Family Of Alpha Research Articles

The Family of Alpha,[a,b] Stochastic Orders: Risk vs. Expected Value

In this paper we provide a novel family of stochastic orders that generalizes second order stochastic dominance, which we call the α,[a,b]-concave stochastic orders. These stochastic orders are generated by a novel set of “very” concave functions where α parameterizes the degree of concavity. The α,[a,b]-concave stochastic orders allow us to derive novel comparative statics results for important applications in economics that cannot be derived using previous stochastic orders. In particular, our comparative statics results are useful when an increase in a lottery’s riskiness changes the agent’s optimal action in the opposite direction to an increase in the lottery’s expected value. For this kind of situation, we provide a tool to determine which of these two forces dominates — riskiness or expected value. We apply our results in consumption–savings problems, self-protection problems, and in a Bayesian game.

Pdgfra and Pdgfrb Genetically Interact in the Murine Neural Crest Cell Lineage to Regulate Migration and Proliferation.

Cranial neural crest cells (cNCCs) are migratory, multipotent cells that originate from the forebrain to the hindbrain and eventually give rise to the cartilage and bone of the frontonasal skeleton, among other derivatives. Signaling through the two members of the platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases, alpha and beta, plays critical roles in the cNCC lineage to regulate craniofacial development during murine embryogenesis. Further, the PDGFRs have been shown to genetically interact during murine craniofacial development at mid-to-late gestation. Here, we examined the effect of ablating both Pdgfra and Pdgfrb in the murine NCC lineage on earlier craniofacial development and determined the cellular mechanisms by which the observed phenotypes arose. Our results confirm a genetic interaction between the two receptors in this lineage, as phenotypes observed in an allelic series of mutant embryos often worsened with the addition of conditional alleles. The defects observed here appear to stem from aberrant cNCC migration, as well as decreased proliferation of the facial mesenchyme upon combined decreases in PDGFRα and PDGFRβ signaling. Importantly, we found that PDGFRα plays a predominant role in cNCC migration whereas PDGFRβ primarily contributes to proliferation of the facial mesenchyme past mid-gestation. Our findings provide insight into the distinct mechanisms by which PDGFRα and PDGFRβ signaling regulate cNCC activity and subsequent craniofacial development in the mouse embryo.

The Family of Alpha,[a,b] Stochastic Orders: Risk vs. Expected Value

In this paper we provide a novel family of stochastic orders that generalizes second order stochastic dominance, which we call the $\alpha,[a,b]$-concave stochastic orders. These stochastic orders are generated by a novel set of ``very concave functions where $\alpha$ parameterizes the degree of concavity. The $\alpha,[a,b]$-concave stochastic orders allow us to derive novel comparative statics results for important applications in economics that cannot be derived using previous stochastic orders. In particular, our comparative statics results are useful when an increase in a lottery's riskiness changes the agent's optimal action in the opposite direction to an increase in the lottery's expected value. For this kind of situation, we provide a tool to determine which of these two forces dominates -- riskiness or expected value. We apply our results in consumption-savings problems, self-protection problems, and in a Bayesian game.

Emergent alpha -like fermionic vacuum structure and entanglement in the hyperbolic de Sitter spacetime

We report a non-trivial feature of the vacuum structure of free massive or massless Dirac fields in the hyperbolic de Sitter spacetime. Here we have two causally disconnected regions, say R and L separated by another region, C. We are interested in the field theory in Rcup L to understand the long range quantum correlations between R and L. There are local modes of the Dirac field having supports individually either in R or L, as well as global modes found via analytically continuing the R modes to L and vice versa. However, we show that unlike the case of a scalar field, the analytic continuation does not preserve the orthogonality of the resulting global modes. Accordingly, we need to orthonormalise them following the Gram–Schmidt prescription, prior to the field quantisation in order to preserve the canonical anti-commutation relations. We observe that this prescription naturally incorporates a spacetime independent continuous parameter, theta _{mathrm{RL}}, into the picture. Thus interestingly, we obtain a naturally emerging one-parameter family of alpha -like de Sitter vacua. The values of theta _{mathrm{RL}} yielding the usual thermal spectra of massless created particles are pointed out. Next, using these vacua, we investigate both entanglement and Rényi entropies of either of the regions and demonstrate their dependence on theta _{mathrm{RL}}.

