The principal neuronal gD-type 3-O-sulfotransferases and their products in central and peripheral nervous system tissues☆

Within the nervous system, heparan sulfate (HS) of the cell surface and extracellular matrix influences developmental, physiologic and pathologic processes. HS is a functionally diverse polysaccharide that employs motifs of sulfate groups to selectively bind and modulate various effector proteins. Specific HS activities are modulated by 3-O-sulfated glucosamine residues, which are generated by a family of seven 3-O-sulfotransferases (3-OSTs). Most isoforms we herein designate as gD-type 3-OSTs because they generate HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of herpes simplex virus 1 (HSV-1) and thereby mediate viral cellular entry. Certain gD-type isoforms are anticipated to modulate neurobiologic events, because a Drosophila gD-type 3-OST is essential for a conserved neurogenic signaling pathway regulated by Notch. Information about 3-OST isoforms expressed in the nervous system of mammals is incomplete. Here, we identify the 3-OST isoforms having properties compatible with their participation in neurobiologic events. We show that 3-OST-2 and 3-OST-4 are principal isoforms of brain. We find these are gD-type enzymes, as they produce products similar to a prototypical gD-type isoform, and they can modify HS to generate receptors for HSV-1 entry into cells. Therefore, 3-OST-2 and 3-OST-4 catalyze modifications similar or identical to those made by the Drosophila gD-type 3-OST that has a role in regulating Notch signaling. We also find that 3-OST-2 and 3-OST-4 are the predominant isoforms expressed in neurons of the trigeminal ganglion, and 3-OST-2/4-type 3-O-sulfated residues occur in this ganglion and in select brain regions. Thus, 3-OST-2 and 3-OST-4 are the major neural gD-type 3-OSTs, and so are prime candidates for participating in HS-dependent neurobiologic events

Development of FISH technology in pathological tissue

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN024925 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

A svm-based method for sentiment analysis in Persian language

Persian language is the official language of Iran, Tajikistan and Afghanistan. Local online users often represent their opinions and experiences on the web with written Persian. Although the information in those reviews is valuable to potential consumers and sellers, the huge amount of web reviews make it difficult to give an unbiased evaluation to a product. In this paper, standard machine learning techniques SVM and naive Bayes are incorporated into the domain of online Persian Movie reviews to automatically classify user reviews as positive or negative and performance of these two classifiers is compared with each other in this language. The effects of feature presentations on classification performance are discussed. We find that accuracy is influenced by interaction between the classification models and the feature options. The SVM classifier achieves as well as or better accuracy than naive Bayes in Persian movie. Unigrams are proved better features than bigrams and trigrams in capturing Persian sentiment orientation

Geometric Optimization of T-shaped Fin and Inverted Fin Based on Minimum Entropy Generation Objective

Since energy management is one of the most critical concerns, it is essential to determine the engineering construct irreversibility. Determination of entropy generation as a basis for evaluation of the irreversibility of heat transfer processes has become a significant method to reflect the heat transfer quality. The current study is dedicated to geometric optimization of T-shaped fins and inverted fins (cavities) using the constructal method to reach the minimum entropy generation as the optimization objective. The temperature distribution is determined according to a 1D analytical model and a 2D numerical model for a T-shaped fin and a T-shaped cavity, respectively. Furthermore, a comparison is made between the present optimal designs relying on entropy generation minimization (EGM) and the optimal designs presented in the literature and based on thermal conductance maximization (TCM) for the fin and hotspot temperature minimization (HTM) for the cavity. While the two optimization approaches have the same constraints, the results reveal that the optimal designs mainly have significant dependence on the type of optimization objective. However, it is shown that the T-shaped fin optimized via EGM produces 24% less entropy than the design optimized by TCM, with the thermal conductance lower only by 4%. On the other hand, the EGM-based optimal cavity generates entropy by about 8% less than that of the HTM-based optimal cavity, with an approximately 19% rise in the hotspot temperature. Considering both objectives for a more comprehensive comparison, the current article introduces a multi-objective optimization for fin and cavity

Synthesis of anticoagulantly active heparan sulfate proteoglycans by glomerular epithelial cells involves multiple 3-O-sulfotransferase isoforms and a limiting precursor pool.

