requires laborious experimental iterations and expert knowledge to meet consumer expectations. To address these problems, we propose a machine learning (ML)-based framework to predict the textural properties of meat analogs. We introduce the proximate compositions of the raw materials, namely protein, fat, carbohydrate, fibre, ash, and moisture, in percentages and the "targeted moisture contents" of the meat analogs as input features of the ML models, such as Ridge, XGBoost, and MLP, adopting a build-in feature selection mechanism for predicting "Hardness" and "Chewiness". We achieved a mean absolute percentage error (MAPE) of 22.9%, root mean square error (RMSE) of 10.101 for Hardness, MAPE of 14.5%, and RMSE of 6.035 for Chewiness. In addition, carbohydrates, fat and targeted moisture content are found to be the most important factors in determining textural properties. We also investigate multicollinearity among the features, linearity of the designed model, and inconsistent food compositions for validation of the experimental design. Our results have shown that ML is an effective aid in formulating plant-based meat analogs, laying out the groundwork to expediently optimize product development cycles to reduce costs.
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Developing meat analogues of superior amino acid (AA) profiles in the food industry is a challenge as plant proteins contain less of some essential AA than animal proteins. Mathematical optimisation models such as linear/non-linear programming models were used to overcome this challenge and create high-moisture meat analogues (HMMA) with AA profiles as close as possible to chicken breast meat. The effect on the physiochemical properties and specific mechanical energy (SME) of the HMMA was investigated. The AA content of HMMA was generally lower than chicken. Strong intermolecular bonds present in the globulin fraction could hinder protein acid hydrolysis of HMMA. Plant proteins also affect the HMMA colour as certain AA forms Maillard reaction products with higher browning intensity. Lastly, different characteristics of plant proteins resulted in different SME values under the same extrusion conditions. While mathematical programming can optimise plant protein combinations, fortification is required to match the AA profile of HMMA to an animal source.
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An extensive study, throughout the valence region, of the electronic structure, ionization spectrum, and electron momentum distributions of ethanol is presented, on the ground of a model that focuses on a mixture of the gauche and anti conformers in their energy minimum form, using weight coefficients obtained from thermostatistical calculations that account for the influence of hindered rotations. The analysis is based on accurate calculations of valence one-electron and shakeup ionization energies and of the related Dyson orbitals, using one-particle Green's Function (1p-GF) theory in conjunction with the so-called third-order Algebraic Diagrammatic Construction scheme [ADC(3)]. The confrontation against available UPS (HeI) measurements indicates the presence in the spectral bands of significant conformational fingerprints at outer-valence ionization energies ranging from approximately 14 to approximately 18 eV. The shakeup onset is located at approximately 24 eV, and a shoulder at approximately 14.5 eV in the He I spectrum can be specifically ascribed to the minor anti (C(s)) conformer fraction. Thermally and spherically averaged Dyson orbital momentum distributions are computed for seven resolvable bands in model (e, 2e) ionization spectra at an electron impact energy of 1.2 keV. A comparison is made with results obtained from standard (B3LYP) Kohn-Sham orbitals and EMS measurements employing a high-resolution spectrometer of the third generation. The analysis is qualitatively in line with experiment and reveals a tremendously strong influence of the molecular conformation on the outermost electron momentum distributions. Quantitatively significant discrepancies with experiment can nonetheless be tentatively ascribed to strong dynamical disorder in the gas phase molecular structure.
