YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils

YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function of YKL-40 is unknown, but the pattern of its expression in normal and disease states suggests that it could function in remodeling or degradation of the extracellular matrix. High levels of YKL-40 are found in synovial fluid from patients with active RA. Neutrophils are abundant in synovial fluid of patients with RA, and the cells are assumed to play a role in joint destruction in that disorder. Therefore, we examined whether neutrophils are a source of YKL-40. YKL-40 was found to colocalize and comobilize with lactoferrin (the most abundant protein of specific granules) but not with gelatinase in subcellular fractionation studies on stimulated and unstimulated neutrophils. Double-labeling immunoelectron microscopy confirmed the colocalization of YKL-40 and lactoferrin in specific granules of neutrophils. Immunohistochemistry on bone marrow cells showed that neutrophil precursors begin to synthesize YKL-40 at the myelocyte-metamyelocyte stage, the stage of maturation at which other specific granule proteins are formed. Assuming that YKL-40 has a role as an autoantigen in RA by inducing T cell-mediated autoimmune response, YKL-40 released from neutrophils in the inflamed joint could be essential for this response. In RA and other inflammatory diseases, YKL-40 released from specific granules of neutrophils may be involved in tissue remodeling or degradation.     

AUTOREGRESSIVE PROCESSES WITH A TIME DEPENDENT VARIANCE

Abstract. We study nonstationary autoregressive time series where the variance of the residual process is allowed to depend on time. In earlier publications the variance has been modelled by a step function. We look at more general classes of functions and propose two estimates of the autoregressive coefficients, both of which are consistent under weak assumptions. We also show how it is possible to obtain an estimate in practice using an iterative regression procedure.     

The case of the vanishing frequency effect: A retest of the verification model.

The assumptions of the activation-verification model regarding the role of word frequency in lexical access were investigated in 2 experiments. Experiment 1 demonstrated that robust frequency effects occur in a standard lexical decision task in which the target remains in view until the subject responds. In Experiment 2 the same materials were followed by a backward pattern mask. Subjects first identified 1 of the 4 letters using a forced-choice task (G. M. Reicher, 1969) and were then probed to make a lexical decision. No frequency effects were observed in the lexical decision task and the significant main effect of frequency found in the subject's analysis of the Reicher task was small and nonmonotonic. A regression analysis on the word data obtained in Experiment 1 indicated that the number of higher frequency neighbors produced a potent interference effect, that the total number of neighbors produced a smaller but significant facilitation effect, and that neither word frequency nor summed bigram frequency accounted for any significant variation once the effects of higher frequency neighbors were partialed out. Regression analyses of other published data showed a similar pattern of results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of an Attrition Resistant Fischer�CTropsch Catalyst for Slurry Operation

Resistance towards attrition, sufficient activity at end-of-run and high selectivity to desired products are some of the requirements for a slurry Fischer?CTropsch catalyst. We have found that modifying an alumina support by 2-valent metals, including magnesium, nickel and zinc, followed by high temperature firing, results in superior mechanical and ??chemical attrition?? (dissolution) resistance of the catalyst. Further, a sufficiently high surface area is being stabilized. The catalyst performance has been verified in a long term test in a semi-commercial plant, including very good wax separation and high wax purity. Combined with appropriate process conditions, stable long-term operation of the catalyst is secured.     

Structural and pharmacological characterization of phenylalanine-based AMPA receptor antagonists at kainate receptors

Continued efforts into the discovery of ligands that target ionotropic glutamate receptors (iGluRs) are important for studies of the physiological roles of the various iGluR subtypes as well as for the search for drugs that can be used in the treatment of diseases of the central nervous system. A new series of phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors. Herein we report our studies of these compounds at the kainate receptors GluK1-3. Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not bind GluK2. The crystal structure of the most potent compound in the ligand binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2, due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a domain closure similar to that observed in GluK1 structures with partial agonists.