A Generalized Nonnegative Tensor Factorization Approach for Distant Speech Recognition With Distributed Microphones

Automatic speech recognition (ASR) using distant (far-field) microphones is a challenging task, in which room reverberation is one of the primary causes of performance degradation. This study proposes a multichannel spectral enhancement method for reverberation-robust ASR using distributed microphones. The proposed method uses the techniques of nonnegative tensor factorization in order to identify the clean speech component from a set of observed reverberant spectrograms from the different channels. The general family of alpha–beta divergences is used for the tensor decomposition task which provides increased flexibility for the algorithm and is shown to provide improvements in highly reverberant scenarios. Unlike many conventional array processing solutions, the proposed method does not require closely-spaced microphones and is independent of source and microphone locations. The algorithm can automatically adapt to unbalanced direct-to-reverberation ratios among different channels, which is useful in blind scenarios in which no information is available about source-to-microphone distances. For a medium vocabulary distant ASR task based on TIMIT utterances, and using clean-trained deep neural network acoustic models, absolute WER improvements of +17.2%, +20.7%, and +23.2% are achieved in single-channel, two-channel, and four-channel scenarios.

ATPS-81SINGLE-AGENT TARGETING OF Eph RECEPTORS A2, A3, B2 AND INTERLUKIN-13 RECEPTOR ALPHA 2 IN GLIOBLASTOMA

Glioblastoma (GBM), is the most common and aggressive primary tumor of the central nervous system, with few treatment options and poor patient outcome. We and others demonstrated that A2, A3 and B2 receptors of the Eph family of protein tyrosine kinase receptors and Interlukin-13 receptor alpha 2 (IL-13RA2), are overexpressed in GBM tumors, but not normal brain. These receptors play important roles in GBM tumor progression and resistance to therapies involving both initiating and differentiating tumor cells, infiltrating tumor cells, tumor-associated macrophages (TAMs), and neovasculature. To this end, we have designed and constructed a bi-valent protein which would recognize all these four receptors using a human IgG1 scaffold. The bi-valent protein (eA5-Fc-IL-13.E13K) consists of ephrin-A5 (eA5, which acts as a ligand for the three Eph receptors), the Fc region of IgG1 followed by a modified IL-13, IL-13.E13K. The bi-valent protein was expressed in Sf9 insect cells using the baculovirus expression system and purified from the cell media to homogeneity using affinity Protein G column. The non-reduced and reduced SDS-PAGE showed the expected size bands of 125 and 65 kDa, respectively. The bi-valent binding and function of protein was tested in GBM cells. The bi-valent protein specifically bound, internalized and down-regulated EphA2 receptor in GBM cells, mimicking the action of eA5 alone. Using the PMS/MTS cell viability assay, we determined that the bi-valent protein effectively prevented an IL-13.E13K based cytotoxin from binding to and killing GBM cells by competing for the cytokine binding sites. Thus, we have generated a bi-valent compound capable of recognizing four receptor targets: IL-13RA2, EphA2, EphA3 and EphB2 that are over-expressed in most of the pathobiologically important tumor compartments in all GBM patients. Therefore, the protein under investigation represents a novel therapeutic route to be exploited in the treatment of patients with a heterogeneous disease like GBM.

