Thioglycosides Are efficient metabolic decoys of glycosylation that reduce selectin dependent leukocyte adhesion

Metabolic decoys are synthetic analogs of naturally occurring biosynthetic acceptors. These compounds divert cellular biosynthetic pathways by acting as artificial substrates that usurp the activity of natural enzymes. While O-linked glycosides are common, they are only partially effective even at millimolar concentrations. In contrast, we report that N-acetylglucosamine (GlcNAc) incorporated into various thioglycosides robustly truncate cell surface N- and O-linked glycan biosynthesis at 10-100 μM concentrations. The >10-fold greater inhibition is in part due to the resistance of thioglycosides to hydrolysis by intracellular hexosaminidases. The thioglycosides reduce β-galactose incorporation into lactosamine chains, cell surface sialyl Lewis-X expression, and leukocyte rolling on selectin substrates including inflamed endothelial cells under fluid shear. Treatment of granulocytes with thioglycosides prior to infusion into mouse inhibited neutrophil homing to sites of acute inflammation and bone marrow by ∼80%-90%. Overall, thioglycosides represent an easy to synthesize class of efficient metabolic inhibitors or decoys. They reduce N-/O-linked glycan biosynthesis and inflammatory leukocyte accumulation

Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements

<p>Abstract</p> <p>Background</p> <p>Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of <it>E. coli </it>activates the expression of <it>atoDAEB </it>operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that <it>atoSC </it>is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the <it>atoDAEB </it>promoter as the single, <it>cis</it>-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the <it>E. coli </it>genome.</p> <p>Results</p> <p>Through the implementation of a computational <it>de novo </it>motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the <it>E. coli </it>genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the <it>in vivo </it>binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences.</p> <p>Conclusions</p> <p>This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.</p

Contemporary management of cancer of the oral cavity

Oral cancer represents a common entity comprising a third of all head and neck malignant tumors. The options for curative treatment of oral cavity cancer have not changed significantly in the last three decades; however, the work up, the approach to surveillance, and the options for reconstruction have evolved significantly. Because of the profound functional and cosmetic importance of the oral cavity, management of oral cavity cancers requires a thorough understanding of disease progression, approaches to management and options for reconstruction. The purpose of this review is to discuss the most current management options for oral cavity cancers

Current status and trends of biological invasions in the Lagoon of Venice, a hotspot of marine NIS introductions in the Mediterranean Sea

This paper provides an updated account of the occurrence and abundance of non-indigenous species (NIS) in an area of high risk of introduction: the Lagoon of Venice (Italy). This site is a known hotspot of NIS introductions within the Mediterranean Sea, hosting all the most important vectors of introduction of marine NIS—shipping, recreational boating, shellfish culture and live seafood trade. The recent literature demonstrates that the number of NIS in Venice is continuously changing, because new species are being introduced or identified, and new evidence shows either an exotic origin of species previously believed to be native, or a native origin of formerly believed ‘‘aliens’’, or demonstrates the cryptogenic nature of others. The number of NIS introduced in the Venetian lagoon currently totals 71, out of which 55 are established. This number exceeds those displayed by some nations like Finland, Portugal or Libya. Macroalgae are the taxonomic group with the highest number of introduced species (41 % of NIS): the most likely vector for their introduction is shellfish culture. The source region of NIS introduced to Venice is mainly represented by other Mediterranean or European sites (76 %). The Lagoon of Venice represents a sink but also a source of NIS in the Mediterranean Sea, as it is the site of first record of several NIS, which have since further spread elsewhere.This paper provides an updated account of the occurrence and abundance of non-indigenous species (NIS) in an area of high risk of introduction: the Lagoon of Venice (Italy). This site is a known hotspot of NIS introductions within the Mediterranean Sea, hosting all the most important vectors of introduction of marine NIS-shipping, recreational boating, shellfish culture and live seafood trade. The recent literature demonstrates that the number of NIS in Venice is continuously changing, because new species are being introduced or identified, and new evidence shows either an exotic origin of species previously believed to be native, or a native origin of formerly believed "aliens", or demonstrates the cryptogenic nature of others. The number of NIS introduced in the Venetian lagoon currently totals 71, out of which 55 are established. This number exceeds those displayed by some nations like Finland, Portugal or Libya. Macroalgae are the taxonomic group with the highest number of introduced species (41 % of NIS): the most likely vector for their introduction is shellfish culture. The source region of NIS introduced to Venice is mainly represented by other Mediterranean or European sites (76 %). The Lagoon of Venice represents a sink but also a source of NIS in the Mediterranean Sea, as it is the site of first record of several NIS, which have since further spread elsewhere