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Transcription-coupled repair (TCR) plays an important role in removing DNA damage from actively transcribed genes. It has been speculated that TCR is the most important mechanism for repairing DNA damage in non-dividing cells such as neurons. Therefore, abnormal TCR may contribute to the development of many age-related and neurodegenerative diseases. However, the molecular mechanism of TCR is not well understood. Oligonucleotide DNA triplex formation provides an ideal system to dissect the molecular mechanism of TCR since triplexes can be formed in a sequence-specific manner to inhibit transcription of target genes. We have recently studied the molecular mechanism of triplex-forming oligonucleotide (TFO)-mediated TCR in HeLa nuclear extracts. Using plasmid constructs we demonstrate that the level of TFO-mediated DNA repair activity is directly correlated with the level of transcription of the plasmid in HeLa nuclear extracts. TFO-mediated DNA repair activity was further linked with transcription since the presence of rNTPs in the reaction was essential for AG30-mediated DNA repair activity in HeLa nuclear extracts. The involvement of individual components, including TFIID, TFIIH, RNA polymerase II and xeroderma pigmentosum group A (XPA), in the triplex-mediated TCR process was demonstrated in HeLa nuclear extracts using immunodepletion assays. Importantly, our studies also demonstrated that XPC, a component involved in global genome DNA repair, is involved in the AG30-mediated DNA repair process. The results obtained in this study provide an important new understanding of the molecular mechanisms involved in the TCR process in mammalian cells.
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Reparo do DNA/genética , DNA/química , DNA/genética , Conformação de Ácido Nucleico , Oligodesoxirribonucleotídeos/genética , Transcrição Gênica/genética , Sequência de Bases , Extratos Celulares , Núcleo Celular/genética , Núcleo Celular/metabolismo , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fibroblastos , Células HeLa , Humanos , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/metabolismo , Plasmídeos/genética , Regiões Promotoras Genéticas/genética , RNA Polimerase II/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição TFIID , Fator de Transcrição TFIIH , Fatores de Transcrição/metabolismo , Fatores de Transcrição TFII/metabolismo , Proteína de Xeroderma Pigmentoso Grupo ARESUMO
Interactions between particles in quantum many-body systems can lead to collective behavior described by hydrodynamics. One such system is the electron-hole plasma in graphene near the charge-neutrality point, which can form a strongly coupled Dirac fluid. This charge-neutral plasma of quasi-relativistic fermions is expected to exhibit a substantial enhancement of the thermal conductivity, thanks to decoupling of charge and heat currents within hydrodynamics. Employing high-sensitivity Johnson noise thermometry, we report an order of magnitude increase in the thermal conductivity and the breakdown of the Wiedemann-Franz law in the thermally populated charge-neutral plasma in graphene. This result is a signature of the Dirac fluid and constitutes direct evidence of collective motion in a quantum electronic fluid.
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Induction of gene expression has great potential in the treatment of many human diseases. Peptide nucleic acid (PNA) as a novel DNA-binding reagent provides an ideal system to induce gene-specific expression. In our recent studies, we have demonstrated that PNA bound to double-stranded DNA targets and, therefore, generated single-stranded D-loops and induced transcription of target genes both in vitro and in vivo. Most importantly, we have demonstrated that treatment of cultured human cells with PNAs led to expression of an endogenous target gene. Therefore, the study of the molecular mechanism of PNA binding-induced gene expression will have great implications for the gene therapy of many human diseases. In the current study, we have investigated the PNA length requirement for PNA binding-induced transcription initiation. Using a series of PNAs with different lengths, we have determined that PNAs with lengths of 16 approximately 18 nt induce very high levels of transcription in a HeLa nuclear extract in vitro transcription system. Transfection of the PNA-bound GFP reporter gene plasmid into human normal fibroblast (NF) cells led to a similar result. Gel-mobility shift assays revealed very strong binding affinities of these PNAs. DNA footprinting analysis further demonstrated the specificity of PNAs binding to the targets. These results lead to important understanding of the molecular mechanism of transcription initiation and highly valuable information in PNA design, especially for PNA binding-induced, gene-specific expression.
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Regulação da Expressão Gênica , Ácidos Nucleicos Peptídicos/química , Ácidos Nucleicos Peptídicos/metabolismo , Transcrição Gênica , Sequência de Bases , Sítios de Ligação , Pegada de DNA , Desoxirribonuclease I/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Genes Reporter/genética , Células HeLa , Humanos , Neurofibroma/genética , Neurofibroma/metabolismo , Plasmídeos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade por Substrato , Transfecção , Células Tumorais CultivadasRESUMO
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.