Nodes of Ranvier Act as Barriers to Restrict Invasion of Flanking Paranodal Domains in Myelinated Axons

Accumulation of voltage-gated sodium (Na(v)) channels at nodes of Ranvier is paramount for action potential propagation along myelinated fibers, yet the mechanisms governing nodal development, organization, and stabilization remain unresolved. Here, we report that genetic ablation of the neuron-specific isoform of Neurofascin (Nfasc(NF¹⁸⁶)) in vivo results in nodal disorganization, including loss of Na(v) channel and ankyrin-G (AnkG) enrichment at nodes in the peripheral nervous system (PNS) and central nervous system (CNS). Interestingly, the presence of paranodal domains failed to rescue nodal organization in the PNS and the CNS. Most importantly, using ultrastructural analysis, we demonstrate that the paranodal domains invade the nodal space in Nfasc(NF¹⁸⁶) mutant axons and occlude node formation. Our results suggest that Nfasc(NF¹⁸⁶)-dependent assembly of the nodal complex acts as a molecular boundary to restrict the movement of flanking paranodal domains into the nodal area, thereby facilitating the stereotypic axonal domain organization and saltatory conduction along myelinated axons.

The conserved UL24 family of human alpha, beta and gamma herpesviruses induces cell cycle arrest and inactivation of the cyclinB/cdc2 complex

The conserved murine gammaherpesvirus 68 ORF20 has recently been demonstrated to induce G2 cell cycle arrest followed by apoptosis in human and mouse cells. Here, we demonstrate that its homologues UL24 in HSV-1, ORF20 in KSHV and UL76 in HCMV are also inducers of cell cycle arrest followed by apoptosis in both human and mouse cells. The mechanism of action is similar to that reported for MHV-68 ORF20, inactivating the mitotic complex cyclinB/Cdc2.

Medullary thyroid carcinoma and biomarkers: past, present and future

The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long-term survival, due to an indolent course of the disease, or develop rapidly progressing disease leading to death from distant metastases. At this moment, it cannot be predicted what will happen within most individual cases. Biomarkers, indicators which can be measured objectively, can be helpful in MTC diagnosis, molecular imaging and treatment, and/or identification of MTC progression. Several MTC biomarkers are already implemented in the daily management of MTC patients. More research is being aimed at the improvement of molecular imaging techniques and the development of molecular systemic therapies. Recent discoveries, like the prognostic value of plasma calcitonin and carcino-embryonic antigen doubling-time and the presence of somatic RET mutations in MTC tissue, may be useful tools in clinical decision making in the future. In this review, we provide an overview of different MTC biomarkers and their applications in the clinical management of MTC patients.

Interaction models of substrate peptides and beta-secretase studied by NMR spectroscopy and molecular dynamics simulation.

The formation of beta-amyloid peptide (Abeta) is initiated from cleavage of amyloid precursor protein (APP) by a family of protease, alpha-, beta-, and gamma-secretase. Sub W, a substrate peptide, consists of 10 amino acids, which are adjacent to the beta-cleavage site of wild-type APP, and Sub M is Swedish mutant with double mutations on the left side of the beta-cleavage site of APP. Sub W is a normal product of the metabolism of APP in the secretary pathway. Sub M is known to increase the efficiency of beta-secretase activity, resulting in a more specific binding model compared to Sub W. Three-dimensional structures of Sub W and Sub M were studied by CD and NMR spectroscopy in water solution. On the basis of these structures, interaction models of beta-secretase and substrate peptides were determined by molecular dynamics simulation. Four hydrogen bonds and one water-mediated interaction were formed in the docking models. In particular, the hydrogen bonding network of Sub M-BACE formed spread over the broad region of the active site of beta-secretase (P5-P3'), and the side chain of P2-Asn formed a hydrogen bond specifically with the side chain of Arg235. These are more favorable to the cleavage of Sub M by beta-secretase than Sub W. The two substrate peptides showed different tendency to bind to beta-secretase and this information may useful for drug development to treat and prevent Alzheimer's disease.

Anti-metastatic properties of RGD-peptidomimetic agents S137 and S247.

