115 research outputs found

    TRYPANOSOMA-CRUZI TRANS-SIALIDASE and NEURAMINIDASE ACTIVITIES CAN BE MEDIATED BY the SAME ENZYMES

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    Trans-sialidase and neuraminidase activities have been detected on the surface membrane of trypomastigotes of Trypanosoma cruzi, and both have been implicated in the parasite's invasion of host cells. We show here that these enzymes are structurally related. They are recognized by two independently derived monoclonal antibodies, are anchored to the membrane by glycosylphosphatidylinositol, copurify by ion exchange, molecular sieving, and hydrophobic chromatography, have maximal activities between pH 6.5 and 7.5, and are inactivated by heating at 56-degrees-C. Furthermore, the neuraminidase and trans-sialidase reactions are coupled. An increase of the concentration of acceptors of the transfer reaction decreases the amount of free sialic acid released through the neuraminidase reaction. We conclude that a single enzyme can catalyze the transfer or the hydrolysis of macromolecular-bound sialic acid. the predominant direction of the reaction will depend on the availability of appropriate oligosaccharide acceptors of sialic acid.NYU MED CTR,DEPT PATHOL,NEW YORK,NY 10016NYU MED CTR,KAPLAN CANC CTR,NEW YORK,NY 10016Web of Scienc

    High-flux beam source for cold, slow atoms or molecules

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    We demonstrate and characterize a high-flux beam source for cold, slow atoms or molecules. The desired species is vaporized using laser ablation, then cooled by thermalization in a cryogenic cell of buffer gas. The beam is formed by particles exiting a hole in the buffer gas cell. We characterize the properties of the beam (flux, forward velocity, temperature) for both an atom (Na) and a molecule (PbO) under varying buffer gas density, and discuss conditions for optimizing these beam parameters. Our source compares favorably to existing techniques of beam formation, for a variety of applications.Comment: 5 Pages, 4 figure

    The US influence in shaping Iraq's sectarian media

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    After the Anglo-American invasion, the US neo-conservative administration established the Iraqi Governing Council in July 2003, which included 25 members selected for their ethnic and religious origins; it was the most obvious sign of the US political separatist strategy. As a result of the new political reality, the Iraqi media was divided into ethno-sectarian lines, resulting from previous policies followed by the US administration. This article argues that the US media policy prior and after the US invasion of Iraq played a part in enhancing and encouraging the sectarian divisions in the Iraqi society. This was mainly done by sending biased media messages through the state-run Iraqi Media Network (IMN) and other US-aligned channels and allowing militant voices from different Iraqi sides to wage wars of words without interfering. In fact, the only time US officials interfered is when they were criticized by Iraqi media outlets. This study cites different US government reports, accounts from media practitioners who worked for IMN and other journalists that monitored the Iraqi media

    Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine.

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    Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP\u27s substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate that homozygous MTAP-deleted primary glioblastoma tumors do not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma. These findings highlight metabolic discrepancies between in vitro models and primary human tumors that must be considered when developing strategies for precision therapies targeting glioblastoma with homozygous MTAP deletion

    The Buffer Gas Beam: An Intense, Cold, and Slow Source for Atoms and Molecules

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    Beams of atoms and molecules are stalwart tools for spectroscopy and studies of collisional processes. The supersonic expansion technique can create cold beams of many species of atoms and molecules. However, the resulting beam is typically moving at a speed of 300-600 m/s in the lab frame, and for a large class of species has insufficient flux (i.e. brightness) for important applications. In contrast, buffer gas beams can be a superior method in many cases, producing cold and relatively slow molecules in the lab frame with high brightness and great versatility. There are basic differences between supersonic and buffer gas cooled beams regarding particular technological advantages and constraints. At present, it is clear that not all of the possible variations on the buffer gas method have been studied. In this review, we will present a survey of the current state of the art in buffer gas beams, and explore some of the possible future directions that these new methods might take

    The Primary Folding Defect and Rescue of ΔF508 CFTR Emerge during Translation of the Mutant Domain

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    In the vast majority of cystic fibrosis (CF) patients, deletion of residue F508 from CFTR is the cause of disease. F508 resides in the first nucleotide binding domain (NBD1) and its absence leads to CFTR misfolding and degradation. We show here that the primary folding defect arises during synthesis, as soon as NBD1 is translated. Introduction of either the I539T or G550E suppressor mutation in NBD1 partially rescues ΔF508 CFTR to the cell surface, but only I539T repaired ΔF508 NBD1. We demonstrated rescue of folding and stability of NBD1 from full-length ΔF508 CFTR expressed in cells to isolated purified domain. The co-translational rescue of ΔF508 NBD1 misfolding in CFTR by I539T advocates this domain as the most important drug target for cystic fibrosis
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