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Hipóxia Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sirtuína 2/metabolismo , Animais , Linhagem Celular Tumoral , Metabolismo Energético/genética , Feminino , Células HeLa , Humanos , Hidroxilação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NAD/metabolismo , Prolil Hidroxilases/metabolismo , Ligação Proteica , Estabilidade Proteica , Interferência de RNA , RNA Interferente Pequeno , Sirtuína 2/genética , UbiquitinaçãoRESUMO
The oncogenic human papillomavirus (HPV) E6/E7 proteins are essential for the onset and maintenance of HPV-associated malignancies. Here, we report that activation of the cellular ubiquitin-proteasome system (UPS) by the omega-3 fatty acid, docosahexaenoic acid (DHA), leads to proteasome-mediated degradation of E6/E7 viral proteins and the induction of apoptosis in HPV-infected cancer cells. The increases in UPS activity and degradation of E6/E7 oncoproteins were associated with DHA-induced overproduction of mitochondrial reactive oxygen species (ROS). Exogenous oxidative stress and pharmacological induction of mitochondrial ROS showed effects similar to those of DHA, and inhibition of ROS production abolished UPS activation, E6/E7 viral protein destabilization, and apoptosis. These findings identify a novel role for DHA in the regulation of UPS and viral proteins, and provide evidence for the use of DHA as a mechanistically unique anticancer agent for the chemoprevention and treatment of HPV-associated tumors.
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Antivirais/farmacologia , Proteínas de Ligação a DNA/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Proteínas Repressoras/metabolismo , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica , Células HeLa , Interações Hospedeiro-Patógeno , Papillomavirus Humano 16/efeitos dos fármacos , Papillomavirus Humano 16/fisiologia , Papillomavirus Humano 18/efeitos dos fármacos , Papillomavirus Humano 18/fisiologia , Humanos , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitinação/efeitos dos fármacosRESUMO
The soil to atmosphere fluxes of greenhouse gases N2O, CH4 and CO2 and their relationships with soil characteristics were investigated in three tropical oceanic mangrove swamps (Teremaal, Likupang and Kema) in North Sulawesi, Indonesia. Mangrove soils in North Sulawesi were rich in organic carbon and nitrogen, but the greenhouse gas fluxes were low in these mangroves. The fluxes ranged -6.05-13.14 µmol m(-2)h(-1), -0.35-0.61 µmol m(-2)h(-1) and -1.34-3.88 mmol m(-2)h(-1) for N2O, CH4 and CO2, respectively. The differences in both N2O and CH4 fluxes among different mangrove swamps and among tidal positions in each mangrove swamp were insignificant. CO2 flux was influenced only by mangrove swamps and the value was higher in Kema mangrove. None of the measured soil parameters could explain the variation of CH4 fluxes among the sampling plots. N2O flux was negatively related to porewater salinity, while CO2 flux was negatively correlated with water content and organic carbon. This study suggested that the low gas emissions due to slow metabolisms would lead to the accumulations of organic matters in North Sulawesi mangrove swamps.
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Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Carbono/análise , Monitoramento Ambiental , Nitrogênio/análise , Áreas Alagadas , Atmosfera , Dióxido de Carbono/análise , Efeito Estufa , Indonésia , Metano/análise , Óxido Nitroso/análise , Estações do Ano , Solo/química , Poluentes do Solo/análiseRESUMO
The surfaces of almost all microbes are decorated with remarkable variations of polysaccharides such as O-antigen, capsular polysaccharides (CPS), and exopolysaccharides (EPS) in bacteria, lipoarabinomannans (LAM) in mycobacteria and lipophosphoglycan (LPG) in Leishmania. These polysaccharides play important roles in many biological processes, and they can function as the virulence determinants in the pathogens. The basic structures of these polysaccharides are known, but they show species-specificity or stage-specificity. For example, there are 186 O-serotypes and 80 capsular serotypes in E. coli. Despite the variation, the range of strategies used for the biosynthesis and assembly of these microbial polysaccharides is limited. Depending on the assembly and translocation mechanisms, O-antigen biosynthesis is subdivided into three pathways, of which the Wzy-dependent pathway is widely used not only in O-antigen, but also in CPS and EPS.