Integrins expressed on endothelial cells modulate cell migration and survival during angiogenesis. Integrins expressed on carcinoma cells potentiate metastasis by facilitating invasion and movement across blood vessels. We describe the activities of two synthetic low-molecular-weight peptidomimetics of the ligand amino acid sequence arg-gly-asp (RGD) in integrin-based functional assays in vitro. We also evaluate efficacy and potential mechanisms of action in models of both spontaneous and experimental metastasis. Broad-spectrum potency against the family of alpha v subunit-containing integrins was observed, with significantly less potency against alpha5beta1 and alpha(IIb)beta3. Both endothelial and tumor cell migration mediated by alpha(v)beta3 was inhibited, whereas proliferation of endothelial cells but not tumor cells was diminished. Continuous infusion of compound by minipumps or oral administration twice daily significantly reduced metastatic tumor burden in the lungs of mice despite no reduction in growth of 435/HAL primary tumors, and only a slight reduction in tumor cells detected in circulating blood. Delaying treatment in this model until after extensive dissemination of tumor cells to the lungs had occurred, and after primary tumor resection, still produced significant efficacy. Conversely, administration of the agent for only the first 18 h after tumor-cell inoculation into the tail vein also resulted in decreased metastases observed after several weeks. These data suggest these compounds or their relatives have potential to interfere with both early and late steps of metastasis involving tumor and endothelial cell functions. Furthermore, the metastatic process can be effectively inhibited independently of primary tumor growth using integrin antagonists.

NMR solution structure of viscotoxin C1 from Viscum album species Coloratum ohwi: toward a structure-function analysis of viscotoxins.

The high resolution three-dimensional structure of the newly discovered plant viscotoxin C1, from the Asiatic Viscum album ssp. Coloratum ohwi, has been determined in solution by (1)H NMR spectroscopy at pH 3.6 and 285 K. The viscotoxin C1-fold, consisting of a helix-turn-helix motif and a short stretch of an antiparralel beta-sheet is very similar to that found for the highly similar viscotoxins A2 and A3 and for other related thionins. Different functional properties of members of the thionin family are discussed here in light of the structural and electrostatic properties. Among the very homologous family of alpha- and beta-thionins, known for their antimicrobial activity, the viscotoxin subfamily differs from the other members because of its high toxicity against tumoral cells. Key residues for the modulation of viscotoxin cytotoxicity have been identified on the basis of sequence and structural alignment.

Albumin and Globulin Proteins of Wheat Flour: Immunological and N-terminal Sequence Characterisation

Several non-storage proteins are encoded by genes on individual wheat chromosomes and these have been used as genome-specific markers. In this study, a library of monoclonal antibodies with differing specificities to water- and salt-soluble proteins has been developed in order to obtain markers for different wheat chromosomes. Two antibodies, BCSAU 9D1 and JGM 1B4 were found to bind polypeptides encoded by chromosomes 3D and 4D respectively. Other antibodies bound to small numbers of polypeptides encoded by more than one chromosome, such as 5A, 7D, 5B and 5D. The proteins recognised by some of the antibodies were isolated by immunoaffinity chromatography, and one protein was identified as an alpha -amylase inhibitor by N-terminal sequence characterisation. In addition, 16 water-soluble and eight salt-soluble proteins were isolated using SDS-PAGE, isoelectric focusing, two-dimensional electrophoresis and reversed-phase high performance liquid chromatography, with the main objective being to confirm the identity of particular proteins, especially those which were able to be assigned to particular chromosomes. The N-terminal sequencing characterisation identified 19 proteins, whereas four proteins were found to be blocked and one did not match with any proteins in the database. Most of the water-soluble proteins belonged to a family of alpha -amylase inhibitors. One protein, assigned to chromosome 4BS, was homologous to serine carboxypeptidase III. N-terminal sequences of some of salt-soluble proteins matched with internal sequences of barley embryo globulin. Other proteins were identified as lipid transfer protein, peroxidase BP-1 precursor and histone H4 proteins. The protein sequences could also potentially be used for making antibody or DNA probes for use in selection in breeding programmes.