Endothelial and other select cell types synthesize a subpopulation of heparan sulfate (HS) proteoglycans (HSPGs), anticoagulant HSPGs (aHSPGs) that bear aHS-HS chains with the cognate 3-O-sulfated pentasaccharide motif that can bind and activate anti-thrombin (AT). Endothelial cells regulate aHSPG production by limiting levels of HS 3-O-sulfotransferase-1 (3-OST-1), which modifies a non-limiting pool of aHS-precursors. By probing kidney cryosections with (125)I-AT and fluorescently tagged AT we found that the glomerular basement membrane contains aHSPGs, with the staining pattern implicating synthesis by glomerular epithelial cells (GECs). Indeed, cultured GECs synthesized aHS with high AT affinity that was comparable with the endothelial product. Disaccharide analyses of human GEC (hGEC) HS in conjunction with transcript analyses revealed that hGECs express predominantly 3-OST-1 and 3-OST-3(A). aHS production has not been previously examined in cells expressing multiple 3-OST isoforms. This unusual situation appears to involve novel mechanisms to regulate aHS production, as HS structural analyses suggest hGECs exhibit excess levels of 3-OST-1 and an extremely limiting pool of aHS-precursor. A limiting aHS-precursor pool may serve to minimize aHS synthesis by non-3-OST-1 isoforms. Indeed, we show that high in vitro levels of 3-OST-3(A) can efficiently generate aHS. Non-3-OST-1 isoforms can generate aHS in vivo, as the probing of kidney sections from 3-OST-1-deficient mice revealed GEC synthesis of aHSPGs. Surprisingly, Hs3st1(-/-) kidney only expresses 3-OST isoforms having a low specificity for aHS synthesis. Thus, our analyses reveal a cell type that expresses multiple 3-OST isoforms and produces minimal amounts of aHS-precursor. In part, this mechanism should prevent aHS overproduction by non-3-OST-1 isoforms. Such a role may be essential, as 3-OST isoforms that have a low specificity for aHS synthesis can generate substantial levels of aHSPGs in vivo

Characteristics of asthma patients overprescribed short-acting beta-agonist (SABA) reliever inhalers stratified by blood eosinophil count in North East London - a cross-sectional observational study.

BACKGROUND: Over-prescription of short-acting beta-agonist (SABA) inhalers and blood eosinophil count have strong associations with exacerbation risk in asthma. However, in our recent publication only a minority of SABA-overprescribed patients (≥6 inhalers in 12 months) were eosinophilic (≥0.3x109 cells/L). AIM: To compare the characteristics of eosinophilic and non-eosinophilic SABA over-prescribed patients, and identify latent classes using clinical variables available in primary care. DESIGN & SETTING: Cross-sectional analysis of asthmatic patients in North East London using primary care electronic health record data. METHOD: Unadjusted and adjusted multi-variate regression models and latent class analysis. RESULTS: Eosinophilia was significantly less likely in female patients, those with multiple mental health comorbidities and those with SABA on repeat prescription. Latent class analysis identified 3 classes of SABA over-prescribed patients representing those with classical Uncontrolled Asthma (oral-steroid requiring exacerbations, step 2-3 asthma medications, high probability of being eosinophilic), Mild Asthma (low exacerbation frequency, low asthma medication step, low probability of being eosinophilic), and Difficult Asthma (high exacerbation frequency despite high-strength preventer inhalers, low probability of being eosinophilic). The Mild Asthma class was the largest. CONCLUSION: Many patients being over-prescribed SABA are non-eosinophilic with a low exacerbation frequency suggesting disproportionately high SABA prescription compared to other asthma control markers. Potential reasons for high SABA prescription in these patients include repeat prescription (being dispensed but not taken) and use of SABA for non-asthma breathlessness (eg, breathing pattern disorders with anxiety). Further research is needed into management of SABA overuse in patients without other markers of uncontrolled asthma