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Bactérias/metabolismo , Polissacarídeos/biossíntese , Animais , Bactérias/química , Leishmania/química , Leishmania/metabolismo , Modelos Biológicos , Antígenos O/biossíntese , Antígenos O/química , Polissacarídeos/química , Especificidade da EspécieRESUMO
A complete study of the valence electronic structure and related electronic excitation properties of cyclopentene in its C(s) ground state geometry is presented. Ionization spectra obtained from this compound by means of photoelectron spectroscopy (He I and He II) and electron momentum spectroscopy have been analyzed in details up to electron binding energies of 30 eV using one-particle Green's function (1p-GF) theory along with the outer-valence (OVGF) and the third-order algebraic diagrammatic construction [ADC(3)] schemes. The employed geometries derive from DFT/B3LYP calculations in conjunction with the aug-cc-pVTZ basis set, and closely approach the structures inferred from experiments employing microwave spectroscopy or electron diffraction in the gas phase. The 1p-GF/ADC(3) calculations indicate that the orbital picture of ionization breaks down at electron binding energies larger than approximately 17 eV in the inner-valence region, and that the outer-valence 7a' orbital is also subject to a significant dispersion of the ionization intensity over shake-up states. This study confirms further the rule that OVGF pole strengths smaller than 0.85 foretell a breakdown of the orbital picture of ionization at the ADC(3) level. Spherically averaged (e, 2e) electron momentum distributions at an electron impact energy of 1200 eV that were experimentally inferred from an angular analysis of EMS intensities have been interpreted by comparison with accurate simulations employing ADC(3) Dyson orbitals. Very significant discrepancies were observed with momentum distributions obtained from several outer-valence ionization bands using standard Kohn-Sham orbitals.
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Simulação por Computador , Ciclopentanos/química , Modelos Químicos , Teoria Quântica , Elétrons , Fotoquímica , Espectrofotometria/métodosRESUMO
The wbsJ gene from Escherichia coli O128:B12 encodes an alpha1,2-fucosyltransferase responsible for adding a fucose onto the galactose residue of the O-antigen repeating unit via an alpha1,2 linkage. The wbsJ gene was overexpressed in E. coli BL21 (DE3) as a fusion protein with glutathione S-transferase (GST) at its N-terminus. GST-WbsJ fusion protein was purified to homogeneity via GST affinity chromatography followed by size exclusion chromatography. The enzyme showed broad acceptor specificity with Galbeta1,3GalNAc (T antigen), Galbeta1,4Man and Galbeta1,4Glc (lactose) being better acceptors than Galbeta-O-Me and galactose. Galbeta1,4Fru (lactulose), a natural sugar, was furthermore found to be the best acceptor for GST-WbsJ with a reaction rate four times faster than that of lactose. Kinetic studies showed that GST-WbsJ has a higher affinity for lactose than lactulose with apparent Km values of 7.81 mM and 13.26 mM, respectively. However, the kcat/appKm value of lactose (6.36 M(-1) x min(-1)) is two times lower than that of lactulose (13.39 M(-1) x min(-1)). In addition, the alpha1,2-fucosyltransferase activity of GST-WbsJ was found to be independent of divalent metal ions such as Mn2+ or Mg2+. This activity was competitively inhibited by GDP with a Ki value of 1.41 mM. Site-directed mutagenesis and a GDP-bead binding assay were also performed to investigate the functions of the highly conserved motif H152xR154R155xD157. In contrast to alpha1,6-fucosyltransferases, none of the mutants of WbsJ within this motif exhibited a complete loss of enzyme activity. However, residues R154 and D157 were found to play critical roles in donor binding and enzyme activity. The results suggest that the common motif shared by both alpha1,2-fucosyltransferases and alpha1,6-fucosyltransferases have similar functions. Enzymatic synthesis of fucosylated sugars in milligram scale was successfully performed using Galbeta-O-Me and Galbeta1,4Glcbeta-N3 as acceptors.