Disruption of cell adhesion and caspase-mediated proteolysis of beta- and gamma-catenins and APC protein in paclitaxel-induced apoptosis.

Cell adhesion is important in the regulation of cell proliferation, migration, survival, and apoptosis. The major components of cell adhesion are the cadherin family of proteins, alpha-, beta- and gamma-catenins, and cytoskeletons. In addition, beta-catenin, when associated with adenomatous polyposis coli (APC) protein, an oncosuppressor, is implicated in the regulation of beta-catenin/APC-related signaling pathways. To examine the correlation between impairment of cell adhesion events and apoptosis, we used human non-small-cell lung cancer H460 and H520 cell lines as models to determine whether paclitaxel-induced apoptosis is associated with disruption of the components of cell adhesion and their functions. Paclitaxel treatment resulted in cells rounding up and losing contact with their neighboring cells, suggesting that the drug does indeed affect cell adhesion and related events. Western blot analysis revealed that paclitaxel caused a time- and concentration-dependent cleavage of beta-catenin, gamma-catenin, and APC protein, but not alpha-catenin or E-cadherin. These cleavages of beta-catenin and gamma-catenin were apoptosis-dependent, not mitosis-dependent. Paclitaxel treatment led to the proteolysis and activation of caspase-3 and -7, but not caspase-1. Furthermore, paclitaxel-induced apoptosis and cleavage of beta-catenin and gamma-catenin were inhibited by the pan-caspase inhibitor Z-VAD-FMK and partially inhibited by the caspase-3 inhibitor Z-DEVD-FMK but were not affected by the caspase-1 inhibitor AC-YVAD-CMK. Although the pan-caspase inhibitor blocked the cleavage of beta-catenin as well as DNA fragmentation, it did not affect paclitaxel-induced M-phase arrest and only partially prevented cell-growth inhibition. Biochemical studies revealed that cleaved beta-catenin was detected only in the Triton X-100 insoluble fraction, suggesting that it might localize in nuclear and/or membrane structures. Interestingly, the paclitaxel-induced beta-catenin fragment lost its ability to bind to E-cadherin, alpha-catenin, or APC protein and to serve as a substrate for tyrosine kinase. All our data demonstrate that the caspase-mediated cleavage of beta-catenin, gamma-catenin, and APC protein might contribute to paclitaxel-induced apoptosis.

Evolution of Fucosyltransferase Genes in Vertebrates

Cloning and expression of chimpanzee FUT3, FUT5, and FUT6 genes confirmed the hypothesis that the gene duplications at the origin of the present human cluster of genes occurred between: (i) the great mammalian radiation 80 million years ago and (ii) the separation of man and chimpanzee 10 million years ago. The phylogeny of fucosyltransferase genes was completed by the addition of the FUT8 family of alpha(1,6)fucosyltransferase genes, which are the oldest genes of the fucosyltransferase family. By analysis of data banks, a new FUT8 alternative splice expressed in human retina was identified, which allowed mapping the human FUT8 gene to 14q23. The results suggest that the fucosyltransferase genes have evolved by successive duplications, followed by translocations, and divergent evolution from a single ancestral gene.

Structures and stereochemistry of the very long alpha, omega-bifunctional alkyl species in the membrane of Sarcina ventriculi indicate that they are formed by tail-to-tail coupling of normal fatty acids.

In a previous study, we demonstrated that Sarcina ventriculi is capable of adjusting to alterations in environmental conditions (such as increase in temperature, lowering of pH, or addition of exogenous organic solvents) by the synthesis of a family of alpha, omega-dicarboxylic acids ranging from 28 to 36 carbons long (Jung, S., et al. 1993. J. Biol. Chem. 268: 2828-2835). The chain lengths and relative abundance of the very long dicarboxylic acids found in S. ventriculi suggest that they may be formed after the perturbation by the (enzymatic) tail-to-tail combinations of existing regular monofunctional fatty acids and not completely de novo by direct 2-carbon addition of acetyl coenzyme A (CoA). If this were true, knowing the structures of the regular fatty acids, we can predict those of the very long chain bifunctional acids. In this work we present definitive chemical results that strongly support this mechanism. This was done by analyzing the structures and stereochemistry of the very long bifunctional species in the light of those of the regular monofunctional species. The exact structures of membrane fatty acid methyl ester derivatives components were determined by various spectroscopic and chemical methods including gas chromatographic (GC) analysis, gas chromatography-mass spectrometry (GC-MS), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, polarimetry, and reductive ozonolysis. This yielded precise structural and stereochemical information on the position of substitution of the acyl chain by methyl groups, position and configuration of double bonds, and optical activity. These results, coupled with the absence of intermediate length acyl species, indicated that the very long alkyl species (without exception) can be formed by tail-to-tail joining of existing fatty acids. The ideas of a dynamically regulated catalytic system is proposed.

Two complementation groups account for most cases of inherited MHC class II deficiency.

MHC class II immuno-deficiency is a rare autosomal recessive disease due to a defect in transacting genes, which control the expression of the entire family of MHC alpha and beta class II genes. Previous analyses classified cells from eight MHC class II-deficient patients and four experimental mutant cell lines into four complementation groups, pointing to the existence of a large number of regulatory genes. We conducted fusion experiments with cell lines from two-thirds of all known patients and found that two complementation groups accounted for 20 of the 22 cases studied. These two complementation groups correspond closely to two ethnic groups: most patients of north African origin were classified into one group, while all patients originating from Spain were classified into a second main group. This suggests the existence of restricted number of ancestor mutations leading to this disease.

Molecular cloning of a fourth member of a human alpha (1,3)fucosyltransferase gene family. Multiple homologous sequences that determine expression of the Lewis x, sialyl Lewis x, and difucosyl sialyl Lewis x epitopes.

We and others have previously described the isolation of three human alpha (1,3)fucosyltransferase genes which form the basis of a nascent glycosyltransferase gene family. We now report the molecular cloning and expression of a fourth homologous human alpha (1,3)fucosyltransferase gene. When transfected into mammalian cells, this fucosyltransferase gene is capable of directing expression of the Lewis x (Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc), sialyl Lewis x (NeuNAc alpha 2-->3Gal beta 1-->4 [Fuc alpha 1-->3]GlcNAc), and difucosyl sialyl Lewis x (NeuNAc alpha 2-->3Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta 1-->3 Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc) epitopes. The enzyme shares 85% amino acid sequence identity with Fuc-TIII and 89% identity with Fuc-TV but differs substantially in its acceptor substrate requirements. Polymerase chain reaction analyses demonstrate that the gene is syntenic to Fuc-TIII and Fuc-TV on chromosome 19. Southern blot analyses of human genomic DNA demonstrate that these four alpha (1,3)fucosyltransferase genes account for all DNA sequences that cross-hybridize at low stringency with the Fuc-TIII catalytic domain. Using similar methods, a catalytic domain probe from Fuc-TIV identifies a new class of DNA fragments which do not cross-hybridize with the chromosome 19 fucosyltransferase probes. These results extend the molecular definition of a family of human alpha (1,3)fucosyltransferase genes and provide tools for examining fucosyltransferase gene expression.

Isolation of a novel human alpha (1,3)fucosyltransferase gene and molecular comparison to the human Lewis blood group alpha (1,3/1,4)fucosyltransferase gene. Syntenic, homologous, nonallelic genes encoding enzymes with distinct acceptor substrate specificities.

Biochemical and genetic evidence indicates that the human genome may encode four or more distinct GDP-fucose:beta-D-N-acetylglucosaminide 3-alpha-L-fucosyltransferase (alpha(1,3)fucosyltransferase) activities. Genes encoding two of these activities have been previously isolated. These correspond to an alpha(1,3/1,4)fucosyltransferase thought to represent the human Lewis blood group locus and an alpha(1,3)fucosyltransferase expressed in the myeloid lineage. We report here the molecular cloning and expression of a third human alpha(1,3)fucosyltransferase gene, homologous to but distinct from the two previously reported human fucosyltransferase genes. When expressed in transfected mammalian cells, this gene determines expression of a fucosyltransferase capable of using N-acetyllactosamine to form the Lewis x epitope, and alpha(2,3)sialyl-N-acetyllactosamine to construct the sialyl Lewis x moiety. This enzyme shares 91% amino acid sequence identity with the human Lewis blood group alpha(1,3/1,4)fucosyltransferase, yet exhibits only trace amounts of alpha(1,4)fucosyltransferase activity. Polymerase chain reaction analyses were used to demonstrate that the gene is syntenic to the Lewis locus on chromosome 19. These analyses also excluded the possibility that this DNA segment represents an allele of the Lewis locus that encodes alpha(1,3)fucosyltransferase but not alpha(1,4)fucosyltransferase activity. These results are consistent with the hypothesis that this gene encodes the human "plasma type" alpha(1,3)fucosyltransferase, and suggest a molecular basis for a family of human alpha(1,3)fucosyltransferase genes.

Purification and characterization of GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1—-3fucosyltransferase from human neuroblastoma cells. Unusual substrate specificities of the tumor enzyme

Fucosyl residues in the alpha 1----3 linkage to N-acetylglucosamine (Fuc alpha 1----3GlcNAc) on oligosaccharides of glycoproteins and glycolipids have been detected in certain human tumors and are developmentally expressed (reviewed in Foster, C. S., and Glick, M. C. (1988) Adv. Neuroblastoma Res. 2, 421-432). In order to understand control mechanisms for the biosynthesis of these fucosylated glycoconjugates, GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1----3fucosyltransferase was purified from human neuroblastoma cells, CHP 134, utilizing either the immobilized oligosaccharide or disaccharide substrates. The enzyme, extracted from CHP 134 cells, was purified by DEAE- and SP-Sephadex chromatography and then by either immobilized substrate. alpha 1----3Fucosyltransferase was obtained in approximately 10% yield and was purified 45,000-fold from the cell extract. The kinetic properties of the enzyme showed an apparent KGDP-Fuc 43 microM, KGal beta 1----4GlcNAc 0.4 mM, KGal beta 1----4Glc 8.1 mM, and KFuc alpha 1----2Gal beta 1----4Glc 1.0 mM. Polyacrylamide gel electrophoresis of the affinity-purified enzyme showed two proteins which migrated, Mr = 45,000-40,000. The enzyme differed in substrate specificity, pH optimum, response to N-ethylmaleimide and ion requirements from the enzymes purified from human milk or serum. The inability of alpha 1----3fucosyltransferase to transfer to substrates containing NeuAc alpha 2----3 or alpha 2----6Gal is in contrast to the reports for the enzyme in other human tumors. This substrate specificity correlates with the oligosaccharide residues thus far defined on glycoproteins of CHP 134 cells since NeuAc and Fuc alpha 1----3GlcNAc have yet to be detected on the same oligosaccharide antenna. However, the enzyme transfers to Fuc alpha 1----2Gal beta 1----4GlcNAc/Glc with higher activity than the unfucosylated disaccharides, although neither alpha 1----2fucosyltransferase nor Fuc alpha 1----2 residues have been detected in CHP 134 cells. The different substrate specificities of alpha 1----3fucosyltransferase isolated from human tumors and normal sources leads to the suggestion that a family of alpha 1----3fucosyltransferases may exist and that they may be differentially expressed in human tumors.